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1,"TITLE: Simvastatin in the treatment of hypercholesterolaemia in patients with essential hypertension.ABSTRACT: Mortality from coronary artery disease is a common problem in treated hypertensive patients, and these people have a high prevalence of elevated cholesterol levels. A study was undertaken to determine whether cholesterol could be lowered effectively without major side effects in patients with treated hypertension. Forty-nine patients (mean age 67.6 years) with cholesterol greater than 5.5 mmol/l were placed on a reduced-fat (less than 30% of calories from fat with a ratio of polyunsaturated to saturated fats of less than 1) diet for 3 months. If the cholesterol was between 5.5 and 7.5 mmol/l and total cholesterol divided by high-density lipoprotein cholesterol was greater than 4.5, the patients were randomly allocated either to the simvastatin (24 patients) or the placebo group (25 patients). Diet and placebo caused minor and insignificant falls in cholesterol and no change in triglycerides or lipids. Treatment with simvastatin reduced cholesterol levels from 6.85 to 4.75 mmol/l (P less than 0.001), triglycerides from 2.7 to 2.1 mmol/l (P less than 0.01), low-density lipoproteins from 4.6 to 2.6 mmol/l (P less than 0.001) and high-density lipoproteins rose from 1.09 to 1.18 mmol/l (P less than 0.01). Total cholesterol divided by high-density lipoprotein cholesterol fell from 6.3 to 4.0 (P less than 0.001). The drug was well tolerated and the side-effect profile did not differ from the placebo in clinical or biochemical events. The active drug was stopped in one patient (abdominal pain, dizziness, headache, tiredness) and in two patients taking the placebo (elevated creatine phosphokinase, cardiovascular collapse). Simvastatin effectively lowered total cholesterol and improved the lipoprotein profile. The dose required in most patients was 40 mg/day. Simvastatin may be an acceptable drug to improve the lipoprotein profile in order to determine whether this improves the prognosis in patients treated for hypertension."
1,"TITLE: Blood coagulation findings and the efficacy of factor XIII concentrate in premature infants with intracranial hemorrhages.ABSTRACT: Coagulation findings were examined in 55 cases of neonatal intracranial hemorrhages (ICH). Marked decreases of the platelet count, fibrinogen, factor XIII (F XIII) activity, were observed in these cases. However, the relatively mild increases in the alpha 2-plasmin inhibitor activity, alpha 2-plasmin inhibitor.plasmin complex and fibrin/fibrinogen degradation products level were observed and only about one third of the cases showed abnormal values. In consideration of these coagulation findings, fifty-eight cases of premature infants were randomly divided into a treated group with a F XIII concentrate and a non-treated group. Thirty cases were administered within 6 hours after delivery to investigate the preventive effects against intraventricular hemorrhages (IVH). Compared in frequencies between both groups limited to the cases with a high risk of IVH, the frequency in the treated group was two out of 13 (15.4%), significantly low (p less than 0.05), while it was six out of eight cases (75.0%) in the non-treated group. From these results it was concluded that a F XIII concentrate is effective in the prophylaxis of IVH in premature infants."
1,"TITLE: A clinical comparison of central and peripheral argon laser panretinal photocoagulation for proliferative diabetic retinopathy.ABSTRACT: Fifty eyes with three or four diabetic retinopathy risk factors received argon laser panretinal photocoagulation (PRP) with treatment randomly assigned to either central or peripheral distribution. Six months after treatment, two or more acuity lines had been lost by 24% of the central PRP, and by only 8% of the peripheral PRP eyes. Mean visual field constriction with the I-4e isopter was 39% for the central and 29% for the peripheral PRP eyes; for the IV-4e isopter, it was 12 and 7%. Pretreatment macular thickening increased in 19% of the central PRP eyes, but decreased in 19% of the peripheral PRP eyes (P less than 0.05). There was complete disc neovascular regression in 38% of the central and 47% of the peripheral PRP eyes. Partial regression was obtained in 31% centrally and 33% peripherally treated eyes."
1,"TITLE: Thrombosis prophylaxis with low molecular weight heparin in total hip replacement.ABSTRACT: In a randomized prospective trial, the efficacy of low molecular weight heparin (LMWH) (Fragmin) and dextran 70 (Macrodex) in preventing deep vein thrombosis (DVT) in the legs was evaluated in 98 consecutive patients undergoing elective total hip replacement. The patients were randomly allocated to receive either 2500 anti-factor Xa units LMWH twice daily for 7 days, with the first dose given 2 h before surgery; or 500 ml dextran 70 twice during the day of operation, followed by a single infusion of 500 ml on the first and again on the third postoperative day. DVT was assessed by 125I-fibrinogen test for 2 weeks postoperatively, a positive test being followed by phlebography. DVT developed in 22 (45 per cent) of 49 patients receiving dextran 70 and in 10 (20 per cent) of 49 patients in the LMWH group (P less than 0.01). LMWH was thus statistically significantly better than dextran 70 in preventing DVT in the legs. It was not firmly established whether this benefit was also valid in the high ileofemoral region. Two patients with non-fatal pulmonary embolism were found in each group. Per- and postoperative blood loss and blood transfusion requirements were significantly lower in the LMWH group."
1,"TITLE: Response of thromboxane B2, malondialdehyde and platelet sensitivity to 3 weeks low-dose aspirin (ASA) in healthy volunteers.ABSTRACT: To examine the effects of low-dose aspirin thromboxane B2 (TXB2), malondialdehyde (MDA) and platelet sensitivity to prostaglandin I2 (PGI2) have been measured in a total of 18 healthy volunteers. They were randomly assigned to 3 groups, 6 volunteers each, receiving either 1, 10 or 20 mg ASA orally a day for 3 weeks in a double-blind fashion. In order to assess the time course of ASA-induced changes, blood was drawn before, 1 hour and 2, 3, 5, 7, 9, 12, 14, 16 and 21 days after the first drug-intake. Serum-TXB2 was depressed time- and dose-dependently, after 1 mg daily to about 60%, after 10 mg to about 30%, after 20 mg to about 5% of controls. MDA-formation and conversion of exogenously added arachidonic acid (AA) to TXB2 also dropped significantly, (p less than 0.01), the extent depending on the ASA-dosage administered. The drop in MDA- and TXB2-values in the 3 groups correlated with r = 0.98, 0.94, 0.98, respectively. The platelet sensitivity during 20 and 10 mg ASA-administration did not change at all, whereas a significant increase (p less than 0.01) in platelet sensitivity during treatment with 1 mg ASA was observed."
1,"TITLE: Metabolic effects of biosynthetic human proinsulin in type 2 diabetes mellitus.ABSTRACT: Due to a longer plasma half-life and half-time of action on glucose metabolism biosynthetic human proinsulin was thought to be an alternative to long-acting insulin preparations. To test this hypothesis we studied 23 type 2 diabetic patients who could no longer be treated sufficiently with oral hypoglycaemic agents. After an initial 1 week phase during which all patients received protamine bound insulin twice daily, the patients either continued on NPH insulin (Group A, n = 11) or were randomly switched to human proinsulin (Group B, n = 12). Glucose profiles and peripheral and hepatic insulin sensitivity (euglycaemic clamp: 120 mU m-2 min-1) were measured at the end of the initial period (Time 1) and 1 week later (Time 2). The insulin-mediated glucose disposal (RD) was not changed after either treatment (group A: 176 +/- 18 vs. 192 +/- 19 mg m-2 min-1; group B: 175 +/- 15 vs. 174 +/- 12 mg m-2 min-1 for times 1 and 2, respectively, NS). Suppression of hepatic glucose output (HGO) was complete in both groups at both times. Fasting blood glucose levels (FBG) and basal HGO were equally low at times 1 and 2 (group A: FBG 118 vs. 123 mg dl-1, BHGO 81 vs. 79 mg m-2 min-1; group B: FBG 118 vs. 106 mg dl-1, BHGO 87 vs. 84 mg m-2 min-1; NS).(ABSTRACT TRUNCATED AT 250 WORDS)"
1,"TITLE: Comparison of continuous and intermittent bolus infusions of metoclopramide during 5-day continuous intravenous infusion with cisplatin.ABSTRACT: In order to decide the administration method of metoclopramide for prevention or control of chemotherapy-induced nausea and vomiting in multidrug chemotherapy, with cisplatin 5-day continuous intravenous infusion (25 mg/m2/day) for patients with advanced lung cancer, a randomised crossover study of intermittent bolus infusion (1 mg/kg, 30 min, every 8 h, day 1-5) and continuous infusion (3 mg/kg/24 h, 120 h) of metoclopramide was performed. Both regimens included methylprednisolone and diphenhydramine given concurrently. The acute and delayed antiemetic effects were examined. 21 cases could be evaluated. There were 6 and 10 cases (P = 0.048), respectively, of no nausea and no vomiting; 14 and 18 cases (P = 0.048), respectively, of no vomiting; and vomiting episodes were seen 27 and 9 times, respectively (P = 0.042). Thus, metoclopramide continuous infusion was significantly superior in antiemetic effect compared to bolus infusion. Neither method had any serious side-effects and both were safe."
1,"TITLE: Influence of beta-blockade on circulating plasma levels of 3-methoxy-4-hydroxy phenylethylene glycol (MHPG) during exercise in moderate hypertension.ABSTRACT: 1. The effect of exercise testing and beta-blockade on plasma norepinephrine (PNE), and secretion of its metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), was assessed in 28 mild-to-moderate hypertensives before and after the administration of dilevalol, a new beta-blocker with beta 2-agonism. 2. This double blind, placebo-controlled study consisted of two successive submaximal exercise tests before and after the administration of a single oral dose of dilevalol (200 mg, 400 mg or 600 mg). Plasma norepinephrine levels were determined at rest, at 100 watts step of exercise and at maximal effort (Emax). 3. During the control test, mean PNE levels increased from 1.73 +/- 0.52 nmol/L (resting value) to 8.01 +/- 4.01 nmol/L at Emax (P less than 0.01) as MHPG levels increased from 11.18 +/- 1.33 nmol/L (rest) to 17.50 +/- 1.15 nmol/L (Emax, P less than 0.01). After dilevalol, PNE increased significantly as compared to controls (P less than 0.05), from 2.32 +/- 0.99 to 12.42 +/- 5.97 nmol/L (P less than 0.01). PNE and MHPG levels were correlated, both at rest and during exercise. PNE levels after beta-blockade were linearly related to the dose of beta-blocker administered. MHPG levels were unaltered by the administration of dilevalol, both before and after exercise. 4. The increase in MHPG that occurs during bicycle exercise is largely generated from an increase in central nervous system noradrenergic activity. While dilevalol increases the peripheral sympathetic nervous system, both at rest and during exercise (which is reflected by increases in PNE levels) the drug does not alter resting central nervous system noradrenergic activity nor amplify the increase in central noradrenergic activity that occurs during exercise."
1,"TITLE: Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study.ABSTRACT: To investigate in the prospective Helsinki Heart Study, whether chronic Chlamydia pneumoniae infection, indicated by elevated antibody titers against the pathogen, chlamydial lipopolysaccharide-containing immune complexes, or both, is a risk factor for coronary heart disease.The Helsinki Heart Study was a randomized, double-blind, 5-year clinical trial to test the efficacy of gemfibrozil in reducing the risk for coronary heart disease. Participants were randomized to receive either gemfibrozil (2046 patients) or placebo (2035 patients). Fatal and nonfatal myocardial infarction and sudden cardiac death were the main study end points. Serum samples were collected at 3-month intervals from all patients.One hundred forty cardiac events occurred during the follow-up period. Serum samples from 103 case patients obtained 3 to 6 months before a cardiac end point were matched with those from controls for time point, locality, and treatment. Samples were tested for markers of chronic chlamydial infection.Immunoglobulin A (IgA) and G (IgG) antibodies to C. pneumoniae were measured using the microimmunofluorescence method. Lipopolysaccharide-containing immune complexes were measured using two antigen-specific enzyme immunoassays, the lipopolysaccharide-capture and immunoglobulin M (IgM)-capture methods.Using a conditional logistic regression model, odds ratios for the development of coronary heart disease were 2.7 (95% CI, 1.1 to 6.5) for elevated IgA titers, 2.1 (CI, 1.1 to 3.9) for the presence of immune complexes, and 2.9 (CI, 1.5 to 5.4) for the presence of both factors. If we adjusted for other coronary heart disease risk factors such as age, hypertension, and smoking, the corresponding values would be 2.3 (CI, 0.9 to 6.2), 1.8 (CI, 0.9 to 3.6), and 2.6 (CI, 1.3 to 5.2), respectively.The results suggest that chronic C. pneumoniae infection may be a significant risk factor for the development of coronary heart disease."
0,"TITLE: The predictive value of silent ischemia at an exercise test before discharge after an episode of unstable coronary artery disease. RISC Study Group.ABSTRACT: The prognostic value of silent ischemia during a symptom-limited predischarge exercise test (ET) was evaluated in 740 men after an episode of unstable angina or non-Q wave myocardial infarction. The 51% of patients with ST depression at the ET had a higher rate of myocardial infarction or death after 1 year (18%) compared with those without ST depression (9%; p less than 0.01). This increased risk was not influenced by the presence or absence of pain at the ET: 18.3% in patients with painful ischemia compared with 18.1% in patients with silent ischemia. However, ST depression combined with pain at the ET predicted a higher incidence of class III or IV angina at follow-up (43.9% compared with 16.7% in the group with asymptomatic ST depression; p less than 0.001). Because revascularization in addition to alleviating symptoms also enhances the prognosis in certain groups of patients, selections for coronary angiography and possible revascularization should not be made only on the basis of symptoms but also on the presence of myocardial ischemia, whether symptomatic or not."
1,"TITLE: Efficacy of orally administered ondansetron in the prevention of postoperative nausea and vomiting: a dose ranging study.ABSTRACT: In a placebo-controlled, double-blind study, we have compared the efficacy of ondansetron 16 mg, 8 mg and 1 mg administered 8-hourly for prevention of postoperative nausea and vomiting. We studied 995 patients undergoing major gynaecological surgery; 982 were included in the analysis. Study medication was administered 1 h before induction of anaesthesia and second and third doses were given 8 and 16 h after the first. The treatment groups were similar for patient characteristics, surgical procedures, anaesthetics administered and opioids given. The frequency of nausea was 75%, 70%, 56% and 55% after placebo and ondansetron 1 mg, 8 mg and 16 mg, respectively; the corresponding frequencies of vomiting were 60%, 55%, 37% and 37%. Ondansetron 8 mg was as effective as 16 mg and both resulted in significant reductions in nausea and vomiting compared with placebo and ondansetron 1 mg (P less than 0.001)."
1,"TITLE: Impact of converting enzyme inhibition on progression of chronic heart failure: results of the Munich Mild Heart Failure Trial.ABSTRACT: Neurohormonal activation has major impact on the pathophysiology of congestive heart failure. The Munich Mild Heart Failure Trial was designed to test the hypothesis that interference with the renin-angiotensin system by angiotensin converting enzyme inhibition favourably influences the natural history of heart failure.170 patients, median New York Heart Association (NYHA) class II, were randomised to double blind treatment with 25 mg captopril twice a day or placebo in addition to standard treatment for a median observation period of 2.7 years.Progression of heart failure to NYHA class IV on an optimally adjusted standard treatment, death due to progressive heart failure, and sudden death.Heart failure progressed to class IV in nine patients (10.8%) treated with captopril and in 23 patients (26.4%) treated with placebo (p = 0.01). The mean survival time until this end point was 223 days longer in the captopril group (Kaplan-Meier life table analysis; p = 0.02). Also, progressive deterioration to severe heart failure was a powerful predictor of total mortality and death from heart failure; 80% of deaths due to progressive heart failure occurred after this end point. There were fewer deaths caused by progressive heart failure in the captopril group than in the placebo group (4 v 11; p = 0.10) but similar numbers of sudden deaths (11 v 10). Progressive heart failure was the cause of death in 18.2% of all deaths in the captopril group and 50% in the placebo group. Total heart failure events (the end point on which power calculation was based) were also more common in the placebo group (19 v 32 events) but not significantly so. Total mortality was similar to both groups (22 of 83 v 22 of 87).Angiotensin converting enzyme inhibition in conjunction with standard therapy early in the course of congestive heart failure slowed the progress of heart failure and thus favourably altered the natural history of the disease."
1,"TITLE: Paroxetine in the treatment of elderly depressed patients in general practice: a double-blind comparison with amitriptyline.ABSTRACT: A total of 101 patients entered a double-blind, parallel-group study in general practice, comparing the efficacy and tolerability of paroxetine and amitriptyline in elderly depressed patients. All patients received placebo for 1 week followed by active therapy for a total of 6 weeks. Medication was randomly allocated, two-thirds of the patients took paroxetine (20 mg daily) and one-third received amitriptyline (50 mg daily); this dose was increased to 30 mg and 100 mg, respectively, after 1 week. Of the patients who entered the placebo run-in, 90 took active treatment and were evaluable on an intention-to-treat basis (56 paroxetine, 32 amitriptyline). The mean age of the patients was 72 years. Significant reductions in Hamilton Depression Rating Scale (HAMD) from baseline to the end of treatment were seen for both groups (p < 0.01), with no difference between treatments. The HAMD score was reduced by half, or more, for 76% of patients taking paroxetine and 86% taking amitriptyline. Significant improvement was observed in the investigators' Clinical Global Impression (CGI) score for 57% of patients taking paroxetine and 52% on amitriptyline. Improvements after treatment were also observed in the Leeds Sleep Evaluation Questionnaire (LSEQ) scores. Significantly fewer patients taking paroxetine reported adverse events (34% vs 63% taking amitriptyline, p = 0.02). Those taking paroxetine experienced significantly fewer anticholinergic side effects (7% vs 25% taking amitriptyline, p = 0.04). Overall, this study confirmed the effectiveness of paroxetine as an antidepressant drug.(ABSTRACT TRUNCATED AT 250 WORDS)"
1,"TITLE: Sodium fluoride prevents bone loss in primary biliary cirrhosis.ABSTRACT: Low-bone-turnover osteoporosis is a common complication of primary biliary cirrhosis (PBC). Since sodium fluoride stimulates bone formation we assessed the effect of this drug on bone mass in a 2-year, prospective, double-blind trial including 22 women with PBC who were randomly assigned to receive sodium fluoride (50 mg/day) or placebo. All received calcium supplements and low doses of vitamin D. Bone mineral density of the lumbar spine was measured by dual-photon absorptiometry initially and every 6 months. Vertebral fractures were evaluated in thoracic and lumbar spine initially, and after 1 and 2 years. Seven patients in the fluoride group and eight in the placebo group completed the trial. In the fluoride group, bone mineral density did not change after 2 years (initial 1.05 +/- 0.07, final 1.07 +/- 0.06 g/cm2; p = n.s.). In the placebo group, however, bone mineral density decreased significantly (initial 1.00 +/- 0.07, final 0.93 +/- 0.06 g/cm2; p = 0.03). Moreover, in the fluoride group bone mineral density increased by 2.9 +/- 3.6%, and in the placebo group decreased by 6.6 +/- 2.6% (p = 0.04). None of the patients developed new vertebral or non-vertebral fractures. Treatment with sodium fluoride did not impair liver function or cholestasis in PBC. These results indicate that sodium fluoride prevents bone loss in PBC and therefore might be considered as a possible therapeutic agent for osteoporosis associated with this liver disease. Since a small number of patients completed the trial, further studies are required."
1,"TITLE: Growth hormone stimulates galactopoiesis in healthy lactating women.ABSTRACT: Sixteen normally lactating women underwent a double-blind randomized placebo-controlled trial of recombinant human growth hormone (hGH) to assess the effect of hGH on milk production in early lactation. Milk volumes were measured by test weighing procedures of the infants and removal of residual milk on a control day and after 7 days of treatment with recombinant hGH (0.1 IU.kg-1 body weight.d-1) or placebo treatment. Although all women were lactating normally before the study commenced, milk volume in 8 hGH treated mothers was increased (p < 0.02) by 18.5 +/- 1.4% (mean +/- SEM) compared to 11.6 +/- 2.0% in the placebo-treated group (N = 8). No adverse effects were seen with hGH treatment and no major changes noted in milk constituents. The hGH concentrations in milk were low and did not change with therapy. Plasma concentrations of IGF-1 increased significantly within 24 h of hGH treatment and increased further towards the end of the trial to values of 2.6-fold above the pretreatment values. The concentration of IGF-1 in milk was approximately 100-fold lower than those observed in plasma and could only be reliably measured after size exclusion chromatography to remove the interfering influence of IGF binding proteins in the radioimmunoassay. All women treated with hGH showed a small increase in milk IGF-1 concentrations but the values remained within the range of values observed in women receiving the placebo treatment (1.2-4.4 micrograms/l). Growth hormone treatment increased milk volume in normal lactating women during early lactation.(ABSTRACT TRUNCATED AT 250 WORDS)"
1,"TITLE: Thrombolysis with recombinant human tissue-type plasminogen activator during instability in coronary artery disease: effect on myocardial ischemia and need for coronary revascularization. TRIC Study Group.ABSTRACT: Two hundred five men, 40 to 70 years of age, admitted to the coronary care unit with unstable coronary artery disease (unstable angina or non-Q wave myocardial infarction), were randomized to double-blind placebo-controlled treatment with an intravenous infusion of recombinant tissue-type plasminogen activator (rTPA), 1 mg/kg body weight (maximum 100 mg) during 4 hours, in addition to aspirin, heparin, and beta-blockade. No severe complications occurred. Myocardial ischemia, defined as myocardial infarction, incapacitating angina despite medication, or signs of ischemia at the exercise test, was reduced by treatment with rTPA compared with placebo both at discharge, 53% compared with 70% (p = 0.02), and at 1 month, 61% compared with 80% (p = 0.005). Signs of myocardial ischemia during the exercise test were reduced at discharge 51.0% compared with 68% (p = 0.03) and at 1 month 48% compared with 62% (p = 0.09). Coronary angiography after 1 month showed no difference in major coronary lesions between the groups, nor was there any reduction in the number of performed coronary revascularization procedures. In conclusion, treatment with rTPA in unstable coronary artery disease in men reduced myocardial ischemia but did not significantly reduce the need for revascularization in long-term follow-up."
1,"TITLE: Epidural lidocaine with sufentanil and epinephrine for abdominal hysterectomy under general anaesthesia: respiratory depression and postoperative analgesia.ABSTRACT: The purpose of this investigation was to compare the analgesic actions and side-effects of a 50 micrograms epidural bolus of sufentanil and 50 micrograms epinephrine, with a control group receiving saline and epinephrine. The method employed was a prospective, randomised, double-blind trial involving 40 ASA I or II patients for total abdominal hysterectomy. All received 1.5% lidocaine with 1/200,000 epinephrine epidurally before operation, until a block to T4 was established. Patients were anaesthetised, their tracheas were intubated, and they were allowed to breathe spontaneously before administration of the test drug. Results showed that sufentanil prolonged the duration of local anaesthesia (198 +/- 35 min vs 174 +/- 29 min; P less than 0.05), and of analgesia (288 +/- 85 min vs 188 +/- 42 min; P less than 0.01). There was an increase in somnolence in the sufentanil group (9/20 vs 2/20; P less than 0.05). Glycopyrollate was given to 11/20 patients in the sufentanil group vs 1/20 in the control group (P less than 0.01) following bradycardia and hypotension. Clinical respiratory depression occurred in the sufentanil group; 5/20 patients required controlled ventilation following apnoea greater than 20 sec. It is concluded that epidural sufentanil causes considerable cardiorespiratory depression in the setting of general anaesthesia, and should be used with caution in the spontaneously breathing, anaesthetised patient."
0,"TITLE: Prevention of lower extremity venous thrombosis by early mobilization. Confirmation in patients with acute myocardial infarction by 125I-fibrinogen uptake and venography.ABSTRACT: To determine the effects of early ambulation on peripheral venous thrombosis in the coronary care unit, 29 patients with acute myocardial infarction had daily 125I-fibrinogen point counting of both legs using a standard portable technique in the first 3 to 7 days after admission. Twenty-one patients underwent early ambulation during the initial 3 days, while 8 remained at complete bed rest for 5 days. Only 2 of 21 early ambulated patients had positive fibrinogen point counts, in contrast to 5 of 8 nonambulated patients (P less than 0.01). With heart failure, only 2 of 9 ambulated patients had positive point counts, compared with 4 of 5 nonambulated patients (P less than 0.05). In 16 patients undergoing venography, point counts were confirmed in 6 positive and 10 negative findings. These results show that the high frequency of peripheral venous thrombosis in immobilized acute myocardial infarction patients, particularly those with heart failure, can be effectively reduced by early ambulation."
1,"TITLE: Effects of coronary artery bypass grafting on resting and exercise hemodynamics in patients with stable angina pectoris: a prospective, randomized study.ABSTRACT: In this prospective randomized study, resting and exercise hemodynamics were determined in the nonmedicated state before (""entry"") and 1 year after coronary bypass surgery in 38 patients, and at entry and 1 year in 40 patients treated medically. The surgical group showed a significant decrease in mean pulmonary arterial wedge pressure during exercise (entry 23.5 +/- 6.1 [standard error of the mean] mm Hg, 1 year 18.9 +/- 1.0, P less than 0.02); an increase in cardiac index during exercise (entry 4.3 +/- 0.1 liter/min per m2, 1 year 4.6 +/- 0.1, P less than 0.05); an increase in resting mean arterial pressure (entry 94.5 +/- 2.2 mm Hg, 1 year 100.2 +/- 2.2, P less than 0.02); and an increase in resting heart rate (entry 68.5 +/- 1.9 beats/min, 1 year: 76.0 +/- 2.0, P less than 0.01). Maximal treadmill exercise performance also improved significantly in the surgical group of patients (entry 285 +/- 24 seconds, 1 year 382 +/- 24, P less than 0.002). There were no significant changes in these variables in the medically treated ""control"" group. The improvement in pulmonary arterial wedge pressure during exercise and in maximal treadmill exercise time in the surgical group as a whole was due to striking improvement in these variables in a subgroup of 16 surgical patients who had a more than 10 mm Hg increase in pulmonary arterial wedge pressure during exercise in their entry study. In this subgoup, considered to contain those patients with marked ""ischemicdysfunction,"" pulmonary arterial wedge pressure during exercise fell from 31.4 +/- 1.5 mm Hg (entry) to 19.l +/- 1.8 (1 year) (P less than 0.0001) and treadmill time increased from 217 +/- 24 seconds (entry) to 357 +/- 37 (1 year) (P less than 0.001). Thus, hemodynamic evidence of ischemic left ventricular dysfunction during stress may identify those patients who will show objective improvement in ventricular performance after bypass graft surgery."
1,"TITLE: Procainamide conversion of acute atrial fibrillation after open-heart surgery compared with digoxin treatment.ABSTRACT: In 30 patients who developed atrial fibrillation after open-heart surgery the efficacy of intravenous procainamide was evaluated and compared with standard acute digoxin digitalisation. The patients were randomized to two groups of 15. One group received procainamide intravenously at a rate of 25 mg/min and with maximum dose 15 mg/kg. In the other group digoxin 0.75-1.0 mg was given intravenously according to renal function and body weight. Conversion to sinus rhythm occurred during or immediately after the infusion in 87% of the procainamide group, but only in 60% of the digoxin group (p < 0.05). The mean time from start of treatment to conversion was 40 min in the procainamide vs. 540 min in the digoxin group (p < 0.002). There were no serious complications of the procainamide treatment. Intravenous procainamide conversion of postoperative atrial fibrillation is concluded to be effective and safe and can be recommended as the treatment of first choice in awake and nonintubated postoperative cardiac patients."
1,"TITLE: Randomised comparison of olsalazine and mesalazine in prevention of relapses in ulcerative colitis.ABSTRACT: Sulphasalazine extends remissions and lessens disease activity during relapses of ulcerative colitis, but it also causes many adverse side-effects. The adverse reactions are mostly attributable to the sulphapyridine carrier moiety rather than the active principle 5-aminosalicylic acid (5-ASA), so agents to deliver 5-ASA to the colon by other means have been designed. We have compared the efficacy and tolerability of two such agents, olsalazine and mesalazine, in maintenance therapy of ulcerative colitis. 100 patients with ulcerative colitis in remission were recruited at one centre and assigned randomly to treatment with olsalazine (Dipentum; 1.0 g daily) or mesalazine (Asacol, with Eudragit-S coating; 1.2 g daily). Compliance, biochemical and haematological variables, and clinical evidence of disease activity were assessed every 3 months for 12 months by observers unaware of treatment allocation. In intention-to-treat analysis, which included as treatment failures patients withdrawn for protocol violations, adverse reactions, intercurrent illness, or non-compliance as well as those with relapses of ulcerative colitis, the olsalazine group had a significantly lower rate of treatment failure than the mesalazine group (12/49 [24%] vs 23/50 [46%]; p = 0.025). Analysis restricted to 64 patients still in remission at 1 year and 18 with relapses also showed a significant difference in relapse rate (olsalazine 5/42 [12%] vs mesalazine 13/40 [33%]; p = 0.024). Both drugs were well tolerated; only 9 patients reported substantial side-effects. Olsalazine was clearly superior to mesalazine in prevention of relapses in ulcerative colitis, especially in patients with left-sided disease."
1,"TITLE: Determinants of the need for early acute intervention in patients treated conservatively after thrombolytic therapy for acute myocardial infarction. TAMI-5 Study Group.ABSTRACT: This study sought to determine whether clinical variables can be used to identify patients at high risk of recurrent spontaneous myocardial ischemia or hemodynamic compromise during the 1st 4 days after intravenous thrombolysis for acute myocardial infarction. Of 288 patients randomly assigned to a conservative postthrombolysis strategy, 54 (19%) required urgent cardiac catheterization within 24 h; 75 (26%) underwent urgent cardiac catheterization within 4 days of admission. Of the clinical variables examined by multiple logistic regression analysis, only patient age and anterior wall myocardial infarction correlated with the need for urgent cardiac catheterization (p = 0.0016 and p = 0.017, respectively). Compared with recombinant tissue-type plasminogen activator or urokinase monotherapy, combination therapy with these agents was associated with a lower need for acute intervention during the 1st 24 h after admission, but the difference did not reach statistical significance (14% for combination therapy vs. 21% for each agent alone, p = 0.30). Of the 75 patients undergoing urgent coronary angiography, only 39% had an occluded infarct-related artery. Emergency coronary angioplasty was performed in 49% of the patients and coronary artery bypass graft surgery was performed urgently in 3%. Despite these interventions, the need for urgent cardiac catheterization was associated with an in-hospital mortality rate of 7% (vs. 3% in the group not requiring urgent angiography, p = 0.36); mean left ventricular ejection fraction was 50.5 +/- 11% (vs. 54.3 +/- 10.8%, p = 0.12) and regional infarct zone wall motion was -2.68 +/- 1.07 SD/chord (vs. -2.46 +/- 1.19 SD/chord; p = 0.44).(ABSTRACT TRUNCATED AT 250 WORDS)"
1,"TITLE: Late streptokinase infusion and antithrombotic treatment in myocardial infarction reduce subsequent myocardial ischemia.ABSTRACT: Of 255 consecutive patients with acute myocardial infarction, 111 were eligible for attempted late thrombolysis. They were randomly assigned to either thrombolytic and antithrombotic treatment (treatment group) or routine treatment (control group). Patients in the treatment group received streptokinase initiated late (mean 32 hours; range 12 to 49) after the onset of symptoms, followed by heparin infusion for at least 5 days and warfarin and dipyridamole for at least 3 months. Patients were examined clinically and by bicycle ergometry on discharge from the hospital and after 3 and 12 months. The two groups did not differ with respect to deaths or reinfarctions. There was a trend toward a lower incidence of angina pectoris in the treatment group. Exercise tolerance in this group was significantly higher than in the control group (at 3 months 124 +/- 39 W vs 107 +/- 41 W; p less than 0.05). The difference was entirely accounted for by patients with no previous history of infarction or angina pectoris (at 3 months 142 +/- 37 W vs 112 +/- 45 W; p = 0.01). ECG signs of myocardial ischemia, silent or symptomatic, occurred at significantly lower levels of exercise among patients in the control group compared with patients in the treatment group. The results support the notion that thrombolytic therapy given as late as 12 to 49 hours after the onset of symptoms may reduce the incidence of residual ischemia during the postinfarction period."
1,"TITLE: Thiazide for the postponement of postmenopausal bone loss.ABSTRACT: The effect of thiazide on bone mineral loss in normal postmenopausal women was examined during a 3 yr placebo-controlled clinical trial. Sixty-three healthy women in their early menopause were randomized to treatment with bendroflumethiazide 5 mg/day or placebo for 2 yr, while both groups received placebo for the third year of the trial. Calcium supplement 0.5 g/day was given throughout the 36 mo to all participants. Bone mineral content (BMC) determined by 125I-photon absorptiometry of the forearms decreased 2% per year in the placebo group (p less than 0.001). In the thiazide group no fall in BMC was seen during the first 6 mo. whereafter BMC declined with the same rats as in the placebo group. At the end of the 3 yr trial BMC averaged 94.1% in the placebo group and 95.2% in the thiazide group (p greater than 0.05). Despite a daily supplement of 0.5 g calcium, thiazide induced a persistent fall in the urinary calcium excretion of 25% (p less than 0.001), whereas the calcium supplement in the placebo group caused a significant increase in mean urine calcium of 10%-20% (p less than .001). At stop of thiazide medication a rebound effect caused a marked rise in urine calcium. One month after withdrawal of the calcium supplement the urinary calcium excretion had returned to the initial level in both groups. It is concluded that despite a sustained urine calcium lowering action the effect of thiazide upon postmenopausal bone loss is shortlived."
1,"TITLE: Cotrimoxazole prophylaxis in patients with leukemia and prolonged granulocytopenia.ABSTRACT: Sixty-three patients with acute nonlymphoid leukemia (ANLL) under cytostatic treatment were investigated in a randomized trial to determine whether oral administration of cotrimoxazole (TMP/STX) would reduce the rate of infection. Four significant differences were observed between the group given TMP/STX (30 patients) and the control group (33 patients): 1) the mean duration of severe granulocytopenia (less than or equal to 500 PMN/mm3) before the first febrile episode was longer in prophylaxis group, 14.26 days versus four in the control group (p less than 0.001); 2) the number of febrile episodes was 37 in TMP/STX group and 69 in control group (p less than 0.01); 3) 23 patients on prophylaxis presented at least one febrile episode versus 33 in the control group (p less than 0.01); 4) deaths due to infection were two in the TMP/STX group versus 11 in control group (p less than 0.05). Prophylaxis with TMP/STX appears to be useful since by reducing the number of febrile episodes and deaths due to infection, it increases the survival of leukemia patients under cytostatic drugs. Nevertheless, further studies on a larger number of patients are necessary in order to confirm the true efficacy of the drug in the reduction of sepsis and death due to infection."
1,"TITLE: Are bile bacteria relevant to septic complications following biliary surgery?ABSTRACT: Bile bacteriology, wound sepsis and the effect of prophylactic antibiotics have been studied in a controlled prospective double blind randomized trial on 375 patients undergoing elective cholecystectomy at a district general hospital. We have examined the overall prevalence of bacteria in bile and have identified several factors associated with an increased incidence. The identity of organisms isolated from a total of 21 patients with infected wound swabs was compared with isolates from the bile at operation, and in only two instances was there a correlation. Cephazolin, given either pre-operatively, or into the wound, reduced wound infection rates compared with a control group (from 11.8 to 2.4 per cent, P less than 0.005). We conclude that the majority of wound infections in this series were caused by organisms from the patients' skin or exogenous sources, rather than by bacteria from the biliary system."
0,"TITLE: Effect of postoperative total parenteral nutrition (TPN) as an adjunct to gastrectomy for advanced gastric carcinoma.ABSTRACT: Clinical staging and immune reactivity were correlated in 39 patients who underwent gastrectomy for primary gastric cancer. Cellular immunity was depressed as the stage of cancer advanced, whereas humoral immunity was unaffected. Gastrectomy for advanced cancer in stage 3 and 4 suppressed cellular immunity. The cellular and humoral immune systems in relation to total parenteral nutrition (TPN) versus non-TPN were evaluated in 57 patients who underwent gastrectomy for stage 3 and 4 advanced cancer. Cell-mediated immunocompetence was restored in all 29 patients who received postoperative TPN, while serum immunoglobulins were unaffected by TPN. Improvement of impaired cell-mediated immunity was also obtained in patients treated with a TPN-5-FU combination as an adjunct to surgery. Treatment with TPN during 5-FU administration restored immunocompetence, increased tolerance for 5-FU and gave a satisfactory 3-year survival rate. There were significant differences in the 3-year survival rates of patients who underwent non-curative gastrectomy (54 per cent for TPN-5-FU v. 0 per cent for non-TPN-5-FU; P less than 0.05). It is concluded that TPN during chemotherapy as an adjunct to surgery leads to diminished morbidity, and possibly to prolonged survival time, in patients undergoing gastrectomy for gastric cancer. A possible mechanism responsible for the gratifying results of TPN treatment may be the increased tolerance for 5-FU resulting from improved nutrition and increased cell-mediated immunity."
1,"TITLE: Larvicidal activity of albendazole against Necator americanus in human volunteers.ABSTRACT: This study evaluated the efficacy and tolerance of a single oral 400-mg dose of albendazole on Necator americanus larvae, and compared its efficacy when administered between meals or with a meal. Twenty-nine healthy and hookworm-free male volunteers were exposed on the forearm to approximately 45 8-day-old N. americanus larvae. All subjects developed discrete maculopapular eruptions at the site of larval application. Following a random double-blind study design, each subject received at the end of the 6th post-infection day either the investigational drug or a placebo as follows: Group I (n = 8)-placebo; Group II (n = 11)-400 mg albendazole with a meal; Group III (n = 10)-400 mg albendazole 3 or more hours after or before a meal. On day 56 post-infection, the stools of all subjects who received placebo were positive for N. americanus eggs (by zinc sulfate flotation technique), compared with 48% positivity (10/21) in those who received albendazole (P = 0.01). By day 63 post-infection, an additional three subjects in the treatment group became positive, for an overall 62% rate of positivity (13/21), i.e., albendazole prevented patent infection in 38%. Administration of albendazole with a meal did not alter drug efficacy. In those subjects in whom patent infections were not prevented, egg output was one-fourth that of the placebo group. There was no difference in viability of eggs appearing in feces of treated and untreated subjects as judged by larval development in Harada-Mori cultures. Our data indicate that albendazole is active against pre-intestinal stages of N. americanus in human infections."
1,"TITLE: Effects of two energy: nitrogen ratios in patients with gastroenterological disease and malnutrition.ABSTRACT: In 10 patients with active gastroenterological disease and protein-malnutrition (weight: 77.3 +/- 2.6 (mean +/- SEM) percent of ideal body weight, serum-albumin levels: 2.59 +/- 0.17 mg/100 ml) a randomized crossover study was performed to assess the effects of two energy:nitrogen ratios on body cell replenishment. After at least 3 days for equilibration, the total parenteral nutrition (TPN) study carried out with 354 +/- 5 mg of casein hydrolysate-nitrogen/kg/day, divided in two 7-day periods during which two nonprotein calorie supplies of 47 +/- 1 kcal/kg/day and 81 +/- 4 kcal/kg/day were given. The same 50 +/- 5% dextrose and fat emulsion energy sources were used in the two periods. Nitrogen (Kjeldahl method) and potassium retention, and weight and serum albumin concentration gains were all significantly better (Student t test) during the hypercaloric regimen than during the normocaloric regimen. In the 10 patients, the protein-sparing effect of nonprotein calories ""added"" during the hypercaloric regimen was demonstrated and represented 17% of the constant infused nitrogen. The more catabolic patient was prior to TPN, the more energy-dependent was the protein-sparing effect observed (r = +0.638). Preliminary data obtained with 3-methylhistidine urine determination suggests that the protein-sparing effect of ""added"" calories was due to an increased protein synthesis. Finally, body cell replenishment was better with the higher 230 +/- 6 energy:nitrogen ratio than with the lower 132 +/- 4 energy:nitrogen ratio, which suggests that the hypercaloric TPN regimen was useful in such patients."
1,"TITLE: Effects of the estrogenicity of levonorgestrel/ethinylestradiol combinations of the lipoprotein status.ABSTRACT: Ninety-eight women seeking contraceptive advice were randomly allocated to 6 months of treatment with one of the following four combinations of ethinylestradiol (EE) and levonorgestrel (NG): 20/250, 30/250, 30/150, and the so-called triphasic drug. The EE/NG ratios were 0.08, 0.12, 0.20 and 0.36 respectively. Blood lipids, HDL-cholesterol and sex hormone binding globulin (SHBG) were determined twice before treatment and after 1, 3 and 6 months of medication. Plasma triglyceride levels were moderately elevated in all groups, with the highest increase in the women taking the triphasic drug. The HDL-cholesterol and HDL-cholesterol to cholesterol ratios were both markedly reduced, by 20/250 and 30/250, while 30/150 and the triphasic drug caused only minor reductions. The mean change in HDL-cholesterol showed a good correlation with the mean changes of SHBG (r = 0.916) and with the EE/NG ratios (r = 0.979). It is concluded that both SHBG and the EE/NG ratio may be used as an index of the estrogenicity of a combined oral contraceptive drug. As reduced HDL-cholestrol levels and HDL-cholesterol to cholesterol ratios have been shown to be directly correlated to the risk of developing ischemic cardiovascular disease it would seem important that the estrogenicity of such a drug should be sufficiently high."
1,"TITLE: Effects of dexfenfluramine on free fatty acid turnover and oxidation in obese patients with type 2 diabetes mellitus.ABSTRACT: To test the potential effects of dexfenfluramine (dF) on enhancing free fatty acid (FFA) turnover and oxidation rates, 11 obese female non-insulin-dependent diabetes mellitus (NIDDM) outpatients (age, 52.5 +/- 1.5 years; weight, 81.3 +/- 3.2 kg; height, 158 +/- 3.04 cm; body mass index, 32.4 +/- 0.7 kg/m2) received a primed-constant infusion of 1-14C-palmitate. The waist to hip ratio (WHR) was 0.91 +/- 0.04. Fat body mass and lean body mass, assessed by dual-energy x-ray densitometry, were 32.0 +/- 1.5 and 49.30 +/- 2.67 kg, respectively. All patients had an average hemoglobin A1 of 6.3% +/- 0.3% in the month preceding the study and had not received oral hypoglycemic agents. Gas exchange was measured both basally and during a ventilated-hood system, indirect-calorimetry session. The protocol was a randomized, placebo-controlled, single-blind design. Subjects received dF 30 mg acutely (n = 6) or a placebo (n = 5). A dose of dF 15 mg twice daily or placebo was then administered over 15 days (chronic). To obtain serum peak level of the drug, dF was administered 2 hours before starting palmitate infusion. A free diet was allowed throughout the study, and the group treated with dF lost approximately 0.5 kg body weight. Acute and chronic dF administration resulted in a significant increase in FFA oxidation, expressed as a percentage of the dose of radiocarbon (respectively, 11.47% +/- 0.46% v 9.50% +/- 0.46% [P < .01] and 12.06% +/- 0.71% v 9.88% +/- 0.62% [P < .01]). FFA turnover rate was higher after both acute and chronic dF administration (respectively, 10.71 +/- 2.18 v 7.79 +/- 1.48 mumol/kg/min [P < .05] and 11.92 +/- 2.74 v 8.43 +/- 1.86 mumol/kg/min [P < .05]). Serum FFA concentration during both acute and chronic dF administration increased, but not significantly. Mean serum glucose level decreased after acute dF from 114.3 +/- 8.6 to 86.5 +/- 5.1 mg/dL (P < .001) and after chronic dF from 120.3 +/- 7.3 to 89.8 +/- 5.8 mg/dL (P < .001). Serum insulin was not affected by dF administration. In conclusion, oral acute and chronic dF administration increase FFA turnover and oxidation rates in NIDDM obese patients. This may play an important role in weight reduction. In addition, dF shows a weight-independent effect on glucose metabolism, reducing serum glucose levels without acting on insulin secretion."
1,"TITLE: Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Metoprolol in Dilated Cardiomyopathy (MDC) Trial Study Group.ABSTRACT: Several small studies have suggested beneficial effects of long-term beta-blocker treatment in idiopathic dilated cardiomyopathy. Our large multicentre study aimed to find out whether metoprolol improves overall survival and morbidity in this disorder. 383 subjects with heart failure from idiopathic dilated cardiomyopathy (ejection fraction < 0.40) were randomly assigned placebo or metoprolol. 94% were in New York Heart Association functional classes II and III, and 80% were receiving background treatment. A test dose of metoprolol (5 mg twice daily) was given for 2-7 days; those tolerating this dose (96%) entered randomisation. Study medication was increased slowly from 10 mg to 100-150 mg daily. There were 34% (95% CI -6 to 62%, p = 0.058) fewer primary endpoints in the metoprolol than the placebo group; 2 and 19 patients, respectively, deteriorated to the point of needing transplantation and 23 and 19 died. The change in ejection fraction from baseline to 12 months was significantly greater with metoprolol than with placebo (0.13 vs 0.06, p < 0.0001). Pulmonary capillary wedge pressure decreased more from baseline to 12 months with metoprolol than with placebo (5 vs 2 mm Hg, p = 0.06). Exercise time at 12 months was significantly greater (p = 0.046) in metoprolol-treated than in placebo-treated patients. In patients with idiopathic dilated cardiomyopathy, treatment with metoprolol prevented clinical deterioration, improved symptoms and cardiac function, and was well tolerated."
1,"TITLE: Vitamin A supplementation and childhood malaria in northern Ghana.ABSTRACT: Two companion, randomized, placebo-controlled trials of prophylactic vitamin A supplementation provided the opportunity to assess the impact of supplementation on malaria parasitemia, morbidity, and mortality in young children in northern Ghana. In the mortality study, 21,906 children were visited every 4 mo over 2 y, and in the morbidity study 1455 children were visited weekly for 1 y. There was no difference between children supplemented with vitamin A and those given placebo in malaria mortality rates (rate ratio = 1.03; 95% CI 0.74, 1.43) or fever incidence based on reported symptoms. Malaria parasitemia rates, parasite densities in children with a positive blood smear, and rates of probable malaria illness also did not differ between treatment groups. There was no correlation between serum retinol at the beginning of the trial and subsequent malaria parasitemia in children who received placebo (r = 0.01). It is concluded that vitamin A supplementation had no impact on malaria in this population."
1,"TITLE: Correcting respiratory rate for the presence of fever.ABSTRACT: This study defines what degree of respiratory rate (RR) elevation can be attributed to fever using a double blind randomized pre- and post-acetaminophen comparison of vital signs of febrile children presenting to an outpatient clinic. Inclusion criteria were aged between 6 weeks and 24 months, fever between 38.5 and 40.1 degrees C, no serious illness such as sepsis, and no recent receipt of antipyretics or antibiotics. RRs counted over 1 min and rectal temperatures were recorded by a trained observer before, and 1 and 1.5 hours (hr) after receipt of 10-15 mg/kg/dose of either acetaminophen (A) or placebo (P). Randomization produced groups A (n = 54), and P (n = 50) with similar mean age (12.3 vs 12.8 mo.), gender distribution (57 vs 54% female), baseline temperature (39.1 vs 39.1 degrees C), baseline RR (44 vs 45), and hours of fever prior to visit (42 vs 37 hr). The most common diagnoses were otitis media (49%), viral syndrome (18%), upper respiratory infection (16%) or gastroenteritis (7%). The mean temperature decrement of group A was 0.4 degrees C at 1 hr and 0.9 degrees C at 1.5 hr compared to slight increases in fever of 0.3 degrees C at 1 hr and 1.5 hr in group P. Significant decreases in RR occurred in group A compared to group P at 1 hr (7.0 vs 1.9, p = 0.009) and 1.5 hr (10.8 vs 4.0, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)"
0,"TITLE: The effect of raw potato starch on energy expenditure and substrate oxidation.ABSTRACT: Because resistant starch (RS) is not absorbed as glucose in the small intestine of healthy humans, postprandial thermogenesis should be lower after the intake of RS as compared with digestible starch. To evaluate this hypothesis, we measured 5-h postprandial thermogenesis and substrate oxidation by indirect calorimetry after ingestion of 50 g pregelatinized (0% RS) and 50 g raw potato starch (54% type II RS) in 15 healthy, normal-weight young males. The subjects consumed each starch (mixed in diluted fruit syrup) twice on separate days and in random order. RS intake was followed by lower thermogenesis (46.5 +/- 13.1 compared with 115.4 +/- 10.4 kJ/5 h; P = 0.008), lower glucose oxidation (P < 0.0005), and greater fat oxidation (P = 0.013) than was pregelatinized starch consumption. Our results suggest that RS has no thermogenic effect and that its presence does not influence the size of the thermic response to digestible starch."
1,"TITLE: One-year acarbose treatment raises fasting serum acetate in diabetic patients.ABSTRACT: alpha-Glucosidase inhibitors such as acarbose improve blood glucose control in diabetes by delaying or reducing carbohydrate absorption. The fermentation of malabsorbed carbohydrate in the colon is associated with the production of gas, leading to flatulence, and short chain fatty acids such as acetate, which may have systemic effects. To see if acarbose raised fasting serum acetate in diabetic patients, we studied 85 subjects selected from the 267 who had completed a 1-year, double-blind, placebo-controlled, parallel design study of the effects of acarbose in the treatment of diabetes. At baseline, there was no significant difference between the 44 subjects subsequently randomized to placebo and the 41 randomized to acarbose, respectively, in fasting serum acetate (80 +/- 5 vs 71 +/- 4 mumoll-1) or glycosylated haemoglobin (HbA1C; 7.2 +/- 0.3 vs 7.4 +/- 0.3%). Compared to placebo, acarbose treatment significantly increased fasting serum acetate by 11 +/- 4 vs 2 +/- 3 mumoll-1 (p < 0.02) and reduced HbA1C by -0.59 +/- 0.16 vs -0.13 +/- 0.20% (p < 0.02). Acarbose treatment had no significant effect on serum cholesterol or non-esterified fatty acids, but was associated with a significant increase in flatulence. There was no relationship between changes in serum acetate and changes in HbA1C, serum cholesterol or symptoms. We conclude, in subjects with diabetes who tolerate therapy for a 1-year period, that acarbose treatment increases serum acetate. The magnitude of change in acetate was unrelated to side-effects or changes in blood glucose control or serum lipids."
1,"TITLE: Characteristics and consequences of myocardial infarction after percutaneous coronary intervention: insights from the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT).ABSTRACT: We examined the results of the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT) to determine the characteristics and consequences of creatine kinase (CK) and creatine kinase, MB myocardial isoenzyme fraction (CK-MB) elevations after percutaneous coronary intervention.Enzyme elevations after interventional procedures have usually been thought to be without long-term clinical consequences. However, recent preliminary reports have suggested that there are important long-term clinical sequelae in patients with even mild enzyme elevations after coronary procedures.Patients with new native lesions undergoing coronary intervention at 35 clinical sites were randomized to undergo percutaneous coronary angioplasty (n = 500) or directional coronary atherectomy (n = 512). Cardiac enzyme levels were measured 12 and 24 h after the interventional procedure and when clinically indicated for recurrent myocardial ischemia. Enzyme profiles were analyzed using a ratio that compared the peak enzyme level and the local laboratory upper limit of normal. Standard 12-lead electrocardiograms (ECGs) recorded before and after the procedure were interpreted by two independent readers who had no knowledge of the randomization data. Postprocedural myocardial infarction was defined as the appearance of new Q waves on the ECG, CK-MB levels three or more times the upper limit of normal or a total CK concentration two or more times the upper limit of normal when CK-MB levels were unavailable. Regression models were used to evaluate the predictive significance of a postintervention myocardial infarction with respect to clinical outcomes at 30 days and 1 year.There were 78 myocardial infarctions in the atherectomy group and 34 in the angioplasty group (15.2% vs. 6.8%, p = 0.001). Patients with a myocardial infarction more often had a repeat intervention or emergency coronary artery bypass surgery. Hospital length of stay was increased among patients with an infarction, as were mean hospital costs ($17,340.65 vs. $11,308.47, p = 0.0003). Postprocedural myocardial infarction was highly predictive of mortality, bypass surgery or repeat intervention within 30 days (p < 0.0001).Myocardial infarction occurred commonly after coronary intervention in CAVEAT and was associated with a worse clinical outcome. Although the incidence of myocardial infarction was higher with atherectomy than with angioplasty, the baseline characteristics and consequences of the infarctions were similar between the treatments with regard to 30-day outcome. Myocardial enzyme elevations after an otherwise successful interventional procedure may identify a population at risk for a future cardiac event."
1,"TITLE: Impact of surgical stress on the haemodynamic profile of isoflurane-induced hypotension.ABSTRACT: It has been suggested that stimulation of adrenoreceptors could be responsible for some of the haemodynamic effects of isoflurane. But there are no solid data demonstrating the role of sympatho-adrenal stimulation induced by pain during isoflurane administration. The impact of surgical stress on the haemodynamic profile of isoflurane-induced hypotension has been investigated in 28 patients (47-76 years), scheduled for total hip arthroplasty. After premedication with morphine hydrochloride (0.1 mg/kg), patients were randomly assigned to receive either no fentanyl (control group) or fentanyl (5 micrograms/kg before tracheal intubation, 5 micrograms/kg before skin incision, and 2 micrograms/kg each 15 min during the 1st hour). Isoflurane was given to maintain mean arterial blood pressure in the range 6.7-8 kPa in both groups. Haemodynamic data and blood samples for determination of plasma renin activity (PRA) and epinephrine (E) and norepinephrine (NE) levels were collected before and during hypotension. The fentanyl group and the control group differed significantly during hypotension: heart rate, cardiac index, oxygen consumption and E, NE and PRA were lower (P less than 0.01) in the fentanyl group than in control group. Fentanyl lowered the required concentration of isoflurane to achieve the same degree of hypotension (end-tidal concentration: 0.8 +/- 0.2% in the fentanyl group and 1.4 +/- 0.15% in the control group; P less than 0.001). Our results demonstrate that the cardiovascular effects of higher isoflurane concentrations in the absence of narcotic analgesia are counterbalanced by adrenergic stress stimulation of released epinephrine and norepinephrine. Among the likely reasons for catecholamine release during isoflurane administration, inadequate analgesia may be considered."
0,"TITLE: Prognostic value of serum lactic dehydrogenase (S-LDH) in multiple myeloma.ABSTRACT: Serum lactic dehydrogenase (S-LDH) was analysed at diagnosis in ninety-three patients with multiple myeloma. The patients were then followed up after a mean observation period of 39 months (SD 29). Serum lactic dehydrogenase was elevated in twenty-seven out of ninety-three patients and found to correlate with the serum concentrations of beta 2-microglobuline, creatinine, and thymidine kinase. In discriminant analysis of pretreatment S-LDH levels in relation to survival, the best discrimination level was 7.0 mukat 1(-1). Patients with values below 7 microkat 1(-1) ahd a median survival time of 45 months compared to 14 months for those with levels above 7 mukat 1(-1) (P less than 0.001). Serum lactic dehydrogenase at diagnosis, thus, has prognostic information in multiple myeloma."
1,"TITLE: The effect of cholinergic blockade on the ACTH, beta-endorphin and cortisol responses to insulin-induced hypoglycaemia.ABSTRACT: To assess the effect of cholinergic blockade on the ACTH, beta-endorphin and cortisol responses to insulin-induced hypoglycaemia, six healthy male volunteers each underwent two insulin tolerance tests in random order, separated by at least 1 week with and without atropine. ACTH levels were significantly greater at +45 min (mean +/- SEM, 223 +/- 21 pg/ml vs 148 +/- 15 pg/ml, P less than 0.01) and at +120 min (54 +/- 11 pg/ml vs 29 +/- 10 pg/ml, P less than 0.05). beta-endorphin levels were significantly greater at +30 min (170 +/- 45 pg/ml vs 96 +/- 32 pg/ml, P less than 0.05) and at +105 min (81 +/- 14 pg/ml vs 54 +/- 7 pg/ml, P less than 0.01). Cholinergic blockade had no effect on plasma glucose or cortisol concentrations. This study demonstrates that cholinergic blockade with atropine facilitates the ACTH and beta-endorphin responses to insulin-induced hypoglycaemia without altering the cortisol responses."
1,"TITLE: Metoprolol in acute myocardial infarction reduces ventricular arrhythmias both in the early stage and after the acute event.ABSTRACT: Fifty three of the 5778 patients included in the MIAMI (Metoprolol in Acute Myocardial Infarction) trial were investigated with long-term ECG recordings in order to evaluate the effect of acute beta-blockade on premature ventricular complexes in and after acute myocardial infarction. Twenty five patients were given placebo and 28 metoprolol in a double-blind randomized fashion for 15 days. After this period the patients were put on open beta-blockade without breaking individual study codes. The mean number of premature ventricular complexes during the inclusion day (day 0) was the same in the two groups. The median numbers were also similar in the two groups: 190 and 154 in the placebo and metoprolol groups, respectively. Metoprolol significantly reduced the median number of premature ventricular complexes in the randomized period. The median numbers on days 1, 2 and 15 were 146, 101, 84 in the placebo group and 73, 59 and 10 in the metoprolol group, respectively (P less than 0.05). Also during the further follow-up, when investigated 1, 3 and 6 months after the infarction, the median number of premature ventricular complexes was lower in the metoprolol group (74, 257, 142 in the placebo group and 7, 5 and 11 in the metoprolol group, P less than 0.05). This indicates that metoprolol treatment in the acute phase of myocardial infarction reduces ventricular arrhythmias both in the early stage and also after the acute event."
1,"TITLE: Enalapril maleate versus captopril. A comparison of the hormonal and antihypertensive effects.ABSTRACT: 24 hypertensive patients were randomised into 2 groups to compare the antihypertensive effects of enalapril and captopril over a 10-week period. In the hydrochlorothiazide run-in period, blood pressure was reduced from 171 +/- 4/109 +/- 1mm Hg to 160 +/- 4/103 +/- 1mm Hg (p less than 0.05). Angiotensin-converting enzyme (ACE) inhibition decreased blood pressure to 132 +/- 3/87 +/- 2mm Hg. Captopril decreased diastolic blood pressure significantly more after 3 hours than enalapril (-24 versus -17mm Hg, p less than 0.05). After 10 weeks of therapy, this antihypertensive response was maintained at 134 +/- 3/83 +/- 1mm Hg. There was no difference between the captopril and enalapril treated groups. Acute and chronic responses of plasma renin activity, plasma aldosterone and ACE were determined. There was an acute positive correlation between the rise in plasma renin activity and the fall in blood pressures with captopril but not with enalapril. With chronic treatment there was no difference in the ability of either of the 2 drugs to reduce blood pressure, inhibit ACE, reduce aldosterone or stimulate plasma renin activity."
1,"TITLE: Efficacy of indobufen in the treatment of intermittent claudication.ABSTRACT: The aim of this trial was to assess the activity of indobufen compared with placebo in peripheral occlusive arterial disease of the lower limbs of atherosclerotic or diabetic origin. Fifty-two outpatients were admitted to the randomized, double-blind study and were given either an indobufen 200-mg tablet (28 subjects) or placebo (24) for six months. Painfree walking distance on a treadmill at a constant speed (4 km/h) and slope (10 degrees) was assessed before and after three and six months' treatment. The painfree walking distance before treatment with indobufen or placebo averaged 153 +/- 23.02 (mean +/- SE) and 199 +/- 30.58 (mean +/- SE) meters respectively. After six months' treatment with active drug or placebo, this parameter reached 610 +/- 115.36 (p less than 0.01) and 243 +/- 32.49 (p greater than 0.05) meters respectively. The difference between the two treatments was statistically significant in favor of indobufen (p less than 0.01 Dunn's test)."
1,"TITLE: A randomized trial comparing cyclosporine with antilymphoblast-globulin-azathioprine for renal allograft recipients. Results at 2 1/2-6 years.ABSTRACT: Between September 1980 and June 1984, 246 splenectomized, transfused renal allograft recipients were stratified according to presence of diabetes and donor source, and randomized to treatment with either cyclosporine (CsA)-prednisone (pred) or antilymphoblast-globulin (ALG--azathioprine (AZA)--prednisone. As of August 1986, mean follow-up is 47 months. Over all, actuarial patient survival is 84% and 83%, respectively at 4 years. Corresponding graft survival is 70% and 63% for CsA-treated and ALG-AZA-treated patients (NS). Within the subgroup of diabetic recipients of cadaver grafts, graft survival is 70% for CsA-treated and 53% for ALG-AZA-treated recipients (P = .035). In the CsA group, 71% required either a significant reduction in CsA dosage with the addition of azathioprine or a complete switch to azathioprine, mainly because of CsA-associated nephrotoxicity. Of those CsA patients switched at a mean time of 21.3 +/- 16.4 months posttransplant with mean serum creatinine of 2.40 +/- .67, current serum creatinine is 1.79 +/- .63. Current mean serum creatinine values are significantly greater for patients randomized to CsA-pred (1.73 +/- .60) vs. ALG-AZA-pred (1.49 +/- .59), P = .014, even though most CsA-treated patients were eventually switched. The causes of graft loss are not different between CsA and ALG-AZA randomized patients. In nondiabetics, rejection is the most common cause of graft loss (17/33), whereas in diabetics loss due to complications from overimmunosuppression or death from cardiovascular events is significantly more common (27/44) than corresponding losses in nondiabetics (6/33, P less than .05). Switching does not seem to influence the incidence or cause of graft loss. Since most patients started on CsA-prednisone are ultimately switched to triple drug therapy, the latter is now the preferred initial treatment modality."
1,"TITLE: A randomized double-blind comparison of diltiazem and nifedipine in stable angina.ABSTRACT: A double-blind crossover trial comparing diltiazem (360 mg/day) and nifedipine (120 mg/day) for treatment of stable angina was conducted in 21 of 27 patients with proven coronary artery disease who completed the trial. All patients started with a 2 week placebo period followed by a random assignment to either drug treatment for 3 weeks and subsequent crossover to the other treatment. The two drug treatment periods were separated by a 1 week placebo washout phase and the study was completed with a 1 week placebo phase. There were no significant differences between patients' responses to diltiazem and nifedipine in relation to time to onset of angina, ST depression responses to exercise, heart rate or systolic or diastolic blood pressure. A total of 37 adverse effects were reported with nifedipine compared with 9 with diltiazem in the 22 patients in whom drug safety was analyzed. Additionally, two patients treated with nifedipine were withdrawn from study participation before crossover. There was a significant (p less than 0.05) difference with respect to incidence of edema (7 of 22 patients taking nifedipine, 1 of 22 taking diltiazem) and dizziness (7 of 22 patients taking nifedipine, 0 of 22 taking diltiazem). The most frequent adverse effect reported with diltiazem was rash (3 of 22 patients). Severe adverse effects were reported in four patients: in one with diltiazem (rash) and in three with nifedipine (palpitation in two and headache in one). A reduction in prescribed dosage was required in 37% of nifedipine-treated compared with 6% of diltiazem-treated patients. Efficacy measures were significantly improved above placebo levels by both diltiazem and nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)"
1,"TITLE: Acute coronary artery obstruction in myocardial infarction: overview of thrombolytic therapy.ABSTRACT: Pump failure, ranging from ventricular dysfunction to acute cardiogenic shock, is now the leading cause of cardiac death. Efforts at temporary mechanical or pharmacologic support of the heart have been largely unsuccessful so that attention is now directed toward prevention of ventricular failure and limitation of myocardial infarct size or even outright prevention of infarction itself. In particular, attention has been refocused on earlier reperfusion efforts with streptokinase. The effect of thrombolysis in acute myocardial infarction on enzymatic infarct size, left ventricular function and early mortality was studied in subsets of patients in a randomized trial (Netherlands Interuniversity Cardiology Institute). Early thrombolytic therapy with intracoronary streptokinase (152 patients) or with intracoronary streptokinase preceded by intravenous streptokinase (117 patients) was compared with conventional treatment (264 patients). All 533 patients were admitted to the coronary care unit within 4 hours after onset of symptoms indicative of acute myocardial infarction. Of the patients eligible for this detailed analysis, 245 were allocated to thrombolytic therapy and 243 to conventional treatment. Early angiography was preformed in 212 of the 245 patients allocated to thrombolytic therapy. Patency of the infarct-related artery was achieved in 181 patients (85%). Enzymatic infarct size, measured from cumulative alpha-hydroxybutyrate dehydrogenase release, was smaller in patients allocated to thrombolytic therapy (median 760 versus 1,179 U/liter in control subjects, p = 0.0001). Left ventricular ejection fraction measured by radionuclide angiography before discharge was higher after thrombolytic therapy (median 50% versus 43% in control subjects, p = 0.0001). Twelve month mortality was lower in patients allocated to thrombolytic therapy (8% versus 16% in the control group, p less than 0.01). In multivariate regression analysis infarct size limitation, improvement of left ventricular ejection fraction and 3 month mortality were predicted by sigma ST, time from onset of symptoms to admission and Killip class at admission. Thrombolysis was most useful in patients admitted within 2 hours after onset of symptoms and in patients with a sigma ST segment of 1.2 mV or more. On the other hand, no beneficial effects of streptokinase on enzymatic infarct size, left ventricular function or mortality were observed in the subset of patients with sigma ST less than 1.2 mV, admitted 2 to 4 hours after onset of symptoms."
1,"TITLE: Effect of an inhaled neutral endopeptidase inhibitor, thiorphan, on airway responsiveness to leukotriene D4 in normal and asthmatic subjects.ABSTRACT: Cysteinyl leukotrienes are potent inflammatory mediators that are considered to play a role in the pathophysiology of asthma. It can be postulated that leukotrienes exert their bronchoconstricting effects, in part, through secondary release of endogenous neuropeptides. We examined the effect of inhaled thiorphan, an inhibitor of a neuropeptide degrading enzyme, on the concentration-response curve to leukotriene D4 (LTD4) in a two-period, double-blind, cross-over and placebo-controlled study, in 16 nonasthmatic and 12 asthmatic subjects. Thiorphan or placebo were aerosolized and administered in two 0.5 ml doses of 1.25 mg.ml-1 each, 10 min prior to LTD4 inhalation. The airway response was measured by forced expiratory volume in one second (FEV1) and partial expiratory flow-volume curves (expiratory flow at 40% of forced vital capacity; V40p), and expressed as % fall from baseline. Complete concentration-response curves to inhaled LTD4 were recorded and characterized by their position (provocative concentration producing a 20% fall in FEV1 and a 40% fall in V40p; PC20FEV1 and PC40 V40p) and, in the nonasthmatics, also by the maximal-response plateau (MFEV1, MV40p). Post-pretreatment baseline values of FEV1 and V40p were not different between thiorphan and placebo pretreatment. In both groups of subjects, there was no significant difference in lnPC40V40p or lnPC20FEV1 to LTD4 between the two pretreatments mean difference +/- SD (in doubling concentrations): 0.12 +/- 0.73 and -0.19 +/- 1.23, respectively, in asthmatics; and 0.17 +/- 0.95 and -0.99 +/- 1.95, respectively, in nonasthmatics. The maximal-response plateau could not be obtained in the majority of the asthmatic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)"
1,"TITLE: Active compression-decompression resuscitation: effect on resuscitation success after in-hospital cardiac arrest.ABSTRACT: The purpose of this study was to test the hypothesis that active compression-decompression would improve resuscitation success in human subjects after cardiac arrest.Active compression-decompression cardiopulmonary resuscitation is a new method that improves cardiopulmonary hemodynamic function in animal models and humans after cardiac arrest.We conducted a prospective randomized clinical trial in patients with in-hospital cardiac arrest. Patients were assigned to receive standard manual or active compression-decompression cardiopulmonary resuscitation. The primary study end points were spontaneous return of circulation, 24-h survival and survival to hospital discharge.Fifty-three consecutive patients after cardiac arrest undergoing 64 resuscitation attempts were studied (30 women, 23 men; mean [+/- SD] age 71 +/- 13 years, range 38 to 96). Spontaneous return of circulation was observed in 24 (47%) of 53 patients and was increased in patients receiving active compression-decompression compared with those receiving standard manual cardiopulmonary resuscitation (15 [60%] of 25 vs. 9 [32%] of 28, respectively, p = 0.042); 24-h survival was increased (12 [48%] of 25 vs. 6 [21%] of 28, respectively, p = 0.041); and there was a trend toward improved survival to hospital discharge (6 [24%] of 25 vs. 3 [11%] of 28, respectively, p = 0.198) when active compression-decompression was compared with standard manual cardiopulmonary resuscitation.Active compression-decompression cardiopulmonary resuscitation improves return of spontaneous circulation and 24-h survival after in-hospital cardiac arrest. Active compression-decompression cardiopulmonary resuscitation appears to be a beneficial adjunct to standard manual cardiopulmonary resuscitation."
1,"TITLE: Perioperative chemotherapy in patients with oral cancer.ABSTRACT: In the final report of a prospective, randomized controlled clinical trial, we report the results of using adjuvant perioperative chemotherapy in patients with oral cancer. Our study is based on the hypothesis of Goldie and Coldman. A total of 135 patients with alveolobuccal carcinoma, classified as clinically stage III and IV, were entered on the protocol. After a curative resection, they were randomized. The patients in the test arm of the study received methotrexate 50 mg/m2 on the 3rd, 10th, and 17th postoperative days. The patients in the control arm underwent observation. This analysis at 24 months showed a disease-free survival rate of 61% in the test arm versus 37% in the control arm, which is statistically highly significant (P < 0.01). Analysis of the recurrence pattern showed that recurrence at the primary site was dramatically reduced during the first 6 postoperative months (P = 0.002). Our study provided further clinical evidence in support of the concepts of Goldie and Coldman that the timing of chemotherapeutic drugs is critical for a successful end result."
1,"TITLE: Laparoscopic salpingostomy versus laparoscopic local methotrexate injection in the management of unruptured ectopic gestation.ABSTRACT: Our goal was to determine whether laparoscopic salpingostomy is preferable to laparoscopic methotrexate injection in the management of unruptured tubal gestation.Forty-eight patients with unruptured tubal pregnancy were prospectively randomized to either laparoscopic salpingostomy or laparoscopic local methotrexate injection in a university medical center. Operation time, duration of hospital stay, decrease in levels of beta-human chorionic gonadotropin, and fertility outcome were compared between the two groups.The salpingostomy group had a longer operative time (p < 0.0001) but a shorter hospital stay (p < 0.01) and a lower incidence of persistent trophoblastic activity (5% vs 14%), although this difference did not reach statistical significance. The time interval until beta-human chorionic gonadotropin disappearance was similar (13.9 and 13.7 days), and the subsequent intrauterine pregnancy rate was similar in the two groups (83.5% and 81%). One repeat tubal pregnancy occurred in the salpingostomy group.Both these methods of conservative management are equally effective and each one has its merits."
1,"TITLE: Hypophosphataemia after renal transplantation: relationship to immunosuppressive drug therapy and effects on muscle detected by 31P nuclear magnetic resonance spectroscopy.ABSTRACT: Plasma phosphate values were examined in 72 renal transplant patients in a randomised trial of immunosuppression with azathioprine and prednisolone versus cyclosporin alone. From 21 to 77 days after transplantation, in patients with plasma creatinine concentrations of 75-150 mumol/l, mean plasma phosphate was 0.98 (SEM 0.04) mmol/l in cyclosporin-treated patients, compared with 0.65 (SEM 0.12) mmol/l in cyclosporin-treated patients receiving pulse methylprednisolone for rejection (P less than 0.003), and 0.68 (SEM 0.02) mmol/l in patients treated with azathioprine and prednisolone (P less than 0.001). There was no difference between the mean plasma creatinine of these groups of patients. A preliminary study by nuclear magnetic resonance spectroscopy of four patients with asymptomatic chronic hypophosphataemia showed reduced concentrations of intracellular phosphate in resting muscle, and further abnormalities developed on exercise. Thus, exogenous steroid administration is a major contributing factor of hypophosphataemia in the early post-transplant period. In addition chronic hypophosphataemia may be associated with reduced intracellular inorganic phosphate concentrations detectable by nuclear magnetic resonance spectroscopy, although these changes are not apparently associated with any clinical symptoms."
0,"TITLE: Lack of effects of angiotensin-converting enzyme (ACE)-inhibitors on glucose metabolism in type 1 diabetes.ABSTRACT: To evaluate the impact of ACE-inhibitors on insulin-mediated glucose uptake, glucose-induced glucose uptake, and hepatic glucose production, a sequential glucose clamp was performed in eight normotensive Type 1 diabetic patients after 3 weeks of enalapril therapy 20 mg day-1 and during control conditions. The experiments were carried out in random order. Mean arterial blood pressure was significantly reduced during ACE-inhibition (95 +/- 3 (+/- SE) vs 84 +/- 3 mmHg; p less than 0.02), while blood glucose control as assessed by HbA1c was unaltered (7.9 +/- 0.5 vs 7.6 +/- 0.5%). The night prior to the study normoglycaemia was maintained by a Biostator. A two-step hyperinsulinaemic euglycaemic clamp (insulin infusion rate 0.3 and 0.8 mU kg-1 min-1) was followed by a hyperinsulinaemic and hyperglycaemic clamp (insulin infusion rate 0.8 mU kg-1 min-1, plasma glucose 11 mmol l-1). Insulin concentrations were comparable with and without enalapril treatment. During the hyperinsulinaemic clamps isotopically determined glucose disposal was unchanged (low dose 2.5 +/- 0.3, high dose 4.3 +/- 0.7 vs 2.6 +/- 0.3 and 4.3 +/- 0.7 mg kg-1 min-1, enalapril vs control). Glucose-induced glucose disposal (9.2 +/- 1.2 vs 9.1 +/- 1.2 mg kg-1 min-1) was also similar, as were non-protein respiratory exchange ratios (indirect calorimetry). Glucose production was not changed by enalapril. In conclusion, treatment with enalapril has no significant effect on glucose metabolism in Type 1 diabetes."
1,"TITLE: The long-term effects of nedocromil sodium and beclomethasone dipropionate on bronchial responsiveness to methacholine in nonatopic asthmatic subjects.ABSTRACT: We investigated the effects of long-term treatment with two anti-inflammatory drugs, nedocromil sodium and beclomethasone dipropionate, on airway hyperresponsiveness to methacholine (PC20), on baseline FEV1 and on the bronchodilating effect of a deep breath in 25 nonsteroid-dependent nonatopic asthmatic adults. In all subjects the prestudy PC20 was less than 8 mg/ml, the postbronchodilator FEV1 was greater than 75% predicted, and skin prick tests and RAST to 13 common allergens were negative. After 2 months run-in, the subjects were randomly allocated into 3 parallel treatment groups to inhale double-blind either 4 mg nedocromil (n = 9) or 100 micrograms beclomethasone (n = 8) or placebo (n = 8) 4 times daily for 4 months. PC20 was measured using the 2-min tidal breathing method. The effect of a deep breath was measured during methacholine-induced bronchoconstriction by standardized maximal and partial expiratory flow-volume curves and was expressed as a flow ratio (M/P ratio). Pretreatment values of FEV1, PC20, and M/P ratio were not different between the 3 groups. PC20 did not change in the placebo group, but increased significantly by a factor of 3 after 8 wk of treatment with beclomethasone or nedocromil (p less than 0.001). FEV1 did not change after treatment with placebo or nedocromil (p greater than 0.2), but increased (mean change 0.2 L, SD 0.2) after 4 wk of treatment with beclomethasone (p less than 0.05). Geometric mean M/P ratio increased from 1.98 to 2.66 after 4 wk of beclomethasone (p less than 0.01), but not after nedocromil or placebo.(ABSTRACT TRUNCATED AT 250 WORDS)"
1,"TITLE: Evaluation of the clinical pharmacology of nilvadipine in patients with mild to moderate essential hypertension.ABSTRACT: Eighty-four patients with diastolic blood pressure ranging from 100-115 mm Hg were randomized into a multicenter, parallel, double-blind, placebo-controlled, dose response study with nilvadipine (6 mg, 8 mg, 10 mg tid for 28 days). The hypotensive response pattern to nilvadipine was similar with all three doses although duration of response was dose dependent. Maximal decreases in diastolic blood pressure occurred at 1 hour when assessed on days 1 and 15 (16.0, 17.4, and 15.8 mm Hg, vs 17.2, 18.7, and 17.5 mm Hg, respectively). The hypotensive effect remained significant compared to placebo for at least 4 hours after dosing. The increase in heart rate associated with the maximal hypotensive response was minimal and not clinically significant (day 1: 7.6, 5.2, and 4.0 beats/min with 6, 8, and 10 mg; day 15: 4.0, 5.1, 2.6 beats/min with 6, 8, 9, and 10 mg, respectively). Finally, a correlation between plasma drug concentrations and nilvadipine-induced hypotensive response was observed (r = 0.48). Black and white hypertensive patients had similar hypotensive responses. Plasma nilvadipine concentrations on day 15 were similar to those on day 1 suggesting no accumulation of drug with a tid regimen. The most common drug related side effect was headache; less frequently seen were dizziness, edema, palpitations, and abdominal pain. Nilvadipine was well tolerated (only three patients were discontinued due to side effects). The efficacy, lack of tachycardia, and side effect profile observed in this study suggest that nilvadipine may be an important addition to the treatment of hypertension."
1,"TITLE: Saccharomyces boulardii prevents diarrhea in critically ill tube-fed patients. A multicenter, randomized, double-blind placebo-controlled trial.ABSTRACT: To assess the preventive effect of Saccharomyces boulardii on diarrhea in critically ill tube-fed patients and to evaluate risk factors for diarrhea.Prospective, multicenter, randomized, double-blind placebo-controlled study.Eleven intensive care units in teaching and general hospitals.Critically ill patients whose need for enteral nutrition was expected to exceed 6 days.S. boulardii 500 mg four times a day versus placebo.Diarrhea was defined by a semiquantitative score based on the volume and consistency of stools. A total of 128 patients were studied, 64 in each group. Treatment with S. boulardii reduced the mean percentage of days with diarrhea per feeding days from 18.9 to 14.2% [odds ratio (OR) = 0.67, 95% confidence interval (CI) = 0.50-0.90, P = 0.0069]. In the control group, nine risk factors were significantly associated with diarrhea: nonsterile administration of nutrients in open containers, previous suspension of oral feeding, malnutrition, hypoalbuminemia, sepsis syndrome, multiple organ failure, presence of an infection site, fever or hypothermia, and use of antibiotics. Five independent factors were associated with diarrhea in a multivariate analysis: fever or hypothermia, malnutrition, hypoalbuminemia, previous suspension of oral feeding, and presence of an infection site. After adjustment for these factors, the preventive effect of S. boulardii on diarrhea was even more significant (OR = 0.61, 95% CI = 0.44-0.84, P < 0.0023).S. boulardii prevents diarrhea in critically ill tube-fed patients, especially in patients with risk factors for diarrhea."
1,"TITLE: Comparison of a lifestyle modification program with propranolol use in the management of diastolic hypertension.ABSTRACT: To compare the management of mild diastolic hypertension (90 to 104 mm Hg) using a nonpharmacologic intervention with that using propranolol or placebo.Randomized, placebo-controlled trial with a 2 x 2 factorial design.University-based ambulatory care center.Two hundred seven men and 105 women, 22 to 59 years of age, 73% white, who had mild diastolic hypertension untreated for at least eight weeks.1) a multicomponent lifestyle modification intervention (lifestyle focus group, or LFG) administered in eight weekly meetings + placebo, 2) LFG + propranolol, 3) propranolol alone, and 4) placebo alone, followed for 12 months.Systolic blood pressure (SBP), diastolic blood pressure (DBP), and self-reported adverse effects at each of nine follow-up visits; fasting total cholesterol, triglycerides, and glucose at baseline and 12 months; 24-hour urine sodium (Na+) and potassium (K+), three-day food records and physical activity questionnaire at three and 12 months; and a quality of life questionnaire at 12 months.The mean decreases in DBP at 12 months were: 8.5 mm Hg in the LFG + propranolol group; 7.7 mm Hg in the propranolol-only group; 5.9 mm Hg in the placebo-only group; and 5.4 mm Hg in the LFG + placebo group. Repeated-measures analysis of covariance showed that level of baseline DBP (p < 0.0001), time of follow-up (p < 0.0001), and propranolol use (p < 0.0001) were significantly associated with a decrease in DBP at 12 months. Despite reductions in urinary Na+ (-35 mEq; 95% CI = -50, -19), dietary Na+ (-521 mg; 95% CI = -710, -332), total calories ingested (-238; 95% CI = -335, -140), and weight (-1.4 lb; 95% CI = -3.7, +0.8), and significant increases in dietary K+ (+294 mg; 95% CI = +107, +480) and in mets-minutes of exercise (+43; 95% CI = +20, +67) at three months, assignment to the LFG intervention had no effect on DBP at three or 12 months. The subjects assigned to take propranolol more frequently reported fatigue during ordinary activities, sleep disturbance, decrease in sexual activity, and depressed feelings, when compared with the subjects taking placebo, but the numbers of study withdrawals did not differ by drug assignment. No significant difference in total cholesterol and glucose levels was observed by group assignment. Triglycerides increased significantly in the subjects assigned to propranolol (mean difference = +20 mg/dL; 95% CI of difference +1.5, +39). There was no difference in the responses to 21 quality of life items between the subjects assigned to propranolol and those assigned to placebo.This multicomponent lifestyle modification intervention was unable to promote persistent behavior changes and thus was inferior to propranolol therapy for the treatment for mild diastolic hypertension. Future research should focus on single modifiable factors to lower blood pressure."
1,"TITLE: Preventing fungal infection in neutropenic patients with acute leukemia: fluconazole compared with oral amphotericin B.ABSTRACT: To compare the efficacy and tolerability of fluconazole and oral amphotericin B in preventing fungal infection in neutropenic patients with acute leukemia.A randomized, controlled, multicenter trial.30 hematologic units in tertiary care or university hospitals.820 consecutive, afebrile, adult patients with acute leukemia and chemotherapy-induced neutropenia.Patients were randomly assigned to receive fluconazole, 150 mg, as a once-daily capsule, or amphotericin B suspension, 500 mg every 6 hours.An intention-to-treat analysis was done for 820 patients: 420 treated with fluconazole and 400 treated with oral amphotericin B.Definite systemic fungal infection occurred in 2.6% of fluconazole recipients and 2.5% of amphotericin B recipients; suspected systemic fungal infection requiring the empiric use of intravenous amphotericin B occurred in 16% of fluconazole recipients and 21% of oral amphotericin B recipients, a difference of 5 percentage points (95% CI for difference, -0.02% to 10%; P = 0.07). Superficial fungal infection was documented in 1.7% of fluconazole recipients compared with 2.7% of amphotericin B recipients, a difference of one percentage point (CI of difference, -0.9% to 3%; P > 0.2). The distribution of fungal isolates in systemic and superficial fungal infection was similar in both groups. The overall mortality rate accounted for 10% in both groups. An excellent compliance was documented for 90% of patients treated with fluconazole compared with 72% of those treated with amphotericin B suspension, a difference of 18 percentage points (CI for difference, 13% to 23%). Side effects were documented less frequently in fluconazole than in amphotericin B recipients (1.4% compared with 7%, a difference of 5.6 percentage points; CI for difference, 2% to 8%; P < 0.01).Fluconazole was at least as effective as oral amphotericin B in preventing systemic and superficial fungal infection and the empiric use of amphotericin B in neutropenic patients with acute leukemia but was better tolerated."
1,"TITLE: Cow's milk versus soy-based formula in mild and moderate diarrhea: a randomized, controlled trial.ABSTRACT: We determined the efficacy of a soy-based formula compared with a cow's milk formula in infant refeeding after acute diarrhea in a randomized controlled double-blind clinical trial. Infants 2-12 months of age with diarrhea of less than one week's duration and mild or moderate dehydration admitted to a pediatric hospital or in the practice of a participating primary care pediatrician were investigated. Seventy-six patients were enrolled and 73 completed the study; 39 infants received a soy-based formula (Isomil) and 34 received a cow's milk formula (SMA). Hospitalized patients were rehydrated with an oral glucose-electrolyte solution or an iv dextrose-sodium solution. Outpatients received oral glucose-electrolyte solution. In all patients, the study formula was commenced ad libitum during the first 24 h as determined by the attending pediatrician. The primary outcome measure was duration of diarrhea, defined as time to first normal stool, when subsequent stools were normal for a 24-h period. In addition, a predetermined secondary outcome was proportion of treatment failures, defined as the need to reinstitute clear fluids because of emesis, refusal to accept study formula, need for iv fluids due to negative fluid balance or diarrhea persisting beyond 7 days after enrollment. Total duration of diarrhea was significantly longer (p = 0.03) in those receiving cow's milk (mean +/- SD 6.6 +/- 4.2 days) than in those receiving soy-based formula (4.5 +/- 3.6 days). Volume of formula intake and weight gain at 14 days were not different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)"
1,"TITLE: Hemodynamic effects of morphine and nalbuphine in acute myocardial infarction.ABSTRACT: Hemodynamic effects of morphine and the new narcotic analgesic, nalbuphine, were compared in a randomized, double-blind study in 15 patients with acute myocardial infarction (11 men and four women, average age 56.2 yr) and normal group mean hemodynamic function. During a 1-hr evaluation the hemodynamic effects were small but there were changes in several parameters. Morphine reduced heart rate (78 to 72 bpm, p less than 0.01) and diastolic and mean arterial pressures (69 to 64 mm Hg, p less than 0.05; and 91 to 84 mm Hg, p less than 0.05); nalbuphine was associated with a decrease in heart rate (82 to 72 bpm, p less than 0.01), decrease in cardiac index, which remained within the normal range (3.16 to 2.75 l/min/m(2), p less than 0.01), and an increase in systemic vascular resistance (1,204 to 1,461 dynes . sec . cm(-5), p less than 0.05). Neither drug altered systolic arterial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, stroke index, stroke work index, or pulmonary vascular resistance. Echocardiographic assessment revealed diminution of left ventricular mean velocity of circumferential fiber shortening after nalbuphine (1.26 to 1.08 circ/sec, p less than 0.05). Both drugs induced small reductions in respiratory rate and arterial pH and increases in PAO2. There were no changes in PaO2. Because of the absence of clinically important deleterious effects on cardiac pump function, nalbuphine merits further investigation as an analgesic in acute myocardial infarction."
1,"TITLE: Perioperative nutritional support in patients undergoing hepatectomy for hepatocellular carcinoma.ABSTRACT: This prospective, randomized, controlled trial from the University of Hong Kong evaluated the efficacy of perioperative parenteral nutrition (PN) in patients requiring hepatectomy for primary hepatocellular carcinoma. From September 1990 through June 1993, 150 consecutive patients with resectable hepatocellular carcinoma were randomly assigned to receive either perioperative PN (n = 75), in addition to usual oral diet, or to no additional therapy (oral diet alone without PN; n = 75). Excluding patients with metastatic disease, a total of 64 patients in the perioperative PN group (39 with associated cirrhosis, 18 with chronic active hepatitis, and 7 without associated liver disease) were compared to 60 control patients (33 with cirrhosis, 12 with chronic active hepatitis and 15 with no associated liver disease). PN was started 7 days before hepatic resection and continued for 7 days after operation in the experimental patients. The PN consisted of standard micronutrients, dextrose, lipid emulsion (containing 50 percent of lipid as medium-chain triglycerides, MCT) and amino acids enriched in branched-chain amino acids (BCAA, 35 percent of PN protein intake), and provided = 1.5 g protein/kg/day and 30 kcal/kg/day. PN was administered via a superior vena cava Broviac catheter cycled over 12 hours each evening preoperatively, and as a 24 hour infusion during the postoperative week. Control patients received only 5 percent dextrose in normal saline postoperatively, with volume and sodium content similar to the experimental PN-treated patients. All patients studied (experimental and control) received 25 grams of albumin intravenously for 5 days postoperatively, and all were allowed to consume enteral diet as tolerated throughout the entire study period. Preoperative assessment included standard anthropometric indices, serum chemistries and proteins, indocyanine green clearance (an index of hepatic function), hand grip strength, and immune function tests (serum immunoglobulin concentrations and peripheral lymphocyte stimulation by phytohemagglutinin). Postoperative assessment included the same preoperative indices (chemistries measured from days 1 to 8 post-operatively), and overall postoperative mortality and morbidity during the hospitalization. Morbidity indices included both infectious complications and non-infectious complications (eg, pleural effusion, ascites, renal failure, hepatic coma). The two groups of patients were similar in age, sex, total and percent weight loss, hepatic carcinoma stage, incidence of cirrhosis, and other preoperative indices. However, a higher percentage of patients in the PN group had abnormal preoperative hepatic function by indocyanine green clearance (67 vs 47%, p = 0.03). The proportion undergoing major hepatectomy and other important intraoperative factors were similar between groups. No significant difference in postoperative hospital mortality occurred between groups (PN 8% vs control 15%; p = 0.30), and PN use did not change hand-grip strength, skin-fold thickness or midarm circumference. However, a significant beneficial effect of PN on hospital morbidity was observed Perioperative PN use was associated with a significant reduction in the overall postoperative morbidity rate (PN group 34% vs control group 55%; p = 0.02). This difference was mainly due to a significant reduction in infectious complications (PN 17% vs control 37%; p = 0.01), and in the need for diuretic drugs to control ascites (PN 25% vs control 50%; p = 0.004). There were no differences between groups in serum immunoglobulins or lymphocyte response to mitogens. There was less deterioration of liver function with PN as measured by the change in the rate of indocyanine green clearance (PN group -2.8% loss vs control group -4.8% loss; p = 0.05). The attenuation of hepatic function loss with PN occurred despite a significant rise in serum transaminase values from days 5 to 8 postoperatively. PN therapy was also associated with le"
1,"TITLE: Obese patients with type 2 diabetes poorly controlled by insulin and metformin: effects of adjunctive dexfenfluramine therapy on glycaemic control.ABSTRACT: Dexfenfluramine is well known for its weight reducing action and has been reported to improve glycaemic control in obese Type 2 diabetic patients not adequately controlled on conventional oral hypoglycaemic therapy. In this double-blind placebo-controlled study, 20 obese Type 2 diabetic patients with mean HbA1c of 8.8 +/- 0.5% (normal range 3.5-6.0%), and mean body mass index (BMI) of 34.4 +/- 1.0 kg m-2, who were poorly controlled on insulin (mean dosage 58.0 +/- 6.1 units day-1) were randomized to receive either additional dexfenfluramine or placebo for 12 weeks. Seventeen of these patients were already taking maximum tolerated metformin therapy (mean dosage 1.6 +/- 0.2 g day-1) and the other three were unable to tolerate any at all. At baseline, the dexfenfluramine and placebo groups were similar in all parameters studied. After the 12-week treatment period, median HbA1c had fallen in dexfenfluramine treated patients from 8.5 (interquartile range (IR): 7.5-10.3) to 7.1% (IR: 6.7-7.5; p < 0.02). The fall in HbA1c in individual patients after treatment with dexfenfluramine was strongly associated with weight loss (r = 0.69; p < 0.04), although as a group the changes in weight and BMI were not statistically significant. Placebo was without effect. These results show that in the obese patient with Type 2 diabetes who is poorly controlled despite large daily doses of insulin and metformin, adjunctive dexfenfluramine can improve glycaemic control without exacerbating weight gain."
1,"TITLE: Treatment of Candida-infected denture stomatitis with a miconazole lacquer.ABSTRACT: The efficacy of a topically administered miconazole denture lacquer was compared with that of a placebo lacquer in the treatment of Candida-infected denture stomatitis. The study was a double-blind, randomized, controlled clinical trial with two parallel treatment groups. The lacquer was applied once on the fitting denture surface. Follow-up examinations took place on days 3, 7, 14, 21, 28, and 35. On day 14 the effect of the treatment was assessed. Thirty-six patients were included in the statistical analysis. Eighteen received miconazole and 18 received placebo lacquer. Primary efficacy endpoints were the number of colonies cultured from the palatal mucosa and denture surface on day 14. Thirteen of 16 patients in the miconazole group A showed < 10 colonies on culture medium on day 14 in the specimens from the palatal mucosa as did 5 of 18 patients in the placebo group B (p < 0.05). Corresponding results for the denture surface were 6 of 17 and 3 of 18, respectively (p < 0.05). Reapplication of lacquer was considered necessary (> 100 colonies in at least one sampling site within 14 days) in 35% of the patients from group A and in 83% of the patients from group B. The results indicate that a single application of a miconazole denture lacquer considerably reduces the number of Candida yeasts for a substantial period of time."
1,"TITLE: Jogging or walking--comparison of health effects.ABSTRACT: The present study compared the different health effects of 6 months' endurance training at two exercise intensities. Seventy-five nonsmoking, sedentary men were randomly assigned to either a home-based, unsupervised exercise program of 4 x 30 min/wk jogging at an intensity of 75% VO2max (n = 28), or of 6 x 30 min/wk walking at an intensity of 50% VO2max (n = 28), or to an inactive control group (n = 19). Exercise adherence and injuries related to exercise training as well as changes in endurance capacity, body fat, and serum lipids were assessed. After 6 months, joggers and walkers showed a similar increase in VO2max as measured by a maximal bicycle ergometer test (2.9 +/- 4.1 ml/kg min, P < 0.01 and 2.5 +/- 5.7 ml/kg min, P < 0.5, respectively). There were no significant changes in blood lipids in either group, although results revealed a significant association between the amount of training (i.e., kilometers exercised) and the increase in high-density lipoprotein-cholesterol (HDL-C) in joggers (Pearson's r = 0.42, P < 0.05). In walkers, a significant association between the amount of exercise and the decrease in sum of skinfolds and the waist-hip ratio was observed (Pearson's r = -0.48 and -0.45, P < 0.05 for both). The adherence rate was similar for both training groups with respect to the prescribed intervention goal with an average of 90 +/- 41 min/wk (joggers) and 121 +/- 72 min/wk (walkers) spent on endurance training.(ABSTRACT TRUNCATED AT 250 WORDS)"
1,"TITLE: Inhibition of 5-hydroxytryptamine re-uptake impairs human gall-bladder emptying.ABSTRACT: 5-Hydroxytryptamine (5-HT) is an important neurotransmitter in the enteric nervous system. The intrinsic neural plexus of the gall-bladder resembles the enteric nervous system and similarly contains 5-HT neurones. The action of 5-HT on gallbladder motility has been investigated in animals but its effect on the human gall-bladder in vivo is unknown.The effect of indirect 5-HT agonism using paroxetine, a specific inhibitor of neuronal 5-HT reuptake, on gall-bladder motility was investigated in 12 healthy volunteers. In a randomized double-blind crossover design, gall-bladder motility was assessed after administration of 30 mg paroxetine daily for two days and after placebo. Ultrasonography was used to determine gall-bladder volumes while fasting and at 5 min intervals following a 250 kcal mixed liquid meal.Fasting gall-bladder volumes of 21.8 +/- 3.2 ml on placebo and 28.0 +/- 3.5 ml on paroxetine were similar. Paroxetine impaired postprandial gall-bladder emptying. Residual gall-bladder volume was 10.2 +/- 2.7 ml with placebo and 17.1 +/- 2.7 ml with paroxetine (P < 0.05). Ejection fraction was 57.3 +/- 7.7% on placebo and 40.9 +/- 4.7% on paroxetine (P < 0.05).5-HT pathways may participate in the regulation of biliary motility, and this study demonstrates an inhibitory role of 5-HT in the control of human gall-bladder emptying."
1,"TITLE: The effects of single oral doses of 17 beta-oestradiol and progesterone on finger skin circulation in healthy women and in women with primary Raynaud's phenomenon.ABSTRACT: The effects of sex, the menstrual cycle, oral contraceptives, pregnancy, and the menopause on skin perfusion in healthy women and in patients with Raynaud's phenomenon suggest a role of female sex hormones. However, no clear relation between skin blood flow and circulating concentrations of oestrogens or progestogens has yet been found. The aim of this study was to investigate the effect of orally administered 17 beta-oestradiol and progesterone on finger skin blood flow before and during heat and cold challenge in 17 healthy normotensive women and in 12 women with Raynaud's phenomenon. In each subject standardized finger heating (45 degrees C water bath, 10 min) and cooling tests (15 degrees C water bath, 5 min and 20 min recovery) were performed twice on the second (or third) day of two consecutive menstrual cycles. 17 beta-Oestradiol (9 mg) or progesterone (300 mg) were given before the second test, after a first test with placebo. Both hormonal doses resulted in (high) physiological concentrations. Fingertip skin temperature and laser Doppler flux were measured. There were no significant differences in the test results after placebo and after progesterone. Although values of fingertip skin temperature and laser Doppler flux after 17 beta-oestradiol tended to be higher only the precooling values in the healthy subjects reached significance: fingertip skin temperature respectively with placebo and with oestradiol (mean (SD)): 32.7 (1.0) and 33.1 (0.8) degrees C; laser Doppler flux with placebo and with oestradiol: 33.6 (11.7) and 42.2 (9.5) perfusion units; both P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)"
0,"TITLE: Effects of oral ranitidine, famotidine and omeprazole on gastric volume and pH at induction and recovery from general anaesthesia.ABSTRACT: We have studied, in 150 patients undergoing elective general surgery, the effect on gastric content of omeprazole 40 mg, ranitidine 300 mg and famotidine 40 mg, given orally the night and the morning before surgery. Volume and pH of gastric content were measured at induction and recovery from anaesthesia. Gastric volumes did not differ between groups. The median gastric pH was lower with omeprazole compared with ranitidine and famotidine at intubation (5.11, 7.05 and 6.99, respectively) (P < 0.001) and extubation (6.41, 6.98 and 6.96) (P < 0.001). The proportion of patients with gastric pH < 2.5 at induction was 40% for omeprazole, 12% for famotidine and 10% for ranitidine (P < 0.02); the proportion did not differ significantly at extubation."
1,"TITLE: Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. RADIANCE Study.ABSTRACT: Although digoxin is effective in the treatment of patients with chronic heart failure who are receiving diuretic agents, it is not clear whether the drug has a role when patients are receiving angiotensin-converting-enzyme inhibitors, as is often the case in current practice.We studied 178 patients with New York Heart Association class II or III heart failure and left ventricular ejection fractions of 35 percent or less in normal sinus rhythm who were clinically stable while receiving digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor (captopril or enalapril). The patients were randomly assigned in a double-blind fashion either to continue receiving digoxin (85 patients) or to be switched to placebo (93 patients) for 12 weeks. Otherwise, their medical therapy for heart failure was not changed.Worsening heart failure necessitating withdrawal from the study developed in 23 patients switched to placebo, but in only 4 patients who continued to receive digoxin (P < 0.001). The relative risk of worsening heart failure in the placebo group as compared with the digoxin group was 5.9 (95 percent confidence interval, 2.1 to 17.2). All measures of functional capacity deteriorated in the patients receiving placebo as compared with those continuing to receive digoxin (P = 0.033 for maximal exercise tolerance, P = 0.01 for submaximal exercise endurance, and P = 0.019 for New York Heart Association class). In addition, the patients switched from digoxin to placebo had lower quality-of-life scores (P = 0.04), decreased ejection fractions (P = 0.001), and increases in heart rate (P = 0.001) and body weight (P < 0.001).These findings indicate that the withdrawal of digoxin carries considerable risks for patients with chronic heart failure and impaired systolic function who have remained clinically stable while receiving digoxin and angiotensin-converting-enzyme inhibitors."
1,"TITLE: Effectiveness of a nicotine patch in helping people stop smoking: results of a randomised trial in general practice. Imperial Cancer Research Fund General Practice Research Group.ABSTRACT: To assess the effectiveness of 12 weeks' treatment with a 24 hour transdermal nicotine patch in helping heavy smokers to stop smoking; also to assess the value of a specially written support booklet about smoking cessation and patch use compared with a simple advice pamphlet.Double blind placebo controlled randomised trial with a 2 x 2 factorial design.19 general practices in Oxfordshire.1686 heavy smokers aged 25-64 (mean cigarette consumption 24/day; mean duration of smoking 25 years).Sustained cessation for the last four weeks of the 12 week treatment period, confirmed by saliva cotinine estimation (226/262 cases; 86.3%) or expired carbon monoxide concentration (36/262; 13.7%). Patients lost to follow up (155/1686; 9%) were assumed to have continued to smoke.Cessation was confirmed in 163 patients (19.4%) using the nicotine patch and 99 patients (11.7%) using the placebo patch (difference 7.6% (95% confidence interval 4.2% to 11.1%); p < 0.0001). There was no significant advantage in using the more detailed written support material. The most important adverse effect of the patch was local skin irritation, which occurred in 15.8% (133/842) and 5.1% (43/844) of patients using the nicotine and placebo patches respectively, was graded as severe in 4.8% (40) and 1.1% (nine), and was stated as a reason for withdrawal from the trial in 9.5% (80) and 2.8% (24).Nicotine patches are effective in a general practice setting with nursing support, but the extent to which this effect is sustained cannot be assessed until the results of longer term follow up are known."
0,"TITLE: Five years of physical exercise and low fat diet: effects on progression of coronary artery disease.ABSTRACT: This study was designed to assess the long-term effects of low-fat diet and intensive physical exercise.Long-term efficacy of exercise and diet was assessed in 18 nonselected, fully employed patients with symptomatic coronary artery disease. Results were compared to 18 patients on usual care.In the intervention group at 1 year, serum lipoproteins were brought to ideal levels, exercise-induced myocardial ischemia was significantly reduced, and progression in coronary atherosclerosis was retarded. After more than 5 years, patients in the intervention group showed a significant reduction in lipoprotein levels (total cholesterol, 248 [179-299] vs 214 [173-272] mg/dL, P < .01; low density lipoprotein, 146 [83-216], vs 152 [121-197] mg/dL, P < .005 vs control; triglycerides; 151 [80-303] mg/dl, vs 98 [46-182] mg/dL; P < .005) and body mass index (26 +/- 2.9 vs 25.4 +/- 3.3 kg/m2; P < .05). Exercise induced myocardial ischemia, measured by 201thallium scintigraphy, decreased by 29% (41 degrees +/- 36 degrees vs 29 degrees +/- 29 degrees, P = NS) and coronary atherosclerosis, assessed by angiography and digital image processing, progressed at a slower pace in light of a 21% increase in physical work capacity (169 +/- 40 vs 205 +/- 50, P < .01) and a 28% increase in maximal rate pressure product (25 +/- 6 vs 32 +/- 4, P < .004). In contrast, patients in the control group showed only poorly controlled coronary risk factors (total cholesterol, 243 [179-306] vs 26 [178-304] mg/dL, P = NS; low density lipoprotein, 151 [79-229] vs 196 [107-238] mg/dL, P < .0005 vs intervention; body mass index 25.7 +/- 2.5 vs 27.5 +/- 3.5 kg/m2, P < .01), whereas their physical work capacity tended to deteriorate (165 +/- 45 vs 142 +/- 62 Watts, P = not significant).These data demonstrate that current usual care is insufficient in controlling risk factors of coronary artery disease. However, intensive physical exercise and low-fat diet remain an effective form of treatment after more than 5 years."
1,"TITLE: Increase of birth weight following chloroquine chemoprophylaxis during the first pregnancy: results of a randomized trial in Cameroon.ABSTRACT: A randomized trial was carried out from 1991 to 1993 among women attending an antenatal clinic in Ebolowa, Cameroon where malaria is hyperendemic and transmission occurs at a high level all year round. All pregnant women attending the clinic for their first prenatal visit between October 1991 and November 1992 were alternately assigned to chloroquine (CQ) or control (CT) groups. Chloroquine was given under observation at a weekly oral dose of 300 mg. At delivery, smears from maternal, cord, and placental blood were made and stained with Giemsa for parasites. An in vivo chloroquine sensitivity investigation was carried out on women attending the postnatal consultation to evaluate the level of chloroquine resistance in the target population. The efficacy of chloroquine was moderate in placental infection (39.2% infected in the CQ group versus 57.8% in the CT group: P = 0.05), probably because of a resistance to chloroquine estimated to be 10.9%. In the CQ group, the mean birth weight was significantly higher (P = 0.02) and the proportion of low birth weight newborns was lower (10.5% versus 27.7%; P = 0.02). A strong correlation between placental infection and birth weight was observed: the mean birth weight difference between infected and noninfected placentae was 359 g (P < 0.0001) and the proportion of low birth weight new born babies was 35.6% versus 5.9% (P = 0.0001). In Cameroon, in spite of a moderate resistance to chloroquine, this drug proved to be highly effective in increasing birth weight when administered to primigravidae. We therefore think such a prophylaxis should be recommended only to primigravidae in high transmission areas."
1,"TITLE: A controlled trial of verapamil in patients after acute myocardial infarction: results of the calcium antagonist reinfarction Italian study (CRIS)ABSTRACT: A multicenter, double-blind, randomized, placebo-controlled trial was conducted to assess the effects of verapamil on total mortality, cardiac mortality, reinfarction, and angina after an acute myocardial infarction. All patients, aged 30 to 75 years, consecutively admitted for acute myocardial infarction between 1985 and 1987 to the participating centers, and without contraindications to verapamil or history of severe heart failure were enrolled. Seven to 21 days (mean 13.8) after myocardial infarction, 531 patients were randomized to verapamil retard 360 mg/day, and 542 patients to placebo. At baseline, the 2 groups of patients had similar characteristics. Mean age was 55.5 years and 91% were men. During a mean follow-up of 23.5 months, 5.5% of the patients died. No differences between verapamil and placebo were observed in total mortality (n = 30 and 29, respectively) and cardiac death (n = 21 and 22, respectively). The verapamil group had nonsignificant lower reinfarction rates (n = 39 vs 49). The number of patients developing angina was significantly less in the verapamil group (n = 100 vs 132, RR = 0.8, 95% confidence interval 0.5 to 0.9). There were no differences in discontinuation of therapy caused by adverse reactions. This trial showed no effect of verapamil on mortality. The lower reinfarction rates found in the verapamil group are in agreement with the results of other studies."
1,"TITLE: Single- versus multiple-dose mezlocillin prophylaxis in emergency cesarean section.ABSTRACT: 163 patients undergoing emergency cesarean section were prospectively and randomized evaluated to determine the effect of mezlocillin in reducing postoperative morbidity. We compared a single 5-gram preoperative dose and a perioperative 3-dose regimen, each of 2 g, with a placebo. Postoperative morbidity was reduced from 65% in the placebo group to 20% in the groups receiving mezlocillin (p less than 0.005). The incidences of febrile morbidity, endometritis and urinary tract infection were all significantly lower in both groups given mezlocillin. There was no difference in the reduction of morbidity between the two groups receiving mezlocillin. The main advantages of the prophylaxis included a shorter hospitalization and the absence of serious infections in the treated groups."
1,"TITLE: Intravenous propafenone for termination of reentrant supraventricular tachycardia. A placebo-controlled, randomized, double-blind, crossover study.ABSTRACT: To assess the antiarrhythmic efficacy of intravenous propafenone, 20 patients with inducible sustained supraventricular tachycardia received propafenone, 2 mg/kg body weight, or placebo in a double-blind, randomized, crossover study. Three patients had intra-atrial reentrant tachycardia, 3 had atrioventricular nodal reentrant tachycardia, and 14 had atrioventricular reciprocating tachycardia associated with the Wolff-Parkinson-White syndrome. Termination of supraventricular tachycardia occurred in 15 of the 20 patients receiving propafenone but 0 of the 11 patients receiving placebo (p less than 0.01). Propafenone prolonged refractoriness and slowed conduction of the atrium, the atrioventricular node, and accessory atrioventricular bypass tracts, and these effects provided antiarrhythmic action to halt tachycardia. No adverse effects were observed in any patient. We conclude that intravenous propafenone is safe and effective in the acute treatment of various forms of reentrant supraventricular tachycardia."
1,"TITLE: Comparison of spectinomycin hydrochloride and aqueous procaine penicillin G in the treatment of uncomplicated gonorrhea.ABSTRACT: Men and women with uncomplicated gonorrhea were randomly assigned to receive aqueous procaine penicillin G (2,400,000 U for men; 2,400,000 U daily for 2 days for women) or spectinomycin hydrochloride (2.0 g for men; 4.0 g for women). Among men who returned for post-treatment evaluation within 10 days, treatment failures were noted among 16 (20.3%) of 79 men who received penicillin and 8 (9.5%) of 84 men who received spectinomycin (P < 0.1). Similarly, 6 (13.3%) of 45 women who received penicillin and 3 (6.5%) of 46 women who received spectinomycin had positive endocervical cultures for Neisseria gonorrhoeae at the time of the post-treatment examination (P = not significant)."
1,"TITLE: Angiotensin converting enzyme during acute and chronic enalapril therapy in essential hypertension.ABSTRACT: The acute and chronic effects of enalapril (MK421) were assessed in a double-blind randomized trial in subjects with essential hypertension. In acute studies, twelve subjects received enalapril (10 mg p.o.), following which there was a fall in blood pressure, maximal at 6 h and lasting for 24 h. Serum MK422 (enalaprilic acid, the bioactive form of enalapril) and serum angiotensin converting enzyme (ACE) inhibition had a similar time course with good correlation between drug levels and ACE inhibition (P less than 0.001, r = 0.98, n = 16) and between ACE inhibition and the hypotensive effect (P less than 0.001, r = 0.84, n = 16). In chronic studies enalapril was titrated from 5 mg to 20 mg twice a day in eleven hypertensive patients to achieve a diastolic blood pressure less than 90 mmHg. Treatment continued for 3-12 months. Increasing serum MK422 was correlated with reducing serum ACE activity (P less than 0.001, r = 0.8, n = 104). The fall in blood pressure correlated both with serum MK422 level (P less than 0.05, r = 0.37, n = 39) as well as ACE inhibition (P less than 0.01, r = 0.45, n = 42). The drug level:ACE inhibition curve was shifted to the right during chronic enalapril treatment. ID50 for serum ACE was 32 ng MK422/ml following the single 10 mg dose of MK421 and 70 ng MK422/ml during chronic treatment. Blood pressure falls during acute and chronic treatment were similar over the range of serum MK422 levels achieved. The shift in the drug level:ACE inhibition curve suggests induction of ACE during chronic treatment with enalapril in man."
1,"TITLE: Desflurane analgesia for vaginal delivery.ABSTRACT: The use of subanaesthetic concentration of inhalational anaesthetic for vaginal delivery offers many advantages to the mother and newborn. Desflurane, with the characteristics of rapid onset and minimal metabolism, may provide better analgesia and safety for labour pain control. Eighty healthy parturients were randomly assigned to receive either desflurane 1.0-4.5% and oxygen (n = 40) or nitrous oxide 30-60% in oxygen (n = 40). Analgesia was assessed using a score from 0 (no relief) to 4+ (excellent analgesia), amnesia for the delivery, blood loss were recorded. Neonates were evaluated by Apgar scores and neurologic and adaptive capacity scores (NACS). Data were analyzed for statistical significance using Student's t-test or Chi-square when appropriate. Analgesia scores were similar for both groups with more amnesia in desflurane group (23% vs 0% P < 0.05). Blood loss did not differ significantly, 364 ml for the desflurane group and 335 ml for the nitrous oxide group. There were no significant differences for neonatal Apgar score at 1 min or at 5 min or the NACS at 2 hr or 24 hr between the two groups. We conclude that desflurane in subanaesthetic doses is safe and effective inhalation agent for normal delivery but might be associated with amnesia."
0,"TITLE: Human immunodeficiency virus type 1 quantitative cell microculture as a measure of antiviral efficacy in a multicenter clinical trial.ABSTRACT: A quantitative cell microculture assay (QMC) was used to measure the human immunodeficiency virus type 1 (HIV-1) peripheral blood mononuclear cell (PBMC)-associated titer in 109 subjects rolled in an open-label phase I/II study of didanosine monotherapy or combination therapy with zidovudine. The titer was inversely correlated with CD4+ cell count at baseline (r = .37, P = .001). After 12 weeks of therapy, subjects showed a significant decreases in virus titer and those with the highest baseline virus titers had the greatest increase in CD4+ cell number (r = .430, P = .002). The QMC assay was more sensitive (98%) for assessing the antiretroviral effect of therapy than was immune complex-dissociated HIV p24 antigen (32%) or plasma culture (3.4%). Estimated sample sizes for phase I/II clinical trials were derived using the within-subject QMC SD of .72 log10 infectious units per 10(6) PMBC."
1,"TITLE: Inhibition of steroid 5 alpha-reductase with finasteride: sleep-related erections, potency, and libido in healthy men.ABSTRACT: To objectively measure the effects of a 5 alpha-reductase inhibitor on erectile function, we studied 20 sexually active men (aged 41-64 yr) during double blind, randomized administration of 5 mg/day finasteride (F) or placebo (P). Serum testosterone and dihydrotestosterone (DHT) were measured every 4 weeks. Sleep-related erections were assessed with comprehensive polysomnography for 2 nights before randomization (session 1) and at week 12 (session 2). Sexual function questionnaires were administered weekly. Serum DHT levels at week 0 were 1.47 +/- 0.11 and 1.16 +/- 0.27 nmol/L (P > 0.05) in the P and F groups, respectively. F group levels fell to 31% and 28% of control values at week 4 and 12. Penile tip peak tumescence time increased on second nights more in the P than the F group at 12 weeks, producing a session main effect (P < 0.02) and a group X session interaction (P < 0.05). No significant group X session interactions were found for any sleep erection measures in a best night analysis or for self-reported sexual activity. Thus, F did not consistently suppress sleep-related erections compared to P. F primarily inhibits type 2 5 alpha-reductase activity; however, type 1 5 alpha-reductase is the major enzyme in the central nervous system. Therefore, DHT involvement in the maintenance of libido and potency is not excluded. Nonetheless, these data support the feasibility of using a type 2 inhibitor to treat benign prostatic hyperplasia without impairing erectile function."
1,"TITLE: Endothelin-1 in pulmonary hypertension associated with high-altitude exposure.ABSTRACT: Endothelin-1 is involved in chronic pulmonary hypertension. Its role in acute pulmonary hypertension due to hypoxia in humans is not clear. We therefore studied the influence of hypoxia caused by exposure to high altitude on plasma endothelin-1 levels, arterial blood gases, and pulmonary arterial pressure in subjects taking nifedipine or placebo.Twenty-two healthy volunteers were investigated at low altitude (490 m) and high altitude (4559 m). Arterial blood gases were analyzed immediately, endothelin-1 was measured by radioimmunoassay, and pulmonary artery pressure was assessed by Doppler echocardiography. After baseline investigations, the mountaineers were allocated in a randomized double-blind fashion to receive either placebo or nifedipine (20 mg TID) during rapid ascent to high altitude within 22 hours. Tests were repeated at the high-altitude research laboratories located in the Capanna ""Regina Margherita"" (Italy, 4559 m). Plasma endothelin-1 was increased twofold at high altitude (5.9 +/- 2.2 pg/mL compared with 2.9 +/- 1.1 pg/mL, P < .05), was inversely related to arterial PO2 (r = -.46, P < .001), and correlated with pulmonary artery pressure (r = .52, P < .002). At high altitude, arterial endothelin-1 was lower (4.3 +/- 1.6 pg/mL) than venous endothelin-1 (5.9 +/= 2.2 pg/mL, P < .001), indicating either predominant production in the venous vasculature or pronounced clearance in the pulmonary circulation. The calcium antagonist nifedipine, which lowered pulmonary artery pressure at high altitude (32 +/- 5 versus 42 +/- 11 mm Hg, P < .05), had no influence on plasma endothelin-1 levels. The administration of 35% O2 at high altitude normalized arterial PO2, tended to decrease endothelin-1, and decreased pulmonary artery pressure accordingly.We conclude that plasma endothelin-1 is increased at high altitude, but whether or not it represents an important pathogenetic factor for pulmonary hypertension remains to be investigated."
1,"TITLE: Indomethacin but not metoprolol reduces exercise-induced albumin excretion rate in type 1 diabetic patients with microalbuminuria.ABSTRACT: The effects of a single oral dose of indomethacin (1 mg kg-1) metoprolol (1.5 mg kg-1) and placebo on exercise-induced albumin excretion rate (AER) were compared in a randomized, crossover design in 14 normotensive, young Type 1 diabetes patients, nine of them with microalbuminuria (AER > 15 micrograms min-1) and five without microalbuminuria at rest. The albumin excretion rate, blood pressure, heart rate, blood glucose, and plasma concentrations of indomethacin and metoprolol were determined before and after 30 min submaximal physical exercise. In microalbuminuric patients the rise in albumin excretion rate after exercise on indomethacin (7 micrograms min-1) was lower than after placebo (29 micrograms min-1, p < 0.001) whereas the rise in albumin excretion rate with metoprolol during exercise (18 micrograms min-1) did not differ from placebo (p = 0.48), in spite of the expected less marked increase in blood pressure. In normoalbuminuric patients no significant increase in albumin excretion rate was noted by exercise in any of the treatment periods. A tendency to a linear correlation (r = -0.54, p = 0.07) was seen between the plasma concentration of indomethacin and the inhibition of exercise-induced increase in albumin excretion rate. No correlations were observed between exercise-induced changes in albumin excretion rate and systolic blood pressure, heart rate or blood glucose. In conclusion, acute indomethacin treatment, presumably through inhibition of renal prostaglandin synthesis, reduces the exercise-induced rise in albumin excretion rate in Type 1 diabetic patients with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)"
1,"TITLE: Efficacy of lenograstim on hematologic tolerance to MAID chemotherapy in patients with advanced soft tissue sarcoma and consequences on treatment dose-intensity.ABSTRACT: This two-arm, double-blind, randomized trial was conducted to determine the effects of lenograstim, a glycosylated recombinant human granulocyte colony-stimulating factor (rHu-G-CSF), on the hematologic tolerance of patients with sarcoma treated with mesna, doxorubicin, ifosfamide, and doxorubicin (MAID) chemotherapy.Forty-eight patients with metastatic or locally advanced soft tissue sarcoma were, following the first cycle of a combination with doxorubicin 60 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2 given on days 1 to 3, randomized to receive either lenograstim 5 micrograms/kg/d by once-daily injection from day 4 to day 13, or its vehicle. For subsequent cycles, 28 patients continued on the same chemotherapy and lenograstim was systematically given as prophylactic treatment in an open manner.Following the first cycle of MAID, the duration of neutropenia was reduced in patients who received lenograstim as compared with those who received placebo, with a median duration of neutropenia ( < 0.5 x 10(9)/L neutrophils) of 0 days (range, 0 to 3) and 5 days (range, 0 to 10), respectively (P < .001). All patients who received lenograstim had recovered at least 1 x 10(9)/L neutrophils (polymorphonuclear lymphocytes [PMN]) on day 14, compared with only one of 26 in the placebo group (P < .001). The median time to recover this neutrophil level was 12 days (range, 10 to 13) and 17 days (range, 14 to 21), respectively (P < .001). Neutropenic fever occurred in five (23%) and 15 (58%) patients respectively (P = .02). Twenty-eight patients received at least two cycles (median, four) of MAID at the same dose. Toxicity remained constant across all treatment cycles. A progressive increase in thrombocytopenia was noted, with median platelet nadirs of 102 x 10(9)/L at cycle 2 and 19.5 x 10(9)/L at cycle 6, but did not result in significant treatment modifications. Consequently, median relative dose-intensities remained greater than 0.95 for up to six consecutive MAID cycles.Lenograstim significantly improved hematologic tolerance in patients treated with the MAID chemotherapy regimen and, therefore, allowed optimal adhesion to the theoretic doses planned for up to six cycles. Whether such an optimization in relative dose-intensity will result in an improvement of treatment efficacy remains to be determined."
0,"TITLE: Open-label study to assess the efficacy, safety, and tolerability of fluvastatin versus bezafibrate for hypercholesterolemia.ABSTRACT: Increased levels of total cholesterol and low density lipoprotein cholesterol (LDL-C) are associated with the development of coronary artery disease, which has become a worldwide public health problem. Clinical trials show that, in the long term, effective lowering of total cholesterol and raising of high density lipoprotein cholesterol (HDL-C) can slow atherosclerosis progression and reduce coronary artery disease risk. This study evaluated the efficacy, safety, and tolerability of fluvastatin versus bezafibrate (slow release) in patients with cholesterol > 241 mg/dL (6.2 mmol/liter) not responding to dietary treatment alone (cholesterol < 300 mg/day for 8 weeks). Patients were divided into 2 groups: group A (13 women, 7 men; mean age, 47.8 +/- 9.7 years; range, 30-70) received 40 mg fluvastatin once daily with their evening meal; group B (14 women, 6 men; mean age, 45 +/- 11 years, range, 25-68) received 400 mg bezafibrate once daily with either breakfast or their evening meal. After 12 weeks of treatment, the mean cholesterol decrease in group A was 27% (from 271 +/- 51.4 to 197.4 +/- 24.3 mg/dL; p < 0.001) versus 8% (from 278.6 +/- 33.2 to 255.8 +/- 20.3 mg/dL; p < 0.005) in group B. At the same time point, LDL-C was significantly decreased in group A (from 197.9 +/- 49 to 107.5 +/- 27.6 mg/dL; p < 0.001) but not in group B (from 181.6 +/- 39.6 to 173.3 +/- 24.3 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)"
1,"TITLE: Hemodynamic responses to intravascular injection of epinephrine-containing epidural test doses in adults during general anesthesia.ABSTRACT: Epidural anesthesia is sometimes initiated during general anesthesia, yet few data exist concerning efficacy of epinephrine-containing test doses.Thirty-six patients were randomized to receive either 0.5 MAC isoflurane, 1 MAC isoflurane, or 0.5 MAC each (1 MAC total) of isoflurane and nitrous oxide. Each subject received intravenous saline followed by three test doses containing 45 mg lidocaine with 7.5, 15, and 30 micrograms epinephrine in a randomized, double-blind fashion. Heart rate and systolic, diastolic, and mean blood pressures were measured for 5 min after injection. Positive hemodynamic criteria identifying intravascular injection were determined from peak increases in hemodynamics during administration of saline. Dose-effect relationships between epinephrine and peak increases in hemodynamics were assessed with linear regression. Minimum required doses of epinephrine to produce peak positive hemodynamic increases on average were determined from linear regression.Positive hemodynamic criteria were identified as increases in heart rate > or = 8 beats/min, systolic blood pressure > or = 13 mmHg, diastolic blood pressure > or = 7 mmHg, and mean blood pressure > or = 9 mmHg. Significant dose-effect relationships were observed for epinephrine and peak increases in hemodynamics (correlation coefficients ranged from 0.61-0.91). Minimum required doses of epinephrine ranged from 6 to 19 micrograms depending on hemodynamic measurement and anesthetic group.Hemodynamic responses to intravascular injection of test doses vary with dose of epinephrine and depth and type of general anesthetic used. Thus, the 15 micrograms epinephrine contained in the standard test dose may not be sufficient during all anesthetic conditions."
1,"TITLE: Effects of nedocromil sodium in steroid-resistant asthma: a randomized controlled trial.ABSTRACT: Some patients with asthma respond poorly to corticosteroids and have persistent airway inflammation and daily clinical symptoms. The aim of this study was to investigate the effects of nedocromil sodium (NS), a nonsteroidal antinflamatory drug, in the treatment of steroid-resistant asthma.Steroid-resistant asthma as diagnosed in any patient who demonstrated 20% improvement in FEV1 after treatment with inhaled salbutamol with failure of FEV1 to improve by at least 15% after a 2-week trial of prednisolone, 30 mg daily. In a double-blind placebo-controlled trial, the patients received either 4 mg of inhaled NS (n = 13) or placebo (n = 13), 4 times daily for 3 months.NS but not placebo resulted in a mean increase in FEV1 of 11.4% after 12 weeks of therapy (p = 0.05) and of 12.4% (p = 0.04) and 15% (0.02) in morning peak expiratory flow after 8 and 12 weeks of treatment, respectively. Changes in FEV1 at 4 and 8 weeks and in peak expiratory flow at 4 weeks of NS therapy were not significant. NS was also effective in reducing variability of peak expiratory flow (p = 0.02) and use of salbutamol (p = 0.005) and in improving quality of life (p = 0.007) by the trial end. Six of the 12 patients treated with NS who completed the treatment period showed a ""good response,"" defined by a reduction in salbutamol use of more than 50% and an increase in morning peak expiratory flow of more than 20% from baseline; there were no clinical predictors of this response. Two patients were withdrawn from the study because of severe asthma exacerbation (one from each treatment group).Inhaled NS improved pulmonary function and decreased asthma severity in steroid-resistant asthma, but its effectiveness is not homogeneous and cannot be predicted from baseline clinical data."
1,"TITLE: Improvement of exercise capacity with treatment of Cheyne-Stokes respiration in patients with congestive heart failure.ABSTRACT: The aim of this study was to determine the impact of nasal nocturnal oxygen therapy on respiration, sleep, exercise capacity, cognitive function and daytime symptoms in patients with congestive heart failure and Cheyne-Stokes respiration.Cheyne-Stokes respiration is common in patients with congestive heart failure and is associated with significant nocturnal oxygen desaturation and sleep disruption with arousals. Oxygen desaturations and arousals cause an increase in pulmonary artery pressure and sympathoneural activity and therefore may reduce exercise capacity. Oxygen is an effective treatment of Cheyne-Stokes respiration and should improve exercise capacity in these patients.The study was designed as a randomized crossover, double-blind, placebo-controlled trial: 22 patients were assigned to 1 week each of nocturnal oxygen and room air. After each week, polysomnography, maximal bicycle exercise with expiratory gas analysis and trail-making test were performed, and a health assessment chart was completed.Nocturnal oxygen significantly reduced the duration of Cheyne-Stokes respiration (162 +/- 142 vs. 88 +/- 105 min [mean +/- SD]; p < 0.005). Sleep improved as evidenced by less stage 1 sleep and fewer arousals (20 +/- 13 vs. 15 +/- 9/h total sleep time; p < 0.05) as well as more stage 2 and slow-wave sleep; nocturnal oxygen saturation also improved. Peak oxygen consumption during exercise testing increased after oxygen treatment (835 +/- 395 vs. 960 +/- 389 ml/min; p < 0.05). Cognitive function evaluated by the trail-making test improved, but daytime symptoms in the health assessment chart did not improve significantly.Successful treatment of Cheyne-Stokes respiration with nocturnal nasal oxygen improves not only sleep, but also exercise tolerance and cognitive function in patients with congestive heart failure."
0,"TITLE: Risks for sensorimotor peripheral neuropathy and autonomic neuropathy in non-insulin-dependent diabetes mellitus (NIDDM).ABSTRACT: Identification of risk factors for development of diabetic sensorimotor peripheral neuropathy (DSPN) and diabetic autonomic neuropathy (DNA) may help to prevent or modify these complications. The ABCD Trial, a prospective study of diabetic complications, has identified risk factors of the presence and staging of peripheral neuropathy based on neurological symptom scores, neurological disability scores, autonomic function testing and quantitative sensory examination. DSPN is independently associated with diabetes duration [odds ratio (OR) = 1.5 per 10 years], body weight (OR = 1.1 per 5 kg), age (OR = 1.8 per 10 years), retinopathy (OR = 2.3), overt albuminuria (OR = 2.5), height (OR = 1.2 per 10 cm), duration of hypertension (OR = 1.1 per 10 years), insulin use (OR = 1.4), and race/ethnicity [African American vs. non-Hispanic white (OR = 0.4) and Hispanic vs. non-Hispanic white (OR = 0.8)]. DAN is independently associated with diabetes duration (OR = 1.2 per 10 years), body weight (OR = 1.1 per 5 kg), glycosylated hemoglobin (OR = 1.1 per 2.5%), overt albuminuria (OR = 1.6), and retinopathy (OR = 1.8)."
1,"TITLE: Healing and recurrence of active duodenal ulcer with nizatidine.ABSTRACT: Nizatidine, a new H2-receptor antagonist for treatment of duodenal ulcer disease, was evaluated in a unique two-phase, placebo-controlled, randomized, double-blind, multicenter clinical trial. Patients received either 150 mg nizatidine twice daily or placebo for 4 weeks (phase I). If ulcer healing did not occur during phase I, patients were randomly reallocated to receive either 150 mg nizatidine twice daily or placebo for an additional 4 weeks (phase II). Patients with a healed ulcer continued on the same therapy. All patients were endoscoped at week 8. Healing rates at week 2 were 93 of 265 (35%) nizatidine-treated patients and 55 of 260 (21%) placebo-treated patients (p less than 0.001); at week 4, healing rates were 198 of 259 (76%) nizatidine-treated patients and 95 of 243 (39%) placebo-treated patients (p less than 0.001). In phase II, ulcer healing occurred in 46 of 86 (53%) nizatidine-treated patients and in 23 of 90 (26%) placebo-treated patients (p = 0.002). In patients who had a healed ulcer at previous endoscopies, 18 of 178 (10%) nizatidine-treated patients and 10 of 81 (12%) placebo-treated patients had a recurrence of duodenal ulcer. Smokers who had histories of previous ulcers were more likely to have an early recurrence."
1,"TITLE: A pilot study of piracetam in cuprophan hemodialysis.ABSTRACT: Twelve patients, 8 male and 4 female, aged from 26 to 70 years were studied. They were on hemodialysis (HD) 4 h three times weekly with cuprophan hollow fiber dialyzers (Gambro 120M) and dialysate containing 35 mEq/L of acetate. The study compares two random HD sessions on each patient. Sixty minutes prior to one random session a placebo was administered orally, and prior to another random session piracetam was given at a dose of 8 g. Heparin dosage was not reduced during HD using QB 200 ml, QD 500 ml, and no ultrafiltration. Blood samples for leukocyte and platelet counts, serum C3, arterial paO2 and paCO2, thromboxane-B2 (TxB2), and beta-thromboglobulin (beta-TG) were taken from the arterial line before and at 15, 60, and 240 min during HD. Leukopenia at 15 min of HD was found to be less severe (p less than 0.01) in the piracetam study than in the placebo, whereas platelet count did not change. Serum C3 was slightly increased in both studies. Arterial oxygen was preserved close to the initial levels by piracetam (91.66 mm Hg versus 81.08, p less than 0.01 at 60 min, and 93.08 versus 80.17 mm Hg, p less than 0.01 at 240 min of HD sessions) but paCO2 did not change significantly. TxB2 increased less with piracetam in comparison to placebo (p less than 0.01 or p less than 0.001), but beta-TG was reduced significantly by piracetam at any time during HD (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)"
1,"TITLE: Experience with terazosin administered in combination with other antihypertensive agents.ABSTRACT: In a randomized, double-blind, placebo-controlled, multicenter trial, the efficacy and safety of terazosin in combination with other antihypertensive agents were assessed using patients with inadequately controlled essential hypertension (supine diastolic blood pressure 95 mm Hg or greater). Of 138 evaluable patients, the terazosin-treated group (n = 84) achieved a significant (p less than 0.05) mean reduction of 7.3 mm Hg in supine diastolic blood pressure when compared with the placebo-treated group (n = 54) who achieved a reduction of 0.6 mm Hg. Analysis of patients by background therapeutic categories (beta blocker, beta blocker plus diuretic, or ""other"") revealed that terazosin caused a significantly greater decrease in supine diastolic blood pressure than did placebo when added to the combination of beta blocker plus diuretic (decrease of 7.2 mm Hg for the terazosin group versus a decrease of 1.5 mm Hg for the placebo group) and to other antihypertensive drugs (decrease of 7.9 mm Hg for the terazosin group versus a decrease of 1.0 mm Hg for the placebo group). Significant differences between treatment groups were also observed for supine systolic and for standing systolic and diastolic blood pressure variables in select subgroups. The addition of terazosin did not cause significant changes in physical examinations or electrocardiograms. Changes in pulse rates and body weight did not differ significantly between treatment groups for any background therapeutic category. The overall incidence of adverse experiences was only somewhat greater for terazosin-treated than placebo-treated patients. These results suggest that terazosin is safe and effective when administered in combination with other antihypertensive drugs."
1,"TITLE: A randomized, double-blind trial of a gonadotropin releasing-hormone agonist (leuprolide) with or without medroxyprogesterone acetate in the treatment of leiomyomata uteri.ABSTRACT: A randomized, double-blind study was performed on 16 women to compare the efficacy of daily subcutaneous (SC) injections of leuprolide acetate (LA; TAP Pharmaceuticals, North Chicago, IL) plus oral placebo tablets (group A, n = 7) with SC LA plus oral medroxyprogesterone acetate (The Upjohn Company, Kalamazoo, MI; group B, n = 9) in the treatment of leiomyomata uteri. Patients in group A had a significant reduction in uterine size from a pretreatment volume of 601 +/- 62 cm3 (mean +/- standard error) to a mean uterine volume of 294 +/- 46 cm3 at 24 weeks of therapy (P less than 0.01). Group B patients had a reduction in uterine volume from 811 +/- 174 cm3 to 688 +/- 154 cm3, which was not statistically significant. However, only one patient in group B experienced hot flashes, whereas six patients in group A had this symptom (P less than 0.01). Both groups demonstrated significant increases in mean hemoglobin concentrations, hematocrits, and serum iron levels at 24 weeks of therapy compared with pretreatment levels."
0,"TITLE: Effects of infant nutrition on cholesterol synthesis rates.ABSTRACT: Nutrient effects on cholesterol fractional synthesis rates (FSR) in infancy by stable isotope determination have not been studied. We hypothesized that FSR is significantly reduced with high dietary cholesterol and phytoestrogen intake and increased with low dietary cholesterol and phytoestrogen intake. We prospectively studied 33 term male infants exclusively fed human milk (high cholesterol, low phytoestrogen, n = 12), cow milk-based formula (low cholesterol, low phytoestrogen, n = 8), soy milk-based formula (zero cholesterol, high phytoestrogen, n = 7), or soy milk-based formula modified to contain cholesterol (low cholesterol, high phytoestrogen, n = 6) during the first 4 mo of life. Cholesterol FSR was determined from rate of incorporation of deuterium into erythrocyte membrane cholesterol, and urinary isoflavone excretion (an index of dietary phytoestrogen exposure) was measured by gas chromatography-mass spectrometry. Significant differences in cholesterol FSR were found. FSR (%/d) was lowest in human milk (2.62 +/- 0.38), highest in soy milk-based formula (9.40 +/- 0.51), and intermediate in cow milk-based and modified soy milk-based formula (6.90 +/- 0.48 and 8.03 +/- 0.28, respectively), p < 0.0001. Cholesterol FSR was significantly lower in modified soy milk-based compared with soy milk-based formula, p < 0.05. We also show for the first time that dietary phytoestrogens are absorbed and excreted by the infant fed soy protein-based formula. Urinary isoflavone excretion was inversely related to cholesterol FSR, but it was not significantly related to serum cholesterol concentration. We conclude that the type of infant nutrition and dietary cholesterol are major factors influencing cholesterol fractional synthesis rates in infancy."
1,"TITLE: Benefits of lipid-lowering therapy in men with elevated apolipoprotein B are not confined to those with very high low density lipoprotein cholesterol.ABSTRACT: Do the benefits of intensive lipid-lowering therapy extend to patients with only borderline or moderately elevated levels of low density lipoprotein (LDL) cholesterol?The merits of the present LDL cholesterol treatment goal of < or = 100 mg/dl need to be clarified for patients without high levels of LDL cholesterol, particularly for those patients previously classified as having only borderline high (130 to 159 mg/dl) or desirable (101 to 130 mg/dl) levels.Disease change and clinical events were examined in LDL cholesterol subgroups in the Familial Atherosclerosis Treatment Study (FATS) trial, a randomized, blinded, quantitative arteriographic comparison of one conventional and two intensive lipid-lowering strategies in men with coronary artery disease, a positive family history and apolipoprotein B > or = 125 mg/dl. The primary end point, disease change per patient, was measured as the mean change in severity of stenosis (delta %SProx) among nine standard proximal segments.Of the 120 patients completing the 30-month protocol, 60 had a baseline LDL cholesterol < 90th percentile (mean LDL cholesterol 152 mg/dl) and 60 > 90th percentile (mean LDL cholesterol 221 mg/dl). Thirty-one patients had levels < 160 mg/dl (mean LDL cholesterol 134 mg/dl) and 89 > 160 mg/dl (mean LDL cholesterol 205 mg/dl). Patients with LDL cholesterol < 90th percentile benefited angiographically from therapy (delta %SProx = -1.5% diameter stenosis [regression] during intensive therapy vs. +2.3% diameter stenosis [progression] during conventional therapy, p < 0.01), as did patients with LDL cholesterol < 160 mg/dl (delta %SProx = -4.2% vs. +3.3% diameter stenosis, p = 0.0001). By comparison, angiographic benefit was less pronounced among those entering with very high LDL cholesterol (delta %SProx = -0.2% vs. +1.9% diameter stenosis, p = 0.07) or with LDL cholesterol > or = 160 mg/dl (delta %SProx = +0.2% vs. +1.6% diameter stenosis, p = 0.13). Intensive therapy resulted in a statistically significant reduction in clinical events only in the subgroup with baseline LDL cholesterol < 90th percentile (2 of 42 vs. 8 of 29 patients initially enrolled, p = 0.01) and a trend toward fewer events in patients with LDL cholesterol < 160 mg/dl (2 of 20 vs. 6 of 15 patients, p = 0.05). No such difference was seen in the higher LDL cholesterol subgroups.Treatment benefit in the FATS trial was not confined to patients with very high levels of LDL cholesterol and was in fact particularly evident in those patients with levels < 160 mg/dl. Such patients should be considered more likely, not less, to benefit from intensive lipid-lowering therapy."
1,"TITLE: Propofol anaesthesia in paediatric ambulatory patients: a comparison with thiopentone and halothane.ABSTRACT: The purpose of this study was to evaluate the haemodynamic changes during induction, as well as the speed and quality of recovery when propofol (vs thiopentone and/or halothane) was used for induction and maintenance of anaesthesia in paediatric outpatients. One hundred unmedicated children, 3-12-yr-old, scheduled for ambulatory surgery were studied. The most common surgical procedures performed were eye muscle surgery (42%), plastic surgery (21%), dental restoration (15%), and urological procedures (15%). The children were randomized to an anaesthetic regimen for induction/maintenance as follows: propofol/propofol infusion; propofol/halothane; thiopentone/halothane; halothane for both induction and maintenance. Succinylcholine 1.5 mg.kg-1 was used to facilitate tracheal intubation and N2O/O2 were used as the carrier gases in each case. All maintenance drugs were titrated according to the clinical response of the patient to prevent movement and/or maintain BP +/- 20% of baseline. Two patients (4%) who received propofol expressed discomfort during injection. The mean propofol dose required to prevent movement was 267 +/- 83 micrograms.kg-1.min-1. The overall pattern of haemodynamic changes, as well as awakening (extubation) times were not different among the four groups. Children who received propofol recovered faster (22 vs 29-36 min) (P < 0.05), were discharged home sooner (101 vs 127-144 min) (P < 0.05), and had less postoperative vomiting (4 vs 24-48%) (P < 0.05) than all others.(ABSTRACT TRUNCATED AT 250 WORDS)"
1,"TITLE: Caloric restriction per se is a significant factor in improvements in glycemic control and insulin sensitivity during weight loss in obese NIDDM patients.ABSTRACT: To examine the effects of caloric restriction, independent of differences in weight loss, on improvements in glycemic control, fasting insulin, and insulin sensitivity.We randomized 93 obese type II diabetic patients to two different degrees of calorie restriction (1,674 or 4,185 kJ/day; 400 or 1,000 kcal/day) and compared the changes in fasting glucose, fasting insulin, and insulin sensitivity that resulted from a comparable reduction in body weight (11% of initial body weight). Insulin sensitivity was assessed using the minimal model analysis of frequently sampled intravenous glucose tolerance tests.Despite equal weight losses, subjects in the 1,674 kJ/day (400 kcal) condition had lower fasting glucose levels (7.61 vs. 10.13 mM, P = 0.03) and greater insulin sensitivity (1.79 vs. 1.13, P = 0.04) after weight loss than did subjects in the 4,185 kJ/day (1,000 calorie) condition. Subjects were restudied 15 weeks later when both groups were consuming a 4,185 kJ/day (1,000 kcal/day) diet. Subjects who increased from 1,674 to 4,185 kJ (400 to 1,000 calories) had worse fasting glycemic control in spite of continued weight loss, whereas subjects who remained on 4,185 kJ (1,000 calories) throughout had further improvements in both blood glucose and insulin sensitivity with increased weight loss.Both degree of calorie restriction and magnitude of weight loss have independent effects on improvements in glycemic control and insulin sensitivity."
1,"TITLE: Clinical evaluation of topical isotretinoin in the treatment of actinic keratoses.ABSTRACT: Retinoids have been shown to improve the manifestations of skin photodamage, including actinic keratoses.The efficacy and tolerability of isotretinoin 0.1% cream in the treatment of actinic keratoses were evaluated in a randomized, double-blind, placebo-controlled, parallel-group study.One hundred patients were randomly assigned to treatment with 0.1% cream or vehicle twice daily for 24 weeks to the face, the scalp, and the upper extremities. Patients were assessed every 4 weeks by the investigators, who counted and recorded the number of lesions in each treatment area. The 93 patients who had at least one postbaseline assessment were included for efficacy analysis. Local tolerability was evaluated at each study visit.On the face, the reduction in number of actinic keratoses (mean +/- SEM) at the end of treatment was greater for patients treated with isotretinoin (3.9 +/- 0.6, i.e., 66% of patients with a reduction > 30%) than with placebo (1.7 +/- 0.5, i.e., 45% of patients with a reduction > 30%); this difference was statistically significant (p = 0.001). No significant drug effect was seen for lesions on the scalp or upper extremities. Mild to moderate local reactions with isotretinoin abated with reduced treatment frequency.Our results suggest that isotretinoin 0.1% cream cannot compete with more rapid treatments of actinic keratoses. However, its effect on facial lesions may be beneficial during long-term treatment of associated sun-damaged skin."
1,"TITLE: Delay in progression of bone metastases in breast cancer patients treated with intravenous pamidronate: results from a multinational randomized controlled trial. The Aredia Multinational Cooperative Group.ABSTRACT: Bone metastases are a major cause of morbidity in breast cancer, resulting in complications that include pain, loss of mobility, pathologic fracture, and tumor-induced hypercalcemia (TIH). Inhibition of osteoclast-mediated bone destruction using bisphosphonates represents a promising new management approach.Breast cancer patients with bone metastases were randomly allocated to receive chemotherapy alone (152 patients) or chemotherapy plus pamidronate 45 mg in 250 mL of saline as a 1-hour intravenous infusion every 3 weeks (143 patients). Whenever possible, treatment continued until progression of disease (PD) in bone appeared on radiographs or bone scan. Time to PD in bone and pain reduction according to a self-assessment six-point scale were selected as primary end points. PD in bone was verified during extramural review (EMR) of all imaging studies by blinded observers, and these data were used as the main efficacy criterion. Analgesic intake, World Health Organization (WHO) performance status, and complications of bone metastases (radiotherapy, TIH, fractures, orthopedic surgery) were also compared in the two groups.At EMR, median time to PD in bone was increased by 48% in patients who received pamidronate (249 v 168 days; P = .02, Wilcoxon test). Marked pain relief, defined as a two-point decrease lasting for > or = 6 weeks, was reported by 44% of pamidronate patients and by 30% of controls (P = .025, chi 2 test). The infusions (median, nine per patient; range, 0 to 39) were well tolerated, with no major toxicities reported. Pamidronate by repeated infusion can significantly slow the progression of bone metastases and reduce attendant morbidity."
1,"TITLE: Effect of aprotinin on insulin sensitivity in non-insulin-dependent diabetes mellitus.ABSTRACT: It has been suggested that kallikrein-kinin system may influence carbohydrate metabolism via a kinin-mediated increment of insulin-mediated glucose uptake. To evaluate the effect of acute inhibition of the kallikrein-kinin system on insulin sensitivity, a randomized, placebo-controlled, double-blind study was performed in 15 male non-insulin-dependent diabetic patients. After basal evaluation of insulin sensitivity with a 2-h euglycaemic hyperinsulinaemic clamp (40 mU m-2 min-1), patients were infused either with aprotinin (200,000 U.I.C. as intravenous bolus injection) or placebo (10 ml isotonic saline) in a cross-over fashion, at 1 week intervals. After both saline and aprotinin infusions, insulin sensitivity was reassessed by continuing the euglycaemic hyperinsulinaemic clamp for a further 1 h. Resulting data showed that aprotinin significantly improved total glucose uptake (from 16.2 +/- 2.9 mumol kg min-1 to 20.6 +/- 4.9 mumol kg min-1 p < 0.01), and decreased metabolic clearance rate of insulin (from 586 +/- 57 ml m-2 min-1 to 442 +/- 155 ml m-2 min-1, p < 0.05). Thus, in spite of the suggested positive effects of kinins on insulin-mediated glucose uptake, acute inhibition of the kallikrein-kinins system resulted in a paradoxical increment of insulin sensitivity, which was probably mediated by the reduced metabolic clearance rate of insulin."
1,"TITLE: Failure of cefonicid prophylaxis for infectious complications related to endoscopic retrograde cholangiopancreatography.ABSTRACT: We performed a controlled study to evaluate the role of cefonicid in preventing infectious complications related to retrograde cholangiopancreatography (ERCP). Consecutive patients were randomized to receive prophylaxis with cefonicid (1 g intravenously) 1 hour before the procedure or to be untreated controls. During a 26-month period, 179 ERCPs, including 93 therapeutic procedures, were performed on 164 patients. Prophylaxis was administered before 88 procedures (49%). The rate of bacteremia among treated patients was similar to that among controls (3% vs. 2%, respectively; P = .4). The rate of cholangitis was also similar among both groups (8% vs. 2%, respectively; P = .07). There were no episodes of sepsis, and none of the patients died. The rate of bacteremia was also similar among patients undergoing diagnostic procedures and patients undergoing therapeutic procedures, but all cases of cholangitis occurred in the latter group (0 vs. 10%, respectively; P = .002). Nevertheless, the rate of cholangitis was not significantly changed by the use of prophylaxis (14% among treated patients vs. 5% among controls, P = .12). Therefore, infectious complications could not be prevented by cefonicid prophylaxis."
1,"TITLE: Bupivacaine decreases epidural meperidine requirements after abdominal surgery.ABSTRACT: The purpose of this study was to determine the optimal of three concentrations of bupivacaine (0.0%, 0.05%, 0.10%) to add to an epidural infusion of meperidine (1 mg.ml-1) for postoperative pain relief.In this prospective, double blind study, 60 patients undergoing abdominal surgery with general anaesthesia were randomized into three groups to receive for postoperative epidural analgesia: 1) 1 mg.ml-1 meperidine (0% group), 2) bupivacaine 0.05% and 1 mg.ml-1 meperidine (0.05% group), 3) bupivacaine 0.10% and 1 mg.ml-1 meperidine (0.10% group). Postoperatively, the epidural infusion rate was titrated to produce adequate analgesia and pain was assessed at rest and on movement.There were no differences in demographic data, average pain scores or side effects among the three groups. However, there was improvement of pain relief at rest over time in the three groups (P < 0.05). Postoperative epidural analgesic infusion rates increased over time for the three groups (P < 0.05) and were lower in the 0.10% group (mean of 10.0 ml.hr-1) than in the 0% group (mean of 12.6 ml.hr-1) (P < 0.05). More than half of the 0% group had serum meperidine concentrations > 400 g.L-1 to control moderate postoperative pain.Although analgesia was identical among groups, the lower serum concentrations of meperidine support the addition of bupivacaine 0.10% to meperidine when administered as a continuous infusion following abdominal surgery."
0,"TITLE: The role of the hypothalamic-pituitary-adrenal (HPA) axis in the regulation of blood pressure.ABSTRACT: The role of the HPA axis in blood pressure regulation was examined in 6 normal male volunteers by comparing haemodynamic and hormonal effects of placebo, captopril, and dexamethasone given in random order for two days. The average 24-hour systolic and mean arterial pressures on placebo (135 +/- 6 and 93 +/- 2 mmHg respectively) were significantly higher than on captopril (118 +/- 1 and 85 +/- 1 mmHg respectively, p < 0.05) but there were no significant changes on dexamethasone compared with placebo (128 +/- 3 and 89 +/- 3 mmHg respectively). There were no differences in the average 24-hour diastolic blood pressures or heart rates, nor the day-night differences, night:day ratios or percentage changes in blood pressure and heart rate between treatments. Captopril significantly increased active plasma renin concentration, whilst dexamethasone decreased cortisol concentration. These results confirm the role of the renin-angiotensin system in the regulation of blood pressure in normal subjects but suggest that the HPA axis does not play a major role in determining ambulatory blood pressure or day-night variability in the short term."
1,"TITLE: Effectiveness of two preventive interventions for coronary heart disease in primary care.ABSTRACT: 1. To compare a patient-centred, self-directive intervention with conventional care; 2. To evaluate longitudinal within-group changes of coronary heart disease risk.Risk factor changes were evaluated in 110 men with high coronary heart disease risk attending a one year intervention study in general practice. The 22 participating general practice centres were randomly allocated to follow either a patient-centred, self-directive intervention or a conventional approach.No significant between-group differences were found in any single risk factor or in the combined risk of coronary heart disease. The improvement of total risk from screening time to conclusion of the study corresponded with changes of relative risks of CHD to 0.64 (95% CI: 0.54-0.77) and 0.65 (0.54-0.77) in the patient-centred, self-directive and the conventional care group respectively (p < 0.0001 in both groups).Everyday general practice clinical work seems as efficacious as a specific intervention method based on currently advocated behaviour change principles."
1,"TITLE: Sulbactam/cefoperazone versus cefotaxime for the treatment of moderate-to-severe bacterial infections: results of a randomized, controlled clinical trial.ABSTRACT: We conducted a randomized, open-label, controlled, multicenter study to compare sulbactam/cefoperazone with cefotaxime in terms of efficacy and safety for the treatment of hospitalized patients with moderate-to-severe bacterial infections. More than two-thirds of the pathogens recovered from these patients produced beta-lactamase. Two hundred-seven (88.1%) of the 235 patients enrolled completed the study and were included in the efficacy and safety evaluations. One hundred-three patients received sulbactam/cefoperazone (2-4 g/d) administered in evenly divided doses every 12 hours by a 30-minute intravenous drip; 104 patients received cefotaxime (6-12 g/d) administered in evenly divided doses every 6 or 8 hours by a 30-minute intravenous drip. The overall efficacy rates (i.e., cure or markedly improved) were 95% for the sulbactam/cefoperazone group and 90% for the cefotaxime group (P = .186), whereas the bacterial eradication rates were 85% for the sulbactam/cefoperazone group and 81% for the cefotaxime group (P = .467). Both drug regimens were well tolerated. Sulbactam/cefoperazone is effective and safe for the treatment of moderate-to-severe bacterial infections caused mainly by beta-lactamase-producing organisms."
1,"TITLE: Comparison of single-dose cefuroxime axetil with ciprofloxacin in treatment of uncomplicated gonorrhea caused by penicillinase-producing and non-penicillinase-producing Neisseria gonorrhoeae strains.ABSTRACT: A randomized, multicenter, investigator-blind trial was conducted to compare the efficacies of cefuroxime axetil and ciprofloxacin for treatment of patients with uncomplicated gonorrhea caused by penicillinase-producing Neisseria gonorrhoeae (PPNG). A total of 832 patients (434 females and 398 males) received a single oral dose of cefuroxime axetil (1,000 mg [417 patients]) or ciprofloxacin (500 mg [415 patients]). N. gonorrhoeae was eradicated from the cervix in 114 of 118 (97%) and 118 of 119 (99%) bacteriologically evaluable females treated with cefuroxime axetil and ciprofloxacin, respectively (P = 0.213; difference, -2%; 95% confidence interval, -6 to 1%), and from the urethra in 154 of 166 (93%) and 171 of 171 (100%) bacteriologically evaluable male patients treated with cefuroxime axetil and ciprofloxacin, respectively (P < 0.001; difference, -7%; 95% confidence interval, -11 to -3%). Both treatments were effective in eradicating N. gonorrhoeae in females with rectal infections (cefuroxime axetil, 29 of 30 [97%]; ciprofloxacin, 25 of 25 [100%]; P = 1.00). In small numbers of patients, cefuroxime axetil was less effective than ciprofloxacin in treating males with pharyngeal infections (eradication in 4 of 10 and in 8 of 8 patients, respectively; P = 0.013). PPNG was eradicated from the cervix in 22 of 23 (96%) and 32 of 32 (100%) bacteriologically evaluable female patients treated with cefuroxime axetil and ciprofloxacin, respectively (P = 0.418; difference, -4%; 95% confidence interval, -13 to 4%), and from the urethra in 35 of 36 (97%) and 34 of 34 (100%) bacteriologically evaluable male patients treated with cefuroxime axetil and ciprofloxacin, respectively (P = 1.00; difference, -3%; 95% confidence interval, -8 to 3%). The incidences of drug-related adverse events were similar for the two study drugs. In summary, treatment with a single oral dose of cefuroxime axetil is as effective as treatment with a single oral dose of ciprofloxacin in eradicating PPNG from males and females with uncomplicated gonorrhea (urethral and endocervical), and both regimens are well-tolerated. However, in the present study, cefuroxime axetil was less effective than ciprofloxacin in treating urethral gonococcal infections in male patients, although both study drugs were highly effective in treating cervical gonococcal infections in female patients."
1,"TITLE: Hirudin in acute myocardial infarction. Safety report from the Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9A Trial.ABSTRACT: The Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9A trial compared the efficacy and safety of intravenous hirudin with heparin as adjunctive therapy to thrombolysis and aspirin in patients with acute myocardial infarction. The primary safety end point was the occurrence of major hemorrhage or anaphylaxis.Based on experience in phase II trials, TIMI 9A used a hirudin bolus of 0.6 mg/kg followed by a fixed-dose 96-hour infusion of 0.2 mg/kg per hour. A modified weight-adjusted heparin regimen was used (5000-U bolus and infusion of 1000 U/h for patients < 80 kg or 1300 U/h for patients > or = 80 kg) with titration to a target activated partial thromboplastin time (aPTT) of 60 to 90 seconds. Because rates of hemorrhage in both treatment arms were higher than expected, randomization was suspended in TIMI 9A after 757 patients had been enrolled. Intracranial hemorrhage occurred in 1.7% of patients treated with hirudin and 1.9% of those treated with heparin (P = NS). Major spontaneous hemorrhage at a nonintracranial site occurred more frequently in hirudin--than in heparin-treated patients (7.0% versus 3.0%; P = .02), whereas major hemorrhage at instrumented sites was similar (5.2% in both hirudin and heparin groups). Patients who developed a major hemorrhage were older (P < .001) and had higher aPTT values, especially in the first 12 hours after thrombolysis (P = .001).The rate of major spontaneous hemorrhage for both heparin and hirudin in TIMI 9A was higher than that seen in TIMI 5, TIMI 6, and GUSTO 1. This was possibly a result of high levels of anticoagulation at the doses of heparin and hirudin used, low previous estimates of the hemorrhage risk at the doses of hirudin used in TIMI 9A due to the relatively small number of patients receiving that dose in earlier studies, and enrollment of patients at higher risk of hemorrhage. Because a prolonged aPTT was associated with an increased risk of major hemorrhage in both heparin- and hirudin-treated patients, it now appears important to monitor aPTT on a regular basis when using either antithrombin to identify those patients who require downward adjustment of the infusion. TIMI 9B has therefore been configured with a lower hirudin bolus (0.1 mg/kg) and infusion (0.1 mg/kg per hour) and lower heparin infusion (1000 U/h without weight adjustment). Infusions of both antithrombins will be titrated to a target aPTT of 55 to 85 seconds."
1,"TITLE: Intravenous amiodarone in treatment of recent-onset atrial fibrillation: results of a randomized, controlled study.ABSTRACT: This study was designed to determine the efficacy of intravenous amiodarone in the management of recent-onset atrial fibrillation.The optimal approach for acute atrial fibrillation has not been established. Amiodarone is a unique antiarrhythmic agent with activity in both supraventricular and ventricular tachyarrhythmias, but its value for the restoration of sinus rhythm in patients with recent-onset atrial fibrillation has not been demonstrated.Sample size was calculated to detect a 25% increase in reversion rate with amiodarone with a statistical power of 80%. One hundred consecutive patients with recent-onset (<1 week) atrial fibrillation and not taking antiarrhythmic agents were randomized to receive either intravenous amiodarone, 5 mg/kg body weight in 30 min followed by 1,200 mg over 24 h, or an identical amount of saline. Both groups received intravenous digoxin, 0.5 mg initially, followed by 0.25 mg at 2 h and 0.25 mg every 6 h thereafter, to complete 24 h while the ventricular rate was >100 beats/min. Amiodarone and digoxin blood levels were determined. Both groups were homogeneous regarding underlying heart disease, time from onset to treatment, initial ventricular rate and left atrial size.By the end of the 24-h treatment period, 34 patients (68%, 95% confidence interval [CI] 53% to 80%) in the amiodarone group and 30 (60%, 95% CI 45% to 74%) in the control group had returned to sinus rhythm (p = 0.532). Mean times (+/-SD) of conversion were 328 +/- 335 and 332 +/- 359 min, respectively (p =0.957). Among patients who did not convert to sinus rhythm, treatment with amiodarone was associated with a slower ventricular rate (82 +/- 15 beats/min in the amiodarone group vs. 91 +/- 23 beats/min in the control group, p = 0.022). After restoration of sinus rhythm, atrial fibrillation recurred during a 15-day follow-up period in 4 (12%) of 34 patients (95% CI 3% to 27%) in the amiodarone group and in 3 (10%) of 30 (95% CI 2% to 26%) in the control group (p = 0.861).Intravenous amiodarone, at the doses used in this study, produces a modest but not significant benefit in converting acute atrial fibrillation to sinus rhythm."
0,"TITLE: Differing metabolism and bioactivity of atrial and brain natriuretic peptides in essential hypertension.ABSTRACT: Plasma concentrations of both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are elevated in severe hypertension, acute myocardial infarction, and heart failure. In the current study of individuals with essential hypertension, we have documented the hemodynamic, hormonal, and endocrine effects of infusions of these two peptides given alone or in combination in equimolar doses calculated to induce increments in plasma peptides to concentrations (30 to 60 pmol/L) observed in these disease states. The metabolic clearance rate of ANP (4.56 +/- 0.62 L/min) was greater than that for BNP (3.4 +/- 0.23 L/min, P <.001). Infusions of each cardiac hormone impaired the clearance of coinfused peptide. All peptide infusions enhanced natriuresis (17% to 70% above preinfusion levels versus placebo, 6%; P <.001), lowered blood pressure (10 to 18 mm Hg fall in mean arterial pressure below placebo levels; P <.001), increased hematocrit, suppressed the renin-angiotensin-aldosterone system, and enhanced plasma norepinephrine concentrations. The natriuretic and blood pressure-lowering effects of BNP were twofold to threefold those of ANP. In contrast, ANP-induced increments in plasma and urinary second messenger (cGMP) levels were greater than those for BNP. Both peptides suppressed the renin-angiotensin-aldosterone system (approximately one-third fall in renin activity and plasma aldosterone) and enhanced plasma norepinephrine concentrations (+30%) to a similar degree. Increments in plasma ANP and BNP that occur simultaneously in cardiovascular disease states appear capable of causing hemodynamic, endocrine, and renal effects that would tend to ameliorate conditions such as hypertension or heart failure."
0,"TITLE: Partial vs full beta-receptor agonism. A clinical study of inhaled albuterol and fenoterol.ABSTRACT: To compare the maximal extrapulmonary effects of the beta-agonists albuterol and fenoterol in eight healthy volunteers.In this double-blind study, we have examined the maximum cardiac effects (electromechanical systole [QS2I]--a measure of inotropy, heart rate, BP) and metabolic effects (plasma K+ and cyclic adenosine monophosphate [cAMP]) of repeated inhalation of albuternol and fenoterol. In eight healthy volunteers, 400 microg of each drug was administered every 10 min until QS2I and plasma K+ had reached a plateau (+/- 0.1 mmo l/L for K+, and +/- 10 ms for QS2I). The maximum response (Emax) and the dose of albuterol required to produce 50% of the maximum response to fenoterol (ED50F) were calculated.The Emax for fenoterol was significantly greater than albuterol for plasma K+ (-1.4 vs -1.03 mmol/L; p<0.002), QS2I (-71.8 vs 57.5 ms; p=0.047), and cAMP (33.8 vs 18.1 nmol/L; p<0.002). The dose required to produce the ED50f was significantly greater for albuterol than for fenoterol with potency ratios of 1.75, 1.61, and 2.26 for plasma K+, QS2I, and cAMP, respectively. There were no significant differences between fenoterol and albuterol with respect to heart rate (Emax, 44.9 vs 32.5 beats/min; p=0.19; potency ratio, 1.98; p=0.052).These findings suggest that albuterol behaves as a partial agonist at beta-receptors when compared with fenoterol, and that when inhaled in doses currently recommended for severe asthma, albuterol will result in lesser maximum cardiac and metabolic effects than fenoterol. These findings are consistent with the hypothesis that the property of full receptor agonism may contribute to the increased risk of death associated with fenoterol."
1,"TITLE: A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome.ABSTRACT: The median survival of patients with myeloma after conventional chemotherapy is three years or less. Promising results have been reported with high-dose therapy supported by autologous bone marrow transplantation. We conducted a randomized study comparing conventional chemotherapy and high-dose therapy.Two hundred previously untreated patients under the age of 65 years who had myeloma were randomly assigned at the time of diagnosis to receive either conventional chemotherapy or high-dose therapy and autologous bone marrow transplantation.The response rate among the patients who received high-dose therapy was 81 percent (including complete responses in 22 percent and very good partial responses in 16 percent), whereas it was 57 percent (complete responses in 5 percent and very good partial responses in 9 percent) in the group treated with conventional chemotherapy (P < 0.001). The probability of event-free survival for five years was 28 percent in the high-dose group and 10 percent in the conventional-dose group (P = 0.01); the overall estimated rate of survival for five years was 52 percent in the high-dose group and 12 percent in the conventional-dose group (P = 0.03). Treatment-related mortality was similar in the two groups.High-dose therapy combined with transplantation improves the response rate, eventfree survival, and overall survival in patients with myeloma."
1,"TITLE: Patient-controlled analgesia for conscious sedation during endoscopic retrograde cholangiopancreatography: a randomized controlled trial.ABSTRACT: Adequate comfort is essential to patients undergoing invasive procedures. This study was designed to evaluate whether patient-controlled analgesia could improve sedation for ERCP.Patients were randomized to receive standard sedation (n = 31) or patient-controlled analgesia (n = 31). The patients were blinded to the randomization. After the procedure the patient, physician, and nurse each rated their satisfaction with sedation using a verbal rating scale.There was no significant difference between the patient's mean satisfaction score for the conventional and patient-controlled analgesia groups (9.3 and 9.6, respectively, p = 0.5). The physicians rated sedation higher in the conventional group compared with the patient-controlled analgesia group (8.6 and 8.2, respectively, p = 0.02). Physicians and nurses' scores correlated (r = 0.53, p = 0.0001), but there was no correlation between scores reported by either physicians or nurses and the patients' scores (r = 0.2 and r = 0.05, respectively). Oxygen saturation less than 90% occurred for more than 1 minute in three patients who received standard sedation but in none who used patient-controlled analgesia.This trial demonstrates that patient-controlled analgesia during ERCP is as effective as standard sedation with respect to patient satisfaction. Physicians and nurses, however, are not good proxies for assessing patient satisfaction."
0,"TITLE: The effects of clonidine premedication on sevoflurane requirements and anesthetic induction time.ABSTRACT: We assessed the effects of oral clonidine preanesthetic medication (4.5 microg/kg) on the vital capacity rapid-inhalation anesthetic induction time (VCRII time) and minimum alveolar anesthetic concentration (MAC) to prevent a response to a verbal command in 50% of patients (MAC-Awake) by its hypnotic effect, and on MAC-Skin incision for the analgesic effect in patients anesthetized with sevoflurane. We studied 104 adult patients (control group: n = 52, clonidine group: n = 52) aged 30-48 yr scheduled to undergo general anesthesia. Fifty-two patients received oral clonidine 4.5 microg/kg 1.5 h before arrival in the operating room (clonidine group). The patients exhaled to residual volume and took three vital capacity breaths of 5% sevoflurane in oxygen. The VCRII time was defined as the time interval between the initiation of the VCRII and the disappearance of the response to verbal command. Anesthesia was maintained with sevoflurane in oxygen and air. The end-tidal (ET) sevoflurane concentration reached a predetermined value, then the ratio of predetermined ET to inspiratory concentration was maintained at > or =0.95 for at least 15 min before skin incision. After skin incision, the patients were observed for gross purposeful muscular movements. MAC was defined as the average of the cross-over midpoints in each cross-over. After maintaining the ET sevoflurane concentration for 15 min, patients were judged to be awake or asleep. Average times for VCRII using 5% sevoflurane were achieved in 44+/-11 s (mean +/- SD) and 27+/-6 s in the control and clonidine groups, respectively (P = 0.0001). MAC-Awake values of sevoflurane were 0.66%+/-0.03% and 0.35%+/-0.02% (P = 0.0001), and MAC-Skin incision values were 1.97%+/-0.19% and 1.29%+/-0.13% (P = 0.0001) in the control and clonidine groups, respectively. These results suggest that clonidine may have a more potent hypnotic effect than analgesic effect.Oral clonidine preanesthetic medication (4.5 microg/kg) significantly reduces vital capacity rapid inhalation anesthetic induction time and minimum alveolar anesthetic concentration awake for sevoflurane."
1,"TITLE: Emergence and clinical relevance of mutations associated with zidovudine resistance in asymptomatic HIV-1 infected patients.ABSTRACT: The dynamics leading to the emergence of a zidovudine-resistant mutation at codon 215 of the reverse transcriptase coding region was investigated in a cohort of HIV-infected individuals who received early zidovudine therapy. Clinical implications and the role of the resistance mutation at codon 41 were also assessed. Thirty-eight initially asymptomatic HIV-infected patients with a CD4+ cell count above 400 cells/mm3 were followed for a mean period of 121 weeks (20 received zidovudine and 18 matching placebo). Specific mutations in the HIV-1 reverse transcriptase coding region conferring resistance to zidovudine were detected using a selective polymerase chain reaction. During the follow-up period a mutation at codon 215 was detected in eight (40%) of the individuals in the zidovudine group, and in two of these eight subjects, a mutation at codon 41 was found. During the study, disease progression occurred in seven of the eight (88%) patients with a mutation at codon 215, compared with 7 of 18 (39%) patients assigned to the placebo group and 3 of the 12 (25%) patients receiving zidovudine treatment who did not develop a 215-mutant strain (p < 0.05). At entry, none of the patients harbored MT-2 tropic virus. Therefore, the emergence of a zidovudine-resistant mutation at codon 215 is associated with subsequent disease progression in asymptomatic HIV-infected patients who receive zidovudine monotherapy. This association suggests that the mutation at codon 215 is involved in a loss of therapeutic efficacy and, therefore, patients should be monitored during treatment with zidovudine."
0,"TITLE: Relationships of blood pressure to fibrinolysis: influence of anthropometry, metabolic profile and behavioural variables.ABSTRACT: To investigate the relationship between blood pressure and the plasma fibrinolytic system and to verify whether this association was independent or mediated by one or more potential confounding factor.A random sample of 94 males aged 38 years subdivided into normotensives, hypertensives and those hypertensives with the highest blood pressure values.Overall and regional obesity, blood lipids, fasting and 2-h post-load glucose, C-peptide and insulin levels, and main behavioural variables, including adipose tissue fatty acid composition (an objective index of dietary fat intake), were measured. The plasma fibrinolytic system was evaluated by determining activities and total plasma concentrations of both tissue-type plasminogen activator before and after venous occlusion, and its inhibitor plasminogen activator inhibitor type-1 (PAI-1).PAI-1 activity was significantly higher in the hypertensives than in the normotensives. PAI-1 antigen tended to parallel PAI-1 activity, and levels of tissue-type plasminogen activator antigen and activity tended to be lower in the hypertensives at baseline and after venous occlusion, but not significantly different from those in the normotensives. The hypertensives also had significantly higher body mass index and body fat content (measured by bio-impedance), increased plasma triglycerides, uric acid, fasting and 2-h glucose, C-peptide and insulin concentrations. In univariate linear regression analysis both systolic and diastolic blood pressures were found to be positively correlated with PAI-1 levels (r = 0.27, P < 0.01, for both). This correlation was maintained after adjustment for total body fat, fasting glucose, fasting insulin concentration or adipose tissue alpha-linolenic acid; however, it was no longer significant after adjustment for plasma 2-h insulin, 2-h C-peptide, 2-h glucose or triglyceride levels. Multivariate regression analysis revealed that only 2-h insulin and triglyceride concentration showed an independent association with PAI-1 levels.This study confirms that, in 38-year-old males, hypertension is associated with increased PAI-1 activity. It supports the possibility that the relationship between blood pressure and PAI-1 may reflect the overall effect of the insulin resistance syndrome (in particular hyperinsulinaemia and hypertriglyceridaemia) rather than a direct effect of blood pressure on the fibrinolytic system."
1,"TITLE: Butorphanol: an opioid for day-care paediatric surgery.ABSTRACT: The purpose of this study was to compare the side effects and efficacy of equianalgesic doses of morphine (M) and butorphanol (B) in children undergoing similar surgical procedures associated with moderate postoperative pain. We studied 156 healthy children aged 1.5-13 yr who underwent elective inguinal herniorrhaphy or orchidopexy. After induction of anaesthesia subjects were given 150 micrograms.kg-1 M or 30 micrograms.kg-1 B following a randomized, stratified, blocked and double-blind design. A standardized anaesthetic was administered, which included 1.5% halothane, vecuronium, droperidol and mechanical ventilation. The postsurgical four-hour follow-up included assessment of pain, vomiting and respiratory depression. Pain was assessed with mCHEOPS and analgesics were administered when indicated in the recovery room. Each opioid was administered to a group of 78 patients. Within each group, 25 subjects had an iv induction, 21 children had an orchidopexy and 57 had inguinal hernia repairs. The groups were similar with respect to age, weight, and length of surgery. The choice of opioid did not affect recovery times from anaesthesia. Analgesic requirements were similar among the groups. Ten minutes after arrival in the recovery room the B-subjects had a lower pain score than the M-patients. Postoperative vomiting was less among the B-subjects: 14% vs 28%, P = 0.03. Two M-patients required an unscheduled admission to hospital because of vomiting. It is concluded that butorphanol has few advantages over morphine in the population studied."
0,"TITLE: Inner city air pollution and respiratory health and atopy in children.ABSTRACT: The impact of inner city air pollution on the development of respiratory and atopic diseases in childhood is still unclear. In a cross sectional study in Dresden, Germany, 5,421 children in two age groups (5-7 yrs and 9-11 yrs) were studied according to the International Study of Asthma and Allergies in Childhood (ISAAC) phase II protocol. The prevalences of wheezing and cough as well as doctor diagnosed asthma and bronchitis were assessed by parental questionnaires. Children also underwent skin-prick testing, venipuncture for the measurement of serum immunoglobulin (Ig)E, lung function testing and a bronchial challenge test (4.5% saline) to assess airway hyperresponsiveness. Exposure was assessed on an individual basis by relating mean annual air pollution levels (SO2, NO2, CO, benzene, and O3) which had been measured on a 1 km2 grid, to the home and school address of each study subject. After adjusting for potential confounding factors an increase in the exposure to benzene of 1 microg x m3 air was associated with an increased prevalence of morning cough (adjusted odds ratio (aOR)): 1.15; 1.04-1.27) and bronchitis (aOR: 1.11; 1.03-1.19). Similar associations were observed for NO2 and CO. In turn, the prevalences of atopic sensitization, symptoms of atopic diseases and bronchial hyperresponsiveness were not positively associated with exposure to any of these pollutants. It is concluded that in this study a moderate increase in exposure to traffic-related air pollution was associated with an increased prevalence of cough and bronchitis, but not with atopic conditions in children."
1,"TITLE: Mibefradil but not isradipine substantially elevates the plasma concentrations of the CYP3A4 substrate triazolam.ABSTRACT: The calcium channel blockers mibefradil and isradipine inhibit CYP3A4 in vitro. However, their in vivo inhibitory effects on CYP3A4 are not known in detail, although mibefradil was recently withdrawn from the market because of serious drug interactions.The effects of mibefradil and isradipine on the pharmacokinetics and pharmacodynamics of oral triazolam, a model substrate of CYP3A4, were studied in a randomized, double-blind crossover study with three phases. Nine healthy subjects took 50 mg mibefradil, 5 mg isradipine, or placebo orally once a day for 3 days. On day 3, each subject received a single 0.25 mg oral dose of triazolam. Thereafter, blood samples were collected up to 18 hours, and pharmacodynamic effects of triazolam were measured up to 8 hours.Mibefradil increased the total area under the plasma triazolam concentration-time curve [AUC(0 - infinity)] 9-fold compared with placebo (P < .001). The peak plasma concentration of triazolam was increased 1.8-fold (3.4+/-0.1 ng/mL versus 1.8+/-0.2 ng/mL [mean +/- SEM]; P < .001), and the elimination half-life (t 1/2) was increased 4.9-fold (18.5+/-1.9 hours versus 4.0+/-0.5 hours; P < .001) by mibefradil. In addition, mibefradil was associated with increased pharmacodynamic effects of triazolam. In contrast to mibefradil, isradipine reduced the AUC(0 - infinity) and t 1/2 of triazolam by about 20% (P < .05) and had no significant effects on the pharmacodynamics of triazolam.Mibefradil but not isradipine markedly increases the plasma concentrations of triazolam and thereby enhances and prolongs its pharmacodynamic effects, consistent with potent inhibition of CYP3A4."
1,"TITLE: Bone densitometry: a new, highly responsive region of interest in the distal forearm to monitor the effect of osteoporosis treatment.ABSTRACT: The bisphosphonates have been introduced as alternatives to hormone replacement therapy (HRT) for the treatment and prevention of postmenopausal osteoporosis. The expected increasing application in at clinical practice demands cost-effective and easily handled methods to monitor the effect on bone. The weak response at the distal forearm during antiresorptive treatment has restricted the use of bone densitometry at this region. We describe a new model for bone densitometry at the distal forearm, by which the response obtained is comparable to the response in other regions where bone densitometry is much more expensive and technically complicated. By computerized iteration of single X-ray absorptiometry forearm scans we defined a region with 65% trabecular bone. The region was analyzed in randomized, double-masked, placebo- controlled trials: a 2-year trial with alendronate (n = 69), a 1-year trial with ibandronate (n = 141) and a 2-year trial with HRT (n = 121). Bone mineral density (BMD) at the distal forearm revealed a highly statistically significant dose-related response and increased 3-5% per year with 2.5 mg ibandronate, 10 mg alendronate or HRT, whereas the decrease in the placebo groups was 1-3% (p<0.001). The response at the distal forearm was similar to the response at the lumbar spine and hip. In conclusion, trabecular bone at the distal forearm is as responsive to antiresorptive treatment as trabecular bone in other skeletal regions. Bone densitometry at the new region of interest in the distal forearm has comparable performance characteristics to more expensive and technically demanding methods. The method is more accessible clinically and has potential as an alternative for monitoring bone mass changes during antiresorptive treatment."
1,"TITLE: Effects of digoxin and digitoxin on circadian blood pressure profile in healthy volunteers.ABSTRACT: The aim of the study was to investigate the potential effects of chronic digoxin or digitoxin treatment or circadian blood pressure profile in normotensive subjects.In two randomized double-blind, placebo-controlled cross-over protocols, 22 healthy normotensive subjects were enrolled, 12 subjects in either study. After adequate loading doses, digoxin 0.25 mg twice daily or digitoxin 0.1 mg daily was given for a total of 10 days. Automatic 24-h ambulatory blood pressure measurements were carried out at days 4 and 10 of either glycoside or placebo.Digoxin treatment significantly decreased heart rate (HR) and diastolic blood pressure (DBP) during the overnight sleeping phase of day 10 compared with placebo (HR, 4 beats min-1; DBP, 8 mmHg; P < 0.05). Digitoxin treatment significantly decreased heart rate and diastolic blood pressure during the overnight sleeping phase of day 4 (HR, 8 beats min-1; DBP, 7 mmHg) and day 10 (HR, 7 beats min-1; DBP, 5 mmHg) compared with placebo (P < 0.05). Neither digoxin nor digitoxin significantly affected systolic blood pressure.Both digoxin and digitoxin, within therapeutic steady-state plasma concentrations, reduced diastolic blood pressure and heart rate during overnight sleep, presumably because of increased parasympathetic activity or decreased sympathetic activity."
1,"TITLE: Efficacy of ondansetron and prochlorperazine for the prevention of postoperative nausea and vomiting after total hip replacement or total knee replacement procedures: a randomized, double-blind, comparative trial.ABSTRACT: Limited data are available on the efficacy of ondansetron hydrochloride compared with prochlorperazine maleate for the treatment of postoperative nausea and vomiting (PONV).To evaluate the comparative efficacy of ondansetron and prochlorperazine for the prophylaxis of PONV in patients undergoing total hip replacement or total knee replacement procedures.A randomized, double-blind, comparative trial was conducted at a tertiary care, university hospital. Seventy-eight patients undergoing elective total hip or total knee replacement procedures received a single dose of ondansetron hydrochloride (n = 37), 4 mg intravenously, or prochlorperazine maleate (n = 41), 10 mg intramuscularly, at the end of the surgical procedure. Rescue therapy was administered every 4 hours as needed during the initial 48 hours. Primary outcome measures were the incidences and severity of PONV. Secondary outcome measures included the number of rescue antiemetic doses required, number of physical therapy cancellations because of PONV, length of hospital stay, and cost of antiemetic agents administered.The incidence of nausea was significantly greater in the ondansetron group compared with the prochlorperazine group (81% vs 56%; odds ratio, 3.4; 95% confidence interval, 1.2-9.4) as was the severity of nausea (P = .04). Multivariate analysis identified administration of ondansetron, history of PONV, obesity, and female sex as risk factors for a nausea event. The incidence of vomiting tended to be greater in the ondansetron group (49% vs 32%; odds ratio, 2.0; 95% confidence interval, 0.8-5.0). The need for rescue antiemetic therapy was also greater in the ondansetron group (46% vs 27%; odds ratio, 2.3; 95% confidence interval, 0.9-6.0). The mean antiemetic drug cost per patient was significantly greater for the ondansetron group ($47.56 vs $2.47; P<.001). However, the proportion of patients who were unable to participate in physical therapy because of PONV and the median length of hospital stay were similar in both groups.Prochlorperazine is associated with superior efficacy and significant cost savings compared with ondansetron for the prevention of PONV in patients undergoing total hip and total knee replacement procedures."
1,"TITLE: Effect of diaspirin cross-linked hemoglobin on endothelin-1 and blood pressure in acute ischemic stroke in man.ABSTRACT: For almost 50 years it has been known that hemolysed blood can increase blood pressure. Although preclinical studies suggest that this pressor response is due to an interaction of hemoglobin with endothelium-derived vasoactive substances, its mechanism in humans is unknown. We investigated the involvement of endothelin-1 in the blood pressure response to the oxygen carrier diaspirin cross-linked hemoglobin (DCLHb) in stroke patients.In a randomized phase II study, increasing doses of DCLHb (25, 50 and 100 mg/kg, n=8, 8 and 11, respectively) or placebo (n=26) were infused intravenously every 6 h for 72 h to patients with an acute ischemic stroke. Blood pressure and heart rate were measured every 15 min and plasma concentrations of endothelin-1, catecholamines, renin, vasopressin and atrial natriuretic peptide were measured before and 24 and 66 h after the start of the infusions.In the placebo group, mean arterial pressure (MAP) was 112 (109-115) mmHg (mean and 95% confidence interval) at baseline and decreased spontaneously by 11.4 (5.4-17.5) and 12.5 (5.4-19.5) mmHg after 24 and 66 h, respectively. This decrease in MAP was attenuated in patients treated with DCLHb, reaching statistical significance in the highest dose group. The plasma endothelin-1 concentration decreased slightly in the placebo group, from 4.2 (3.1-5.3) pg/ml (median and range) at baseline to 2.4 (1.9-3.7) pg/ml after 24 h (P=0.0044) and 2.8 (1.9-3.7) pg/ml after 66 h (P=0.0042), but increased dose-dependently in response to DCLHb infusion. With the highest dose of DCLHb, the plasma endothelin-1 concentration rose from 4.8 (0.1-7.8) pg/ml at baseline to 21.2 (13.4-53.2) pg/ml after 24 h (P< 0.001) and to 27.6 (11.9-47.8) pg/ml after 66 h (P< 0.001). The increases in the plasma endothelin-1 concentration and in MAP were correlated (r=0.30, P=0.02). Other vasoactive hormones were not affected by the DCLHb infusion.Infusion of DCLHb in patients with acute ischemic stroke was associated with a dose-dependent increase in plasma endothelin-1 concentration. This may underlie the attenuation by DCLHb of the natural decrease in blood pressure that we observed in these patients."
1,"TITLE: Effects of an ionic versus a nonionic low osmolar contrast agent on the thrombotic complications of coronary angioplasty.ABSTRACT: An increasing body of evidence suggests that the potential for thrombotic complications is greater with nonionic than with ionic contrast agents. This is a particularly important consideration in the highly thrombogenic setting of percutaneous transluminal coronary angioplasty (PTCA). To explore this issue further, 500 consecutive patients undergoing PTCA were prospectively randomized to receive the low osmolality ionic ioxaglate or the nonionic agent iohexol. The number of acute thrombotic in-laboratory events was significantly less in the ioxaglate than in the iohexol group (8 versus 18; P < 0.05), but there was no significant difference between the 2 groups as regards the number of out-of-laboratory acute rethrombotic events. With multivariate analysis, use of the nonionic agent rather than the ionic agent emerged as an independent predictor of acute in-laboratory rethrombosis. These data suggest that, in the performance of PTCA, an ionic, rather than a nonionic, should be the preferred contrast agent."
1,"TITLE: Weight gain of Kenyan school children infected with hookworm, Trichuris trichiura and Ascaris lumbricoides is improved following once- or twice-yearly treatment with albendazole.ABSTRACT: We studied growth in infected children given one dose (600 mg) or two doses of albendazole per school year. Children were examined and allocated at random within sex by descending hookworm egg count to one of three groups: placebo (n = 93), one dose (1x, n = 96) or two doses (2x, n = 95). Each child was treated and then re-examined and treated 3.6 and 8.2 mo later (Exams 2 and 3). The 1x and 2x groups gained significantly more by Exam 3 than the placebo group in weight (1.1 and 0.9 kg more, respectively), percent weight-for-age (3.3 and 2.7 percentage points more), percent weight-for-height (3.1 and 2.9 percentage points more), percent arm circumference-for-age (2.3 and 2.0 percentage points more) and triceps and subscapular skinfolds but did not differ significantly from each other. The placebo group showed significant decreases between exams (P < 0.0002) in percent weight-for-age and percent arm circumference-for-age and no change in percent weight-for-height, whereas the 1x and 2x groups exhibited significant increases (P < 0.005). At Exam 3, arithmetic mean egg reduction rates for the 1x and 2x groups were 84 and 95% for hookworm, 42 and 32% for Trichuris and 55 and 87% for Ascaris, respectively. We conclude that one or two doses of albendazole per year resulted in similar growth improvements, despite reinfection, in school-age children in an area where these helminths and poor growth are prevalent."
1,"TITLE: Effects of enalapril on ventricular volumes and neurohumoral status after inferior wall myocardial infarction.ABSTRACT: The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system and its beneficial modification with the use of angiotensin-converting enzyme inhibin after inferior wall myocardial infarction (MI) was evaluated. Fifty patients with acute inferior MI were randomly assigned to receive 5 mg per day of either enalapril or placebo after admission. Blood tests for neurohormone levels and echocardiograms were performed at initial examination and 4 weeks later. Baseline characteristics were similar in the two groups. Four weeks after randomization, patients treated with enalapril had lower end-diastolic volume (146 +/- 29 vs 167 +/- 15 ml; p = 0.04), end-systolic volume (56 +/- 18 vs 107 +/- 17 ml; p = 0.03), serum norepinephrine levels (320 +/- 93 vs 465 +/- 77 pg/ml; p < 0.01), angiotensin II levels (18 +/- 6 vs 54 +/- 11 pg/ml; p < 0.01), and atrial natriuretic polypeptide levels (106 +/- 9 vs 122 +/- 17 pg/ml; p = 0.05) than patients given placebo. The incidence of heart failure after MI was also lower in this group (4% vs 16%; p = 0.009). Results show that there is early neurohumoral activation in the course of acute inferior wall MI. Enalapril reduces neurohumoral levels and preserves ventricular volumes. These effects were associated with a reduction in the incidence of heart failure 4 weeks after MI in these patients."
1,"TITLE: Relationship between salt and blood pressure in hypertensive patients on chronic ACE-inhibition.ABSTRACT: We investigated the effect of a 4-day oral salt load (150 mmol NaCl extra per day) on blood pressure, erythrocyte sodium transport and the activity in the renin-angiotensin system in six males with primary hypertension, who had attained normotension on chronic enalapril treatment for 4 years. The design was a placebo-controlled, randomized, two-way cross over, double-blind study, i.e. each patient served as his own control. Intracellular erythrocyte sodium and potassium content were measured by flame photomometry. The increase in the intracellular sodium concentration during 1 h in 37 degrees C incubation of whole-blood with ouabain (compared with no-ouabain) was measured to determine the rate of active sodium efflux. 24-h blood pressure registration was performed with Space-lab equipment (SL 90202) before and at the end of the salt load. Left ventricular morphology was evaluated with echocardiography and the minimal vascular resistance of the hand vascular bed with water plethysmography at baseline and after 4 years on enalapril. Four years' enalapril treatment caused a significant decrease in blood pressure, left ventricular mass and minimal vascular resistance. During the 4-day salt load average 24-h blood pressure was significantly elevated, 129+/-3/85+/-2 mmHg as compared to 124+/-2/82+/-2 mmHg during placebo treatment (p=0.025). The change (delta) in MAP during high salt intake showed a negative relationship to delta-sodium efflux rate constant (r=-0.65, p=0.047). No significant relationship was found between the blood pressure response to the salt load and structural cardiovascular changes. In conclusion, a short-term oral salt load in hypertensive patients on chronic enalapril treatment caused a blood pressure rise, which was related to cellular sodium transport but not to structural cardiovascular changes."
1,"TITLE: Re-evaluation of i.m. ephedrine as prophylaxis against hypotension associated with spinal anaesthesia for Caesarean section.ABSTRACT: To assess the safety and efficacy of 37.5 mg ephedrine i.m. in preventing hypotension associated with spinal anaesthesia for Caesarean section.In a double-blind randomised controlled study, 40 patients (20 in each group) were given either 37.5 mg ephedrine or placebo i.m. The following parameters were recorded: (i) blood pressure; (ii) heart rate; (iii) ephedrine i.v. supplementation; (iv) umbilical venous blood gases and neonatal Apgar scores.The incidence of hypertension in the study group was 30% compared with 20% for the control group (P:NS). There was no difference in mean highest blood pressure or mean highest heart rate between the groups. The incidence of hypotension was lower but not significantly lower in the study group (50%) than in the control group (80%) (P:NS). However, the incidence of delayed hypotension was only 10% in the study group patients compared with 50% in the control group patients (P < 0.05).Giving 37.5 mg ephedrine i.m. prior to spinal anaesthesia was not associated with reactive hypertension or tachycardia. Intramuscular ephedrine provided more sustained cardiovascular support than intravenous ephedrine."
0,"TITLE: Insulin therapy in burn patients does not contribute to hepatic triglyceride production.ABSTRACT: Lipid kinetics were studied in six severely burned patients who were treated with a high dose of exogenous insulin plus glucose to promote protein metabolism. The patients were 20+/-2-yr-old (SD) with 63+/-8% total body surface area burned. They were studied in a randomized order (a) in the fed state on the seventh day of a control period (C) of continuous high-carbohydrate enteral feeding alone, and (b) on the seventh day of enteral feeding plus exogenous insulin (200 pmol/h = 28 U/h) with extra glucose given as needed to avoid hypoglycemia (I+G). Despite a glucose delivery rate approximately 100% in excess of energy requirements, the following lipid parameters were unchanged: (a) total hepatic VLDL triglyceride (TG) secretion rate (0.165+/-0.138 [C] vs. 0.154+/- 0.138 mmol/kg . d-1 [I+G]), (b) plasma TG concentration (1.58+/-0.66 [C] vs. 1. 36+/-0.41 mmol/liter [I+G]), and (c) plasma VLDL TG concentration (0. 68+/-0.79 [C] vs. 0.67+/- 0.63 mmol/liter [I+G]). Instead, the high-carbohydrate delivery in conjunction with insulin therapy increased the proportion of de novo-synthesized palmitate in VLDL TG from 13+/-5% (C) to 34+/-14% (I+G), with a corresponding decreased amount of palmitate from lipolysis. In association with the doubling of the secretion rate of de novo-synthesized fatty acid (FA) in VLDL TG during insulin therapy (P > 0.5), the relative amount of palmitate and stearate increased from 35+/-5 to 44+/-8% and 4+/-1 to 7+/-2%, respectively, in VLDL TG, while the relative concentration of oleate and linoleate decreased from 43+/-5 to 37+/-6% and 8+/-4% to 2+/-2%, respectively. A 15-fold increase in plasma insulin concentration did not change the rate of release of FA into plasma (8.22+/-2.86 [C] vs. 8.72+/-6.68 mmol/kg.d-1 [I+G]. The peripheral release of FA represents a far greater potential for hepatic lipid accumulation in burn patients than the endogenous hepatic fat synthesis, even during excessive carbohydrate intake in conjunction with insulin therapy."
0,"TITLE: An oral sodium citrate-citric acid non-particulate buffer in humans.ABSTRACT: We have investigated the effect on the pH of the gastric fluid of a single dose of sodium citrate 0.3 mol litre-1 (antacid) and a solution containing sodium citrate dehydrate (100 mg ml-1) with citric acid monohydrate (66 mg ml-1) (buffer). The dose for both solutions was 0.4 ml kg-1 via a nasogastric tube. Each group comprised 10 patients undergoing neurosurgical operations of 5-7 h duration. A control group of 10 patients received no gastric solution. The pH of the gastric aspirate was measured hourly using a Metrohm 632 digital pH meter (Synectics Medical, Sweden). Mean baseline gastric pH was 2.64 (SD 1.71). In the control group, pH increased to 4.4 (1.51) at 5 h, returning to baseline at 7 h. In the antacid group, pH increased to 6.11 (0.47) at 15 min and decreased to 3.70 (1.94) at 7 h (P < 0.01). In the buffer group, pH was stable at 3.80-3.95 (0.22) over 7 h (P > 0.01). Total mean gastric aspirate was 0.5 ml kg-1."
1,"TITLE: A randomised, double-blind, parallel-group study to compare the efficacy and safety of ondansetron (GR38032F) plus dexamethasone with metoclopramide plus dexamethasone in the prophylaxis of nausea and emesis induced by carboplatin chemotherapy.ABSTRACT: A double-blind, parallel-group study in 189 ovarian cancer patients compared the efficacy of ondansetron 8 mg i.v. (OND) and metoclopramide 60 mg i.v. (MET) both in combination with dexamethasone 20 mg i.v. in the prevention of carboplatin-induced emesis. On day 1, complete or major control of emesis (0-2 emetic episodes) was observed in 97% patients from the OND group compared with 74% patients from the MET group (p < 0.001). Similarly, a worst-day analysis over days 1-3 showed complete or major control of emesis in 87% patients (OND) compared wth 66% patients (MET) (p < 0.001). Similar findings in favour of the OND group were observed for nausea grade on day 1 and the worst-day grade during days 1-3. OND was better tolerated than MET. Fewer patients from the OND group (13%) reported adverse events compared with the MET group (21%). Extrapyramidal type symptoms were observed in 6 (6%) patients from the MET group (paraesthesia, involuntary movement of the jaw and tongue, and restlessness), compared with none from the OND group. Ondansetron plus dexamethasone is a highly effective and well-tolerated treatment and is significantly superior to metoclopramide plus dexamethasone in the prevention of carboplatin-induced emesis."
1,"TITLE: Randomized trial of two versus five years of adjuvant tamoxifen for postmenopausal early stage breast cancer. Swedish Breast Cancer Cooperative Group.ABSTRACT: Postsurgical treatment with tamoxifen has been shown to improve overall survival among patients with early stage breast cancer. However, the optimal duration of tamoxifen treatment remains controversial.A multicenter, randomized trial was initiated in Sweden in the early 1980s to compare 2 years with 5 years of adjuvant tamoxifen in the treatment of postmenopausal women younger than 75 years of age who had early stage, axillary lymph node-negative or -positive, invasive disease.The trial was planned and organized by the Swedish Breast Cancer Group, and it involved five regional breast cancer study organizations (South Sweden, South-East Sweden, Stockholm, Uppsala-Orebro, and North Sweden). During the period from 1983 through 1991, a total of 3887 patients were entered in the trial; 3545 (91%) women remained alive and recurrence free at 2 years and could thus contribute meaningful information to the 2-year (n = 1801) versus 5-year (n = 1744) comparison. Primary surgery consisted of either modified radical mastectomy or breast-conserving surgery. Radiation therapy was indicated for patients with lymph node-positive disease and was generally offered to all women who were treated with breast-conserving surgery. Only 89 (2.5%) of the 3545 women who were recurrence free at 2 years received adjuvant chemotherapy concurrently with tamoxifen. Twenty-milligram daily doses of tamoxifen were used at two centers, and 40-mg daily doses were used at the remaining three centers. Estrogen receptor status of the tumor was known for 2987 women (77% of the entered patients). Primary end points in the trial were event-free survival (local-regional recurrence, distant metastasis, contralateral breast cancer, or death) and overall survival. Survival curves were estimated by use of the life-table method. The Cox proportional hazards model was used to make comparisons between the 2- and 5-year treatment groups.Patients assigned to receive 5 years of tamoxifen, compared with 2 years of tamoxifen, experienced statistically significant improvements in event-free survival (relative hazard = 0.82; 95% confidence interval [CI] = 0.71-0.96) and overall survival (relative hazard = 0.82; 95% CI = 0.69-0.99). These findings translate into an 18% relative reduction in both first events (95% CI = 4%-29%) and mortality (95% CI = 1%-31%) with the longer treatment. Overall survival at 10 years was estimated to be 80% among patients in the 5-year tamoxifen group who were alive and recurrence free at 2 years, compared with 74% among corresponding patients in the 2-year treatment group. The benefit associated with the longer treatment extended to women with lymph node-positive as well as lymph node-negative disease, but it appeared to be restricted to women whose tumors were classified as estrogen receptor positive.Five years of adjuvant tamoxifen is more beneficial than 2 years in the treatment of postmenopausal women with estrogen receptor-positive, early stage, invasive breast cancer."
1,"TITLE: Hemodynamic effects of the class III antiarrhythmic drug, d-sotalol, in patients with congestive heart failure.ABSTRACT: In contrast to Vaughan Williams class I drugs, class III drugs, such as d-sotalol, may not be negative inotropic. These drugs block potassium ion channels and prolong repolarization, theoretically leading to improved contractility. We investigated the hemodynamic actions of acute intravenous administration of 1.5 mg/kg of d-sotalol in 28 patients with congestive heart failure randomized to receive placebo (n = 10) or active drug (n = 18) in a double-blind study. A Swan-Ganz catheter was placed in all patients > or = 16 hours before drug administration. All hemodynamic variables were assessed at baseline and 30 minutes and 1, 2, 4, 8, and 12 hours after administration of the drug. Electrocardiograms were obtained before and 1, 2, 4, and 12 hours after drug administration. The QT interval increased from 370 +/- 9 to 426 +/- 14 ms at 1 hour, whereas the QTc increased from 433 +/- 5 to 470 +/- 12 ms (both p < 0.001). The increase was still statistically significant at 12 hours. There was no change in the placebo group. Although heart rate decreased in the d-sotalol group (84 +/- 2 to 76 +/- 2 at 1 hour, p < 0.001), there were no changes in blood pressure or right atrial pressure. Cardiac index decreased slightly (2.0 +/- 0.2 to 1.9 +/- 0.1 mm Hg), consistent with the lower heart rate. Pulmonary capillary wedge pressure decreased from 18.9 +/- 2.4 to 17.9 +/- 1.9 mm Hg at 1 hour despite reduced cardiac index. We conclude that in contrast to class I, II, and IV antiarrhythmic drugs, d-sotalol exerts no clinically important acute hemodynamic actions at doses that produce electrophysiologic effects."
1,"TITLE: Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized, controlled trial. Montelukast/Beclomethasone Study Group.ABSTRACT: Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma.To compare the clinical benefit of montelukast, a once-daily oral leukotriene receptor antagonist; placebo; and inhaled beclomethasone.Randomized, double-blind, double-dummy, placebo-controlled, parallel-group, 12-week study.36 sites worldwide.895 patients 15 to 85 years of age with chronic asthma and an FEV1 50% to 85% of predicted.Montelukast, 10 mg once daily at bedtime; inhaled beclomethasone, 200 microg twice daily, administered with a spacer device; or placebo.Primary end points were daytime asthma symptom score and FEV1. Secondary end points were peak expiratory flow rates in the morning and evening, as-needed beta-agonist use, nocturnal awakenings, asthma-specific quality of life, and worsening asthma episodes.Over the 12-week treatment period, the average percentage change from baseline in FEV1 was 13.1% with beclomethasone, 7.4% with montelukast, and 0.7% with placebo (P < 0.001 for each active treatment compared with placebo; P < 0.01 for beclomethasone compared with montelukast). The average change from baseline in daytime symptom score was -0.62 for beclomethasone, -0.41 for montelukast, and -0.17 for placebo (P < 0.001 for each active treatment compared with placebo; P < 0.01 for beclomethasone compared with montelukast). Each agent improved peak expiratory flow rates and quality of life, reduced nocturnal awakenings and asthma attacks, increased the number of asthma-control days, and decreased the number of days with asthma exacerbations (P < 0.001 for each active treatment compared with placebo for each end point; P < 0.01 for beclomethasone compared with montelukast for each end point). Although beclomethasone had a greater mean clinical benefit than montelukast, montelukast had a faster onset of action and a greater initial effect. The two agents caused similar decreases in peripheral blood eosinophil counts (P < 0.05 for each agent compared with placebo). Both agents had tolerability profiles similar to that of placebo over the 12-week study.Although beclomethasone had a larger mean effect than montelukast, both drugs provided clinical benefit to patients with chronic asthma. This finding is consistent with the use of these agents as controller medications for chronic asthma."
1,"TITLE: The contribution of the swallowed fraction of an inhaled dose of salmeterol to it systemic effects.ABSTRACT: Salmeterol is approximately eight times as potent as salbutamol for systemic effects. This may be because the drug is eight times more potent on receptors or there may be differences in systemic bioavailability. The systemic effects of salbutamol are limited by its fairly high first-pass metabolism, but the oral bioavailability of salmeterol is unknown. The contribution of the swallowed fraction of an inhaled dose of salmeterol to its systemic effects were analysed in a randomized, double-blind, crossover study. Twelve healthy subjects were given inhaled salmeterol 400 microg, inhaled salmeterol 400 microg plus oral activated charcoal or inhaled placebo plus oral activated charcoal on three separate days. Cardiac frequency (fC), Q-T interval corrected for heart rate (QTc), plasma potassium and glucose concentrations were measured for 4 h following the inhaled drug. Salmeterol with and without oral charcoal produced significant changes for all measures compared to placebo. The magnitude of effect following salmeterol alone was significantly greater than that following salmeterol plus charcoal for fC and glucose (mean (95% confidence interval) differences 8 (2-13) beats x min(-1), 0.59 (0.04, 1.13) mmol x L(-1), respectively) and nonsignificantly greater for QTc interval and potassium concentration. The differences between salmeterol given with and without charcoal suggest that 28-36% of the systemic response to salmeterol administered from a metered-dose inhaler are due to drug absorbed from the gastrointestinal tract. Thus, most of the systemic effects are due to the inhaled fraction of the drug."
1,TITLE: Corticosteroid treatment of erythema multiforme major (Stevens-Johnson syndrome) in children.ABSTRACT: The effectiveness of systemic corticosteroids in erythema multiforme major (EMM) is controversial. We therefore evaluated the efficacy of corticosteroids in the treatment of EMM in a prospective study of 16 children with EMM admitted to our department within 3 days from the onset of rash. Ten patients (group A) received bolus infusions of methylprednisolone (4 mg/kg/day) while six had only supportive treatment (group B). The early use of corticosteroids compared to supportive treatment resulted in: (1) significant reduction of the period of fever (4.0 +/- 1.9 vs 9.5 +/- 4.2 days P = 0.01); (2) reduction of the period of acute eruption (7.0 +/- 3.3 versus 9.8 +/- 3.0 days P = 0.08); and (3) milder signs of prostration. Complications were minimal in both groups.The early and short course of corticosteroids favourably influences the course of erythema multiforme major in children.
1,"TITLE: Triazolam is ineffective in patients taking rifampin.ABSTRACT: Triazolam is metabolized predominantly by cytochrome P450 3A4 (CYP3A4). Rifampin (rifampicin) is a potent inducer of CYP3A4 and it is known to markedly reduce plasma concentrations and effects of drugs such as midazolam. The possible interaction between rifampin and triazolam was examined in this study.The pharmacokinetics and pharmacodynamics of triazolam were investigated in a randomized, double-blind crossover study with two phases. Ten young healthy volunteers took either 600 mg rifampin once daily or placebo for 5 days. On the sixth day, 0.5 mg triazolam was administered orally. Timed blood samples were collected and the effects of triazolam were measured with five psychomotor tests for 10 hours.The area under the plasma triazolam concentration-time curve in the rifampin phase was only 5.1% of that in the placebo phase (0.74 +/- 0.14 versus 14.8 +/- 1.0 ng.hr/ml [mean +/- SEM; p < 0.001]). Rifampin pretreatment decreased the maximum plasma concentration of triazolam to 12.4% of the control value (i.e., from 2.9 +/- 0.2 to 0.36 +/- 0.06 ng/ml [p < 0.001]) and the elimination half-life from 2.8 +/- 0.1 to 1.3 +/- 0.1 hours (p < 0.001). All psychomotor tests showed markedly reduced effects (p < 0.01) of triazolam after rifampin pretreatment.Triazolam is ineffective during rifampin treatment. This is most likely due to increased metabolism of triazolam after induction of CYP3A4 in the gut wall and liver by rifampin. It is advisable to use hypnotic agents that are not metabolized by CYP3A4 during treatment with rifampin or other potent inducers of CYP3A4."
1,"TITLE: Post-partum urinary retention: a comparison between two methods of epidural analgesia.ABSTRACT: To compare two methods of epidural labor analgesia regarding the incidence of post-partum urinary retention.One thousand parturients who requested epidural analgesia for the relief of labor pain received, at random, either bupivacaine 0.25% with adrenaline 1:200 000 (n = 500) or bupivacaine 0.125% with 10 micrograms sufentanil (n = 500). During the same observation period all women with clinically significant urinary retention (> 500 ml, requiring indwelling catheter) were registered.Altogether 30/3.364 parturients had clinically significant urinary retention. Twenty-seven of these had received epidural analgesia (EDA) (17 with bupivacaine/adrenaline and ten with bupivacaine/sufentanil, a non-significant differences). The number of parturients with urinary retention was highly increased following EDA (27/1000) as compared to those not receiving EDA (3/2364), P < 0.001 (Fisher's exact test). In patients with EDA and urinary retention there were no difference between the groups in the incidence of instrumental deliveries or vaginal/perirectal tears. All parturients regained normal bladder function.EDA significantly increased the risk of post-partum urinary retention but no difference was found between the two epidural techniques."
1,"TITLE: Use of tunneled femoral catheters to prevent catheter-related infection. A randomized, controlled trial.ABSTRACT: The risk for catheter-related infection seems higher with femoral catheters than with catheters inserted at other sites.To evaluate the effect of catheter tunneling on femoral catheter-related infection in critically ill patients.Randomized, controlled trial.Three intensive care units at academic hospitals in Paris, France.345 adult patients requiring a femoral venous catheter for more than 48 hours.Tunneled or nontunneled femoral catheters.Time to occurrence of systemic catheter-related sepsis, catheter-related bloodstream infection, and quantitative catheter tip culture with a cutoff of 10(3) colony-forming units/mL.Of 345 randomly assigned patients, 336 were evaluable. Probable systemic catheter-related sepsis occurred in 15 of 168 patients who received a nontunneled femoral catheter (controls) and in 5 of 168 patients who received a tunneled femoral catheter (estimated absolute risk reduction, 6% [95% CI, 0.9% to 11%]). Time to occurrence of catheter-related bloodstream infection was not significantly modified (relative risk, 0.28 [CI, 0.03 to 1.92]; P = 0.18); 3 events occurred in the control group and 1 event occurred in the tunneled-catheter group. After stratification by treatment center and adjustment for variables that were prognostic (use of broad-spectrum antimicrobial agents at catheter insertion) or imbalanced between both groups (mechanical ventilation at insertion), tunnelized catheterization reduced the proportion of patients who developed systemic catheter-related sepsis (relative risk, 0.25 [CI, 0.09 to 0.72]; P = 0.005) and positive quantitative culture of the catheter tip (relative risk, 0.48 [CI, 0.23 to 0.99]; P = 0.045).The incidence of femoral catheter-related infections in critically ill patients can be reduced by using subcutaneous tunneling."
1,"TITLE: A high dose of albuterol does not overcome bronchoprotective subsensitivity in asthmatic subjects receiving regular salmeterol or formoterol.ABSTRACT: Regular treatment with inhaled, long-acting beta2 -agonists is associated with subsensitivity for bronchoprotective effects. It is not known whether a high dose of short-acting beta2 -agonist could overcome this subsensitivity.The objective of this study was to investigate the acute effects of a high dose of inhaled albuterol on methacholine-induced bronchoconstriction in patients receiving regular treatment with salmeterol or formoterol.Ten stable asthmatic subjects (mean age, 34 years; FEV1, 77% of predicted value), all taking inhaled corticosteroids (methacholine PD20 < 500 microg), were recruited into a randomized, single-blind, crossover study. After an initial 1-week run-in period, subjects underwent 3 separate treatment periods each of 9 days (separated by a washout of at least 5 days) comprising inhaled placebo twice daily, inhaled salmeterol dry powder 50 microg twice daily, or inhaled formoterol dry powder 12 microg twice daily. Methacholine challenge was performed 1 hour after the first dose and after 7 days of treatment. After 9 days of treatment, a third methacholine challenge was performed 1 hour after inhalation of a single 1600 microg dose of albuterol dry powder.There was significant (P <.001) improvement in geometric mean PD20 after the first dose of active treatment as compared with placebo (78 microg) versus salmeterol (266 microg, a 3.4-fold difference [95% CI 1.9 to 6.1]) and versus formoterol (318 microg, a 4.1-fold difference [95% CI 2.3 to 7.3]). This bronchoprotection diminished with regular treatment, although it remained significant (P <.01) compared with placebo (68 microg) versus salmeterol (144 microg, a 2.1-fold difference [95% CI 1.2 to 3.8]) and versus formoterol (230 microg, 3.4-fold difference [95% CI 1.9 to 6.2]). After 9 days, the protection afforded by a single dose of albuterol after placebo pretreatment (889 microg) was significantly (P =.005) higher in comparison with albuterol protection after salmeterol pretreatment (338 microg, a 2.7-fold difference [95% CI 1.1 to 6.8]) and after formoterol pretreatment (247 microg, a 3.6-fold difference [95% 1.4 to 9.1]).Thus in stable asthmatic subjects receiving regular salmeterol or formoterol, bronchoprotective subsensitivity was not overcome by administering a high dose of albuterol. Further studies are required to evaluate the clinical relevance of this pharmacologic phenomenon when albuterol is used in acute asthma."
1,"TITLE: Serum S100beta release after coronary artery bypass grafting: roller versus centrifugal pump.ABSTRACT: Microemboli generated during cardiopulmonary bypass (CPB) are implicated in the cerebral injury seen after coronary artery bypass grafting. Centrifugal pumps generate fewer microemboli than roller pumps. Increased S100beta levels have been reported after coronary artery bypass grafting, with levels greater than 1 ng/mL resulting in poorer neuropsychologic outcome. This study investigated the potential neurologic benefits of centrifugal pumps, by using S100beta as a marker for cerebral injury.Thirty-two patients who had coronary artery bypass grafting were randomly assigned to two groups. Serial blood samples (preoperative, end of bypass, 30 minutes, and 2 and 24 hours after cardiopulmonary bypass) were taken and the serum analyzed for S100beta using a new immunoluminometric assay.Both groups were matched for age, number of grafts, and cardiopulmonary bypass and cross-clamp times. Postoperative serum S100beta levels were significantly higher in both groups than preoperative levels. Peak S100beta levels did not correlate with cardiopulmonary bypass time; however, 24-hour S100beta levels correlated with intubation time r = 0.40, p = 0.04). Th ere was no significant difference in S100beta levels between the groups at any of the time points.S100beta levels increased after coronary artery bypass grafting. Centrifugal pumps do not significantly decrease S100beta release. Persistently increased S100beta levels are associated with longer intubation times."
1,"TITLE: A vitamin E concentrate rich in tocotrienols had no effect on serum lipids, lipoproteins, or platelet function in men with mildly elevated serum lipid concentrations.ABSTRACT: Tocotrienols, lipid-soluble antioxidants with vitamin E activity, have been reported to lower LDL-cholesterol concentrations and platelet aggregation in men, but results are contradictory.To examine in detail the effects of a vitamin E concentrate rich in tocotrienols on serum lipoproteins and on platelet function in men at risk for cardiovascular disease.In this randomized, double-blind, placebo-controlled parallel trial, 20 men received daily for 6 wk 4 capsules, each containing 35 mg tocotrienols and 20 mg alpha-tocopherol; 20 other men received 4 capsules daily, each providing 20 mg alpha-tocopherol. All men had concentrations of serum total cholesterol between 6.5 and 8.0 mmol/L or lipoprotein(a) concentrations > 150 mg/L.Compliance was confirmed by changes in serum tocopherol and tocotrienol concentrations. Serum LDL cholesterol in the tocotrienol group was 4.80 mmol/L before and 4.79 mmol/L after intervention, and increased from 4.70 to 4.86 mmol/L in the placebo group (95% CI for the difference: -0.54, 0.19 mmol/L; P = 0.333). Also, changes in HDL cholesterol, triacylglycerol, lipoprotein(a), and lipid peroxide concentrations did not differ between the groups. After adjustment for differences in initial values, no effects were found on collagen-induced platelet aggregation velocity, maximum aggregation, or thromboxane B2 formation in citrated whole blood. ATP release, however, was lower in the tocotrienol group. Urinary thromboxane B2 and 11-keto-thromboxane B2 concentrations and coagulation and fibrinolytic measures did not change.The tocotrienol supplements used had no marked favorable effects on the serum lipoprotein profile or on platelet function in men with slightly elevated lipid concentrations."
0,"TITLE: Clonidine premedication modifies responses to adrenoceptor agonists and baroreflex sensitivity.ABSTRACT: To evaluate the effects of clonidine on responses to adrenoceptor agonists and baroreflex sensitivity, we examined arterial blood pressure (AP) responses to phenylephrine and heart rate (HR) responses to isoproterenol and baroreflex sensitivity (HR response to AP changes due to phenylephrine or nitroglycerin).We studied 60 anaesthetized patients who either did or did not receive 5 micrograms.kg-1 clonidine po before they were anaesthetized. After induction of general anaesthesia, the patients received 3 micrograms.kg-1 phenylephrine, 0.02 microgram.kg-1 isoproterenol, or 2-3 micrograms.kg-1 nitroglycerin, and haemodynamic measurements were taken. Baroreflex sensitivity was expressed as the slope of the linear regression line (msec.mmHg-1; in msec of R-R interval change vs mmHg change in systolic arterial pressure) following the administration of phenylephrine and nitroglycerin.Patients who received clonidine had greater augmented responses in AP to phenylephrine and in HR to isoproterenol (47.2 +/- 15.6% vs 23.7 +/- 11.9% for increase in systolic AP and 59.8 +/- 22.6% vs 26.2 +/- 11.0% for increase in HR, P < 0.05 respectively). There were no differences between the baroreflex sensitivities in the pressor (phenylephrine) test groups (3.77 +/- 1.08 vs 4.41 +/- 1.66 msec.mmHg-1). In contrast, the slopes of depressor (nitroglycerin) test groups were decreased in patients receiving clonidine (1.98 +/- 0.73 vs 3.68 +/- 1.72 msec.mmHg-1, P < 0.05).The results suggest that premedication with clonidine might enhance critical hypotension during anaesthesia and surgery, but restoration both of AP and HR decrease can be achieved effectively by phenylephrine and isoproterenol i.v., respectively."
1,"TITLE: Effect of soy protein foods on low-density lipoprotein oxidation and ex vivo sex hormone receptor activity--a controlled crossover trial.ABSTRACT: Plant-derived estrogen analogs (phytoestrogens) may confer significant health advantages including cholesterol reduction, antioxidant activity, and possibly a reduced cancer risk. However, the concern has also been raised that phytoestrogens may be endocrine disrupters and major health hazards. We therefore assessed the effects of soy foods as a rich source of isoflavonoid phytoestrogens on LDL oxidation and sex hormone receptor activity. Thirty-one hyperlipidemic subjects underwent two 1-month low-fat metabolic diets in a randomized crossover study. The major differences between the test and control diets were an increase in soy protein foods (33 g/d soy protein) providing 86 mg isoflavones/2,000 kcal/d and a doubling of the soluble fiber intake. Fasting blood samples were obtained at the start and at weeks 2 and 4, with 24-hour urine collections at the end of each phase. Soy foods increased urinary isoflavone excretion on the test diet versus the control (3.8+/-0.7 v 0.0+/-0.0 mg/d, P < .001). The test diet decreased both oxidized LDL measured as conjugated dienes in the LDL fraction (56+/-3 v 63+/-3 micromol/L, P < .001) and the ratio of conjugated dienes to LDL cholesterol (15.0+/-1.0 v 15.7+/-0.9, P = .032), even in subjects already using vitamin E supplements (400 to 800 mg/d). No significant difference was detected in ex vivo sex hormone activity between urine samples from the test and control periods. In conclusion, consumption of high-isoflavone foods was associated with reduced levels of circulating oxidized LDL even in subjects taking vitamin E, with no evidence of increased urinary estrogenic activity. Soy consumption may reduce cardiovascular disease risk without increasing the risk for hormone-dependent cancers."
1,"TITLE: Effects of supplemental alpha-tocopherol and beta-carotene on colorectal cancer: results from a controlled trial (Finland)ABSTRACT: Some epidemiological investigations suggest that higher intake or biochemical status of vitamin E and beta-carotene might be associated with reduced risk of colorectal cancer.We tested the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of colorectal cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, placebo-controlled trial among 29,133 50-69-year-old male cigarette smokers. Participants were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or a placebo daily for 5-8 years. Incident colorectal cancers (n = 135) were identified through the nationwide cancer registry, and 99% were histologically confirmed. Intervention effects were evaluated using survival analysis and proportional hazards models.Colorectal cancer incidence was somewhat lower in the alpha-tocopherol arm compared to the no alpha-tocopherol arm, but this finding was not statistically significant (relative risk (RR) = 0.78, 95% confidence interval (CI) 0.55-1.09; log-rank test p = 0.15). Beta-carotene had no effect on colorectal cancer incidence (RR = 1.05, 95% CI 0.75-1.47; log-rank test p = 0.78). There was no interaction between the two substances.Our study found no evidence of a beneficial or harmful effect for beta-carotene in colorectal cancer in older male smokers, but does provide suggestive evidence that vitamin E supplementation may have had a modest preventive effect. The latter finding is in accord with previous research linking higher vitamin E status to reduced colorectal cancer risk."
1,"TITLE: Improvement in exercise capacity with nitric oxide inhalation in patients with precapillary pulmonary hypertension.ABSTRACT: Patients with precapillary pulmonary hypertension (PH) exhibit a poor exercise capacity due to an impaired vasodilatory response of their pulmonary arteries. By causing the pulmonary artery to dilate, inhaled nitric oxide (NO) may allow an increase in exercise capacity in patients with PH.On 2 separate days, 3 days apart, 14 patients with precapillary PH (10 primary PH, 4 residual PH after correction of an intracardiac shunt; age, 40+/-12 years; mean pulmonary artery pressure, 60+/-23 mm Hg) performed exercise, with and without inhalation of 20 ppm NO, on a cycle ergometer. The work rate was increased 15 W/min until their symptom-limited maximum, with breath-by-breath gas analysis. Patients were randomly and blindly selected to inhale NO on either their first or second test. Peak exercise load and anaerobic threshold tended to increase, but not significantly. Peak oxygen consumption (f1.gif"" BORDER=""0"">O(2)) and Deltaf1.gif"" BORDER=""0"">O(2)/DeltaW ratio increased significantly, by 18% and 22%, respectively (peak f1.gif"" BORDER=""0"">O(2), 13.6+/-3.6 to 16.0+/-4. 1 mL. kg(-1). min(-1); Deltaf1.gif"" BORDER=""0"">O(2)/DeltaW ratio, 5. 8+/-2.4 to 7.1+/-2.3 mL. kg(-1). min(-1). W(-1); both P<0.01). Peak f1.gif"" BORDER=""0"">O(2) increased >10% in 12 of the 14 patients. However, respiratory quotient at peak exercise decreased from 1. 22+/-0.15 to 1.09+/-0.15 (P<0.01).Inhaled NO substantially increases oxygen consumption at the same workload during exercise. This finding supports the possibility of ambulatory NO inhalation therapy in patients with precapillary PH."
1,"TITLE: Pulmonary effects of short-term exposure to low levels of toluene diisocyanate in asymptomatic subjects.ABSTRACT: Isocyanates may be involved in the development of chronic obstructive airway disease among exposed workers. A short-term exposure to toluene diisocyanate (TDI) at concentrations near the permissible levels was investigated to examine whether there was an association with changes in pulmonary function tests and in potential markers of airway injury and inflammation in bronchial lavage (BL) and bronchoalveolar lavage (BAL). Seventeen subjects without respiratory symptoms (eight smokers and nine nonsmokers) were exposed once to ambient air and once to TDI (5 parts per billion (ppb) for 6 h followed by 20 ppb for 20 min) in a randomized, single-blind sequence. Pulmonary function tests were repeatedly assessed during exposure and BAL was performed 1 h after each exposure. Biochemical studies on lavage fluids included albumin, immunoglobulins, antiproteases (alpha2-macroglobulin and alpha1-proteinase inhibitor), potential indicators of epithelial cell function (secretory component and Clara cell protein), and cytokines (tumour necrosis factor-alpha, interleukin (IL)-4, IL-5, IL-6, and IL-8). Exposure to TDI caused a modest decrease in specific airway conductance (sGaw) (p=0.053) and in maximal expiratory flow at 25% of forced vital capacity (MEF25%) (p=0.015) when compared with ambient air. Exposure to TDI resulted in a slight increase in BAL albumin level (TDI: 26.4+/-12.5 versus air: 21.8+/-8.6 microg x mL(-1), p=0.044) and in BL alpha2-macroglobulin concentration (TDI: 0.07+/-0.061 versus air: 0.05+/-0.04 microg x mL(-1), p=0.021). This study suggests that exposure to low toluene disocyanate concentrations is associated with minimal but detectable changes in airway calibre and in epithelial barrier permeability. The pulmonary effects of long-term exposure to low levels of isocyanates require further investigation."
1,"TITLE: Oestrogen has no short-term effect on intestinal strontium absorption in healthy postmenopausal women.ABSTRACT: Impaired intestinal calcium absorption in postmenopausal women is often indirectly linked to decreased serum 1,25(OH)2D or to intestinal resistance to its action rather than directly to low circulating oestrogen levels following the menopause. The purpose of this clinical study was to investigate the short-term effect of oral 17 beta-oestradiol on intestinal calcium absorption, with strontium as a marker.Twenty-five healthy postmenopausal women participated in this randomised double blind placebo controlled clinical trial. Twelve women received oestradiol therapy (2 mg/day) and thirteen placebo for 2 months. Fractional strontium absorption (Fc240) was assessed at baseline and after 2 months of oestradiol/placebo therapy.Intestinal strontium absorption (Fc240) was unchanged after treatment with 17 beta-oestradiol (10.1 +/- 5.0 vs. 10.2 +/- 3.8(%)). Serum total calcitriol (1,25(OH)2D) was unchanged after treatment with placebo (88 +/- 22 vs. 79 +/- 21 (pmol/l)) but increased after treatment with oestradiol (88 +/- 30 vs. 116 +/- 33 (pmol/l); P < 0.005). Serum vitamin D binding protein (DBP) increased after oestradiol but not after placebo treatment. The free serum 1,25(OH)2D index was calculated. This index did not change after oestrogen therapy (1.6 +/- 0.5 vs. 1.8 +/- 0.5).In healthy postmenopausal women, short-term suppletion with exogenous oral oestrogen did not influence intestinal calcium absorption as measured by the strontium absorption test."
1,"TITLE: Comparative efficacy and safety of calcium carbasalate plus metoclopramide versus ergotamine tartrate plus caffeine in the treatment of acute migraine attacks.ABSTRACT: This randomized, double-blind, double-dummy, multicenter, parallel-group study aimed at comparing the efficacy and safety of calcium carbasalate (equivalent to 900 mg aspirin) plus metoclopramide 10 mg (CM) with ergotamine tartrate 1 mg plus caffeine 100 mg (EC) administered in the treatment of 2 acute migraine attacks. A total of 296 patients fulfilling the International Headache Society diagnostic criteria for migraine were enrolled. In total, one or two migraine attacks were treated in 268 and 235 patients, respectively. The primary endpoint for the first treated attack was headache relief, with intensity decreasing from moderate or severe to mild or absent 2 h after drug intake. Usual secondary efficacy endpoints were assessed. A superiority of CM over EC was observed for both treated attacks for the main endpoint: success in 54 versus 36%, p = 0.003 for the first attack and 60 versus 44%, p = 0.02 for the second attack. CM was also significantly superior to EC during the first attack for complete headache relief (20 vs. 8%, p = 0.006), nausea (42 vs. 63%, p = 0. 007) and willingness to take the drug again (90 vs. 80%, p = 0.043). The global efficacy evaluation, rated by the investigators, was significantly more favorable to CM for both attacks (p = 0.001 for the first attack and p = 0.02 for the second). The patients' evaluation was significant for the first attack (p = 0.002). The global incidence of adverse events was 45% higher with EC, though not significant (32 vs. 22%, p = 0.075). They were most often unspecific and mild to moderate in intensity. Gastrointestinal side effects were significantly less frequent with CM than EC (7 vs. 21%, p = 0.001). Thus, CM is more effective and has a better gastrointestinal safety than EC in the acute treatment of migraine attacks."
1,"TITLE: Benzalkonium chloride in a decongestant nasal spray aggravates rhinitis medicamentosa in healthy volunteers.ABSTRACT: A randomized double-blind parallel study with 20 healthy volunteers was performed to research the effect of a preservative in a decongestant nasal spray on the development of rhinitis medicamentosa. Ten subjects received oxymetazoline nasal spray with benzalkonium chloride and the others used oxymetazoline nasal spray without the preservative three times daily for 30 days. Before starting the course of treatment and after its conclusion, recordings of the mucosal surface positions were made with rhinostereometry followed by histamine challenge tests. Symptoms of nasal stuffiness were estimated on visual analogue scales (0-100) in the morning and the evening just before using the nasal spray. After 30 days, rebound swelling and nasal stuffiness were found in both groups. In the group receiving oxymetazoline nasal spray with benzalkonium chloride the mean rebound swelling was 1.1 mm and the estimated mean evening symptom score for nasal stuffiness was 43. In the group without benzalkonium chloride the corresponding variables were significantly less marked, with a mean rebound swelling of 0.5 mm (P < 0.05) and a mean evening symptom score of 25 (P < 0.05). The increase in histamine sensitivity in both groups was interpreted as a sign of nasal hyperreactivity. A new type of nasal spray bottle was used that has been shown to prevent bacterial contamination. In conclusion, the long-term use of benzalkonium chloride in oxymetazoline nasal spray accentuates the severity of rhinitis medicamentosa in healthy volunteers."
1,"TITLE: Randomized comparison of oral misoprostol and oxytocin for labor induction in term prelabor membrane rupture.ABSTRACT: To compare labor induction intervals between oral misoprostol and intravenous oxytocin in women who present at term with premature rupture of membranes.One hundred eight women were randomly assigned to misoprostol 50 microg orally every 4 hours as needed or intravenous oxytocin. The primary outcome measure was time from induction to vaginal delivery. Sample size was calculated using a two-tailed alpha of 0.05 and power of 80%.Baseline demographic data, including maternal age, gestation, parity, Bishop score, birth weight, and group B streptococcal status, were similar. The mean time +/-standard deviation to vaginal birth with oral misoprostol was 720+/-382 minutes compared with 501+/-389 minutes with oxytocin (P = .007). The durations of the first, second, and third stages of labor were similar. There were no differences in maternal secondary outcomes, including cesarean birth (eight and seven, respectively), infection, maternal satisfaction with labor, epidural use, perineal trauma, manual placental removal, or gastrointestinal side effects. Neonatal outcomes including cord pH, Apgar scores, infection, and admission to neonatal intensive care unit were not different.Although labor induction with oral misoprostol was effective, oxytocin resulted in a shorter induction-to-delivery interval. Active labor intervals and other maternal and neonatal outcomes were similar."
1,"TITLE: The safety and efficacy of prophylactic ondansetron in patients undergoing modified radical mastectomy.ABSTRACT: We aimed to evaluate the antiemetic efficacy, safety, and clinical utility of prophylactic ondansetron administered at the end of the surgery for the prevention of postoperative nausea and vomiting (PONV) in a homogenous population of 54 women undergoing modified radical mastectomy (MRM). A standard general anesthetic and perioperative analgesic technique were used. After surgery, patients received either saline placebo or ondansetron 4 mg IV. Episodes of PONV, as well as rescue antiemetic requirements, were recorded for the first 24 h after surgery. The 24-h incidence of PONV (33.3% vs 81.5%; P = 0.0010) was significantly lower in the ondansetron group. The severity of PONV, evaluated by the number of emetic episodes per patient (1.59+/-1.90 vs 0.29+/-0.66; P = 0.0029), and the rescue antiemetic requirement (59.2% vs 14.8%; P = 0.0019) was significantly lower, in the ondansetron group. Patient satisfaction scores and number needed to prevent PONV (2.07) were significantly better and therapeutically more favorable in the ondansetron group. The incidence of adverse events such as headache, dizziness, and increased liver enzyme levels (number needed to harm = infinity) was similar in both groups. Administered at the end of the surgery in adult female patients undergoing general anesthesia for MRM, ondansetron 4 mg is effective and safe in preventing PONV. We recommend the clinical practice of routine prophylactic ondansetron to prevent PONV after MRM, as it significantly improves perioperative patient satisfaction and outcome.We evaluated the antiemetic efficacy, safety, and routine use of prophylactic ondansetron, a ""gold standard"" antiemetic, in women undergoing radical breast surgery who were at a high risk of postoperative vomiting. We analyzed more meaningful ""true"" and ""therapeutic"" outcome measures, and we conclude that prophylactic ondansetron is safe and effective and that its routine use is justified."
1,"TITLE: Effect of chronic magnesium supplementation on magnesium distribution in healthy volunteers evaluated by 31P-NMRS and ion selective electrodes.ABSTRACT: The role of magnesium (Mg) intake in the prevention and treatment of diseases is greatly debated. Mg biodistribution after chronic Mg supplementation was investigated, using state-of-the-art technology to detect changes in free ionized Mg, both at extra- and intracellular levels.Thirty young healthy male volunteers participated in a randomised, placebo (P)-controlled, double-blind trial. The treated group (MgS) took 12 mmol magnesium lactate daily for 1 month. Subjects underwent in vivo 31P-NMR spectroscopy and complete clinical and biological examinations, on the first and last day of the trial. Total Mg was measured in plasma, red blood cells and 24 h urine ([Mg]U ). Plasma ionized Mg was measured by ion-selective electrodes. Intracellular free Mg concentrations of skeletal muscle and brain tissues were determined noninvasively by in vivo 31P-NMR at 3T. NMR data were automatically processed with the dedicated software MAGAN.Only [Mg]U changed significantly after treatment (in mmol/24 h, for P, from 4.2+/-1.4 before to 4.1+/-1.3 after and, for MgS, from 3.9+/-1.1 before to 5. 1+/-1.1 after, t=2.15, P=0.04). The two groups did not differ, either before or after the trial, in any other parameter, whether clinical, biological or in relation with the Mg status.Chronic oral administration of Mg tablets to young healthy male volunteers at usual pharmaceutical doses does not alter Mg biodistribution. This study shows that an adequate and very complete noninvasive methodology is now available and compatible with the organization of clinical protocols which aim at a thorough evaluation of Mg biodistribution."
0,"TITLE: Metformin-induced resumption of normal menses in 39 of 43 (91%) previously amenorrheic women with the polycystic ovary syndrome.ABSTRACT: In 43 amenorrheic women with polycystic ovary syndrome (PCOS), 31 (74%) with fasting hyperinsulinemia (> or =20 microU/mL), our aim was to determine whether Metformin (Bristol-Myers Squibb, Princeton, NJ), which reduces hyperinsulinemia, would reverse the endocrinopathy of PCOS, allowing resumption of regular normal menses. A second aim was to assess the effects of weight loss versus other Metformin-induced effects on ovarian function, and to determine if there were different responses to Metformin between those who lost weight and those who did not. A third aim was to assess associations between PCOS, 4G/5G polymorphism in the promoter sequence of the plasminogen activator inhibitor-1 gene (PAI-1 gene), and PAI activity (PAI-Fx). Of the 43 women, 40 (93%) had normal fasting blood glucose and 37 had normal hemoglobin A1C (HgA1C); onlythree (7%) had type 2 diabetes mellitus. Metformin (1.5 to 2.25 g/d) was given for 6.1+/-5.1 months (range, 1.5 to 24), to 16 patients for less than 3 months, to 12 for 3 to 6 months, and to 15 for at least 6 months. On Metformin, 39 of 43 patients (91%) resumed normal menses. The percentage of women resuming normal menses did not differ among treatment duration groups (P<.1) or among dose groups (P>.1). The body mass index (BMI) decreased from 36.4 + 7 Kg/m2 at study entry to 35.1+/-6.7 on Metformin (P=.0008). Of 43 patients, 28 (67%) lost weight (1 to 69 pounds), with nine (21%) losing at least 12 pounds. On Metformin, the median fasting serum insulin decreased from 26 microU/mL to 22 (P=.019), testosterone decreased from 61 ng/dL to 47 (P=.003), and estradiol increased from 41 pg/mL to 71 (P=.0001). Metformin-induced improvements in ovarian function were independent of weight loss (testosterone decrease, P<.002; estradiol increase, P<.0004). The change in response variables on Metformin did not differ (P>.05) between those who lost weight and those who did not, excepting Lp(a), which increased 4 mg/dL in those who lost weight and decreased 9 mg/dL in those who did not (P = .003). The change in response variables on Metformin did not differ among the five quintiles of weight loss, excepting fasting glucose (P<.05), which increased 6 mg/dL in those who lost the least weight on Metformin versus those in the 60th to 80th percentile for weight loss, in whom glucose decreased 33 mg/dL. Although the pretreatment fasting serum insulin was not significantly correlated with testosterone (r=.24, P=.13) or androstenedione (r=.27, P=.09), on Metformin, the change in insulin correlated positively with the change in testosterone (r=.35, P=.047) and with the change in androstenedione (r=.48, P=.01). Patients were more likely than normal controls (83% v 64%, P=.016) to be heterozygous or homozygous for 4G polymorphism of the PAI-1 gene and were also more likely to have high PAI-Fx (> or =22 U/mL, 28% v3%, chi(2)=10.1, P=.001). Metformin reduces the endocrinopathy of PCOS, allowing resumption of normal menses in most (91%) previously amenorrheic women with PCOS."
0,"TITLE: CYP2D6 status of extensive metabolizers after multiple-dose fluoxetine, fluvoxamine, paroxetine, or sertraline.ABSTRACT: The aim of this study was to evaluate the CYP2D6 inhibitory effects of four selective rerotonin re-uptake inhibitors (SSRIs). Thirty-one healthy subjects were phenotyped as extensive metabolizers using the dextromethorphan/dextrorphan (DM/DX) urinary ratio as a marker for CYP2D6 activity before and after 8 days of administration of fluoxetine 60 mg (loading dose strategy), fluvoxamine 100 mg, paroxetine 20 mg, or sertraline 100 mg in a parallel-group design. Statistical analysis was performed on log-transformed DM/DX ratios because of variability within and between treatment groups. DM/DX ratios before (DM/DX(BL)) and after (DM/DX(SSRI)) were compared within and between the four SSRI groups. DM/DX(BL) ratios were not significantly different between the four SSRI treatment groups. Comparing within groups, significant differences between DM/DX(BL) and DM/DX(SSRI) were found for the fluoxetine (p < 0.001; ratio values, 0.020 vs. 0.364) and paroxetine (p = 0.0005, ratio values 0.029 vs. 1.085) but not for the fluvoxamine or sertraline groups. Comparing between groups, significant differences in DM/DX(SSRI) ratios were found for fluoxetine versus sertraline (p = 0.0019, DM/DX = 0.364 vs. 0.057), fluoxetine versus fluvoxamine (p < 0.0001, DM/DX = 0.364 vs. 0.019), paroxetine versus sertraline (p = 0.0026, DM/DX = 1.085 vs. 0.057), and paroxetine versus fluvoxamine (p < 0.0001, DM/DX = 1.085 vs. 0.019). No significant differences were noted between the two potent CYP2D6 inhibitors, fluoxetine and paroxetine, or the two weakest inhibitors, fluvoxamine and sertraline. Five subjects in the fluoxetine and four subjects in the paroxetine groups changed to poor metabolizer phenotype (DM/DX > or = 0.3) after treatment. Although CYP2D6 inhibitory effects of fluvoxamine and sertraline did not yield significant differences from baseline, some subjects exhibited DM/DX ratio increases of 150 to 200%. One paroxetine-treated subject did not exhibit any CYP2D6 inhibition. SSRI dose and plasma concentration may be correlated with the extent of CYP2D6 inhibition and should be further investigated."
1,"TITLE: Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group.ABSTRACT: To confirm the promising phase II results of docetaxel monotherapy, this phase III trial was conducted of chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) who had previously failed platinum-containing chemotherapy.A total of 373 patients were randomized to receive either docetaxel 100 mg/m(2) (D100) or 75 mg/m(2) (D75) versus a control regimen of vinorelbine or ifosfamide (V/I). The three treatment groups were well-balanced for key patient characteristics.Overall response rates were 10.8% with D100 and 6.7% with D75, each significantly higher than the 0.8% response with V/I (P =.001 and P =.036, respectively). Patients who received docetaxel had a longer time to progression (P =.046, by log-rank test) and a greater progression-free survival at 26 weeks (P =.005, by chi(2) test). Although overall survival was not significantly different between the three groups, the 1-year survival was significantly greater with D75 than with the control treatment (32% v 19%; P =.025, by chi(2) test). Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel, nor did it impact survival. There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2. Toxicity was greatest with D100, but the D75 arm was well-tolerated.This first randomized trial in this setting demonstrates that D75 every 3 weeks can offer clinically meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy."
0,"TITLE: Human vascular renin-angiotensin system and its functional changes in relation to different sodium intakes.ABSTRACT: A growing body of evidence supports the existence of a tissue-based renin-angiotensin system (RAS) in the vasculature, but the functional capacity of vascular RAS was not investigated in humans. In 28 normotensive healthy control subjects, the metabolism of angiotensins through vascular tissue was investigated in normal, low, and high sodium diets by the measurement of arterial-venous gradient of endogenous angiotensin (Ang) I and Ang II in two different vascular beds (forearm and leg), combined with the study of 125I-Ang I and 125I-Ang II kinetics. In normal sodium diet subjects, forearm vascular tissue extracted 36+/-6% of 125I-Ang I and 30+/-5% of 125I-Ang II and added 14.9+/-5.1 fmol x 100 mL(-1) x min(-1) of de novo formed Ang I and 6.2+/-2.8 fmol x 100 mL(-1) x min(-1) of Ang II to antecubital venous blood. Fractional conversion of 125I-Ang I through forearm vascular tissue was about 12%. Low sodium diet increased (P<.01) plasma renin activity, whereas de novo Ang I and Ang II formation by forearm vascular tissue became undetectable. Angiotensin degradation (33+/-7% for Ang I and 30+/-7% for Ang II) was unchanged, and vascular fractional conversion of 125I-Ang I decreased from 12% to 6% (P<.01). In high sodium diet subjects, plasma renin activity decreased, and de novo Ang I and Ang II formation by forearm vascular tissue increased to 22 and 14 fmol x 100 mL(-1) x min(-1), respectively (P<.01). Angiotensin degradation did not significantly change, whereas fractional conversion of 125I-Ang I increased from 12% to 20% (P<.01). Leg vascular tissue functional activities of RAS paralleled those of forearm vascular tissue both at baseline and during different sodium intake. These results provide consistent evidence for the existence of a functional tissue-based RAS in vascular tissue of humans. The opposite changes of plasma renin activity and vascular angiotensin formation indicate that vascular RAS is independent from but related to circulating RAS."
1,"TITLE: A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group.ABSTRACT: Critically ill patients who require mechanical ventilation are at increased risk for gastrointestinal bleeding from stress ulcers. There are conflicting data on the effect of histamine H2-receptor antagonists and the cytoprotective agent sucralfate on rates of gastrointestinal bleeding, ventilator-associated pneumonia, and mortality.In a multicenter, randomized, blinded, placebo-controlled trial, we compared sucralfate with the H2-receptor antagonist ranitidine for the prevention of upper gastrointestinal bleeding in 1200 patients who required mechanical ventilation. Patients received either nasogastric sucralfate suspension (1 g every six hours) and an intravenous placebo or intravenous ranitidine (50 mg every eight hours) and a nasogastric placebo.The patients in the two groups had similar base-line characteristics. Clinically important gastrointestinal bleeding developed in 10 of 596 (1.7 percent) of the patients receiving ranitidine, as compared with 23 of 604 (3.8 percent) of those receiving sucralfate (relative risk, 0.44; 95 percent confidence interval, 0.21 to 0.92; P=0.02). In the ranitidine group, 114 of 596 patients (19.1 percent) had ventilator-associated pneumonia, as compared with 98 of 604 (16.2 percent) in the sucralfate group (relative risk, 1.18; 95 percent confidence interval, 0.92 to 1.51; P=0.19). There was no significant difference between the groups in mortality in the intensive care unit (ICU) (23.5 percent in the ranitidine group and 22.9 percent in the sucralfate group) or the duration of the stay in the ICU (median, nine days in both groups).Among critically ill patients requiring mechanical ventilation, those receiving ranitidine had a significantly lower rate of clinically important gastrointestinal bleeding than those treated with sucralfate. There were no significant differences in the rates of ventilator-associated pneumonia, the duration of the stay in the ICU, or mortality."
0,"TITLE: The course of labor with and without epidural analgesia.ABSTRACT: Our purpose was to measure effects of epidural analgesia on labor compared with boluses of meperidine in a cohort of women with similar clinical circumstances.One hundred ninety-nine nulliparous women who were delivered spontaneously at term and who received oxytocin for labor augmentation before the initiation of analgesia were identified for analysis. All these women were managed in a low-risk labor unit according to a standardized protocol. This management protocol encouraged early amniotomy and the use of oxytocin when ineffective labor was diagnosed.The demographic characteristics of the two study groups were similar with respect to age, height, weight, and maternal age. The two groups had the same cervical dilatation on admission (3.3 cm) and at the time of analgesia administration (4.1 vs 4.2 cm), indicating similar progress of labor before oxytocin administration. The length of the active phase of labor was longer in the epidural group (7.9 vs 6.3 hours, p = 0.005), as was the second stage (60 vs 48 minutes, p = 0.03). The mean and maximal rates of oxytocin infusion were similar between the two study groups; however, the amount of oxytocin required for each centimeter of cervical change was more in the epidural group (22 vs 16 mU per cm of cervical change, p = 0.009). Neonatal outcomes were unaffected by the type of labor analgesia.Epidural analgesia decreases uterine performance during oxytocin-stimulated labor, resulting in an increase in the length of the first and second stages of labor."
0,"TITLE: Associations between carcinogen-DNA damage, glutathione S-transferase genotypes, and risk of lung cancer in the prospective Physicians' Health Cohort Study.ABSTRACT: DNA damage from polycyclic aromatic hydrocarbons (PAH) and other aromatic/hydrophobic compounds has been implicated in case-control studies as a risk factor for lung cancer, as have common polymorphisms in the glutathione S-transferase (GST) genes involved in carcinogen detoxification. However, their joint effects have not been evaluated in prospective studies, leaving open questions about predictive value of these biomarkers. In this matched case-control study nested within the prospective Physicians' Health Study, we evaluated whether biomarkers measured in white blood cells (WBC) significantly predicted risk, alone and in combination, after controlling for level of smoking. The biomarkers reported here are aromatic/hydrophobic-DNA adducts and polymorphisms in genes coding for the GSTM1 and GSTP1 enzymes. Our study population was composed of 89 cases of primary lung cancer and 173 controls, matched in a 1:2 ratio on smoking, age and duration of follow up. Adducts were measured in WBC DNA by the nuclease P1-enhanced (32)P-post-labeling method. Genotypes (GSTM1 null versus non-null and GSTP1 Val versus GSTP1 Ile) were determined by genomic amplification and restriction fragment length polymorphism analysis. Among current smokers, adducts were significant predictors of lung cancer risk (after adjusting for GST genotypes, OR = 3.10, 95% CI 1.07, 9.01). The combined GSTM1 null/GSTP1 Val genotype was associated with lung cancer overall and especially among former smokers, before and after adjusting for adducts (OR for former smokers = 4.21, CI 1.08, 16.41; adjusted OR = 4.68, CI 1.17, 18.71). Among cases only, adducts were significantly higher among current or former smokers with the GSTM1 non-null/GSTP1 Ile genotype. The two risk factors (adducts and genotypes) appear to be independent predictors of risk. The findings underscore the complex and important role of biological susceptibility as a determinant of risk from carcinogens found in tobacco smoke and other environmental compounds."
1,"TITLE: A study of hormone replacement therapy in postmenopausal women with ischaemic heart disease: the Papworth HRT atherosclerosis study.ABSTRACT: To assess the possible benefit of hormone replacement therapy (HRT) in the secondary prevention of ischaemic heart disease.A prospective randomised trial of transdermal HRT in women with definite ischaemic heart disease.A regional cardiac unit.Postmenopausal women with angiographically proven ischaemic heart disease.A total of 255 postmenopausal women with angiographically proven ischaemic heart disease were recruited and randomised; 134 were treated with transdermal HRT and 121 acted as controls. The women were seen at six monthly intervals. The primary end points, which were determined by a blinded assessor, were admission to hospital with unstable angina, proven myocardial infarction or cardiac death. A total of 53 (40%) patients withdrew from the HRT group and eight (7%) from the control group. The mean duration of follow up was 30.8 months.Admission to hospital with unstable angina, proven myocardial infarction or cardiac death.During follow up, there were 53 primary end-point events in the HRT group and 37 in the control group. Using an intention-to-treat analysis, the primary end-point event rate was 15.4 events per 100 patient years for the HRT group compared with 11.9 for the control group (event rate ratio 1.29 (95% CI 0.84-1.95, P = 0.24)). Using a per-protocol analysis, there was an event rate ratio of 1.49 (0.93-2.36, P = 0.11) for the HRT arm compared with the control arm. Particularly during the first two years of follow up, the HRT group had a higher, but not statistically significant, event rate than the control group.Our findings suggest that transdermal HRT should not be commenced for the purpose of secondary prevention in postmenopausal women with angiographically proven ischaemic heart disease."
0,"TITLE: Calcium and zinc absorption from lactose-containing and lactose-free infant formulas.ABSTRACT: Calcium absorption is enhanced by the presence of lactose, but the quantitative significance of this effect in infant formulas is uncertain. It is also not known whether lactose affects zinc absorption.We measured the absorption of calcium and zinc from infant formulas by using a multitracer, stable-isotope technique.Eighteen full-term infants (aged 8-12 wk at enrollment) were fed 2 partially hydrolyzed whey-protein-based formulas ad libitum for 2 wk per formula. The carbohydrate source was lactose in one formula and glucose polymers in the other (lactose-free). Infants were studied in a blinded crossover fashion after 2 wk of adaptation to each formula. Isotope absorption studies were conducted with a 4-tracer method in which (70)Zn and (44)Ca were provided orally and (67)Zn and (46)Ca intravenously. Zinc and calcium absorption was measured from the fractional excretion of the oral and intravenous isotopes in urine.Fractional and total calcium absorption was significantly greater from the lactose-containing formula than from the lactose-free formula. For total calcium absorption, the mean difference between formulas was 10.3% (P = 0.002) and 60 mg/d (P = 0.006). For zinc, fractional absorption (32 +/- 11%), total absorption, and intake did not differ significantly between the 2 formulas.The presence of lactose in a formula based on cow-milk protein increases absorption of calcium but not of zinc. Absorption of calcium from a lactose-free infant formula is, however, adequate to meet the calcium needs of full-term infants when the formula's calcium content is similar to that of lactose-containing, cow-milk-based infant formulas."
1,"TITLE: The dose-sparing effect of clonidine added to ropivacaine for labor epidural analgesia.ABSTRACT: To determine the effects of clonidine with ropivacaine during epidural labor analgesia, we studied 66 nulliparous women in early active labor. Women were randomized to receive ropivacaine 0.1% 8 mL plus 75 microg of clonidine (Group 1), ropivacaine 0.2% 8 mL plus 0.5 mL of NaCl 0.9% (Group 2), or ropivacaine 0.2% 8 mL plus 75 microg of clonidine (Group 3) 5 min after a bupivacaine 7.5 mg with epinephrine 15 microg test dose. Upon request, additional analgesia with ropivacaine 0.1% 8 mL followed by ropivacaine 0.2% 8 mL/h was administered. With clonidine, duration of analgesia was increased (132 +/- 48 min [Group 1] and 154 +/- 42 min [Group 3] versus 91 +/- 44 min [Group 2]; P < 0.05), and total ropivacaine dose over the first 4 h was significantly reduced (40.5 +/- 15 mg [Group 1] and 47.0 +/- 16 mg [Group 3] versus 72.5 +/- 18 mg [Group 2]; P < 0.01). The incidence of more profound motor block was more frequent in Group 2 (P < 0.05). Although there was a trend for more women receiving clonidine to require ephedrine for treatment of hypotension, this did not seem to have an impact on fetal outcome or incidence of cesarean deliveries for nonreassuring fetal heart rate tracings. This study demonstrates the dose-sparing effect of clonidine when added to ropivacaine.The effect of adding 75 microg of clonidine to ropivacaine for epidural labor analgesia was studied. Clonidine increased analgesia duration and produced dose sparing compared with ropivacaine alone. Despite a tendency for hypotension in women receiving clonidine, there was no apparent effect on delivery mode or neonatal outcome."
1,"TITLE: Increased presence of anti-HLA antibodies early after allogeneic granulocyte colony-stimulating factor-mobilized peripheral blood hematopoietic stem cell transplantation compared with bone marrow transplantation.ABSTRACT: We have recently shown that the use of allogeneic granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood hematopoietic stem cell transplantation (PBHSCT), as compared with bone marrow transplantation (BMT), is associated with increased titers of antibodies (Abs) directed against red blood cell ABO antigens. To further evaluate the influence of a G-CSF-mobilized PBHSCT graft on alloimmune Ab responses, we examined the frequency of anti-HLA Abs after transplantation in the setting of the same randomized study, comparing PBHSCT with BMT in adults. Anti-HLA Ab presence was determined by complement-dependent cytotoxicity assay (CDC) and flow cytometry in the recipient before and 30 days after transplantation as well as in the donor before graft donation. The use of PBHSCT was significantly associated with increased detection of anti-HLA immunoglobulin G (IgG) Abs early after transplantation as evidenced by flow cytometry (11 of 24 versus 4 of 27 transplant recipients, P =.03) and, less so, by CDC (5 of 24 versus 1 of 27 transplant recipients, P =.09). The difference between PBHSCT and BMT was further heightened when analysis was restricted to anti-HLA IgG Ab-negative donor/recipient pairs. In such a setting, early anti-HLA Ab was never detected after BMT but was repeatedly detected after PBHSCT (flow cytometry, 6 of 18 versus 0 of 17 transplant recipients, P =.02; CDC, 4 of 23 versus 0 of 26 transplant recipients, P =.04). Importantly, the PBHSCT-associated increase in anti-HLA Ab detection was observed despite a reduction in the median number of platelet-transfusion episodes per patient in PBHSC transplant versus BM transplant recipients (3 platelet-transfusion episodes [range, 1-21] in PBHSCT group vs 6 platelet-transfusion episodes [range, 3-33] in the BMT group; P =.02). In conclusion, this study strongly suggests that G-CSF-mobilized PBHSCT results in an increased incidence of circulating anti-HLA Abs and further confirms that the use of such a graft alters alloimmune Ab responses."
1,"TITLE: Midodrine in neurally mediated syncope: a double-blind, randomized, crossover study.ABSTRACT: Neurally mediated syncope is the most frequent cause of syncope in patients without structural heart disease. Its most common trigger is a reduction in venous return to the heart due to excessive venous pooling in the legs. We conducted a double-blind, randomized, crossover trial to investigate the efficacy of midodrine, a selective alpha-1 adrenergic agonist that decreases venous capacitance, in preventing neurally mediated syncope triggered by passive head-up tilt. Twelve patients with history of recurrent neurally mediated syncope, which was reproduced during head-up tilt, were randomized to receive a nonpressor dose of midodrine (5mg) or placebo on day 1 and the opposite on day 3. One hour after drug or placebo administration, patients underwent 60-degree head-up tilt lasting 40 minutes (unless hypotension or bradycardia developed first). In the supine position, midodrine produced no significant change in blood pressure or heart rate. The responses to head-up tilt were significantly different on the midodrine and the placebo day: on the placebo day, 67% (8/12) of the subjects suffered neurally mediated syncope, whereas only 17% (2/12) of the subjects developed neurally mediated syncope on the midodrine day (p < 0.02). These results indicate that midodrine significantly improves orthostatic tolerance during head-up tilt in patients with recurrent neurally mediated syncope."
1,"TITLE: Improved suppression of recurrent atrial fibrillation with dual-site right atrial pacing and antiarrhythmic drug therapy.ABSTRACT: We compared the safety, tolerance and effectiveness of overdrive high right atrial (RA), dual-site RA and support (DDI or VDI) pacing (SP) in patients with symptomatic atrial fibrillation (AF) and bradycardias.Optimal pacing methods for AF prevention remain unclear.Patients (n = 118) were randomized to each of three pacing modes in a crossover trial.Mode adherence was superior for dual-site RA (5.8 months) compared with SP (3.3 months; p < 0.001) and high RA pacing (4.7 months; p = 0.006). Adverse event-free survival improved with dual-site RA (p = 0.007 vs. SP) and was comparable to high RA (p = 0. 75). AF-free survival trended to improve with dual-site RA (hazard ratio [HR] 0.715, p = 0.07 vs. SP) but not high RA (HR = 0.71, p = 0.19) or when dual-site RA was compared with high RA (HR = 0.835, p = 0.175). Time-to-recurrence was longer in dual-site RA (1.77 months) compared with high RA (0.62 months, p < 0.09) or SP (0.44 months, p < 0.05). In antiarrhythmic drug-treated patients, dual-site RA reduced recurrence risk compared with SP (HR = 0.638, p = 0.011) and high RA (HR = 0.669, p = 0.06). In patients with < or =1 AF event/week, dual-site RA improved AF suppression (HR = 0.464, p = 0.004 vs. SP; HR = 0.623, p = 0.006 vs. high RA). Dual-site RA improved AF-free and mode survival (p < 0.03 vs. high RA, p < 0.001 vs. SP) and reduced asymptomatic AF (p < 0.01 vs. high RA).Dual-site RA is safe and better tolerated than high RA and SP. In patients on antiarrhythmics, dual-site RA prolonged and high RA trended to prolong time-to-recurrent AF compared with SP. Dual-site RA provides superior symptomatic and asymptomatic AF prevention compared with high RA in patients with symptomatic AF frequency of < or =1/week."
1,"TITLE: Two-site phacotrabeculectomy with intraoperative mitomycin-C: fornix- versus limbus-based conjunctival opening in fellow eyes.ABSTRACT: To prospectively compare the influence of fornix-based and limbus-based conjunctival flaps on the final outcome and complications of 2-site phacotrabeculectomy with mitomycin-C in fellow eyes of patients with bilateral open-angle glaucoma (OAG). Glaucoma Unit, Department of Ophthalmology, University of Crete, Crete, Greece.Twenty-two patients with bilateral primary OAG and 8 patients with bilateral exfoliative glaucoma had 2-site phacotrabeculectomy in both eyes. Eyes were randomly assigned to the fornix-based flap or limbus-based flap group by the use of random tables. The intraocular pressure (IOP) decreased significantly in both groups (P <.01); however, there was no statistically significant difference between the groups in the amount of IOP decrease or the number of postoperative antiglaucoma medications after a 1-year follow-up. Faster improvement in visual acuity was observed in the fornix-based group during the first week. The mean time of surgery was 3.5 minutes less in the fornix-based group. An increased incidence of fibrin exudation, pupillary membrane formation, and capsule opacification was found in eyes with exfoliative glaucoma. The early bleb leakage was 3 times more frequent in the fornix-based group. The type of conjunctival flap in a 2-site phacotrabeculectomy did not seem to influence the final outcome. The main advantage of the fornix-based conjunctival flap is the shorter surgical time and the relatively faster improvement in vision postoperatively. The main disadvantage is more frequent early bleb leakage."
1,"TITLE: Ofloxacin for the treatment of urinary tract infections and biofilms in spinal cord injury.ABSTRACT: Forty two paraplegic and quadriplegic hospitalized spinal cord injured patients with urinary tract infections (UTI) were included in a double blind, randomized treatment study comparing 7 days ofloxacin (300 mg bd) with trimethoprim-sulphamethoxazole (TMPSMX; 160-800 mg bd) or an alternative, chosen because of resistance to TMPSMX. The 4-day clinical cure rate, defined as an asymptomatic patient with sterile urine, was 90% (19/21) with ofloxacin, significantly greater than 48% (10/21) for the comparison group (P=0.003) and the rate at end of therapy was 90% (19/21) with ofloxacin, against 57% (12/21) (P=0.015). Bacterial biofilms were detected on bladder epithelial cells in 39/41 (95%) patients. The biofilm score fell significantly following ofloxacin therapy (P < 0.001) or alternative therapy (P < 0.001). Ofloxacin treatment led to significantly more biofilm eradication than the other antibiotic group on day 4 (62 vs. 24%) (P=0.005) and day 7 (67 vs. 35%) (P=0.014). The study showed that ofloxacin was better than TMPSMX and alternatives at relieving clinical infection and eradicating bladder cell biofilms."
1,"TITLE: Early identification of neutropenic patients at risk of grampositive bacteraemia and the impact of empirical administration of vancomycin.ABSTRACT: The aim of this multicentre randomised trial was to determine whether it was possible to predict grampositive bacteraemia, and whether the empirical use of vancomycin would lead to reduced morbidity and mortality. 35 of 113 patients (31%; confidence interval, CI 8.5), who presented with a skin or soft tissue infection and had received empirical vancomycin in addition to either ceftazidime or piperacillin-tobramycin, had initial bacteraemia with a single gram-positive bacterium compared with 135 of the 784 (17%; CI 2.6), who presented with another infection and who had been given ceftazidime or piperacillin-tobramycin without vancomycin (P < 0.001). Empirical vancomycin resulted in a higher rate of eradication (P = 0.033, relative risk 1.2), but not a better clinical outcome and was associated with more toxicity (P = 0.042, relative risk 1.6). Irrespective of the initial treatment regimen, fever lasted an average of 8 days, the empirical regimen was modified in more than 50% of cases and mortality attributed to gram-positive infection was less than 2%. Incorporating vancomycin in the initial empirical antibiotic regimen for febrile neutropenic patients does not appear necessary, even for skin and soft tissue infections associated with gram-positive bacteraemia."
1,"TITLE: Effect of flumazenil on ventilatory drive during sedation with midazolam and alfentanil.ABSTRACT: Patients who receive a combination of a benzodiazepine and an opioid for conscious sedation are at risk for developing respiratory depression. While flumazenil effectively antagonizes the respiratory depression associated with a benzodiazepine alone, its efficacy in the presence of both a benzodiazepine and an opioid has not been established. This study was designed to determine whether flumazenil can reverse benzodiazepine-induced depression of ventilatory drive in the presence of an opioid.Twelve healthy volunteers completed this randomized, double-blind, crossover study. Ventilatory responses to carbon dioxide and to isocapnic hypoxia were determined during four treatment phases: (1) baseline, (2) alfentanil infusion; (3) combined midazolam and alfentanil infusions, and (4) combined alfentanil, midazolam, and ""study drug"" (consisting of either flumazenil or flumazenil vehicle) infusions. Subjects returned 2-6 weeks later to receive the alternate study drug.Alfentanil decreased the slope of the carbon dioxide response curve from 2.14 +/- 0.40 to 1.43 +/- 0.19 l.min-1.mmHg-1 (x +/- SE, P < 0.05), and decreased the minute ventilation at P(ET)CO2 = 50 mmHg (VE50) from 19.7 +/- 1.2 to 14.8 +/- 0.9l.min-1 (P < 0.05). Midazolam further reduced these variables to 0.87 +/- 0.17 l.min-1.mmHg-1 (P < 0.05) and 11.7 +/- 0.8 l.min-1 (P < 0.05), respectively. With addition of flumazenil, slope and VE50 increased to 1.47 +/- 0.37 l.min-1.mmHg-1 (P < 0.05) and 16.4 +/- 2.0l.min-1 (P < 0.05); after placebo, the respective values of 1.02 +/- 0.19 l.min-1.mmHg-1 and 12.5 +/- 1.2 l.min-1 did not differe significantly from their values during combined alfentanil and midazolam administration. The effect of flumazenil differed significantly from that of placebo (P < 0.05). Both the slope and the displacement of the hypoxic ventilatory response, measured at P(ET)CO2 = 46 +/- 1 mmHG, were affected similarly, with flumazenil showing a significant improvement compared to placebo.Flumazenil effectively reverses the benzodiazepine component of ventilatory depression during combined administration of a benzodiazepine and an opioid."
1,"TITLE: Effects of the new class III antiarrhythmic drug dofetilide on the atrial and ventricular intracardiac monophasic action potential in patients with angina pectoris.ABSTRACT: The class III antiarrhythmic drug dofetilide is known to prolong action potential duration by specific blockade of the delayed rectifier potassium channel Ik. As dofetilide is likely to be used in the treatment of atrial arrhythmias it is important to determine the relative sensitivity of the atrium and ventricle in man. Twelve male patients underwent monophasic action potential and refractory period recordings from the high right atrium and right ventricular septum. The patients received either 8 micrograms.kg-1 dofetilide or placebo intravenously. The mean QTc was prolonged by 11% (SD 5%, P < 0.00001) in the active group; the mean monophasic action potential increased by 31% (SD 15%, P < 0.0005) in the atrium and 27% (SD 9%, P < 0.00005) in the ventricle; the mean effective refractory period increased by 30% (SD 16%, P < 0.0005) in the atrium and 20% (SD 6%, P < 0.0001) in the ventricle. No significant change occurred in the placebo group. There was no significant difference in effect between the two chambers. The change in QTc did not accurately reflect acute changes in refractory period or monophasic action potential duration. This has important implications for the use of QT prolongation to assess the acute effect of class III drugs."
1,"TITLE: Changes in the cerebral arteriovenous oxygen content difference by surgical incision are similar during sevoflurane and isoflurane anaesthesia.ABSTRACT: To investigate changes of cerebral arteriovenous oxygen content difference (AVDO2) induced by surgical incision and to determine carbon dioxide (CO2) reactivity of the cerebral circulation during sevoflurane and isoflurane anaesthesia.Twenty-one ASA 1-2 patients undergoing elective surgery for supratentorial tumours were randomly allocated to receive either 1.3 MAC sevoflurane/N2O anaesthesia (n = 10) or equi-MAC isoflurane/N2O anaesthesia (n = 11). Before and after incision, haemodynamic measurements and AVDO2 determinations were performed. After opening the dura, AVDO2 was determined before and after the respiration rate was increased by 50%.Incision produced an increase in mean arterial pressure from 69 +/- 11 to 97 +/- 22 mmHg (mean +/- SD) (P < 0.0005) and from 71 +/- 6 to 89 +/- 12 mmHg (P < 0.0001) in the sevoflurane and isoflurane groups, respectively, whereas the heart rate increased from 60 +/- 9 to 72 +/- 8 bpm (P < 0.001) and from 65 +/- 6 to 70 +/- 7 bpm (P < 0.001), respectively. Arterial carbon dioxide tension (PaCO2) was increased from 33.6 +/- 2.3 to 34.6 +/- 1.8 mmHg (P < 0.05) with incision in the sevoflurane group. The AVDO2 was decreased from 6.5 +/- 1.6 to 5.3 +/- 1.6 vol% (P < 0.0005) in the sevoflurane group and from 6.7 +/- 1.1 to 6.0 +/- 1.1 vol% (P < 0.01) in the isoflurane group. The % change of AVDO2 was larger in the sevoflurane group than in the isoflurane group (-18.3 +/- 8.4% vs -9.1 +/- 9.0%; P < 0.05) but no difference remained after the post-incisional AVDO2 value of the sevoflurane group was corrected for pre-incisional PaCO2. Carbon dioxide reactivity, calculated as the percent change in AVDO2 per mmHg change in PaCO2, was 6.1 +/- 3.0%.mmHg-1 in the sevoflurane group and 5.9 +/- 2.4%.mmHg-1 in the isoflurane group (P = NS).Sevoflurane and isoflurane are associated with similar impairment of cerebral flow-metabolism coupling at incision, while CO2 reactivity is maintained during both anaesthetics."
1,"TITLE: The effect of glimepiride on pancreatic beta-cell function under hyperglycaemic clamp and hyperinsulinaemic, euglycaemic clamp conditions in non-insulin-dependent diabetes mellitus.ABSTRACT: The comparative effects of glimepiride (Amaryl; HOE 490) and glibenclamide on insulin and glucose metabolism under hyperglycaemic and hyperinsulinaemic, euglycaemic clamp conditions were studied in a double-blind, placebo-controlled, cross-over trial. Patients with sulfonylurea-controlled non insulin-dependent diabetes were allocated in random order to placebo, glimepiride (5 mg) or glibenclamide (5 mg) and received one week treatment of each with no wash-out period. At the end of each treatment week a clamp study was performed. Two protocols were used. Protocol 1 used a 5 h hyperglycaemic clamp at 10.9 mmol/l whole blood glucose concentration and Protocol II used a 3 h hyperinsulinaemic, euglycaemic damp at 3.5 mmol/l whole blood glucose concentration. Both glimepiride and glibenclamide exhibited a hypoglycaemic effect. A significant reduction in fasting whole blood glucose concentration was observed after one-week treatment of each active agent (fasting glucose: glimepiride v. placebo, 9.3 +/- 0.7 v. 10.7 +/- 0.8 mmol/l, p < 0.02; glibenclamide v. placebo, 8.9 +/- 0.9 v. 10.7 +/- 0.8 mmol/l, p < 0.005). This hypoglycaemic action of both preparations administered in equivalent daily dose appeared comparable. Glimepiride and glibenclamide stimulated beta-cell secretion and in the basal state both beta-cell secretory products insulin and C-peptide, were elevated in the plasma (basal C-peptide concentration: glimepiride v. placebo, 0.79 +/- 0.08 v. 0.68 +/- 0.07 nmol/l, p < 0.01; glibenclamide v. placebo, 0.79 +/- 0.07 v. 0.68 +/- 0.07 nmol/l, p < 0.004). This insulinotropic effect appeared to be comparable with no demonstrable difference in the efficacy of the two preparations. Under steady-state hyperglycaemic conditions both agents promoted insulin release (stimulated C-peptide concentration; glimepiride v. placebo, 1.39 +/- 0.16 v. 1.11 +/- 0.20 nmol/l, p < 0.006; glibenclamide v. placebo. 1.60 +/- 0.18 v. 1.11 +/- 0.20 nmol/l, p < 0.001) and there was no statistically significant difference between active treatments. Under steady-state euglycaemia both preparations continued to stimulate insulin release as evidenced by the mean plasma C-peptide concentrations (glimepiride v. placebo, 0.69 +/- 0.10 v. 0.28 +/- 0.06 nmol/l, p < 0.01; glibenclamide v. placebo, 0.76 +/- 0.12 v. 0.28 +/- 0.06 nmol/l, p < 0.01). Both glimepiride and glibenclamide had a comparable and significant enhancing effect on glucose metabolism (Protocol II: M: glimepiride v. placebo 4.4 +/- 1.3 v. 1.3 +/- 0.7 mg/kg.min, p < 0.05; glibenclamide v. placebo 4.7 +/- 1.3 v. 1.3 +/- 0.7 mg/kg min, p < 0.03) and improved tissue sensitivity to the action of insulin as determined by the quantity of glucose metabolised per unit insulin (Protocol II: M/l ratio: glimepiride v. placebo, 0.09 +/- 0.03 v. 0.03 +/- 0.01 kg.min per mU/l, p < 0.02; glibenclamide v. placebo, 0.1 +/- 0.03 v. 0.03 +/- 0.01 kg.min per mU/l, p < 0.01). In conclusion, glimepiride is a ""second-generation"" sulfonylurea agent which stimulates pancreatic beta-cell insulin secretion, lowers blood glucose and improves tissue insulin sensitivity in non-insulin-dependent diabetic subjects. Its insulinotropic effect is comparable with that of glibenclamide but may diminish in the presence of normoglycaemia. The magnitude and hence, the clinical relevance of a selective beta-cytotropic action, determined by blood glucose concentration, remains to be demonstrated."
1,"TITLE: Progesterone alone versus progesterone combined with HCG as luteal support in GnRHa/HMG induced IVF cycles: a randomized clinical trial.ABSTRACT: Two different regimens of luteal support in gonadotrophin hormone-releasing hormone (GnRH) analogue/human menopausal gonadotrophin (GnRHa/HMG)-induced in-vitro fertilization cycle (IVF) were compared in a randomized clinical trial. After embryo transfer, either vaginal progesterone alone was administered (n = 89, P group), or a combination of vaginal progesterone and human chorionic gonadotrophin (n = 87, P/HCG group). The primary aim of this study was to assess the effect of the different regimens of luteal support on the pregnancy rate. The secondary aim was to compare oestradiol and progesterone concentrations in the luteal phase between the two groups, and assess their effect on the pregnancy rate. A clinical pregnancy rate of 15% was found in the P/HCG group in comparison with 26% in the P group (odds ratio 0.49; 99% confidence interval: 0.18-1.3). The luteal serum oestradiol and progesterone values in the P/HCG group were significantly higher when compared with the P group on the 6th, 9th and 12th day after oocyte retrieval (Wilcoxon P < 0.001). In accordance with the high oestradiol concentrations, more cases of ovarian hyperstimulation syndrome (OHSS) were found in the P/HCG group. Oestradiol values on the 9th day after oocyte retrieval, presumably the day of implantation, appeared to be higher in women who did not become clinically pregnant. We conclude that vaginal progesterone alone provides sufficient luteal support in GnRHa/HMG induced IVF cycles. The combination of vaginal progesterone and HCG as luteal support leads to significant high luteal oestradiol and progesterone concentrations. But a high concentration of oestradiol seems to have a deleterious effect on the implantation process, resulting in a low pregnancy rate."
1,"TITLE: Effectiveness of diclofenac eyedrops in reducing inflammation and the incidence of cystoid macular edema after cataract surgery.ABSTRACT: To evaluate the effectiveness of diclofenac eyedrops in reducing inflammation and the incidence of angiographic cystoid macular edema (CME) after cataract surgery and intraocular lens (IOL) implantation.Eye Clinic, Institute of Biomedical Sciences, San Paolo Hospital, Milan, Italy.Eighty-eight patients having cataract extraction were enrolled in a randomized clinical trial: 42 were given diclofenac eyedrops and 46, placebo. Postoperative inflammation in both groups was graded for 6 months using a dedicated system.Eight patients (9%) had evidence of angiographic CME approximately 1 month after surgery: seven of these were in the placebo group (P = .039). This difference was not significant 3 and 6 months postoperatively. The signs of ocular inflammation were greater in the eyes receiving placebo; the difference was particularly evident up to 1 week after surgery. There was no significant difference in visual acuity between the two groups at any follow-up point, but the contrast sensitivity of the eyes that received diclofenac improved significantly at 10.5 cycles per degree 1 month postoperatively.Diclofenac eyedrops effectively reduced ocular inflammation and the occurrence of angiographic CME after cataract surgery."
1,"TITLE: Hormonal regulation of lipoprotein(a) levels: effects of estrogen replacement therapy on lipoprotein(a) and acute phase reactants in postmenopausal women.ABSTRACT: Estrogen lowers lipoprotein(a) [Lp(a)] levels, but the mechanisms involved have not been clarified. To address the relationship between estrogenic effects on Lp(a) and serum lipids, and on other plasma proteins of hepatic origin, 15 healthy postmenopausal women participated in a randomized, double-blinded, placebo-controlled, crossover study with 4 weeks of oral conjugated estrogens (0.625 mg/d) and placebo, separated by a 6-week period. Lp(a) levels decreased during estrogen treatment in 14 of the 15 subjects (mean decrease, 23%; P < .001). In response to estrogen, apolipoprotein A-I (apoA-I), HDL cholesterol, and triglyceride levels increased by 12% (P = .001), 11% (P < .001), and 10% (P = .02), respectively. Apolipoprotein B (apoB) and LDL cholesterol levels decreased by 7% (P = .01) and 12% (P = .03), respectively, ApoB, LDL cholesterol, and Lp(a) levels fell within 1 week of treatment, whereas apoA-I and HDL cholesterol levels rose more slowly. Levels of acid alpha 1-glycoprotein (AAG) and haptoglobin (HPT), two hepatically derived acute phase proteins, also decreased during estrogen treatment by 18% (P < .001) and 25% (P = .002), respectively. Although the changes in AAG and HPT in response to estrogen were highly correlated (r = .67, P = .009), we were unable to detect a correlation between change in either acute phase protein and change in Lp(a) (r = -.14 and -.24, P = .64 and .41). The lack of correlation between the changes in two acute phase reactants and Lp(a) suggests different underlying mechanisms for the effects of estrogen on these liver-derived proteins."
1,"TITLE: Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation.ABSTRACT: Whether antiarrhythmic drugs improve the rate of successful resuscitation after out-of-hospital cardiac arrest has not been determined in randomized clinical trials.We conducted a randomized, double-blind, placebo-controlled study of intravenous amiodarone in patients with out-of-hospital cardiac arrest. Patients who had cardiac arrest with ventricular fibrillation (or pulseless ventricular tachycardia) and who had not been resuscitated after receiving three or more precordial shocks were randomly assigned to receive 300 mg of intravenous amiodarone (246 patients) or placebo (258 patients).The treatment groups had similar clinical profiles. There was no significant difference between the amiodarone and placebo groups in the duration of the resuscitation attempt (42+/-16.4 and 43+/-16.3 minutes, respectively), the number of shocks delivered (4+/-3 and 6+/-5), or the proportion of patients who required additional antiarrhythmic drugs after the administration of the study drug (66 percent and 73 percent). More patients in the amiodarone group than in the placebo group had hypotension (59 percent vs. 48 percent, P=0.04) or bradycardia (41 percent vs. 25 percent, P=0.004) after receiving the study drug. Recipients of amiodarone were more likely to survive to be admitted to the hospital (44 percent, vs. 34 percent of the placebo group; P=0.03). The benefit of amiodarone was consistent among all subgroups and at all times of drug administration. The adjusted odds ratio for survival to admission to the hospital in the amiodarone group as compared with the placebo group was 1.6 (95 percent confidence interval, 1.1 to 2.4; P=0.02). The trial did not have sufficient statistical power to detect differences in survival to hospital discharge, which differed only slightly between the two groups.In patients with out-of-hospital cardiac arrest due to refractory ventricular arrhythmias, treatment with amiodarone resulted in a higher rate of survival to hospital admission. Whether this benefit extends to survival to discharge from the hospital merits further investigation."
1,"TITLE: Postdural puncture headache is not an age-related symptom in children: a prospective, open-randomized, parallel group study comparing a22-gauge Quincke with a 22-gauge Whitacre needle.ABSTRACT: Many reports have shown a low incidence of postdural puncture headache (PDPH) and other complaints in young children. The objective of this open-randomized, prospective, parallel group study was to compare the use of a cutting point spinal needle (22-G Quincke) with a pencil point spinal needle (22-G Whitacre) in children. We studied the puncture characteristics, success rate and incidence of postpuncture complaints in 57 children, aged 8 months to 15 years, following 98 lumbar punctures (LP). The patient/parents completed a diary at 3 and 7 days after LP. The response rate was 97%. The incidence of PDPH was similar, 15% in the Quincke group and 9% in the Whitacre group (P=0.42). The risk of developing a PDPH was not dependent on the age (r < 0.00, P=0.67). Eight of the 11 PDPHs developed in children younger than 10 years, the youngest being 23-months-old."
1,"TITLE: Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic Hypertension in Europe Trial Investigators.ABSTRACT: The clinical use of ambulatory blood pressure (BP) monitoring requires further validation in prospective outcome studies.To compare the prognostic significance of conventional and ambulatory BP measurement in older patients with isolated systolic hypertension.Substudy to the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial, started in October 1988 with follow up to February 1999. The conventional BP at randomization was the mean of 6 readings (2 measurements in the sitting position at 3 visits 1 month apart). The baseline ambulatory BP was recorded with a noninvasive intermittent technique.Family practices and outpatient clinics at primary and secondary referral hospitals.A total of 808 older (aged > or =60 years) patients whose untreated BP level on conventional measurement at baseline was 160 to 219 mm Hg systolic and less than 95 mm Hg diastolic.For the overall study, patients were randomized to nitrendipine (n = 415; 10-40 mg/d) with the possible addition of enalapril (5-20 mg/d) and/or hydrochlorothiazide (12.5-25.0 mg/d) or to matching placebos (n = 393).Total and cardiovascular mortality, all cardiovascular end points, fatal and nonfatal stroke, and fatal and nonfatal cardiac end points.After adjusting for sex, age, previous cardiovascular complications, smoking, and residence in western Europe, a 10-mm Hg higher conventional systolic BP at randomization was not associated with a worse prognosis, whereas in the placebo group, a 10-mm Hg higher 24-hour BP was associated with an increased relative hazard rate (HR) of most outcome measures (eg, HR, 1.23 [95% confidence interval [CI], 1.00-1.50] for total mortality and 1.34 [95% CI, 1.03-1.75] for cardiovascular mortality). In the placebo group, the nighttime systolic BP (12 AM-6 AM) more accurately predicted end points than the daytime level. Cardiovascular risk increased with a higher night-to-day ratio of systolic BP independent of the 24-hour BP (10% increase in night-to-day ratio; HR for all cardiovascular end points, 1.41; 95% CI, 1.03-1.94). At randomization, the cardiovascular risk conferred by a conventional systolic BP of 160 mm Hg was similar to that associated with a 24-hour daytime or nighttime systolic BP of 142 mm Hg (95% CI, 128-156 mm Hg), 145 mm Hg (95% CI, 126-164 mm Hg) or 132 mm Hg (95% CI, 120-145 mm Hg), respectively. In the active treatment group, systolic BP at randomization did not significantly predict cardiovascular risk, regardless of the technique of BP measurement.In untreated older patients with isolated systolic hypertension, ambulatory systolic BP was a significant predictor of cardiovascular risk over and above conventional BP."
1,"TITLE: Diabetes mellitus, glycoprotein IIb/IIIa blockade, and heparin: evidence for a complex interaction in a multicenter trial. EPILOG Investigators.ABSTRACT: After angioplasty, major complications and ischemic events occur more frequently in diabetic than nondiabetic patients. To determine whether treatment with abciximab is effective in reducing these events in diabetics, we analyzed characteristics and outcomes of diabetic patients enrolled in a large multicenter study (EPILOG).Of 2792 patients enrolled, 638 (23%) were diabetic. Diabetic patients were older, shorter, and heavier; more likely to be female and have three-vessel disease, prior coronary artery bypass graft surgery, a history of hypertension, or a recent myocardial infarction; and less likely to be current smokers than their nondiabetic counterparts. During hospitalization, death, myocardial infarction, or urgent revascularization occurred in 7.1% of diabetics and 7.5% of nondiabetics. By 6 months, the composite of death and myocardial infarction had occurred in 8.8% of diabetic patients and 7.4% of nondiabetics, whereas death, myocardial infarction, or revascularization had occurred in 27.2% and 22.6%, respectively. Abciximab treatment reduced death or myocardial infarction among diabetic and nondiabetic patients (hazard ratios, 0.28 [95% confidence interval (CI), 0.13 to 0.57] and 0.47 [95% CI, 0.33 to 0.70] at 30 days for diabetics and nondiabetics, respectively, and 0.36 [95% CI, 0.21 to 0.61] and 0.60 [95% CI, 0.44 to 0.82] at 6 months for diabetics and nondiabetics, respectively). Abciximab reduced target vessel revascularization among nondiabetic patients (hazard ratio, 0.78 [95% CI, 0.63 to 0.96]) but not among diabetics (hazard ratio, 1.4 [95% CI, 0.94 to 2.08]). When standard- and low-dose heparin adjuncts were compared, diabetics receiving abciximab with standard-dose heparin had marginally greater reductions in the composite of death and myocardial infarction and in target vessel revascularization than diabetics assigned to abciximab with low-dose heparin.Abciximab treatment in diabetic patients led to a reduction in the composite of death and myocardial infarction, which was at least as great as that seen in nondiabetic patients. However, target vessel revascularization was reduced in nondiabetic but not diabetic patients. This effect may be associated in part with lower doses of heparin. These differences may be related to differences in the platelet and coagulation systems between diabetics and nondiabetics, the greater extent of coronary artery disease in diabetics, or patient selection and management factors."
1,"TITLE: Piperacillin/tazobactam versus imipenem: a double-blind, randomized formulary feasibility study at a major teaching hospital.ABSTRACT: With the introduction of piperacillin/tazobactam to the North American market, hospitals have been faced with the task of making a decision regarding its formulary role. In view of its broad spectrum of activity, piperacillin/tazobactam could be considered as a formulary alternative to imipenem. To evaluate the formulary feasibility of substituting piperacillin/tazobactam for imipenem, a comparative assessment of these agents in the empiric treatment of serious bacterial infections was undertaken at this tertiary care hospital. This trial was conducted as a randomized, double-blind, single-center study. Consenting adult patients (>16 years of age) who were prescribed imipenem were randomized to receive either 4 g of i.v. piperacillin/tazobactam or imipenem 500 mg of i.v. Q6H with or without concurrent antibiotics. Doses were adjusted according to renal function. There were no restrictions regarding the use of nonstudy antibiotics before and during the study period. Patients with beta-lactam allergies or meningitis or who had received greater than 72 h of previous imipenem therapy were excluded. Patients were evaluated at the end of treatment, at discharge, and at 30 days postdischarge. Endpoints included both clinical and microbiologic efficacy as well as drug toxicity. Over the 433-day study period, 360 imipenem treatment courses were initiated. Of these, 150 treatment courses (75 piperacillin/tazobactam courses and 75 imipenem courses) met study criteria and were subsequently randomized. The distribution of prescriber services for enrolled patients was similar to that for all patients receiving imipenem during the study period (p = 0.15). Also, there were no statistically significant differences in demographic parameters between enrolled and excluded patients. For those patients enrolled in the study, demographic characteristics, treatment course indication(s), and accompanying antibiotics were similar across treatment arms. The mean duration of study drug therapy was 7.7 days (SD, 6.2) for imipenem and 7.5 days (SD, 6.7)for piperacillin/tazobactam (p = 0.84). In the majority of cases, treatment discontinuation occurred as a result of a favorable treatment course outcome, stepdown to a narrower spectrum parenteral agent, or stepdown to an oral agent and did not differ between study drugs (p = 0.73). Clinical and microbiologic treatment course outcomes were also similar across treatment arms. Clinical outcome was deemed successful or improved for 68% of imipenem and 70% of the piperacillin/tazobactam treatment courses (p = 0.54). Fifty-three percent of treatment courses were microbiologically confirmed. Of the 58 courses that were assessed for microbiological outcome, 93% demonstrated successful eradication of the causative pathogens. There was no difference between study drugs (96% imipenem; 90% piperacillin/tazobactam; p = 0.61). The proportion of treatment courses with at least one adverse event was similar between the study drugs (p = 1.0). Nausea and/or vomiting were/was observed more commonly in the imipenem arm (p = 0.03). Discontinuation of therapy due to drug toxicity occurred in 16% of imipenem and 5% of piperacillin/tazobactam treatment courses (p = 0.06). There was no statistically significant difference between the mean treatment course cost for imipenem ($762; range, $55-$3192) versus piperacillin/tazobactam ($696; range, $79-$2967; p = 0.59). In summary, piperacillin/tazobactam seems to represent a suitable alternative to imipenem for several clinical indications including intraabdominal infections, pneumonia, febrile neutropenia, and skin/soft tissue infections in which the causative pathogens are susceptible. However, in view of the prevalence of multiresistant Gram-negative aerobic pathogens at this institution, we do not believe that imipenem can be removed from the drug formulary. In addition, at the currently studied dosing regimen, there seems to be no evidence of a direct cost advantage associated with"
0,"TITLE: Effect of oral antidiabetic agents on plasma amylin level in patients with non-insulin-dependent diabetes mellitus (type 2).ABSTRACT: The purpose of the study was the comparison of the effect of the oral therapy of non-insulin-dependent diabetes mellitus (NIDDM) with either a sulphonylurea or biguanide derivative on plasma amylin level. In 10 healthy individuals the fasting plasma amylin level was 1.56 +/- 0.27 pmol/l (mean +/- SEM) and 6 min after i.v. injection of 1 mg glucagon a fourfold increase was observed. In 10 patients with NIDDM receiving glibenclamide (CAS 10238-21-8) the fasting plasma amylin level was twofold higher than in healthy control (2.72 +/- 0.38 pmol/l; p < 0.025) but following glucagon administration it increased only twofold. In 15 patients treated with metformin (CAS 657-24-9) the fasting plasma amylin level was similar to that in healthy individuals (1.64 +/- 0.25 pmol/l), but after glucagon stimulation the increment of plasma amylin was minimal and the relevant mean value was significantly lower when compared with those in healthy individuals and with NIDDM patients treated with glibenclamide. In 10 untreated obese patients with newly diagnosed NIDDM the administration of glibenclamide (14 days) resulted in the increase of basal (2.47 +/- 0.23 and 3.16 +/- 0.29 pmol/l; p < 0.1), and glucagon stimulated (3.34 +/- 0.39 and 4.56 +/- 0.38; p < 0.05) plasma amylin concentrations, whereas other 10 patients receiving metformin showed a decrease in fasting plasma level of this peptide before (2.64 +/- 0.59 and 1.28 +/- 0.38 pmol/l; p < 0.1), and after glucagon injection (5.02 +/- 0.55 and 2.83 +/- 0.65 pmol/l; p < 0.02). With the respect to the trophic effect of amyloid deposits in the pancreatic islets and to a hypothetic effect of amylin increasing insulin resistance, the present results emphasize the particular usefulness of metformin in the pharmacological treatment of NIDDM. All contraindications and side effects of metformin should be taken into account before drug administration."
1,"TITLE: Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy.ABSTRACT: Teriparatide (rhPTH[1-34]), a bone-forming agent for the treatment of osteoporosis, increases bone mineral density in men and women, and reduces the risk of fractures in women with osteoporosis. However, fracture efficacy has not yet been confirmed in men. Further, there is limited information on the effect of withdrawal of teriparatide. The purpose of this manuscript is to report on bone mineral density and vertebral fracture incidence during a 42-month observation period, from the baseline of the previously reported treatment study in men [1] through 30 months of posttreatment follow-up. Three hundred fifty-five men who were treated with once-daily self-injections of either placebo or 20 or 40 microg of teriparatide participated in the follow-up study. Bone mineral density gradually decreased following discontinuation of teriparatide therapy. However, the lumbar spine and total hip values remained significantly higher than baseline after 30 months of follow-up (p< or =0.001). Antiresorptive treatment prevented the decline and tended to further increase bone mineral density. Lateral thoracic lumbar radiographs obtained at baseline and 18 months after discontinuation of teriparatide were available for 279 men. Of these men, 11.7% assigned to placebo, 5.4% treated with teriparatide 20 microg, and 6.0% treated with teriparatide 40 microg had an incident vertebral fracture. In the combined teriparatide treated groups vs placebo, the risk of vertebral fracture was reduced 51% (nonsignificant, p=0.07). The incidence of moderate or severe fractures was significantly reduced by 83% (p=0.01). In conclusion, men who received teriparatide and who may have received follow-up antiresorptive therapy had a decreased risk of moderate and severe vertebral fractures."
1,"TITLE: Levobupivacaine 0.2% or 0.125% for continuous sciatic nerve block: a prospective, randomized, double-blind comparison with 0.2% ropivacaine.ABSTRACT: In 60 patients receiving elective hallux valgus repair, we compared the efficacy of continuous popliteal sciatic nerve block produced with 0.2% ropivacaine (n = 20), 0.2% levobupivacaine (n = 20), or 0.125% levobupivacaine (n = 20) infused with a patient-controlled system starting 3 h after a 30-mL bolus of the 0.5% concentration of the study drug and for 48 h (baseline infusion rate, 6 mL/h; incremental dose, 2 mL; lockout time, 15 min; maximum incremental doses per hour, 3). No differences were reported in the intraoperative efficacy of the nerve block. The degree of pain was similar in the three groups throughout the study period, both at rest and during motion. Total consumption of local anesthetic solution during the first 24 h was 148 mL (range, 144-228 mL) with 0.2% ropivacaine, 150 mL (range, 144-200 mL) with 0.2% levobupivacaine, and 148 mL (range, 144-164 mL) with 0.125% levobupivacaine (P = 0.59). The volume of local anesthetic consumed during the second postoperative day was 150 mL (range, 144-164 mL) with 0.2% ropivacaine, 154 mL (range, 144-176 mL) with 0.2% levobupivacaine, and 151 mL (range, 144-216 mL) with 0.125% levobupivacaine (P = 0.14). A smaller proportion of patients receiving 0.2% levobupivacaine showed complete recovery of foot motor function as compared with 0.2% ropivacaine and 0.125% levobupivacaine, both at 24 h (35% vs 85% and 95%; P = 0.0005) and at 48 h (60% vs 100% and 100%; P = 0.001). We conclude that sciatic infusion with both 0.125% and 0.2% levobupivacaine provides adequate postoperative analgesia after hallux valgus repair, clinically similar to that provided by 0.2% ropivacaine; however, the 0.125% concentration is preferred if early mobilization of the operated foot is required."
1,"TITLE: Raloxifene to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: a randomized controlled trial.ABSTRACT: GnRH agonists decrease bone mineral density and increase fracture risk in men with prostate cancer. Raloxifene increases bone mineral density in postmenopausal women, but its efficacy in hypogonadal men is not known. In a 12-month open-label study, men with nonmetastatic prostate cancer (n = 48) who were receiving a GnRH agonist were assigned randomly to raloxifene (60 mg/d) or no raloxifene. Bone mineral densities of the posteroanterior lumbar spine and proximal femur were measured by dual energy x-ray absorptiometry. Mean (+/-se) bone mineral density of the posteroanterior lumbar spine increased by 1.0 +/- 0.9% in men treated with raloxifene and decreased by 1.0 +/- 0.6% in men who did not receive raloxifene (P = 0.07). Bone mineral density of the total hip increased by 1.1 +/- 0.4% in men treated with raloxifene and decreased by 2.6 +/- 0.7% in men who did not receive raloxifene (P < 0.001). Similar between-group differences were observed in the femoral neck (P = 0.06) and trochanter (P < 0.001). In men receiving a GnRH agonist, raloxifene significantly increases bone mineral density of the hip and tends to increase bone mineral density of the spine."
0,"TITLE: Another way to estimate outcome of advanced nasopharyngeal carcinoma--is concurrent chemoradiotherapy adequate?ABSTRACT: To evaluate a simple risk grouping system and determine whether concurrent chemoradiotherapy (CCRT) is adequate for patients with advanced nasopharyngeal carcinoma (NPC).A total of 284 patients with 1992 American Joint Committee on Cancer (AJCC) Stage III to IV (M0) NPC were analyzed retrospectively. They were treated by either radiotherapy (RT) alone or CCRT. We divided patients into high-risk and low-risk subgroups according to our experience. High-risk patients met at least one of the following criteria: (1) nodal size >6 cm, (2) supraclavicular node metastases, (3) 1992 AJCC stage T4N2, (4) multiple neck node metastases with 1 node >4 cm. The disease extent of each patient was stratified by our risk grouping system, AJCC 1992 and 1997 staging systems. Survival analyses-including nasopharynx disease free (TS), neck disease free (NS), distant metastasis disease free (MS), overall survival (OS), and progression-free (PFS) survival curves-were compared between these three different classifications.According to the 1992 AJCC staging system, 80.3% (228/284) of NPC patients are Stage IV, whereas only 19.7% are Stage III. Most patients are downstaged by the 1997 AJCC staging system with 28.5% (81/284) Stage IV and 71.5% (203/284) Stage III/II. Our risk criteria stratify more even patient distribution, because 119 patients (41.9%) are assigned to the high-risk group and 165 patients (58.1%) to the low-risk group. Log-rank test of Kaplan-Meier survival curves, multivariate comparison of the Cox proportional hazards model, and 3 goodness-of-fit indices validated that our risk grouping system seemed to be at least as efficacious as, or slightly superior to, the 1992 and 1997 AJCC systems. The 5-year TS (95.1% vs. 76.8%, p = 0.0012), NS (100% vs. 95.7%, p = 0.0974), MS (90.5% vs. 78.1%, p = 0.0282), OS (83.2% vs. 59.7%, p = 0.0041), and PFS (87.3% vs. 61.5%, p = 0.0003) were significantly better in patients receiving CCRT than RT alone for the low-risk group. However, the corresponding survival rates between CCRT and RT for high-risk patients were 74.9% vs. 67.6% (p = 0.2545) for TS, 92.1% vs. 86.8% (p = 0.4744) for NS, 59.7% vs. 60.0% (p = 0.5537) for MS, 55.8% vs. 46.3% (p = 0.1761) for OS, and 44.5% vs. 43.1% (p = 0.3911) for PFS, respectively.Concurrent chemoradiotherapy is superior to RT alone for low-risk patients but inadequate for high-risk patients. Adding neoadjuvant and/or adjuvant chemotherapy would be a reasonable approach for high-risk patients. Our risk grouping criteria are a simple and useful guide that will have important implications in the design of future therapeutic trials."
1,"TITLE: Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis.ABSTRACT: Oral daily (2.5 mg) and intermittent ibandronate (between-dose interval of >2 months), delivering a similar cumulative exposure, were evaluated in 2946 osteoporotic women with prevalent vertebral fracture. Significant reduction in incident vertebral fracture risk by 62% and 50%, respectively, was shown after 3 years. This is the first study to prospectively show antifracture efficacy for the intermittent administration of a bisphosphonate.Bisphosphonates are important therapeutics in postmenopausal osteoporosis. However, they are currently associated with stringent dosing instructions that may impair patient compliance and hence therapeutic efficacy. Less frequent, intermittent administration may help to overcome these deficiencies. This study assessed the efficacy and safety of oral ibandronate administered either daily or intermittently with a dose-free interval of >2 months.This randomized, double-blind, placebo-controlled, parallel-group study enrolled 2946 postmenopausal women with a BMD T score < or = -2.0 at the lumbar spine in at least one vertebra (L1-L4) and one to four prevalent vertebral fractures (T4-L4). Patients received placebo or oral ibandronate administered either daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months).After 3 years, the rate of new vertebral fractures was significantly reduced in patients receiving oral daily (4.7%) and intermittent ibandronate (4.9%), relative to placebo (9.6%). Thus, daily and intermittent oral ibandronate significantly reduced the risk of new morphometric vertebral fractures by 62% (p = 0.0001) and 50% (p = 0.0006), respectively, versus placebo. Both treatment groups also produced a statistically significant relative risk reduction in clinical vertebral fractures (49% and 48% for daily and intermittent ibandronate, respectively). Significant and progressive increases in lumbar spine (6.5%, 5.7%, and 1.3% for daily ibandronate, intermittent ibandronate, and placebo, respectively, at 3 years) and hip BMD, normalization of bone turnover, and significantly less height loss than in the placebo group were also observed for both ibandronate regimens. The overall population was at low risk for osteoporotic fractures. Consequently, the incidence of nonvertebral fractures was similar between the ibandronate and placebo groups after 3 years (9.1%, 8.9%, and 8.2% in the daily, intermittent, and placebo groups, respectively; difference between arms not significant). However, findings from a posthoc analysis showed that the daily regimen reduces the risk of nonvertebral fractures (69%; p = 0.012) in a higher-risk subgroup (femoral neck BMD T score < -3.0). In addition, oral ibandronate was well tolerated. Oral ibandronate, whether administered daily or intermittently with an extended between-dose interval of >2 months, is highly effective in reducing the incidence of osteoporotic fractures in postmenopausal women. This is the first time that significant fracture efficacy has been prospectively shown with an intermittently administered bisphosphonate in the overall study population of a randomized, controlled clinical trial. Thus, oral ibandronate holds promise as an effective and convenient alternative to current bisphosphonate therapies."
1,"TITLE: Comprehensive lifestyle modification and blood pressure control: a review of the PREMIER trial.ABSTRACT: The PREMIER trial assessed the aggregate effect on blood pressure (BP) of nationally recommended lifestyle modifications in free-living adults with high-normal (stage 1) hypertension. Participants (N=810) were randomized to the advice-only group; the established group (consisting of weight loss, increased physical activity, and reduced sodium and alcohol intake); or the established plus Dietary Approaches to Stop Hypertension (DASH) diet group (consisting of the established interventions in addition to the DASH dietary pattern). The primary outcome was change in systolic BP at 6 months. Net of advice only, mean systolic BP declined by 3.7 mm Hg for members of the established group (p<0.001) and 4.3 mm Hg for the established plus DASH group (p<0.001). The prevalence of hypertension decreased from a baseline of 38% to 17% in the established group (p=0.01) and to 12% in the established plus DASH group (p<0.001) compared with a decrease to 26% in the advice-only group. The PREMIER trial demonstrated that persons with above-optimal BP and stage 1 hypertension can make multiple lifestyle changes leading to better control of BP."
1,"TITLE: Once-daily insulin glargine compared with twice-daily NPH insulin in patients with type 1 diabetes.ABSTRACT: To present the findings in a randomized, parallel-group study, comparing once-daily insulin glargine with twice-daily NPH insulin in patients with type 1 diabetes previously treated with multiple daily injections of basal and regular insulin.Of 394 patients with type 1 diabetes treated for up to 28 weeks, 195 received insulin glargine and 199 received NPH insulin, in addition to preprandial regular insulin. Glycemic control and hypoglycemic episodes were assessed.A greater mean decrease in fasting blood glucose (FBG) was achieved at endpoint with insulin glargine than with NPH insulin (-21 mg/dL versus -10 mg/dL [-1.17 mmol/L versus -0.56 mmol/L]; P = 0.015), and a greater percentage of patients treated with insulin glargine reached the target FBG (32.6% versus 21.3%; P = 0.015). Similar percentages of patients in both treatment groups achieved glycosylated hemoglobin values of 7.0% or less at endpoint (insulin glargine, 35.8%; NPH insulin, 35.4%). After the 1-month titration phase, the percentage of patients who reported at least one symptomatic hypoglycemic event confirmed by a blood glucose value of less than 50 mg/dL (2.8 mmol/L) was significantly lower with insulin glargine than with NPH insulin (73.3% versus 81.7%; P = 0.021). Furthermore, the percentage of patients who reported at least one symptomatic hypoglycemic event confirmed by a blood glucose value of less than 36 mg/dL (2.0 mmol/L) was significantly lower with insulin glargine than with NPH insulin (36.6% versus 46.2%; P = 0.033).Once-daily insulin glargine was at least as effective as twice-daily NPH insulin in improving fasting glycemic control and resulted in fewer reported symptomatic hypoglycemic events."
0,"TITLE: Low-dose international normalized ratio self-management: a promising tool to achieve low complication rates after mechanical heart valve replacement.ABSTRACT: International normalized ratio (INR) self-management can significantly reduce INR fluctuations, bleeding, and thromboembolic events compared with INR control managed by general practitioners. However, even patients with INR self-management may have an increased risk of bleeding if their INR value is above 3.5. This study evaluated the compliance, clinical complications, and survival of patients after mechanical heart valve replacement with low-dose INR self-management compared with conventional-dose anticoagulation.Group 1 (n = 908) received low-dose anticoagulation with a target INR range of 1.8 to 2.8 for aortic valve replacement and 2.5 to 3.5 for mitral or double valve replacement. Group 2 (n = 910) received conventional-dose anticoagulation with a target INR range of 2.5 to 4.5 for all heart valve prostheses.In groups 1 and 2, 76% and 75% of INR values, respectively, were in the target range. Results did not differ according to schooling and age. The rate of thromboembolic events per patient year was 0.18% in group 1 and 0.40% in group 2 (p = 0.210). The rate of bleeding complications was 0.74% for group 1 and 1.20% for group 2 (p = 0.502). In most patients with clinically relevant bleeding, these complications occurred although their measured INR values were below 3.5. The survival rate did not differ between the study groups (p = 0.495).Low-dose INR self-management is a promising tool to achieve low hemorrhagic complications without increasing the risk of thromboembolic complications. INR self-management is applicable for all patients in whom permanent anticoagulation therapy is indicated. Even INR values below 3.5 can bear the risk of bleeding complications."
1,"TITLE: Rectal paracetamol has a significant morphine-sparing effect after hysterectomy.ABSTRACT: We have evaluated the morphine-sparing effect of rectal paracetamol during the first 24 h after abdominal hysterectomy in a placebo-controlled, double-blind study. We studied 72 patients receiving patient-controlled analgesia (PCA) with i.v. morphine after a standardized anaesthetic, allocated randomly to receive rectal paracetamol 1.3 g, diclofenac 50 mg or placebo, after wound closure and at 8 and 16 h. Suppositories were blinded by the hospital pharmacy. Study violations excluded data from seven patients. Patient data, morphine doses during anaesthesia and recovery, and sedation and nausea scores were comparable. Mean morphine consumption during PCA was 35.0 (SD 20.4) mg, 32.7 (27.4) mg and 54.9 (28.3) mg in the paracetamol (n = 24), diclofenac (n = 20) and placebo (n = 21) groups, respectively (P < 0.05). Morphine sparing during PCA for paracetamol and diclofenac (36% vs 40% over 24 h) was significant from 4 h. Global scores of average pain over 24 h were lower after diclofenac compared with paracetamol (P < 0.01) and placebo (P = 0.08). We conclude that rectal paracetamol was an efficacious adjuvant analgesic after regular dosing."
1,"TITLE: Randomised controlled trial of thiopental for intubation in neonates.ABSTRACT: To determine the effects of premedication with thiopental on heart rate, blood pressure, and oxygen saturation during semi-elective nasotracheal intubation in neonates.A randomised, placebo controlled, non-blinded study design was used to study 30 neonates (mean birthweight 3.27 kg) requiring semi-elective nasotracheal intubation. The babies were randomly allocated to receive either 6 mg/kg of thiopental (study group) or an equivalent volume of physiological saline (control group) one minute before the start of the procedure. Six infants were intubated primarily and 24 were changed from orotracheal to a nasotracheal tube. The electrocardiogram, arterial pressure wave, and transcutaneous oxygen saturation were recorded continuously 10 minutes before, during, and 20 minutes after intubation. Minute by minute measurements of heart rate, heart rate variability, mean blood pressure (MBP) and transcutaneous oxygen saturation (SpO(2)) were computed. The differences for all of these between the baseline measurements and those made during and after intubation were determined. Differences in the measurements made in the study and the control groups were compared using Student's t test.During intubation, heart rate increased to a greater degree (12.0 vs -0.5 beats per minute, p < 0.03) and MBP increased to a lesser degree (-2.9 vs 4.4 mm Hg; p < 0.002) in the infants who were premedicated with thiopental. After intubation only the changes in MBP differed significantly between the two groups (-3.8 vs 4.6 mm Hg; p < 0.001). There were no significant changes in the oxygen saturation between the two groups during or after intubation. The time taken for intubation was significantly shorter in the study group (p < 0.04).The heart rate and blood pressure of infants who are premedicated with thiopental are maintained nearer to baseline values than those of similar infants who receive no premedication. Whether this lessening of the acute drop in the heart rate and increase in blood pressure typically seen during intubation of unmedicated infants is associated with long term advantages to the infants remains to be determined."
1,"TITLE: The misoprostol third stage of labour study: a randomised controlled comparison between orally administered misoprostol and standard management.ABSTRACT: To compare misoprostol with standard oxytocic regimens in the prevention of postpartum haemorrhage.Randomised controlled trial.Obstetric unit in a large teaching hospital.One thousand women randomised to 500 microg misoprostol given orally or to standard oxytocic regimens of oxytocin, oxytocin with ergometrine, or ergometrine.Incidence of postpartum haemorrhage and the incidence and severity of side effects.Postpartum haemorrhage occurred in 12% of women given misoprostol and in 11% of women given standard oxytocic drugs (relative risk (RR) 1.10, 95% confidence interval (CI) 0.79, 1.55). Blood loss of 1000 mL or more occurred in 2% of women in each group. Nausea, headache, dizziness and tiredness were less frequent with misoprostol (RR (95% CI) 0.71 (0.59, 0.84); 0.53 (0.38, 0.74); 0.73 (0.61, 0.87) and 0.88 (0.83, 0.94) respectively). The main side effects of misoprostol were shivering (RR 1.95, 95% CI 1.69, 2.25) and a rise in temperature (difference in mean rise 0.34 degrees C, 95% CI 0.26, 0.42).Oral misoprostol for the prevention of postpartum haemorrhage was comparable to standard oxytocics. Many side effects were less common with misoprostol but shivering and pyrexia were more common. Larger randomised trials are needed before establishing the equivalence between misoprostol and standard oxytocic drugs in the prevention of postpartum haemorrhage."
0,"TITLE: Long-term, open-label study of the safety and efficacy of atomoxetine in adults with attention-deficit/hyperactivity disorder: an interim analysis.ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neuropsychiatric disorder that affects 3% to 7% of school-age children and 4% of adults. Its pathophysiology is thought to involve the dopaminergic and nor-adrenergic pathways associated with attention control and impulsivity. These symptoms have largely been defined in the childhood population, but the course of the condition and expression in the adult population are not as well characterized.This is an ongoing, 3-year, open-label study consisting of adults with DSM-IV ADHD who were previously enrolled in 1 of 2 double-blind, acute-treatment studies of atomoxetine. The results of the interim analysis reported here were derived from the study of 384 patients at 31 sites who had been studied for a period of up to 97 weeks. The primary efficacy measure was the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) total ADHD symptom score. In addition, safety, adverse events, and vital sign measurements were assessed.Significant improvement was noted with atomoxetine therapy, with mean CAARS-Inv:SV total ADHD symptom scores decreasing 33.2% from 29.2 (baseline of open-label therapy) to 19.5 (endpoint of open-label therapy) (p < .001). Similar and significant decreases were noted for the secondary efficacy measures. Adverse events consisted primarily of pharmacologically (noradrenergic) expected effects, such as increases in heart rate and blood pressure and a slight decrease in weight.The results of this interim analysis of an ongoing, open-label study of adults with ADHD support the long-term efficacy, safety, and tolerability of atomoxetine for the treatment of adult ADHD."
1,"TITLE: Add-on melatonin improves sleep behavior in children with epilepsy: randomized, double-blind, placebo-controlled trial.ABSTRACT: This double-blind, randomized, placebo-controlled study in epileptic children, aged 3 to 12 years, evaluated the effect of add-on melatonin on the sleep behavior of these children on sodium valproate monotherapy using a parental questionnaire. Of the 31 patients, 16 randomly received add-on melatonin, whereas 15 received add-on placebo. The questionnaire showed good internal consistency in our patient population (Cronbach's alpha = .83). The percentage decrease in the median total sleep score was 24.4 (range 0.0-34.9) in the valproate + melatonin group compared with 14.0 (range -2.2-18.8) in the valproate + placebo group, the difference being statistically significant (P < .05). The median percentage decrease in the parasomnias score was 60 (range 0.0-70.8) in the valproate + melatonin group compared with 36.4 (range 0.0-63.2) in the valproate + placebo group, the difference being statistically significant (P < .05). There was no significant difference between the percentage decrease in the daytime drowsiness scores and sleep fragmentation scores. Parent-child interaction subscale scores were not significantly different between age groups. The age at onset of seizures and the type of seizures did not correlate significantly to the total sleep scores. Given that sleep problems are known to complicate epilepsy, add-on melatonin, which has a wide safety window, can be of promise in the pharmacotherapy of pediatric epilepsy."
1,"TITLE: A randomized trial of electronic clinical reminders to improve quality of care for diabetes and coronary artery disease.ABSTRACT: The aim of this study was to evaluate the impact of an integrated patient-specific electronic clinical reminder system on diabetes and coronary artery disease (CAD) care and to assess physician attitudes toward this reminder system.We enrolled 194 primary care physicians caring for 4549 patients with diabetes and 2199 patients with CAD at 20 ambulatory clinics. Clinics were randomized so that physicians received either evidence-based electronic reminders within their patients' electronic medical record or usual care. There were five reminders for diabetes care and four reminders for CAD care.The primary outcome was receipt of recommended care for diabetes and CAD. We created a summary outcome to assess the odds of increased compliance with overall diabetes care (based on five measures) and overall CAD care (based on four measures). We surveyed physicians to assess attitudes toward the reminder system.Baseline adherence rates to all quality measures were low. While electronic reminders increased the odds of recommended diabetes care (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.01-1.67) and CAD (OR 1.25, 95% CI 1.01-1.55), the impact of individual reminders was variable. A total of three of nine reminders effectively increased rates of recommended care for diabetes or CAD. The majority of physicians (76%) thought that reminders improved quality of care.An integrated electronic reminder system resulted in variable improvement in care for diabetes and CAD. These improvements were often limited and quality gaps persist."
1,"TITLE: Losartan benefits over atenolol in non-smoking hypertensive patients with left ventricular hypertrophy: the LIFE study.ABSTRACT: We studied the impact of smoking in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, which showed superiority of losartan over atenolol for reduction of composite risk of cardiovascular death, stroke and myocardial infarction in hypertensives with left ventricular hypertrophy. We compared hazard ratios in 4656 never-smokers, and 3033 previous and 1499 current smokers, adjusting for gender, age, alcohol intake, exercise and race. Composite endpoint rate was higher in previous (28/1000 years), as well as current (39/1000 years) smokers than in never-smokers (21/1000 years). Composite (hazard ratio 0.78, 95% CI 0.65-0.94, p < 0.01) and stroke (hazard ratio 0.61, 95% CI 0.47-0.80], p < 0.001) risks were lower with losartan than atenolol in never-smokers, but not significantly in previous smokers. Drug regimens did not differ in current smokers (composite hazard ratio 0.99, stroke hazard ratio 0.94). Smoking-treatment interactions were non-significant, but a borderline significant trend (p = 0.05) suggested decreasing benefit of losartan vs atenolol for stroke prevention from never- to previous to current smoking status. Smoking increased cardiovascular risk markedly in the LIFE study. The benefit of losartan vs atenolol is consistent with the overall conclusion of the LIFE study, although the treatment effect appeared largest in non-smokers."
1,"TITLE: Analysis of morbidity in patients with endometrial cancer: is there a commitment to offer laparoscopy?ABSTRACT: Benefits of laparoscopy over laparotomy in patients with endometrial cancer (EC) are well known. As many patients with EC carry co-morbid conditions, surgery is exposing them to increased risk of complications. A review of the patients with EC recruited so far in a clinical trial comparing laparoscopy to laparotomy was performed. The goal was to identify patients carrying specific risk factors for complications, who would most benefit of laparoscopy and be the ideal candidates for this surgical approach.Between July 1995 and December 2002, 122 patients with uterine cancer entered the study. Sixty-three patients were allocated to the laparoscopy (LPS) arm (group A), while 59 were allocated to the laparotomy (LPT) arm (group B). Rate and type of intra-, early and late post-operative complications were prospectively recorded. Risk factors for complications are analyzed to define a group of patients truly benefiting from laparoscopy.Overall, 12 patients out of 122 (9.8%) have experienced intra-operative, 43 patients out of 122 (35.2%) early post-operative and 25 patients out of 122 (20.4%) late post-operative complications. Rate of intra-operative complications was 4.7% in group A (3 patients out of 63) vs. 15.2% in group B (9 patients out of 59), P = 0.082. Early post-operative complications rate was 23.8% in group A (15 out of 63) and 47.4% in group B (28 out of 59), P = 0.011. Rate of late post-operative complications was 7.9% (5 out of 63) in group A vs. 35.5% (21 out of 59), P = 0.001. Univariate analysis shows co-morbid medical conditions, weight >80 kg, Quetelet index >30 and age >65 years to be predictive of complications and, in fact, a subgroup of patients presenting with these characteristics (n = 57, 30 in group A and 27 in group B) has been recognized to accumulate 60% of the overall complications. In these patients, multivariate analysis identifies the surgical technique (LPS vs. LPT) to be the only significant risk factor for complications.At least one third of the patients with EC carry serious co-morbidities with an increased surgical risk for complications. For this subgroup of patients, a laparoscopic-vaginal approach significantly reduces the rate of complications and should be the standard of surgical treatment."
1,"TITLE: Impact of an adherence clinic on behavioral outcomes and virologic response in treatment of HIV infection: a prospective, randomized, controlled pilot study.ABSTRACT: The aim of this randomized, controlled pilot study was to examine the impact of a pharmacist operated adherence clinic on adherence to highly active antiretroviral therapy (HAART) and viral suppression in patients with HIV over 28 weeks.Consecutive eligible patients initiating HAART at an indigent-care clinic were randomized to an adherence clinic or to standard care (information provided by physician or nurse practitioner) for education and monitoring. Group assignment was stratified before randomization according to regimen complexity and potential tolerability. Adherence (electronic monitoring and patient self-report) and viral load (reverse-transcription polymerase chain reaction) were assessed at weeks 4, 16, and 28.Thirty-three randomized patients (adherence clinic, n = 16; standard care, n = 17) comprised the intent-to-treat population. The groups were well-matched for demographics and antiretroviral regimen. The median age was 38.0 years in both groups. Most patients were male (85%), had previously used HAART (78%), and had an AIDS diagnosis (79%). Mean (SD) adherence at weeks 4, 16, and 28 was 86% (27%), 77% (28%), and 74% (31%) in the adherence clinic group versus 73% (32%), 56% (39%), and 51% (41%) in the standard care group (week-16 difference, 21% [90% CI, 1%-42%]; week-28 difference, 23% [90% CI, 1%-44%]). Sixty-nine percent of patients in the adherence clinic group took their medication on schedule versus 42% in the standard care group (P = 0.025); mean decline in adherence from weeks 4 to 28 was 12% in the adherence clinic group (P = 0.15) versus 22% in the standard care group (P = 0.002). HIV-1 RNA levels were <400 copies/mL at weeks 4, 16, and 28 in 63%, 100%, and 94% of the adherence clinic group and 29% (P = NS), 71% (P = 0.04), and 65% (P = NS) of the standard care group.In this preliminary trial, an adherence clinic model improved adherence to HAART and virologic response over 28 weeks in the patients studied."
1,"TITLE: Comparative trial of short-course ofloxacin for uncomplicated typhoid fever in Vietnamese children.ABSTRACT: An open, randomised comparison of 2 or 3 days of oral ofloxacin (10 mg/kg/day) for uncomplicated typhoid fever was conducted in 235 Vietnamese children. Multi-drug-resistant Salmonella typhi was isolated from 182/202 (90%) children and 5/166 (3%) tested isolates were nalidixic acid-resistant (Na(R)). Eighty-nine of 116 children randomised to 2 days and 107/119 randomised to 3 days were blood culture-positive and eligible for analysis. There were 12 (13.5%) failures in the 2-day group (six clinical failures, four blood culture-positive post treatment, two relapses) compared with eight (7.5%) failures in the 3-day group (four clinical failures, one blood culture-positive post treatment, three relapses) (OR 1.9, 95% CI 0.7-5.5,p = 0.17). There were no significant differences in the mean (95% confidence interval) fever clearance times (h) [92 (82-102) vs 101 (93-110), p = 0.18] or duration of hospitalisation (d) [7.6 (7.2-8.1) vs 8.0 (7.6-8.4), p = 0.19] between the two groups. There was one failure in the four eligible children infected with an Na(R) isolate of S. typhi. No adverse events were attributable to the ofloxacin. These results extend previous observations on the efficacy of short courses of ofloxacin for children with uncomplicated multi-drug-resistant typhoid fever."
1,"TITLE: Twenty-four-hour diurnal curve comparison of commercially available latanoprost 0.005% versus the timolol and dorzolamide fixed combination.ABSTRACT: To evaluate the efficacy and safety of commercially available latanoprost 0.005% given every evening versus timolol 0.5% and dorzolamide 2% fixed combination (TDFC) given twice daily to white Greeks with primary open-angle glaucoma and ocular hypertensive patients.A single-masked, two-center, crossover comparison with two 6-week treatment periods occurring after at least a 3-week medicine-free period. Diurnal curve intraocular pressures were taken at 2:00 AM, 6:00 AM, 10:00 AM, 2:00 PM, 6:00 PM, and 10:00 PM.Thirty-four subjects with primary open-angle glaucoma or ocular hypertension were enrolled.Latanoprost 0.005% given every evening and TDFC twice daily.The primary efficacy variable was diurnal intraocular pressure.Thirty-three patients completed the study. On the last day of treatment, the mean diurnal intraocular pressure for latanoprost was 15.9 +/- 2.3 mmHg and for TDFC was 15.3 +/- 2.0 mmHg (P = 0.05). Individual time points for intraocular pressure were not statistically different between groups except at the 10:00 PM time point, when the mean for TDFC was 14.6 +/- 2.7 mmHg and for latanoprost was 16.6 +/- 3.1 mmHg (P < 0.006). Eighteen patients overall preferred latanoprost versus 2 patients for the fixed combination, generally because of the greater convenience of once daily dosing. Adverse events were not significantly different between groups except that a bitter taste was found more frequently with TDFC (n = 9) than with latanoprost (n = 0; P = 0.009). Despite screening to exclude intolerance to beta-blockers, a single patient had to discontinue the TDFC because of new-onset asthma.This study indicates that the 24-hour diurnal intraocular pressure is lowered more, by a small but statistically significant amount, with TDFC compared with latanoprost in primary open-angle glaucoma and ocular hypertensive patients."
1,"TITLE: Oral choline decreases brain purine levels in lithium-treated subjects with rapid-cycling bipolar disorder: a double-blind trial using proton and lithium magnetic resonance spectroscopy.ABSTRACT: Oral choline administration has been reported to increase brain phosphatidylcholine levels. As phospholipid synthesis for maintaining membrane integrity in mammalian brain cells consumes approximately 10-15% of the total adenosine triphosphate (ATP) pool, an increased availability of brain choline may lead to an increase in ATP consumption. Given reports of genetic studies, which suggest mitochondrial dysfunction, and phosphorus (31P) magnetic resonance spectroscopy (MRS) studies, which report dysfunction in high-energy phosphate metabolism in patients with bipolar disorder, the current study is designed to evaluate the role of oral choline supplementation in modifying high-energy phosphate metabolism in subjects with bipolar disorder.Eight lithium-treated patients with DSM-IV bipolar disorder, rapid cycling type were randomly assigned to 50 mg/kg/day of choline bitartrate or placebo for 12 weeks. Brain purine, choline and lithium levels were assessed using 1H- and 7Li-MRS. Patients received four to six MRS scans, at baseline and weeks 2, 3, 5, 8, 10 and 12 of treatment (n = 40 scans). Patients were assessed using the Clinical Global Impression Scale (CGIS), the Young Mania Rating Scale (YRMS) and the Hamilton Depression Rating Scale (HDRS) at each MRS scan.There were no significant differences in change-from-baseline measures of CGIS, YMRS, and HDRS, brain choline/creatine ratios, and brain lithium levels over a 12-week assessment period between the choline and placebo groups or within each group. However, the choline treatment group showed a significant decrease in purine metabolite ratios from baseline (purine/n-acetyl aspartate: coef = -0.08, z = -2.17, df = 22, p = 0.030; purine/choline: coef = -0.12, z = -1.97, df = 22, p = 0.049) compared to the placebo group, controlling for brain lithium level changes. Brain lithium level change was not a significant predictor of purine ratios.The current study reports that oral choline supplementation resulted in a significant decrease in brain purine levels over a 12-week treatment period in lithium-treated patients with DSM-IV bipolar disorder, rapid-cycling type, which may be related to the anti-manic effects of adjuvant choline. This result is consistent with mitochondrial dysfunction in bipolar disorder inadequately meeting the demand for increased ATP production as exogenous oral choline administration increases membrane phospholipid synthesis."
0,"TITLE: Effects of iron(II) salts and iron(III) complexes on trace element status in children with iron-deficiency anemia.ABSTRACT: Iron-deficiency anemia (IDA) is the most common nutritional deficiency in childhood throughout the world. Although it has been shown that IRA is associated with elevated plasma copper and depleted zinc levels in children, there are conflicting results on the effect of iron supplementation on the absorption of these elements. The aim of this study was to investigate the effects of ferrous and ferric iron supplementation on the trace element status in children (n=25, aged 8-168 mo) with IDA. Fourteen of them were treated with ferric hydroxide-polymaltose complex (Ferrum, Vifor, Switzerland) (6 mg/d in the first 3 mo for initial therapy and 3 mg/kg for 3 mo as maintenance); the others were treated with a ferrous sulfate complex (FerroSanol, Schwarz, Germany) (6 mg/d in the first 3 mo for initial therapy and 3 mg/kg for 3 mo as maintenance). Plasma copper, zinc, and ceruloplasmin levels as well as hematological parameters were determined at baseline and the first, third, and sixth month of the treatment period. The hemoglobin and iron levels of patients in both groups were higher in the first and sixth months compared to baseline. Although the ceruloplasmin levels were depleted (48.9 mg/dL vs 41.4 mg/dL, p=0.035) during ferrous iron treatment, the copper and zinc levels remained unchanged. On the other hand, ferric iron supplementation led to an increase in zinc levels in the sixth month of treatment (0.77 mg/L vs 1.0 mg/L, p=0.021). The plasma copper levels were lower in the ferrous iron-treated group at the end of the first month of treatment than in the ferric irontreated group (1.06 mg/L vs 1.29 mg/L, p=0.008). In conclusion, our data showed that copper and ceruloplasmin metabolisms were affected by ferrous iron supplementation, whereas ferric iron kept them to normal levels of zinc, possibly by affecting their absorption. We conclude that the copper and zinc status of patients with IDA should be taken into consideration before and after iron therapy."
1,"TITLE: The effects of sevelamer and calcium acetate on proxies of atherosclerotic and arteriosclerotic vascular disease in hemodialysis patients.ABSTRACT: We recently determined that in hemodialysis patients, the use of calcium salts to correct hyperphosphatemia led to progressive coronary artery and aortic calcification as determined by sequential electron beam tomography (EBT) while the use of the non-calcium-containing binder sevelamer did not. Whether the specific calcium preparation (acetate vs. carbonate) might influence the likelihood of progressive calcification was debated.To determine whether treatment with calcium acetate was specifically associated with hypercalcemia and progressive vascular calcification, we conducted an analysis restricted to 108 hemodialysis patients randomized to calcium acetate or sevelamer and followed for one year.The reduction in serum phosphorus was roughly equivalent with both agents (calcium acetate -2.5 +/- 1.8 mg/dl vs. sevelamer -2.8 +/- 2.0 mg/dl, p = 0.53). Subjects given calcium acetate were more likely to develop hypercalcemia (defined as an albumin-corrected serum calcium > or =10.5 mg/dl) (36 vs. 13%, p = 0.015). Treatment with calcium acetate (mean 4.6 +/- 2.1 g/day - equivalent to 1.2 +/- 0.5 g of elemental calcium) led to a significant increase in EBT-determined calcification of the coronary arteries (mean change 182 +/- 350, median change +20, p = 0.002) and aorta (mean change 181 +/- 855, median change +73, p < 0.0001). These changes were similar in magnitude to those seen with calcium carbonate. There were no significant changes in calcification among sevelamer-treated subjects.Despite purported differences in safety and efficacy relative to calcium carbonate, calcium acetate led to hypercalcemia and progressive vascular calcification in hemodialysis patients."
1,"TITLE: Efficacy of albendazole and short-course dexamethasone treatment in children with 1 or 2 ring-enhancing lesions of neurocysticercosis: a randomized controlled trial.ABSTRACT: To determine the efficacy of albendazole plus dexamethasone in children with 1 or 2 ring-enhancing lesions (by computed tomography scan) on resolution of lesions and recurrence of seizure.Randomized controlled open trial.Children of either sex, 1 to 14 years of age, with seizures and 1 or 2 ring-enhancing lesions <20 mm in diameter on computed tomography scan, likely to have neurocysticercosis, were assigned to treatment l groups. Children assigned to the treatment group (n=61) were given 0.15 mg/kg per day dexamethasone for 5 days plus 15 mg/kg per day albendazole for 28 days, starting on the third day of dexamethasone. Control group (n=62) children were given neither dexamethasone or albendazole. Anti-epileptic therapy was given to both the study groups.The lesions resolved completely or partially in more children in the treated group compared with the control group (79% versus 57%; P=.02). The proportion of children who had seizures was significantly lower in the treated group compared with the control group at 3 months (10% versus 32%; P=.006) and 6 months (13% versus 33%; P=.03).Albendazole plus dexamethasone increased complete or partial resolution of lesions and reduced the risk of subsequent recurrence of seizures among children with neurocysticercosis who had with seizures and 1 or 2 ring-enhancing lesions on computed tomography."
1,"TITLE: Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).ABSTRACT: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind, active, controlled clinical trial conducted to determine whether newer antihypertensive agents, including doxazosin, an alpha-blocker, differ from chlorthalidone, a diuretic, with respect to coronary heart disease (CHD) and other cardiovascular disease (CVD) events in hypertensive patients at high risk of CHD. In February 2000, the doxazosin treatment arm was discontinued, and findings through December 1999 were reported. This report includes an additional 9232 participant-years and 939 CVD events. At 623 clinical centers, patients (aged >or=55 years) with hypertension and at least 1 other CHD risk factor were randomly assigned to either chlorthalidone or doxazosin. The primary outcome measure was the combined occurrence of fatal CHD or nonfatal myocardial infarction (MI), analyzed by intent to treat; prespecified secondary outcome measures included all-cause mortality, stroke, combined CHD (fatal CHD, nonfatal MI, hospitalized angina, and coronary revascularization), and combined CVD (combined CHD, stroke, angina treated outside the hospital, heart failure, and peripheral arterial disease). Mean follow-up was 3.2 years. There was no difference in primary outcome between the arms (relative risk [RR], 1.02; 95% confidence interval [CI], 0.92 to 1.15). All-cause mortality also did not differ (RR, 1.03; 95% CI, 0.94 to 1.13). However, the doxazosin arm compared with the chlorthalidone arm had a higher risk of stroke (RR, 1.26; 95% CI, 1.10 to 1.46) and combined CVD (RR 1.20; 95% CI, 1.13 to 1.27). These findings confirm the superiority of diuretic-based over alpha-blocker-based antihypertensive treatment for the prevention of CVD."
0,"TITLE: Clinical observations on postoperative vomiting treated by auricular acupuncture.ABSTRACT: We studied the effect of auricular acupuncture on postoperative nausea and vomiting (PONV). One hundred female patients undergoing transabdominal hysterectomy were entered into the study. The patients were divided into two groups (auricular acupuncture treatment group and non-treatment group) in order to test the effectiveness of auricular acupuncture. There was no significant difference in age, weight, height or duration of anesthesia among the two groups of patients. There was a significant difference between the control and auricular acupuncture treatment groups in the incidence of vomiting 12 hours after surgery (68% and 30%, respectively, p < 0.01). No noteworthy side effects from treatment were observed. Auricular acupuncture is effective in reducing vomiting following transabdominal hysterectomy in female patients."
1,"TITLE: Timing of the effect of acetaminophen on body temperature in patients with acute ischemic stroke.ABSTRACT: The authors assessed the time of onset of the hypothermic effect of acetaminophen in 102 patients with acute ischemic stroke. These patients were randomized to treatment with either 1000 mg of acetaminophen (n = 52) or placebo (n = 50), given six times daily. Treatment with high-dose acetaminophen resulted in a 0.26 degrees C (95% CI 0.07 to 0.46 degrees C) lower mean body temperature than placebo treatment within 4 hours. This effect remained present throughout the next 20 hours. A large phase III trial seems warranted."
1,"TITLE: Acupuncture facilitates neuromuscular and oculomotor responses to skin incision with no influence on auditory evoked potentials under sevoflurane anaesthesia.ABSTRACT: More sevoflurane was recently found to be required to prevent movement in response to surgical incision in anaesthetized patients subjected to electro-acupuncture (EA) than to sham procedures. The present study was designed to compare differences in movement, dilatation of the pupils, divergence of the eye axes and activity of auditory evoked potentials (AEPs) between patients given and those not given EA under standardized sevoflurane anaesthesia.Neuromuscular, oculomotor and AEP responses to skin incision were assessed with and without a bilateral 2-Hz burst EA in patients under steady-state anaesthesia maintained with 1.8% of sevoflurane. Forty-five healthy patients, scheduled for laparoscopic sterilization, were randomized for EA (n = 22) or sham (n = 23) procedures between induction of anaesthesia and start of surgery. Middle latency AEP activity was recorded and interpreted by the A-line ARX (autoregression with exogenous input) index (AAI).More acupuncture than sham patients were found to respond to skin incision with movement of the neck or limbs (77% vs. 43%; P = 0.021), dilatation of the pupils (77% vs. 39%; P = 0.001) and divergence of the eye axes (72% vs. 39%; P = 0.023), whereas there was no difference in AAI response.Electro-acupuncture facilitates physiological responses to nociceptive stimulation under sevoflurane anaesthesia. Differences in neuromuscular and oculomotor responses between acupuncture and sham patients under general anaesthesia are probably not associated with interaction between EA and the depth of anaesthesia, as AEP activity was similar in the two groups."
1,"TITLE: Oral appliance therapy reduces blood pressure in obstructive sleep apnea: a randomized, controlled trial.ABSTRACT: To investigate the short-term effect (4 weeks) of oral appliance therapy for obstructive sleep apnea on blood pressure.Randomized, controlled, crossover trial.Multidisciplinary sleep disorders clinic in a university teaching hospital.Sixty-one patients diagnosed with obstructive sleep apnea on polysomnography (apnea hypopnea index > or = 10 per hour and at least 2 of the following symptoms--daytime sleepiness, snoring, witnessed apneas, fragmented sleep; age > 20 years; and minimum mandibular protrusion of 3 mm).A mandibular advancement splint (MAS) and control oral appliance for 4 weeks each.Polysomnography and 24-hour ambulatory blood pressure monitoring were carried out at baseline and following each 4-week intervention period. Patients showed a 50% reduction in mean apnea hypopnea index with MAS compared with the control and a significant improvement in both minimum oxygen saturation and arousal index. There was a significant reduction with the MAS in mean (+/- SEM) 24-hour diastolic blood pressure (1.8 +/- 0.5 mmHg) compared with the control (P = .001) but not in 24-hour systolic blood pressure. Awake blood-pressure variables were reduced with the MAS by an estimated mean (+/- SEM) of 3.3 +/- 1.1 mmHg for systolic blood pressure (P = .003) and 3.4 +/- 0.9 mmHg for diastolic blood pressure (P < .0001). There was no significant difference in blood pressure measured asleep.Oral appliance therapy for obstructive sleep apnea over 4 weeks results in a reduction in blood pressure, similar to that reported with continuous positive airway pressure therapy."
1,"TITLE: Effect of short-term hyperglycaemia on haemodynamics in type 1 diabetic patients.ABSTRACT: Mechanisms underlying glucose-mediated development and progression of diabetic complications are incompletely understood. We tested the impact of short-term hyperglycaemia on systemic blood pressure and regulatory hormones in type 1 diabetic patients.We included 18 patients [13 men, mean (SEM) diabetes duration 10 (1) years] without signs of autonomic neuropathy or renal complications in a randomized single-blinded cross-over trial using insulin-glucose clamp technique. Patients were clamped for 90 min to blood glucose of 5 mmol L(-1) (euglycaemia) and 15 mmol L(-1) (hyperglycaemia) in random order. Blood pressure was measured noninvasively every 5 min (Takeda TM2421 device). Regulatory hormones were determined at the end of each clamp period.Systolic blood pressure increased [mean (95% CI)] 3 (1, 5) mmHg during hyperglycaemia from 123 (SEM 2) during euglycaemia, P=0.01. Diastolic blood pressure remained unchanged at 78 (2) mmHg. Hyperglycaemia reduced plasma concentrations of: renin [14 (4, 23)%, P=0.02], angiotensin II [17 (8, 25)%, P<0.01] and adrenaline [20 (10, 29)%, P<0.01]. Plasma concentration of atrial natriuretic peptide increased by 11 (6, 17) pg mL(-1) (P<0.01) from 43 (2) pg mL(-1). We calculated a median (range) increase in extracellular volume and plasma volume (PV) of 2.6 (0.7-5.3)% and 5.0 (-4.7 to 8.6)%, respectively.In type 1 diabetic patients without signs of autonomic neuropathy short-term hyperglycaemia induced a modest increase in systolic blood pressure and suppression of the renin-angiotensin system, possibly caused by PV expansion because of fluid shift from intra- to extracellular compartment."
1,"TITLE: Abciximab reduces monocyte tissue factor in carotid angioplasty and stenting.ABSTRACT: Abciximab, a nonselective glycoprotein IIb/IIIa inhibitor, was shown to reduce peri-interventional stroke rate in carotid stenting. We evaluated the effect of adjunct abciximab therapy on monocyte-platelet cross talk and neurological deficit in unprotected carotid stenting and compared its efficacy with distal filter protection.Fifty patients were randomized to either standard antithrombotic therapy (n=30) consisting of aspirin, clopidogrel, and heparin or adjunct bolus (0.25 mg/kg) and 12-hour infusion (0.125 microg x kg(-1) x min(-1)) of abciximab (n=20). A third cohort of patients was stented with filter protection (n=30). Monocyte-platelet aggregate formation and monocyte tissue factor expression were determined by whole blood flow cytometry, and F1.2 generation and soluble CD40 ligand (sCD40L) were determined by immunoassay.The incidence of peri-interventional ischemic episodes (23% versus 10%; P=0.2) and the number of de novo ischemic lesions detected by diffusion-weighted MRI (47% versus 30%; P=0.17) were not significantly different between standard antithrombotic therapy and adjunct abciximab but were reduced with filter protection (P=0.023). However, the number of transient ischemic attacks was lower (P=0.05) and the National Institutes of Health Stroke Score rapidly decreased in patients with adjunct abciximab. This clinical improvement was paralleled by a reduction in the postinterventional percentage of activated monocyte-platelet aggregates (CD62P+/CD14+; P=0.018) and the number of tissue factor-positive monocytes (TF+/CD14+; P=0.005). Both abciximab and filter protection suppressed F1.2 generation and significantly reduced sCD40L.Abciximab limits thrombus propagation and thrombus stabilization after carotid stenting by reducing monocyte-platelet cross talk and sCD40L. Although abciximab seems inferior to filter devices in peri-interventional cerebral protection, it may be considered in patients who do not allow placement of protection devices."
1,"TITLE: Evidence of a lack of effect of a phytoestrogen regimen on the levels of C-reactive protein, E-selectin, and nitrate in postmenopausal women.ABSTRACT: Phytoestrogens are thought to be beneficial to vascular health. Possible mechanisms of action could involve C-reactive protein (CRP), endothelial E-selectin, and nitric oxide. We therefore designed a randomized, placebo-controlled, double-blind trial in which we studied the effects of isoflavonoids on CRP, E-selectin, and nitrate-nitrite (NO(x); reflecting the release of nitric oxide) in postmenopausal women. Fifty-six postmenopausal women (FSH > 30 U/liter) with a history of breast cancer used (in a randomized order) phytoestrogen (114 mg isoflavonoids) or placebo tablets daily for 3 months; the treatment regimens were crossed over after a 2-month washout period. The serum levels of CRP and E-selectin, and plasma levels of NO(x) were measured before and on the last day of each treatment. The phytoestrogen regimen did not affect the levels of either CRP (P = 0.584) or NO(x) (P = 0.270), but the levels of E-selectin were reduced by 4.0% (2.9 ng/ml; P = 0.031) during phytoestrogen use and by 2.2% (1.3 ng/ml; P = 0.023) during placebo use. No difference was found at any marker at 3 months between the groups. In conclusion, our data, suggesting neutral effects of phytoestrogens on CRP, E-selectin, and nitric oxide, fail to support a vasoprotective role of phytoestrogens."
1,"TITLE: Effects of high-flux hemodialysis on clinical outcomes: results of the HEMO study.ABSTRACT: Among the 1846 patients in the HEMO Study, chronic high-flux dialysis did not significantly affect the primary outcome of the all-cause mortality (ACM) rate or the main secondary composite outcomes, including the rates of first cardiac hospitalization or ACM, first infectious hospitalization or ACM, first 15% decrease in serum albumin levels or ACM, or all non-vascular access-related hospitalizations. The high-flux intervention, however, seemed to be associated with reduced risks of specific cardiac-related events. The relative risks (RR) for the high-flux arm, compared with the low-flux arm, were 0.80 [95% confidence interval (CI), 0.65 to 0.99] for cardiac death and 0.87 (95% CI, 0.76 to 1.00) for the composite of first cardiac hospitalization or cardiac death. Also, the effect of high-flux dialysis on ACM seemed to vary, depending on the duration of prior dialysis. This report presents secondary analyses to further explore the relationship between the flux intervention and the duration of dialysis with respect to various outcomes. The patients were stratified into a short-duration group and a long-duration group, on the basis of the mean duration of dialysis of 3.7 yr before randomization. In the subgroup that had been on dialysis for >3.7 yr, randomization to high-flux dialysis was associated with lower risks of ACM (RR, 0.68; 95% CI, 0.53 to 0.86; P = 0.001), the composite of first albumin level decrease or ACM (RR, 0.74; 95% CI, 0.60 to 0.91; P = 0.005), and cardiac deaths (RR, 0.63; 95% CI, 0.43 to 0.92; P = 0.016), compared with low-flux dialysis. No significant differences were observed in outcomes related to infection for either duration subgroup, however, and the trends for beneficial effects of high-flux dialysis on ACM rates were considerably weakened when the years of dialysis during the follow-up phase were combined with the prestudy years of dialysis in the analysis. For the subgroup of patients with <3.7 yr of dialysis before the study, assignment to high-flux dialysis had no significant effect on any of the examined clinical outcomes. These data suggest that high-flux dialysis might have a beneficial effect on cardiac outcomes. Because these results are derived from multiple statistical comparisons, however, they must be interpreted with caution. The subgroup results that demonstrate that patients with different durations of dialysis are affected differently by high-flux dialysis are interesting and require further study for confirmation."
1,"TITLE: The effect of body mass index and wound irrigation on outcome after bilateral breast reduction.ABSTRACT: Thirty patients undergoing bilateral breast reduction by inferior pedicle technique were entered into a prospective, randomized study to determine the effect of unilateral saline wound irrigation and body mass index (BMI) on outcome. Each patient was assessed at 1, 4, and 8 weeks after surgery for wound dehiscence, infection, fat necrosis, and breast comfort by means of a visual analog pain score. The mean patient age was 33 years; mean weight, 67.7 kg; mean BMI, 26.3; and mean weight of breast tissue excised per patient, 1270 g. In 60 breasts there were 13 cases of minor wound breakdown, all of which had healed by 8 weeks postoperatively. Wound irrigation had no significant effect on the rate of T-junction breakdown or on postoperative pain. BMI was associated significantly with wound breakdown (BMI > 26.3, 33% wound breakdown rate; BMI < 26.3, 10% wound breakdown rate; P < 0.05, chi2 test). Patients with a high BMI are more likely to have delayed healing after breast reduction."
1,"TITLE: Improvement in postoperative pain relief by the addition of midazolam to an intrathecal injection of buprenorphine and bupivacaine.ABSTRACT: Intrathecal injections of the benzodiazepine midazolam have been reported to cause antinociception in animals and pain relief in human beings, including the potentiation of opioid analgesia. This study compared the efficacy of the addition of midazolam to a mixture of buprenorphine and bupivacaine used for spinal anaesthesia.The study was prospective, randomized, and observer blinded. It involved 60 patients (30 per group), ASA I and II, age 20-40 yr, undergoing minor and intermediate lower abdominal surgery under spinal anaesthesia. Patients were randomized into two groups: the control group received a spinal injection of hyperbaric bupivacaine (15 mg) plus buprenorphine (0.15 mg) and the experimental group received a spinal injection of the same two drugs and doses but supplemented with intrathecal midazolam (2 mg).The duration of postoperative analgesia in the control group was 9.24 +/- 2.57 h (mean +/- SEM), and 21.33 +/- 12.69 h in the midazolam treated group (P < 0.001). Patients treated with intrathecal midazolam had better pain relief judged by visual analogue score on coughing (P = 0.0013) and a nursing mobility score (P < 0.0001). Adverse effects were minor and their incidence was similar in both groups.We conclude that intrathecal midazolam 2 mg improves the quality and duration of postoperative pain relief afforded by intrathecal buprenorphine and bupivacaine."
1,"TITLE: A comparison of duration of analgesia of intrathecal 2.5 mg of bupivacaine, ropivacaine, and levobupivacaine in combined spinal epidural analgesia for patients in labor.ABSTRACT: We assessed the duration of labor analgesia rendered by intrathecal (IT) local anesthetics as the sole drugs. In this randomized, controlled, and double-blinded study, labor analgesia was induced using combined spinal-epidural technique in 60 ASA physical status I nulliparous parturients with IT bupivacaine 2.5 mg (group B), ropivacaine 2.5 mg (group R), or levobupivacaine 2.5 mg (group L). Pain scores (0-100 visual analog scale) and blood pressure were recorded pre-block and for the first 30 min post-block. The degree of motor block and the highest sensory block were also monitored. The duration of analgesia (our primary outcome) was the longest in group B but was similar between groups R and L (mean +/- SE, 76.3 +/- 5.9 min versus 52.6 +/- 4.0 min and 51.5 +/- 3.4 min, respectively, P < 0.05). Group B had the most frequent incidence of lower limb motor block but there was no difference between groups R and L (5 of 20 parturients versus 2 of 20 and 0 of 20, respectively, P < 0.05). The profile of the other side effects was indistinguishable between the groups. With the current regimen, IT bupivacaine produced the longest duration of labor analgesia.Intrathecal 2.5 mg bupivacaine significantly prolongs the duration of analgesia in laboring patients compared with ropivacaine or levobupivacaine. This suggests that, at clinically relevant doses, bupivacaine may have greater potency."
1,"TITLE: Favorable effects of pioglitazone and metformin compared with gliclazide on lipoprotein subfractions in overweight patients with early type 2 diabetes.ABSTRACT: To compare effects of different oral hypoglycemic drugs as first-line therapy on lipoprotein subfractions in type 2 diabetes.Sixty overweight type 2 diabetic patients not on lipid-lowering therapy were randomized to metformin, pioglitazone, or gliclazide after a 3-month dietary run-in. Drug doses were uptitrated for 3 months to optimize glycemia and were kept fixed for a further 3 months. LDL subfractions (LDL(1), LDL(2), and LDL(3)) were prepared by density gradient ultracentrifugation at randomization and study end. Triglycerides, cholesterol, total protein, and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. The primary end point was change in proportion of LDL as LDL(3).HbA(1c), triglycerides, glucose, and cholesterol were comparable across groups at baseline and over time. LDL(3) mass and the LDL(3)-to-LDL ratio fell with pioglitazone (LDL(3) mass 36.2 to 28.0 mg/dl, P < 0.01; LDL(3)-to-LDL 19.2:13.3%, P < 0.01) and metformin (42.7 to 31.5 mg/dl, P < 0.01; 21.3:16.2%, P < 0.01, respectively) with no change on gliclazide. LDL(3) reductions were associated with reciprocal LDL(1) increases. Changes were independent of BMI, glycemic control, and triglycerides. Total HDL cholesterol increased on pioglitazone (1.28 to 1.36 mmol/l, P = 0.02) but not gliclazide (1.39 to 1.37 mmol/l, P = NS) or metformin (1.26 to 1.18 mmol/l, P = NS), largely due to an HDL(2) increase (0.3 to 0.4 mmol/l, P < 0.05). HDL(3) cholesterol fell on metformin (0.9 to 0.85 mmol/l, P < 0.01). On pioglitazone and metformin, the HDL(2)-to-HDL(3) ratio increased compared with no change on gliclazide.For the same improvement in glycemic control, pioglitazone and metformin produce favorable changes in HDL and LDL subfractions compared with gliclazide in overweight type 2 diabetic patients. Such changes may be associated with reduced atherosclerosis risk and may inform the choice of initial oral hypoglycemic agent."
1,"TITLE: A comparison of albumin and saline for fluid resuscitation in the intensive care unit.ABSTRACT: It remains uncertain whether the choice of resuscitation fluid for patients in intensive care units (ICUs) affects survival. We conducted a multicenter, randomized, double-blind trial to compare the effect of fluid resuscitation with albumin or saline on mortality in a heterogeneous population of patients in the ICU.We randomly assigned patients who had been admitted to the ICU to receive either 4 percent albumin or normal saline for intravascular-fluid resuscitation during the next 28 days. The primary outcome measure was death from any cause during the 28-day period after randomization.Of the 6997 patients who underwent randomization, 3497 were assigned to receive albumin and 3500 to receive saline; the two groups had similar baseline characteristics. There were 726 deaths in the albumin group, as compared with 729 deaths in the saline group (relative risk of death, 0.99; 95 percent confidence interval, 0.91 to 1.09; P=0.87). The proportion of patients with new single-organ and multiple-organ failure was similar in the two groups (P=0.85). There were no significant differences between the groups in the mean (+/-SD) numbers of days spent in the ICU (6.5+/-6.6 in the albumin group and 6.2+/-6.2 in the saline group, P=0.44), days spent in the hospital (15.3+/-9.6 and 15.6+/-9.6, respectively; P=0.30), days of mechanical ventilation (4.5+/-6.1 and 4.3+/-5.7, respectively; P=0.74), or days of renal-replacement therapy (0.5+/-2.3 and 0.4+/-2.0, respectively; P=0.41).In patients in the ICU, use of either 4 percent albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days."
1,"TITLE: Biventricular pacing reduces the induction of monomorphic ventricular tachycardia: a potential mechanism for arrhythmia suppression.ABSTRACT: The aim of the present study was to evaluate in a prospective randomized fashion the electrophysiologic effects of acute biventricular (BV) pacing. We hypothesized that (1) the local coupling interval in the left ventricle in response to right-sided ventricular premature beats is prolonged when BV pacing is applied during the drive train compared with right ventricular (RV) pacing, and (2) BV programmed electrical stimulation (PES) decreases the induction of ventricular arrhythmias compared with standard RV-PES, regardless of the presence of intraventricular conduction delay.Previous studies have suggested that BV pacing might decrease the frequency of ventricular arrhythmias; however, the mechanism of arrhythmia suppression remains unclear.Eighteen patients with coronary artery disease were randomized to RV-PES or BV-PES with a repeat study using the other pacing mode. The RV effective refractory periods were measured during RV-PES and BV-PES. In addition, the local LV S(1)-S(2) coupling interval was measured at 600/450 ms and 400/350 ms during RV-PES and BV-PES.BV-PES had no effect on RV effective refractory periods. On the other hand, the local LV S(1)-S(2) coupling intervals increased significantly during BV-PES compared with RV-PES (P < .0001). Ventricular tachycardia was induced in six patients using RV-PES but in only one patient with BV-PES (RR = 83%, P = .01). No difference was observed in the induction of ventricular fibrillation.BV-PES significantly reduced the induction of ventricular tachycardia compared to RV-PES, with no significant effect on ventricular fibrillation induction. Our findings may help explain the reduced incidence of ventricular arrhythmias noted with chronic BV pacing."
1,"TITLE: Laryngeal mask airway can be inserted with inhaled desflurane induction.ABSTRACT: In this prospective, randomized, controlled trial, we investigated the reliability of laryngeal mask airway (LMA) insertion with inhaled desflurane.Eighty patients undergoing elective surgery were randomized into two groups to receive either 2.5 mg x kg(-1) propofol (n = 40) or tidal breath desflurane (n = 40) induction followed by LMA insertion. All patients received fentanyl 1 microg x kg(-1) 2 min before induction. Inhalation of desflurane was started at 3% and increased by 3% every 3-5 breaths up to settings of 12%.Insertion of the LMA was faster in the propofol group (131.8 s versus 228.6 s, P < 0.01). The number of patients in whom the jaw opening was described as good (95% versus 72.5%, P = 0.27, for the desflurane and propofol groups, respectively) and the ease of LMA insertion described as good (87.5% versus 72.5%, P = 0.6) were comparable. The LMA was inserted in a single attempt in the majority of patients in both groups (80% versus 77.5%, P = 0.90). There were more complications at insertion in the propofol group than in the desflurane group (2.5% versus 19.5%, P < 0.01), especially for apnea (7.5% versus 70%, P < 0.01) and excitatory movements (2.5% versus 25%, P < 0.01). There were significant decreases in the mean arterial pressure in the propofol group compared to baseline data over the first 5 min of induction. Mean arterial pressure, heart rate, and S(p)(O2) remained stable during the same period in the desflurane group.We demonstrated that inhaled desflurane when used with caution in a controlled manner provided acceptable conditions for LMA insertion."
1,"TITLE: Safety and efficacy of phacoemulsification compared with manual small-incision cataract surgery by a randomized controlled clinical trial: six-week results.ABSTRACT: To compare the efficacy, safety, and refractive errors of astigmatism after cataract surgery by phacoemulsification and manual small-incision cataract surgery techniques.Masked randomized control clinical trial.Four hundred eyes of 400 patients, 1:1 randomization with half in each arm of the trial.A total of 400 eyes was assigned randomly to either phacoemulsification or small-incision groups after informed consent and were operated on by 4 surgeons. They were masked to the technique of surgery before, during, and after cataract surgery and followed up to 1 year after surgery. The intraoperative and postoperative complications, uncorrected and best-corrected visual acuity, and astigmatism were recorded at 1 and 6 weeks postoperatively.The proportion of patients achieving visual acuity better than or equal to 6/18 with and without spectacles after cataract surgery in the operated eye up to 6 weeks, postoperative astigmatism, and complications during and after surgery.This article reports clinical outcomes up to 6 weeks. Three hundred eighty-three of 400 (95.75%) patients completed the 1-week follow-up, and 372 of 400 (93%) patients completed the 6-week follow-up. One hundred thirty-one of 192 (68.2%) patients in the phacoemulsification group and 117 of 191 (61.25%) patients in the small-incision group had uncorrected visual acuity better than or equal to 6/18 at 1 week (P = 0.153). One hundred fifty of 185 (81.08%) patients of the phacoemulsification group and 133 of 187 (71.1%) patients of the small-incision group (P = 0.038) were better than or equal to 6/18 at the 6-week follow-up for presenting visual activity. Visual acuity improved to > or = 6/18 with best correction in 182 of 185 patients (98.4%) and 184 of 187 (98.4%) patients (P = 0.549), respectively. Poor outcome (postoperative visual acuity < 6/60) was noted in 1 of 185 (0.5%) in the phacoemulsification group and none in the small-incision group. The mode of astigmatism was 0.5 diopters (D) for the phacoemulsification group and 1.5 D for the small-incision group, and the average astigmatism was 1.1 D and 1.2 D, respectively. There was an intra-surgeon variation in astigmatism. The phacoemulsification group had 7 posterior capsular rents compared with 12 in the small-incision group, but the phacoemulsification group had more corneal edema on the first postoperative day.Both the phacoemulsification and the small-incision techniques are safe and effective for visual rehabilitation of cataract patients, although phacoemulsification gives better uncorrected visual acuity in a larger proportion of patients at 6 weeks."
1,"TITLE: Percutaneous translaryngeal versus surgical tracheostomy: A randomized trial with 1-yr double-blind follow-up.ABSTRACT: To compare the outcomes and the short- and long-term complications of percutaneous translaryngeal tracheostomy (TLT) and surgical tracheostomy (ST).Prospective, randomized clinical trial with 1-yr double-blind follow-up.A general intensive care unit of a university hospital.A total of 139 consecutive critically ill patients who required a tracheostomy between February 2001 and June 2002 were randomly assigned to receive either ST or TLT.TLTs were performed more rapidly than STs (17 +/- 10 mins vs. 22 +/- 6 mins, p = .003). Early complications were rare in both groups. Major postoperative bleeding was less frequent with TLT (0 [0%] vs. 6 [8%], p = .03). Only one case of bleeding (in the ST group) required blood transfusion. Immediately after tracheostomy, six TLT patients (9%) and six patients (8%) in the ST group (p = .56) developed culture-confirmed bacteremia with microbes previously isolated from the pharynx or trachea. Group rates for stomal infections and pneumonia after tracheostomy were similar. At 1-yr follow-up, the overall survival rate was 27%, and 14 patients (45% of survivors) still had open tracheostomies. Both groups rated their quality of life as moderately to severely compromised, and the deterioration was strictly related to the presence of tracheostomy. One TLT and two ST survivors (p = .53) had clinical signs of tracheal stenosis, and bronchoscopy revealed narrowing of >50%.Compared with ST, the main advantages of TLT are that it is more rapid and associated with less postoperative bleeding. Infectious complications, particularly postoperative bacteremia, and long-term effects (physical and emotional) are similar with the two procedures."
1,"TITLE: Urinary sucrose and fructose as biomarkers for sugar consumption.ABSTRACT: The use of 24-hour urinary sucrose and fructose as potential biomarkers for sugars consumption was investigated in two studies of 21 healthy participants living in a volunteer suite where dietary intake was known and all specimens collected. The dose-response was assessed in 12 males using a randomized crossover design of three diets containing constant levels of 63, 143, and 264 g of sugars for 10 days each. Both sugars and sucrose intake were significantly correlated with the sum of sucrose and fructose concentration in urine (0.888; P < 0.001). To assess effects with volunteers consuming their habitual varying diets, seven males and six females were fed their usual diet (assessed beforehand from four consecutive self-completed 7-day food diaries) for 30 days under controlled conditions in the volunteer suite. The mean (+/-SD) calculated total sugars intake was 202 +/- 69 g/d, 41% from sucrose. Mean (+/-SD) urinary sucrose and fructose were 36.6 +/- 16.6 and 61.8 +/- 61.3 mg/d, respectively. The sum of sucrose and fructose in urine was significantly correlated with sugars (0.841; P < 0.001) and sucrose intake (0.773; P = 0.002). In the regression, 200 g of sugars intake predicted approximately 100 mg of sucrose and fructose in urine. The correlation between individual means of randomized 16 days of sugars intake and 8 days of sugars excretion data (as used in validation studies) remained as high as that obtained with the means of 30-day measurements and the regression estimates were very similar. Twenty-four-hour urinary sucrose and fructose could be grouped into a new category of biomarkers, predictive biomarkers, that can be used in studies determining the structure of dietary measurement error in free living individuals and to relate sugars intake to disease risk."
1,"TITLE: Increasing smoking cessation care in a preoperative clinic: a randomized controlled trial.ABSTRACT: Evidence suggests that preoperative clinics, like other hospital outpatient clinics and inpatient wards, fail to systematically provide smoking cessation care to patients having planned surgery.The aim of the study was to assess the efficacy, acceptability, and cost of a multifaceted intervention to facilitate the provision of comprehensive smoking cessation care to patients attending a preoperative clinic. Two hundred ten smoking patients attending a preoperative clinic at a major teaching hospital in Australia took part in the study. One hundred twenty-four patients were randomly assigned to an experimental group and 86 patients to a usual cessation care group. A multifaceted intervention was developed that included the use of opinion leaders, consensus processes, computer-delivered cessation care, computer-generated prompts for care provision by clinic staff, staff training, and performance feedback.Ninety-six percent of experimental group patients received behavioral counseling and tailored self-help material. Experimental group patients were significantly more likely than usual care patients to report receiving brief advice by nursing (79% vs. 47%; P < 0.01) and anaesthetic (60% vs. 39%; P < 0.01) staff. Experimental group patients who were nicotine dependent were also more likely to be offered preoperative nicotine replacement therapy (NRT) (82% vs. 8%; P < 0.01) and be prescribed postoperative NRT (86% vs. 0%; P < 0.01). The multifaceted intervention was found to be acceptable by staff.A multifaceted clinical practice change intervention may be effective in improving the delivery of smoking cessation care to preoperative surgical patients."
1,"TITLE: Cardiovascular risk estimates and risk factors in renal transplant recipients.ABSTRACT: Cardiovascular morbidity, including coronary artery disease and left ventricular hypertrophy, and mortality are high in patients following renal transplantation. Cardiovascular disease is thought to be due to traditional (hypertension, hyperlipidemia, diabetes mellitus and smoking) as well as nontraditional cardiovascular risk factors (microinflammation). Furthermore, immunosuppressive drugs, namely, calcineurin inhibitors, sirolimus, and steroids, have been reported to adversely affect cardiovascular risk factors (e.g., hypertension, hyperlipidemia, hyperglycemia). Evidence from comparative trials and from conversion studies suggest that blood pressure, hyperlipidemia, and hyperglycemia after renal transplantation may be differentially affected by the calcineurin inhibitors cyclosporine and tacrolimus. In the European Tacrolimus versus Cyclosporin A Microemulsion Renal Transplantation Study, 557 patients were randomly allocated to therapy with tacrolimus (n = 286) versus cyclosporine (n = 271). In addition, to blood pressure, serum cholesterol, HDL cholesterol, triglycerides, and blood glucose, we estimated the 10-year risk of coronary heart disease (Framingham risk score). Tacrolimus resulted in a significantly lower time-weighted average of serum cholesterol (P < .001), and mean arterial blood pressure (P < .05), but a higher time-weighted average of blood glucose (P < .01) than cyclosporine. Mean 10-year coronary artery disease risk estimate was significantly lower in men treated with tacrolimus, (10.0% versus 13.2%; P < .01) but was unchanged in women (4.7% versus 7.0%). Tacrolimus and cyclosporine microemulsion have compound-specific effects on cardiovascular risk factors that differentially affect the predicted rate of coronary artery disease."
1,"TITLE: Oral famciclovir for the suppression of recurrent genital herpes: the combined data from two randomized controlled trials.ABSTRACT: Genital herpes is a very common sexually transmitted disease. Safe and effective therapies are needed for patients with frequent recurrences.The aim of our study was to determine the efficacy and safety of famciclovir for suppression of herpes simplex virus (HSV) infection in patients with history of clinically diagnosed recurrent genital HSV infection.An analysis was conducted of the combined data from two randomized, double-blind, placebo-controlled studies of 52 weeks' duration involving a total of 469 patients (201 men, 268 women) from 47 university, hospital, or private referral centers in Europe and North America. The patients were 18 years or older with a history of six or more episodes of genital herpes during 12 of the 14-months prior to study entry and were not receiving suppressive therapy. They were randomized to receive oral famciclovir 250 mg twice daily or placebo for 52 weeks. The primary outcome measures were (1) the proportion of patients who remained free from clinical HSV recurrences, confirmed by viral culture, for at least 6 months after the start of study medication; (2) the time to first clinically confirmed lesional episode; and (3) the frequency of adverse events.A significantly greater proportion of famciclovir-treated patients (151/191, 79%) were free from HSV recurrences at 6 months compared with placebo recipients (48/184, 26%) (p<0.001); efficacy was maintained at 12 months. The median time for the first clinically confirmed lesional episode was significantly prolonged for famciclovir recipients (more than one year) compared with placebo recipients (59 days; p<0.0001). Famciclovir was well tolerated, with an adverse-experience profile comparable with placebo.Oral famciclovir 250 mg twice daily is an effective, well-tolerated treatment for the suppression of genital HSV infection in patients with frequent recurrences."
1,"TITLE: Long term efficacy and safety of cyclosporin versus parenteral gold in early rheumatoid arthritis: a three year study of radiographic progression, renal function, and arterial hypertension.ABSTRACT: To compare the three year safety and efficacy of cyclosporin and parenteral gold in the treatment of early, active, severe rheumatoid arthritis (RA), and to study the reversibility of cyclosporin associated renal dysfunction in patients who discontinued cyclosporin treatment.The patients continued to receive cyclosporin or parenteral gold in an 18 month open extension to an 18 month randomised, parallel group study. The main efficacy variable was blinded evaluation of radiographic progression of joint damage. Safety variables included serum creatinine, calculated creatinine clearance, and blood pressure.Radiographic progression during follow up was similar in both groups. About 60% of the patients in the intention to treat groups (n=272) and about half of the patients in the completer groups (n=114) had definite radiographic progression in joint damage (increases >6 in the Larsen-Dale score), and about one in three also had substantial progression (>18 increase in Larsen-Dale score). Both systolic and diastolic blood pressure were significantly increased in the cyclosporin group compared with the gold group, and 12/139 (9%) versus 3/139 (2%) (p=0.03) had notably raised blood pressure. The mean serum creatinine increased by 28% at the treatment end point in the cyclosporin group as compared with 7% in the gold group. The mean calculated creatinine clearance was reduced by 16% and increased by 1% in the cyclosporin and gold groups, respectively, at the end of the study. At the final follow up visit after discontinuation of cyclosporin (at least three months after treatment was stopped) the mean serum creatinine was increased by 15% and creatinine clearance reduced by 16%. Sustained increases in serum creatinine at this post-treatment end point were mostly seen in patients with a raised serum creatinine during treatment of at least 50%.Three year changes in radiographic damage during cyclosporin and parenteral gold were similar in patients with early, active RA. Abnormal renal function and raised blood pressure were often seen in the cyclosporin treated patients."
1,"TITLE: Hydroxocobalamin reduces hyperhomocysteinemia in end-stage renal disease.ABSTRACT: Renal failure causes hyperhomocysteinemia, an important risk factor for cardiovascular disease and venous access thrombosis in end-stage renal disease (ESRD). Folic acid is necessary for homocysteine (Hcy) metabolism, and therapy with 1 mg/d or more of folic acid reduces plasma total Hcy (tHcy) concentrations in ESRD, although seldom to normal. In contrast to folic acid, the Hcy-lowering effect of vitamin B(12) has not been well studied in ESRD. We performed a prospective randomized controlled clinical trial involving 24 maintenance hemodialysis patients with normal or supranormal serum folate and vitamin B(12) concentrations who received either standard therapy, which included 5 to 6 mg folic acid, 5 to 10 mg pyridoxine, and 6 to 10 microg oral vitamin B(12) per day, or standard therapy plus 1 mg hydroxocobalamin administered subcutaneously once per week after dialysis. Plasma tHcy and serum methylmalonic acid (MMA) concentrations were measured before and after 8 and 16 weeks of continuous treatment. Hydroxocobalamin reduced plasma tHcy by an average of 32% (P <.005) and serum MMA by an average of 19% (P <.001). The Hcy-lowering effect of hydroxocobalamin was independent of baseline serum vitamin B(12), folic acid, and MMA concentrations. Patients with higher baseline plasma tHcy concentrations had the greatest response (r = 0.80; P <.002). These results show that parenteral hydroxocobalamin reduces plasma tHcy dramatically in vitamin B(12)-replete hemodialysis patients. Persons with considerable persisting hyperhomocysteinemia despite high-dose folic acid therapy are likely to respond to the addition of hydroxocobalamin, irrespective of their serum vitamin B(12) concentrations."
1,"TITLE: Acute haemodynamic effects of a hypertonic saline/dextran solution in stable patients with severe sepsis.ABSTRACT: To study the haemodynamic effects of a hypertonic saline/dextran solution compared with a normal saline solution in patients with severe sepsis.Prospective double blind and control-randomised study.Adult intensive care unit in a university hospital.Twenty-nine patients with sepsis with a pulmonary artery occlusion pressure (PAOP) lower than 12 mmHg.Patients were randomised to receive 250 ml of blinded solutions of either normal saline (SS group, n=16) or hypertonic saline (NaCl 7.5%)/dextran 70 8% (HSS group, n=13) solutions.Haemodynamic, blood gas, and sodium data were collected at the following time points: baseline, 30 min, 60 min, 120 min, and 180 min. PAOP was higher in the HSS group at 30 min (10.7+/-3.2 mmHg vs 6.8+/-3.2 mmHg) and 60 min (10.3+/-3 mmHg vs 7.4+/-2.9 mmHg); P<0.05. The cardiac index increased in the HSS group and it was greater than the SS group at 30 min (6.5+/-4.7 l min(-1) m(-2) vs 3.8+/-3.4 l min(-1) m(-2)), 60 min (4.9+/-4.5 l min(-1) m(-2) vs 3.7+/-3.3 l min(-1) m(-2)), and 120 min (5.0+/-4.3 l min(-1) m(-2) vs 4.1+/-3.4 l min(-1) m(-2)); P<0.05. The stroke volume index followed a comparable course and it was higher at 30 min [53.6(39.2-62.8) ml m(-2) vs 35.6(31.2-49.2) ml m(-2)] and 60 min [46.8(39.7-56.6) ml m(-2) vs 33.9(32.2-47.7) ml m(-2)]; P<0.05. Systemic vascular resistance decreased in the HSS group and became significantly lower at 30 min (824+/-277 dyne s(-1) cm(-5) m(-2) vs 1139+/-245 dyne s(-1) cm(-5) m(-2)), 60 min (921+/-256 dyne s(-1) cm(-5) m(-2) vs 1246+/-308 dyne s(-1) cm(-5) m(-2)), and 120 min (925+/-226 dyne s(-1) cm(-5) m(-2) vs 1269+/-494 dyne s(-1) cm(-5) m(-2)). Sodium levels increased in the HSS group (P=0.056) and were higher than in the SS group at 30 min (145+/-3 mEq l(-1)vs 137+/-7 mEq l(-1)), 60 min (143+/-4 mEq l(-1) vs 136+/-7 mEq l(-1)), 120 (142+/-5 mEq l(-1)vs 136+/-7 mEq l(-1)), and 180 min (142+/-5 mEq l(-1) vs 136+/-8 mEq l(-1)).Hypertonic saline/dextran solution may improve cardiovascular performance in severe sepsis without significant side effects. The haemodynamic effect appears related mainly to a volume effect."
1,"TITLE: Basal-bolus insulin therapy in Type 1 diabetes: comparative study of pre-meal administration of a fixed mixture of insulin lispro (50%) and neutral protamine lispro (50%) with human soluble insulin.ABSTRACT: To ascertain whether pre-meal administration of 50% insulin lispro and 50% neutral protamine lispro (NPL), given as a fixed mixture (Humalog Mix50, human soluble (regular) insulin as a basal-bolus regimen in people with Type 1 diabetes. Both regimens included bedtime human isophane (NPH) insulin.This was a multinational, multicentre, randomized, open-label, two-period crossover comparison of two insulin treatments for two 12-week periods in 109 patients with Type 1 diabetes. The protocol provided preliminary evaluations of dose requirements and recommendations for insulin dose adjustment when switching regimens on the basis of blood glucose (BG) values. Eight-point BG profiles, frequency of hypoglycaemia, HbA1c, insulin dose, time of injection, and frequency of snacking were assessed during each treatment.Total daily insulin dose was similar for both treatments, but the total pre-meal doses were higher (P < 0.001) and the bedtime dose of isophane was lower (P < 0.001) with Mix50. The pre-meal dose before breakfast and lunch, although statistically different (P = 0.006 and P < 0.001, respectively), was of similar magnitude, but the pre-evening meal dose was higher with Mix50 (P < 0.001). Median (interquartile range) time of insulin injection before meals was: Mix50 4.2 (25th percentile = 1.0; 75th percentile = 6.3) min, human soluble insulin 24.6 (25th percentile = 16.6; 75th percentile = 30.0) min. Pre-meal and bedtime BG concentrations did not differ between treatments. The BG 2 h after the evening meal was lower with Mix50 (8.40 +/- 2.95 mmol/l vs. 9.60 +/- 3.47 mmol/l) (P = 0.049). BG after breakfast and lunch, mean HbA1c, frequency of hypoglycaemia, frequency of snacks, and body weight were not different.The use of Mix50 in a basal-bolus regimen achieved similar control of pre-meal BG to human soluble insulin, and overall glycaemic control and hypoglycaemia risk were equivalent. This suggests that Mix50 can provide an adequate supply of insulin to control BG between meals while providing the convenience of injecting immediately before meals."
1,"TITLE: A new calcipotriol/betamethasone dipropionate formulation (Daivobet) is an effective once-daily treatment for psoriasis vulgaris.ABSTRACT: Topical corticosteroids and calcipotriol have been used separately for many years to treat psoriasis. A new combination ointment has been formulated, which contains both calcipotriol and the corticosteroid betamethasone dipropionate.To compare the combination ointment with betamethasone dipropionate ointment, calcipotriol ointment and ointment vehicle in patients with psoriasis vulgaris.1,603 patients were randomised to one of the 4 double-blind treatments used once daily for 4 weeks.The mean percentage change in the PASI at the end of treatment was -71.3 (combination), -57.2 (betamethasone), -46.1 (calcipotriol) and -22.7 (vehicle). The mean difference of combination minus betamethasone was -14.2 (95% CI: -17.6 to -10.8, p < 0.001), of combination minus calcipotriol -25.3 (95% CI: -28.7 to -21.9, p < 0.001) and of combination minus vehicle -48.3 (95% CI: -53.2 to -43.4, p < 0.001). 6.0% of patients (combination) reported local adverse reactions compared to 4.9% (betamethasone), 11.4% (calcipotriol) and 13.6% (vehicle).Calcipotriol/betamethasone dipropionate combination ointment used once daily is well tolerated and more effective than either active constituent used alone."
1,"TITLE: Comparative randomized trial of azithromycin versus erythromycin and amoxicillin for treatment of community-acquired pneumonia in children.ABSTRACT: Our objective was to compare the clinical efficacy of azithromycin vs. erythromycin and amoxicillin in the treatment of presumed bacterial community-acquired pneumonia in ambulatory children, and to evaluate the etiologies of these illnesses. One hundred and ten children, aged 1 month to 14 years, were enrolled between January 1996-January 1999. Children were distributed into two groups according to clinical and radiological patterns: classic or atypical pneumonia. Patients with classic pneumonia were randomly assigned to receive oral amoxicillin 75 mg/kg/day for 7 days, or azithromycin 10 mg/kg/day for 3 days; patients with atypical pneumonia received azithromycin 10 mg/kg/day for 3 days, or erythromycin 50 mg/kg/day for 14 days. Chest X-ray, clinical, and laboratory parameters were obtained on enrollment. Clinic visits were performed on days 3, 7, and 14, and chest X-ray follow-up on days 7 and 14. Microbiological diagnosis of classic pathogens was based on blood and bronchial secretion cultures. The diagnosis of atypical pathogens C. pneumoniae, C. trachomatis, and M. pneumoniae was based on PCR and serologic tests.Forty-seven children met the criteria for classic pneumonia (23 children received azithromycin, and 24 received amoxicillin), and 59 children had atypical pneumonia (33 children were treated with azithromycin, and 26 with erythromycin). Demographic characteristics at enrollment were similar between children with classic pneumonia treated with azithromycin and erythromycin and children treated with azithromycin and erythromycin for atypical pneumonia. However, on day 7, children with classic pneumonia who received azithromycin normalized their chest X-ray more often than those who received amoxicillin (81.0% vs. 60.9%, respectively, P = 0.009). The same was true for children with atypical pneumonia; their chest X-rays had normalized by day 14 (100% in those with azithromycin vs. 81% in those with erythromycin, P = 0.059). Also, children with atypical pneumonia treated with azithromycin had earlier cessation of cough than children treated with erythromycin (3.6 +/- 1.9 vs. 5.5 +/- 3.6 days respectively, P = 0.02). There were only three children with side effects (mild diarrhea, all in the erythromycin group). Etiological agents were identified in 41% of children. In conclusion, azithromycin is an effective therapeutic option for the treatment of community-acquired classic and atypical pneumonia in children."
1,"TITLE: G-CSF application in patients with severe bacterial pneumonia increases IL-10 expression in neutrophils.ABSTRACT: In severe pneumonia, the application of granulocyte-colony stimulating factor (G-CSF) was associated with reduced complications possibly by an induction of anti-inflammatory cytokines. It is not clear, whether G-CSF induces interleukin-10 (IL-10) synthesis in neutrophils. In a randomized study, 15 patients with severe community acquired pneumonia were treated either by a single dose of G-CSF and antibiotic therapy (n=8) or antibiotics alone (n=7). Messenger ribonucleic acid (mRNA) expression of IL-10 and tumor necrosis factor alpha of peripheral blood leukocytes was measured using in-situ hybridization (ISH) and reverse-transcription-polymerase-chain-reaction (RT-PCR). In addition, the cytokine release of lipopolysaccharide (LPS)-stimulated whole blood was measured by ELISA. We detected increased IL-10 mRNA by ISH (140 +/- 8% vs. -11 +/- 5%, P<0.01) and RT-PCR (126 +/- 16% vs. -28 +/- 3%, P<0.01) in the G-CSF-treated group only. In contrast, LPS-stimulated whole blood cells in vitro released significantly less IL-10 compared to the control group (-38.2 +/- 97 vs. -14.8 +/- 6 pg/ml, P<0.02). There was no significant effect on IL-10 serum protein levels and the TNF-alpha release and expression. IL-10 mRNA was detected predominantly in cluster designation 66b (CD66b) positive nucleated blood cells indicating that polymorphonuclear leukocytes are the main source of IL-10 expression after G-CSF stimulation. G-CSF induces transcription of IL-10 mRNA in neutrophils without increased release. This may be due to posttranscriptional effects."
1,"TITLE: The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial.ABSTRACT: Because alpha-lipoic acid (ALA), a potent antioxidant, prevents or improves nerve conduction attributes, endoneurial blood flow, and nerve (Na(+) K(+) ATPase activity in experimental diabetes and in humans and may improve positive neuropathic sensory symptoms, in this report we further assess the safety and efficacy of ALA on the Total Symptom Score (TSS), a measure of positive neuropathic sensory symptoms.Metabolically stable diabetic patients with symptomatic (stage 2) diabetic sensorimotor polyneuropathy (DSPN) were randomized to a parallel, double-blind study of ALA (600 mg) (n = 60) or placebo (n = 60) infused daily intravenously for 5 days/week for 14 treatments. The primary end point was change of the sum score of daily assessments of severity and duration of TSS. Secondary end points were sum scores of neuropathy signs (NIS), symptoms (NSC), attributes of nerve conduction, quantitative sensation tests (QSTs), and an autonomic test.At randomization, the groups were not significantly different by the criteria of metabolic control or neuropathic end points. After 14 treatments, the TSS of the ALA group had improved from baseline by an average of 5.7 points and the placebo group by an average of 1.8 points (P < 0.001). Statistically significant improvement from baseline of the ALA, as compared with the placebo group, was also found for each item of the TSS (lancinating and burning pain, asleep numbness and prickling), NIS, one attribute of nerve conduction, and global assessment of efficacy.Intravenous racemic ALA, a potent antioxidant, rapidly and to a significant and meaningful degree, improved such positive neuropathic sensory symptoms as pain and several other neuropathic end points. This improvement of symptoms was attributed to improved nerve pathophysiology, not to increased nerve fiber degeneration. Because of its safety profile and its effect on positive neuropathic sensory symptoms and other neuropathic end points, this drug appears to be a useful ancillary treatment for the symptoms of diabetic polyneuropathy."
1,"TITLE: Significant enhancement of gastric mucin content after rabeprazole administration: its potential clinical significance in acid-related disorders.ABSTRACT: Rabeprazole is the only proton pump inhibitor that enhances the content of gastric mucin in experimental animals. We have studied, therefore, the effect of rabeprazole on the content of gastric mucin, mucus, and its viscosity in 21 asymptomatic volunteers in a double-blind study. The mucus content during rabeprazole administration significantly increased both in pentagastrin-stimulated (3.36 +/- 0.39 vs 1.50 +/- 0.32 mg/ml, P < 0.001) and basal (3.31 +/- 0.38 vs 2.28 +/- 0.36 mg/ml, P < 0.01) conditions. The content of mucin during rabeprazole was 2.6-fold (0.96 +/- 0.08 vs 0.36 +/- 0.06 mg/ml, P < 0.0001) and 41% (0.82 +/- 0.09 vs 0.58 +/- 0.09 mg/ml, P < 0.05) higher in stimulated and basal conditions, respectively. The viscosity of gastric juice during rabeprazole administration was also significantly higher both in stimulated (P < 0.01) and basal (P < 0.05) conditions. In conclusion, the unique pharmacological property of rabeprazole, significantly augmenting production of gastric mucus and mucin, may translate to additional clinical benefits in protecting the upper alimentary tract mucosa during the acid-related challenge."
1,"TITLE: Pneumoperitoneum after concomitant resection of the right middle and lower lobes (bilobectomy).ABSTRACT: Removal of the right middle and lower lobes often leaves a pleural space problem that can cause prolonged air leaks.A single surgeon prospectively randomized 16 patients who underwent bilobectomy. Eight patients had 1200 mL of air injected under the right hemidiaphragm after bilobectomy and 8 did not. The air was injected through a small transdiaphragmatic opening made in the right hemidiaphragm at the time of pulmonary resection.The age of the patients, preoperative pulmonary function, preoperative comorbidities, indications for surgery, and final pathology were not significantly different between the two groups. On postoperative day #1, a pneumothorax was present in 1 patient (13%) in the pneumoperitoneum group (P group) and in 4 patients (50%) in the nonpneumoperitoneum group (N-P group). On postoperative day 1, an air leak was present in 1 patient (13%) in the P group and 5 patients (63%) in the N-P group (p < 0.001). By the third postoperative day, no patient in the P group had an air leak; however, a leak was present in 4 patients (50%) in the N-P group (p < 0.001). Median hospital stay in the P group was 4 days (range, 3 to 6 days), compared with 6 days (range, 4 to 8 days) in the N-P group (p < 0.001). Three patients in the N-P group were sent home with a Heimlich valve. There was no operative mortality and no complications from the pneumoperitoneum.We conclude that pneumoperitoneum after bilobectomy is safe and easy to do. It decreases the incidence of air leaks and of pneumothoraces and shortens hospital stay without increasing morbidity. We recommend pneumoperitoneum after bilobectomy at the time of thoracotomy, especially if there are residual small air leaks that cannot be sealed before chest closure."
1,"TITLE: A randomized, double-blind placebo-controlled trial of moclobemide in patients with chronic fatigue syndrome.ABSTRACT: Chronic fatigue syndrome is characterized by prolonged and disabling fatigue and a range of neuropsychiatric symptoms including depressed and/or irritable mood. To date, no medical or psychotropic therapies have provided clear symptomatic benefit.Ninety patients with chronic fatigue syndrome, diagnosed with our system that approximates CDC criteria, participated in a randomized, placebo-controlled, double-blind trial of 450 to 600 mg/day of moclobemide, a novel reversible inhibitor of monoamine oxidase-A.Fifty-one percent (24/47) of patients receiving moclobemide improved compared with 33% (14/43) of patients receiving placebo (odds ratio = 2.16, 95% confidence interval [CI] = 0.9 to 5.1). Drug response was best characterized symptomatically by an increase in the subjective sense of vigor and energy rather than a reduction in depressed mood. The effect of moclobemide on subjective energy was detectable within the first 2 weeks of treatment and increased across the course of the study. The greatest reduction in clinician-rated disability was in patients with concurrent immunologic dysfunction (mean difference in standardized units of improvement = 0.8, 95% CI = 0.03 to 1.6).Moclobemide produces some improvement in key symptoms experienced by patients with chronic fatigue syndrome. This effect is not dependent on the presence of concurrent psychological distress and is likely to be shared with other monoamine oxidase inhibitors."
1,"TITLE: Failure of epoprostenol (prostacyclin, PGI2) to inhibit platelet aggregation and to prevent restenosis after coronary angioplasty: results of a randomised placebo controlled trial.ABSTRACT: To study the effect of epoprostenol (prostacyclin, PGI2) given before, during, and for 36 h after coronary angioplasty on restenosis at six months and to evaluate the transcardiac gradient of platelet aggregation before and after percutaneous transluminal coronary angioplasty (PTCA) in treated and placebo groups.Double blind placebo controlled randomised study.135 patients with successful coronary angioplasty.Intravenous infusion of PGI2 (4 ng/kg/ml) or buffer was started before balloon angioplasty and continued for 36 hours. Platelet aggregation was measured in blood from the aorta and coronary sinus before and after PTCA in each group. Routine follow up was at six months with repeat angiography and there was quantitative assessment of all angiograms (those undertaken within the follow up period and at routine follow up). PRESENTATION OF RESULTS: Restenosis rates in treated and placebo groups determined according to the National Heart, Lung and Blood Institute definition IV. Comparison at follow up between the effect of treatment on mean absolute luminal diameter and mean absolute follow up diameter in the placebo group. Comparison of acute gain and late loss between groups.Of 125 patients available for assessment 23 were re-admitted because of angina within the follow up period. Quantitative angiography showed restenosis in 15 (10 in the PGI2 group and five in the placebo group). Of 105 patients evaluated at six month angiography there was restenosis in nine more in the PGI2 group and 18 more in the placebo group. Total restenosis rates (for patients) were 29.2% for PGI2 and 38.3% for placebo (NS). The mean absolute gain in luminal diameter was 1.84 (0.76) mm in the PGI2 group and 1.58 (0.56) mm in the placebo group (p = 0.04); the late loss in the PGI2 group was also greater (0.65 (0.94) mm vs 0.62 (0.89) mm (NS) and there was no significant difference in final luminal diameter at follow up between the two groups (1.83 (0.88) mm v 1.59 (0.60) mm). The transcardiac gradient of quantitative platelet aggregation increased after PTCA in both groups, indicating that PGI2 in this dose did not affect angioplasty-induced platelet activation. Mean (SD) platelet activation indices in the PGI2 group were pre PTCA aorta 8.4 (4.1) v coronary sinus 8.8 (4.0) (p = 0.001) and post PTCA aorta 8.9(3.0) v coronary sinus 12.9 (5.7) (p = 0.001). In the placebo group the values were pre PTCA aorta 7.6 (3.3) v coronary sinus 7.4 (3.6) (p = 0.001) and post PTCA aorta 7.6(2.8) v coronary sinus 11.2(4.3) (p = 0.001).The dose of PGI2 given was designed to limit side effects and as a short-term infusion did not significantly decrease the six month restenosis rate after PTCA. The sample size, which was determined by the original protocol and chosen because of the potency of the agent being tested, would have detected only a 50% reduction in restenosis rate. There was, however, no effect in the treated patients on the increased platelet aggregation seen in placebo group as a result of angioplasty. Angioplasty is a powerful stimulus to blood factor activation. Powerful agents that prevent local platelet adhesion and aggregation are likely to be required to reduce restenosis."
0,"TITLE: Cigarette smoking and stroke in a cohort of U.S. male physicians.ABSTRACT: To examine the association between cigarette smoking and the risk for stroke in men.Prospective cohort study.Participants in the Physicians' Health Study, a randomized trial of aspirin and beta-carotene among U.S. male physicians.22,071 men, 40 to 84 years of age at entry, free from self-reported myocardial infarction, stroke, and transient ischemic attack; followed for an average of 9.7 years; and classified as never-smokers, current smokers, and former smokers based on self-report.Incidence rates of total, ischemic, and hemorrhagic stroke.With never-smokers as the reference group (relative risk, 1.00), relative risks (adjusted for age and treatment assignment) for total nonfatal stroke (n = 312) were as follows: former smoking, 1.20 (95% CI, 0.94 to 1.53); currently smoking fewer than 20 cigarettes daily, 2.02 (CI, 1.23 to 3.31); and currently smoking 20 or more cigarettes daily, 2.52 (CI, 1.75 to 3.61) (P for trend, < 0.0001). For participants who had total fatal stroke (n = 28), the risk for stroke was not increased with smoking (P > 0.2). In proportional-hazards models that controlled simultaneously for other risk factors, these associations were not materially altered.Current but not former cigarette smoking was significantly associated with an increased risk for stroke in men. Smoking may account for a substantial amount of stroke-associated morbidity and mortality."
0,"TITLE: Risk stratification by early exercise testing after an episode of unstable coronary artery disease. The RISC Study Group.ABSTRACT: After stabilization of symptoms by medication a predischarge exercise test was performed in 855 men admitted with suspected unstable angina (54%) or non-Q-wave myocardial infarction (46%). Multiple logistic regression analysis demonstrated that the number of leads with ST-depression at exercise, low maximal work load, increasing age and ST-elevation in electrocardiogram at rest had independent prognostic value concerning the risk of myocardial infarction or death during the following year. Therefore a combination of extension of ST-depression and peak work load was used to define 'high and low risk response' at the exercise test. After 1 year the mortality in patients with 'high risk' compared to 'low risk' exercise response was 3.6% and 0% (P < 0.001) and the risk of either myocardial infarction or death was 15.4% and 3.9% (P < 0.0001), respectively. ST-depression, occurrence of angina and low peak load at exercise were independent predictors of future severe angina. After 1 year 29.5% of patients with any of these indicators at exercise had incapacitating symptoms that necessitated referral for coronary angiography compared to 4.8% in the group without these findings (P < 0.0001). The predictive value of the exercise test remained high in subgroups based on inclusion diagnosis, age or findings in electrocardiogram at rest and independently of treatment with beta-blockade, other antianginal medication or aspirin at the time of the exercise test."
1,"TITLE: Differential effects of fluticasone and montelukast on allergen-induced asthma.ABSTRACT: Early asthmatic responses (EAR) and late asthmatic responses (LAR) to allergen are induced by the local release of a series of bronchoconstrictor mediators, including leukotrienes and histamine. Both anti-leukotrienes and other anti-asthma drugs, such as inhaled glucocorticoids, have been shown to reduce both EAR and LAR. The aim of the present study was to directly compare the effects of regular treatment with an oral anti-leukotriene, montelukast (Mont; 10 mg once daily, for 8 days), and an inhaled glucocorticoid [fluticasone propionate (FP) 250 microg twice daily for 8 days] on the EAR and LAR to an inhaled allergen challenge. Patients with a documented EAR and LAR at a screening visit were randomized to these treatments, or placebo, in a double-blind, double-dummy, crossover fashion. Allergen challenge at a dose causing both an EAR and LAR was given on the eighth day of treatment. The maximum fall in FEV1 during the EAR was 17.8% during placebo treatment, 8.3% during Mont and 16.3% during FP (P <0.05 for Mont vs placebo). The maximum fall during the EAR was 13.8% during placebo treatment, 11.8% during Mont and 2% during FP treatment (P <0.05 for FP vs placebo and FP vs Mont). PC20 methacholine was significantly higher 24 h after allergen challenge during FP-treatment compared with Mont (P <0.05). Both montelukast and fluticasone reduced the relative amount of sputum eosinophils after allergen compared with placebo treatment. This study shows that anti-leukotrienes are effective to attenuate the EAR, whereas inhaled glucocorticoids are more effective than anti-leukotrienes in attenuating the EARs and improves bronchial hyperresponsiveness to a greater extent. In conclusion, inhaled glucocorticoids have overall greater efficacy than oral anti-leukotrienes to attenuate allergen-induced airway responses in mild asthmatic patients."
1,"TITLE: A randomized controlled trial of cyclosporine withdrawal in renal-transplant recipients: 15-year results.ABSTRACT: In renal transplantation, the immunosuppressive efficacy of cyclosporine is counterbalanced by its nephrotoxicity. Although cyclosporine improves short-term graft survival, its long-term effects are unclear.Recipients of first cadaver renal transplants were randomized into three groups between 1983 and 1986: azathioprine and prednisolone alone (AP, n = 158), long term cyclosporine alone (Cy, n = 166), and short-term cyclosporine followed by azathioprine and prednisolone (CyAP, n = 165). All groups received methylprednisolone induction.There were no significant differences in patient survival at 15 years (48 vs. 56 vs. 51%, P = 0.14), and 15-year graft survival (censored for death) in those patients in the CyAP group (47 vs. 44 vs. 59%, P = 0.06) was not significantly different statistically. When deaths or graft losses before 12 months were censored, the differences in 15-year graft survival between the groups were significant (58%, 51%, 70%, P = 0.01). The CyAP group also had lower mean serum creatinine at all time points beyond 3 months posttransplant out to 10 years (143 vs. 169 vs. 131 micromoles/L, P = 0.04). Per protocol analysis, after censoring patients at change in therapy, increased the observed differences in 15-year graft survival between the groups (54 vs. 38 vs. 65%, P = 0.01).Survival and function of first cadaveric kidney transplants is improved by use of short-term cyclosporine followed by azathioprine and prednisolone. Long-term cyclosporine use reduces long-term graft survival."
1,"TITLE: Using cost of infection as a tool to demonstrate a difference in prophylactic antibiotic efficacy: a prospective randomized comparison of the pharmacoeconomic effectiveness of ceftriaxone and cefotaxime prophylaxis in abdominal surgery.ABSTRACT: The purpose of this study was to test the hypothesis that cost, as well as frequency of infection, could be used to demonstrate a difference in the performance of prophylactic antibiotics. In a prospective, randomized, double-blind study, 1013 patients undergoing abdominal surgery were given 1 g of intravenous ceftriaxone (R) or cefotaxime (C) at induction of anesthesia, and an additional 500 mg of metronidazole for colorectal surgery. Infection was checked for during the hospital stay and at 30 days postoperatively. The inpatient, outpatient, and community costs of infection were prospectively collected. The frequency of wound infection for appendectomies when additional metronidazole was not administered was greater with cefotaxime (R 6%, C 18%, p < 0.05), but the cost of infection was the same (average cost R $994 +/- SD $1101, C $878 +/- $1318). For all other procedures, the frequency of wound infection was similar (R 8%, C 10%), but the cost was less with ceftriaxone (R $887 +/- $1743, C $2995 +/- $6592, p < 0.05). Ceftriaxone decreased the frequency but not the cost of chest and urinary infection (frequency R 6%, C 11%, p < 0.02, cost R $1273 +/- 2338, C $1615 +/- 4083). Differences in both the frequency and cost of all infection are also presented. Ceftriaxone decreased either the frequency or the cost of different postoperative infections. The cost of infection can increase the discriminatory power of trials comparing antibiotic effectiveness."
1,"TITLE: Consistency of the beneficial effect of metoprolol succinate extended release across a wide range dose of angiotensin-converting enzyme inhibitors and digitalis.ABSTRACT: The effects of beta-blockade with different extent of angiotensin-converting enzyme inhibitors (ACEI) and digitalization are unknown. To assess the effect of metoprolol succinate controlled release/extended release (CR/XL) combined with high versus low doses of ACEI and digitalis, we analyzed data from The Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) in which patients with heart failure and left ventricular ejection fraction < or =40% were randomized to metoprolol CR/XL versus placebo.Outcome was analyzed separately for those on a low dose (< or =median) of the ACEI or digitalis versus high dose (> median). The mean dose of ACEI in the high-dose group (n = 1457) was 3 times higher than that in the low-dose group (n = 2094). Mortality was reduced to a similar extent in the high- and low-dose ACEI subgroups (RR = .69 versus .64, respectively). Corresponding figures for combined mortality/all hospitalization and for mortality/hospitalization for heart failure were .85 versus .83, and .70 versus .68, respectively. Likewise, reduction in total mortality with metoprolol CR/XL was similar in patients receiving no digitalis (n = 1447; RR = .56), low dose (n = 1122; RR = .71), or high dose (n = 1421; RR = .71).This analysis of MERIT-HF demonstrates consistent and similar improvement in outcome of patients receiving metoprolol CR/XL when combined with either a high or low dose of an ACEI or digitalis, or no digitalis at all. Thus regardless of ACEI and digitalis dose and whether patients are treated with digitalis or not, it is very important to add a beta-blocker to the existing heart failure therapy. beta-blockers should not be withheld until target doses of ACEI have been achieved."
1,"TITLE: Reaching recommended lipid and blood pressure targets with amlodipine/atorvastatin combination in patients with coronary heart disease.ABSTRACT: The effects of combined atorvastatin and amlodipine on blood pressure (BP) and low-density lipoprotein (LDL) cholesterol levels were investigated in 134 patients with documented coronary heart disease treated for 1 year. BP at baseline was 128 +/- 15/79 +/- 9 mm Hg and was controlled by the treating physician; no calcium channel blockers were allowed. Baseline means for plasma cholesterol were 6.4 +/- 1.1 mmol/L (147 +/- 39 mg/dl), triglycerides 2.0 +/- 0.9 mmol/L (177 +/- 88 mg/dl), LDL cholesterol 4.4 +/- 1.0 mmol/L (170 +/- 39 mg/dl), and high-density lipoprotein cholesterol 1.2 +/- 0.3 mmol/L (46 +/- 12 mg/dl). Patients were all given atorvastatin 10 mg, then increased to 80 mg if the LDL cholesterol was <2.5 mmol/L (100 mg/dl). At 3 months, patients were randomized to amlodipine 10 mg or placebo. Plasma LDL cholesterol was decreased by 50%, and the LDL cholesterol target of <2.5 mmol/L was achieved in 81% of the patients. BP targets were achieved in 69% of the atorvastatin + placebo group, versus 96% in the atorvastatin + amlodipine group (p = 0.0002). With use of combination atorvastatin + amlodipine at doses ranging from 10 to 80 mg and 5 to 10 mg, respectively, recommended therapeutic goals were reached in most select subjects with coronary artery disease who were concomitantly receiving aspirin and antihypertensive therapy."
1,"TITLE: Exercise in the fasted state facilitates fibre type-specific intramyocellular lipid breakdown and stimulates glycogen resynthesis in humans.ABSTRACT: The effects were compared of exercise in the fasted state and exercise with a high rate of carbohydrate intake on intramyocellular triglyceride (IMTG) and glycogen content of human muscle. Using a randomized crossover study design, nine young healthy volunteers participated in two experimental sessions with an interval of 3 weeks. In each session subjects performed 2 h of constant-load bicycle exercise ( approximately 75% ), followed by 4 h of controlled recovery. On one occasion they exercised after an overnight fast (F), and on the other (CHO) they received carbohydrates before ( approximately 150 g) and during (1 g (kg bw)(-1) h(-1)) exercise. In both conditions, subjects ingested 5 g carbohydrates per kg body weight during recovery. Fibre type-specific relative IMTG content was determined by Oil red O staining in needle biopsies from m. vastus lateralis before, immediately after and 4 h after exercise. During F but not during CHO, the exercise bout decreased IMTG content in type I fibres from 18 +/- 2% to 6 +/- 2% (P = 0.007) area lipid staining. Conversely, during recovery, IMTG in type I fibres decreased from 15 +/- 2% to 10 +/- 2% in CHO, but did not change in F. Neither exercise nor recovery changed IMTG in type IIa fibres in any experimental condition. Exercise-induced net glycogen breakdown was similar in F and CHO. However, compared with CHO (11.0 +/- 7.8 mmol kg(-1) h(-1)), mean rate of postexercise muscle glycogen resynthesis was 3-fold greater in F (32.9 +/- 2.7 mmol kg(-1) h(-1), P = 0.01). Furthermore, oral glucose loading during recovery increased plasma insulin markedly more in F (+46.80 microU ml(-1)) than in CHO (+14.63 microU ml(-1), P = 0.02). We conclude that IMTG breakdown during prolonged submaximal exercise in the fasted state takes place predominantly in type I fibres and that this breakdown is prevented in the CHO-fed state. Furthermore, facilitated glucose-induced insulin secretion may contribute to enhanced muscle glycogen resynthesis following exercise in the fasted state."
1,"TITLE: Chronic angiotensin II receptor blockade reduces (intra)renal vascular resistance in patients with type 2 diabetes.ABSTRACT: Increased (intra)renal activity of the renin-angiotensin system may cause a persistent increase in renovascular resistance and intraglomerular pressure in patients with diabetes, thus contributing to the development of diabetic renal damage. The effect of chronic angiotensin II subtype 1 receptor blockade on (intra)renal hemodynamics in patients with type 2 diabetes was examined in a double-blind parallel group study. Patients were treated with 40 mg of olmesartan (n = 19) or placebo (n = 16), and renal hemodynamics were assessed before and after 12 wk of treatment using inulin and para-aminohippurate clearance techniques. Olmesartan significantly reduced 24-h ambulatory systolic and diastolic BP (both P < 0.05). In parallel, effective renal plasma flow increased significantly from 602 +/- 76 to 628 +/- 87 ml/min per 1.73 m(2), whereas filtration fraction and renovascular resistance decreased significantly (all P < 0.05). With placebo treatment, effective renal plasma flow decreased and filtration fraction increased significantly (both P < 0.05). GFR was not affected by both treatments. Active plasma renin concentration increased considerably (P < 0.05) with olmesartan therapy but remained unchanged with placebo treatment. Nitric oxide metabolism (plasma nitrate and nitrite) and asymmetric dimethylarginine blood levels were not affected by olmesartan and placebo therapy. In contrast, plasma 8-isoprostane 15(S)-8-iso-prostaglandin F(2a) concentration, a biochemical marker of oxidative stress, decreased significantly (P < 0.05) with olmesartan treatment. Chronic angiotensin II subtype 1 receptor blockade decreases (intra)renal vascular resistance and increases renal perfusion despite significant BP reduction. In addition, it significantly reduces oxidative stress. These effects of angiotensin II receptor antagonists may contribute to their beneficial long-term renal effects in patients with type 2 diabetes."
1,"TITLE: Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial.ABSTRACT: We assessed the relationship between antibodies to infliximab (ATI) and the loss of response postinfliximab, infusion reactions and, in a randomized trial, investigated whether intravenous hydrocortisone premedication can reduce ATI.Initially, we prospectively evaluated clinical response, adverse events, and ATI levels in 53 consecutive patients with Crohn's disease who received 199 infliximab (5 mg/kg) infusions. Subsequently, 80 patients with Crohn's disease were randomized to intravenous hydrocortisone 200 mg or placebo immediately before their first and subsequent infliximab infusions. The primary endpoint was reduction in median ATI levels at week 16. Analysis was by intention to treat.Nineteen of our initial 53 patients (36%) developed ATI, including all 7 patients with serious infusion reactions (median ATI level, 19.6 microg/mL). Eleven of 15 patients (73%) who lost their initial response were ATI positive compared with none of 21 continuous responders, (8.9 vs. 0.7 microg/mL, P < 0.0001). Administering a second infusion within 8 weeks of the first (OR, 0.13; 95% CI, 0.03-0.5; P = 0.0007) or concurrent immunosuppressants (OR, 0.19; 95% CI, 0.04-1.03; P = 0.007) significantly reduced ATI formation. In the placebo-controlled trial, ATI levels were lower at week 16 among hydrocortisone-treated patients (1.6 vs. 3.4 microg/mL, P = 0.02), and 26% of hydrocortisone-treated patients developed ATI compared with 42% of placebo-treated patients, P = 0.06.Loss of initial response and infusion reactions post-infliximab is strongly related to ATI formation and level. Administering a second infusion within 8 weeks of the first and concurrent immunosuppressant therapy significantly reduce ATI formation. Intravenous hydrocortisone premedication significantly reduces ATI levels but does not eliminate ATI formation or infusion reactions."
1,"TITLE: A prospective randomized multicenter study to evaluate the best day for embryo transfer: does the outcome justify prolonged embryo culture?ABSTRACT: This study aimed to evaluate the best day for embryo transfer in a prospective unrestricted randomized multicenter trial.Data were collected on a preformed Excel-sheet which contained random numbers from 1 to 5 for each subsequent patient as a preprogrammed day for embryo transfer. Information was requested on patient's age, indication for sterility treatment, stimulation protocol used, numbers of oocytes retrieved, fertilized oocytes, cryopreserved embryos, and cell stage of embryos transferred.A total of 329 embryo transfers were performed, resulting in 106 clinical pregnancies (32.2%). Pregnancy rates achieved were 20.0% on day 1, 30.4% on days 2 and 3, and 50.0% on days 4 and 5 (p = 0.03).Within the scope of the present randomized multicenter trial, embryo transfers performed on days 4 and 5 enhanced the pregnancy rate significantly, compared to those of days 1, 2, and 3."
1,"TITLE: Bicêtre hospital experience with sirolimus-based therapy in human renal transplantation: the Sirolimus European Renal Transplant Study.ABSTRACT: In 11 European centers, first cadaveric renal allograft recipients were randomized to CsA (n = 42) or sirolimus (n = 41). Dosing of these agents was concentration-controlled and open-labeled. All patients received corticosteroids and azathioprine. At 12 months, graft survival (98% sirolimus vs 93% CsA), patient survival (100% vs 98%), and incidence of biopsy-confirmed acute rejection (41% vs 38%) were similar. Serum creatinine was lower with sirolimus, significantly (P </=.05) so at 3 and 4 months, and serum uric acid and magnesium were normal. Laboratory abnormalities were reported significantly more often with sirolimus, which included hypertriglyceridemia (51% vs 12%), hypercholesterolemia (44% vs 14%), thrombocytopenia (37% vs 0%), leukopenia (39% vs 14%), and, of lesser importance, increased liver enzymes and hypokalemia. These abnormalities improved 2 months after transplantation when the sirolimus target trough level was lowered from 30 to 15 ng/mL. Occurrence of cytomegalovirus was comparable (14% vs 12%), but incidence of herpes simplex (24% vs 10%, P =.08) and pneumonia (17% vs 2%, P =.03) were higher with sirolimus. No gingival hyperplasia was seen with sirolimus, tremor was rare, and hypertension was less frequent (17% vs 33%). Two malignancies were observed with CsA, none with sirolimus. Results at 12 months suggest that sirolimus can be used as base therapy in the prophylaxis of acute renal transplant rejection, and has a safety profile that differs from that of CsA."
1,"TITLE: Serum HER-2/neu and response to the aromatase inhibitor letrozole versus tamoxifen.ABSTRACT: To determine the effect of elevated serum HER-2/neu on the response of metastatic breast cancer patients to an aromatase inhibitor versus an antiestrogen.Five hundred sixty-two estrogen receptor-positive metastatic breast cancer patients were randomized to first-line hormone therapy with either letrozole or tamoxifen. An automated enzyme-linked immunosorbent assay was used to detect serum HER-2/neu.For patients with normal serum HER-2/neu (70.5%), objective response rate (ORR; 39% in letrozole-treated patients v 26% in tamoxifen-treated patients; P =.008), clinical benefit (CB; 57% v 45%; P =.016), time to progression (TTP; median, 12.2 v 8.5 months; P =.0019), and time to treatment failure (TTF; median, 11.6 v 6.2 months; P =.0066) were significantly better in patients treated with letrozole. In the elevated HER-2/neu group (29.5%), there was no significant difference in ORR (17% in letrozole-treated patients v 13% in tamoxifen-treated patients; P =.45) or CB (33% v 26%; P =.31), but there was a strong trend in favor of a longer TTP with letrozole (median, 6.1 v 3.3 months; P =.0596) and a significantly longer TTF with letrozole (median, 6.0 v 3.2 months; P =.0418). Multivariate analysis revealed that elevated serum HER-2/neu was a negative predictor for ORR and TTP.Patients with normal serum HER-2/neu receiving letrozole demonstrated a significantly greater ORR and CB and longer TTP and TTF than patients receiving tamoxifen. Although in patients with elevated serum HER-2/neu there was no significant difference between letrozole and tamoxifen in ORR or CB, there was a strong trend favoring longer TTP and significantly longer TTF with letrozole."
1,"TITLE: Patient education strategies to improve pneumococcal vaccination rates: randomized trial.ABSTRACT: The pneumococcal vaccine is widely underused. Patient education is one mechanism not widely explored for increasing vaccination rates.To evaluate the effects of a culturally appropriate patient education videotape on pneumococcal vaccination rates among the clinic population of an inner-city public hospital.Randomized, controlled trial comparing (1) a videotape-brochure group who both viewed the videotape and received a low-literacy brochure, (2) a videotape only group, and (3) a control group.Of 2,962 charts reviewed, 558 patients were randomized. The study population was 94% black, 73% female, and elderly (mean age 63.0 years) and 64% had less than a high school education. Patients in the videotape-brochure group were 2.5 (1.8, 3.5 95% CI) times more likely to discuss the vaccine with their physician (p < .001) and 3.5 (1.9, 6.5 95% CI) times more likely to receive the vaccine (p < .001) than the control group. The videotape-brochure group was 1.6 (1.2, 2.1 95% CI) times more likely to discuss the vaccine (p < .001) and 2.3 (1.4, 3.8 95% CI) times more likely to receive the vaccine (p = .002) than the video only group. Patients in the video only group were 1.6 (1.1, 2.3 95% CI) times more likely to discuss the vaccine with their physician than the control group (p = .041) but were not more likely to receive the vaccine.A culturally appropriate videotape along with a low-literacy brochure significantly increased pneumococcal vaccination rates and physician-patient discussion about the vaccine. These significant outcomes were not observed with use of videotape alone and were likely attributable to the effect of the brochure. We recommend that patient education initiatives to increase vaccination rates not focus solely on audiovisual media."
0,"TITLE: The effect of rosiglitazone on serum lipoprotein(a) levels in Korean patients with type 2 diabetes mellitus.ABSTRACT: The aim of the study was to determine if rosiglitazone increases serum levels of lipoprotein(a) [Lp(a)] in Korean patients with type 2 diabetes mellitus. A total of 118 patients were divided into 2 groups: those with rosiglitazone (rosiglitazone group, n = 49) and those without rosiglitazone (control group, n = 69). The rosiglitazone group was given rosiglitazone (4 mg/d) with previous treatment, insulin, or sulfonylurea, for 12 weeks, whereas the control group continued previous treatment with some dose modification for glycemic control. The patients had their blood glucose, lipid levels, as well as Lp(a) levels assessed to obtain a baseline, which were remeasured 12 weeks later. The fasting blood glucose and glycosylated hemoglobin (HbA(1c)) levels decreased significantly in both groups as compared with the baseline. The fasting glucose and HbA(1c) levels in both groups were similar at 12 weeks. The total cholesterol levels increased significantly in the rosiglitazone group (190.6 +/- 32.4 to 212.2 +/- 47.2 mg/dL, P =.002), while they were unchanged in the control group (185.4 +/- 36.8 to 188.0 +/- 35.8 mg/dL, P =.615). The triglyceride levels did not change in either group. Significant increases in high-density lipoprotein (HDL) cholesterol levels were observed in the rosiglitazone group as compared with the baseline (41.7 +/- 10.6 to 45.9 +/- 11.4 mg/dL, P =.004). The low-density lipoprotein (LDL) cholesterol levels increased significantly in the rosiglitazone group (120.5 +/- 29.9 to 136.3 +/- 40.0 mg/dL, P =.012), while they did not change in the control group (113.0 +/- 29.1 to 118.3 +/- 31.7 mg/dL, P =.234). Significant increases in Lp(a) levels were observed in the rosiglitazone group as compared with the baseline (22.4 +/- 17.4 to 25.7 +/- 20.5 mg/dL, P =.015), approximately a 15% increase in average values. In contrast, there was no change in Lp(a) levels in the control group. There was no correlation between the changes in Lp(a) and changes in fasting blood glucose or HbA(1c) levels in all study subjects. In summary, rosiglitazone increased serum total cholesterol, LDL cholesterol, as well as Lp(a) levels in patients with type 2 diabetes mellitus. Considering that patients with type 2 diabetes mellitus have increased risks for cardiovascular disease, caution should be taken when prescribing rosiglitazone to patients who already have other risk factors, such as hypertension and smoking."
1,"TITLE: Uric acid reduces exercise-induced oxidative stress in healthy adults.ABSTRACT: Uric acid (UA) possesses free-radical-scavenging properties, and systemic administration is known to increase serum antioxidant capacity. However, it is not known whether this protects against oxidative stress. The effects of raising UA concentration were studied during acute aerobic physical exercise in healthy subjects, as a model of oxidative stress characterized by increased circulating 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) concentrations. Twenty healthy subjects were recruited to a randomized double-blind placebo-controlled crossover study, and underwent systemic administration of 0.5 g of UA in 250 ml of 0.1% lithium carbonate/4% dextrose vehicle or vehicle alone as control. Subjects performed high-intensity aerobic exercise for 20 min to induce oxidative stress. Plasma 8-iso-PGF2alpha concentrations were determined at baseline, after exercise and after recovery for 20 min. A single bout of high-intensity exercise caused a significant increase in plasma 8-iso-PGF2alpha concentrations from 35.0 +/- 4.7 pg/ml to 45.6 +/- 6.7 pg/ml (P<0.01). UA administration raised serum urate concentration from 293 +/- 16 to 487 +/- 16 micromol/l (P<0.001), accompanied by increased serum antioxidant capacity from 1786+/-39 to 1899 +/- 45 micromol/l (P<0.01). UA administration abolished the exercise-induced elevation of plasma 8-iso-PGF2alpha concentrations. High UA concentrations are associated with increased serum antioxidant capacity and reduced oxidative stress during acute physical exercise in healthy subjects. These findings indicate that the antioxidant properties of UA are of biological importance in vivo."
1,"TITLE: Study comparing the stroke unit outcome and conventional ward treatment: a randomized study in Joinville, Brazil.ABSTRACT: To assess the impact of a stroke unit (SU) on acute phase treatment when compared to a conventional general ward treatment (GW).Seventy-four patients with acute stroke were randomized between a SU and conventional general ward (GW). We compared both groups regarding the length of hospital stay, lethality and functional and clinical status within 6 months, using the Scandinavian scale and Barthel index.Thirty-five and thirty-nine patients were allocated at SU and GW, respectively. Lethality on the 10th day at SU and GW achieved 8.5% and 12.8% respectively (p= 0.41), whereas 30-days mortality rates achieved 14.2% and 28.2% (p= 0.24), 17.4% and 28.7% on the 3rd month (p= 0.39), and 25.7% and 30.7% on the 6th month (p= 0.41). Thirty-day survival curve achieved 1.8 log rank (p= 0.17), with a trend for lower lethality in the SU. In order to save one death in 6 months in SU, NNT (the number need to treat) was 20; to get one more home independent patient NNT was 15. No significant difference was found between the length of hospital stay and morbidity.No significant benefit was found in SU patients compared to GW group. However,an evident benefit in absolute numbers was observed in lethality, survival curve and NNT in thirty days period after stroke. Further collaborative studies or incresead number of patients are required to define the role of SU."
1,"TITLE: Efficacy and tolerability of acarbose in Asian patients with type 2 diabetes inadequately controlled with diet and sulfonylureas.ABSTRACT: The objective of this study was to investigate the efficacy, tolerability, and safety of acarbose in the improvement of glycemic control in Asian patients with type 2 diabetes inadequately controlled by diet and sulfonylureas. A 24-week, double-blind, placebo-controlled multicenter group comparison study was conducted. Patients were randomized to receive acarbose titrated up to 100-mg tid (n=36) or matching placebo (n=33). Concomitant sulfonylurea treatment remained unchanged throughout the study. The primary efficacy parameter was the change in HbA(1c) from baseline to double-blind endpoint. Secondary efficacy variables consisted of the change from baseline to endpoint in blood glucose (fasting and 1-h postprandial), serum insulin (fasting and 1-h postprandial), and urinary glucose. In the intention-to-treat (ITT) analysis, acarbose treatment was associated with significantly greater reductions in glycated hemoglobin (HbA(1c)) (-0.91% vs. placebo 0.13%, P=.0018) and 1-h postprandial blood glucose levels (-2.84 mmol/l vs. placebo -0.28 mmol/l, P=.002) compared to placebo. There were no significant differences between the treatment groups regarding changes in fasting blood glucose, fasting or 1-h postprandial serum insulin, urinary glucose, or body weight. Adverse events occurred with similar frequency in both treatment arms except for drug-related gastrointestinal side-effects associated with acarbose (acarbose 48.5% and placebo 12.5%). This study has shown that the use of acarbose in Asian patients with type 2 diabetes inadequately controlled by diet and sulfonylureas is efficacious in improving metabolic control and that acarbose is safe and well tolerated."
1,"TITLE: Prognostic factors in lateral epicondylitis: a randomized trial with one-year follow-up in 266 new cases treated with minimal occupational intervention or the usual approach in general practice.ABSTRACT: To determine whether minimal intervention by occupational specialists involving information about the disorder, encouragement to stay active and instruction in graded self-performed exercises could enhance the prognosis of lateral epicondylitis compared with the treatment usually given in general practice, to quantify workplace factors associated with the prognosis, and to consider treatments given in general practice.A randomized controlled trial was performed in a cohort of 266 consecutive new cases of lateral epicondylitis diagnosed in general practice. Workplace factors were assessed with questionnaires at the time of inclusion, and patients completed follow-ups at 3, 6 and 12 months. Status at 1 yr was assessed as overall improvement and pain reduction compared with the time of diagnosis. General practitioners (GPs) registered the treatments given for both cases and controls during follow-up. Numbers of contacts with GPs and physiotherapists were obtained from the National Health Insurance registry. Prognostic factors were analysed by multiple logistic regression analysis.After 1 yr, 83% of cases showed improvement in the condition, but the intervention was found to have had no advantage. Poor overall improvement was associated with employment in manual jobs [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.0-8.7], a high level of physical strain at work (OR 8.5, CI 1.0-74.7) and a high level of pain at baseline (OR 2.3, CI 1.0-5.3). Pain reduction less than 50% was associated with manual jobs (OR 2.3, CI 1.1-5.1), high physical strain at work (OR 3.6, CI 1.0-12.9), high baseline distress (OR 1.9, CI 1.0-4.0) and tennis elbow on the dominant side (OR 3.1, CI 1.4-6.8). The intervention group received less treatment and fewer treatment modalities, but the intervention was not followed by a reduction in the number of visits to GPs and physiotherapist clinics during 12 months of follow-up.Poor prognosis at 1 yr of follow-up for lateral epicondylitis was related to manual work and high baseline pain, whilst no relation was found between the type of medical treatment given/chosen and prognosis. This may have implications for the future management of lateral epicondylitis in terms of a greater focus on interaction with the workplace regarding job modification to reduce physical demands during recovery."
1,"TITLE: Improved cardiovascular risk profile and renal function in renal transplant patients after randomized conversion from cyclosporine to tacrolimus.ABSTRACT: Cyclosporine is considered to contribute to the high cardiovascular morbidity and mortality in patients after renal transplantation. Tacrolimus may be more favorable in this respect, but controlled data are scarce. In this prospective randomized study in 124 stable renal transplant patients, the effects of conversion from cyclosporine to tacrolimus on cardiovascular risk factors and renal function were investigated. Follow-up was 6 mo. Statistical analysis was performed by ANOVA for repeated measurements. The serum creatinine level decreased from 137 +/- 30 micromol/L to 131 +/- 29 micromol/L (P < 0.01). Three months after conversion from cyclosporine to tacrolimus, mean BP significantly decreased from 104 +/- 13 to 99 +/- 12 mmHg (P < 0.001). Serum LDL cholesterol decreased from 3.48 +/- 0.80 to 3.11 +/- 0.74 mmol/L (P < 0.001,) and serum apolipoprotein B decreased from 1018 +/- 189 to 935 +/- 174 mg/L (P < 0.001). Serum triglycerides decreased from 2.11 +/- 1.12 to 1.72 +/- 0.94 mmol/L (P < 0.001). In addition, both rate and extent of LDL oxidation were reduced. The fibrinogen level decreased from 3638 +/- 857 to 3417 +/- 751 mg/L (P < 0.05). Plasma homocysteine concentration did not change. Three months after conversion, plasma fasting glucose level temporarily increased from 5.4 +/- 1.3 mmol/L to 5.8 +/- 1.9 mmol/L (P < 0.05). Conversion to tacrolimus resulted in a significant reduction of the Framingham risk score. In conclusion, conversion from cyclosporine to tacrolimus in stable renal transplant patients has a beneficial effect on renal function, BP, serum concentration and atherogenic properties of serum lipids, and fibrinogen."
1,"TITLE: Combined interferon alpha2b and cyclosporin A in the treatment of chronic hepatitis C: controlled trial.ABSTRACT: Only 15% to 20% of patients with chronic hepatitis C have a sustained virological response to interferon monotherapy. The aim of the present study was to compare the efficacy and safety of interferon, in combination with oral cyclosporin A, with interferon monotherapy in the treatment of chronic hepatitis C.We assigned 120 patients with chronic hepatitis C to receive the standard Japanese dose of interferon alpha2b alone for 24 weeks or that dose of interferon alpha2b in combination with cyclosporin A, at doses of 200 mg daily for the first 4 weeks and 100 mg daily for the following 20 weeks. All patients were assessed for drug safety, tolerance, and efficacy at the end of weeks 4, 12, 24, and 48. Efficacy was assessed by the disappearance of serum hepatitis C virus (HCV)-RNA by polymerase chain reaction and normalization of serum aminotransferase. The primary endpoint was a sustained virological response; i.e., sustained undetectable serum HCV RNA at 48 weeks.The sustained virological response rate was significantly higher in the combination therapy group (42/76) than in the monotherapy group (14/44; P = 0.01). The sustained biochemical response rate was also higher in the combination therapy group (46/76) than in the monotherapy group (17/44; P = 0.017). In patients with genotype 1 and high viral loads, the sustained virological response rate was markedly higher in the combination therapy group (16/38) than in the monotherapy group (1/21; P = 0.006). Side-effect profiles were similar in the two groups.In patients with chronic hepatitis C; combined interferon and cyclosporin A treatment was more effective than interferon monotherapy. The benefit was mostly achieved in patients with a high viral load and HCV genotype 1."
0,"TITLE: Effects of enalaprilat on venoconstriction to norepinephrine: role of prostaglandins.ABSTRACT: Most patients with cardiovascular disease continue to receive both aspirin and an angiotensin-converting enzyme (ACE) inhibitor. This is despite the fact that ACE inhibition also inhibits the enzyme kininase II and leads to accumulation of bradykinin which increases prostaglandins. We hypothesized that in normal veins, vasodilator prostaglandins contribute significantly to ACE inhibitor dilation of norepinephrine-induced venoconstriction, and this would be blocked by cyclooxygenase inhibition.The study was performed using the in vivo dorsal hand vein technique for measuring vascular responses directly. Venoconstriction to norepinephrine infusions (0.5-1024 ng/min) was assessed in eight normal subjects (46+/-5 years, mean+/-S.E.M.) during coinfusion of saline in one hand (control) and enalaprilat (1000 microg/min) in the contralateral hand. On a second morning (7+/-1 days apart, mean+/-S.E.M., random order), the same procedure was repeated with indomethacin (3 microg/min) coinfusion in both hands.Enalaprilat shifted the norepinephrine dose-response curve to the right (P=0.024) and increased the norepinephrine log ED(50) (dose required to cause 50% venoconstriction) from 1.70+/-0.08 to 2.31+/-0.11 log ng/min (P=0.001). Indomethacin shifted the norepinephrine dose-response curve to the left (P=0.018) and decreased the norepinephrine log ED(50) from 1.70+/-0.08 to 1.09+/-0.18 log ng/min (P=0.002). In the presence of indomethacin, enalaprilat caused only a small but significant increase in the norepinephrine log ED(50), from 1.09+/-0.18 to 1.29+/-0.18 log ng/min (P=0.041).The results suggest that vasodilator prostaglandins contribute significantly to the attenuation of sympathetic venoconstriction by enalaprilat. This may have clinical relevance in patients receiving aspirin and ACE inhibitors in the setting of increased sympathetic activity."
1,"TITLE: Effect of atorvastatin on postcardiac transplant increase in low-density lipoprotein cholesterol reduces development of intimal hyperplasia and progression of endothelial dysfunction.ABSTRACT: Following cardiac transplantation, accelerated coronary disease limits long-term survival. Because statins may reduce the progression of the disease in part by their anti-inflammatory effects, this study was designed to assess if atorvastatin prevented neointimal hyperplasia and endothelial dysfunction independently of baseline cholesterol levels. Patients were randomized to usual therapy (n = 13) or to 10 to 20 mg of atorvastatin (n = 12). Control subjects received niacin when their low-density lipoprotein (LDL) cholesterol levels were >130 mg/dl (n = 4). Neointimal hyperplasia by intracoronary ultrasonography, endothelial dependent vascular reactivity, and coronary flow reserve were measured at baseline and 1 year. Control group total cholesterol (203 +/- 11 to 200 +/- 13 mg/dl) and LDL (116 +/- 10 to 119 +/- 11 mg/dl) remained stable, whereas there was a nonsignificant reduction at 12 months in the atorvastatin group (total cholesterol 216 +/- 28 to 178 +/- 21 mg/dl; LDL 126 +/- 17 to 100 +/- 18 mg/dl). At 2 to 3 months there was a significant increase in total cholesterol and LDL cholesterol that was reduced with atorvastatin. At 1 year, patients taking atorvastatin showed a decrease in new or progressing lesions (2.5 +/- 1.7 vs 4.2 +/- 1.8 lesions/patient, p = 0.02), progression of maximal intimal thickness (0.12 +/- 0.07 vs 0.52 +/- 0.17 mm, p = 0.04), and percent area stenosis (5.9 +/- 2.2% vs 19.0 +/- 5.5%, p = 0.04). Atorvastatin ameliorated progressive endothelial dysfunction, whereas coronary flow reserve was unchanged in both groups. Atorvastatin administered to patients with normal or mild hypercholesterolemia in the initial year after transplant reduced the initial increase in LDL cholesterol, and, by doing so, prevented the development and progression of coronary artery lesions and endothelial dysfunction with only mild long-term decreases in cholesterol levels."
1,"TITLE: Two-year clinical follow-up of 90Sr/90 Y beta-radiation versus placebo control for the treatment of in-stent restenosis.ABSTRACT: It is an ongoing concern that intracoronary brachytherapy may possibly just delay the problem of in-stent restenosis (""late catch up""). For gamma-radiation, 3 placebo-controlled studies have shown the maintenance of the initially positive effect after 2 years, but similar data do not exist for beta-radiation. STents And Restenosis Trial (START) was the first placebo-controlled randomized trial for in-stent restenosis with beta-radiation; herein, we report the 2-year clinical follow-up.Two hundred and forty-four patients were randomized to active treatment, 232 patients to placebo (nonactive source train) treatment. The primary end point of efficacy was target vessel revascularization (TVR); primary safety end point was any major adverse cardiac event (MACE) at 8 months and 2 years. Two-year clinical outcome in patients receiving brachytherapy was based on 195 of 244 original patients (79.9%) and in the placebo arm on 183 of 232 original patients (78.9%). TVR was significantly reduced by 25%; from 36.6% (placebo) to 27.5% (brachytherapy) remained significant after 2 years (RR .7 [.57-.98], 95% CI -9.2 [-17.5-0.8]). The Kaplan-Meier analysis for TVR and MACE showed improvement beginning approximately 90 days after radiation and remained almost constant for the 2 following years. Freedom from TVR was significantly increased from 62.4% +/- 3.8% to 71.6% +/- 3.3% (P = .027) and freedom from MACE from 58.9% +/- 3.7% to 68.0% +/- 3.4% (P = .035).The START trial shows for the first time that the initial beneficial effects of intracoronary brachytherapy with beta-radiation using 90 Sr/ 90 Y are maintained at 2-year clinical follow-up period."
1,"TITLE: Guided tissue regeneration associated with bovine-derived anorganic bone in mandibular class II furcation defects. 6-month results at re-entry.ABSTRACT: The use of graft materials with guided tissue regeneration (GTR) in Class II furcation defects is aimed at improving the outcome of the regenerative technique. In this regard, however, there are a limited number of studies discussing the results obtained when GTR and graft materials are used in the treatment of Class II furcation defects. Furthermore, most studies employ either allogeneic or autogenous materials. The present trial sought to determine whether the use of a bovine-derived anorganic bone (ABB) in conjunction with GTR influenced the outcome of mandibular Class II furcation treatment.This study included 14 patients who provided 15 pairs of similar periodontal defects. Each defect was randomly assigned to treatment with either a cellulose membrane in combination with bovine-derived anorganic bone (GTR+ABB) or membrane alone (GTR). Following basic therapy, baseline measurements were recorded including probing depth (PD), clinical attachment level (CAL), and gingival margin position (GMP). Hard tissue measurements were performed during surgery to determine alveolar crestal height (CEJ-AC), and vertical (VDD) and horizontal defect depth (HDD). Membranes remained in position for at least 4 weeks. After 6 months, all sites were re-entered and soft and hard tissue measurements were recorded.Both surgical procedures resulted in statistically significant probing depth reduction and gain in clinical attachment levels, with no significant difference between groups. Gingival recession was more pronounced in the GTR+ABB group (0.87 +/- 0.83 mm), but not statistically different from the GTR group (0.46 +/- 1.19 mm). Vertical defect resolution was significant in both groups (GTR: 1.60 +/- 1.50 mm; GTR+ABB: 1.80 +/- 2.11 mm), without differences between groups. Only horizontal furcation resolution (GTR: 2.47 +/- 0.99 mm; GTR+ABB: 3.27 +/- 1.39 mm) was significantly different between groups (P <0.05).The use of ABB with GTR techniques improved horizontal defect resolution in mandibular Class II furcation defects, but did not yield superior results regarding soft tissue changes when compared to sites treated with GTR alone. Evaluation of a larger sample could indicate differences and advantages between the evaluated approaches and confirm the real necessity of associating filling materials with GTR."
1,"TITLE: Does ascorbic acid prevent retinopathy during interferon therapy in patients with chronic hepatitis C?ABSTRACT: Ascorbic acid was administered to patients with chronic hepatitis C to elucidate the mechanism of onset of retinopathy during interferon (IFN) therapy, and its prevention.The subjects were 62 patients with chronic hepatitis C who had been admitted to our hospital. For the IFN therapy, 6 MIU of natural IFN-alpha, or 10 MIU of recombinant human IFN-alpha 2b was administered every day for the first 2 weeks, followed by administration three times a week for 22 weeks. The patients were randomly assigned to a group receiving 600 mg/day of ascorbic acid or a group not receiving ascorbic acid (control group). The optic fundi were examined by ophthalmologists before the IFN therapy began and subsequently at weeks 2 and 4 and then every 4 weeks during the IFN therapy.Retinopathy was found in 9 of the 31 patients (29%) in the ascorbic acid-treated group and in 11 of the 31 patients (35%) in the control group. The cumulative incidence of hemorrhage in the ascorbic acid-treated group was lower than that in the control group during the IFN therapy, but the difference between the two groups was not significant (P = 0.186). The cumulative incidence of cotton-wool spots in the ascorbic acid-treated group was almost same as that in the control group during the IFN therapy. The median platelet counts before the therapy was begun were 11.8 x 10(4)/mm2 in the group with hemorrhage and 16.6 x 10(4)/mm2 in the group without, and the lowest platelet counts during IFN therapy were 7.3 x 10(4)/mm3 in the group with hemorrhage and 9.5 x 10(4)/mm3 in the group without, indicating significantly lower values in the group with hemorrhage (P = 0.018 and P = 0.020, respectively). The lowest platelet counts during IFN therapy were 7.4 x 10(4)/mm3 in the group with cotton-wool spots and 9.7 x 10(4)/mm3 in the group without, indicating a significantly lower value in the group with cotton-wool spots (P = 0.036).Ascorbic acid was not considered to be useful for the prevention of the retinopathy associated with IFN therapy in patients with chronic hepatitis C."
1,"TITLE: Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure.ABSTRACT: This study evaluated whether cyclosporine (CsA) could be eliminated from a sirolimus (Rapamune, rapamycin, SRL)-CsA-steroid (ST) regimen at 3 months.This was an open-label study conducted in Europe, Australia, and Canada. Upon enrollment, 525 primary (90%) or secondary (10%) renal allograft recipients with cadaveric (89%) or living (11%) donors received 2 mg of sirolimus (troughs>5 ng/ml), CsA, and steroids. At 3 months+/-2 weeks, eligible patients were randomized (1:1) to remain on SRL-CsA-ST or to have CsA withdrawn and therapy continued with SRL (troughs 20-30 ng/ml)-ST.At 12 months, overall graft and patient survival were 89.1% and 94.9%, respectively. In the 430 (82%) randomized patients, there was no difference in graft survival (95.8% vs. 97.2%, SRL-CsA-ST vs. SRL-ST) or patient survival (97.2% vs. 98.1%, respectively). The incidence of biopsy-confirmed primary acute rejection was 13.1% during the prerandomization period. After randomization, the acute rejection rates were 4.2% and 9.8% for SRL-CsA-ST and SRL-ST, respectively (P=0.035). Renal function (calculated glomerular filtration rate, 57 vs. 63 ml/min, P<0.001) and blood pressure significantly improved when CsA was withdrawn. Hypertension, CsA nephrotoxicity, hyperuricemia, and Herpes zoster occurred statistically more frequently in patients remaining on CsA, whereas thrombocytopenia, abnormal liver function tests, and hypokalemia were reported more often for SRL-ST therapy.Sirolimus, CsA, and steroids for 3 months posttransplant, followed by elimination of CsA, is a safe and effective alternative to continuous therapy with sirolimus, CsA, and steroids that can result in better renal function and lower blood pressure."
1,"TITLE: Effective blood pressure treatment improves LDL-cholesterol susceptibility to oxidation in patients with essential hypertension.ABSTRACT: LDL-cholesterol particles from hypertensive patients exhibit enhanced susceptibility to in vitro oxidation, an abnormality thought to increase cardiovascular risk. We tested whether blood pressure (BP) normalization can reverse this abnormality.Double-blind, randomized pharmacological intervention trial.Clinical research centre. Subjects. A total of 29 nondiabetic, normolipidaemic patients with essential hypertension (BP= 151 +/- 3/99 +/- 1 mmHg) and 11 normotensive controls (BP=125 +/- 3/85 +/- 1 mmHg) matched for gender, age, obesity, glucose tolerance and lipid profile. Intervention. Anti-hypertensive treatment for 3 months with a calcium-antagonist in randomized combination with either an ACE inhibitor or a beta-blocker.Lag phase of copper-induced LDL oxidation, cell-mediated (human umbilical vein endothelium) generation of malondialdehyde (MDA) by LDL and vitamin E content in LDL.At baseline in hypertensives versus controls, lag phase was shorter (89 +/- 3 vs. 107 +/- 6 min, P < 0.04), MDA generation was higher (5.8 +/- 0.1 vs. 5.1 +/- 0.2 nmol L(-1), P=0.002), and vitamin E was reduced (6.40 +/- 0.05 vs. 6.67 +/- 0.11 microg mg(-1), P=0.03). At 3 months, BP was normalized (124 +/- 3/81 +/- 1, P < 0.0001 vs. baseline, P=ns versus controls), lag phase was prolonged (to 98 +/- 3 min, P=0.0005), MDA generation was reduced (5.6 +/- 0.1 nmol L-1, P = 0.001), and vitamin E was increased (6.53 +/- 0.05 microg mg(-1), P=0.003), with no significant differences between the randomized groups.In nondiabetic, nonobese, normolipidaemic patients with essential hypertension, LDL susceptibility to copper- and cell-mediated oxidation is increased. BP normalization is associated with a significant improvement, but not a full reversal, of this abnormality."
1,"TITLE: A comparison of propofol and remifentanil for sedation and limitation of movement during periretrobulbar block.ABSTRACT: To compare clinical conditions in patients sedated with propofol or remifentanil during combined peri-bulbar and retrobulbar block (PRBB) for cataract surgery.Prospective, randomized, double-blind study.Private clinic.106 ASA physical status I and II patients scheduled for cataract surgery.Patients were randomized to receive either 0.5 mg/kg propofol (Group P) or 0.3 microg/kg remifentanil (Group R) as an intravenous (IV) bolus 1 minute prior to PRBB. At the same time, patients in both groups also received 0.5 to 1 mg midazolam IV. Movement of the hands, arms, head, and eyes were counted during each stage of the procedure by an observer who was blinded to the sedation used. Heart rate (HR), blood pressure (BP), respiratory rate (RR), expiratory CO(2) (PECO(2)), and hemoglobin oxygen saturation (SaO(2)) were recorded every minute for 10 minutes after the PRBB. Anesthetic complications, recall, and the pain experienced with the block and surgery were compared between the two groups. Means and variance of the results were compared with one-way analysis of variance and Fisher's exact test.Movements of the hands, arms, and head were significantly greater in Group P during all stages of the block. Almost no movements were recorded in the remifentanil group. Immediately after the PRBB (1 to 6 min), HRs were higher in Group P (73 +/- 11 bpm vs. 67 +/- 10 bpm; p = 0.0075), whereas the RRs were slower in Group R for the period 1 to 5 minutes after the PRBB (16 +/- 5 breaths/min vs.14 +/- 4 breaths/min; p = 0.0206). At these times, the mean PECO(2) was higher in Group R (36 +/- 7 mmHgvs. 32 +/- 9 mmHg; p = 0.0125). Nineteen patients in the propofol group sneezed during the medial peribulbar injection compared with none in the remifentanil group. Anesthetic and surgical complications were unremarkable and similar for the two groups.Respiratory depression with remifentanil was mild and not clinically significant. Remifentanil sedation for this application was superior to sedation with propofol."
1,"TITLE: TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study).ABSTRACT: This study evaluated the effect of physiological, TSH-guided, L-thyroxine treatment on serum lipids and clinical symptoms in patients with subclinical hypothyroidism. Sixty-six women with proven subclinical hypothyroidism (TSH, 11.7 +/- 0.8 mIU/liter) were randomly assigned to receive L-thyroxine or placebo for 48 wk. Individual L-thyroxine replacement (mean dose, 85.5 +/- 4.3 microg/d) was performed based on blinded TSH monitoring, resulting in euthyroid TSH levels (3.1 +/- 0.3 mIU/liter). Lipid concentrations and clinical scores were measured before and after treatment. Sixty-three of 66 patients completed the study. In the L-thyroxine group (n = 31) total cholesterol and low density lipoprotein cholesterol were significantly reduced [-0.24 mmol/liter, 3.8% (P = 0.015) and -0.33 mmol/liter, 8.2% (P = 0.004), respectively]. Low density lipoprotein cholesterol decrease was more pronounced in patients with TSH levels greater than 12 mIU/liter or elevated low density lipoprotein cholesterol levels at baseline. A significant decrease in apolipoprotein B-100 concentrations was observed (P = 0.037), whereas high density lipoprotein cholesterol, triglycerides, apolipoprotein AI, and lipoprotein(a) levels remained unchanged. Two clinical scores assessing symptoms and signs of hypothyroidism (Billewicz and Zulewski scores) improved significantly (P = 0.02). This is the first double blind study to show that physiological L-thyroxine replacement in patients with subclinical hypothyroidism has a beneficial effect on low density lipoprotein cholesterol levels and clinical symptoms of hypothyroidism. An important risk reduction of cardiovascular mortality of 9-31% can be estimated from the observed improvement in low density lipoprotein cholesterol."
1,"TITLE: Effectiveness of colesevelam hydrochloride in decreasing LDL cholesterol in patients with primary hypercholesterolemia: a 24-week randomized controlled trial.ABSTRACT: To evaluate the efficacy, tolerability, and safety of colesevelam hydrochloride, a new nonsystemic lipid-lowering agent.In this double-blind, placebo-controlled trial performed in 1998, 494 patients with primary hypercholesterolemia (low-density lipoprotein [LDL] cholesterol level > or = 130 mg/dL and < or = 220 mg/dL) were randomized to receive placebo or colesevelam (2.3 g/d, 3.0 g/d, 3.8 g/d, or 4.5 g/d) for 24 weeks. Fasting serum lipid profiles were measured to assess efficacy. Adverse events were monitored, and discontinuation rates and compliance rates were analyzed. The primary outcome measure was the mean absolute change of LDL cholesterol from baseline to the end of the 24-week treatment period.Colesevelam lowered mean LDL cholesterol levels 9% to 18% in a dose-dependent manner (P<.001), with a median LDL cholesterol reduction of 20% at 4.5 g/d. The reduction in LDL cholesterol levels was maximal after 2 weeks and sustained throughout the study. Mean total cholesterol levels decreased 4% to 10% (P<.001), while median high-density lipoprotein cholesterol levels increased 3% to 4% (P<.001). Median triglyceride levels increased by 5% to 10% in placebo and colesevelam treatment groups relative to baseline (P<.05), but none of these differences were significantly different from placebo. Mean apolipoprotein B levels decreased 6% to 12% in an apparent dose-dependent manner (P<.001). No significant differences occurred in adverse events or discontinuation rates between groups, and compliance rates were between 88% and 92% for all groups.Colesevelam was efficacious, decreasing mean LDL cholesterol levels by up to 18%, and well tolerated without serious adverse events."
1,"TITLE: Temporary portocaval shunt during liver transplantation with vena cava preservation. Results of a prospective randomized study.ABSTRACT: This study aims to determine whether the use of a temporary portocaval shunt (PCS) improves hemodynamic and metabolic evolution during orthotopic liver transplantation (OLT). Preservation of the vena cava during OLT has gained wide acceptance. However, benefits of adding a temporary PCS to the piggyback technique during the anhepatic phase in patients with cirrhosis have not been shown. Eighty patients with cirrhosis were studied prospectively. They were randomly distributed into two groups: patients with a temporary PCS (n = 40) and those without a PCS (n = 40). In all cases, the piggyback technique was used. Hemodynamic profiles and biochemical data during OLT and clinical evolution after OLT were evaluated. Preoperative data were similar in both groups. Surgical time also was similar (403 +/- 77 v 387 +/- 56 minutes; P = .3). Red blood cell requirements were lower in the PCS group (2.3 +/- 2.5 v 3.3 +/- 2.9 units), although differences were not significant. In the PCS group, 45% of patients did not need red blood cell transfusion, whereas in the other group, only 22% were not administered a transfusion (P = .03). During the anhepatic phase, the decrease in cardiac output was lower in the PCS group (-9.6% v -19%; P = .05), whereas diuresis during the anhepatic phase was greater in the PCS group (3.6 +/- 2.97 v 2.1 +/- 1.38 mL/kg/h; P = .005). There were no differences in liver biochemical parameters during the first 3 postoperative days. Nevertheless, creatinine levels increased significantly during this period only in the no-PCS group. The use of a temporary PCS during OLT improves hemodynamic status, reduces intraoperative transfusion requirements, and preserves renal function during and after OLT."
0,"TITLE: Availability of on-site catheterization and clinical outcomes in patients receiving fibrinolysis for ST-elevation myocardial infarction.ABSTRACT: To compare management and clinical outcomes in hospitals stratified by the availability of on-site catheterization in InTIME-II, a multicentre trial comparing alteplase with lanoteplase for acute myocardial infarction.We studied 15,078 patients enrolled in 35 countries and 855 hospitals. Thirty-one percent of hospitals had 24-h, 25% day-only, and 44% no on-site catheterization facilities. Rates of cardiac angiography (57%, 38%, 26%) and revascularization (37%, 21%, 17%) were higher in hospitals with increasing access to on-site facilities(P<0.0001). The presence of a 24-h on-site facility was the strongest predictor of angiography during the index admission (odds ratio 4.17, 95% CI 3.85-4.54). There were no major differences in patient outcomes at 30 days when hospitals were stratified by availability of on-site catheterization. Adjusted 1-year mortality was similar between groups of hospitals (odds ratio for day-only 0.94 [0.80-1.09] and odds ratio for no availability 0.95 [0.83-1.10] compared to hospitals with 24-h facilities).There is a marked variation in procedure use by the availability of on-site catheterization with no major differences in patient outcomes. There is a need for additional randomized trials in the current era to address both the appropriate selection of patients and timing of invasive procedures in ST-elevation acute myocardial infarction."
1,"TITLE: Effects of cisapride on gall bladder emptying, intestinal transit, and serum deoxycholate: a prospective, randomised, double blind, placebo controlled trial.ABSTRACT: Octreotide inhibits gall bladder emptying and prolongs intestinal transit. This leads to increases in the proportion of deoxycholic acid in, and cholesterol saturation of, gall bladder bile, factors that contribute to the pathogenesis of octreotide induced gall stones.To see if an intestinal prokinetic, cisapride, could overcome these adverse effects of octreotide and if so, be considered as a candidate prophylactic drug for preventing iatrogenic gall bladder stones.A randomised, double blind, placebo controlled, crossover design was used to examine the effects of cisapride (10 mg four times daily) on gall bladder emptying, mouth to caecum and large bowel transit times, and the proportions of deoxycholic acid and other bile acids, in fasting serum from: (i) control subjects (n=6), (ii) acromegalic patients not treated with octreotide (n=6), (iii) acromegalics on long term octreotide (n=8), and (iv) patients with constipation (n=8).Cisapride had no prokinetic effect on the gall bladder. In fact, it significantly increased both fasting and postprandial gall bladder volumes. However, it shortened mouth to caecum (from 176 (13) to 113 (11) minutes; p<0.001) and large bowel (from 50 (3.0) to 31 (3.4) h; p<0.001) transit times. It also reduced the proportion of deoxycholic acid in serum from 26 (2.3) to 15 (1.8)% (p<0.001), with a reciprocal increase in the proportion of cholic acid from 40 (3.5) to 51 (3.8)% (p<0.01). There were significant linear relationships between large bowel transit time and the proportions of deoxycholic acid (r=0.81; p<0.001) and cholic acid (r=-0.53; p<0.001) in fasting serum. INTERPRETATION/SUMMARY: Cisapride failed to overcome the adverse effects of octreotide on gall bladder emptying but it countered octreotide induced prolongation of small and large bowel transit. Therefore, if changes in intestinal transit contribute to the development of octreotide induced gall bladder stones, enterokinetics such as cisapride may prevent their formation."
0,"TITLE: Relationship between endogenous estrogen concentrations and serum cholesteryl ester transfer protein concentrations in Chinese women.ABSTRACT: CETP plays an important role in HDL metabolism and in the reverse cholesterol transport pathway.The relationship between the changes of endogenous estrogen and the concentration of cholesteryl ester transfer protein (CETP) in the serum of Chinese women was investigated. Serum concentrations of estradiol (E(2)), follicle-stimulating hormone (FSH), CETP and lipid profile were determined in 196 Chinese women (52 premenopausal with ages ranging from 18 to 40 years, 57 perimenopausal from 41 to 60 years, and 87 postmenopausal from 61 to 81 years).Serum CETP concentration was significantly lower in postmenopausal women compared with those in perimenopausal and premenopausal women (1.39+/-1.06, 2.36+/-1.50 and 2.31+/-1.25 mg/l, respectively, P<0.0001). Even in the women around the menopausal, CETP concentration in postmenopause was significantly lower than that in premenopause (1.93+/-1.33 vs. 3.42+/-1.35 mg/l, P<0.01). In addition, CETP concentration had a highly positive correlation with serum concentration of E(2) (r=0.243, P<0.001), while negative correlation of CETP concentration with serum concentration of FSH was found (r=-0.273, P<0.001).Estrogen may affect the concentration of CETP."
1,"TITLE: Prospective randomized study of post-operative chemotherapy with levamisole and UFT for head and neck carcinoma.ABSTRACT: A prospective randomized study was conducted to evaluate the benefit of adjuvant levamisole/UFT (futraful and uracil) chemotherapy in head and neck squamous cell carcinoma.Sixty-five patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx, hypopharynx and larynx with no distant metastasis were randomized for the chemotherapy study. Thirty-one patients were randomized for chemotherapy and two of them were subsequently excluded. In this study, a total of 29 patients on levamisole/UFT therapy and 34 patients on the control group were analysed. The main outcome was measured by the 5-year disease-free actuarial survival rate.The rates of distant metastasis were 10% for chemotherapy group and 32% for control group (P=0.06). The 5-year disease-free actuarial survival rates for patients with and without adjuvant chemotherapy were 57% and 39% respectively (P=0.207).A trend of better distant control in head and neck cancer patients with post-operative adjuvant oral chemotherapy was observed. The side effects were minimal. However, there was no statistically significant improvement in the overall long-term survival. It may be of value to conduct a large-scale multi-centre prospective randomized study to verify the efficacy of levamisole and UFT as post-operative adjuvant chemotherapy for the control of distant metastasis in high-risk population."
1,"TITLE: Economic evaluation of propofol for sedation of patients admitted to intensive care units.ABSTRACT: The goal of the current study was to evaluate the economic impact of propofol as compared with midazolam for sedating patients in the intensive care unit (ICU).A randomized, unblinded, multicenter pharmacoeconomic trial captured health resource utilization and outcome measurements associated with sedation and treatment of patients in four ICUs across Canada. Statistical analysis was performed to investigate the difference in sedation quality, ICU length of stay, and other health resources used. The authors compared the costs (1997 Canadian dollars) associated with the two treatments. Two types of sensitivity analyses were performed.Although overall sedation duration was similar, propofol patients spent more time at adequately sedated status (60.2% vs. 44%; P = 0.01) and were extubated faster (median extubation time, 2.5 vs. 7.1 h; P = 0.001). The ICU length of stay and health resource utilization did not differ. The total cost per patient, including drug cost and ICU stay cost, did not differ between groups (median, $5,718 for propofol vs. $5,950 for midazolam; P = 0.94). The first sensitivity analysis suggested that the incremental cost (per patient) of propofol varies from an extra cost of $114 to a savings of $2,709. Based on a hypothetical model, the second sensitivity analysis showed a potential saving of $479 per patient as a result of improved discharge planning.The analysis demonstrated that using propofol resulted in a reduction of time to extubation and higher sedative regimen costs. There was no difference in intensity of resource use or ICU length of stay and hence in costs. Issues regarding discharge delay among propofol-treated patients remain to be explored."
1,"TITLE: Monochromatic infrared irradiation (890 nm): effect of a multisource array upon conduction in the human median nerve.ABSTRACT: Antidromic conduction studies in the human median nerve were used to assess the neurophysiological effects of irradiation of the skin overlying the nerve using a novel treatment unit comprising a multisource monochromatic infrared diode array (Equilight, Denver, CO).Healthy human volunteers (n = 40) were recruited and randomly allocated to one of four groups: control, placebo, or one of two treatment groups (1.7 and 4.0 J/cm2). After baseline recordings of negative peak latency (NPL) were completed on the nondominant arm, subjects were treated according to group allocation. Recordings were subsequently repeated at 5-min intervals over a 45-min period.Analysis of negative peak latency difference scores (ANOVA) demonstrated significant differences in NPL between groups and over time (p < 0.05). While in the control and placebo groups NPL values remained relatively stable, in the two treatment groups such values decreased marginally, with the greatest effects observed in the 4.0 J/cm2 group (e.g., at 5 min, differences in NPL [mean +/- SEM]: control group, 0.02+/-0.03 msec; treatment group 2, 4 J/cm2, -0.07+/-0.03 msec). Similar significant differences were observed in skin temperature; correlation analysis indicated a weak (but expected) positive linear relationship between skin temperature and nerve conduction velocity (r = 0.125).These results suggest that irradiation at the parameters and under the conditions used here produce a direct neurophysiological effect. The magnitude of such effects are in keeping with previous findings using single source arrays at higher radiant exposures or thermal effects of the treatment unit."
1,"TITLE: A randomized comparison of the value of additional stenting after optimal balloon angioplasty for long coronary lesions: final results of the additional value of NIR stents for treatment of long coronary lesions (ADVANCE) study.ABSTRACT: We sought to investigate the clinical benefit of additional stent implantation after achieving an optimal result of balloon angioplasty (BA) in long coronary lesions (>20 mm).Long coronary lesions are associated with increased early complications and late restenosis after BA. Stenting improves the early outcome, but stent restenosis is also related to both lesion length and stent length.A total of 437 patients with a single native lesion 20 to 50 mm in length were included and underwent BA, using long balloons matched to lesion length and vessel diameter (balloon/artery ratio 1.1) to achieve a diameter stenosis (DS) <30% by on-line quantitative coronary angiography (QCA). ""Bail-out stenting"" was performed for flow-limiting dissections or >50% DS. Patients in whom an optimal BA result was achieved were randomized to additional stenting (using NIR stents) or no stenting. The primary end point was freedom from major adverse cardiac events (MACE) at nine months, and core laboratory QCA was performed on serial angiograms.Bailout stenting was necessary in 149 patients (34%) and was associated with a significantly increased risk of peri-procedural infarction (p < 0.02). Among the 288 randomized patients, the mean lesion length was 27+/-9 mm, and the vessel diameter was 2.78+/-0.52 mm. The procedural success rate was 90% for the 143 patients assigned to BA alone (control group), as compared with 93% in the 145 patients assigned to additional stenting (stent group), which resulted in a superior early minimal lumen diameter (0.54 mm, p < 0.001) and led to reduced angiographic restenosis (27% vs. 42%, p = 0.022). Freedom from MACE at nine months was 77% in both groups.A strategy of provisional stenting for long coronary lesions led to bailout stenting in one-third of patients, with a threefold increase in peri-procedural infarction. Additional stenting yielded a lower angiographic restenosis rate, but no reduction in MACE at nine months."
1,"TITLE: Radiotherapy for subfoveal choroidal neovascularization in age-related macular degeneration: a randomized clinical trial.ABSTRACT: To report results of 18-month follow up of external beam radiation therapy with photons for subfoveal classic or occult choroidal neovascularization (CNV) in age-related macular degeneration (ARMD).Randomized clinical trial.A total of 161 patients with subfoveal CNV in ARMD were recruited in a prospective double-masked study. The posterior pole of the afflicted eye was given 1 Gy (4 x 0.25 Gy) in the control group and 8 Gy (4 x 2 Gy) or 16 Gy (4 x 4 Gy) in the treatment groups. At the time of treatment, and 6, 12, and 18 months post treatment, best-corrected visual acuity (BCVA), reading ability, and CNV size were measured.At the completion of the study 150 (93.2%), 139 (86.3%), and 137 (85.1%) patients were followed for 6, 12, and 18 months, respectively. The mean number of lines lost in the BCVA was -1.69, -2.2, and -3.23 in the 1 Gy group; -0.94, -1.25, and -1.73 in the 8 Gy group; -0.51, -0.67, and -1.93 in the 16 Gy group. The difference was significant after 12 months (P =.016 for 8 Gy vs. 1 Gy; P =.006 for 16 Gy vs. 1 Gy), and 18 months (P =.011 for 8 Gy vs. 1 Gy; P =.05 for 16 Gy vs. 1 Gy). The patients with classic CNV, or with an initial distance visual acuity >or=20/100, benefited more from treatment. A significant difference was not found between control group and treatment groups in the reading ability and in the CNV size. No radiation-associated side effects were reported thus far.The number of lines lost in the BCVA was less in the 8 Gy and 16 Gy treatment groups than in the control group during the complete follow up examination. Radiation therapy with 8 Gy and 16 Gy, without showing any difference in efficacy, resulted in a near stabilization of the BCVA in patients with subfoveal classic or occult CNV in ARMD. Further studies are necessary to determine the significance of repeated radiotherapy series with a dose of 8 Gy to improve the effect on the CNV size and thereby to prolong stabilization of distance visual acuity."
1,"TITLE: Use of delayed pushing with epidural anesthesia: findings from a randomized, controlled trial.ABSTRACT: To compare outcomes between women receiving epidural anesthesia assigned to a group following either a 1-hour ""delayed"" pushing protocol or directed to initiate pushing at full cervical dilation.Using a randomized, controlled design, multivariate analyses were used to evaluate second stage labor duration and Apgar scores. An estimated odds ratio equation evaluated fetal descent progress.A 13.68-minute difference occurred in second stage labor length (p = 0.225). No differences were found in Apgar scores (p > 0.09). An estimated odds ratio, that progress in terms of one fetal station unit would occur for control group subjects as compared with subjects with similar progress in the experimental group, was 1.51 (95% confidence interval: 1.16, 1.95).Second stage labor was not significantly lengthened, and a similar rate of fetal descent occurred in the absence of directed pushing. Findings support further research on the potential advantages of minimizing the duration of pushing in labor."
1,"TITLE: Perioperative myocardial ischemia in cataract surgery patients: general versus local anesthesia.ABSTRACT: Patients having cataract surgery are usually elderly and have risk factors for ischemic heart disease. We sought to determine the incidence of perioperative myocardial ischemia in patients having cataract surgery and compare the influence of local anesthesia (LA) and general anesthesia (GA). Eighty-one patients undergoing cataract surgery with at least two risk factors for ischemic heart disease were monitored continuously for 24 h by using electrocardiogram leads II and V5 and a Holter recorder (Medilog 4500, Oxford Ltd, UK). Patients were randomly allocated to two groups, either LA (n = 39) or GA (n = 42). In the LA group, a peribulbar block was performed, whereas a similar block was performed in the GA group after tracheal intubation. The study demonstrated that cataract patients suffered from a frequent incidence of perioperative myocardial ischemia (31%). There was no difference in the incidence rate between the groups: 12 of 39 in the LA group and 13 of 42 in the GA group (P: = NS). However, the number of ischemic episodes was significantly increased in the GA group (18 vs. 13 in the LA group) (P<0.05), and there were significantly more intraoperatively in the GA group (8 vs. 1) (P<0.01). All intraoperative ischemic events were associated with tachycardia (> or =20% of baseline), whereas postoperative ischemic changes were mostly independent of heart rate. Only one of the ischemic patients (in the GA group) was admitted as a result of intractable chest pain. There were significantly less intraoperative episodes in the LA group, suggesting that LA may be safer than GA in patients during this type of surgery."
1,"TITLE: Total parenteral nutrition enriched with arginine and glutamate generates glutamine and limits protein catabolism in surgical patients hospitalized in intensive care units.ABSTRACT: To study the effect of a parenteral nutrition solution enriched with potential precursors of glutamine, i.e., arginine and glutamate, on plasma glutamine concentrations and protein metabolism.Prospective, randomized, single-blind, comparative study.Two intensive care units in two different hospitals.Fifteen surgical patients.Patients were randomized to receive total parenteral nutrition for 5 days with the enriched glutamine precursor solution (GlnP+ group) or a conventional solution (control group), both total parenteral nutrition providing 0.25 gN/kg per day and 35 kcal/kg per day (glucose/lipids, 70%:30%).Plasma amino acid concentrations before (T0) and after 3 hrs (T3) of perfusion, nitrogen balance (daily and cumulated), and urinary excretion of 3-methylhistidine were measured daily from day 1 to day 5. The two groups were identical for age, weight, severity score, and nitrogen and energy intakes. After a 3-hr perfusion, plasma concentrations of arginine, ornithine, and glutamine increased, and the differences (T3 - T0) were significantly higher in the GlnP+ group: arginine, 107.6+/-7.0 vs. 51.9+/-3.3 (mean over 5 days; p < .001); ornithine, 78.9+/-7.1 vs. 43.6+/-3.1 (p < .001); and glutamine, 32.4+/-8.6 vs. 6.7+/-5.0 micromol/L (p < .05), respectively. A positive correlation was found between arginine and glutamine plasma increases only in the GlnP+ group: r = .45; p < .01 (Spearman's rank-correlation test). Daily and cumulated nitrogen balances were not significantly different between the two groups but were positive (difference from 0) only in the GlnP+ group. The urinary 3-methylhistidine/creatinine ratio decreased significantly from day 1 to day 5 only in the GlnP+ group: 24.5+/-2.7 vs. 18.8+/-2.7 micromol/mmol (p < .05).Total parenteral nutrition enriched with arginine and glutamate promotes a better nitrogen balance, limits protein myofibrillar catabolism, and generates glutamine, with arginine (not glutamate) probably being the main contributor to the glutamine-generating effect of the solution through the formation of ornithine."
1,"TITLE: 5-day vs. 7-day triple therapy with rabeprazole, clarithromycin and amoxicillin for Helicobacter pylori eradication.ABSTRACT: To determine whether a 5-day regimen with rabeprazole, clarithromycin and amoxicillin (RCA) was as effective as a 7-day regimen.A total of 139 H. pylori-infected patients were randomized to receive either a 5-day or 7-day course of rabeprazole 10 mg b.d., clarithromycin 400 mg b.d. and amoxicillin 750 mg b.d. Eradication was assessed by CLO test, histology and 13C-urea breath test.On the intention-to-treat basis, eradication rates were 66% (46 out of 70) and 84% (58 out of 69) for the 5- and 7-day regimens, respectively (P < 0.05). Using per protocol analysis, eradication rates were 70% (46 out of 66) and 91% (58 out of 64) for the 5- and 7-day regimens, respectively (P < 0.01). Adverse events, which were observed in 14 patients from each group, caused discontinuation of treatment in only two patients, resulting in excellent compliance.Our 5-day regimen of RCA yielded inferior results, whereas the 7-day regimen achieved an eradication rate exceeding 90% on the per protocol basis. Therefore, treatment regimens of less than 7 days for proton pump inhibitor-clarithromycin-amoxicillin therapies cannot be recommended."
1,"TITLE: Effects of pravastatin in 3260 patients with unstable angina: results from the LIPID study.ABSTRACT: The LIPID study is a major trial of secondary prevention of coronary-heart-disease events that includes hospital admission with unstable angina (as well as myocardial infarction) as a qualifying event. In this substudy of LIPID, we compared subsequent cardiovascular risks and the effects of pravastatin in patients with previous unstable angina or previous myocardial infarction.3260 patients diagnosed with unstable angina and 5754 with acute myocardial infarction 3-36 months previously were randomly assigned 40 mg pravastatin daily or placebo over a mean of 6.0 years. The risk reduction of a range of cardiovascular events was estimated by means of the hazard ratio in Cox's proportional hazards model.Among patients assigned placebo, survival in the two diagnosis groups was similar. The relative risk reduction for mortality with pravastatin was 20.6% in the myocardial infarction group and 26.3% in the unstable angina group (p=0.55). Pravastatin significantly reduced the rates of all prespecified coronary endpoints in the myocardial infarction group. In patients with previous unstable angina, coronary heart disease mortality, total mortality, myocardial infarction, a need for coronary revascularisation, the number of admissions to hospital, and the number of days in hospital were significantly lower with pravastatin. Overall, hospital admission for unstable angina was the most common endpoint (24.6% of the placebo group; 22.3% of the pravastatin group).Patients who have survived acute myocardial infarction or unstable angina have a similar long-term prognosis, a high occurrence of subsequent unstable angina, and benefit similarly from therapy with pravastatin."
1,"TITLE: Immunomodulatory effects of acupuncture in the treatment of allergic asthma: a randomized controlled study.ABSTRACT: According to Traditional Chinese Medicine (TCM) acupuncture is a suitable treatment for complex chronic diseases such as bronchial asthma. In a randomized, controlled study we investigated immunologic effects of Chinese acupuncture on patients with allergic asthma.The effects of acupuncture treatment given according to the principles of TCM (TCM group, n = 20) were compared with those of acupuncture treatment using points not specific for asthma (control group, n = 18). All patients were treated 12 times for 30 minutes over a time period of 4 weeks. Patients' general well-being and several peripheral blood parameters (eosinophils, lymphocyte subpopulations, cytokines, in vitro lymphocyte proliferation) were determined before and after acupuncture treatment.In the TCM group, significantly more patients indicated an improvement in general well-being (79% in the TCM group versus 47% in the control group; p = 0.049) after acupuncture treatment. The following changes were found in the TCM group: within the lymphocyte subpopulations the CD3+ cells (p = 0.005) and CD4+ cells (p = 0.014) increased significantly. There were also significant changes in cytokine concentrations: interleukin (IL)-6 (p = 0.026) and IL-10 (p = 0.001) decreased whereas IL-8 (p = 0.050) rose significantly. Additionally, the in vitro lymphocyte proliferation rate increased significantly (p = 0.035) while the number of eosinophils decreased from 4.4% to 3.3% after acupuncture (p > 0.05). The control group, however, showed no significant changes apart from an increase in the CD4+ cells (p = 0.012).The results imply that asthma patients benefit from acupuncture treatment given in addition to conventional therapy. Furthermore, acupuncture performed in accordance with the principles of TCM showed significant immune-modulating effects."
0,"TITLE: Influence of leisure time physical activity and television watching on atherosclerosis risk factors in the NHLBI Family Heart Study.ABSTRACT: Physical activity favorably influences atherosclerosis risk factors but only a few studies in adults considered the time watching television (TV) as a measure of physical inactivity. We therefore determined in a population-based sample of 1778 subjects from the NHLBI Family Heart Study (FHS) whether leisure time physical activity and TV watching have independent or interactive associations with cardiovascular disease risk factors and carotid artery intima-media wall thickness (IMT). Subjects were free from diabetes mellitus and clinically-ascertained coronary artery disease and did not take lipid-lowering or antihypertensive drugs. Only 0.7 and 1.3% of the variance in leisure time physical activity in women and men, respectively, was explained by the amount of TV watching. Leisure time physical activity had a clearly favorable, and TV watching an unfavorable association with anthropometric measurements (BMI (body mass index), waist girth, waist-hip ratio, subscapular and triceps skinfold thickness). The odds ratio (95% CI) of being overweight was 0.41 (0.28-0.62) in women and 0.69 (0.46-1.04) in men in the highest quartile of leisure time physical activity compared to the lowest quartile. The odds ratio increased for increasing quartiles of TV watching to 2.12 (1.45-3.10) in women and 1.61 (1.07-2.43) in men. Watching TV only 1 h per day in women with a BMI of 30 kg/m2 and doing about 75 min of moderate exercise per week was associated with a BMI 1.8 kg/m2 lower than in women watching TV 3 h per day and doing the same amount of exercise. Those with twice the amount of moderate exercise and watching TV 1 h per day had a BMI 0.45 kg/m2 lower. Furthermore, leisure time physical activity was negatively associated with concentrations of triglycerides and positively with HDL cholesterol in both genders. TV watching was significantly positively associated with triglycerides and slightly negatively with HDL cholesterol in men. The observed associations of leisure time physical activity and TV watching with atherosclerosis risk factors were independent from each other. Finally, we analyzed the relation between leisure time physical activity, TV watching and the degree of IMT of the carotid arteries. Neither of these two measures was significantly associated with IMT. In summary, TV watching, in addition to leisure time physical activity, shows an independent association with obesity-related anthropometric measurements, HDL and triglycerides. Decreasing the amount of TV watching might be effective as a first step in reducing atherosclerosis risk factors, especially overweight."
1,"TITLE: Sustained benefit over four years from an initial combined antiplatelet regimen after coronary stent placement in the ISAR trial. Intracoronary Stenting and Antithrombotic Regimen.ABSTRACT: Combined antiplatelet therapy after coronary stent placement is superior to anticoagulation with respect to early outcome. It is unclear if this benefit is maintained during long-term follow-up. This study reports on the 4-year clinical outcome of patients randomized in the Intracoronary Stenting and Antithrombotic Regimen trial. In the Intracoronary Stenting and Antithrombotic Regimen trial, 517 patients were randomized after successful placement of Palmaz-Schatz stents: 257 to aspirin and ticlopidine, and 260 to aspirin and phenprocoumon. Ticlopidine and phenprocoumon were given for 4 weeks. At 30 days, patients with ticlopidine had significantly fewer adverse cardiac events (1.6% vs 6.2%; p = 0.007), nonfatal myocardial infarction (0.8% vs 3.5%; p = 0.034), and target vessel revascularization procedures (1.2% vs 5.4%; p = 0.007). At 4 years, rates for any adverse cardiac events were 22.6% versus 28.5% (p = 0.078), for nonfatal myocardial infarction 0.9% versus 5.8% (p = 0.003), and for target vessel revascularization 18.3% versus 22.7% (p = 0.21). The absolute difference in event rates (4.6% after 30 days) was maintained after 4 years (5.9%). Event rates beyond day 30 were not significantly different (21.1% vs 22.5%; p = 0.78), nor were the rates beyond the first year, which were very low (5.2% vs 3.6%; p = 0.50). This study shows that the benefit of combined antiplatelet therapy evident after 30 days is maintained after 4 years. Independent of the initial regimen, rates of adverse cardiac events are low beyond the first year."
1,"TITLE: Effect of alendronate and MK-677 (a growth hormone secretagogue), individually and in combination, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women.ABSTRACT: GH increases bone turnover and stimulates osteoblast activity. We hypothesized that administration of MK-677, an orally active GH secretagogue, together with alendronate, a potent inhibitor of bone resorption, would maintain a higher bone formation rate relative to that seen with alendronate alone, thereby generating greater enhancement of bone mineral density (BMD) in women with postmenopausal osteoporosis. We determined the individual and combined effects of MK-677 and alendronate administration on insulin-like growth factor I levels and biochemical markers of bone formation (osteocalcin and bone-specific alkaline phosphatase) and resorption [urinary N-telopeptide cross-links (NTx)] for 12 months and BMD for 18 months. In a multicenter, randomized, double blind, placebo-controlled, 18-month study, 292 women (64-85 yr old) with low femoral neck BMD were randomly assigned in a 3:3:1:1 ratio to 1 of 4 daily treatment groups for 12 months: MK-677 (25 mg) plus alendronate (10 mg); alendronate (10 mg); MK-677 (25 mg); or a double dummy placebo. Patients who received MK-677 alone or placebo through month 12 received MK-677 (25 mg) plus alendronate (10 mg) from months 12-18. All other patients remained on their assigned therapy. All patients received 500 mg/day calcium. The primary results, except for BMD, are provided for month 12. MK-677, with or without alendronate, increased insulin-like growth factor I levels from baseline (39% and 45%; P < 0.05 vs. placebo). MK-677 increased osteocalcin and urinary NTx by 22% and 41%, on the average, respectively (P < 0.05 vs. placebo). MK-677 and alendronate mitigated the reduction in bone formation compared with alendronate alone based on mean relative changes in serum osteocalcin (-40% vs. -54%; P < 0.05, combination vs. alendronate) and reduced the effect of alendronate on resorption (NTx) as well (-52% vs. -61%; P < 0.05, combination vs. alendronate). MK-677 plus alendronate increased BMD at the femoral neck (4.2% vs. 2.5% for alendronate; P < 0.05). However, similar enhancement was not seen with MK-677 plus alendronate in BMD of the lumbar spine, total hip, or total body compared with alendronate alone. GH-mediated side effects were noted in the groups receiving MK-677, although adverse events resulting in discontinuation from the study were relatively infrequent. In conclusion, the anabolic effect of GH, as produced through the GH secretagogue MK-677, attenuated the indirect suppressive effect of alendronate on bone formation, but did not translate into significant increases in BMD at sites other than the femoral neck. Although the femoral neck is an important site for fracture prevention, the lack of enhancement in bone mass at other sites compared with that seen with alendronate alone is a concern when weighed against the potential side effects of enhanced GH secretion."
1,"TITLE: Improving outcomes in acute coronary syndromes--the FRISC II trial.ABSTRACT: The FRISC II study addressed two key questions in the management of acute coronary syndromes: is it beneficial to extend low-molecular-weight heparin (LMWH) therapy with dalteparin beyond the initial period of acute treatment; and, is a strategy of early invasive therapy, including angioplasty and surgical revascularization, preferable to a more conservative strategy? The study focused on patients with unstable coronary artery disease (UCAD), that is, angina and non-ST-segment-elevation myocardial infarction (MI). Patients were allocated in a randomized, factorial study design to either an invasive or a conservative management strategy. Within each of these groups, patients were further randomized to receive either 3 months of extended treatment with dalteparin or placebo, following at least 5 days' treatment with open-label dalteparin. After 1 year, patient survival and MI-free survival were significantly higher in the invasive therapy group than in the noninvasive group. Patients who received extended dalteparin treatment had a significantly reduced probability of death or MI after 1 month (relative risk reduction 47%; p = 0.002), a benefit still evident after 60 days, but after 3 months there was no longer any significant clinical advantage compared with placebo. There was, however, a significant reduction in the combined incidence of death, MI, or revascularization at 3 months in the extended dalteparin treatment group (relative risk reduction 13%; p = 0.031). The benefits of extended dalteparin treatment were particularly marked in patients with elevated troponin-T or ST-segment depression. A subgroup analysis of conservatively managed patients who underwent revascularization in the first 45 days revealed that the probability of death or MI at 1 year was significantly lower among patients who received extended dalteparin treatment (relative risk reduction 35%; p = 0.02). Extended dalteparin treatment is, however, associated with a small increase in bleeding risk. In conclusion, early invasive therapy (following combined treatment with aspirin and dalteparin) is recommended in a majority of patients with UCAD. Furthermore, extended dalteparin treatment for up to 45 days is efficacious and well tolerated, and therefore provides a useful ""bridge"" to revascularization when early revascularization is not immediately available."
1,"TITLE: Is a dissection balloon beneficial in totally extraperitoneal endoscopic hernioplasty (TEP)? A randomized prospective multicenter study.ABSTRACT: Laparoscopic hernioplasty has been criticized because of its technical complexity and increased costs. Disposable dissection balloons can be used to facilitate the creation of the initial working space in totally extraperitoneal endoscopic hernioplasty (TEP), but their use adds to the cost of the operation.A total of 322 men with unilateral, primary, or recurrent inguinal hernias were randomized to undergo TEP with or without a dissection balloon.In the group with the balloon, three of 161 patients (2.5%) required conversion to transabdominal preperitoneal hernioplasty (TAPP), or open herniorraphy, whereas 17 of 161 patients (10.6%) were converted to TAPP or open herniorraphy in the group without the balloon (p = 0.002). The mean operation time was 55 min in the group with the balloon and 63 min in the group without the balloon (p = 0.004). There was no difference between them in postoperative morbidity, and there were no major complications in either group. The recurrence rate was 3.1% in the group with the balloon and 3.7 % in the group without the balloon (p = 0.8).The use of a dissection balloon in TEP reduces the conversion rate and may be especially beneficial early in the learning curve."
1,"TITLE: Fish oil (Eicosapen) is less effective than metronidazole, in combination with pantoprazole and clarithromycin, for Helicobacter pylori eradication.ABSTRACT: In vitro omega-3-fatty acids (Eicosapen) are bacteriostatic to Helicobacter pylori and have a variety of immuno-modulating effects.To investigate the efficacy and tolerability of eicosapen (E) as an antibiotic-sparing component of a triple H. pylori eradication regimen in non-ulcer dyspepsia patients in a randomized, double-blind trial.Non-ulcer dyspepsia patients (n=199), with a normal upper endoscopy and a positive (13)C-urea breath test (UBT) were randomly assigned to either pantoprazole, clarithromycin and metronidazole (PCM) or pantoprazole, clarithromycin and eicosapen (PCE) for 7 days. Four weeks after treatment, H. pylori eradication was determined by UBT. Symptoms were followed up to 16 months.In the intention-to-treat population, PCM eradicated infection in 78% but PCE was successful in only 34% (P < 0.001). Symptomatic improvement occurred in both groups, and was not related to H. pylori eradication.Eicosapen is unlikely to be useful in H. pylori eradication regimens."
1,"TITLE: Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial.ABSTRACT: Glycoprotein IIb/IIIa blockers reduce procedure-related thrombotic complications of percutaneous coronary intervention, and the risk of death and myocardial infarction in patients with acute coronary syndromes. The effect on risk of death and myocardial infarction is particularly apparent in patients undergoing early percutaneous coronary interventions. We did a randomised, multicentre trial to study the effect of the glycoprotein IIb/IIIa blocker abciximab on patients with acute coronary syndromes who were not undergoing early revascularisation.We enrolled 7800 patients who were admitted to hospital with chest pain and either ST-segment depression or raised troponin T or I concentrations. 2598 were randomly assigned placebo, 2590 an abciximab bolus and 24 h infusion, and 2612 an abciximab bolus and 48 h infusion; all patients received aspirin and either unfractionated or low-molecular-weight heparin. The primary endpoint was death or myocardial infarction at 30 days after randomisation. Analysis was by intention to treat.There were no drop-outs. 209 (8.0%) patients on placebo, 212 (8.2%) on 24 h abciximab, and 238 (9.1%) on 48 h abciximab died or had a myocardial infarction before day 30 (odds ratio 1.0 [95% CI 0.83-1.24], for difference between placebo and 24 h abciximab, and 1.1 [0.94-1.39] for difference between placebo and 48 h abciximab). The lack of benefit from treatment with abciximab was consistent in most subgroups investigated; in particular, no benefit was seen in patients with raised cardiac troponin T or I concentrations at enrolment, although these patients did have a strongly increased risk of subsequent events. Bleeding rates were low, but increased with abciximab, particularly when continued for 48 h. Additionally, thrombocytopenia was more frequent with abciximab than with placebo.Although the explanations for our findings are unclear, this study indicates that abciximab is not beneficial as first-line medical treatment in patients admitted with acute coronary syndromes."
0,"TITLE: Vascular adhesion molecule-1 and markers of platelet function before and after a treatment with iloprost or a supervised physical exercise program in patients with peripheral arterial disease.ABSTRACT: Platelet function and levels of vascular adhesion molecule-1 (VCAM-1) were investigated in 24 patients with peripheral arterial disease at Fontaine stage II undergoing a 2 weeks treatment with iloprost (0.5-2 ng/kg/h i.v. infused, 6 h/day) or a 2 weeks supervised physical training, randomly assigned. Patients were studied before (T0) and after (T14) treatments and 10 days later (T24). The adhesion of washed platelets to fibrinogen coated microwells was reduced after treatment both with iloprost (1.9+/-0.4 vs 6.8+/-0.7%; T24 vs T0; M+/-SEM; p<0.05) and physical exercise (3.0+/-1.0 vs 6.7+/-0.7; p<0.05) while adhesion to human plasma coated microwells was reduced only after treatment with iloprost (1.9+/-0.8 vs 5.8+/-0.9; p<0.05). The expression of fibrinogen receptor (glycoprotein IIb/IIIa) on platelets, measured by flow-cytometry was also reduced after iloprost treatment (17.1+/-1.5 vs 31.8+/-4.8 AU; p<0.05) and physical exercise (14.6+/-1.5 vs 34.0+/-3.3; p<0.05). Theurinaryexcretion of platelet thromboxane A2 metabolite 2,3-dinor-thromboxane B2 decreased only in patients treated with iloprost (154.7+/-97.9 vs 256.2+/-106.4 pg mg creatinine(-1); p<0.05). Similarly plasma VCAM-1 was lower in patients who were treated with iloprost (827.7+/-77.4 vs 999.0+/-83.8 ng ml(-1); p<0.05). In conclusion, both iloprost and physical exercise seem to act on reversible phenomena such as the expression of adhesion molecules or ex vivo adhesion, whereas only iloprost reduces thromboxane A2 biosynthesis in vivo. This anti-platelet activity seems to be extended in time and to be associated with an improvement in vascular function."
1,"TITLE: Randomized comparison of T-type versus L-type calcium-channel blockade on exercise duration in stable angina: results of the Posicor Reduction of Ischemia During Exercise (PRIDE) trial.ABSTRACT: Mibefradil is a T-type calcium-channel antagonist and arterial vasodilator with negative chronotropic effects. It is not known if T-type calcium-channel blockade is superior to L-type calcium-channel blockade in patients with stable angina pectoris.A multicenter, randomized, double-blind trial was conducted in patients with documented coronary disease and stable angina to compare a 360 mg dose of diltiazem CD with 100 mg dose of mibefradil. The primary end point was change in time to symptom-limited exercise termination from baseline to 8 weeks. Secondary efficacy parameters included time to onset of persistent ST-segment depression, time to awareness of angina, and change in exercise duration from baseline to 2 and 4 weeks of treatment.A total of 121 patients were randomized to mibefradil and 113 to diltiazem CD. At 8 weeks, the increase in exercise duration was 24.5 seconds greater in the mibefradil group (P =.017; 95% CI 4.4-44.7 seconds). At 8 weeks, time to development of > or =1 mm ST-segment depression was greater by 45.3 seconds (P =.0025; 95% CI 16.2-74.5) with mibefradil, but time to development of angina was not significantly different.T-type calcium-channel antagonism with mibefradil improved treadmill exercise parameters compared with diltiazem in patients with chronic stable angina. Further investigation and development of antagonists of T-type calcium channels with fewer adverse drug interactions is warranted and may be promising in the management of ischemic heart disease."
1,"TITLE: A randomized controlled trial of enteral versus parenteral feeding in patients with predicted severe acute pancreatitis shows a significant reduction in mortality and in infected pancreatic complications with total enteral nutrition.ABSTRACT: Infectious complications are the main cause of late death in patients with acute pancreatitis. Routine prophylactic antibiotic use following a severe attack has been proposed but remains controversial. On the other hand, nutritional support has recently yielded promising clinical results. The aim of study was to compare enteral vs. parenteral feeding for prevention of infectious complications in patients with predicted severe acute pancreatitis.We screened 466 consecutive patients with acute pancreatitis. A total of 70 patients with objectively graded severe acute pancreatitis were randomly allocated to receive either total enteral nutrition (TEN) or total parenteral nutrition (TPN), within 72 h of onset of symptoms. Baseline characteristics were well matched in the two groups.The incidence of pancreatic infectious complications (infected pancreatic necrosis, pancreatic abscess) was significantly lower in the enterally fed group (7 vs. 16, p = 0.02). In the TEN group, 7 patients developed multiple organ failure whereas 17 parenterally fed patients developed multiple organ failure (p = 0.02). Overall mortality was 20% with two deaths in the TEN group and twelve in the TPN group (p < 0.01).Early TEN could be used as prophylactic therapy for infected pancreatic necrosis since it significantly decreased the incidence of pancreatic infectious complications as well as the frequency of multiple organ failure and mortality."
0,"TITLE: Non-randomised patients in a cholecystectomy trial: characteristics, procedures, and outcomes.ABSTRACT: Laparoscopic cholecystectomy is now considered the first option for gallbladder surgery. However, 20% to 30% of cholecystectomies are completed as open operations often on elderly and fragile patients. The external validity of randomised trials comparing mini-laparotomy cholecystectomy and laparoscopic cholecystectomy has not been studied. The aim of this study is to analyse characteristics, procedures, and outcomes for all patients who underwent cholecystectomy without being included in such a trial.Characteristics (age, sex, co-morbidity, and ASA-score), operation time, hospital stay, and mortality were compared for patients who underwent cholecystectomy outside and within a randomised controlled trial comparing mini-laparotomy and laparoscopic cholecystectomy.During the inclusion period 1719 patients underwent cholecystectomy. 726 patients were randomised and 724 of them completed the trial; 993 patients underwent cholecystectomy outside the trial. The non-randomised patients were older--and had more complications from gallstone disease, higher co-morbidity, and higher ASA--score when compared with trial patients. They were also more likely to undergo acute surgery and they had a longer postoperative hospital stay, with a median 3 versus 2 days (p < 0.001 for all comparisons). Standardised mortality ratio within 90 days of operation was 3.42 (mean) (95% CI 2.17 to 5.13) for non-randomised patients and 1.61 (mean) (95%CI 0.02 to 3.46) for trial patients. For non-randomised patients, operation time did not differ significantly between mini-laparotomy and open cholecystectomy in multivariate analysis. However, the operation for laparoscopic cholecystectomy lasted 20 minutes longer than open cholecystectomy. Hospital stay was significantly shorter for both mini-laparotomy and laparoscopic cholecystectomy compared to open cholecystectomy.Non-randomised patients were older and more sick than trial patients. The assignment of healthier patients to trials comparing mini-laparotomy cholecystectomy and laparoscopic cholecystectomy limits the external validity of conclusions reached in such trials."
1,"TITLE: Comparison of remifentanil with fentanyl for deep sedation in oral surgery.ABSTRACT: The aim of this study was to compare recovery for oral surgery patients given a deep sedation regimen of midazolam, propofol, and remifentanil with a standard control of fentanyl in place of remifentanil.This investigation was designed as a randomized, prospective, single-blinded controlled study. Group 1, the control, received midazolam 0.03 mg/kg, fentanyl 1 microg/kg, and propofol initially at 140 microg/kg/min. Group 2 received midazolam 0.03 mg/kg, remifentanil: propofol (1:500) given at an initial propofol infusion rate of 40 microg/kg/min. Outcome measures included time to response to verbal command, Aldrete score = 9, Postanesthesia Discharge Scoring System = 7, and assessment by the Digit Symbol Substitution Test.Forty-seven subjects were entered in the study. Baseline findings were homogenous between the 2 groups. Subjects in group 2 recovered earlier (P < .005) and required less propofol for both the induction (0.8 +/- 0.4 versus 1.2 +/- 0.6 mg/kg; mean +/- SD, P < .01) and maintenance of deep sedation (46 +/- 9 versus 131 +/- 17 microg/kg/min; P < .005). There were minor differences in vital signs.This study demonstrated that this remifentanil regimen provided significantly more rapid recovery and used significantly less propofol compared with the fentanyl regimen."
1,"TITLE: Allograft versus no graft with a posterior multisegmented hook system for the treatment of idiopathic scoliosis.ABSTRACT: A prospective, randomized study.To compare the clinical results of posterior spinal fusion (PSF) with allograft augmentation versus no graft for patients with adolescent idiopathic scoliosis (AIS).The use of allograft has become a standard means of augmenting a PSF. Many studies have shown equal rates of fusion when comparing allograft with autogenous iliac crest. There have been no studies to directly compare the results obtained with allograft with those achieved without the use of any bone graft at all.Ninety-one patients with AIS were randomized into two treatment groups. Seventy-six patients had greater than 2-year follow-up and are included in this review. The Allograft Group consisted of 37 patients who underwent a standard PSF using a multisegmented hook-screw and rod system with the use of corticocancellous allograft for augmentation. The No Graft Group included 39 patients with AIS who underwent the same procedure without any bone graft. All autogenous bone resulting from a thoracoplasty and any local bone (for example, that removed from spinous processes) was discarded in both groups. Patients with at least 2 years of radiographic and clinical follow-up were evaluated using established criteria for possible or definite pseudarthrosis. Treatment groups were similar with respect to age, preoperative deformity, and correction obtained.The overall definitive pseudarthrosis rate for this study was 1.3% (1 of 76 patients). The 1 patient with pseudarthrosis was in the Allograft Group (1 of 37, or 2.7%, P = 0.98 as defined by our criteria), versus none of 39 in the No Graft Group. Two patients in each group (5.4% in the Allograft Group and 5.1% in the No Graft Group) met the radiographic criteria for possible pseudarthrosis. This establishes a P value of 0.65 comparing risk of possible pseudarthrosis in the two groups.Our results suggest that a PSF using newer-generation multisegmented hook-screw and rod systems can be successful with allograft and/or local bonegraft without the use of supplemental autogenous bone graft (from the iliac crest or ribs) in patients with AIS."
1,"TITLE: Regular vs ad-lib albuterol for patients hospitalized with acute asthma.ABSTRACT: Inhaled, short-acting beta-agonists and systemic corticosteroids form the mainstay of therapy in acute asthma exacerbation. Asthma, however, is an inflammatory disease of the airways, and its underlying pathology is not impacted by short-acting beta-agonists. While the efficacy of ad-lib beta-agonist administration in outpatient management of asthma symptoms is well established, little data exist to support this strategy in patients with acute, severe asthma. We postulate that as long as patients hospitalized with severe asthma exacerbation receive systemic corticosteroids, regular, scheduled administration of short-acting beta-agonists is unnecessary. Similar therapeutic outcomes can be achieved with the ad-lib administration of the short-acting beta-agonists.Prospective, randomized, double-blind, placebo-controlled trial.Pulmonary floor of a 600-bed municipal hospital.Sixty-two patients hospitalized for acute asthma.Patients were randomized to receive either albuterol nebulizations (regular albuterol group) or saline solution nebulizations (ad-lib group) every 4 h with management of breakthrough symptoms with albuterol metered-dose inhaler or nebulizations for both groups. All patients received systemic corticosteroids. Peak expiratory flows, asthma symptoms, and need for rescue bronchodilator were followed up on each patient until discharge.There was no significant difference in the length of hospitalization (median length, 48 h for ad-lib group vs 57.5 h for regular albuterol group, p = 0.82), rate of improvement in peak flow, or symptoms between the two groups. Ad-lib beta-agonist use compared to regular albuterol scheduled use resulted in a significant reduction in the total number of albuterol treatments administered (median, 7 treatments vs 19 treatments, p = 0.001) during hospitalization.In the management of asthma exacerbation, ad-lib administration of albuterol is therapeutically as effective as regular, scheduled administration. This method of drug administration also reduces the total dose of beta-agonists received by the hospitalized patient."
1,"TITLE: Low-fat, high fruit and vegetable diets and weight loss do not affect biomarkers of cellular proliferation in Barrett esophagus.ABSTRACT: Risk factors for esophageal adenocarcinoma include obesity, high fat intake, and low consumption of fruits and vegetables. This trial tested whether an intervention to reduce these risk factors in patients with Barrett esophagus, a preneoplastic condition for esophageal adenocarcinoma, could reduce biomarkers of cellular proliferation and, by inference, the risk of neoplastic progression. Eighty-seven men and women with Barrett esophagus were randomized to an intensive dietary intervention or control group. At baseline, 18 and 36 months after intervention, biopsies were obtained at 2-cm intervals throughout the length of the Barrett segment. Ki67/DNA content flow cytometry was used to assess (a) % Ki67-positive proliferating diploid G(1) cells, (b) % total Ki67-positive proliferating cells, (c) presence of aneuploidy, and (d) presence of >6% of cells in the 4N (G(2)/tetraploid) fraction of the cell cycle. We also assessed re-epithelialization and length of the Barrett segment, reflux symptoms, and medication use. The intervention effects for energy, fat, fruits and vegetables, and weight were, respectively, -314 kcal, -12.2% energy, 1.8 servings/d, and -4.0 kg at 18 months (all P < 0.005) and were smaller but remained significant at 36 months. There were no significant effects of the intervention on any biomarker of cellular proliferation. The intervention effects +/- SE for mean %G(1) Ki67+ cells were 0.98 +/- 1.58 at 18 months and 1.79 +/- 1.31 at 36 months; the relative risks (95% confidence interval) for developing >6% of cells in 4N were 0.5 (0.1-2.6) at 18 months and 0.75 (0.2-3.1) at 36 months. A single control participant developed aneuploidy. There were no significant effects on re-epithelialization, segment length, or reflux medication use. We conclude that substantial dietary change has no short-term effects on biomarkers of cellular proliferation in Barrett esophagus or on clinical observations of the Barrrett segment."
1,"TITLE: Respiratory symptom relief related to reduction in cigarette use.ABSTRACT: Many smokers reduce their cigarette consumption during failed attempts to quit. We report the impact of changes in consumption on smoking-related respiratory symptom severity (SRRSS).Between February 2002 and May 2004 we recruited 383 smokers from 5 methadone maintenance programs for a randomized trial of nicotine replacement plus behavioral treatment versus nicotine replacement alone for smoking cessation. Cigarette use in the 28 days prior to the interview, and severity of SRRSS using a 7-item respiratory index, were assessed at baseline and at 3-month follow-up.Baseline minus 3-month assessment difference in SRRSS score.Follow-up of 319 participants (83.3%), mean age 40.4 years, 51.4% male, who smoked 26.4 cigarettes per day, demonstrated a mean reduction of 16.7 cigarettes per day. A reduction in cigarette use was positively and significantly (b=0.29, t=5.16, P<.001) associated with a reduction in smoking-related symptom severity after adjusting for age, gender, race, years of regular smoking, baseline nicotine dependence, and history of treatment for asthma or emphysema. A 1 standard deviation reduction in average daily smoking (about 14.1 cigarettes) was associated with a 0.28 standard deviation decrease in smoking-related symptom severity.Reduction in symptom severity increases as absolute reduction in daily smoking increases. This is the first study to demonstrate an association between subjective short-term health changes and reduction in smoking."
1,"TITLE: Recurrence of esophageal varices following endoscopic treatment and its impact on rebleeding: comparison of sclerotherapy and ligation.ABSTRACT: Endoscopic variceal ligation is superior to sclerotherapy because of its lower rebleeding and complication rates. However, ligation is not without drawbacks due to a higher tendency to variceal recurrence. We conducted a randomized cohort study to delineate the long-term history of variceal recurrence following ligation and sclerotherapy, and to clarify the impact of recurrence on rebleeding and on the consumption of endoscopic treatment resources.Two hundred cirrhotic patients with esophageal variceal bleeding were randomized to undergo maintenance endoscopic variceal sclerotherapy or ligation.One hundred and forty-one patients achieved variceal eradication and were regularly followed up for 2.2 to 6.7 (mean: 5.1 +/- 1.2) years. The demographic data, hepatic reserve, bleeding severity, and endoscopic features of both sclerotherapy (n=70) and ligation (n=71) showed no difference. Forty (57.1%) patients who underwent sclerotherapy experienced 58 recurrences of esophageal varices, in contrast to the 46 (64.8%) patients who underwent ligation and experienced 81 episodes of recurrence. Kaplan-Meier analysis showed that within 2 years variceal recurrence was more frequent for ligation than sclerotherapy, and the difference decreased thereafter. Multiple recurrence appeared more common with ligation (1/2/3/4/5 episodes of recurrence: 46/23/8/3/1 vs. 40/14/3/1/0, p=0.08). On multifactorial analysis, the endoscopic treatment method and red wale markings were the two factors determining variceal recurrence. Rebleeding from recurrent esophageal varices was unusual and showed no difference between the two groups (7/58 vs. 6/81, p>0.05). Rebleeding from gastric varices was more common after eradication by sclerotherapy (7/19 vs. 1/16, p=0.085) than by ligation. The number of sessions required for eradication of recurrent varices was no different between the two groups.Early recurrence and multiple recurrence of esophageal varices are more likely in patients undergoing endoscopic ligation, compared to sclerotherapy; however, the recurrence did not lead to a higher risk of rebleeding or require more endoscopic treatment."
1,"TITLE: The addition of bicalutamide 150 mg to radiotherapy significantly improves overall survival in men with locally advanced prostate cancer.ABSTRACT: Castration therapy adjuvant to radiotherapy can significantly improve overall survival compared with radiotherapy alone in patients with locally advanced prostate cancer. Although many of the adverse effects of castration therapy are manageable, they can have a detrimental effect on quality of life. Here we evaluate the efficacy and tolerability of the non-castration-based therapy bicalutamide ('Casodex') 150 mg adjuvant to radiotherapy in patients with T1-4, M0, any n prostate cancer.The subset of patients within the early prostate cancer (EPC) program who received radiotherapy with curative intent (n = 1,370) were included in the analysis. These patients were randomized to receive oral bicalutamide 150 mg once daily (n = 699) or placebo (n = 671).The median follow-up for patients included in this analysis was 7.2 years. In patients with locally advanced disease (n = 305), bicalutamide adjuvant to radiotherapy significantly improved: progression-free survival (PFS), reducing the risk of objective progression by 44% compared with radiotherapy alone [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.40, 0.78; P < 0.001). Prostate-specific antigen (PSA)-PFS, reducing the risk of PSA progression by 59% compared with radiotherapy alone (HR 0.41; 95% CI 0.30, 0.55; P < 0.001). Overall survival, reducing the risk of death by 35% compared with radiotherapy alone (HR 0.65; 95% CI 0.44, 0.95; P = 0.03). This significant overall survival benefit for bicalutamide was driven by a lower risk of prostate cancer-related deaths (16.1 vs 24.3%, respectively). There was no significant difference in PFS or overall survival in patients with localized disease (n = 1,065).In patients with locally advanced disease, bicalutamide 150 mg adjuvant to radiotherapy demonstrates significant clinical benefits in terms of overall survival, PFS and PSA-PFS compared with radiotherapy alone. The overall survival benefit in these patients is consistent with prior studies evaluating castration-based therapies adjuvant to radiotherapy (Bolla et al. in Lancet 360:103-108, 2002; Pilepich et al. in Int J Radiat Oncol Biol Phys 61:1285-1290, 2005). In addition, the clinical benefit of bicalutamide 150 mg in locally advanced patients, but not in those with localized disease, is consistent with the overall results from the EPC program (McLeod et al. BJU Int 97:247-254, 2006). Given the quality-of-life advantages of bicalutamide relative to castration, bicalutamide 150 mg adjuvant to radiotherapy is an attractive alternative for men with locally advanced prostate cancer."
1,"TITLE: Effect of ramipril on the incidence of diabetes.ABSTRACT: Previous studies have suggested that blockade of the renin-angiotensin system may prevent diabetes in people with cardiovascular disease or hypertension.In a double-blind, randomized clinical trial with a 2-by-2 factorial design, we randomly assigned 5269 participants without cardiovascular disease but with impaired fasting glucose levels (after an 8-hour fast) or impaired glucose tolerance to receive ramipril (up to 15 mg per day) or placebo (and rosiglitazone or placebo) and followed them for a median of 3 years. We studied the effects of ramipril on the development of diabetes or death, whichever came first (the primary outcome), and on secondary outcomes, including regression to normoglycemia.The incidence of the primary outcome did not differ significantly between the ramipril group (18.1%) and the placebo group (19.5%; hazard ratio for the ramipril group, 0.91; 95% confidence interval [CI], 0.81 to 1.03; P=0.15). Participants receiving ramipril were more likely to have regression to normoglycemia than those receiving placebo (hazard ratio, 1.16; 95% CI, 1.07 to 1.27; P=0.001). At the end of the study, the median fasting plasma glucose level was not significantly lower in the ramipril group (102.7 mg per deciliter [5.70 mmol per liter]) than in the placebo group (103.4 mg per deciliter [5.74 mmol per liter], P=0.07), though plasma glucose levels 2 hours after an oral glucose load were significantly lower in the ramipril group (135.1 mg per deciliter [7.50 mmol per liter] vs. 140.5 mg per deciliter [7.80 mmol per liter], P=0.01).Among persons with impaired fasting glucose levels or impaired glucose tolerance, the use of ramipril for 3 years does not significantly reduce the incidence of diabetes or death but does significantly increase regression to normoglycemia. (ClinicalTrials.gov number, NCT00095654 [ClinicalTrials.gov].)."
1,"TITLE: Oral misoprostol for induction of labour at term: randomised controlled trial.ABSTRACT: To compare oral misoprostol solution with vaginal prostaglandin gel (dinoprostone) for induction of labour at term to determine whether misoprostol is superior.Randomised double blind placebo controlled trial.Maternity departments in three hospitals in Australia. Population Pregnant women with a singleton cephalic presentation at > or = 36+6 weeks' gestation, with an indication for prostaglandin induction of labour.20 mug oral misoprostol solution at ourly intervals and placebo vaginal gel or vaginal dinoprostone gel at six hourly intervals and placebo oral solution.Vaginal birth within 24 hours; uterine hyperstimulation with associated changes in fetal heart rate; caesarean section (all); and caesarean section for fetal distress.741 women were randomised, 365 to the misoprostol group and 376 to the vaginal dinoprostone group. There were no significant differences between the two treatment groups in the primary outcomes: vaginal birth not achieved in 24 hours (misoprostol 168/365 (46.0%) v dinoprostone 155/376 (41.2%); relative risk 1.12, 95% confidence interval 0.95 to 1.32; P = 0.134), caesarean section (83/365 (22.7%) v 100/376 (26.6%); 0.82, 0.64 to 1.06; P = 0.127), caesarean section for fetal distress (32/365 (8.8%) v 35/376 (9.3%); 0.91, 0.57 to 1.44; P = 0.679), or uterine hyperstimulation with changes in fetal heart rate (3/365 (0.8%) v 6/376 (1.6%); 0.55, 0.14 to 2.21; P = 0.401). Although there were differences in the process of labour induction, there were no significant differences in adverse maternal or neonatal outcomes.This trial shows no evidence that oral misoprostol is superior to vaginal dinoprostone for induction of labour. However, it does not lead to poorer health outcomes for women or their infants, and oral treatment is preferred by women.National Health and Medical Research Council, Perinatal Trials, PT0361."
1,"TITLE: Efficacy and safety of formoterol Turbuhaler when added to inhaled corticosteroid treatment in children with asthma.ABSTRACT: This double-blind, placebo-controlled, randomized, parallel-group, multicenter study was conducted in 302 children aged 6-11 years with asthma not optimally treated with inhaled corticosteroids alone. Patients continued with their existing dose of inhaled corticosteroids and in addition received placebo, formoterol 4.5 microg or formoterol 9 microg b.i.d., for 12 weeks (all delivered via Turbuhaler). Terbutaline was available as reliever medication. The primary efficacy variable was change from baseline in morning peak expiratory flow (PEF); secondary efficacy variables included forced expiratory volume in 1 sec (FEV(1)), serial PEF measured over 12 hr, evening PEF, asthma symptom score, and quality of life. Compared with placebo, formoterol 4.5 microg and 9 microg improved morning PEF by 8 l/min (P = 0.035) and 11 l/min (P = 0.0045), respectively. Evening PEF and FEV(1) were also significantly increased compared with placebo, with no statistically significant difference between formoterol doses. Lung-function improvements compared with placebo were greater in the middle of the day. Twelve-hour average serial PEF after 3 months increased by 24 l/min (95% CI, 9, 39 l/min) in the formoterol 9-microg group, and by 14 l/min (95% CI, 0, 29 l/min) in the formoterol 4.5-microg group. The incidence of severe exacerbations in both formoterol groups was numerically lower than in the placebo group, indicating that formoterol may have the potential to improve exacerbation control in children. Both formoterol doses were well-tolerated, and tolerance to the drug's bronchodilator effect was not observed. Formoterol provided sustained improvements in lung function and was well-tolerated in children with asthma suboptimally treated with inhaled corticosteroids alone."
1,"TITLE: Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial.ABSTRACT: To compare the effectiveness of an electrocautery strategy with ovulation induction using recombinant follicle stimulating hormone in patients with polycystic ovary syndrome.Randomised controlled trial.Secondary and tertiary hospitals in the Netherlands.168 patients with clomiphene citrate resistant polycystic ovary syndrome: 83 were allocated electrocautery and 85 were allocated recombinant follicle stimulating hormone.Laparoscopic electrocautery of the ovaries followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or induction of ovulation with recombinant follicle stimulating hormone.Ongoing pregnancy within 12 months.. The cumulative rate of ongoing pregnancy after recombinant follicle stimulating hormone was 67%. With only electrocautery it was 34%, which increased to 49% after clomiphene citrate was given. Subsequent recombinant follicle stimulating hormone increased the rate to 67% at 12 months (rate ratio 1.01, 95% confidence interval 0.81 to 1.24). No complications occurred from electrocautery with or without clomiphene citrate. Patients allocated to electrocautery had a significantly lower risk of multiple pregnancy (0.11, 0.01 to 0.86).The ongoing pregnancy rate from ovulation induction with laparoscopic electrocautery followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or recombinant follicle stimulating hormone, seems equivalent to ovulation induction with recombinant follicle stimulating hormone, but the former procedure carries a lower risk of multiple pregnancy."
1,"TITLE: Cigarette smoking during pregnancy in rural Nepal. Risk factors and effects of beta-carotene and vitamin A supplementation.ABSTRACT: We examined risk factors of smoking and the association between smoking and pregnancy-related and 6-month infant mortality in rural Nepal, where 30% women reported smoking during pregnancy.Cross-sectional analysis of risk factors associated with smoking status and health consequences of smoking, using prospective data collected as part of a randomized community trial to examine the effect of maternal vitamin A or beta-carotene supplementation on maternal mortality.Rural, southeastern plains of Nepal.A total of 17 767 women contributed at least one pregnancy during 3.5 y of the study. Data on cigarette or bidi (rolled tobacco) smoking were collected using a 7-day recall, twice during pregnancy. Associations between smoking status and maternal diet, morbidity profile, household socioeconomic status and serum concentration of retinol, carotenoids and tocopherols were examined. Further, relative risk (RR) and 95% confidence intervals (CI) were calculated to estimate supplement effects on pregnancy-related mortality, stratified by smoking status during pregnancy.Smokers were more likely to be older, illiterate and poor compared to nonsmokers. Fruit and vegetable consumption among smokers and nonsmokers did not vary. However, smokers were more likely to consume meat/fish/eggs and less likely to consume milk than nonsmokers. They were also more likely to report symptoms of vaginal bleeding, edema, severe headache and convulsions during pregnancy relative to nonsmokers. Mortality per 100,000 pregnancies appeared to be higher among smokers than nonsmokers in the placebo group (915 vs 584, RR=1.57, 95% CI: 0.80-3.08). beta-Carotene supplementation reduced pregnancy-related mortality both among smokers (RR=0.31 95% CI: 0.11-0.89) and nonsmokers (RR=0.41, 95% CI: 0.19-0.89). Similar results obtained with vitamin A supplementation were not statistically significant. Infant mortality up to 6 months was approximately 30% higher among smokers compared to nonsmokers in the placebo group both before and after adjusting for confounding factors. Neither supplement given to women reduced infant mortality.Cigarette smoking during pregnancy is associated with an increased risk of maternal and infant mortality in rural Nepal. beta-Carotene and to some extent vitamin A may reduce the risk of pregnancy-related mortality, but not infant mortality, among both smokers and nonsmokers."
1,"TITLE: Effect of caudal epidural xylazine on intraoperative distress and post-operative pain in Holstein heifers.ABSTRACT: To compare the effects of caudal epidural xylazine versus saline on tolerance of paravertebral nerve block and flank surgery and on post-operative pain in heifers used for a veterinary student training laboratory.Randomized controlled prospective study.Fourteen one-year-old, nongravid, healthy Holstein heifers, weighing 360 +/- 5 kg.Xylazine (0.05 mg kg(-1)) or 0.9% saline (5 mL) was injected using a caudal epidural technique to seven heifers undergoing a flank surgery. Nerve block of the right paravertebral fossa was performed using equal parts of lidocaine 2% and bupivacaine 0.5%. Heart and respiratory rates, rectal temperature, rumination frequency, and appetite were recorded before and at 4, 8, and 24 hours after surgery. Scores were recorded for: tolerance of local anesthesia injections (pre-operatively), sedation, ataxia and distress (intraoperatively, every 30 minutes), and pain (4, 8, and 24 hours post-operatively).The animals reaction to local anesthetic injection was judged to be less in the xylazine group by both an experienced observer (p<0.001) and student surgeons (p<0.01). The xylazine group required less local anesthetic (82.9 +/- 13.8 mL) versus the saline group (108.4 +/- 19.6 mL, p=0.035). Intraoperatively, xylazine heifers were more sedated at all times (p-values from <0.001 to 0.017), were more ataxic for the first 1.5 hours (p-values from <0.001 to 0.026), and lower in distress at all times (p-values from <0.001 to 0.007). No difference in post-operative pain or physiologic variables was found, except immediately post-operatively, rectal temperature was higher in the xylazine group (39.5 +/- 0.3 degrees C) than in the saline group (38.6 +/- 0.2 degrees C, p<0.001).Compared with epidural saline, caudal epidural xylazine reduced distress of anesthetic injection and surgical manipulation in heifers and an improvement in animal well-being was apparent. This effect may have been as a result of sedation. Pre-operative epidural xylazine did not appear to improve post-surgical analgesia in our study."
1,"TITLE: Repaglinide is more efficient than glimepiride on insulin secretion and post-prandial glucose excursions in patients with type 2 diabetes. A short term study.ABSTRACT: To compare the effect of Repaglinide vs Glimepiride on glucose- and meal-induced insulin secretion and on meal-test induced postprandial glucose excursions.After 2 weeks washout period, a 3-Month randomised, cross-over parallel group trial of R (1 mg x 2/die) vs G (2 mg/die) in 14 patients with type 2 diabetes ""naive"" in diet treatment was made.Both R and G significantly but similarly lowered fasting glucose levels and improved fasting plasma insulin levels vs baseline. Hyperglycemic clamp showed that both 1st (129.15 +/- 23.6 vs 106.90 +/- 18.6 pmol/L; p=0.01) and 2nd phase (189.42 +/- 34.4 vs 144.21 +/- 37.3 pmol/L; p=0.003) B-cell response to glucose as well as area under the curve (52.07 +/- 10.86 vs 39.54 +/- 10.27 micromol/L x 120'; p=0.005) were greater in R than G groups. Insulin action (4.0 +/- 1.1 vs 3.2 +/- 0.9 mg x Kg x 60'/microU/mL; p=0.046) was also improved by R than G administration. In the meal test, R therapy produced a more rapId induction of insulin secretion during the first part. In fact, the mean rise in insulin secretion peaked at 45 min in R (p=0.001 vs G) and at 60 min in G (p=0.001 vs R). Consequently, glucose spike at 60 min was higher in G group compared to glucose spike at 45 min in R group (p=0.002).Our study demonstrates that R is more efficient that G on improving glucose- and meal- induced insulin secretion as well as on controlling for postprandial glucose excursion."
1,"TITLE: Perioperative topical nitrate and sphincter function in patients undergoing transanal stapled anastomosis: a randomized, placebo-controlled, double-blinded trial.ABSTRACT: The use of transanal stapling devices may impair continence because of digital dilatation and/or instrumentation. This study assessed the effect of pharmacological dilatation of the sphincter prior to stapler insertion.A randomized, placebo-controlled, double-blinded study of 60 patients undergoing transanal stapled anastomosis was undertaken. Consenting patients were randomly assigned to receive a single intraoperative dose of topical 0.2 percent nitroglycerin (glyceryl trinitrate) ointment or nitroglycerin-free placebo. All patients were assessed preoperatively and postoperatively by clinical methods (Wexner incontinence scores and examination), anorectal manometry by a station pull-through technique, and endoanal ultrasonography.Intraoperative mean (+/-SEM) resting pressures (mmHg) were significantly reduced by nitroglycerin compared with prenitroglycerin levels (9.9 +/- 0.9 vs. 50.5 +/- 2.7; P = 0.002) or controls (56.0 +/- 3.2; P = 0.001). Twenty-one of the 28 controls (75 percent) but only 4 of the 32 patients in the nitroglycerin group (12.5 percent) required digital dilatation to insert the stapling instrument ( P = 0.003). Squeeze pressures were unaltered by the intervention but mean resting pressures were higher in the nitroglycerin group postoperatively (52.9 +/- 3.2 - 31.6 +/- 1.3 = 21.3 mmHg; 95 percent confidence interval, 14-27). Incontinence scores were lower in the nitroglycerin group at the 3-month (1.1 +/- 0.2 vs. 4.6 +/- 0.3; P = 0.003) and 12-month (0.9 +/- 0.1 vs. 4.4 +/- 0.3; P = 0.002) clinic visits.Preoperative nitroglycerin dilatation protects sphincter function in patients undergoing transanal stapled anastomoses."
1,"TITLE: A prospective randomised trial of atosiban versus hexoprenaline for acute tocolysis and intrauterine resuscitation.ABSTRACT: The aim of this study was to compare the efficacy and side effect profile of atosiban with hexoprenaline when used for intrauterine resuscitation of intrapartum fetal distress.Women in labour with acute intrapartum fetal distress detected by cardiotocography were randomly assigned to receive intravenous atosiban or hexoprenaline.Department of Obstetrics and Gynecology, Karl Franzens University of Graz and General Hospital Graz, Austria.One thousand and four hundred and thirty-one women with singleton pregnancy at term and cephalic presentation were enrolled in the study during October 2000 and May 2001.A prospective, randomised, pilot study with no a priori sample size calculation.Efficacy of treatment for stopping uterine contractions and the resumption of contractions determined by fetal heart rate monitoring.Tocolysis was achieved in 92% (12/13) of the women receiving atosiban and 100% (13/13) of those receiving hexoprenaline. Maternal tachycardia developed in 1/13 women, receiving atosiban and 10/13 women hexoprenaline. Hypertension occurred in 1/13 on atosiban and 3/13 women on hexoprenaline. Palpitations were only reported by 10/13 women receiving hexoprenaline. Uterine contractions resumed after 8 minutes (+/-3) in the atosiban group and 14 minutes (+/-4) in the hexoprenaline group (P < 0.001).Atosiban and hexoprenaline were similarly effective for stopping uterine contractions. Women receiving atosiban had significantly fewer adverse events than those receiving hexoprenaline. Uterine contractions resumed more promptly in the atosiban group. Considering the low incidence of mild maternal adverse events, atosiban may be an option for acute intrapartum tocolysis for fetal distress."
0,"TITLE: Activation of nuclear factor-kappa B and macrophage invasion in cyclosporin A-and tacrolimus-treated renal transplants.ABSTRACT: This retrospective study was designed to compare the efficacy of cyclosporin A (CyA) and tacrolimus (FK506) on chronic rejection (CR) associated with nuclear factor-kappa B (NF-kappaB) activation and macrophage invasion. Non-episodic day 50 protocol renal biopsy was performed in 63 consecutive patients with renal transplants from living donors, treated with either CyA or FK506. Southwestern histochemistry for NF-kappaB, immunostaining for CD68, and Banff classification were performed, and these findings were compared with outcome over 34 +/- 13 months. Compared with specimens from FK506-treated patients (n = 20), specimens from CyA-treated patients (n = 43) showed a significant increase in tubulointerstitial CD68-positive cells (1.5 +/- 0.9 vs. 0.9 +/- 0.8, p < 0.01), although no significant differences were observed in NF-kappaB activation. Specimens with Banff acute rejection (AR) grade > or = 1A (n = 20) showed increased macrophages (p < 0.01) compared with specimens with AR < 1A (n = 43). Specimens from patients with clinical AR prior to day 50 biopsy (n = 23) also showed increased macrophage invasion (p < 0.01) compared with specimens from patients without prior clinical AR (n = 40). The cumulative well-functioning (serum creatinine < 1.5 mg/dL) graft survival rate was significantly lower in patients with increased tubulointerstitial CD68-positive cells (n = 63, p < 0.05). Our findings suggest that tacrolimus is more effective than CyA against CR with respect to macrophage invasion and AR."
1,"TITLE: Safety and efficacy of intranasal ketamine for the treatment of breakthrough pain in patients with chronic pain: a randomized, double-blind, placebo-controlled, crossover study.ABSTRACT: Few placebo-controlled trials have investigated the treatment of breakthrough pain (BTP) in patients with chronic pain. We evaluated the efficacy and safety of intranasal ketamine for BTP in a randomized, double-blind, placebo-controlled, crossover trial. Twenty patients with chronic pain and at least two spontaneous BTP episodes daily self-administered up to five doses of intranasal ketamine or placebo at the onset of a spontaneous BTP episode (pain intensity > or =5 on a 0-10 scale). Two BTP episodes at least 48 h apart were treated with either ketamine or placebo. Patients reported significantly lower BTP intensity following intranasal ketamine than after placebo (P < 0.0001) with pain relief within 10 min of dosing and lasting for up to 60 min. No patient in the ketamine group required his/her usual rescue medication to treat the BTP episode, while seven out of 20 (35%) patients in placebo group did (P = 0.0135). Intranasal ketamine was well tolerated with no serious adverse events. After ketamine administration, four patients reported a transient change in taste, one patient reported rhinorrhea, one patient reported nasal passage irritation, and two patients experienced transient elevation in blood pressure. A side effect questionnaire administered 60 min and 24 h after drug or placebo administration elicited no reports of auditory or visual hallucinations. These data suggest that intranasal administration of ketamine provides rapid, safe and effective relief for BTP."
0,"TITLE: Effect of ingested fluid composition on exercise-related transient abdominal pain.ABSTRACT: The present study investigated the effect of ingested fluid composition on the experience of exercise-related transient abdominal pain (ETAP). Forty subjects, susceptible to ETAP, completed 4 treadmill exercise trials: a no-fluid trial and flavored water (FW, no carbohydrate, osmolality = 48 mosmol/L, pH = 3.3), sports drink (SD, freshly mixed Gatorade, 6% total carbohydrate, 295 mosmol/L, pH = 3.3), and reconstituted fruit juice (FJ, BERRI trade mark orange, 10.4 % total carbohydrate, 489 mosmol/L, pH= 3.2) trials. Measures of the experience of ETAP and gastrointestinal disturbances, particularly bloating, were quantified. The FJ was significantly (p =.01) more provocative of both ETAP and bloating than all other trials. There was no difference among the no-fluid, FW, and SD in the severity of ETAP experienced, although the difference between the no-fluid and SD approached significance at the.05 level (p =.056). There was a significant relationship between both the mean (r = 0.40, p =.01) and peak (r= 0.44, p=.01) levels of ETAP and bloating. When the level of bloating was controlled for, the FJ remained significantly (p =.01) more provocative of ETAP than the other conditions, with no difference between the FW and SD (p =.37). The results indicate that in order to avoid ETAP, susceptible individuals should refrain from consuming reconstituted fruit juices and beverages similarly high in carbohydrate content and osmolality, shortly before and during exercise. Further, the mechanism responsible for the heightened experience of ETAP in the FJ trial extends beyond a gastric mass explanation."
1,"TITLE: Five-year outcome of patients with acute myocardial infarction enrolled in a randomised trial assessing the value of abciximab during coronary artery stenting.ABSTRACT: The aim of the study was to investigate the long-term (five years) efficacy of glycoprotein IIb/IIIa inhibition with abciximab given as an adjunct therapy to coronary stenting in patients with acute myocardial infarction (MI) using the patient cohort of the Intracoronary Stenting and Antithrombotic Regimen-2 (ISAR-2) randomised trial.The patient cohort of ISAR-2 trial (401 patients) was followed up for 5 years after enrollment. There were 201 patients in the abciximab group (stenting plus abciximab) and 200 patients in the control group (stenting without abciximab). The primary end-point of the study was mortality at 5 years. Recurrent MI and target vessel re-vascularisation were also assessed at 5 years after enrollment. On the basis of the Kaplan-Meier analyses, the 5-year mortality was 17.8% (35 patients) in the group with abciximab and 14.6% (29 patients) in the control group (relative risk, 1.20 [95% confidence interval, 0.73-1.96]; P=0.47). The 5-year combined incidence of death, recurrent MI and target vessel re-vascularisation was 38.2% (76 patients) in the group of abciximab and 37.7% (75 patients) in the control group (relative risk, 0.97 [95% confidence interval, 0.70-1.33]; P=0.83). Multivariable analysis showed no significant independent association of abciximab with 5-year mortality (adjusted hazard ratio, 1.16 [95% confidence interval, 0.70-1.92]; P=0.55).These findings are not in support of a sustained clinical benefit at 5 years with the use of abciximab during coronary artery stenting in patients with acute MI."
1,"TITLE: A randomised, double-blind trial of topical ketorolac vs artificial tears for the treatment of episcleritis.ABSTRACT: To determine whether topical ketorolac (Acular) is more effective than artificial tears in treating the signs and symptoms of idiopathic episcleritis.In this prospective, randomised, double-blind study, 38 eyes of 37 patients presenting with idiopathic episcleritis were allocated to receive either topical ketorolac (0.5%) or artificial tears three times a day for 3 weeks. The severity of patients' signs (episcleral injection and the number of clock hours affected) were recorded at weekly intervals. Patients' symptoms (perceived redness and pain scores) were recorded using a daily diary.There was no significant difference in the ophthalmic signs between the two groups at each assessment, including intensity of episcleral injection and the number of clock hours affected. No significant difference was found in the time to halve the baseline redness intensity scores (4.4 vs 6.1 days, P=0.2) or pain scores (3.6 vs 4.3 days, P=0.55). Significantly more patients on ketorolac reported stinging at the first follow-up visit (P<0.001).Topical ketorolac is not significantly better than artificial tears in treating the signs or symptoms of idiopathic episcleritis."
1,"TITLE: Benefits of treating highly disabled migraine patients with zolmitriptan while pain is mild.ABSTRACT: Clinical trials of migraine therapy often require treatment when migraine pain intensity is moderate or severe, but many physicians find this practice artificial and patients often prefer to treat while pain is mild. This randomized, placebo-controlled study assessed the efficacy of zolmitriptan 2.5 mg in treating migraine while pain is mild, in patients who typically experience migraine attacks that are initially mild, but progress to moderate or severe. The intent-to-treat population comprised 280 patients (138 zolmitriptan; 148 placebo), with mean MIDAS grades of 29.6 (zolmitriptan) and 27.6 (placebo). Zolmitriptan 2.5 mg provided a significantly higher pain-free rate at 2 h (43.4% vs. 18.4% placebo; P < 0.0001). Significantly fewer zolmitriptan patients reported progression of headache pain to moderate or severe intensity 2 h postdose (53.7% vs. 70.4% placebo; P < 0.01), or required further medication within 24 h (46.4% vs. 71.1% placebo; P < 0.0001). The efficacy of zolmitriptan was more pronounced in patients treating during the first 15 min following pain onset. Adverse events were reported in 31.2% of patients treated with zolmitriptan (vs. 11.3% for placebo), and the incidence was lower in patients who treated early after attack onset. Zolmitriptan provides high efficacy when treating migraine while pain is mild, with the clinical benefits being more pronounced when treating early after migraine onset."
1,"TITLE: A comparison of the effects of oral montelukast and inhaled salmeterol on response to rescue bronchodilation after challenge.ABSTRACT: To compare the effects of addition of montelukast or salmeterol to inhaled corticosteroids (ICS) on the response to rescue beta2-agonist use after exercise-induced bronchoconstriction.A double-blind, placebo-controlled study was performed at 16 centers in the United States. Patients with asthma (n = 122, ages 15-58) whose symptoms were uncontrolled on Low-dose inhaled fluticasone and who had a history of exercise-induced worsening of asthma were randomized to receive either montelukast (10 mg once daily), salmeterol (50microg twice daily), or placebo for 4 weeks. Standardized spirometry after exercise challenge and beta2-agonist rescue was performed at baseline, week 1 and 4.Maximum achievable forced expiratory volume in 1 s (FEV1) percent predicted after rescue beta2-agonist improved in the montelukast (+1.5%) and placebo (+1.2%) groups at 4 weeks, but diminished in the salmeterol (-3.9%) group (P < 0.001). Although pre-exercise FEV1 was greatest with salmeterol (P = 0.10), patients taking montelukast had significantly greater protection from an exercise-induced decrease in FEV1 than those taking salmeterol (P < 0.001). Both the magnitude and rate of rescue bronchodilation were greater with montelukast compared with salmeterol (P < 0.001). Five minutes after rescue beta2-agonist, 92% of patients taking montelukast and 68% of those taking placebo had recovered to pre-exercise levels, whereas only 50% of those taking salmeterol had recovered to pre-exercise levels.In patients whose asthma symptoms remain uncontrolled using ICS, addition of montelukast permits a greater and more rapid rescue bronchodilation with a short-acting beta2-agonist than addition of salmeterol and provides consistent and clinically meaningful protection against exercise-induced bronchoconstriction."
1,"TITLE: Effect of methylprednisolone on return of sexual function after nerve-sparing radical retropubic prostatectomy.ABSTRACT: To determine whether postoperative methylprednisolone improves the recovery of sexual function after nerve-sparing radical retropubic prostatectomy.We randomized men undergoing bilateral nerve-sparing radical retropubic prostatectomy by a single surgeon to receive 6 days of placebo or methylprednisolone beginning on postoperative day 1. At 3, 6, and 12 months postoperatively, we assessed potency with the abbreviated International Index of Erectile Function questionnaire and urinary continence with participant-reported pad use. We used the chi-square test, Fisher's exact test, and the two-sample t test with equal variances for comparisons between study groups.No operative complications occurred and 70 (100%) of 70 participants experienced normal wound healing. The odds of being potent for participants who received methylprednisolone (n = 34) compared with those who received placebo (n = 36) did not significantly differ at 3 (odds ratio 0.29, 95% confidence interval 0.08 to 1.05), 6 (odds ratio 0.63, 95% confidence interval 0.17 to 2.4), or 12 (odds ratio 1.18, 95% confidence interval 0.29 to 4.8) months. The mean International Index of Erectile Function scores did not significantly differ at 3 (P = 0.08), 6 (P = 0.50), or 12 (P = 0.71) months. At 12 months, 74% of the methylprednisolone and 71% of the placebo participants were potent (P = 0.8). The proportions of participants who were continent did not differ significantly at 3 (P = 0.89), 6 (P = 0.25), or 12 (P = 0.49) months. At 12 months, 96% of the methylprednisolone and 100% of the placebo participants were continent.At doses sufficient to produce a systemic anti-inflammatory effect, postoperative methylprednisolone was not associated with improved potency at up to 12 months after bilateral nerve-sparing radical retropubic prostatectomy in men 40 to 60 years old."
1,"TITLE: Efficacy and safety of lercanidipine versus hydrochlorothiazide as add-on to enalapril in diabetic populations with uncontrolled hypertension.ABSTRACT: Angiotensin-converting enzyme inhibitors plus dihydropyridine calcium channel blockers or low-dose thiazide diuretics are considered first-line therapies in hypertensive diabetic patients as glucose metabolism is not relevantly affected. Most diabetic patients require at least two different drug classes to achieve the recommended target blood pressure of 130/85 mmHg. This controlled clinical trial investigated the calcium channel blocker lercanidipine versus hydrochlorothiazide (HCTZ) as add-on in diabetic patients with uncontrolled hypertension on enalapril monotherapy.Overall, 174 patients (18-80 years old, well-controlled diabetes type 1 or 2, mild to moderate hypertension) were included in a 2-week placebo run-in followed by 4 weeks on enalapril 20 mg. Subsequently, 135 non-responders (90 mmHg < or = mean sitting diastolic blood pressure < or = 109 mmHg) were randomized to 20 weeks of double-blind add-on therapy to enalapril with either lercanidipine 10 mg (n = 69) or HCTZ 12.5 mg (n = 66). The primary study objective was to prove non-inferiority of lercanidipine add-on versus HCTZ add-on in reducing sitting diastolic blood pressure; response rates and tolerability data were also observed.Both add-on treatments clearly decreased diastolic blood pressure to a greater extent than enalapril monotherapy (mean +/- SD changes at study end: lercanidipine, -9.3 mmHg; HCTZ, -7.4 mmHg); non-inferiority of lercanidipine versus HCTZ was formally proven. Blood pressure response rates reached 69.6% on enalapril plus lercanidipine as compared with 53.6% on enalapril plus HCTZ (difference between treatments, P > 0.05). Blood pressure of 130/85 mmHg or less was achieved in 30.4% of patients on lercanidipine add-on and in 23.2% of those randomized to HCTZ add-on (P > 0.05). Both treatment regimens were well tolerated.Lercanidipine add-on showed comparable efficacy to HCTZ add-on in diabetic patients with hypertension badly controlled on angiotensin-converting enzyme inhibitor monotherapy. The blood pressure response rates seemed to be somewhat higher following enalapril plus lercanidipine than enalapril plus HCTZ."
0,"TITLE: Symptoms of postpartum depression and breastfeeding.ABSTRACT: Despite important health benefits, the presence of depressive symptoms may decrease the prevalence of breastfeeding. The current study assessed the relationship between depressive symptoms and breastfeeding at 6 and 12 weeks postpartum. Participants were recruited from a cohort completing a clinical trial of calcium for prevention of preeclampsia. At 6 weeks postpartum, the Edinburgh Postnatal Depression Scale (EPDS) was completed by mail. At 12 weeks postpartum, the EPDS was completed at an outpatient visit. There was an inverse relationship between depressive symptoms and breastfeeding at 6 weeks postpartum (P<.001) but not at 12 weeks. This relationship persisted even after controlling for prior history of depression, increased life stress, and current psychoactive medication. The results suggest that depressive symptoms early in the postpartum period may lower the prevalence of breastfeeding."
1,"TITLE: Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial.ABSTRACT: Physicians may use either insulin or exenatide injections for patients with type 2 diabetes mellitus who have poor glycemic control despite taking oral blood glucose-lowering drugs.To compare effects of exenatide and insulin glargine on glycemic control in patients with type 2 diabetes mellitus that is suboptimally controlled with metformin and a sulfonylurea.26-week multicenter, open-label, randomized, controlled trial.82 outpatient study centers in 13 countries.551 patients with type 2 diabetes and inadequate glycemic control (defined as hemoglobin A1c level ranging from 7.0% to 10.0%) despite combination metformin and sulfonylurea therapy.Exenatide, 10 microg twice daily, or insulin glargine, 1 daily dose titrated to maintain fasting blood glucose levels of less than 5.6 mmol/L (<100 mg/dL).Hemoglobin A1c level, fasting plasma glucose level, body weight, 7-point self-monitored blood glucose, standardized test-meal challenge, safety, and tolerability.Baseline mean hemoglobin A1c level was 8.2% for patients receiving exenatide and 8.3% for those receiving insulin glargine. At week 26, both exenatide and insulin glargine reduced hemoglobin A1c levels by 1.11% (difference, 0.017 percentage point [95% CI, -0.123 to 0.157 percentage point]). Exenatide reduced postprandial glucose excursions more than insulin glargine, while insulin glargine reduced fasting glucose concentrations more than exenatide. Body weight decreased 2.3 kg with exenatide and increased 1.8 kg with insulin glargine (difference, -4.1 kg [CI, -4.6 to -3.5 kg]). Rates of symptomatic hypoglycemia were similar, but nocturnal hypoglycemia occurred less frequently with exenatide (0.9 event/patient-year versus 2.4 events/patient-year; difference, -1.6 events/patient-year [CI, -2.3 to -0.9 event/patient year]). Gastrointestinal symptoms were more common in the exenatide group than in the insulin glargine group, including nausea (57.1% vs. 8.6%), vomiting (17.4% vs. 3.7%) and diarrhea (8.5% vs. 3.0%).The trial was open-label and did not assess clinical complications related to diabetes. Of the 551 participants, 19.4% of those receiving exenatide and 9.7% of those receiving insulin glargine withdrew from the study. Only 21.6% of the insulin glargine group and 8.6% of the exenatide group achieved the target level for fasting plasma glucose of less than 5.6 mmol/L (<100 mg/dL).Exenatide and insulin glargine achieved similar improvements in overall glycemic control in patients with type 2 diabetes that was suboptimally controlled with oral combination therapy. Exenatide was associated with weight reduction and had a higher incidence of gastrointestinal adverse effects than insulin glargine."
1,"TITLE: Efficacy and tolerability of budesonide Clickhaler and Turbuhaler in adult asthma.ABSTRACT: New dry powder inhalers should be clinically comparable with established devices to ensure the continuity of effective therapy for asthma patients. This randomized, open, parallel group study compared the clinical efficacy and tolerability of budesonide delivered via Clickhaler or Turbuhaler dry powder inhalers in adults with mild to moderate stable asthma. Following a 4-week stabilizing period using budesonide Turbuhaler adults aged 18 years or older, who had been treated with inhaled corticosteroids for at least the previous 12 weeks, were randomized to receive budesonide twice daily (<or=1600 microg/day) via either Clickhaler (n=110) or Turbuhaler (n=112) for 12 weeks. Morning peak expiratory flow (PEF), evening PEF, asthma symptoms, and use of inhaled short-acting beta2-agonist were recorded daily by the patients on diary cards. Lung function and tolerability data were recorded at clinic visits following 4, 8, and 12 weeks' treatment. Efficacy was measured primarily by mean change from the run-in baseline in weekly morning PEF. Of the 222 patients randomized to treatment, 167 completed the study according to the protocol. Repeated-measures analysis of covariance indicated that the devices were clinically equivalent; a treatment difference of--2.3 L/min separated the group mean changes in weekly morning PEF (95% confidence interval--7.9 to 3.3). Secondary analyses also supported clinical comparability. This study demonstrates the comparable clinical efficacy and tolerability of budesonide Clickhaler and Turbuhaler devices in adult patients with stable asthma."
1,"TITLE: Open right colectomy is still effective compared to laparoscopy: results of a randomized trial.ABSTRACT: The primary goal of this study was to clarify whether a laparoscopic (LPS) approach could be considered the dominant strategy in patients undergoing right colectomy.Because few nonrandomized or small sized studies have been carried out so far, definitive conclusions about the role of LPS right colectomy cannot be drawn.Two hundred twenty-six patients, candidates for right colectomy, were randomly assigned to LPS (n = 113) or open (n = 113) resection. The postoperative care protocol was the same for both groups. Trained members of the surgical staff who were not involved in the study registered postoperative morbidity. Follow-up was carried out for 30 days after hospital discharge. The following costs were calculated: surgical instruments, operative room occupation, routine care, postoperative morbidity, and hospitalization.Conversion rate in the LPS group was 2.6% (3 of 113). Operative time (in minutes) was longer in the LPS group (131 vs. 112, P = 0.01). Postoperative morbidity rate was 18.6% in the open group and 13.3% in the LPS group (P = 0.31). Postoperative stay was one day longer in the open group (P = 0.002). No difference was found in postoperative quality of life. The additional operative charge in the LPS group was euro980 per patient randomized (euro821 for surgical instruments and euro159 for longer operative time). The savings in the LPS group was euro390 per patient randomized (euro144 for shorter length of hospital stay and euro246 for the lower cost of postoperative morbidity). The net balance resulted in a euro590 extra charge per patient randomly allocated to the LPS group.LPS slightly improved postoperative recovery. This translated into a savings that covered only 40% of the extra operative charge. Therefore, open right colectomy could be still considered an effective procedure."
1,"TITLE: Two-year follow-up of posterior capsule opacification after implantation of a hydrophilic or hydrophobic acrylic intraocular lens.ABSTRACT: To evaluate posterior capsule opacification (PCO) 2 years after cataract surgery following implantation of a hydrophilic or a hydrophobic single-piece acrylic intraocular lens (IOL) with a sharp edge.Phacoemulsification cataract surgery was performed in one eye of 120 patients with senile cataract in this prospective study. They were randomized to implantation of either a hydrophilic acrylic IOL (BL27; Bausch & Lomb, Rochester, NY, USA) or a hydrophobic acrylic IOL (AcrySof) SA60AT; Alcon Laboratories, Fort Worth, TX, USA). Two years after surgery, retroillumination images were obtained and PCO area and severity were evaluated using pocoman software. Best corrected visual acuity (VA) (both high-contrast [100%] and low-contrast [2.5%]), glare, laser flare and intraocular pressure were measured. Capsulotomy rates were recorded.Patients implanted with the hydrophilic IOL had a greater percentage area and severity of PCO compared with patients with the hydrophobic IOL (p < 0.001). There was no difference in PCO between men and women in the hydrophilic group. However, in the hydrophobic group, women had significantly more PCO than men (p < 0.05). Patients with the hydrophobic acrylic IOL had better high- and low-contrast visual activity (VA) (p < 0.01) and less glare (p < 0.001) than those with a hydrophilic acrylic IOL. Of the patients with the hydrophilic IOL, 42% underwent capsulotomy, compared with 10% in the hydrophobic group (p < 0.001).Two years after surgery, patients with the SA60AT hydrophobic acrylic IOL had less PCO and better high- and low-contrast VA than patients with the BL27 hydrophilic acrylic IOL."
1,"TITLE: Five-year follow up of a randomised controlled trial comparing NovaSure and ThermaChoice endometrial ablation.ABSTRACT: We have previously reported that NovaSure was more effective than balloon ablation at 12 months follow up in the treatment of menorrhagia. In this paper, we report the 5-year outcome of this study. The objective was to evaluate amenorrhoea rates, hysterectomy rate, and quality of life associated with the bipolar impedance-controlled endometrial ablation technique (NovaSure) in comparison with balloon ablation technique (ThermaChoice) at 5 years after administration.Double-blind randomised controlled trial, 2:1 randomisation NovaSure versus ThermaChoice.A teaching hospital with 500 beds in The Netherlands.A total of 126 premenopausal women suffering from menorrhagia with a pictorial blood loss assessment count > or = 150 without intracavitary abnormalities.Women were randomly allocated to bipolar radio-frequency ablation and balloon ablation in a 2:1 ratio.The main outcome measures were amenorrhoea rate, hysterectomies, and health-related quality of life (HRQol) as reported at 5 year follow up.At 5 years of follow up, the total response rate was 96% in the bipolar group and 90% in the balloon group. Amenorrhoea was reported in the bipolar group by 48% of women and in the balloon arm by 32% (relative risk 1.6 [.93-2.6]). There were eight women in the bipolar group (9.8%) and five in the balloon group (12.9%) who had undergone a hysterectomy. Furthermore, there was a significant equal improvement of HRQoL over time in both groups.At 5 years follow up, bipolar thermal ablation was superior over balloon ablation in the treatment of menorrhagia."
0,"TITLE: Leukocyte count and vascular risk in symptomatic intracranial atherosclerosis.ABSTRACT: Few data exist about the prognostic value of serum white blood cell (WBC) count among patients with symptomatic cerebrovascular disease. We investigated the relationship between WBC count and vascular risk in patients with symptomatic intracranial atherosclerotic disease enrolled in the Warfarin-Aspirin Symptomatic Intracranial Disease(WASID) study.The relationships between baseline serum WBC count (categorized into quartiles) and both ischemic stroke alone and the combined endpoint of ischemic stroke, myocardial infarction or vascular death were evaluated using the log-rank test and Cox proportional hazards regression.Compared with the quartile with the lowest WBC counts at baseline (< or =5.9 x 10(9)/l), WASID subjects in both upper WBC quartiles (7.3-8.8; > or =8.9 x 10(9)/l) were more likely to be younger (p = 0.022), diabetic (p = 0.013), on statin treatment (p = 0.015), or have higher mean body mass index (p = 0.015) and triglyceride (p = 0.0065) values. The rate of the primary endpoint was greater among WASID subjects in the upper two WBC quartiles compared with the lower two quartiles (28 vs. 16%, hazard ratio = 1.7; 95% CI = 1.2-2.5, p = 0.003). After adjusting for baseline factors found to be significantly related to the time of primary endpoint in multivariate analysis, both upper WBC quartiles (vs. lowest quartile) were independently associated with a greater risk for the primary endpoint (hazard ratio of 1.5; 95% CI = 1.06-2.2, p = 0.024).An elevated WBC count at study entry was associated with an increased risk of stroke and vascular death in patients with symptomatic intracranial atherosclerotic disease enrolled in the WASID trial."
1,"TITLE: Salmeterol/fluticasone propionate via Diskus once daily versus fluticasone propionate twice daily in patients with mild asthma not previously receiving maintenance corticosteroids.ABSTRACT: The efficacy and safety of twice-daily inhaled salmeterol/fluticasone propionate combination (SFC) therapy have been well established in the treatment of adults and adolescents with asthma. Once-daily administration of SFC could also be appropriate in patients with mild persistent asthma. This study aimed to investigate whether once-daily SFC 50 microg/100 microg was at least as effective as fluticasone propionate (FP) 100 microg twice daily, and more effective than twice-daily placebo, over 52 weeks as initial maintenance therapy in patients with mild persistent asthma.This was a randomized, double-blind, double-dummy, placebo-controlled, multicentre, parallel-group study carried out in primary and secondary care. Patients aged between 12 and 79 years with a documented clinical history of asthma for > or =6 months who were currently receiving inhaled short-acting beta(2)-adrenoceptor agonists only were enrolled. Patients were randomized to receive either once-daily inhaled SFC 50 microg/100 microg, twice-daily inhaled FP 100 microg (i.e. twice the dose of FP compared with SFC) or placebo for 52 weeks. The primary efficacy endpoints were mean morning peak expiratory flow (PEF), as recorded by patients prior to the use of bronchodilator or study medication, and the rate of investigator-recorded asthma exacerbations.Patients receiving twice-daily FP and once-daily SFC showed greater improvements in mean morning PEF compared with those receiving placebo (FP, difference in means 20.1 L/min; 95% CI 14.7, 25.5; p < 0.001; SFC, difference in means 14.8 L/min; 95% CI 9.4, 20.2; p < 0.001). The difference in adjusted mean PEF between once-daily SFC and twice-daily FP was -5.3 L/min (95% CI -9.1, -1.6). PEF results showed that once-daily SFC was non-inferior to twice-daily FP. Over 52 weeks, there was a 35% reduction in exacerbation rates with once-daily SFC, which in this respect demonstrated superiority over placebo (p < 0.001). Non-inferiority between once-daily SFC and twice-daily FP with respect to exacerbation rates was not shown. Once-daily SFC significantly improved clinic forced expiratory flow between 25% and 75% of forced vital capacity (difference in means 0.129 L/s; p < 0.001) and clinic PEF (difference in means 10.8 L/min; p < 0.001) compared with twice-daily FP. Both treatments were well tolerated and the safety profile of each was similar to that seen with placebo.In patients with mild persistent asthma not previously receiving maintenance therapy, once-daily SFC 50 microg/100 microg is an effective treatment compared with placebo, and was non-inferior to twice-daily FP 100 microg with respect to mean morning PEF. However, in this study, once-daily SFC was not as efficacious as twice-daily FP in reducing asthma exacerbation rates. This study confirms the benefits of regular maintenance treatment in patients with mild persistent asthma."
1,"TITLE: Infusion of albumin attenuates changes in serum protein binding of drugs in surgical patients compared with volume replacement with HAES.ABSTRACT: In vitro studies have indicated that stabilizers present in pharmaceutical-grade albumin influence albumin-binding capacity for highly protein bound drugs.A randomized study including 40 surgical patients, treated with either albumin or starch solutions, was performed. Volumes of colloids were given based on clinical indication. Blood samples were obtained. The serum samples were analyzed to determine the concentrations of albumin, tryptophan, N-acetyl-dl-tryptophan, caprylate and alpha-1-acid glycoprotein as well as in vitro drug binding of naproxen, warfarin and digitoxin.During surgery, the albumin concentration declined in the Starch group from 26.8 to 15.3 g/l. It remained unchanged in the Albumin group (29.2 g/l). The two groups were analyzed with the pre-operative sample acting as the control. In the starch group, the percent free concentration of the drugs increased significantly (P<0.01): for naproxen from 0.2% to 0.6%, for warfarin from 1.2% to 1.8% and for digitoxin from 6.8% to 11.1%. In the Albumin group, the % free fraction of naproxen doubled from 0.1% to 0.2% (P<0.05), whereas the % free fraction of warfarin decreased from 1.1% to 1.0% (P<0.05). The free fraction of digitoxin remained unchanged.Infusion of albumin during surgery resulted in maintained albumin values and almost maintained binding parameters for the study drugs, although some statistically significant changes were found. The use of starch solutions, however, led to in a reduction in albumin values and a significant reduction in binding parameters."
1,"TITLE: Community-based weight management in long-term heart transplant recipients: a pilot study.ABSTRACT: Heart transplant recipients often suffer from obesity, dyslipidemia, and hypertension thought to be related to triple-drug immunosuppression and poor adherence to diet and exercise. A lifestyle intervention that allows recipients to attend a community-based weight management program may improve health outcomes.To determine (1) the effects of attending a community-based weight management program on weight, systolic and diastolic blood pressure, and the lipid profile; and (2) the feasibility of a community-based program for weight management.Twenty-one patients (81% male; age 57 years, 99.7 months since transplantation) participated in a randomized clinical trial and received either weight management counseling (control) or a 6-month scholarship to a structured commercial program (treatment). Using simple analysis of covariance models, group differences were assessed and reported as marginal means.At baseline, there were no demographic differences between groups. There were no differences in outcome variables except weight (control, 102.1 kg vs treatment, 98.3 kg; P= .05). After 6 months, significant differences were found in weight (control, 100.5 kg vs treatment, 95.6 kg; P= .047) and high-density lipoprotein cholesterol (control, 40.6 mg/dL vs treatment, 49.1 mg/dL; P= .044). A marginally significant difference was found in systolic blood pressure (control, 138 mm Hg vs treatment, 121 mm Hg; P= .07). A decrease in diastolic blood pressure (6 mm Hg) was attributed to treatment effect (P = .16). No differences were noted in total cholesterol, triglycerides, or low-density lipoprotein cholesterol.The structured commercial program appears to be an effective, feasible alternative to usual care. Findings need to be confirmed in future research with a larger sample."
1,"TITLE: Role of nitric oxide in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass.ABSTRACT: Nitric oxide is the most potent vasodilator among inflammation-mediated vasoactive substances. Tepid cardiopulmonary bypass has been known to maintain low vascular resistance and nitric oxide may also be involved. There has been no previous clinical study elucidating a role of nitric oxide in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass.Thirty-one patients who underwent valvular surgery were randomly divided into two comparable groups; consisting of the hypothermic cardiopulmonary bypass (28 degrees C:14 patients) and the tepid cardiopulmonary bypass group (34 degrees C:17 patients). The serum levels of nitric oxide (NO(2)(-)+NO(3)(-)), prostaglandin E(2), bradykinin, 6-keto PGF1alpha, thromboxane B(2), endothelin-1, systemic vascular resistance index were measured before, 0, 12 and 24 h after cardiopulmonary bypass.The pattern of change in systemic vascular resistance index and nitric oxide during and after cardiopulmonary bypass were significantly different between the two groups (P=0.0008, P=0.02). The tepid group showed significantly lower levels of systemic vascular resistance index after cardiopulmonary bypass than the hypothermic group (0 h: 2278+/-735 vs. 4387+/-1289, 12 h: 1827+/-817 vs. 2817+/-1146 and 24 h: 1690+/-548 vs. 2761+/-641 dyne s cm(-5) m(2), P=0.0001, P=0.03, P=0. 0006). The nitric oxide levels were significantly higher at 0, 12 and 24 h after cardiopulmonary bypass in the tepid group than those in the hypothermic group (84.7+/-33.3 vs. 46.3+/-18.1, 69.8+/-31.1 vs. 40.1+/-17.5 and 80.1+/-38.5 vs. 39.1+/-15.6 micromol/l, P=0.008, P=0.03, P=0.01). The prostaglandin E(2) levels in the tepid group was significantly higher just after cardiopulmonary bypass than that in the hypothermic group (37.3+/-20.0 vs. 15.8+/-8.6 pg/ml, P=0.02). The bradykinin level in the hypothermic group was significantly higher just after cardiopulmonary bypass than that in the tepid group (2.40+/-0.32 vs. 1.85+/-0.21 log(10) (pg/ml), P=0.005). Only nitric oxide showed a significant negative correlation with the systemic vascular resistance index both during and after cardiopulmonary bypass (r=-0.60, P<0.0001) as compared with prostaglandin E(2) and bradykinin.These findings demonstrated that serum nitric oxide levels in tepid cardiopulmonary bypass were significantly higher than those in hypothermic cardiopulmonary bypass. Nitric oxide correlated with systemic vascular resistance. Thus, nitric oxide may play a pivotal role in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass."
1,"TITLE: Efficacy and safety of two whole IgG polyvalent antivenoms, refined by caprylic acid fractionation with or without beta-propiolactone, in the treatment of Bothrops asper bites in Colombia.ABSTRACT: The efficacy and safety of two whole IgG polyvalent antivenoms (A and B) were compared in a randomised, blinded clinical trial in 67 patients systemically envenomed by Bothrops asper in Colombia. Both antivenoms were fractionated by caprylic acid precipitation and had similar neutralising potencies, protein concentrations and aggregate contents. Antivenom B was additionally treated with beta-propiolactone to lower its anticomplementary activity. Analysing all treatment regimens together, there were no significant differences between the two antivenoms (A=34 patients; B=33 patients) in the time taken to reverse venom-induced bleeding and coagulopathy, to restore physiological fibrinogen concentrations and to clear serum venom antigenaemia. Blood coagulability was restored within 6-24 h in 97% of patients, all of whom had normal coagulation and plasma fibrinogen levels 48 h after the start of antivenom treatment. Two patients (3.0%) had recurrent coagulopathy and eight patients suffered recurrence of antigenaemia within 72 h of treatment. None of the dosage regimens of either antivenom used guaranteed resolution of venom-induced coagulopathy within 6 h, nor did they prevent recurrences. A further dose of antivenom at 6 h also did not guarantee resolution of coagulopathy within 12-24 h in all patients. The incidence of early adverse reactions (all mild) was similar for both antivenoms (15% and 24%; P>0.05)."
0,"TITLE: Predictors of sustained intraocular pressure elevation in eyes receiving intravitreal anti-vascular endothelial growth factor therapy.ABSTRACT: To determine the intravitreal anti-vascular endothelial growth factor (VEGF) injection techniques and preferences within the retinal community and to identify potential factors associated with the development of sustained intraocular pressure (IOP) elevation in patients treated with intravitreal anti-VEGF therapy for neovascular age-related macular degeneration (AMD).Cross-sectional physician survey.Five hundred and thirty retina specialists spanning both private and academic practices were surveyed regarding current anti-VEGF intravitreal injection protocols, including the anti-VEGF drug of choice, needle gauge, injection volume, injection technique, and self-reported prevalence of sustained IOP elevation. Multivariate logistic regressions were performed to assess the potential influence of these factors on long-term IOP.Two hundred ninety-two specialists (55%) reported believing that intravitreal anti-VEGF therapy may cause sustained IOP elevation. Of these responses, the most common reported prevalence was 1%-2% (48%), followed by 3%-5% (34%). There was no relationship between the frequency of sustained IOP elevation and anti-VEGF drug of choice. Physicians who injected greater than 0.05 cc in less than 1 second were 5.56 times more likely to observe a high frequency of sustained IOP elevation (P=.006, 95% CI 1.64-18.89).Based on physician survey data, serial anti-VEGF injections using higher injection volumes with a rapid injection technique may potentially lead to sustained IOP elevation. The underlying mechanism for this complication may be injury to the trabecular meshwork resulting from rapid elevations in IOP. Further investigation of the relationship between injection techniques and sustained IOP elevation in the form of retrospective or prospective clinical studies is warranted."
1,"TITLE: Varenicline efficacy and safety among methadone maintained smokers: a randomized placebo-controlled trial.ABSTRACT: To test the efficacy and safety of varenicline as an aid to smoking cessation in methadone-maintained smokers.Multicenter, randomized, double-blind, placebo-controlled trial with random assignment to 12 weeks of varenicline 1 mg twice daily (n = 57) or matched placebo (n = 55), with in-person and telephone counseling.Urban methadone programs in the Bronx, New York City, New York, USA.Methadone maintenance patients, smoking ≥5 cigarettes/day, interested in quitting, stable in methadone treatment, without current Axis I psychiatric disorders, suicidal ideation or recent suicide attempts.Seven-day point prevalence abstinence verified by expired carbon monoxide (CO) < 8 parts per million at week 12 (primary outcome); carbon monoxide (CO)-verified abstinence, cigarettes/day, incident Axis I psychiatric illness, suicidal ideation or serious adverse events (SAEs) at weeks 2, 4, 8, 12 or 24 (secondary outcomes).Baseline demographic, smoking and clinical factors were similar between groups. Retention at 24 weeks was 90%. Subjects receiving varenicline were more likely than those receiving placebo to achieve abstinence (10.5 versus 0%, P = 0.03; effect size 10.5%, 95% confidence interval (CI) = 4.4-19.3%) and to reduce smoking (median five versus two cigarettes/day, P < 0.001) at 12 weeks. These effects were not maintained after drug treatment ceased. Incident psychiatric illness (OR= 0.84, 95% CI = 0.16, 4.4) and suicidality [odds ratio (OR) = 0.88, 95% CI 0.2, 3.9] were not different between groups. There were no psychiatric or cardiac SAEs.Varenicline can aid short-term smoking abstinence in methadone-maintained smokers."
1,"TITLE: The optimum initial pediatric epidural bolus: a comparison of four local anesthetic solutions.ABSTRACT: There is no consensus on the concentration or type of local anesthetic used for initiation of epidural anesthesia. The aim of this randomized, double-blind, controlled trial was to compare the clinical effectiveness of epidural administration of both levobupivacaine and bupivacaine in 0.2% and 0.25% concentrations in pediatric patients undergoing abdominal and urological surgery.One hundred and forty-one children scheduled for lower abdominal and urological surgery were randomized to receive 0.4-0.6 ml.kg(-1) epidural, 0.25% bupivacaine, 0.2% bupivacaine, 0.25% levobupivacaine or 0.2% levobupivacaine. Initial epidural volumes, onset times; hemodynamic consequences, postoperative pain scores and degree of residual postoperative motor block were all recorded.There were no significant differences in the proportion of children with effective analgesia after incision [0.20% bupivacaine 97%, 0.25% bupivacaine 94%, 0.20% levobupivacaine 91%, 0.25% levobupivacaine 92% (P=0.73)] when a median volume of 0.55 ml.kg(-1) was used. There was no association between the volume used for thoracic, lumbar, or sacral epidural anesthesia and the effectiveness of the agents used. There was a significantly greater incidence of pain on awakening with the 0.2% solutions compared with the 0.25% solutions, but no differences in the incidence of residual motor block between groups.While there is no difference in the proportion of effective surgical anesthesia, the lower incidence of pain and distress with the 0.25% solutions suggests that this concentration has clinical advantages over the 0.2% solutions for pediatric epidural anesthesia."
1,"TITLE: Randomized evaluation of atorvastatin in patients with coronary heart disease: a serial intravascular ultrasound study.ABSTRACT: It is unclear whether a marked reduction of low-density lipoprotein-cholesterol (LDL-C) in patients with coronary heart disease (CHD) and mild hypercholesterolemia leads to less progression of atherosclerosis.Patients with CHD and hypercholesterolemia (100<LDL-C<140 mg/dl) who underwent coronary angiography (CAG) and intravascular ultrasound (IVUS) were randomly assigned to the atorvastatin (10-20 mg/day) group or ;usual care' group. After 12 months 58 patients had follow-up CAG and IVUS studies that could be evaluated. Cross-sectional areas of the vessel, lumen, and plaque were measured at 1-mm intervals, and volumetric calculations were based on Simpson's rule. After 12 months, the mean reduction of LDL-C was 34% in the atorvastatin group and 0% in the usual care group (p<0.01). The mean absolute plaque volume showed a larger increase in the usual care group than in the atorvastatin group (atorvastatin -1.4+/-11.6 mm3, usual care 7.6+/-10.3 mm3; p<0.01). Vessel volume also showed a larger increase in the usual care group than in the atorvastatin group (atorvastatin 2.2+/-10.9 mm3, usual care 10.9+/-17.7 mm3; p=0.03).Atorvastatin treatment prevented the further progression of atherosclerosis by maintaining LDL-C below 100 mg/dl in patients with CHD and hypercholesterolemia (100<LDL-C<140 mg/dl)."
1,"TITLE: Randomized comparison of the continuous vs point-by-point radiofrequency ablation of the cavotricuspid isthmus for atrial flutter.ABSTRACT: Achievement of complete conduction block in the cavotricuspid isthmus (CTI) is a curative ablation technique in patients with common atrial flutter (AFL). The present study was a prospective comparison of the efficacy of 2 ablation strategies in patients with common AFL: the continuous and point-by-point radiofrequency (RF) delivery techniques.Forty patients with common AFL were randomly assigned to either a group treated with a continuous RF delivery or to a group undergoing point-by-point RF ablation. In the first group, the RF energy was continuously delivered during a slow drag of the catheter tip from the tricuspid annulus to the inferior vena cava without stopping the application. In the second group, the RF ablation was performed using a point-by-point approach for 60 s at each point. All patients underwent ablation with an 8-mm-tip ablation catheter with a power limit of 50 W and a target temperature of 55 degrees C. Complete CTI conduction block was achieved in all patients. The patient characteristics, including the anatomy of the CTI estimated by 3-dimensional computed tomography, were no different between the 2 groups. The procedure time (time from the start of RF delivery to the completion of CTI block), fluoroscopic time and total RF energy required to create the CTI block between the continuous and point-by-point groups were 7.3+/-5.6 vs 21.2+/-22.2 min (p<0.01), 7.2+/-4.4 vs 16.2+/-14.1 min (p<0.05), and 15,631+/-6,001 vs 24,072+/-16,140 joules (p<0.05), respectively. There were no complications or recurrences of AFL during the follow-up period in any of the patients.In the curative treatment of common AFL, the continuous RF delivery approach could shorten the procedure and fluoroscopic time and reduce the total RF energy compared with the point-by-point RF ablation approach."
1,"TITLE: Effects of strict blood pressure control by a long-acting calcium channel blocker on brain natriuretic peptide and urinary albumin excretion rate in Japanese hypertensive patients.ABSTRACT: Strong adherence to antihypertensive therapy has been shown to reduce the frequency of cardiovascular events by strictly controlling blood pressure. Although calcium channel blockers (CCBs) are among the most popular antihypertensive drugs in Japan, few trials have been conducted using high CCB doses in Japanese patients. In this study, we administered amlodipine 5 mg or 10 mg to patients with hypertension in order to compare the efficacy and tolerability of low and high doses, and measured two surrogate markers of hypertensive target organ damage, i.e., brain natriuretic peptide (BNP) as a risk marker of cardiac overload and microalbuminuria as a measure of renal damage. Seventy-two patients were randomly assigned to either amlodipine 5 mg (n = 35) or 10 mg (n = 37) dose groups. The latter group achieved greater reductions in clinic as well as both morning and evening home BP levels without an increase in pulse rate (the differences between the two groups in clinic/morning/evening systolic BP were 4.7/4.7/5.4 mmHg, and for diastolic BP they were 4.2/3.6/3.8 mmHg). Reductions in BNP and urinary albumin/creatinine ratio (UAR) levels were significantly correlated with the reductions in systolic BP levels (BNP, clinic/morning BP: r = 0.256, p = 0.030/r = 0.330, p = 0.005; UAR, clinic BP: r = 0.316, p = 0.007). In conclusion, the higher dose (10 mg) of amlodipine induced greater reductions in all BP levels than did the lower dose, without increasing the pulse rate. These additional reductions were significantly correlated with reductions in hypertensive cardiac overload, as evaluated by BNP levels, and a reduction in renal damage, as evaluated by microalbuminuria levels. Moreover, a reduction in the microalbuminuria may have occurred concomitant with a reduction in clinic systolic BP level."
1,"TITLE: Can validated wrist devices with position sensors replace arm devices for self-home blood pressure monitoring? A randomized crossover trial using ambulatory monitoring as reference.ABSTRACT: Electronic devices that measure blood pressure (BP) at the arm level are regarded as more accurate than wrist devices and are preferred for home BP (HBP) monitoring. Recently, wrist devices with position sensors have been successfully validated using established protocols. This study assessed whether HBP values measured with validated wrist devices are sufficiently reliable to be used for making patient-related decisions in clinical practice.This randomized crossover study compared HBP measurements taken using validated wrist devices (wrist-HBP, Omron R7 with position sensor) with those taken using arm devices (arm-HBP, Omron 705IT), and also with measurements of awake ambulatory BP (ABP, SpaceLabs), in 79 subjects (36 men and 43 women) with hypertension. The mean age of the study population was 56.7 +/- 11.8 years, and 33 of the subjects were not under treatment for hypertension.The average arm-HBP was higher than the average wrist-HBP (mean difference, systolic 5.2 +/- 9.1 mm Hg, P < 0.001, and diastolic 2.2 +/- 6.7, P < 0.01). Twenty-seven subjects (34%) had a > or =10 mm Hg difference between systolic wrist-HBP and arm-HBP and twelve subjects (15%) showed similar levels of disparity in diastolic HBP readings. Strong correlations were found between arm-HBP and wrist-HBP (r 0.74/0.74, systolic/diastolic, P < 0.0001). However, ABP was more strongly correlated with arm-HBP (r 0.73/0.76) than with wrist-HBP (0.55/0.69). The wrist-arm HBP difference was associated with systolic ABP (r 0.34) and pulse pressure (r 0.29), but not with diastolic ABP, sex, age, arm circumference, and wrist circumference.There might be important differences in HBP measured using validated wrist devices with position sensor vs. arm devices, and these could impact decisions relating to the patient in clinical practice. Measurements taken using arm devices are more closely related to ABP values than those recorded by wrist devices. More research is needed before recommending the widespread use of wrist monitors in clinical practice. American Journal of Hypertension doi:10.1038/ajh.2008.176American Journal of Hypertension (2008); 21, 7, 753-758. doi:10.1038/ajh.2008.176."
1,"TITLE: Randomized, multicenter study comparing expanded polytetrafluoroethylene-covered endoprosthesis placement with percutaneous transluminal angioplasty in the treatment of superficial femoral artery occlusive disease.ABSTRACT: To compare the safety and effectiveness of the Viabahn endoprosthesis with that of percutaneous transluminal angioplasty (PTA) alone in the treatment of symptomatic peripheral arterial disease (PAD) affecting the superficial femoral artery (SFA).From 1998 to 1999, patients with symptomatic SFA PAD were enrolled in a prospective, multicenter randomized study and underwent either PTA alone (n = 100) or PTA followed by stent-graft placement (expanded polytetrafluoroethylene/nitinol self-expanding stent-graft) (n = 97) for stenoses or occlusions of the SFA that were 13 cm long or shorter. At baseline, there were no significant differences between the PTA and stent-graft treatment groups, including chronic limb ischemia status and treated lesion length.The stent-graft group had a significantly higher technical success rate (95% vs 66%, P < .0001) and 1-year primary vessel patency rate at duplex ultrasonography (65% vs 40%, P = .0003). A patency benefit was seen for lesions at least 3 cm long. At 12 months, chronic limb ischemia status was 15% further improved for the stent-graft group (P = .003). There were no significant differences between treatment groups with regard to the occurrence of early or late major adverse events.In this multicenter study, the patency, technical success, and clinical status results obtained with stent-grafts were superior to those obtained with PTA alone."
1,"TITLE: Normobaric hypoxia training causes more weight loss than normoxia training after a 4-week residential camp for obese young adults.ABSTRACT: Intermittent normobaric hypoxia training, an alternative to altitude training for athletes, may be beneficial to treat overweight and obesity. The purpose of this study is to investigate whether normobaric hypoxia training combined with low-caloric diet has the additive effect on weight loss compared with normoxia training in obese young adults.Twenty-two subjects (age 17-25 years, body mass index >27.5 kg/m(2)) were recruited for a 4-week residential camp of weight loss with low caloric intake, and trained at 60-70% maximal heart rate of aerobics and 40-50% of maximal strength of training. They were randomly assigned to either a normobaric hypoxia (HT, FiO2 = 16.4-14.5 %) or normoxia training group (NT, FiO2 = 21%), and subjects in HT and NT groups experienced weekly 16-h normoxia and 6-h hypoxia or 22-h normoxia training, respectively. Body composition, resting blood pressure (BP) and brachial-ankle pulse wave velocity (baPWV) were determined before and after the intervention.Weight loss was found in HT (-6.9 kg or -7.0%, p < 0.01) and NT groups (-4.3 kg or -4.2%, p < 0.01) significantly, and the former lost more weight than the latter (p < 0.01). Hypoxia training improved systolic BP (-7.6%) and mean BP (-7.1%) significantly (p < 0.05) despite having no effect on baPWV.Four weeks of normobaric hypoxia residential training with low caloric diet has an additive improvement on weight loss. It seems that normobaric hypoxia training might be a promising method to treat obesity."
0,"TITLE: The Diet of Higher Insulinemic Potential Is Not Associated with Worse Survival in Patients with Stage III Colon Cancer (Alliance).ABSTRACT: Hyperinsulinemia is considered to be important in the development of colon cancer, but few studies have investigated the associations of hyperinsulinemia with colon cancer survival via dietary scores.Empirical dietary index for hyperinsulinemia (EDIH) was derived to assess the insulinemic potential of daily diets reflecting the long-term insulin exposure, with higher (more positive) scores indicating higher insulinemic diets. We prospectively estimated the HRs and 95% confidence intervals (CI) to investigate the association of EDIH with disease-free, recurrence-free, and overall survival among patients with stage III colon cancer (1999-2009) enrolled in a randomized adjuvant chemotherapy trial (CALGB 89803).Of 1,024 patients (median follow-up: 7.3 years), 311 died, 350 had recurrences, and 394 had events for disease-free survival. Compared with patients in the lowest quintile of EDIH, the corresponding HRs of patients in the highest quintile for disease-free survival events, cancer recurrence, and overall mortality were 0.80 (95% CI, 0.56-1.15), 0.76 (95% CI, 0.51-1.11), and 0.77 (95% CI, 0.52-1.14).Higher EDIH was not associated with the risk of colon cancer recurrence or mortality in this population of patients with stage III colon cancer.EDIH, as a measure of dietary insulinemic potential, may be associated with colon cancer risk but not survival in patients with late-stage colon cancer."
1,"TITLE: Comparison between shockpulse and pneumatic lithotripsy in percutaneous nephrolithotomy.ABSTRACT: To compare the effectiveness and safety of shockpulse with pneumatic lithotripsy in percutaneous nephrolithotomy.A prospective randomized comparative study was performed in Department of Urology, Bir Hospital for 1-year duration with 61 patients in shockpulse (Group 1) and 58 patients in pneumatic lithoclast (Group 2) groups, respectively. Patient's demographics, stone characteristics, hemoglobin drop, hospital stay, operative duration, stone fragmentation time and postoperative complications were compared.The two groups did not differ significantly in terms of patient's demographic and stone characteristics. The mean hemoglobin drop was 1.96 ± 1.48 g/dl in Group 1 and 2.32 ± 1.38 g/dl in Group 2 (p = 0.16) and hospital stay was 3.14 ± 1.42 days in Group 1 and 3.29 ± 1.82 days in Group 2 (p = 0.62). The number of cases that required multiple tracts were six (9.8%) in Group 1 and 12 (20.68%) in Group 2 (p = 0.12). The stone-free rates were 78.69% in Group 1 and 74.13% in Group 2 (p = 0.66). Mean total operation time was 43.23 ± 18.49 min in Group 1 as compared to 51.53 ± 19.48 min in Group 2 (p = 0.0188). Mean stone fragmentation time was 17.95 ± 15.25 min in Group 1 and 24.37 ± 11.12 min in Group 2 (p = 0.0096). Overall complications were not significant between the two Groups (p = 0.58). On sub-analysis of the patients with single tracts in both groups the results were comparable to patients with single and multiple tracts combined.Despite similar stone-free rates and complications between the two Groups, shockpulse has significantly lower stone fragmentation time and total operation time as compared to pneumatic lithotripsy."
1,"TITLE: Comparison of nateglinide and gliclazide in combination with metformin, for treatment of patients with Type 2 diabetes mellitus inadequately controlled on maximum doses of metformin alone.ABSTRACT: To compare the effects of nateglinide plus metformin with gliclazide plus metformin on glycaemic control in patients with Type 2 diabetes.Double-blind, double-dummy, parallel group, randomized, multicentre study over 24 weeks. Patients with inadequate glucose control on maximal doses of metformin were randomized to additionally receive nateglinide (n = 133) or gliclazide (n = 129). Changes from baseline in HbA1c, fasting plasma glucose (FPG) and mealtime glucose and insulin excursions were examined.HbA1c was significantly (P < 0.001) decreased from baseline in both treatment groups (mean changes: nateglinide -0.41%, gliclazide -0.57%), but with no significant difference between treatments. Proportions of patients achieving a reduction of HbA1c >or= 0.5% or an end point HbA1c < 7% were also similar (nateglinide 58.1%, gliclazide 60.2%). Changes from baseline in FPG were similarly significant in both treatment groups (nateglinide -0.63, gliclazide -0.82 mmol/l). Reduction from baseline in maximum postprandial glucose excursion were significant in the nateglinide group only (nateglinide -0.71, gliclazide -0.10 mmol/l; P = 0.037 for difference). Postprandial insulin levels were significantly higher with nateglinide compared with gliclazide. The overall rate of hypoglycaemia events was similar in the nateglinide group compared with the gliclazide group.No significant difference was seen between nateglinide plus metformin and gliclazide plus metformin in terms of HbA1c. However, the nateglinide combination demonstrated better postprandial glucose control."
1,"TITLE: Does EVAR alter the rate of cardiovascular events in patients with abdominal aortic aneurysm considered unfit for open repair? Results from the randomised EVAR trial 2.ABSTRACT: To investigate whether endovascular aneurysm repair (EVAR) influences the rate of cardiovascular events (fatal or non-fatal myocardial infarction or stroke) in patients with abdominal aortic aneurysm (AAA) considered unfit for open repair.Randomised controlled trial.Between 1999 and 2004, 404 patients with large AAA considered unfit for open repair were randomised to EVAR or no surgical intervention across 33 UK hospitals and followed until July 2009.The Customised Probability Index was used to determine fitness for each patient and Cox regression was used to compare time to first cardiovascular event between randomised groups and levels of fitness.During an average of 2.8 years of follow-up, 67 first cardiovascular events occurred with a non-significantly higher event rate in the EVAR group compared to the no intervention group (6.6 versus 5.1 events per 100 person years); adjusted hazard ratio 1.42 [95% CI 0.87-2.34], p=0.156. There was no evidence to suggest that the hazard ratio between randomised groups changed with level of fitness (p=0.378).Cardiovascular event rates were high in these unfit patients and medical therapy was sub-optimal. Events rates were slightly higher in the EVAR group but this was not statistically significant."
1,"TITLE: Effects of anaesthesia method and tourniquet use on recovery following total knee arthroplasty: a randomised controlled study.ABSTRACT: We investigated the effects of spinal and general anaesthesia and surgical tourniquet on acute pain and early recovery after total knee arthroplasty (TKA).Patients (n=413) were randomised to four parallel groups: spinal anaesthesia with or without tourniquet, and general anaesthesia with or without tourniquet. The primary outcome was patient-controlled i.v. oxycodone consumption over 24 postoperative hours.Results from 395 subjects were analysed. Median i.v. oxycodone consumption did not differ between the four groups (spinal anaesthesia without [36.6 mg] and with tourniquet [38.0 mg], general anaesthesia without [42.3 mg] and with tourniquet [42.5 mg], P=0.42), between spinal (37.7 mg) and general anaesthesia (42.5 mg) groups (median difference -3.1, 95% confidence interval [CI] -7.4 to 1.2, P=0.15) and between tourniquet and no-tourniquet groups (40.0 vs 40.0 mg, median difference -0.8, CI -5.1 to 3.5, P=0.72). Vomiting incidence was higher with spinal than with general anaesthesia (21% [42/200] vs 13% [25/194], CI 1.05 to 3.1, P=0.034). The mean haemoglobin decrease was greater without than with tourniquet (-3.0 vs -2.5 g dl, mean difference -0.48, CI -0.65 to -0.32, P<0.001). No differences were observed in pain, pain management, incidences of blood transfusions, in-hospital complications, or length of hospital stay.For TKA, spinal and general anaesthesia with or without tourniquet did not differ in 24-h postoperative opioid consumption, pain management, blood transfusions, in-hospital complications, and length of hospital stay. Vomiting incidence was higher in the spinal than in the general anaesthesia group. Tourniquet use caused smaller decreases in haemoglobin levels.EudraCT 2016-002035-15."
0,"TITLE: Relative and Absolute Risk Reductions in Cardiovascular and Kidney Outcomes With Canagliflozin Across KDIGO Risk Categories: Findings From the CANVAS Program.ABSTRACT: Canagliflozin reduces the risk for cardiovascular and kidney outcomes in type 2 diabetes. This study aimed to assess the relative and absolute effects of canagliflozin on clinical outcomes across different KDIGO (Kidney Disease: Improving Global Outcomes) risk categories based on estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio.Post hoc analysis of the CANagliflozin cardioVascular Assessment Study (CANVAS) Program.The CANVAS Program randomly assigned 10,142 participants with type 2 diabetes at high cardiovascular risk and with eGFR≥30mL/min/1.73m to treatment with canagliflozin or placebo.Canagliflozin or matching placebo.The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with a set of other cardiovascular and kidney prespecified outcomes.Of 10,142 participants, 10,031 (98.9%) had available baseline eGFR and urinary albumin-creatinine ratio data. The proportion of participants in low-, moderate-, high-, and very high-risk KDIGO categories was 58.6%, 25.8%, 10.6%, and 5.0%, respectively. The relative effect of canagliflozin on the primary outcome (HR, 0.86; 95% CI, 0.75-0.97) was consistent across KDIGO risk categories (P trend=0.2), with similar results for other cardiovascular and kidney outcomes. Absolute reductions in the primary outcome were greater within higher KDIGO risk categories (P trend=0.03) with a similar pattern of effect for the composite of cardiovascular death or hospitalization for heart failure (P trend=0.06) and for chronic eGFR slope (P trend = 0.04).Predominantly a low kidney risk population, relatively few participants in higher KDIGO risk categories, and exclusion of individuals with eGFR<30mL/min/1.73m.Although the relative effects of canagliflozin are similar across KDIGO risk categories, absolute risk reductions are likely greater for individuals at higher KDIGO risk. The KDIGO classification system may be able to identify individuals who might derive greater benefits for end-organ protection from treatment with canagliflozin.This post hoc analysis was not specifically funded. The original CANVAS Program trials were funded by Janssen Research & Development, LLC and were conducted as a collaboration between the funder, an academic steering committee, and an academic research organization, George Clinical.The original trials of the CANVAS Program were registered at ClinicalTrials.gov with study numbers NCT01032629 and NCT01989754."
1,"TITLE: An open label, randomized, fixed-dose, crossover study comparing efficacy and safety of sildenafil citrate and saffron (Crocus sativus Linn.) for treating erectile dysfunction in men naïve to treatment.ABSTRACT: Saffron (Crocus sativus Linn.) have been perceived by the public as a strong aphrodisiac herbal product. However, studies addressing the potential beneficial effects of saffron on erectile function (EF) in men with ED are lacking. Our aim was to evaluate the efficacy and safety of saffron administration on EF in men with ED. After a 4-week baseline assessment, 346 men with ED (mean age 46.6+/-8.4 years) were randomized to receive on-demand sildenafil for 12 weeks followed by 30 mg saffron twice daily for another 12 weeks or vice versa, separated by a 2-week washout period. To determine the type of ED, penile color duplex Doppler ultrasonography before and after intracavernosal injection with 20 microg prostaglandin E(1), pudendal nerve conduction tests and impaired sensory-evoked potential studies were performed. Subjects were assessed with an International Index of Erectile Function (IIEF) questionnaire, Sexual Encounter Profile (SEP) diary questions, patient and partner versions of the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire and the Global Efficacy Question (GEQ) 'Has the medication you have been taking improved your erections?' No significant improvements were observed with regard to the IIEF sexual function domains, SEP questions and EDITS scores with saffron administration. The mean changes from baseline values in IIEF-EF domain were +87.6% and +9.8% in sildenafil and placebo groups, respectively (P=0.08). We did not observe any improvement in 15 individual IIEF questions in patients while taking saffron. Treatment satisfaction as assessed by partner versions of EDITS was found to be very low in saffron patients (72.4 vs 25.4, P=0.001). Mean per patient 'yes' responses to GEQ was 91.2 and 4.2% for sildenafil and saffron, respectively (P=0.0001). These findings do not support a beneficial effect of saffron administration in men with ED."
1,"TITLE: Regular vs prn nebulized treatment in wheeze preschool children.ABSTRACT: International guidelines recommend regular treatment with inhaled glucocorticoids for children with frequent wheezing; however, prn inhaled bronchodilator alone or in combination with glucocorticoid is also often used in practice. We aimed to evaluate whether regular nebulized glucocorticoid plus a prn bronchodilator or a prn nebulized bronchodilator/glucocorticoid combination is more effective than prn bronchodilator alone in preschool children with frequent wheeze.Double-blind, double-dummy, randomized, parallel-group trial. After a 2-week run-in period, 276 symptomatic children with frequent wheeze, aged 1-4 years, were randomly assigned to three groups for a 3-month nebulized treatment: (1) 400 microg beclomethasone bid plus 2500 microg salbutamol prn; (2) placebo bid plus 800 microg beclomethasone/1600 microg salbutamol combination prn; (3) placebo bid plus 2500 microg salbutamol prn. The percentage of symptom-free days was the primary outcome measure. Secondary outcomes included symptom scores, use of relief medication and exacerbation frequency.As compared with prn salbutamol (61.0 +/- 24.83 [SD]), the percentage of symptom-free days was higher with regular beclomethasone (69.6%, SD 20.89; P = 0.034) but not with prn combination (64.9%, SD 24.74). Results were no different in children with or without risk factors for developing persistent asthma. The effect of prn combination was no different from that of regular beclomethasone on the primary and on several important secondary outcomes.Regular inhaled glucocorticoid is the most effective treatment for frequent wheezing in preschool children. However, prn bronchodilator/glucocorticoid combination might be an alternative option, but it requires further study."
1,"TITLE: Sildenafil citrate 100 mg starting dose in men with erectile dysfunction in an international, double-blind, placebo-controlled study: effect on the sexual experience and reducing feelings of anxiety about the next intercourse attempt.ABSTRACT: Sildenafil citrate 50 mg is the recommended starting dose for men with erectile dysfunction (ED); however, most men are later titrated to sildenafil 100 mg for improved efficacy.Assess the tolerability and efficacy of sildenafil initiated at the 100-mg dose in men with ED.Men with ED (score < or =25 on the Erectile Function domain of the International Index of Erectile Function) who had received < or =6 total doses of a phosphodiesterase type 5 inhibitor and none within 4 weeks were randomized to 8 weeks of double-blind, placebo-controlled (DBPC), fixed-dose treatment (50 or 100 mg sildenafil or placebo) followed by 4 weeks of open-label flexible-dose sildenafil (50 or 100 mg).Efficacy, tolerability, treatment satisfaction, and other end points were measured at baseline and/or the end of the double-blind and open-label phases and compared between placebo and sildenafil initiated at doses of 50 and 100 mg.Improvements in DBPC patient-reported outcomes from baseline were statistically significant for both sildenafil 50 and 100 mg compared with placebo. At the end of DBPC treatment, 56% of men on the 100-mg dose felt no anxiety about the next intercourse attempt compared with 39% in the 50-mg group (odds ratio 2.03; P = 0.0197). Changes in functional scores from baseline were not statistically significant with the 100-mg dose compared with the 50-mg dose in the DBPC. Measures of treatment satisfaction and sexual experience significantly favored the 100-mg dose compared with the 50-mg dose in the DBPC. There was no increase in adverse events with the higher dose.Sildenafil at 50 mg or 100 mg significantly improved erection quality, treatment satisfaction, anxiety levels, and the sexual experience compared with placebo during DBPC. Sildenafil 100 mg improved the sexual experience and treatment satisfaction, and reduced feelings of anxiety compared with the 50-mg dose."
1,"TITLE: OnabotulinumtoxinA for chronic migraine: efficacy, safety, and tolerability in patients who received all five treatment cycles in the PREEMPT clinical program.ABSTRACT: Chronic migraine (CM) is a prevalent and disabling neurological disorder. Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program assessed efficacy and safety of onabotulinumtoxinA (BOTOX(®)) for prophylaxis of headaches in adults with CM. This secondary analysis assessed patients who received all five treatment cycles and completed the study.PREEMPT (two phase III studies: 24-week double-blind, placebo-controlled [DBPC], parallel-group phase, followed by 32-week open-label [OL] phase) evaluated the efficacy and safety of onabotulinumtoxinA in CM (≥15 days/month with headache lasting ≥4 h a day). Patients were randomized (1:1) to onabotulinumtoxinA or placebo every 12 weeks for two cycles, followed by onabotulinumtoxinA for three cycles. Multiple headache symptom measures were evaluated. Results for the completer (five cycles) subgroup of patients are reported.Of 1384 total PREEMPT patients, 1005 received all five treatment cycles (513 received onabotulinumtoxinA only [onabotulinumtoxinA/onabotulinumtoxinA (O/O)] and 492 received two cycles of placebo then three cycles of onabotulinumtoxinA [placebo/onabotulinumtoxinA (P/O)]). Demographics were similar between treatment groups. At Week 56, after all patients were treated with onabotulinumtoxinA, there continued to be significant between-group differences favoring the O/O vs P/O group for the following headache symptom measures: LS mean change from baseline in frequencies of headache days (-12.0 O/O, -11.1 P/O; P = 0.035), migraine days (-11.6 O/O, -10.7 P/O; P = 0.038), and moderate/severe headache days (-11.0 O/O, -10.1 P/O; P = 0.042). For other measures (cumulative hours of headache on headache days, frequency of headache episodes, and percentage with severe Headache Impact Test (HIT)-6 score, and total HIT-6 and Migraine-Specific Quality of Life Questionnaire scores), there were also large mean improvements from baseline. The percent of patients with a ≥50% reduction from baseline in frequency of headache days was significantly greater for the onabotulinumtoxinA-only group at Week 56 (69.6% O/O, 62.8% P/O; P = 0.023). The treatment-related adverse event rate was 28.5% for onabotulinumtoxinA vs 12.4% for placebo in the DBPC phase and 34.8% for patients treated with onabotulinumtoxinA for all five cycles throughout the 56-week trials.This subgroup analysis demonstrated improvements with onabotulinumtoxinA treatment (five cycles) vs placebo (two cycles)/onabotulinumtoxinA (three cycles) for multiple headache symptom measures and suggests that at Week 56, patients treated earlier with onabotulinumtoxinA had better outcomes. These findings demonstrate the continued need and cumulative benefit over time with continued prophylaxis, an important and clinically pragmatic observation for clinicians and patients."
1,"TITLE: The Likelihood of Change in Fetal Presentation During the Third Trimester in Twin Pregnancies.ABSTRACT: To estimate the likelihood and identify predictors of spontaneous fetal version during the third trimester in twins using data from a multicenter randomized controlled trial on mode of delivery in twin pregnancies.Women with twin pregnancies after 32 weeks of gestation in which twin A was vertex were randomized to planned cesarean or planned vaginal delivery. In the current study we analyzed the likelihood of a spontaneous version of any of the twins between ultrasound assessment at the time of randomization and delivery.A total of 2,603 women were analyzed. Twin A tended to persist in the vertex presentation after 32 weeks of gestation with a spontaneous version rate to nonvertex presentation of 3.0% (95% confidence interval [CI] 2.3-3.7%). Twin B was less stable and underwent spontaneous version in 24.8% (95% CI 23.1-26.5%) of cases; the rate remained higher than 20% even after 34 weeks of gestation. On multivariable analysis, twin A was more likely to undergo version when twin B was smaller (adjusted odds ratio [OR] 2.0, 95% CI 1.04-3.3), when twin B was breech (adjusted OR 3.7, 95% CI 2.2-6.4) or transverse (adjusted OR 2.9, 95% CI 1.6-5.5), and when the interval to delivery exceeded 4 weeks (adjusted OR 2.5, 95% CI 1.3-5.0). Twin B was more likely to undergo version when it was in the breech presentation (adjusted OR 1.7, 95% CI 1.4-2.1) or transverse lie (adjusted OR 3.1, 95% CI 2.5-3.9) compared with vertex presentation, when it was smaller (adjusted OR 1.7, 95% CI 1.1-2.0), when the interval to delivery exceeded 4 weeks (adjusted OR 1.7, 95% CI 1.3-2.4), and in multiparous women (adjusted OR 1.3, 95% CI 1.04-1.5).The likelihood of spontaneous version of twin A after 32 weeks of gestation is low when twin A is in the vertex presentation but is much higher for twin B, even late during the third trimester.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00187369.II."
1,"TITLE: The use of mHealth to deliver tailored messages reduces reported energy and fat intake.ABSTRACT: Evidence supports the role of feedback in reinforcing motivation for behavior change. Feedback that provides reinforcement has the potential to increase dietary self-monitoring and enhance attainment of recommended dietary intake.The aim of this study was to examine the impact of daily feedback (DFB) messages, delivered remotely, on changes in dietary intake.This was a secondary analysis of the Self- Monitoring And Recording using Technology (SMART) Trial, a single-center, 24-month randomized clinical trial of behavioral treatment for weight loss. Participants included 210 obese adults (mean body mass index, 34.0 kg/m²) who were randomized to either a paper diary (PD), personal digital assistant (PDA), or PDA plus daily tailored feedback messages (PDA + FB). To determine the role of daily tailored feedback in dietary intake, we compared the self-monitoring with DFB group (DFB group; n = 70) with the self-monitoring without DFB group (no-DFB group, n = 140). All participants received a standard behavioral intervention for weight loss. Self-reported changes in dietary intake were compared between the DFB and no-DFB groups and were measured at baseline and at 6, 12, 18, and 24 months. Linear mixed modeling was used to examine percentage changes in dietary intake from baseline.Compared with the no-DFB group, the DFB group achieved a larger reduction in energy (-22.8% vs -14.0%; P = .02) and saturated fat (-11.3% vs -0.5%; P = .03) intake and a trend toward a greater decrease in total fat intake (-10.4% vs -4.7%; P = .09). There were significant improvements over time in carbohydrate intake and total fat intake for both groups (P values < .05).Daily tailored feedback messages designed to target energy and fat intake and delivered remotely in real time using mobile devices may play an important role in the reduction of energy and fat intake."
1,"TITLE: Testosterone patch for the treatment of hypoactive sexual desire disorder in naturally menopausal women: results from the INTIMATE NM1 Study.ABSTRACT: To evaluate the efficacy and safety of a testosterone patch for the treatment of women with hypoactive sexual desire disorder after natural menopause.A multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was conducted in naturally menopausal women with hypoactive sexual desire disorder receiving a stable dose of oral estrogen with or without progestin (N = 549). Women were randomized to receive testosterone 300 microg/day or placebo patches twice weekly for 24 weeks. The primary efficacy measure was change from baseline in frequency of total satisfying sexual activity over a 4-week period (weeks 21-24).A total of 483 women (88%) were included in the primary analysis population (those with baseline sex hormone binding globulin levels < or = 160 nmol/L). The change from baseline in number of total satisfying sexual episodes was significantly greater for testosterone compared with placebo (participants with baseline sex hormone binding globulin levels < or = 160 nmol/L, mean change of 2.1 +/- 0.28 versus 0.5 +/- 0.23 episodes/4 weeks; P < 0.0001; intent-to-treat population, mean change from baseline of 1.9 +/- 0.26 versus 0.5 +/- 0.21 episodes/4 weeks, P < 0.0001). Testosterone also produced statistically significant improvements compared with placebo in all secondary efficacy measures, including sexual desire and personal distress. The testosterone patch was well tolerated.Testosterone patch treatment increased the frequency of satisfying sexual activity and sexual desire, decreased personal distress, and was well tolerated in naturally menopausal women with hypoactive sexual desire disorder."
1,"TITLE: Diarrhoeal disease knowledge among diarrhoea patient housholds: findings from the randomised controlled trial of the Cholera-Hospital-Based-Intervention-for-7-days (CHoBI7) mobile health program.ABSTRACT: The objective of this study was to evaluate the impact of the Cholera-Hospital-Based-Intervention-for-7-days (CHoBI7) handwashing with soap and water treatment mobile health (mHealth) program on diarrhoeal disease knowledge among diarrhoea patients and their household members in urban Dhaka, Bangladesh.A cluster-randomised controlled trial of the CHoBI7 mHealth program was conducted among diarrhoea patient households in Dhaka, Bangladesh. Patients were randomised to three arms: standard recommendation on oral rehydration solution use; health facility delivery of CHoBI7 plus mHealth (weekly voice and text messages) (no home visits); and health facility delivery of CHoBI7 plus two home visits and mHealth. An open-ended questionnaire was administered to 1468 participants 12 years of age or older on diarrhoeal disease transmission and prevention. These items were combined to form a diarrhoeal disease knowledge score measured at baseline and at a 1 week, 6 month and 12 month follow-up.At baseline, when participants were asked to report three ways diarrhoeal diseases were spread 37% (546/1468) of participants reported by water, 13% (187/1468) by lack of handwashing and 4% (53/1468) by food not being covered properly. At baseline when asked to name three ways diarrhoeal diseases could be prevented, 35% (515/1468) of participants reported safe water, and 16% (228/1468) reported handwashing with soap. At the 12-month follow-up, the overall diarrhoeal disease knowledge score was significantly higher in the mHealth with no home visits arm (score coefficient: 0.69, 95% Confidence Interval: 0.36, 1.01, P < 0.0001) and the mHealth with two home visits arm (score coefficient: 1.18, 95% CI: 0.87, 1.49, P < 0.0001) compared with the standard recommendation arm.The CHoBI7 mHealth program significantly increased knowledge of diarrhoeal disease transmission and prevention among diarrhoea patients and their household members 12 months after in-person visits for program delivery were conducted."
1,"TITLE: Prospective randomized comparison of tongue base resection techniques: Robotic vs coblation.ABSTRACT: The objective of this study was to determine the effectiveness and morbidities of two different tongue base surgical approaches in patients with obstructive sleep apnoea (OSA).We carried out a prospective analysis in order to understand in detail the relative impact on apnoeas of the two different tongue base procedures. Seventy cases in 85 patients with OSA were divided into two operating groups and randomized. Altogether, 37 transoral robotic surgeries (TORS) and 33 coblations were performed. The patency of retrolingual passage was investigated by Muller's manoeuvere, polysomnography. Apnoea-hypopnea index (AHI) was the primary outcome measure with the Epworth Sleepiness Score (ESS). The final follow-up visit was at 6 months.The AHI index improved from 29.7 ± 9 to 10.7 ± 3.9 (P < .005) following TORS and from 27.2 ± 6.4 to 10.3 ± 4 in the coblation group. Selecting a threshold of a 50% reduction in AHI and AHI less than 20 events/h, the overall success rate was 75.6% in TORS compared with 78.7% in coblation (P = .785). Similar results were seen in AHI reduction rates (36%, 37.8%, respectively). ESS showed a significant improvement 6 months following surgery in both groups.Transoral robotic surgery technique showed higher complication rates than coblation. TORS and coblation of the tongue base represent a promising treatment option with a similar AHI improvement. However, coblation promises lower complication rates unlike TORS."
1,"TITLE: Rigid Mini-Thoracoscopy Versus Semirigid Thoracoscopy in Undiagnosed Exudative Pleural Effusion: The MINT Randomized Controlled Trial.ABSTRACT: There is debate regarding the ideal instrument for medical thoracoscopy. The authors compared rigid mini-thoracoscopy with semirigid thoracoscopy for thoracoscopic pleural biopsy.Consecutive subjects with undiagnosed exudative pleural effusion were randomized (1:1 ratio) to mini-thoracoscopy or semirigid thoracoscopy groups. The primary objective was a comparison of the diagnostic yield of pleural biopsy. Key secondary outcomes were the comparison of sedative/analgesic dose, operator-rated and patient-rated pain on visual analog scale (VAS), operator-rated overall procedural satisfaction (VAS), pleural biopsy size, and complications between the groups.Of the 88 screened subjects, 73 were randomized: 36 to mini-thoracoscopy and 37 to semirigid thoracoscopy. Diagnostic yield of pleural biopsy in the mini-thoracoscopy (69.4%) and semirigid thoracoscopy groups (81.1%) was similar on intention-to-treat analysis (P=0.25). Although the operator-rated overall procedure satisfaction scores were similar between groups (P=0.87), operator-rated pain [VAS (mean±SD), 43.5±16.7 vs. 31.7±15.8; P<0.001] and patient-rated pain (VAS, 41.9±17.3 vs. 32.1±16.5; P=0.02) scores were greater in the mini-thoracoscopy group. Mean dose of fentanyl and midazolam received was similar between the 2 groups (P=0.28 and 0.68, respectively). Biopsy size was larger in the mini-thoracoscopy group (16.1±4.5 vs. 8.3±2.9 mm; P<0.001). Three minor complications occurred in the mini-thoracoscopy group and 6 in the semirigid thoracoscopy group (P=0.11). There were no serious adverse events or procedure-related mortality.Diagnostic yield of rigid mini-thoracoscopy is not superior to semirigid thoracoscopy. Use of semirigid thoracoscope may provide greater patient comfort."
1,"TITLE: On-line haemodiafiltration versus haemodialysis: stable haematocrit with less erythropoietin and improvement of other relevant blood parameters.ABSTRACT: Controlled randomised studies to prove improved cardiovascular stability and improved anaemia management during on-line haemodiafiltration (oHDF) are scarce.70 patients were treated with both haemodialysis (HD) and oHDF in a cross-over design during 2 x 24 weeks at a dialysis dose of eKt/V> or =1.2. Patients randomised into group A started on HD and switched over to oHDF, whereas patients in group B began with oHDF and were treated with HD afterwards. Intradialytic morbid events (IME), such as symptomatic hypotension or muscle cramps, were noted in case of appearance. Blood parameters reflecting anaemic status, phosphate status, lipid metabolism, oxidative stress, and accumulation of advanced glycation end products were recorded either monthly or at the end of each study phase.The mean incidence of IME was 0.15 IME per treatment, and there was no statistical difference between oHDF and HD. A higher haematocrit (oHDF 31.5% vs. HD 30.5%, p < 0.01) at a lower erythropoietin dose (oHDF 4,913 vs. HD 5,492 IU/week, p = 0.02) was found during oHDF, when the sequence of HD and oHDF had not been taken into account. For the study groups, the results were less distinct: in group A, a higher haematocrit (HD 30.4% vs. oHDF 32.0%, p < 0.01) at a comparable erythropoietin dose (HD 5,421 vs. oHDF 5,187 IU/week, ns) was observed during oHDF, whereas in group B an identical haematocrit (oHDF 30.8% vs. HD 30.7%, ns) was achieved at a reduced erythropoietin dose (oHDF 4,622 vs. HD 5,568 IU/week, p < 0.01). During oHDF, lower levels of free and protein-bound pentosidine and of serum phosphate were found.In contrast to other studies, no benefit regarding cardiovascular stability for oHDF was found, but oHDF could well offer a potential benefit regarding anaemia correction, inflammation, oxidative stress, lipid profiles, and calcium-phosphate product."
1,"TITLE: Managing migraine headaches experienced by patients who self-report with menstrually related migraine: a prospective, placebo-controlled study with oral sumatriptan.ABSTRACT: The objective was to evaluate the efficacy and tolerability of oral sumatriptan (100 mg) in patients who self-reported with menstrually related migraine. A prospective, multicentre, randomised, double-blind, placebo-controlled, two-group crossover study was carried out in 20 UK primary and secondary care surgeries. Of 115 patients with a self-reported history of menstrually related migraine that entered the study, 93 patients completed it. Patients treated all migraine attacks for 2 months with sumatriptan (100 mg) and for 2 months with placebo. The primary endpoint was the proportion of patients reporting headache relief at 4 hours for the first treated attack. Only 11% of patients fulfilled the protocol definition of menstrually related migraine. Patients reported a variable pattern of migraine attacks occurring inside and outside the menstrual window. For the first attack, significantly more patients receiving sumatriptan than placebo reported headache relief for attacks occurring inside (67% vs. 33%, p=0.007) and outside (79% vs. 31%, p<0.001) the menstrual period. Sumatriptan was generally well tolerated. Oral sumatriptan (100 mg) is an effective and well tolerated acute treatment for patients who report menstrually related migraine."
1,"TITLE: French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC).ABSTRACT: Unresectable carcinomas of the oropharynx and hypopharynx still have a poor long-term prognosis. Following a previous phase II study, this phase III multicenter trial was conducted between November 1997 and March 2002.Nontreated, strictly unresectable cases were eligible. Twice-daily radiation: two fractions of 1.2 Gy/day, 5 days per week, with no split (D1-->D46). Total tumor doses: 80.4 Gy/46 day (oropharynx), 75.6 Gy/44 day (hypopharynx). Chemotherapy (arm B): Cisplatin 100 mg/m2 (D1, D22, D43); 5FU, continuous infusion (D1-->D5), 750 mg/m2/day cycle 1; 430 mg/m2/day cycles 2 and 3.A total of 163 evaluable patients. Grade 3-4 acute mucositis 82.6% arm B/69.5% arm A (NS); Grade 3-4 neutropenia 33.3% arm B/2.4% arm A (p < 0.05). Enteral nutrition through gastrostomy tube was more frequent in arm B before treatment and at 6 months (p < 0.01). At 24 months, overall survival (OS), disease-free survival (DFS), and specific survival (SS) were significantly better in arm B. OS: 37.8% arm B vs. 20.1% arm A (p = 0.038); DFS: 48.2% vs. 25.2% (p = 0.002); SS: 44.5% vs. 30.2% (p = 0.021). No significant difference between the two arms in the amount of side effects at 1 and 2 years.For these unresectable cases, chemoradiation provides better outcome than radiation alone, even with an ""aggressive"" dose-intensity radiotherapy schedule."
0,"TITLE: Marine n-3 fatty acids in adipose tissue and development of atrial fibrillation: a Danish cohort study.ABSTRACT: Consumption of fish and marine n-3 polyunsaturated fatty acids (PUFA) may be associated with a lower risk of atrial fibrillation (AF), but results have been inconsistent. The aim was to investigate this further by measurements of marine n-3 PUFA in adipose tissue.Cohort study.A total of 57 053 Danish participants 50-64 years of age were enrolled into the Diet, Cancer and Health Cohort Study.A randomly drawn subcohort of 3440 participants with available data from baseline adipose tissue biopsies.Exposure was the adipose tissue content of marine n-3 PUFA, which reflects the endogenous exposure and is also an objective marker of the long-term dietary intake.Incident AF during follow-up.179 cases of AF occurred over 13.6 years. Multivariate, sex-stratified Cox proportional hazards regression analyses using cubic splines showed a monotonic, negative, dose-response trend, but not statistically significant association, between total marine n-3 PUFA in adipose tissue and incident AF. A similar trend towards a lower risk of AF was seen in the second (HR 0.87, 95% CI 0.60 to 1.24) and third tertiles (HR 0.77, 95% CI 0.53 to 1.10) of marine n-3 PUFA compared with the lowest tertile. Similar trends, but also not statistically significant, were found separately for eicosapentaenoic, docosahexaenoic and docosapentaenoic acids.There was no statistically significant association between the content of marine n-3 PUFA in adipose tissue and the development of AF; however, data showed a monotonic, negative dose-response trend suggestive of a negative association."
0,"TITLE: Clinical predictors of severe cetuximab-induced rash: observations from 933 patients enrolled in north central cancer treatment group study N0147.ABSTRACT: Epidermal growth factor receptor inhibitors can result in a severe rash in 5-10% of patients and can detract from quality of life. The objective of this study was to identify clinical predictors of severe rash in the hope of utilizing such factors in the design of future rash palliative and prevention trials.933 cetuximab-treated patients enrolled on N0147, an adjuvant chemotherapy trial for colon cancer, were evaluated for clinical risk factors of severe rash.Within this cohort, 50 patients (5%) developed a severe rash (grade 3). More men compared to women developed such a rash: 34 (7%) versus 16 (3%) (multivariate odds ratio = 2.12; 95% confidence interval: 1.14-3.88; p = 0.017). A greater number of younger patients (<70 years of age) also developed a rash: 48 (6%) versus 2 (1%) (multivariate odds ratio = 0.21; 95% confidence interval: 0.05-0.88; p = 0.032). Race and performance score were not predictive.Men and younger patients are at greater risk for a severe cetuximab-induced rash although overall the risk is low. These observations are particularly important in designing future rash prevention and palliation trials."
1,"TITLE: A comparative analysis between the effects of galactose and glucose supplementation on endurance performance.ABSTRACT: To determine beneficial effects of short-term galactose (GAL) supplementation over a 50:50 glucose-maltodextrin (GLUC) equivalent on self-paced endurance cycling performance.On 2 separate occasions, subjects performed a 100-km self-paced time trial (randomized and balanced order). This was interspersed with four 1-km and four 4-km maximal efforts reflecting the physical requirements of racing. Before each trial 38±3 g of GAL or GLUC was ingested in a 6% concentrate fluid form 1 hr preexercise and then during exercise at a rate of 37±3 g/hr. Performance variables were recorded for all 1- and 4-km efforts, all interspersed intervals, and the total 100-km distance. Noninvasive indicators of work intensity (heart rate [HR] and rating of perceived exertion) were also recorded.Times taken to complete the 100-km performance trial were 8,298±502 and 8,509±578 s (p=.132), with mean power outputs of 271±37 and 256±45 W (p=.200), for GAL and GLUC, respectively. Mean HR did not differ (GAL 157±7 and GLUC 157±7 beats/min, p=.886). A main effect of carbohydrate (CHO) type on time to complete 4-km efforts occurred, with no CHO Type×Effort Order interaction observed. No main effect of CHO type or interaction of CHO Type×Sequential Order occurred for 1-km efforts.A 6% GAL drink does not enhance performance time during a self-paced cycling performance trial in highly trained endurance cyclists compared with a formula typically used by endurance athletes but may improve the ability to produce intermediate self-paced efforts."
1,"TITLE: Effects of enalapril in systolic heart failure patients with and without chronic kidney disease: insights from the SOLVD Treatment trial.ABSTRACT: Angiotensin-converting enzyme inhibitors improve outcomes in systolic heart failure (SHF). However, doubts linger about their effect in SHF patients with chronic kidney disease (CKD).In the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial, 2569 ambulatory chronic HF patients with left ventricular ejection fraction ≤ 35% and serum creatinine level ≤ 2.5mg/dl were randomized to receive either placebo (n=1284) or enalapril (n=1285). Of the 2502 patients with baseline serum creatinine data, 1036 had CKD (estimated glomerular filtration rate <60 ml/min/1.73 m(2)).Overall, during 35 months of median follow-up, all-cause mortality occurred in 40% (502/1252) and 35% (440/1250) of placebo and enalapril patients, respectively (hazard ratio {HR}, 0.84; 95% confidence interval {CI}, 0.74-0.95; p=0.007). All-cause mortality occurred in 45% and 42% of patients with CKD (HR, 0.88; 95% CI, 0.73-1.06; p=0.164), and 36% and 31% of non-CKD patients (HR, 0.82; 95% CI, 0.69-0.98; p=0.028) in the placebo and enalapril groups, respectively (p for interaction=0.615). Enalapril reduced cardiovascular hospitalization in those with CKD (HR, 0.77; 95% CI, 0.66-0.90; p<0.001) and without CKD (HR, 0.80; 95% CI, 0.70-0.91; p<0.001). Among patients in the enalapril group, serum creatinine elevation was significantly higher in those without CKD (0.09 versus 0.04 mg/dl in CKD; p=0.003) during first year of follow-up, but there was no differences in changes in systolic blood pressure (mean drop, 7 mm Hg, both) and serum potassium (mean increase, 0. /L, both).Enalapril reduces mortality and hospitalization in SHF patients without significant heterogeneity between those with and without CKD."
1,"TITLE: A reduced-carbohydrate and lactose-free formulation for stabilization among hospitalized children with severe acute malnutrition: A double-blind, randomized controlled trial.ABSTRACT: Children with medically complicated severe acute malnutrition (SAM) have high risk of inpatient mortality. Diarrhea, carbohydrate malabsorption, and refeeding syndrome may contribute to early mortality and delayed recovery. We tested the hypothesis that a lactose-free, low-carbohydrate F75 milk would serve to limit these risks, thereby reducing the number of days in the stabilization phase.In a multicenter double-blind trial, hospitalized severely malnourished children were randomized to receive standard formula (F75) or isocaloric modified F75 (mF75) without lactose and with reduced carbohydrate. The primary endpoint was time to stabilization, as defined by the World Health Organization (WHO), with intention-to-treat analysis. Secondary outcomes included in-hospital mortality, diarrhea, and biochemical features of malabsorption and refeeding syndrome. The trial was registered at clinicaltrials.gov (NCT02246296). Four hundred eighteen and 425 severely malnourished children were randomized to F75 and mF75, respectively, with 516 (61%) enrolled in Kenya and 327 (39%) in Malawi. Children with a median age of 16 months were enrolled between 4 December 2014 and 24 December 2015. One hundred ninety-four (46%) children assigned to F75 and 188 (44%) to mF75 had diarrhea at admission. Median time to stabilization was 3 days (IQR 2-5 days), which was similar between randomized groups (0.23 [95% CI -0.13 to 0.60], P = 0.59). There was no evidence of effect modification by diarrhea at admission, age, edema, or HIV status. Thirty-six and 39 children died before stabilization in the F75 and in mF75 arm, respectively (P = 0.84). Cumulative days with diarrhea (P = 0.27), enteral (P = 0.42) or intravenous fluids (P = 0.19), other serious adverse events before stabilization, and serum and stool biochemistry at day 3 did not differ between groups. The main limitation was that the primary outcome of clinical stabilization was based on WHO guidelines, comprising clinical evidence of recovery from acute illness as well as metabolic stabilization evidenced by recovery of appetite.Empirically treating hospitalized severely malnourished children during the stabilization phase with lactose-free, reduced-carbohydrate milk formula did not improve clinical outcomes. The biochemical analyses suggest that the lactose-free formulae may still exceed a carbohydrate load threshold for intestinal absorption, which may limit their usefulness in the context of complicated SAM.ClinicalTrials.gov NCT02246296."
0,"TITLE: The impact of tranexamic acid on mortality in injured patients with hyperfibrinolysis.ABSTRACT: In 2011, supported by data from two separate trauma centers, we implemented a protocol to administer tranexamic acid (TXA) in trauma patients with evidence of hyperfibrinolysis (HF) on admission. The purpose of this study was to examine whether the use of TXA in patients with HF determined by admission rapid thrombelastography was associated with improved survival.Following institutional review board approval, we evaluated all trauma patients 16 years or older admitted between September 2009 and September 2013. HF was defined as LY-30 of 3% or greater. Patients with LY-30 less than 3.0% were excluded. Patients were divided into those who received TXA (TXA group) and those who did not (no-TXA group). After univariate analyses, a purposeful, logistic regression model was developed a priori to evaluate the impact of TXA on mortality (controlling for age, sex, Injury Severity Score (ISS), arrival physiology, and base deficit).A total of 1,032 patients met study criteria. Ninety-eight (10%) received TXA, and 934 (90%) did not. TXA patients were older (median age, 37 years vs. 32 years), were more severely injured (median ISS, 29 vs. 14), had a lower blood pressure (median systolic blood pressure 103 mm Hg vs. 125 mm Hg), and were more likely to be in shock (median, base excess, -5 mmol/dL vs. -2 mmol/dL), all p < 0.05. Twenty-three percent of the patients had a repeat thrombelastography within 6 hours; 8.8% of the TXA patients had LY-30 of 3% or greater on repeat rapid thrombelastography (vs. 10.1% in the no-TXA group, p = 0.679). Unadjusted in-hospital mortality was higher in the TXA group (40% vs. 17%, p < 0.001). There were no differences in venous thromboembolism (3.3% vs. 3.8%). Logistic regression failed to find a difference in in-hospital mortality among those receiving TXA (odds ratio, 0.74; 95% confidence interval, 0.38-1.40; p 0.80).In the current study, the use of TXA was not associated with a reduction in mortality. Further studies are needed to better define who will benefit from an administration of TXA.Therapeutic study, level IV."
1,"TITLE: Effect of Amitriptyline and Escitalopram on Functional Dyspepsia: A Multicenter, Randomized Controlled Study.ABSTRACT: Antidepressants are frequently prescribed to treat functional dyspepsia (FD), a common disorder characterized by upper abdominal symptoms, including discomfort or postprandial fullness. However, there is little evidence of the efficacy of these drugs in patients with FD. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effects of antidepressant therapy on symptoms, gastric emptying (GE), and meal-induced satiety in patients with FD.We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use antidepressants. Patients (n = 292; 44 ± 15 years old, 75% were female, 70% with dysmotility-like FD, and 30% with ulcer-like FD) were randomly assigned to groups given placebo, 50 mg amitriptyline, or 10 mg escitalopram for 10 weeks. The primary end point was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks (of 12). Secondary end points included GE time, maximum tolerated volume in Nutrient Drink Test, and FD-related quality of life.An adequate relief response was reported by 39 subjects given placebo (40%), 51 given amitriptyline (53%), and 37 given escitalopram (38%) (P = .05, after treatment, adjusted for baseline balancing factors including all subjects). Subjects with ulcer-like FD given amitriptyline were >3-fold more likely to report adequate relief than those given placebo (odds ratio = 3.1; 95% confidence interval: 1.1-9.0). Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10-week period in any group. Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE (odds ratio = 0.4; 95% confidence interval: 0.2-0.8). Both antidepressants improved overall quality of life.Amitriptyline, but not escitalopram, appears to benefit some patients with FD, particularly those with ulcer-like (painful) FD. Patients with delayed GE do not respond to these drugs. ClinicalTrials.gov ID: NCT00248651."
0,"TITLE: Implications of ventricular arrhythmia ""bursts"" with normal epicardial flow, myocardial blush, and ST-segment recovery in anterior ST-elevation myocardial infarction reperfusion: a biosignature of direct myocellular injury ""downstream of downstream"".ABSTRACT: Establishing epicardial flow with percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is necessary but not sufficient to ensure nutritive myocardial reperfusion. We evaluated whether adding myocardial blush grade (MBG) and quantitative reperfusion ventricular arrhythmia ""bursts"" (VABs) surrogates provide a more informative biosignature of optimal reperfusion in patients with Thrombolysis in Myocardial Infarction (TIMI) 3 flow and ST-segment recovery (STR).Anterior STEMI patients with final TIMI 3 flow had protocol-blinded analyses of simultaneous MBG, continuous 12-lead electrocardiogram (ECG) STR, Holter VABs, and day 5-14 SPECT imaging infarct size (IS) assessments. Over 20 million cardiac cycles from >4500 h of continuous ECG monitoring in subjects with STR were obtained. IS and clinical outcomes were examined in patients stratified by MBG and VABs. VABs occurred in 51% (79/154) of subjects. Microcirculation (MBG 2/3) was restored in 75% (115/154) of subjects, of whom 53% (61/115) had VABs. No VABs were observed in subjects without microvascular flow (MBG of 0). Of 115 patients with TIMI 3 flow, STR, and MBG 2/3, those with VABs had significantly larger IS (median: 23.0% vs 6.0%, p=0.001). Multivariable analysis identified reperfusion VABs as a factor significantly associated with larger IS (p=0.015).Despite restoration of normal epicardial flow, open microcirculation, and STR, concomitant VABs are associated with larger myocardial IS, possibly reflecting myocellular injury in reperfusion settings. Combining angiographic and ECG parameters of epicardial, microvascular, and cellular response to STEMI intervention provides a more predictive ""biosignature"" of optimal reperfusion than do single surrogate markers."
1,"TITLE: A randomized control trial of bupivacaine and fentanyl versus fentanyl-only for epidural analgesia during the second stage of labor.ABSTRACT: The purpose of this prospective, double-blinded, parallel-arm, randomized trial was to examine the effects of epidural bupivacaine on the length of the second stage of labor in nulliparous women.The authors assessed length of second-stage labor, degree of motor blockade, mode of delivery, and visual analog scores in 310 nulliparous women with labor epidurals randomized to receive either: (1) 0.125% bupivacaine and fentanyl 2 μg/ml or (2) fentanyl 10 μg/ml alone via epidural using double blinding.The median duration of the second stage was 75 min (41, 128) in the bupivacaine/fentanyl group versus 73 min (42, 120) in the fentanyl-only group (P = 0.17) with a median difference of 6.0 (95% CI, -6.0 to 18.0). Furthermore, there was no difference in degree of motor blockade, incidence of operative delivery, visual analog scores, or neonatal outcomes between the two groups. No adverse events were reported.Use of epidural bupivacaine/fentanyl or a fentanyl-only infusion during the second stage of labor did not affect the duration of the second stage of labor, degree of motor blockade, mode of delivery, pain relief, and maternal or neonatal outcomes. However, in the fentanyl-only infusion group, there was a fivefold increase in opioid exposure to the fetus with unknown effects on neurobehavior, an outcome not assessed beyond the immediate postnatal period in this study."
0,"TITLE: High-intensity statin therapy alters the natural history of diabetic coronary atherosclerosis: insights from SATURN.ABSTRACT: Although statins can induce coronary atheroma regression, this benefit has yet to be demonstrated in diabetic individuals. We tested the hypothesis that high-intensity statin therapy may promote coronary atheroma regression in patients with diabetes.The Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN) used serial intravascular ultrasound measures of coronary atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg for 24 months. This analysis compared changes in biochemistry and coronary percent atheroma volume (PAV) in patients with (n = 159) and without (n = 880) diabetes.At baseline, patients with diabetes had lower LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels but higher triglyceride and CRP levels compared with patients without diabetes. At follow-up, diabetic patients had lower levels of LDL-C (61.0 ± 20.5 vs. 66.4 ± 22.9 mg/dL, P = 0.01) and HDL-C (46.3 ± 10.6 vs. 49.9 ± 12.0 mg/dL, P < 0.001) but higher levels of triglycerides (127.6 [98.8, 163.0] vs. 113.0 mg/dL [87.6, 151.9], P = 0.001) and CRP (1.4 [0.7, 3.3] vs. 1.0 [0.5, 2.1] mg/L, P = 0.001). Both patients with and without diabetes demonstrated regression of coronary atheroma as measured by change in PAV (-0.83 ± 0.13 vs. -1.15 ± 0.13%, P = 0.08). PAV regression was less in diabetic compared with nondiabetic patients when on-treatment LDL-C levels were >70 mg/dL (-0.31 ± 0.23 vs. -1.01 ± 0.21%, P = 0.03) but similar when LDL-C levels were ≤70 mg/dL (-1.09 ± 0.16 vs. -1.24 ± 0.16%, P = 0.50).High-intensity statin therapy alters the progressive nature of diabetic coronary atherosclerosis, yielding regression of disease in diabetic and nondiabetic patients."
1,"TITLE: Gastrointestinal Tolerance, Growth and Safety of a Partly Fermented Formula with Specific Prebiotics in Healthy Infants: A Double-Blind, Randomized, Controlled Trial.ABSTRACT: This study evaluated the effect of a partly fermented infant formula (using the bacterial strains Bifidobacterium breve C50 and Streptococcus thermophilus 065) with a specific prebiotic mixture (short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS; 9:1)) on the incidence of gastrointestinal symptoms, stool characteristics, sleeping and crying behaviour, growth adequacy and safety. Two-hundred infants ≤28 days of age were assigned either to experimental infant formula containing 30% fermented formula and 0.8 g/100 mL scGOS/lcFOS or to non-fermented control infant formula without scGOS/lcFOS. A group of breastfed infants served as a reference. No relevant differences in parent-reported gastrointestinal symptoms were observed. Stool consistency was softer in the experimental versus control group with values closer to the breastfed reference group. Daily weight gain was equivalent for both formula groups (0.5 SD margins) with growth outcomes close to breastfed infants. No clinically relevant differences in adverse events were observed, apart from a lower investigator-reported prevalence of infantile colic in the experimental versus control group (1.1% vs. 8.7%;  < 0.02). Both study formulae are well-tolerated, support an adequate infant growth and are safe for use in healthy term infants. Compared to the control formula, the partly fermented formula with prebiotics induces stool consistencies closer to breastfed infants."
0,"TITLE: Integrative analysis of the intestinal metabolome of childhood asthma.ABSTRACT: The intestinal metabolome reflects the biological consequences of diverse exposures and might provide insight into asthma pathophysiology.We sought to perform an untargeted integrative analysis of the intestinal metabolome of childhood asthma in this ancillary study of the Vitamin D Antenatal Asthma Reduction Trial.Metabolomic profiling was performed by using mass spectrometry on fecal samples collected from 361 three-year-old subjects. Adjusted logistic regression analyses identified metabolites and modules of highly correlated metabolites associated with asthma diagnosis by age 3 years. Sparse canonical correlation analysis identified associations relevant to asthma between the intestinal metabolome and other ""omics"": the intestinal microbiome as measured by using 16S rRNA sequencing, the plasma metabolome as measured by using mass spectrometry, and diet as measured by using food frequency questionnaires.Several intestinal metabolites were associated with asthma at age 3 years, including inverse associations between asthma and polyunsaturated fatty acids (adjusted logistic regression β = -6.3; 95% CI, -11.3 to -1.4; P = .01) and other lipids. Asthma-associated intestinal metabolites were significant mediators of the inverse relationship between exclusive breast-feeding for the first 4 months of life and asthma (P for indirect association = .04) and the positive association between a diet rich in meats and asthma (P = .03). Specific intestinal bacterial taxa, including the family Christensenellaceae, and plasma metabolites, including γ-tocopherol/β-tocopherol, were positively associated with asthma and asthma-associated intestinal metabolites.Integrative analyses revealed significant interrelationships between the intestinal metabolome and the intestinal microbiome, plasma metabolome, and diet in association with childhood asthma. These findings require replication in future studies."
1,"TITLE: An open, randomized, controlled, phase II, single centre, two-period cross-over study to compare the quality of life and toxicity experienced on PEG interferon with interferon-alpha2b in patients with multiple myeloma maintained on a steady dose of interferon-alpha2b.ABSTRACT: To compare the effects of pegylated interferon-alpha2b (P-IFN) and interferon-alpha2b (IFN) on quality of life (QoL) and toxicity in patients with multiple myeloma maintained on a steady dose of IFN.Consenting, eligible myeloma patients on IFN maintenance therapy for at least 6 weeks were randomly (1:1) allocated to receive P-IFN for 3 months followed by IFN for 3 months, or to continue with IFN for 3 months followed by P-IFN for 3 months (cross-over design). Patients were assessed for toxicity and QoL. Dose of P-IFN was equivalent to IFN.The study enrolled 60 patients. At enrollment, 35 patients were in complete remission, 20 in partial remission and 5 were minimal responders. P-IFN was associated with significantly better global QoL score (mean difference 8.4; P = 0.0002). There was a significant improvement in functional scales--physical (P = 0.03), emotional (P = 0.04), social (P = 0.0008) with P-IFN. Fatigue (P = 0.0003), pain (P = 0.02) and appetite loss (P = 0.003) symptom scales were less in patients while on P-IFN. There were no statistically significant differences between treatment arms in QoL as measured by QLQ-MY24.These data suggest that patients on P-IFN have a better QoL. Dose escalation studies are warranted to investigate potential impact on survival."
1,"TITLE: Preferences of adult patients with allergic rhinitis for the sensory attributes of fluticasone furoate versus fluticasone propionate nasal sprays: a randomized, multicenter, double-blind, single-dose, crossover study.ABSTRACT: Product attributes influence patient preference for intranasal corticosteroid therapy in allergic rhinitis (AR).The aim of the study was to compare the product sensory attributes and patient preferences of fluticasone furoate (FF) and fluticasone propionate (FP) nasal sprays in patients with symptomatic perennial and/or seasonal AR.This randomized, multicenter, double-blind, single-dose, crossover study enrolled 127 patients with a diagnosis of AR as determined by respiratory symptoms and a positive skin test to perennial and/or seasonal allergens within 12 months prior to the study. Patients could not use FF or FP within 4 weeks prior to the start of the study. Patients were randomized 1:1 to receive FF (110 microg) followed by FP (200 microg) or FP followed by FF. A 10-minute washout period occurred before crossover dosing. Following each treatment, patient-rated sensory attributes were assessed immediately and 2 minutes after treatment on 2 questionnaires using a 7-point Likert scale (scored from 0-6) rating odor, taste, aftertaste, drip down the throat, urge to sneeze, soothing feeling, irritation, and nose runoff. At the end of the crossover dosing and after completion of the attributes questionnaires, preference for individual attributes of FF or FP nasal spray and overall patient preference were evaluated in a third questionnaire that asked ""Based on these attributes, which product did you prefer overall?"" Additionally, a follow-up phone call was conducted 24 hours after the study to assess any adverse events following study treatment.Patients (mean age, 39.7 years; 80% white; 65% women) preferred FF nasal spray over FP nasal spray overall (60% vs 33%; P = 0.003) and based on the individual attributes of odor (64% vs 29%; P < 0.001), taste (47% vs 21%; P < 0.001), aftertaste (44% vs 22%; P = 0.002), drip down the throat (43% vs 27%; P = 0.037), and nose runoff (49% vs 19%; P < 0.001). Patient ratings favored FF versus FP (median differences, P < 0.001) with respect to odor, taste, dripping down the throat, and nose runoff, both immediately and 2 minutes after dosing, but there were no significant differences with respect to whether the medication felt soothing, caused nasal irritation, or made patients sneeze. Fifty-two percent (63/121) of patients replied that they were very likely to comply with FF treatment versus FP treatment (38% [45/120]; P = 0.02) if the medications were prescribed. Three patients (2%) reported adverse events (dizziness, headache, nasal congestion) during treatment with FF.In this study of adult AR patients, the sensory attributes of FF were preferred over those of FP following single-dose administration."
1,"TITLE: The Risk of Subclinical Breast Cancer-Related Lymphedema by the Extent of Axillary Surgery and Regional Node Irradiation: A Randomized Controlled Trial.ABSTRACT: To compare the risk of subclinical breast cancer-related lymphedema (sBCRL) using bioimpedance spectroscopy (BIS) or tape measure (TM) by the extent of axillary surgery and regional nodal irradiation (RNI).Patients were randomized to surveillance with TM or BIS. A BIS ≥6.5 L-Dex units or TM volume change ≥5 and <10% above presurgical baselines ""triggered"" sBCRL. The incidence of sBCRL by sentinel node biopsy or axillary lymph node dissection (ALND) with or without RNI was examined for 484 patients. Radiation was categorized as ""limited RNI"" (axilla level I/II only) or ""extensive RNI"" (axilla level III or supraclavicular fossa with or without level I/II).At a median follow-up of 20.5 months, 109 of 498 patients (21.9%) triggered sBCRL (BIS 13.5% vs TM 25.6%; P <.001). In patients not receiving RNI, BIS triggered 12.9% of patients undergoing SNB and 25.0% undergoing ALND (P = .18). Extensive RNI significantly increased triggering with BIS versus no RNI after sentinel node biopsy (SNB; 33.3% vs 12.9%; P = .03) but not ALND (30.8% vs 25.0%; P = .69). Triggering by TM was greater than 25% for most subgroups and was inferior to BIS in discriminating the risk of sBCRL by utilization of RNI or axillary surgery.The lower triggering rates with BIS and its better discrimination of the risk of sBCRL by receipt and type of RNI compared with TM support its use for posttreatment surveillance to detect sBCRL and to initiate early intervention. The risk of sBCRL increased with more extensive axillary treatment. Patients having ALND or extensive RNI require close surveillance for BCRL. Longer follow-up is required to determine rates of progression to clinical lymphedema."
1,"TITLE: Food cravings and energy regulation: the characteristics of craved foods and their relationship with eating behaviors and weight change during 6 months of dietary energy restriction.ABSTRACT: To examine characteristics of craved foods in relation to dietary energy restriction (ER) with high (HG) and low glycemic load (LG) diets.Assessments of food cravings before and during a randomized controlled trial of HG and LG diets provided for 6 months.Thirty-two healthy, overweight women aged 20-42 years.Self-reported food cravings and dietary intake, body weight, weight history and measures of eating behaviors.Foods craved at baseline were more than twice as high in energy density as the habitual diet (3.7+/-1.5 vs 1.7+/-0.3 kcal/g; P<0.001), and on average were lower in protein (P<0.001) and fiber (P<0.001) and higher in fat (P=0.002). There were no statistically significant changes in nutritional characteristics of craved foods after 6 months of ER. There was a significant relationship between reported portion size of craved food consumed at baseline and lifetime high body mass index (r=0.49, P=0.005). Additionally, there was a significant association between susceptibility to hunger and craving frequency at baseline, and there were significant relationships between hunger score, craving frequency, strength and percentage of time that cravings are given in to after 6 months of ER. In multiple regression models, subjects who lost a greater percentage of weight craved higher energy-dense foods at month 6 of ER, but also reported giving in to food cravings less frequently (adjusted R (2)=0.31, P=0.009).High energy density and fat content, and low protein and fiber contents were identifying characteristics of craved foods. The relationships between craving variables and hunger score suggest that the relative influence of hunger susceptibility on cravings may be important before and especially after ER. Portion size of craved foods and frequency of giving in to food cravings appear to be important areas for focus in lifestyle modification programs for long-term weight loss."
1,"TITLE: Subcutaneous tanezumab for osteoarthritis of the hip or knee: efficacy and safety results from a 24-week randomised phase III study with a 24-week follow-up period.ABSTRACT: Tanezumab, a nerve growth factor inhibitor, was investigated for osteoarthritis (OA) of the hip or knee in a study with 24-week treatment and 24-week safety follow-up.This double-blind, randomised, phase III study enrolled adults in Europe and Japan with moderate-to-severe OA who had not responded to or could not tolerate standard-of-care analgesics. Patients were randomised to tanezumab 2.5 mg or 5 mg subcutaneously or matching placebo every 8 weeks (three doses). Co-primary end points were change from baseline to week 24 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function, and Patient's Global Assessment of OA (PGA-OA). Joint safety and neurological assessments continued throughout the 48-week study.From March 2016 to December 2017, 849 patients were randomised and evaluated (placebo n=282, tanezumab 2.5 mg n=283, tanezumab 5 mg n=284). At week 24, there was a statistically significant improvement from baseline for tanezumab 5 mg compared with placebo for WOMAC Pain (least squares mean difference±SE -0.62±0.18, p=0.0006), WOMAC Physical Function (-0.71±0.17, p<0.0001) and PGA-OA (-0.19±0.07, p=0.0051). For tanezumab 2.5 mg, there was a statistically significant improvement in WOMAC Pain and Physical Function, but not PGA-OA. Rapidly progressive osteoarthritis (RPOA) was observed in 1.4% (4/283) and 2.8% (8/284) of patients in the tanezumab 2.5 mg and tanezumab 5 mg groups, respectively and none receiving placebo. Total joint replacements (TJRs) were similarly distributed across all three treatment groups (6.7%-7.8%). Tanezumab-treated patients experienced more paraesthesia (5 mg) and hypoaesthesia (both doses) than placebo.Tanezumab 5 mg statistically significantly improved pain, physical function and PGA-OA, but tanezumab 2.5 mg only achieved two co-primary end points. RPOA occurred more frequently with tanezumab 5 mg than tanezumab 2.5 mg. TJRs were similarly distributed across all three groups.NCT02709486."
1,"TITLE: Efficacy of a multifactorial intervention on therapeutic adherence in patients with chronic obstructive pulmonary disease (COPD): a randomized controlled trial.ABSTRACT: Therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is poor. This study evaluated the effectiveness of a multifactorial intervention on improving the therapeutic adherence in chronic obstructive pulmonary disease (COPD) patients with scheduled inhalation therapy.The study design consisted of a randomised controlled trial in a primary care setting. 146 patients diagnosed with COPD were randomly allocated into two groups using the block randomisation technique. One-year follow-ups with three visits were performed. The intervention consisted of motivational aspects related to adherence (beliefs and behaviour) in the form of group and individual interviews, cognitive aspects in the form of information about the illness and skills in the form of training in inhalation techniques. Cognitive-emotional aspects and training in inhalation techniques were reinforced during all visits of the intervention group. The main outcome measure was adherence to the medication regimen. Therapeutic adherence was determined by the percentage of patients classified as good adherent as evaluated by dose or pill count.Of the 146 participants (mean age 69.8 years, 91.8% males), 41.1% reported adherence (41.9% of the control group and 40.3% of the intervention group). When multifactorial intervention was applied, the reported adherence was 32.4% for the control group and 48.6% for the intervention group, which showed a statistically significant difference (p = 0.046). Number needed to treat is 6.37. In the intervention group, cognitive aspects increased by 23.7% and skilled performance of inhalation techniques increased by 66.4%. The factors related to adherence when multifactorial intervention was applied were the number of exacerbations (OR = 0.66), visits to health centre (OR = 0.93) and devices (OR = 2.4); illness severity (OR = 0.67), beta-2-adrenergic (OR = 0.16) and xantine (OR = 0.19) treatment; activity (OR = 1.03) and impact (OR = 1.03) scales of the Saint George Respiratory Questionnaire.Application of the multifactorial intervention designed for this study (COPD information, dose reminders, audio-visual material, motivational aspects and training in inhalation techniques) resulted in an improvement in therapeutic adherence in COPD patients with scheduled inhalation therapy.Current Controlled Trials ISRCTN18841601."
0,"TITLE: Impaired fasting glucose and body mass index as determinants of mortality in ALLHAT: is the obesity paradox real?ABSTRACT: Emerging literature suggests that obesity may be ""protective"" against mortality and cardiovascular outcomes, while dysglycemia may worsen outcomes regardless of obesity. The authors measured the association of weight, smoking, and glycemia with mortality in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Among 5423 ALLHAT participants without established diabetes or cardiovascular disease, 3980 (73%) had normal fasting glucose and 1443 (27%) had impaired fasting glucose (IFG) levels at study entry. After a median of 4.9 years follow-up, 554 (10%) had died (37% cardiovascular). IFG was associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.02-1.50), while obesity was associated with lower all-cause mortality (adjusted HR, 0.76; 95% CI, 0.60-0.96). However, after excluding underweight individuals (body mass index [BMI] <22 kg/m(2) ) and smokers, neither obesity nor IFG was associated with all-cause mortality [corrected]. Although obesity appeared protective against mortality, this association was not significant in never-smokers or after exclusion of BMI <22 kg/m(2) . The obesity paradox may result from confounding by a sicker, underweight referent population and smoking."
1,"TITLE: Ginger for prevention of antiretroviral-induced nausea and vomiting: a randomized clinical trial.ABSTRACT: In this randomized clinical trial ginger efficacy for prevention of antiretroviral-induced nausea and vomiting (N/V) was investigated.From July 2011 until the end of June 2013, 102 HIV positive patients attending the HIV clinic of Imam Khomeini Hospital participated in the study. In a double blinded manner, participants randomly received either 500 mg ginger or placebo two times per day, 30 min before each dose of antiretroviral regimen for 14 days. The severity of nausea was assessed based on the visual analogue scale. The number of vomiting episodes were also recorded during the study period.A total of 46 (90.2%) and 29 (56.4%) of the patients in placebo and ginger groups experienced some degree of nausea during the first 2 weeks of antiretroviral therapy (ART), respectively (p = 0.001). Frequency of mild, moderate and severe nausea were significantly lower in the ginger than placebo group (p = 0. 001). Also, 24 (47.1%) and 5 (9.8%) of the patients in the placebo and ginger groups reported at least one episode of vomiting during their time on ART, respectively (p = 0.01).Ginger was effective in ameliorating of antiretroviral-induced N/V."
1,"TITLE: Prospective comparison of the use of sirolimus and cyclosporine in recipients of a kidney from an expanded criteria donor.ABSTRACT: A 6-month, open-label, multicenter prospective pilot study was conducted to evaluate the effects of sirolimus (SRL) versus cyclosporine (CsA) in recipients of kidneys from expanded criteria donors. All patients also received antithymocyte globulins induction, mycophenolate mofetil, and steroids. Sixty-nine patients (33 SRL, 36 CsA) were randomized. More patient were withdrawn in the SRL group (16 vs. 6, P<0.01), because of delayed graft function and surgical complications. Delayed graft function tended to be more frequent with SRL than with CsA (45.4% vs. 30.6%, P=0.22). Graft survival was numerically lower in the SRL group (87.5% vs. 97%, P=0.19). At 6 months, there were no significant differences in biopsy-proven acute rejection or calculated creatinine clearance (SRL 12.1% vs. CsA 8.3%; P=0.7 and 44.7+/-16.6 vs. 41.9+/-15.2 mL/min; P=0.54 respectively). These results do not support the use of SRL immediately after transplantation in expanded criteria donor recipients."
1,"TITLE: Electrocautery for cutaneous flap creation during thyroidectomy: a randomised, controlled study.ABSTRACT: Although electrocautery has been used widely in surgery, the fear of delayed wound healing and infection persists. We aimed to evaluate the risk factors for wound complications and the rate of wound complications, comparing the use of electrocautery or scissors in cutaneous flap creation during thyroidectomy.The study group comprised 239 consecutive patients scheduled for thyroidectomy.Patients were randomly assigned to cutaneous flap dissection by either electrocautery (group one, n = 126) or scissors (group two, n = 113). Age, gender, body mass index, American Society of Anesthesiology score, tissue weight, operating time, incision length, cutaneous tissue depth, thyroid function and surgeon experience were recorded and compared with the rate of post-operative wound complications in both groups.There were no significant differences between the overall rate of post-operative wound complications, comparing groups one and two (7.9 vs 10.6 per cent, respectively; p = 0.74). Significant positive correlations were found between wound complication and age (Spearman's rank coefficient (rs) = 0.135, p = 0.036), body mass index (rs = 0.379, p = 0.0001), cutaneous tissue depth (rs = 0.677, p = 0.0001) and tissue weight (rs = 0.643, p = 0.0001). According to logistic regression analysis, a body mass index of more than 27.5 kg/m2 was associated with a 13.7-fold increased rate of post-operative wound complications.When creating cutaneous flaps during thyroidectomy, the use of electrocautery is as safe as the use of scissors. Such electrocautery does not increase the risk of wound complications in thyroid surgery."
1,"TITLE: Comparison of unilateral renal artery embolization versus bilateral for treatment of severe refractory hypertension in hemodialysis patients.ABSTRACT: Hypertension in ESRD patients is common, and often refractory to common medical interventions. Bilateral renal embolization (BRE) is an alternative to nephrectomy in treating severe refractory hypertension in hemodialysis patients, but has drawbacks in residual renal function preservation and post-infarction syndrome. We evaluated the efficacy and safety of unilateral renal embolization (URE) for the treatment of severe refractory hypertension in hemodialysis patients.From January 2000 to May 2007, 16 hemodialysis patients with severe refractory hypertension were randomized to URE or BRE group, and received percutaneous transcatheter unilateral or bilateral renal embolization, respectively. The efficacy and complications of these two procedures were compared. The plasma renin activity (PRA), plasma angiotensin II, aldosterone and endothelin-1 (ET-1) were measured pre- and post-renal embolization in both groups.The procedures were completed successfully without severe immediate complications. The blood pressure decreased from 211/122 to 127/81 mmHg in URE group (P < 0.0001), and in BRE group from 208/117 to 124/76 mmHg (P < 0.0001) with significantly reduced need for antihypertensive medications. The residual renal function was reasonably kept and post-infarction syndrome was milder in URE group compared with BRE group. No activation of RAS was observed in this series and no RAS activity dynamic change occurred post-procedure. Decreased circulating ET-1 was accompanied with the lowering of blood pressure after the procedure (P < 0.0001).Unilateral renal embolization is as effective as BRE in treating severe refractory hypertension in hemodialysis patients, with advantages over BRE in residual renal function preservation and milder post-infarction syndrome."
1,"TITLE: Soy isoflavones have an antiestrogenic effect and alter mammary promoter hypermethylation in healthy premenopausal women.ABSTRACT: We determined if soy isoflavones have dose-related estrogenic and methylation effects. Thirty-four healthy premenopausal women were randomized to 40 mg or 140 mg isoflavones daily through one menstrual cycle. Breast specific and systemic estrogenic effects were assessed measuring the estrogenic marker complement (C)3 and changes in cytology, whereas methylation assessment of 5 cancer related genes (p16, RASSF1A, RARbeta2, ER, and CCND2) was performed on intraductal specimens. Serum genistein significantly increased after consuming both isoflavone doses. Cytology did not significantly change at either isoflavone dose. Serum C3 levels posttreatment were inversely related to change in serum genistein (r =-0.76, P = 0.0045) in women consuming low but not high dose isoflavones. The RAR beta 2 hypermethylation increase posttreatment correlated with the posttreatment genistein level considering the entire group (r = 0.67, P = 0.0017) and those receiving high-dose isoflavones (r = 0.68, P = 0.021). At the low but not the high isoflavone dose, CCND2 hypermethylation increase correlated with posttreatment genistein levels (r = 0.79, P = 0.011). In summary, the inverse correlation between C3 and genistein suggests an antiestrogenic effect. Isoflavones induced dose-specific changes in RARbeta2 and CCND2 gene methylation, which correlated with genistein levels. This work provides novel insights into estrogenic and methylation effects of dietary isoflavones."
1,"TITLE: Total Occlusive Ionic Silver-Containing Dressing vs Mupirocin Ointment Application vs Conventional Dressing in Elective Colorectal Surgery: Effect on Incisional Surgical Site Infection.ABSTRACT: Several pre- and intraoperative factors have been associated with incisional surgical site infection (SSI), but little is known about the influence of postoperative wound care and especially, the use of different dressings on incisional SSI. The aim of this study was to compare 3 methods of wound dressings (conventional dressing, silver-containing dressing, and mupirocin ointment dressing) for their ability to prevent SSI, as measured by SSI rates, in patients with colorectal cancer undergoing elective open surgery.A prospective, randomized study was performed. Inclusion criteria were diagnosis of colorectal neoplasms and plans to undergo elective surgery with curative aims. Patients were randomized using a 1:1:1 allocation into 3 groups: patients receiving an ionic silver-containing dressing (ISD) (group 1), a mupirocin ointment application (MOA) (group 2), and a conventional dressing (group 3 or standard dressing). The primary outcomes variable was occurrence of incisional SSI. Follow-up was 30 days postoperatively.A total of 147 patients were included, 49 in each group. Incisional SSI occurred in 9 patients (18.4%) in the ISD group, 2 (4.1%) in the MOA group, and 10 (20.4%) in the standard dressing group (p = 0.028). Adjusting for multiple comparisons, there were no significant differences between ISD and standard dressing groups; a significant difference was observed between ISD and MOA (relative risk [RR] 4.5; 95% CI (1.1 to 19.8); p = 0.046) and between the standard group and the MOA group (RR 5; 95% CI (1.2 to 21.7); p = 0.031).Topical application of mupirocin ointment achieves better results for the prevention of SSI than ionic silver-containing dressing or standard dressing in patients undergoing elective open colorectal surgery."
0,"TITLE: Serum vitamin D, vitamin D binding protein, and risk of colorectal cancer.ABSTRACT: We previously reported a positive association between serum 25-hydroxyvitamin D (25(OH)D) and colorectal cancer risk. To further elucidate this association, we examined the molar ratio of 25(OH)D to vitamin D binding protein (DBP), the primary 25(OH)D transport protein, and whether DBP modified the association between 25(OH)D and colorectal cancer risk.In a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, controls were 1∶1 matched to 416 colorectal cancer cases based on age and date of blood collection. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for quartiles of 25(OH)D, DBP, and the molar ratio of 25(OH)D:DBP, a proxy for free, unbound circulating 25(OH)D.Comparing highest to lowest quartiles, DBP was not associated with colorectal cancer risk (OR = 0.91; 95% CI: 0.58, 1.42, p for trend  = 0.58); however, a positive risk association was observed for the molar ratio of 25(OH)D:DBP (OR = 1.44; 95% CI: 0.92, 2.26, p for trend  = 0.04). In stratified analyses, the positive association between 25(OH)D and colorectal cancer was stronger among men with DBP levels above the median (OR = 1.89; 95% CI: 1.07, 3.36, p for trend  = 0.01) than below the median (OR = 1.20; 95% CI: 0.68, 2.12, p for trend  = 0.87), although the interaction was not statistically significant (p for interaction  = 0.24).Circulating DBP may influence the association between 25(OH)D and colorectal cancer in male smokers, with the suggestion of a stronger positive association in men with higher DBP concentrations. This finding should be examined in other populations, especially those that include women and non-smokers."
1,"TITLE: Bystander fatigue and CPR quality by older bystanders: a randomized crossover trial comparing continuous chest compressions and 30:2 compressions to ventilations.ABSTRACT: This study sought to measure bystander fatigue and cardiopulmonary resuscitation (CPR) quality after five minutes of CPR using the continuous chest compression (CCC) versus the 30:2 chest compression to ventilation method in older lay persons, a population most likely to perform CPR on cardiac arrest victims.This randomized crossover trial took place at three tertiary care hospitals and a seniors' center. Participants were aged ≥55 years without significant physical limitations (frailty score ≤3/7). They completed two 5-minute CPR sessions (using 30:2 and CCC) on manikins; sessions were separated by a rest period. We used concealed block randomization to determine CPR method order. Metronome feedback maintained a compression rate of 100/minute. We measured heart rate (HR), mean arterial pressure (MAP), and Borg Exertion Scale. CPR quality measures included total number of compressions and number of adequate compressions (depth ≥5 cm).Sixty-three participants were enrolled: mean age 70.8 years, female 66.7%, past CPR training 60.3%. Bystander fatigue was similar between CPR methods: mean difference in HR -0.59 (95% CI -3.51-2.33), MAP 1.64 (95% CI -0.23-3.50), and Borg 0.46 (95% CI 0.07-0.84). Compared to 30:2, participants using CCC performed more chest compressions (480.0 v. 376.3, mean difference 107.7; p<0.0001) and more adequate chest compressions (381.5 v. 324.9, mean difference. 62.0; p=0.0001), although good compressions/minute declined significantly faster with the CCC method (p=0.0002).CPR quality decreased significantly faster when performing CCC compared to 30:2. However, performing CCC produced more adequate compressions overall with a similar level of fatigue compared to the 30:2 method."
1,"TITLE: A prospective randomised controlled trial of the fibular nail versus standard open reduction and internal fixation for fixation of ankle fractures in elderly patients.ABSTRACT: The fundamental concept of open reduction and internal fixation (ORIF) of ankle fractures has not changed appreciably since the 1960s and, whilst widely used, is associated with complications including wound dehiscence and infection, prominent hardware and failure. Closed reduction and intramedullary fixation (CRIF) using a fibular nail, wires or screws is biomechanically stronger, requires minimal incisions, and has low-profile hardware. We hypothesised that fibular nailing in the elderly would have similar functional outcomes to standard fixation, with a reduced rate of wound and hardware problems.A total of 100 patients (25 men, 75 women) over the age of 65 years with unstable ankle fractures were randomised to undergo standard ORIF or fibular nailing (11 men and 39 women in the ORIF group, 14 men and 36 women in the fibular nail group). The mean age was 74 years (65 to 93) and all patients had at least one medical comorbidity. Complications, patient related outcome measures and cost-effectiveness were assessed over 12 months.Significantly fewer wound infections occurred in the fibular nail group (p = 0.002). At one year, there was no evidence of difference in mean functional scores (Olerud and Molander Scores 63; 30 to 85, versus 61; 10 to 35, p = 0.61) or scar satisfaction. The overall cost of treatment in the fibular nail group was £91 less than in the ORIF group despite the higher initial cost of the implant.We conclude that the fibular nail allows accurate reduction and secure fixation of ankle fractures, with a significantly lower rate of soft-tissue complications, and is more cost-effective than ORIF. Cite this article: Bone Joint J 2016;98-B:1248-52."
0,"TITLE: Effect of evolocumab on cholesterol synthesis and absorption.ABSTRACT: The effects of cholesterol-lowering drugs, including those that reduce cholesterol synthesis (statins) and those that reduce cholesterol absorption (ezetimibe), on cholesterol absorption and synthesis are well understood. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a novel class of cholesterol-lowering drugs that robustly reduce LDL-cholesterol (LDL-C), but little is known about their effects on cholesterol absorption and synthesis. We evaluated how treatment with evolocumab, a fully human monoclonal IgG2 antibody to PCSK9, affects markers of cholesterol synthesis and absorption by measuring these markers in patients from an evolocumab clinical trial. At 2 weeks, changes in β-sitosterol/total cholesterol (TC) from baseline were 4% for placebo, 10% for evolocumab 140 mg (nonsignificant vs. placebo), and 26% for evolocumab 420 mg (P < 0.001 vs. placebo). Changes in campesterol/TC at week 2, relative to baseline between placebo and evolocumab, were all nonsignificant. Evolocumab had a modest effect on markers of cholesterol synthesis. At 2 weeks, changes in desmosterol/TC were 1% for placebo, 7% for evolocumab 140 mg (nonsignificant vs. placebo), and 15% for evolocumab 420 mg (P < 0.01 vs. placebo). Changes from baseline in lathosterol/TC at week 2 between placebo and evolocumab were nonsignificant. These results suggest that evolocumab has a modest effect on cholesterol synthesis and absorption despite significant LDL-C lowering."
1,"TITLE: Use of oral topiramate to promote smoking abstinence among alcohol-dependent smokers: a randomized controlled trial.ABSTRACT: Previously, our group has shown that topiramate, a sulfamate-substituted fructopyranose derivative, is an effective treatment for alcohol dependence. Herein, we extend that proof-of-concept study by determining whether cigarette-smoking, alcohol-dependent individuals from the earlier study also experienced improved smoking outcomes.As a subgroup analysis of a larger double-blind, randomized, controlled, 12-week study comparing topiramate vs placebo as treatment for alcohol dependence, a 12-week clinical trial compared topiramate vs placebo in 94 cigarette-smoking, alcohol-dependent individuals. Of these, 45 were assigned to receive topiramate (escalating dose from 25 to 300 mg/d) and the remaining 49 had placebo as an adjunct to weekly standardized medication compliance management. The primary outcome was smoking cessation ascertained by self-report and confirmed by the level of serum cotinine (nicotine's major metabolite).Topiramate recipients were significantly more likely than placebo recipients to abstain from smoking (odds ratio, 4.46; 95% confidence interval, 1.08-18.39; P = .04). Using a serum cotinine level of 28 ng/mL or lower to segregate nonsmokers from smokers, we found that the topiramate group had 4.97 times the odds of being nonsmokers (95% confidence interval, 1.1-23.4;P = .04). Smoking cessation rates for topiramate recipients were 19.4% and 16.7% at weeks 9 and 12, respectively, compared with 6.9% at both time points for placebo recipients.In this trial, topiramate (up to 300 mg/d) showed potential as a safe and promising medication for the treatment of cigarette smoking in alcohol-dependent individuals."
1,"TITLE: Teleconferenced educational detailing: diabetes education for primary care physicians.ABSTRACT: Formal didactic continuing medical education (CME) is relatively ineffective for changing physician behaviour. Diabetes mellitus is an increasingly prevalent disease, and interventions to improve adherence to clinical practice guidelines (CPGs) are needed.A stratified, cluster-randomized, controlled trial design was used to evaluate the effects of a teleconferenced educational detailing (TED) CME on glycemic control (hemoglobin [Hb] A1c) and family physician adherence to national diabetes guidelines. TED employed sequential, small-group, case-based education using CPGs delivered by a diabetes specialist. Medical record audit data from baseline through the end of a 12-month postintervention period were compared for the control and intervention groups. Satisfaction with the intervention was evaluated.Sixty-one physicians provided 660 medical records. The intervention did not affect mean Hb A1c levels but did significantly (p = .04) alter the distribution of patients by category of glycemic control, with fewer in the intervention group in inadequate control (15.8% versus 23.9%). More patients took insulin (alone or with oral agents) in the intervention group (21.2% versus 12.0%, p = .03), and more took oral agents only in the control group (89.0% versus 82.9%, p = .005). More patients in the intervention group had documentation of body mass index (7.8% versus 1.9%, p < .02), eye exam (12.1% versus 5.1%, p = .02), and treatment plan (43.5% versus 23.6%, p = .01) and used a flow sheet (14.6% versus 7.7%, p < .03). Although there was general satisfaction with the teleconferencing format, specialist educators found the format more challenging than the family physicians.CME delivered by teleconference was feasible, well attended, well received by participants, and improved some key diabetes management practices and outcomes."
1,"TITLE: Effects of tadalafil treatment on erectile function recovery following bilateral nerve-sparing radical prostatectomy: a randomised placebo-controlled study (REACTT).ABSTRACT: The potential rehabilitative and protective effect of phosphodiesterase type 5 inhibitors (PDE5-Is) on penile function after nerve-sparing radical prostatectomy (NSRP) remains unclear.The primary objective was to compare the efficacy of tadalafil 5mg once daily and tadalafil 20mg on demand versus placebo taken over 9 mo in improving unassisted erectile function (EF) following NSRP, as measured by the proportion of patients achieving an International Index of Erectile Function-Erectile Function domain (IIEF-EF) score ≥ 22 after 6-wk drug-free washout (DFW). Secondary measures included IIEF-EF, Sexual Encounter Profile question 3 (SEP-3), and penile length.Randomised, double-blind, double-dummy, placebo-controlled trial in men ≤ 68 yr of age with adenocarcinoma of the prostate (Gleason ≤ 7) and normal preoperative EF who underwent NSRP at 50 centres from nine European countries and Canada.1:1:1 randomisation to 9 mo of treatment with tadalafil 5mg once daily, tadalafil 20mg on demand, or placebo followed by a 6-wk DFW and 3-mo open-label tadalafil once daily (all patients).Logistic regression, mixed-effects model for repeated measures, and analysis of covariance, adjusting for treatment, age, and country, were applied to IIEF-EF scores ≥ 22, SEP-3, and penile length.Four hundred twenty-three patients were randomised to tadalafil once daily (n=139), on demand (n=143), and placebo (n=141). The mean age was 57.9 yr of age (standard deviation: 5.58 yr); 20.9%, 16.9%, and 19.1% of patients in the tadalafil once daily, on demand, and placebo groups, respectively, achieved IIEF EF scores ≥ 22 after DFW; odds ratios for tadalafil once daily and on demand versus placebo were 1.1 (95% confidence interval [CI], 0.6-2.1; p=0.675) and 0.9 (95% CI, 0.5-1.7; p=0.704). At the end of double-blind treatment (EDT), least squares (LS) mean IIEF-EF score improvement significantly exceeded the minimally clinically important difference (MCID: ΔIIEF-EF ≥ 4) in both tadalafil groups; for SEP-3 (MCID ≥ 23%), this was the case for tadalafil once daily only. Treatment effects versus placebo were significant for tadalafil once daily only (IIEF-EF: p=0.016; SEP-3: p=0.019). In all groups, IIEF-EF and SEP-3 decreased during DFW but continued to improve during open-label treatment. At month 9 (EDT), penile length loss was significantly reduced versus placebo in the tadalafil once daily group only (LS mean difference 4.1mm; 95% CI, 0.4-7.8; p=0.032).Tadalafil once daily was most effective on drug-assisted EF in men with erectile dysfunction following NSRP, and data suggest a potential role for tadalafil once daily provided early after surgery in contributing to the recovery of EF after prostatectomy and possibly protecting from penile structural changes. Unassisted EF was not improved after cessation of active therapy for 9 mo.ClinicalTrials.gov identifier NCT01026818."
1,"TITLE: Maintenance of elevated versus physiological iron indices in non-anaemic patients with chronic kidney disease: a randomized controlled trial.ABSTRACT: An optimal haemoglobin (Hb) response to erythropoietin requires elevated iron indices in dialysis patients; however, it is unknown if the same applies in chronic kidney disease (CKD).One hundred patients [CKD Stages 3-5, Hb >or= 110 g/L, iron replete, erythropoietin-stimulating agent (ESA)-naive, 47% diabetic, median age 69.5 years] were block-randomized in an open-label study to receive up to 200 mg intravenous iron sucrose (Group A, n = 52) bimonthly or oral iron sulphate (Group B) to maintain raised and normal iron indices (respectively) over 12 months. The primary endpoint was the change in Hb concentration at 12 months or at termination after at least 6 months of treatment.Eighty-five patients reached the primary endpoint (43, Group A; 42, Group B). Initial Hb was 119 +/- 7 vs 116 +/- 12 g/L (mean +/- standard deviation); ferritin 122 (71-176), median (inter-quartile range), vs 90 microg/L (58-150); transferrin saturation (TSat) 22 (18-26) vs 21% (15-24); and creatinine 240 (195-313) vs 230 micromol/L (184-352). Ferritin and TSat differed by month 2 [157 (103-220) vs 96 microg/L (73-162), P = 0.003] and month 6 [25 (20-31) vs 21% (17-27), P = 0.02], respectively. At study end, Hb did not differ between groups (121 +/- 10 vs 117 +/- 13 g/L). Ferritin was 362 (310-458) vs 125 microg/L (84-190), P < 0.001; TSat 30 (23-34) vs 21% (18-24), P < 0.001; and creatinine 229 (188-326) vs 272 micromol/L (195-413), P = NS. For patients (Groups A and B, n = 27 in each group) whose creatinine regression slope increased (indicating worsening function), the fall in Hb over 12 months also did not differ between groups despite adequate separation in iron indices. Serious adverse events overall did not differ between groups.Elevated iron indices did not increase Hb synthesis in ESA-naive, iron replete, pre-dialysis patients with Hb >110 g/L."
1,"TITLE: Immediate compared with delayed cord clamping in the preterm neonate: a randomized controlled trial.ABSTRACT: The comparative risks and benefits of early compared with delayed cord clamping in the preterm neonate remain unclear. Our objective was to evaluate the short-term effects of delayed clamping of the umbilical cord in preterm neonates.We conducted a randomized controlled trial comparing immediate with delayed cord clamping among preterm neonates born between 24 and 34 weeks of gestation. The primary study outcome was the need for blood transfusion. To detect a 33% reduction in this outcome (from 65 to 43.5%) with a two-tailed α of 0.5 and β of 0.8 required 178 patients equally divided into two groups.A total of 200 women were randomized, 99 to the delayed and 101 to the immediate clamp group. The groups were similar with respect to baseline characteristics. The mean gestational age at delivery was 30.8±3.1 weeks in the delayed compared with 30.7±2.8 weeks in the immediate clamp group (P=.64). There was no statistically significant difference between groups with regard to the need for blood transfusion: 25 of 99 (25.3%) in the delayed cord clamp group received one or more blood transfusion compared with 24 of 101 (23.7%) in the immediate clamp group (P=.8). The rates of various neonatal outcomes including respiratory distress syndrome, periventricular leukomalacia, necrotizing enterocolitis, anemia of prematurity, and neonatal morality did not differ significantly between the groups. However, the mean initial hemoglobin (17.4±2.5 compared with 16.3±2.3 g/dL, P=.001) and hematocrit (51.3±7.3 compared with 47.4±7.3, P=.001) was significantly higher in the delayed group. In the delayed clamp group, 11.1% (11/99) of neonates had intraventricular hemorrhage compared with 19.8% (20/101) in the immediate clamp group (P=.09).Delayed cord clamping for 30 seconds did not decrease the need for blood transfusion among preterm neonates.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00579839."
1,"TITLE: Minimal impact of adjuvant exemestane or tamoxifen treatment on mammographic breast density in postmenopausal breast cancer patients: a Dutch TEAM trial analysis.ABSTRACT: Mammographic breast density is one of the strongest independent risk factors for developing breast cancer. We examined the effect of exemestane and tamoxifen on breast density in Dutch postmenopausal early breast cancer patients participating in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial.Analogue mammograms of selected TEAM participants before start, and after one and two (and if available after three) years of adjuvant endocrine therapy were collected centrally and reviewed. Study endpoints were change in breast density over time, and correlations between breast density and locoregional recurrence (LRR), distance recurrence (DR), and contralateral breast cancer (CBC).Mammograms of 378 patients (181 tamoxifen, 197 exemestane) were included in the current per protocol analyses. Baseline breast density was low (breast density score<50% in 75% of patients) and not different between patients randomised to exemestane or tamoxifen (coefficient 0.16, standard error 0.17). Breast density did not change during treatment in exemestane (p=0.25) or tamoxifen users (p=0.59). No relation was observed between breast density and the occurrence of a LRR [hazards ratio (HR) 0.87, 95% CI 0.45-1.68, p=0.67], a DR (HR 1.02, 95% CI 0.77-1.35, p=0.90), or CBC (HR 1.31, 95% CI 0.63-2.72, p=0.48).The in general low breast density score in early postmenopausal breast cancer patients did not substantially change over time, and this pattern was not different between tamoxifen and exemestane users. Breast density was not a predictive marker for efficacy of adjuvant endocrine therapy."
1,"TITLE: Epoetin alpha improves the response to antiviral treatment in HCV-related chronic hepatitis.ABSTRACT: The conventional antiviral treatment of chronic hepatitis related to hepatitis C virus (HCV) often leads to anemia. In this case, it is necessary to reduce ribavirin dose or stop treatment, thus reducing the rate of sustained virological response.We investigated whether epoetin alpha administration improves treatment adherence and leads to higher percentage of response at the end of therapy and sustained virological response.Two hundred and fourteen individuals with genotype 1b HCV-related chronic hepatitis underwent treatment with pegylated (peg)-interferon alpha-2A 180 μg once weekly and ribavirin 1,000-1,200 mg/day; 174 were responders. Forty individuals completed treatment with no hemoglobin reduction; 134 developed anemia during therapy. Anemic responders were distributed randomly into two groups: group 1 continued therapy with epoetin alpha addiction; group 2 continued antiviral therapy with ribavirin reduction only.Patients in group 1 achieved better control of hemoglobin levels (13.8 ± 1.2 g/dl at the end of therapy) than those in group 2 (11.5 ± 0.8 g/dl). Sustained virological response was 59.7% in group 1 compared with 34.4% in group 2 (p<0.01).In patients with 1b HCV-related chronic hepatitis who develop anemia during antiviral treatment, administration of epoetin alpha increases hemoglobin levels and the end-of-treatment rate and sustains virological response by improving treatment adherence."
1,"TITLE: Addition of Exercise Increases Plasma Adiponectin and Release from Adipose Tissue.ABSTRACT: Adiponectin is an adipose tissue-derived anti-inflammatory protein that is down-regulated in obesity. The effects of caloric restriction and exercise-induced weight loss on adiponectin are not clear.To determine whether addition of aerobic exercise training to caloric restriction has additive effects over caloric restriction alone on circulating adiponectin concentrations and adiponectin release from abdominal and gluteal adipose tissue.Overweight or obese (body mass index, 25-40 kg·m(-2); waist >88 cm) postmenopausal women were randomized to 20-wk caloric restriction with and without aerobic exercise (CR + EX, n = 48; and CR, n = 22). Blood samples were collected for measuring plasma adiponectin concentration, and abdominal and gluteal subcutaneous adipose tissue biopsies were performed in a subgroup to determine in vitro adiponectin release, before and after the interventions.The interventions elicited similar amounts of weight loss (CR + EX, -11.3 ± 4.6 kg; CR,-11.2 ± 3.4 kg) and fat loss (CR + EX, -8.0 ± 3.5 kg; CR, -7.4 ± 2.7 kg). The two groups had differential changes in plasma adiponectin concentrations (for interaction, P = 0.014); CR + EX increased (6.9 ± 3.9 to 8.5 ± 4.9 μg·mL(-1); P = 0.0001), whereas CR did not alter (6.4 ± 4.4 to 6.5 ± 4.5 μg·mL(-1); P = 0.42) plasma adiponectin. Likewise, adiponectin release from abdominal and gluteal subcutaneous adipose tissue increased with CR + EX (P = 0.0076 and P = 0.089, respectively) but did not change with CR (P = 0.13 and P = 0.95, respectively).Despite similar reductions in body weight and fat mass, the addition of aerobic exercise to caloric restriction increased plasma adiponectin concentrations, which may be partly explained by increased adiponectin release from abdominal and gluteal subcutaneous adipose tissue."
1,"TITLE: Multicenter Randomized Study of Obesity Treatment with Minimally Invasive Injection of Hyaluronic Acid Versus and Combined with Intragastric Balloon.ABSTRACT: Research into minimally invasive techniques is worthwhile for greater acceptance in bariatric surgery, a useful first step being to evaluate the combination of these with current procedures. We suggest that intragastric balloon (IGB) can be performed with hyaluronic acid (HA) injections at the level of the gastroesophageal junction.A submucosal restriction is created by circular injection of an absorbable material within a defined area based on endoscopic anatomy. We included 101 patients in a prospective multicenter randomized trial, with average body mass index (BMI) 33.4 (range 27-44), treated from April 2010 to April 2012 by IGB and/or HA injection, sequentially, and followed for two more years. Patients were divided into group 1 (IGB alone), group 2 (IGB followed by HA at IGB removal, at 6 months), and group 3 (HA and IGB at 6 months).BMI loss at 6 months was inferior in the HA group (32 patients) compared with the IGB groups (68 patients) (2.1 ± 0.4 versus 3.4 ± 0.3, p < 0.05). The efficacy of IGB alone compared with combined treatments (groups 2 and 3) was significantly inferior at 18 months only, but the impact of the treatment sequence (HA before or after IGB) on BMI loss was not statistically significant, although in favor of HA first.This study did not demonstrate the efficacy of HA injections as an obesity treatment."
1,"TITLE: Promoting physical activity in older people in general practice: ProAct65+ cluster randomised controlled trial.ABSTRACT: Regular physical activity reduces falls, hip fractures, and all-cause mortality, but physical activity levels are low in older age groups.To evaluate two exercise programmes promoting physical activity among older people.Pragmatic three-arm, parallel-design cluster randomised controlled trial involving 1256 people aged ≥65 years (of 20 507 invited) recruited from 43 general practices in London, Nottingham, and Derby.Practices were randomised to the class-based Falls Management Exercise programme (FaME), the home-based Otago Exercise Program (OEP), or usual care. The primary outcome was the proportion reaching the recommended physical activity target 12 months post-intervention. Secondary outcomes included falls, quality of life, balance confidence, and costs.In total, 49% of FaME participants reached the physical activity target compared with 38% for usual care (adjusted odds ratio 1.78, 95% confidence interval [CI] =1.11 to 2.87, P = 0.02). Differences between FaME and usual care persisted 24 months after intervention. There was no significant difference comparing those in the OEP (43% reaching target at 12 months) and usual-care arms. Participants in the FaME arm added around 15 minutes of moderate-to-vigorous physical activity per day to their baseline level; this group also had a significantly lower rate of falls (incident rate ratio 0.74, 95% CI = 0.55 to 0.99, P = 0.042). Balance confidence was significantly improved in both intervention arms. The mean cost per extra person achieving the physical activity target was £1740. Attrition and rates of adverse reactions were similar.The FaME programme increases self-reported physical activity for at least 12 months post-intervention and reduces falls in people aged ≥65 years, but uptake is low. There was no statistically significant difference in reaching the target, or in falls, between the OEP and usual-care arms."
1,"TITLE: Growth hormone is effective in treatment of short stature associated with short stature homeobox-containing gene deficiency: Two-year results of a randomized, controlled, multicenter trial.ABSTRACT: The short stature homeobox-containing gene, SHOX, located on the distal ends of the X and Y chromosomes, encodes a homeodomain transcription factor responsible for a significant proportion of long-bone growth. Patients with mutations or deletions of SHOX, including those with Turner syndrome (TS) who are haplo-insufficient for SHOX, have variable degrees of growth impairment, with or without a spectrum of skeletal anomalies consistent with dyschondrosteosis.Our objective was to determine the efficacy of GH in treating short stature associated with short stature homeobox-containing gene deficiency (SHOX-D).Fifty-two prepubertal subjects (24 male, 28 female; age, 3.0-12.3 yr) with a molecularly proven SHOX gene defect and height below the third percentile for age and gender (or height below the 10th percentile and height velocity below the 25th percentile) were randomized to either a GH-treatment group (n = 27) or an untreated control group (n = 25) for 2 yr. To compare the GH treatment effect between subjects with SHOX-D and those with TS, a third study group, 26 patients with TS aged 4.5-11.8 yr, also received GH. Between-group comparisons of first-year and second-year height velocity, height sd score, and height gain (cm) were performed using analysis of covariance accounting for diagnosis, sex, and baseline age.The GH-treated SHOX-D group had a significantly greater first-year height velocity than the untreated control group (mean +/- se, 8.7 +/- 0.3 vs. 5.2 +/- 0.2 cm/yr; P < 0.001) and similar first-year height velocity to GH-treated subjects with TS (8.9 +/- 0.4 cm/yr; P = 0.592). GH-treated subjects also had significantly greater second-year height velocity (7.3 +/- 0.2 vs. 5.4 +/- 0.2 cm/yr; P < 0.001), second-year height sd score (-2.1 +/- 0.2 vs.-3.0 +/- 0.2; P < 0.001) and second-year height gain (16.4 +/- 0.4 vs. 10.5 +/- 0.4 cm; P < 0.001) than untreated subjects.This large-scale, randomized, multicenter clinical trial in subjects with SHOX-D demonstrates marked, highly significant, GH-stimulated increases in height velocity and height SDS during the 2-yr study period. The efficacy of GH treatment in subjects with SHOX-D was equivalent to that seen in subjects with TS. We conclude that GH is effective in improving the linear growth of patients with various forms of SHOX-D."
1,"TITLE: Effectiveness of pelvic floor muscle training with and without electromyographic biofeedback for urinary incontinence in women: multicentre randomised controlled trial.ABSTRACT: To assess the effectiveness of pelvic floor muscle training (PFMT) plus electromyographic biofeedback or PFMT alone for stress or mixed urinary incontinence in women.Parallel group randomised controlled trial.23 community and secondary care centres providing continence care in Scotland and England.600 women aged 18 and older, newly presenting with stress or mixed urinary incontinence between February 2014 and July 2016: 300 were randomised to PFMT plus electromyographic biofeedback and 300 to PFMT alone.Participants in both groups were offered six appointments with a continence therapist over 16 weeks. Participants in the biofeedback PFMT group received supervised PFMT and a home PFMT programme, incorporating electromyographic biofeedback during clinic appointments and at home. The PFMT group received supervised PFMT and a home PFMT programme. PFMT programmes were progressed over the appointments.The primary outcome was self-reported severity of urinary incontinence (International Consultation on Incontinence Questionnaire-urinary incontinence short form (ICIQ-UI SF), range 0 to 21, higher scores indicating greater severity) at 24 months. Secondary outcomes were cure or improvement, other pelvic floor symptoms, condition specific quality of life, women's perception of improvement, pelvic floor muscle function, uptake of other urinary incontinence treatment, PFMT self-efficacy, adherence, intervention costs, and quality adjusted life years.Mean ICIQ-UI SF scores at 24 months were 8.2 (SD 5.1, n=225) in the biofeedback PFMT group and 8.5 (SD 4.9, n=235) in the PFMT group (mean difference -0.09, 95% confidence interval -0.92 to 0.75, P=0.84). Biofeedback PFMT had similar costs (mean difference £121 ($154; €133), -£409 to £651, P=0.64) and quality adjusted life years (-0.04, -0.12 to 0.04, P=0.28) to PFMT. 48 participants reported an adverse event: for 23 this was related or possibly related to the interventions.At 24 months no evidence was found of any important difference in severity of urinary incontinence between PFMT plus electromyographic biofeedback and PFMT alone groups. Routine use of electromyographic biofeedback with PFMT should not be recommended. Other ways of maximising the effects of PFMT should be investigated.ISRCTN57756448."
1,"TITLE: Comparison of the modified Early Treatment Diabetic Retinopathy Study and mild macular grid laser photocoagulation strategies for diabetic macular edema.ABSTRACT: To compare 2 laser photocoagulation techniques for treatment of diabetic macular edema: the modified Early Treatment Diabetic Retinopathy Study (ETDRS) direct/grid photocoagulation technique and a potentially milder (but potentially more extensive) mild macular grid (MMG) laser technique in which microaneurysms are not treated directly and small mild burns are placed throughout the macula, whether or not edema is present.Two hundred sixty-three subjects (mean age, 59 years) with previously untreated diabetic macular edema were randomly assigned to receive laser photocoagulation by either the modified ETDRS (162 eyes) or MMG (161 eyes) technique. Visual acuity, fundus photographs, and optical coherence tomography measurements were obtained at baseline and at 3.5, 8, and 12 months. Treatment was repeated if diabetic macular edema persisted.Change in optical coherence tomography measurements at 12-month follow-up.Among eyes with a baseline central subfield thickness of 250 microm or greater, central subfield thickening decreased by an average of 88 microm in the modified ETDRS group and by 49 microm in the MMG group at 12-month follow-up (adjusted mean difference, 33 microm; 95% confidence interval, 5-61 microm; P = .02). Weighted inner zone thickening by optical coherence tomography decreased by 42 microm in the modified ETDRS group and by 28 microm in the MMG group (adjusted mean difference, 14 microm; 95% confidence interval, 1-27 microm; P = .04); maximum retinal thickening (maximum thickening of the central and 4 inner subfields) decreased by 66 and 39 microm, respectively (adjusted mean difference, 27 microm; 95% confidence interval, 6-47 microm; P = .01), and retinal volume decreased by 0.8 and 0.4 mm3, respectively (adjusted mean difference, 0.3 mm3; 95% confidence interval, 0.02-0.53 mm3; P = .03). At 12 months, the mean change in visual acuity was 0 letters in the modified ETDRS group and 2 letters worse in the MMG group (adjusted mean difference, 2 letters; 95% confidence interval, -0.5 to 5 letters; P = .10).At 12 months after treatment, the MMG technique was less effective at reducing optical coherence tomography-measured retinal thickening than the more extensively evaluated current modified ETDRS laser photocoagulation approach. However, the visual acuity outcome with both approaches is not substantially different. Given these findings, a larger long-term trial of the MMG technique is not justified.Modified ETDRS focal photocoagulation should continue to be a standard approach for treating diabetic macular edema.clinicaltrials.gov Identifier: NCT00071773."
1,"TITLE: Once-daily cefepime versus ceftriaxone for nursing home-acquired pneumonia.ABSTRACT: To compare once-daily intramuscular cefepime with ceftriaxone controls.Double-blind study.Six skilled nursing facilities.Residents aged 60 and older with nursing home-acquired pneumonia.Cultures were obtained, and patients were randomized to cefepime or ceftriaxone 1 g intramuscularly every 24 hours.Clinical success: cure or improvement. Cure was defined as complete resolution of all symptoms and signs of pneumonia or a return to the patient's baseline state. Improvement was defined as clear improvement but incomplete resolution of all pretherapy symptoms or signs or incomplete return to the patient's usual baseline status. Safety and pharmacoeconomics were also assessed.Sixty-nine patients were randomized; 61 were evaluable: (32 to cefepime, 29 ceftriaxone). Patients were predominately female (76%). They had a mean age+/-standard deviation of 85+/-6, with a mean 5.8+/-1.9 comorbidities; they had age-appropriate renal dysfunction, with a mean estimated creatinine clearance of 35+/-7 mL/min. Clinical success occurred in 78% of cefepime- and 66% of ceftriaxone-treated patients (P=.39). Fifty-seven patients (93%) were switched to oral antibiotics after 3 days. Antibiotic-related adverse events occurred in 5% of patients. Seven patients (11.5%) were hospitalized. The overall mortality rate was 8%. Mean antibiotic costs were 117+/-40 dollars for cefepime- and 215+/-68 dollars for ceftriaxone-treated patients (P<.001). Cost-effectiveness analysis of total costs showed that cefepime would cost 597 dollars and ceftriaxone 1,709 dollars per expected successfully treated patient. One- and two-way sensitivity analyses using a generic price for ceftriaxone and improving its comparative efficacy revealed that the results were robust.Once-daily cefepime was a cost-effective alternative to ceftriaxone for the treatment of elderly nursing home residents who developed pneumonia and did not require hospitalization."
1,"TITLE: Effects of valsartan alone versus valsartan/simvastatin combination on ambulatory blood pressure, C-reactive protein, lipoproteins, and monocyte chemoattractant protein-1 in patients with hyperlipidemia and hypertension.ABSTRACT: Angiotensin receptor blockers have been hypothesized to have synergistic effects with statins. We evaluated the effects of valsartan alone or combined with simvastatin on blood pressure (BP) and indexes of inflammation and oxidant stress in hypertensive patients with hyperlipidemia. In this double-blind trial, 404 patients were randomized to 12 weeks valsartan 160 mg (V) or valsartan 160 mg plus simvastatin 20 mg (V/S20) or 80 mg (V/S80). Twenty-four-hour mean ambulatory BP and biochemical marker measurements were recorded at baseline and study end. There were no statistically significant between-treatment differences for least-square mean reductions from baseline in systolic BP (V, -9.22; V/S20, -9.25; V/S80, -9.58 mm Hg; p <0.0001 for all within-treatment changes vs baseline). Plasma high-sensitivity C-reactive protein decreased with the combinations but not with V alone (least-square mean median change from baseline, -0.16, -0.20, -0.70 mg/L; p = 0.0001 for V/S80 vs baseline; p = 0.045 for V/S20 vs baseline; p = 0.0023 for V/S80 vs V/S20; p = 0.0045 for V/S80 vs V). Monocyte chemoattractant protein-1 was reduced by V, with no evidence for additional lowering with V/S combinations. In conclusion, addition of simvastatin to valsartan did not incrementally lower BP. However, V/S80 was superior to V and V/S20 in reducing high-sensitivity C-reactive protein."
1,"TITLE: Efficacy and tolerability of naratriptan for short-term prevention of menstrually related migraine: data from two randomized, double-blind, placebo-controlled studies.ABSTRACT: In a pilot study, naratriptan was significantly more effective than placebo in preventing menstrually related migraine (MRM) when given as 1 mg twice daily for 5 days beginning 2 days before the predicted onset of MRM for up to 4 menstrual cycles.To evaluate the efficacy and tolerability of naratriptan for short-term prevention of MRM in 2 large, identically designed, randomized, double-blind, placebo-controlled, parallel-group studies.MRM was defined as any migraine beginning during the perimenstrual period (PMP). By definition, the PMP consisted of Days -2, -1, 1, 2, 3, and 4, with Day 1 being the first day of menstrual flow. Adult women were eligible if they reported a history of MRM, had regular menstrual cycles, and could predict within 2 days both the onset of menstrual flow and MRM. The studies comprised a baseline phase and a treatment phase. During the baseline phase, patients prophylactically treated their first PMP after the screening visit with single-blind placebo. Patients who documented an MRM while receiving placebo were eligible for the treatment phase. During the treatment phase, patients were randomized to receive either naratriptan 1 mg twice daily or placebo beginning 3 days before the predicted onset of MRM for a total of 6 days for 4 PMPs or 6 months, whichever occurred sooner. The primary efficacy endpoint was the mean percentage of treated PMPs without MRM per patient. Secondary efficacy endpoints included the percentage of patients who were free of MRM during all treated PMPs, the median number of days with MRM over 4 PMPs, and patient satisfaction. Safety and tolerability measures included adverse events, standard clinical laboratory tests, and vital signs.The intent-to-treat population was 287 in Study 1 (149 in the naratriptan group and 138 in the placebo group) and 346 in Study 2 (173 in each treatment group). Approximately 20% of randomized patients in each treatment group in Study 1 and 10% in each treatment group in Study 2 withdrew prematurely from the studies over the 4-month treatment period. The mean percentage of PMPs without MRM per patient was 38% and 34% among naratriptan-treated patients treating at least 1 PMP compared with 29% and 24% among placebo-treated patients in each respective study (P < .05 naratriptan vs placebo for both studies). Efficacy of naratriptan did not vary as a function of age, use of oral contraceptives, or use of migraine prophylaxis. More patients who had received naratriptan reported attacks posttreatment compared to patients who had received placebo. Among patients treating at least 1 PMP, the percentage of patients with no MRM in any treated PMP was significantly (P < .05) higher in the naratriptan group (11%; 19/173) than the placebo group (3%; 6 of 173) in Study 2. There were no differences in the percentages of patients with no MRM in any treated PMP in Study 1. The number of MRM days per patient across 4 PMPs was significantly lower in the naratriptan group than in the placebo group in both studies (median 5.0 days vs 6.5 days in Study 1 [P= .005] and 5.3 days vs 6.0 days in Study 2 [P= .018]). Significantly more patients receiving naratriptan were satisfied with the ability of naratriptan to control MRM either by preventing their occurrence or reducing their severity or duration compared with patients receiving placebo. No single drug-related adverse event was reported by more than 2% of patients in a treatment group in either study, and no serious drug-related adverse events were reported.Naratriptan 1 mg twice daily for 6 days per month is effective and well tolerated when used for short-term prevention of MRM. More patients receiving naratriptan than placebo were satisfied with treatment. The observed increase in posttreatment attacks needs further study."
1,"TITLE: Continuous versus interrupted sutures for repair of episiotomy or second-degree perineal tears: a randomised controlled trial.ABSTRACT: To evaluate the repair techniques of continuous and interrupted methods for episiotomy or perineal tears.A randomised controlled trial.The Hospital Universitario Principe de Asturias, a state hospital belonging to the community of Madrid.Four hundred forty-five women who had undergone vaginal deliveries with episiotomies or second-grade tearing of the perineum between September 2005 and July 2007.One group was repaired with continuous, nonlocking sutures involving the vagina, perineum, and subcutaneous tissues. The other group had continuous, locking sutures of the vagina, interrupted sutures in the perineal muscles, and interrupted transcutaneous sutures. The threads used for stitching were identical in both groups.The participants were questioned regarding the sensation of pain and the use of painkillers on the second and the tenth days, and 3 months postpartum.When comparing the group with continuous suture to the group with interrupted sutures, the differences included less repair time (1 minute; P= 0.017) and less suture material used (relative risk [RR], 3.2, 95% CI: 2.6-4.0). The comparison of pain on the second and tenth days, and 3 months postpartum were not statistically different between the two techniques (RR, 1.08, 95% CI: 0.74-1.57; RR, 0.96, 95% CI: 0.59-1.55; and RR, 0.68, 95% CI: 0.19-2.46, respectively).Although we did not demonstrate that one technique was better than the other in the incidence of pain in the short or long term, we showed that episiotomy and perineal tear repairs with continuous suturing were quicker and used less suture material without an increase in complication than interrupted suturing."
1,"TITLE: Efficacy and safety of a routine early invasive strategy in relation to time from symptom onset to fibrinolysis (a subgroup analysis of TRANSFER-AMI).ABSTRACT: The aim of this study was to assess the efficacy and safety of an early invasive strategy post-fibrinolysis in relation to time from symptom onset to fibrinolysis in patients with ST-elevation myocardial infarction (STEMI). The Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized 1,059 patients receiving fibrinolysis for STEMI to an early invasive strategy versus standard therapy. The primary end point was the composite of death, reinfarction, recurrent ischemia, new or worsening heart failure, or cardiogenic shock at 30 days. In this post hoc subgroup analysis, we examined the effect of an early invasive strategy on efficacy and safety outcomes after stratification by time from symptom onset to fibrinolysis (<2 or ≥2 hours). Of 1,059 patients in TRANSFER-AMI, 557 (53%) received fibrinolysis <2 hours and 502 (47%) ≥2 hours after symptom onset. Compared to patients who received fibrinolysis within 2 hours of symptoms, patients who received fibrinolysis ≥2 hours after symptom onset had higher Global Registry of Acute Coronary Events risk scores (median 127 vs 122, p = 0.004). The effect of an early invasive strategy did not differ between symptom-to-fibrinolysis time strata for the primary efficacy end point (p-heterogeneity = 0.67), 30-day mortality, the composite of death or reinfarction at 30 days, 6 months, or 1 year, or bleeding (all p-heterogeneity >0.40). In conclusion, the efficacy and safety of an early invasive strategy in patients undergoing fibrinolysis for STEMI do not vary in relation to time (<2 or ≥2 hours) from symptom onset to fibrinolysis."
1,"TITLE: Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF): a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study.ABSTRACT: Most patients admitted for acute heart failure have normal or increase blood pressure. Relaxin is a natural human peptide that affects multiple vascular control pathways, suggesting potential mechanisms of benefit for such patients. We assessed the dose response of relaxin's effect on symptom relief, other clinical outcomes, and safety.In a placebo-controlled, parallel-group, dose-ranging study, 234 patients with acute heart failure, dyspnoea, congestion on chest radiograph, and increased brain natriuretic peptide (BNP) or N-terminal prohormone of BNP, mild-to-moderate renal insufficiency, and systolic blood pressure greater than 125 mm Hg were recruited from 54 sites in eight countries and enrolled within 16 h of presentation. Patients were randomly assigned, in a double-blind manner via a telephone-based interactive voice response system, to standard care plus 48-h intravenous infusion of placebo (n=62) or relaxin 10 microg/kg (n=40), 30 microg/kg (n=43), 100 microg/kg (n=39), or 250 microg/kg (n=50) per day. Several clinical endpoints were explored to assess whether intravenous relaxin should be pursued in larger studies of acute heart failure, to identify an optimum dose, and to help to assess endpoint selection and power calculations. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00520806.In the modified intention-to-treat population, 61 patients were assessed in the placebo group, 40 in the relaxin 10 microg/kg per day group, 42 in the relaxin 30 microg/kg per day group, 37 in the relaxin 100 microg/kg per day group, and 49 in the relaxin 250 microg/kg per day group. Dyspnoea improved with relaxin 30 microg/kg compared with placebo, as assessed by Likert scale (17 of 42 patients [40%] moderately or markedly improved at 6 h, 12 h, and 24 h vs 14 of 61 [23%]; p=0.044) and visual analogue scale through day 14 (8214 mm x h [SD 8712] vs 4622 mm x h [9003]; p=0.053). Length of stay was 10.2 days (SD 6.1) for relaxin-treated patients versus 12.0 days (7.3) for those given placebo, and days alive out of hospital were 47.9 (10.1) versus 44.2 (14.2). Cardiovascular death or readmission due to heart or renal failure at day 60 was reduced with relaxin (2.6% [95% CI 0.4-16.8] vs 17.2% [9.6-29.6]; p=0.053). The number of serious adverse events was similar between groups.When given to patients with acute heart failure and normal-to-increased blood pressure, relaxin was associated with favourable relief of dyspnoea and other clinical outcomes, with acceptable safety."
1,"TITLE: Effect of heart rate on the pharmacokinetics of fentanyl in dogs anesthetized with isoflurane and hydromorphone.ABSTRACT: To compare the pharmacokinetics of fentanyl at lower (LHR) or higher heart rate (HHR) in dogs anesthetized with isoflurane.Prospective, randomized, crossover controlled trial.A group of six healthy 13-month-old male Beagle dogs weighing 9.9 ± 0.7 kg (mean ± standard deviation).Dogs were allocated to two treatments: LHR (HR: 45-75 beats minute) and HHR (HR: 100-130 beats minute). Anesthesia was maintained with isoflurane and hydromorphone (0.1 mg kg followed by 0.02-0.10 mg kg hour) for both treatments. Glycopyrrolate was administered in HHR to maintain HR within the desired range. Afterwards, fentanyl (20 μg kg) was intravenously administered over 5 minutes. Arterial blood samples were collected for plasma fentanyl concentration measurement by liquid chromatography/mass spectrometry. The pharmacokinetics of fentanyl were compared between treatments and the differences were considered significant at p < 0.05.A three-compartment model best fitted the changes in plasma fentanyl concentration. Clearance (CL; mL minute kg) was 33.2 (24.0-48.0) and 61.3 (44.5-72.7), maximum concentration (ng mL) 33.6 (23.4-36.6) and 20.0 (16.7-28.0), apparent volume of the rapid peripheral compartment (mL kg) 436 (352-723) and 925 (499-1887), apparent volume at steady state (mL kg) 4064 (3453-6546) and 7195 (5077-8601), cardiac index (CI; mL minute m) 2.83 (1.98-3.67) and 4.91 (3.22-6.09) and HR (beats minute) 68 (49-72) and 120 (102-129) for LHR and HHR, respectively, with significant differences between treatments. Significant correlations (0.92 and 0.90) were found between CI and CL, and between HR and CL, respectively.The increase in HR and the resultant improvement in cardiac output increased fentanyl CL and volume of distribution, which resulted in a decrease in plasma fentanyl concentration in isoflurane-anesthetized dogs."
1,"TITLE: Quercetin reduces illness but not immune perturbations after intensive exercise.ABSTRACT: To investigate the effects of quercetin supplementation on incidence of upper respiratory tract infections (URTI) and exercise-induced changes in immune function.Trained male cyclists (N=40) were randomized to quercetin (N=20) or placebo (N=20) groups and, under double-blind procedures, received 3 wk quercetin (1000 mg.d(-1)) or placebo before, during, and for 2 wk after a 3-d period in which subjects cycled for 3 h.d(-1) at approximately 57% Wmax. Blood and saliva samples were collected before and after each of the three exercise sessions and assayed for natural killer cell activity (NKCA), PHA-stimulated lymphocyte proliferation (PHA-LP), polymorphonuclear oxidative-burst activity (POBA), and salivary IgA output (sIgA).Pre- to postexercise changes in NKCA, PHA-LP, POBA, and sIgA did not differ significantly between quercetin and placebo groups. URTI incidence during the 2-wk postexercise period differed significantly between groups (quercetin=1/20 vs placebo=9/20, Kaplan-Meier analysis statistic=8.31, P=0.004).Quercetin versus placebo ingestion did not alter exercise-induced changes in several measures of immune function, but it significantly reduced URTI incidence in cyclists during the 2-wk period after intensified exercise."
1,"TITLE: Pattern of iron chelation therapy in Egyptian beta thalassemic patients: Mansoura University Children's Hospital experience.ABSTRACT: The simultaneous use of deferoxamine (DFO) and deferiprone (DFP) has an additive effect in iron excretion in transfusion-dependent thalassemic patients.To evaluate the efficacy and safety of a prospective alternating therapy with DFO and DFP in patients with beta-thalassemia major (TM) and increased serum ferritin with DFO monotherapy alone.Sixty patients with beta-TM (mean age +/- SD, 13.05 +/- 6.1, range 10-20 years) with iron overload (serum ferritin > 2000 ng/ml) were studied. They received DFO at a daily dose of 40 mg/kg/day for 5-7 nights/week for the past several years. These patients were randomly assigned either to continue treatment with DFO alone (DFO group, n = 30) or prospectively receive additional alternating therapy with DFP at 75 mg/kg/day for 4 days/week and DFO for the other 2 days/week (alternating therapy group, n = 30). The efficacy of both groups was assessed by measurements of serum ferritin, echocardiography, and 24 h urine iron excretion (UIE) levels throughout 1 year follow-up.In the 60 evaluable patients, the mean serum ferritin ( +/- SD) fell dramatically from 4500 ( +/- 1250) ng/ml at the start of the study to 1250 ( +/- 750) ng/ml (alternate therapy group; P < 0.001) at the end of the study. There was also a significant improvement in the myocardial function as assessed by the ejection fraction (P < 0.002) and fractional shortening (P < 0.01) in those patients on alternate therapy for 1 year. Their mean urinary iron excretion elevated from 0.41 +/- 0.27 to 0.76 +/- 0.49 mg/kg/24 h (P < 0.003). There was a significant difference between both groups as regard the studied parameters at the end of the study. Whereas, there was no statistical difference as regard the studied parameters at the start and the end of the study in the DFO group. No significant adverse effects had occurred in both groups that necessitated withdrawal from the study.beta-Thalassemic major patients with transfusional iron overload can be safely and effectively treated with an alternate therapy of DFO/DFP with a progressive fall in the mean serum ferritin and significant improvement of myocardial performance."
1,"TITLE: The effect of a multispecies probiotic on the intestinal microbiota and bowel movements in healthy volunteers taking the antibiotic amoxycillin.ABSTRACT: One of the side effects of antimicrobial therapy is a disturbance of the intestinal microbiota potentially resulting in antibiotic-associated diarrhea (AAD). In this placebo-controlled double-blind study, the effect of a multispecies probiotic on the composition and metabolic activity of the intestinal microbiota and bowel habits was studied in healthy volunteers taking amoxycillin.Forty-one healthy volunteers were given 500 mg amoxycillin twice daily for 7 days and were randomized to either 5 g of a multispecies probiotic, Ecologic AAD (10(9) cfu/g), or placebo, twice daily for 14 days. Feces and questionnaires were collected on day 0, 7, 14, and 63. Feces was analyzed as to the composition of the intestinal microbiota, and beta-glucosidase activity, endotoxin concentration, Clostridium difficile toxin A, short chain fatty acids (SCFAs), and pH were determined. Bowel movements were scored according to the Bristol stool form scale.Mean number of enterococci increased significantly from log 4.1 at day 0 to log 5.8 (day 7) and log 6.9 (day 14) cfu/g feces (P < 0.05) during probiotic intake. Although no other significant differences were observed between both intervention groups, within each group significant changes were found over time in both microbial composition and metabolic activity. Moreover, bowel movements with a frequency >or=3 per day for at least 2 days and/or a consistency >or=5 for at least 2 days were reported less frequently in the probiotic compared to the placebo group (48%vs 79%, P < 0.05).Apart from an increase in enterococci no significant differences in microbial composition and metabolic activity were observed in the probiotic compared with the placebo group. However, changes over time were present in both groups, which differed significantly between the probiotic and the placebo arm, suggesting that the amoxycillin effect was modulated by probiotic intake. Moreover, the intake of a multispecies probiotic significantly reduced diarrhea-like bowel movements in healthy volunteers receiving amoxycillin."
1,"TITLE: Prophylactic mesh placement to prevent parastomal hernia, early results of a prospective multicentre randomized trial.ABSTRACT: Parastomal hernia (PSH) is a common complication after colostomy formation. Recent studies indicate that mesh implantation during formation of a colostomy might prevent a PSH. To determine if placement of a retromuscular mesh at the colostomy site is a feasible, safe and effective procedure in preventing a parastomal hernia, we performed a multicentre randomized controlled trial in 11 large teaching hospitals and three university centres in The Netherlands.Augmentation of the abdominal wall with a retromuscular light-weight polypropylene mesh (Parietene Light™, Covidien) around the trephine was compared with traditional colostomy formation. Patients undergoing elective open formation of a permanent end-colostomy were eligible. 150 patients were randomized between 2010 and 2012. Primary endpoint of the PREVENT trial is the incidence of parastomal hernia. Secondary endpoints are morbidity, pain, quality of life, mortality and cost-effectiveness. This article focussed on the early results of the PREVENT trial and, therefore, operation time, postoperative morbidity, pain, and quality of life were measured.Outcomes represent results after 3 months of follow-up. A total of 150 patients were randomized. Mean operation time of the mesh group (N = 72) was significantly longer than in the control group (N = 78) (182.6 vs. 156.8 min; P = 0.018). Four (2.7 %) peristomal infections occurred of which one (1.4 %) in the mesh group. No infection of the mesh occurred. Most of the other infections were infections of the perineal wound, equally distributed over both groups. No statistical differences were discovered in stoma or mesh-related complications, fistula or stricture formation, pain, or quality of life.During open and elective formation of an end-colostomy, primary placement of a retromuscular light-weight polypropylene mesh for prevention of a parastomal hernia is a safe and feasible procedure. The PREVENT trial is registered at: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2018 ."
1,"TITLE: Bone mineral density and inflammatory and bone biomarkers after darunavir-ritonavir combined with either raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults with HIV-1: a substudy of the NEAT001/ANRS143 randomised trial.ABSTRACT: Osteopenia, osteoporosis, and low bone mineral density are frequent in patients with HIV. We assessed the 96 week loss of bone mineral density associated with a nucleoside or nucleotide reverse transcriptase inhibitor (NtRTI)-sparing regimen.Antiretroviral-naive adults with HIV were enrolled in 78 clinical sites in 15 European countries into a randomised (1:1), open-label, non-inferiority trial (NEAT001/ANRS143) assessing the efficacy and safety of darunavir (800 mg once per day) and ritonavir (100 mg once per day) plus either raltegravir (400 mg twice per day; NtRTI-sparing regimen) or tenofovir (245 mg once per day) and emtricitabine (200 mg once per day; standard regimen). For this bone-health substudy, 20 of the original sites in six countries participated, and any patient enrolled at one of these sites who met the following criteria was eligible: plasma viral loads greater than 1000 HIV RNA copies per mL and CD4 cell counts of fewer than 500 cells per μL, except in those with symptomatic HIV infection. Exclusion criteria included treatment for malignant disease, testing positive for hepatitis B virus surface antigen, pregnancy, creatinine clearance less than 60 mL per min, treatment for osteoporosis, systemic steroids, or oestrogen-replacement therapy. The two primary endpoints were the mean percentage changes in lumbar spine and total hip bone mineral density at week 48, assessed by dual energy x-ray absorptiometry (DXA) scans. We did the analysis with an intention-to-treat-exposed approach with antiretroviral modifications ignored. The parent trial is registered with ClinicalTrials.gov, number NCT01066962, and is closed to new participants.Between Aug 2, 2010, and April 18, 2011, we recruited 146 patients to the substudy, 70 assigned to the NtRTI-sparing regimen and 76 to the standard regimen. DXA data were available for 129, 121 and 107 patients at baseline, 48 and 96 weeks respectively. At week 48, the mean percentage loss in bone mineral density in the lumbar spine was greater in the standard group than in the NtRTI-sparing group (mean percentage change -2.49% vs -1.00%, mean percentage difference -1.49, 95% CI -2.94 to -0.04; p=0.046). Total hip bone mineral density loss was similarly greater at week 48 in the standard group than in the NtRTI-sparing group (mean percentage change -3.30% vs -0.73%; mean percentage difference -2.57, 95% CI -3.75 to -1.35; p<0.0001). Seven new fractures occurred during the trial (two in the NtRTI-sparing group and five in the standard group).A raltegravir-based regimen was associated with significantly less loss of bone mineral density than a standard regimen containing tenofovir disoproxil fumarate, and might be a treatment option for patients at high risk of osteopenia or osteoporosis who are not suitable for NtRTIs such as abacavir or tenofovir alafenamide.The European Union Sixth Framework Programme, Inserm-ANRS, Ministerio de Sanidad y Asuntos Sociales de España, Gilead Sciences, Janssen Pharmaceuticals, and Merck Laboratories."
1,"TITLE: Singular and combined effects of nebivolol and lifestyle modification on large artery stiffness in hypertensive adults.ABSTRACT: We hypothesized that the combination of nebivolol and lifestyle modification would reduce large artery stiffness in middle-aged and older hypertensive adults more than either intervention alone.To address this, 45 men and women (age 40-75 years) with stage I hypertension were randomized to receive either nebivolol (NB; forced titration to 10 mg OD; n = 15; age 57.2 ± 11.4 years; body mass index [BMI] 30.8 ± 5.8 kg/m(2)), lifestyle modification (LM; 5-10% weight loss via calorie restriction and physical activity; n = 15; age 52.7 ± 8.5 years; BMI 33.9 ± 7.2 kg/m(2)) or nebivolol plus lifestyle modification (NBLM; n = 15; age 58.9 ± 9.4 years; BMI 32.5 ± 4.9 kg/m(2)) for 12 weeks. β-stiffness index, a blood-pressure-independent measure of arterial stiffness, and arterial compliance were measured via high-resolution ultrasound and tonometry at baseline and after the 12-week intervention. There was no difference between groups in age, body weight or composition, blood pressure, or in β-stiffness index or arterial compliance at baseline (all p > 0.05).Following the 12-week intervention, body weight decreased ~5% (p < 0.05) in the LM and NBLM groups but did not change from baseline in the NB group (p > 0.05). Supine brachial and carotid systolic and diastolic blood pressure declined following treatment in each of the groups (p < 0.05). However, the magnitude of reduction was not different (p < 0.05) between groups. β-stiffness index declined (-2.03 ± 0.60, -1.87 ± 0.83 and -2.51 ± 0.90 U) and arterial compliance increased similarly (both p > 0.05) in the NB, LM and NBLM groups, respectively.In summary, our findings indicate that the combination of nebivolol and lifestyle modification reduced large artery stiffness to a similar degree as either intervention alone in middle-aged and older hypertensive adults."
1,"TITLE: Metoclopramide role in preventing ileus after cesarean, a clinical trial.ABSTRACT: Ileus is a common event following cesarean section. Early post-cesarean recovery is very important not only for the mother but also for the baby who is dependent on breastfeeding. This article aims to demonstrate the efficacy of metoclopramide for the prevention of ileus after cesarean.In this randomized controlled trial, 696 women scheduled for cesarean were randomized in two groups. Three hundred fifty-three persons settled in control group and 343 were assigned in intervention group who received an injection of 10-mg intramuscular metoclopramide prior to operation. After cesarean, the participants recorded the first flatus, defecation, feeling of hunger, feeding and ambulation in a questionnaire, and also their sense of bloating in a visual analog scale under supervision of a research assistant. The data was analyzed by SPSS 17, t test, and chi-square, while p < 0.05 was considered significant.The interval between cesarean and the first flatus (p < 0.0001), defecation (p < 0.0001), feeling of hunger (p < 0.0001), feeding (p = 0.007), and ambulation (p < 0.0001) were significantly shorter in the metoclopramide group. In addition, polytomous logistic regression analysis showed the metoclopramide group had less bloating with significant difference (OR = 2.83 and CI 1.91-4.21).Our study proved the functionality of metoclopramide in preventing ileus. As this drug is safe, tolerable, harmless, inexpensive and available, and also no definite method has been developed to prevent ileus after cesarean; yet, metoclopramide could be considered as a suitable option. Certainly with regard to some limitations in our study, further comprehensive studies are still required to ensure validity of the obtained results."
1,"TITLE: The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: A randomized, double-blind, placebo-controlled trial in petrochemical workers.ABSTRACT: The aim of this study was to determine effects of probiotic yogurt and multispecies probiotic capsule supplementation on mental health and hypothalamic-pituitary-adrenal axis in petrochemical workers.The present randomized double-blind, placebo-controlled trial was conducted on 70 petrochemical workers. Subjects were randomly divided into three groups to receive 100 g/day probiotic yogurt + one placebo capsule (n = 25) or one probiotic capsule daily + 100 g/day conventional yogurt (n = 25) or 100 g/day conventional yogurt + one placebo capsule (n = 20) for 6 weeks. Mental health parameters including general health questionnaire (GHQ) and depression anxiety and stress scale (DASS) scores were measured. Fasting blood samples were obtained at the beginning and 6 weeks after the intervention to quantify hypothalamic-pituitary-adrenal axis.After 6 weeks of intervention, a significant improvement of GHQ was observed in the probiotic yogurt (18.0 ± 1.5 vs. 13.5 ± 1.9, P = 0.007) and in the probiotic capsule group (16.9 ± 1.8 vs. 9.8 ± 1.9, P = 0.001), as well as a significant improvement in DASS scores in the probiotic yogurt (23.3 ± 3.7 vs. 13.0 ± 3.7, P = 0.02) and the probiotic capsule group (18.9 ± 3.2 vs. 9.4 ± 4.0, P = 0.006). However, there was no significant improvement in the conventional yogurt group (P = 0.05 for GHQ and P = 0.08 for DASS).The consumption of probiotic yogurt or a multispecies probiotic capsule had beneficial effects on mental health parameters in petrochemical workers."
1,"TITLE: Docosahexaenoic acid supplementation and time at achievement of gross motor milestones in healthy infants: a randomized, prospective, double-blind, placebo-controlled trial.ABSTRACT: Docosahexaenoic acid (DHA) intake throughout the first year of life is associated with neurodevelopmental and neuropsychological benefits. Few studies have evaluated the role of DHA intakes on age at achievement of gross motor milestones.The objective was to assess the effects of DHA supplementation throughout the first year of life on the achievement of four gross motor milestones in healthy infants.In this multicenter prospective, randomized, double-blind, placebo-controlled trial, 1160 healthy neonates were assigned to receive supplementation with either 20 mg liquid DHA (n = 580) or placebo (n = 580) orally once daily throughout the first year of life. The primary endpoint was the time at achievement of 4 gross motor milestones (sitting without support, hands-and-knees crawling, standing alone, and walking alone). All analyses were performed on an intention-to-treat basis.The time to achievement of sitting without support was shorter (P < 0.001) in infants who received DHA [median: 26 wk; interquartile range (IQR): 24-29 wk] than in those who received placebo (27 wk; 26-31 wk). No significant difference between infants who received DHA or placebo was found for hands-and-knees crawling [39 wk (34-44 wk) compared with 40 wk (35-44 wk), respectively], standing alone [49 wk (43-55 wk) compared with 49 wk (44-57 wk), respectively], and walking alone [55 wk (50-60 wk) compared with 56 wk (52-61 wk), respectively].Despite the 1-wk advance in sitting without support associated with DHA supplementation, no demonstrable persistent effects of DHA supplementation on later motor development milestones were found. Thus, the long-term clinical significance of the 1-wk change in sitting without support, if any, remains unknown. This trial is registered at (clinicaltrials.gov) as NCT00610922."
1,"TITLE: Fixation Using Alternative Implants for the Treatment of Hip Fractures (FAITH-2): The Clinical Outcomes of a Multicenter 2 × 2 Factorial Randomized Controlled Pilot Trial in Young Femoral Neck Fracture Patients.ABSTRACT: To assess whether the fixation method and vitamin D supplementation affect the risk of patient-important outcomes within 12 months of injury in nongeriatric femoral neck fracture patients.A pilot factorial randomized controlled trial.Fifteen North American clinical sites.Ninety-one adults 18-60 years of age with a femoral neck fracture requiring surgical fixation.Participants were randomized to a surgical intervention (sliding hip screw or cancellous screws) and a vitamin D intervention (vitamin D3 4000 IU daily vs. placebo for 6 months).The primary clinical outcome was a composite of patient-important complications (reoperation, femoral head osteonecrosis, severe femoral neck malunion, and nonunion). Secondary outcomes included fracture-healing complications and radiographic fracture healing.Eighty-six participants with a mean age of 41 years were included. We found no statistically significant difference in the risk of patient-important outcomes between the surgical treatment arms (hazard ratio 0.90, 95% confidence interval 0.40-2.02, P = 0.80) and vitamin D supplementation treatment arms (hazard ratio 0.96, 95% confidence interval 0.42-2.18, P = 0.92).These pilot trial results continue to describe the results of current fixation implants, inform the challenges of improving outcomes in this fracture population, and may guide future vitamin D trials to improve healing outcomes in young fracture populations. Although the pilot trial was not adequately powered to detect treatment effects, publishing these results may facilitate future meta-analyses on this topic.Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence."
1,"TITLE: Randomized phase 2 study of irinotecan plus cisplatin versus gemcitabine plus vinorelbine as first-line chemotherapy with second-line crossover in patients with advanced nonsmall cell lung cancer.ABSTRACT: The current study was performed to compare the nonplatinum-based combination of gemcitabine and vinorelbine (GV) with the combination of irinotecan and cisplatin (IP) as first-line chemotherapy with second-line crossover in patients with advanced nonsmall cell lung cancer (NSCLC).Patients were randomly assigned to received either irinotecan at a dose of 65 mg/m(2) plus cisplatin at a dose of 30 mg/m(2) (Arm A) or gemcitabine at a dose of 900 mg/m(2) plus vinorelbine at a dose of 25 mg/m(2) (Arm B), each of which was administered on Days 1 and 8 every 3 weeks as the first-line therapy followed by crossover at the time of disease progression.A total of 146 patients were enrolled (75 patients in Arm A and 71 patients in Arm B); 138 patients were evaluable for tumor response and toxicity. During first-line therapy, IP was found to result in more grade 2+ nausea and vomiting (toxicity was graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) (41% vs 12%; P = .0001) and alopecia (36% vs 10%; P = .0003). Pneumonitis was noted only with GV therapy (7% vs 0%; P = .058). During second-line therapy, IP was found to result in more grade 3 diarrhea (17% vs 2%; P = .039) and GV featured more cases of grade 3+ neutropenia (78% vs 40%; P = .0003). IP tended to generate more tumor responses (38% vs 26% as first-line therapy, and 30% vs 13% as second-line therapy) compared with GV. IP also demonstrated a favorable trend in median progression-free survival (4.6 months vs 3.8 months as first-line therapy and 4.5 months vs 2.6 months as second-line therapy) and overall survival (15.9 months vs 13.1 months; P = .3), but this difference was not statistically significant. The majority of patients who were refractory to IP also failed to respond to GV in the second-line setting.The platinum-based IP regimen appeared to be superior to the GV combination in terms of response rate. However, given the similar survival and better tolerability of the nonplatinum GV regimen, either treatment sequence would appear to be acceptable for the treatment of patients with advanced NSCLC."
1,"TITLE: Luteal phase administration of paroxetine for the treatment of premenstrual dysphoric disorder: a randomized, double-blind, placebo-controlled trial in Canadian women.ABSTRACT: To evaluate the efficacy and safety of intermittent, luteal phase-only administration of paroxetine (10 mg and 20 mg) in the treatment of premenstrual dysphoric disorder (PMDD).In this multicenter trial, female outpatients (aged 18-45 years) from 4 Canadian health centers meeting DSM-IV criteria for PMDD were asked to perform daily ratings of their premenstrual symptoms for 2 consecutive menstrual cycles. Those displaying the symptoms of irritability and/or depressed mood in the luteal phases but not in the follicular phases of their menstrual cycles were randomly assigned to intermittent, luteal phase-only treatment with paroxetine 10 mg or 20 mg or placebo for 4 additional cycles. The primary efficacy endpoint was the percent change from baseline at study endpoint on the visual analog scale irritability score. Treatment differences were tested using analysis of covariance ad hoc. Estimated treatment mean differences and their associated 95% confidence intervals were also calculated. Data were collected from May 1999 to November 2002.Ninety-nine patients were included in the intention-to-treat population. When compared with placebo, patients treated with paroxetine 20 mg attained a significant reduction in irritability (difference in median percent change: -23.9, 95% CI = -51.3 to -6.2, p = .014; difference in mean absolute change: -18.6, 95% CI = -32.5 to -4.6, p = .007). A statistically significant difference was not observed when the patients treated with the lower dose of paroxetine (10 mg) were compared with placebo. Treatment was well tolerated with no unexpected side effects.Intermittent administration of paroxetine 20 mg significantly reduced irritability symptoms in patients with PMDD. These results are consistent with previous studies suggesting that PMDD may be treated effectively by luteal phase-only administration of a selective serotonin reuptake inhibitor.clinicaltrials.gov Identifier: NCT00620581."
1,"TITLE: Randomized clinical trial comparing LigaSure haemorrhoidectomy with open diathermy haemorrhoidectomy.ABSTRACT: Milligan-Morgan excision haem-orrhoidectomy remains a very popular treatment modality for third and fourth degree haemorrhoids due to its cost effectiveness and good long-term results. The LigaSure tissue-sealing device is an alternative technique used in haemorrhoidectomy that has been shown to produce favourable results. The aim of this study was to assess the effectiveness of the LigaSure tissue sealing device in comparison with conventional diathermy haemorrhoidectomy.A prospective clinical trial was conducted. Patients with newly diagnosed haemorrhoids requiring haemorrhoidectomy were randomized to either LigaSure haemorrhoidectomy or diathermy haemorrhoidectomy. Surgical technique and postoperative care was standardized. Outcome measures were operative time and bleeding, postoperative pain (measured on a visual analogue scale) and rate of wound healing.We randomized 44 patients, 22 to LigaSure and 22 to diathermy; 43 patients were evaluated. They were aged between 19 and 71 years. There were no differences in patient demographics or type of haemorrhoid being operated on. LigaSure haemorrhoidectomy had a significantly lower mean operative time and intraoperative bleeding. At 3 weeks after surgery, haemorrhoidectomy performed with LigaSure had an odds ratio for complete epithelialization of 3.1 over diathermy (95% CI 1.2-8.2). There was no difference in postoperative pain.LigaSure haemorrhoidectomy is superior to diathermy for open haemorrhoidectomy."
1,"TITLE: A randomised, parallel-group comparison study of diquafosol ophthalmic solution in patients with dry eye in China and Singapore.ABSTRACT: To compare the efficacy and safety of 3% diquafosol ophthalmic solution with those of 0.1% sodium hyaluronate ophthalmic solution in patients with dry eye in China and Singapore.A total of 497 patients with dry eye (Schirmer's test, 5 mm; fluorescein and RB score, 3 points) from China and Singapore were randomised to receive either diquafosol ophthalmic solution (diquafosol) or sodium hyaluronate ophthalmic solution (HA) at 1:1 ratio. The fluorescein staining scores and rose bengal (RB) subjective symptom scores and tear film breakup time were evaluated before treatment and 2 and 4 weeks after start of treatment.In the diquafosol group, changes in fluorescein and RB scores compared with baseline at week 4 or at the time of discontinuation were -2.1±1.5 and -2.5±2.0, respectively. Compared with the HA group, changes in fluorescein score were non-inferior and changes in RB score were superior (p=0.019). In addition, diquafosol and HA improved tear film breakup time by 1.046±1.797 and 0.832±1.775 s, respectively (no significant intergroup difference). Adverse event onset rates were 16.3% (40 of 246 subjects) and 10.0% (25 of 251 subjects) in the diquafosol group and HA group, respectively, with borderline significant intergroup differences (p=0.046), while adverse drug reaction incidence rates were 12.2% (30 of 246 subjects) and 6.0% (15 of 251 subjects), respectively (p=0.019). Only mild adverse drug reactions (>2%) in the form of eye discharge, itching or irritation were observed.Diquafosol improved fluorescein staining score in a manner similar to HA, and significantly improved RB score compared with HA.NCT01101984."
1,"TITLE: Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest.ABSTRACT: Patients who are treated with targeted temperature management after out-of-hospital cardiac arrest with shockable rhythm are at increased risk for ventilator-associated pneumonia. The benefit of preventive short-term antibiotic therapy has not been shown.We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving adult patients (>18 years of age) in intensive care units (ICUs) who were being mechanically ventilated after out-of-hospital cardiac arrest related to initial shockable rhythm and treated with targeted temperature management at 32 to 34°C. Patients with ongoing antibiotic therapy, chronic colonization with multidrug-resistant bacteria, or moribund status were excluded. Either intravenous amoxicillin-clavulanate (at doses of 1 g and 200 mg, respectively) or placebo was administered three times a day for 2 days, starting less than 6 hours after the cardiac arrest. The primary outcome was early ventilator-associated pneumonia (during the first 7 days of hospitalization). An independent adjudication committee determined diagnoses of ventilator-associated pneumonia.A total of 198 patients underwent randomization, and 194 were included in the analysis. After adjudication, 60 cases of ventilator-associated pneumonia were confirmed, including 51 of early ventilator-associated pneumonia. The incidence of early ventilator-associated pneumonia was lower with antibiotic prophylaxis than with placebo (19 patients [19%] vs. 32 [34%]; hazard ratio, 0.53; 95% confidence interval, 0.31 to 0.92; P = 0.03). No significant differences between the antibiotic group and the control group were observed with respect to the incidence of late ventilator-associated pneumonia (4% and 5%, respectively), the number of ventilator-free days (21 days and 19 days), ICU length of stay (5 days and 8 days if patients were discharged and 7 days and 7 days if patients had died), and mortality at day 28 (41% and 37%). At day 7, no increase in resistant bacteria was identified. Serious adverse events did not differ significantly between the two groups.A 2-day course of antibiotic therapy with amoxicillin-clavulanate in patients receiving a 32-to-34°C targeted temperature management strategy after out-of-hospital cardiac arrest with initial shockable rhythm resulted in a lower incidence of early ventilator-associated pneumonia than placebo. No significant between-group differences were observed for other key clinical variables, such as ventilator-free days and mortality at day 28. (Funded by the French Ministry of Health; ANTHARTIC ClinicalTrials.gov number, NCT02186951.)."
0,"TITLE: Treatment-Induced Changes in Plasma Adiponectin Do Not Reduce Urinary Albumin Excretion in the Diabetes Prevention Program Cohort.ABSTRACT: Molecular data suggests that adiponectin may directly regulate urinary albumin excretion. In the Diabetes Prevention Program (DPP) we measured adiponectin and albuminuria before and after intervention, and we previously reported increases in adiponectin with interventions. Here we have used the DPP dataset to test the hypothesis that treatment-related increases in adiponectin may reduce albuminuria in obesity.We evaluated cross-sectional correlations between plasma adiponectin and urinary albumin excretion at baseline, and the relationship of treatment-related changes in adiponectin and albuminuria. Baseline and follow-up urine albumin to creatinine ratios (ACR (albumin to creatinine ratio)) and plasma adiponectin concentration were available in 2553 subjects.Adjusting for age, sex and race/ethnicity, we observed a statistically significant but weak inverse relationship between adiponectin and ACR at baseline (conditional Spearman's rho = (-) 0.04, p = 0.04). Although DPP treatments significantly increased plasma adiponectin, there were no treatment effects on ACR and no differences in ACR across treatment groups. There was a weak direct (not inverse) association between change in adiponectin and change in albuminuria (adjusted Spearman's rho = (+) 0.04, p = 0.03).In a large, well-characterized cohort of obese dysglycemic subjects we observed a weak inverse association between circulating adiponectin concentrations and urinary albumin excretion at baseline. Contrary to the hypothesized effect, treatment-related increases in plasma adiponectin were not associated with a reduction in ACR. The association of change in adiponectin with change in ACR should be assessed in populations with overt albuminuria before excluding a beneficial effect of increasing adiponectin to reduce ACR in obesity."
1,"TITLE: A behavioral intervention reduces HIV transmission risk by promoting sustained serosorting practices among HIV-infected men who have sex with men.ABSTRACT: To examine factors that explain the effect of a cognitive-behavioral intervention on reductions in HIV transmission risk among HIV-infected men who have sex with men (MSM).Of the 1910 HIV-infected MSM screened, 616 participants considered to be at risk of transmitting HIV were randomized to a 15-session, individually delivered cognitive-behavioral intervention (n=301) or a wait-list control (n=315).Consistent with previous intent-to-treat findings, there was an overall reduction in transmission risk acts among MSM in both intervention and control arms, with significant intervention effects observed at the 5-, 10-, 15-, and 20-month assessments (risk ratios=0.78, 0.62, 0.48, and 0.38, respectively). These intervention-related decreases in HIV transmission risk acts seemed to be partially due to sustained serosorting practices. MSM in the intervention condition reported a significantly greater proportion of sexual partners who were HIV infected at the 5- and 10-month assessments (risk ratios=1.14 and 1.18).The Healthy Living Project, a cognitive-behavioral intervention, is efficacious in reducing transmission risk acts among MSM. This seems to have been due in large part to the fact that MSM in the intervention condition reported sustained serosorting practices."
1,"TITLE: Assessment of the efficacy of a novel tailored vitamin K dosing regimen in lowering the International Normalised Ratio in over-anticoagulated patients: a randomised clinical trial.ABSTRACT: Current guidelines advocate using fixed-doses of oral vitamin K to reverse excessive anticoagulation in warfarinised patients who are either asymptomatic or have minor bleeds. Over-anticoagulated patients present with a wide range of International Normalised Ratio (INR) values and response to fixed doses of vitamin K varies. Consequently a significant proportion of patients remain outside their target INR after vitamin K administration, making them prone to either haemorrhage or thromboembolism. We compared the performance of a novel tailored vitamin K dosing regimen to that of a fixed-dose regimen with the primary measure being the proportion of over-anticoagulated patients returning to their target INR within 24 h. One hundred and eighty-one patients with an index INR > 6·0 (asymptomatic or with minor bleeding) were randomly allocated to receive oral administration of either a tailored dose (based upon index INR and body surface area) or a fixed-dose (1 or 2 mg) of vitamin K. A greater proportion of patients treated with the tailored dose returned to within target INR range compared to the fixed-dose regimen (68·9% vs. 52·8%; P = 0·026), whilst a smaller proportion of patients remained above target INR range (12·2% vs. 34·0%; P < 0·001). Individualised vitamin K dosing is more accurate than fixed-dose regimen in lowering INR to within target range in excessively anticoagulated patients."
1,"TITLE: Predictors of Recurrent Ischemic Stroke in Patients with Embolic Strokes of Undetermined Source and Effects of Rivaroxaban Versus Aspirin According to Risk Status: The NAVIGATE ESUS Trial.ABSTRACT: Embolic stroke of undetermined source (ESUS) identifies patients with cryptogenic ischemic stroke presumed due to embolism from several unidentified sources. Among patients with recent ESUS, we sought to determine independent predictors of recurrent ischemic stroke during treatment with aspirin or rivaroxaban and to assess the relative effects of these treatments according to risk.Exploratory analyses of 7213 participants in the NAVIGATE ESUS international trial who were randomized to aspirin 100 mg/day or rivaroxaban 15 mg/day and followed for a median of 11 months, during which time there were 309 first recurrent ischemic strokes (4.6% per year). Baseline features were correlated with recurrent stroke by multivariate analysis.The 7 independent predictors of recurrent stroke were stroke or transient ischemic attack (TIA) prior to the qualifying stroke (hazard ratio [HR] 2.03 95% confidence internal [CI] 1.58-2.60), current tobacco user (HR 1.62, 95% CI 1.24-2.12), age (HR 1.02 per year increase, 95%CI 1.01-1.03), diabetes (HR 1.28, 95% CI 1.01-1.64), multiple acute infarcts on neuroimaging (HR 1.49, 95% CI 1.09-2.02), aspirin use prior to qualifying stroke (HR 1.34, 95% CI 1.02-1.70), and time from qualifying stroke to randomization (HR .98, 95% CI .97-.99). The rate of recurrent stroke rate was 2.6% per year for participants without any of these risk factors, and increased by an average of 45% for each independent predictor (P < .001). There were no significant interactions between treatment effects and independent stroke predictors or stroke risk status.In this large cohort of ESUS patients, several features including prior stroke or TIA, advanced age, current tobacco user, multiple acute infarcts on neuroimaging, and diabetes independently identified those with an increased risk of ischemic stroke recurrence. The relative effects of rivaroxaban and aspirin were similar across the spectrum of independent stroke predictors and recurrent stroke risk status."
1,"TITLE: Impact of male partner involvement on mother-to-child transmission of HIV and HIV-free survival among HIV-exposed infants in rural South Africa: Results from a two phase randomised controlled trial.ABSTRACT: The Sub-Saharan Africa region still remains the epicentre of the global HIV/AIDS epidemic. With regards to new paediatric HIV infections, almost 90% of new HIV infections are among children (aged 0-14 years), largely through mother to child transmission. Male Partner Involvement in Prevention of Mother to Child Transmission programmes is now strongly advocated as being key in improving infant outcomes. This study describes the role of Male Partner Involvement on infant HIV infection and mortality survival in the first year among HIV-exposed infants born from HIV positive mothers.This study was a two-phase, two condition (intervention or control) longitudinal study as part of a clinic-randomized Prevention of Mother to Child Transmission controlled trial. For Phase 1, female participants were recruited without their male partners. In Phase 2, both female and male participants were enrolled in the study as couples in order to encourage active Male Partner Involvement during pregnancy. Participants had two assessments prenatally (8-24 weeks and 32 weeks) and three assessments postnatally (6 weeks, 6 months, and 12 months).About 1424 women were eligible for recruitment into the study and 18 eligible women declined to participate. All women had a partner; 54% were unmarried, 26% were cohabiting, and 20% were married. Just over half (55%) of the women had been diagnosed with HIV during the current pregnancy. Phase 1 had significantly more HIV-infected infants than Phase 2 at 12-months postpartum (aOR = 4.55 [1.38, 15.07]). Increased depressive symptoms were associated with infant HIV infection at 12-months (aOR = 1.06 [1.01, 1.10]). Phase 1 also had a significantly greater proportion of dead and HIV-infected infants than Phase 2 at 12-months (aOR = 1.98 [1.33, 2.94]).Male partner involvement in antenatal care is critical in ensuring infant survival and HIV infection among children born to HIV-positive mothers. This study highlights the high risk of ante-and-post natal depression and underscores the need of screening for depression during pregnancy.ClinicalTrials.Gov; Trial Number NCT02085356."
1,"TITLE: Efficacy and safety of etanercept in children and adolescents aged > or = 8 years with severe plaque psoriasis.ABSTRACT: Etanercept, a fully human soluble tumor necrosis factor (TNF)-alpha receptor, is approved in Europe for treatment of severe plaque psoriasis in children > or = 8 years. The efficacy and safety of etanercept for this population was evaluated in a retrospective analysis of a previous study, which included 211 children (4-17 years) with psoriasis involving > or = 10% body surface area and Psoriasis Area and Severity Index (PASI) > or = 12. In this subanalysis, subjects aged 8-17 years received once-weekly subcutaneous etanercept 0.8 mg/kg (< or = 50 mg) or placebo in double-blind fashion for 12 weeks, followed by 24 weeks of open-label etanercept. Baseline demographics and disease characteristics were similar across treatment arms (etanercept n = 95, placebo n = 97). At week 12, 54.7% subjects receiving etanercept versus 11.3% receiving placebo achieved 75% or greater improvement in PASI (PASI 75) compared with baseline (p < 0.001). PASI 50, PASI 90, and static Physician Global Assessment of psoriasis followed a similar pattern (p < 0.001). Efficacy during the open-label phase was sustained through Week 36. Exposure-adjusted rates of adverse events for etanercept were similar or lower than those for placebo. No appreciable differences were noted in the efficacy and safety profiles between the subjects aged > or = 8 years in this analysis and those in the original study population aged 4-17 years. In conclusion, etanercept provided significant, sustained improvement in disease severity and was well tolerated in children > or = 8 years with severe plaque psoriasis."
0,"TITLE: Prediction of nonspecific side effects in rheumatoid arthritis patients by beliefs about medicines.ABSTRACT: This study examines the determinants of patients' side effects from arthritis medication. Proposed predictors were patients' beliefs about medications, objective disease activity, treatment regimen, and psychiatric and rheumatoid arthritis symptoms.In a longitudinal design, 100 rheumatoid arthritis outpatients were investigated at baseline and again at 6 months after receiving both pharmacologic and psychosocial treatment.Multivariate analyses showed no influence of disease status, type of treatment, or psychiatric or arthritis symptoms on side effects. Heightened concerns about arthritis medication at baseline predicted side effects at baseline (partial correlation r = 0.37, P < 0.001) and at 6 months (partial correlation r = 0.25, P < 0.001) after controlling for relevant disease- and treatment-related variables. In a cross-lagged panel analysis, prior experience with side effects from arthritis medication was ruled out as a cause of heightened concerns, indicating that negative beliefs genuinely contribute to side effects. A comparison of patients who did and did not start new medications showed no difference in side effects in patients with positive beliefs about medications, but led to significantly more side effects in patients with negative beliefs.Patients' beliefs about arthritis medications were stable and consistently associated with side effects. Patients with greater concerns about their arthritis medications are at higher risk for developing side effects, especially when starting new drugs. Identifying those patients is important to avoid premature drug discontinuation. Research into cause and preventability of negative attitudes to prescribed medicines is needed."
1,"TITLE: Sex hormone binding globulin and sex steroids among premenopausal women in the diabetes prevention program.ABSTRACT: It is unknown whether intensive lifestyle modification (ILS) or metformin changes sex steroids among premenopausal women without a history of polycystic ovarian syndrome (PCOS).We examined 1-year intervention impact on sex steroids (estradiol, testosterone, dehydroepiandrosterone, and androstenedione [A4]) and SHBG and differences by race/ethnicity.A subgroup of Diabetes Prevention Program participants who were premenopausal, not using estrogen, without a history of PCOS or irregular menses, and who reported non-Hispanic white (NHW), Hispanic, or African-American race/ethnicity (n = 301).Randomization arms were 1) ILS with the goals of weight reduction of 7% of initial weight and 150 minutes per week of moderate intensity exercise, 2) metformin 850 mg twice a day, or 3) placebo.Neither intervention changed sex steroids compared to placebo. ILS, but not metformin, increased median SHBG by 3.1 nmol/L (~11%) compared to decreases of 1.1 nmol/L in the placebo arm (P < .05). This comparison remained significant after adjustment for changes in covariates including waist circumference. However, associations with glucose were not significant. Median baseline A4 was lower in Hispanics compared to NHWs (5.7 nmol/L vs 6.5 nmol/L, P < .05) and increases in A4 were greater in Hispanics compared to NHWs (3.0 nmol/ vs 1.2 nmol/L, P < .05), and these differences did not differ significantly by intervention arm. No other racial/ethnic differences were significant.Among premenopausal glucose-intolerant women, no intervention changed sex steroids. ILS increased SHBG, although associations with glucose were not significant. SHBG and sex steroids were similar by race/ethnicity, with the possible exception of lower baseline A4 levels in Hispanics compared to NHWs."
1,"TITLE: Postoperative fentanyl patch versus subacromial bupivacaine infusion in arthroscopic shoulder surgery.ABSTRACT: The purpose of our study was to compare the effectiveness of subacromial bupivacaine infusion and a transdermal fentanyl patch in the treatment of postoperative pain after arthroscopic shoulder surgery.Sixty patients with rotator cuff disease scheduled for elective arthroscopic shoulder surgery were enrolled in the study. For the treatment of postoperative pain, 30 patients constituted group F and received a 12.0-μg/h fentanyl patch for 72 hours and saline solution infusion in a subacromial manner at the rate of 4 mL/h. The remaining 30 patients constituted group B and received a placebo patch and an infusion of 2.5-mg/mL bupivacaine in a subacromial manner for 72 hours. The primary outcome measure was the postoperative numerical rating scale pain score. The consumption of opioids, ibuprofen, and acetaminophen was also recorded. The Constant scores and general recovery were followed up until the 90th postoperative day.There was no statistically significant difference in the numerical rating scale scores (P = .60) between the groups. No differences in the use of rescue analgesic were observed except that the patients receiving bupivacaine used more ibuprofen (median, 1,200 mg v 600 mg) during the day of surgery (P = .042). No difference was found in general recovery between the groups.A fentanyl patch delivering 12-μg/h fentanyl offers an easy and safe treatment option as a part of multimodal analgesia with few adverse effects in the treatment of postoperative pain in a carefully selected patient group after arthroscopic shoulder surgery.Level I, randomized controlled trial."
1,"TITLE: The role of therapeutic alliance in mindfulness interventions: therapeutic alliance in mindfulness training for smokers.ABSTRACT: Mindfulness-based interventions have enjoyed a marked increase in support within biomedical and psychological research and practice in the past two decades. Despite the widespread application of these treatments for a range of psychological and medical conditions, there remains a lack of consensus regarding mechanisms through which these interventions effect change. One plausible yet underexplored mechanism is the therapeutic alliance between participants and mindfulness instructors.In this report, data are presented on therapeutic alliance from the mindfulness arm (n = 37) of a randomized controlled trial of a mindfulness-based smoking cessation treatment.Results suggest that client-reported therapeutic alliance measured midtreatment did not significantly predict primary smoking outcomes. Alliance did predict improvement in posttreatment scores on several outcome variables linked to mindfulness practice, including emotion regulation (β = -.24, p = .042), mindfulness (β = .33, p = .007), negative affect (β = -.33, p = .040), as well as treatment compliance (β = .39, p = .011).Implications of these relationships and the possible role of therapeutic alliance in mindfulness treatments are explored."
1,"TITLE: The long-term efficacy of medical male circumcision against HIV acquisition.ABSTRACT: In three randomized trials, medical male circumcision (MMC) reduced HIV acquisition in heterosexual men in sub-Saharan Africa by approximately 60%, after 21-24 months of follow-up. We estimated the 72-month efficacy of MMC against HIV among men retained in the Kisumu randomized trial, in which HIV acquisition was reduced by 60% after 24 months.From 2002 to 2005, 2784 men aged 18-24 were enrolled and randomized 1 : 1 to immediate circumcision or control. At trial end in December 2006, control men were offered free circumcision. Follow-up continued to September 2010. Cox proportional hazards regression incorporating stabilized inverse probability of treatment and censoring weights generated through marginal structural modeling, was used to account for potential time-varying confounding and censoring to estimate the efficacy of MMC on HIV risk.The cumulative 72-month HIV incidence was 7.21% [95% confidence interval (CI): 5.98-8.68%]: 4.81% among circumcised men, 11.0% among uncircumcised men. The crude hazard ratio of HIV seroconversion for circumcised vs. uncircumcised men was 0.38 [95% CI: 0.26-0.55]. In weight-adjusted Cox regression, the hazard ratio was 0.42 [95% CI: 0.26-0.66].The efficacy of MMC was sustained at 58% at 72 months, similar to overall findings of the three trials under conditions of randomization. These findings provide an estimate of the long-term efficacy of circumcision against HIV acquisition. Our results support programmatic scale-up recommendations that are based on assumptions of sustained efficacy."
1,"TITLE: Combined effects of goserelin and tamoxifen on estradiol level, breast density, and endometrial thickness in premenopausal and perimenopausal women with early-stage hormone receptor-positive breast cancer: a randomised controlled clinical trial.ABSTRACT: This study is to investigate the effects of geserelin+tamoxifen (TAM) on estradiol level, breast density (BD), endometrial thickness (ET), and blood lipids in premenopausal and perimenopausal women with hormone receptor-positive early-stage breast cancer.This study recruited 110 premenopausal and perimenopausal patients with hormone receptor-positive early-stage breast cancer between 22 June 2008 and 31 December 2009 and randomly assigned them to receive either goserelin plus TAM or TAM alone for 1.5 years. Blood levels of sex hormones and lipids and ET were determined at 0, 3, 6, 12, and 18 months. Contralateral BD was also measured at 0, 12, and 18 months.Five participants dropped out of the goserelin plus TAM group, and two participants dropped out of the TAM-alone group before initiation of endocrine therapy. The rest of patients received scheduled treatment and 3 years of median follow-up. No serious adverse effects were observed, and only two local recurrences have been observed in these patients. Estradiol level and BD were lower in the goserelin plus TAM group than in the TAM-alone group (P<0.05). The endometrium in the goserelin plus TAM group was significantly thinner than that in the TAM-alone group (P<0.05), and women in the TAM-alone group exhibited endometrial thickening over the course of the study. Furthermore, no significant differences in blood lipid levels were reported between the two groups.The data from the current study demonstrated that the addition of goserelin to TAM results in downregulation of estradiol level, followed by significant reduction in BD and ET in premenopausal and perimenopausal women with hormone receptor-positive breast cancer, which may eventually lead to better outcome in these patients."
1,"TITLE: The effect of bevacizumab versus ranibizumab in the treatment of corneal neovascularization: a preliminary study.ABSTRACT: To compare the short term effects of bevacizumab and ranibizumab injections on the regression of corneal neovascularization (NV).Sixteen eyes of 16 patients with corneal NV were randomly assigned for an injection with 2.5 mg of bevacizumab (group 1, n = 8) or 1 mg of ranibizumab (group 2, n = 8) through subconjunctival and intrastromal routes. The patients were prospectively followed-up for one month after the injections. Corneal NV areas, as shown on corneal slit-lamp photographs stored in JPEG format, were calculated using Image J software before the injection, one week after the injection, and one month after the injection. The corneal NV areas were compared before and after the injections.Seven women and nine men, with an average age of 51 years, presented with corneal NV secondary to herpetic keratitis (7 cases), graft rejection (6), chemical burn (1), pemphigoid (1), and recurrent ulcer (1). In group I, the preoperative corneal NV area (8.75 ± 4.33%) was significantly decreased to 5.62 ± 3.86% one week after the injection and to 6.35 ± 3.02% one month after the injection (p = 0.012, 0.012, respectively). The corneal NV area in group 2 also exhibited a significant change, from 7.37 ± 4.33% to 6.72 ± 4.16% one week after the injection (p = 0.012). However, no significant change was observed one month after the injection. The mean decrease in corneal NV area one month after injection in group 1 (28.4 ± 9.01%) was significantly higher than in group 2 (4.51 ± 11.64%, p = 0.001).Bevacizumab injection resulted in a more effective and stable regression of corneal NV compared to the ranibizumab injection. The potency and dose of these two drugs for the regression of corneal NV require further investigation."
0,"TITLE: Insecticide-treated plastic sheeting for emergency malaria prevention and shelter among displaced populations: an observational cohort study in a refugee setting in Sierra Leone.ABSTRACT: A double-blind phase III malaria prevention trial was conducted in two refugee camps using pre-manufactured insecticide-treated plastic sheeting (ITPS) or untreated polyethylene sheeting (UPS) randomly deployed to defined sectors of each camp. In Largo camp the ITPS or UPS was attached to inner walls and ceilings of shelters, whereas in Tobanda the ITPS or UPS was used to line only the ceiling and roof. In Largo the Plasmodium falciparum incidence rate in children up to 3 years of age who were cleared of parasites and monitored for 8 months was 163/100 person-years under UPS and 63 under ITPS (adjusted odds ratio [AOR] = 0.40, 95% confidence interval [CI] = 0.33-0.47). In Tobanda incidence was 157/100 person-years under UPS and 134 under ITPS (AOR = 0.85, 95% CI = 0.75-0.95). Protective efficacy was 61% under fully lined ITPS and 15% under roof lined ITPS. Anemia rates improved under ITPS in both camps. This novel tool proved to be a convenient, safe, and long-lasting method of malaria control when used as a full shelter lining in an emergency setting."
1,"TITLE: Lurasidone in the treatment of schizophrenia: a 6-week, placebo-controlled study.ABSTRACT: There is an unmet need in the treatment of schizophrenia for effective medications with fewer adverse effects.This study aims to evaluate the efficacy and safety of lurasidone, an atypical antipsychotic, for the treatment of schizophrenia.Patients with an acute exacerbation of schizophrenia were randomized to 6 weeks of double-blind treatment with once-daily, fixed-dose lurasidone 40 mg (N = 50), lurasidone 120 mg (N = 49), or placebo (N = 50). The primary efficacy measure was mean change from baseline to day 42 (last observation carried forward) in the Brief Psychiatric Rating Scale derived (BPRSd) from the Positive and Negative Syndrome Scale (PANSS).Mean change in BPRSd was significantly greater in patients receiving lurasidone 40 and 120 mg/day versus placebo (-9.4 and -11.0 versus -3.8; p = 0.018 and 0.004, respectively). Treatment with lurasidone 120 mg/day was superior to placebo across all secondary measures, including PANSS total (p = 0.009), PANSS positive (p = 0.005), PANSS negative (p = 0.011), and PANSS general psychopathology (p = 0.023) subscales and Clinical Global Impression of Severity (CGI-S; p = 0.001). Treatment with lurasidone 40 mg/day was superior to placebo on the PANSS positive subscale (p = 0.018) and CGI-S (p = 0.002). The most common adverse events for patients receiving lurasidone were nausea (16.2 versus 4.0 % for placebo) and sedation (16.2 versus 10.0 % for placebo). Minimal changes in weight, cholesterol, triglyceride, and glucose levels were observed.In this study, which was limited by a relatively high discontinuation rate, lurasidone provided effective treatment for patients with acute exacerbation of chronic schizophrenia and had minimal effects on weight and metabolic parameters."
1,"TITLE: Epidural fentanyl for postoperative analgesia after lumbar canal decompression: a randomized controlled trial.ABSTRACT: Postoperative back pain is common after decompression surgery for lumbar stenosis and often delays discharge from hospital. Achieving regional analgesia by intraoperative delivery of epidural opiates after lumbar canal decompression is a promising approach to reduce postoperative pain and enhance early mobilization. However, there have been concerns about opiate-related complications, such as respiratory depression and urinary retention in what is generally an elderly population of patients.To assess the analgesic efficacy of bolus epidural fentanyl administered intraoperatively after lumbar decompression for degenerative canal stenosis.Patient-blinded randomized controlled trial conducted at two university neurosurgical centers.Adults (older than 18 years) with neurogenic claudication and/or lower limb radiculopathy and concordant lumbar spinal canal stenosis demonstrated on magnetic resonance imaging. Patients with previous lumbar spinal surgery, a contraindication to fentanyl, or requiring instrumentation were excluded.The primary outcome measure was patient-reported Visual Analogue Score (VAS) for pain recorded preoperatively, in recovery, and on the first and second postoperative days if the patient remained in the hospital. Secondary outcomes were duration of surgery, length of stay, and any side effects or complications.Patients underwent a one to three level lumbar canal decompression as required, via a midline incision, under general anesthesia. Before wound closure either no drug (control) or a 100-μg bolus of fentanyl was administered via an epidural catheter inserted 10 cm rostral to the operated level. Patients were blinded to group allocation, and analysis was by intention to treat. The trial was approved by the National Health Service Research Ethics Service and the Medicines and Healthcare products Regulatory Agency. No commercial or other source of funding was received.Sixty patients were randomized, 29 to fentanyl and 31 to control. Demographics, duration of surgery, and preoperative VAS were not significantly different between the groups. VAS in recovery was significantly lower in patients treated with fentanyl (mean [standard deviation]: 2.6 [2.7] vs. 4.7 [2.4]; p=.003). Later VAS and postoperative length of stay were similar between groups. More patients in the fentanyl group required temporary urinary catheterization, but there was no significant difference in the incidence of side effects.Bolus epidural fentanyl provides effective short-term postoperative analgesia after lumbar canal decompression and may be a useful adjunct to pain management in patients undergoing lumbar spine surgery."
1,"TITLE: 2-year clinical and angiographic outcomes from a randomized trial of polymer-free dual drug-eluting stents versus polymer-based Cypher and Endeavor [corrected] drug-eluting stents.ABSTRACT: In the ISAR-TEST-2 (Intracoronary Stenting and Angiographic Results: Test Efficacy of Three Limus-Eluting Stents) randomized trial, a new-generation sirolimus- and probucol-eluting stent (Dual-DES) demonstrated a 12-month efficacy that was comparable to sirolimus-eluting stents (SES) (Cypher, Cordis Corp., Warren, New Jersey) and superior to zotarolimus-eluting stents (ZES) (Endeavor, Medtronic CardioVascular, Santa Rosa, California). The aim of the current study was to investigate the comparative clinical and angiographic effectiveness of SES, Dual-DES, and ZES between 1 and 2 years.Long-term polymer residue is implicated in adverse events associated with delayed vessel healing after drug-eluting stent therapy. The second-generation ZES utilizes an enhanced biocompatibility polymer system whereas a new-generation Dual-DES employs a polymer-free drug-release system.A total of 1,007 patients undergoing coronary stenting of de novo lesions in native vessels were randomized to treatment with SES (n = 335), Dual-DES (n = 333), or ZES (n = 339). Clinical follow-up was performed to 2 years. Angiographic follow-up was scheduled at 6 to 8 months and 2 years.There were no significant differences between groups regarding death/myocardial infarction (SES: 10.2% vs. Dual-DES: 7.8% vs. ZES: 9.2%; p = 0.61) or definite stent thrombosis (SES: 0.9% vs. Dual-DES: 0.9% vs. ZES: 0.6%; p = 0.87). Two-year target lesion revascularization (TLR) was 10.7%, 7.7%, and 14.3% lesions in the SES, Dual-DES, and ZES groups, respectively (p = 0.009). Incident TLR between 1 and 2 years in the Dual-DES group (0.9%) was significantly lower than in the Cypher SES group (3.6%) (p = 0.009), but comparable to the Endeavor ZES group (0.7%) (p = 0.72). These findings mirrored those observed for binary restenosis.At 2 years, there was no signal of a differential safety profile between the 3 stent platforms. Furthermore, the antirestenotic efficacy of both Dual-DES and ZES remained durable between 1 and 2 years, with Dual-DES maintaining an advantage over the entire 2-year period. (Intracoronary Stenting and Angiographic Results: Test Efficacy of Three Limus-Eluting Stents [ISAR-TEST-2]; NCT00332397)."
1,"TITLE: Piperacillin-tazobactam versus carbapenem therapy with and without amikacin as empirical treatment of febrile neutropenia in cancer patients: results of an open randomized trial at a university hospital.ABSTRACT: Empirical beta-lactam monotherapy has become the standard therapy in febrile neutropenia. The aim of this study was to compare the efficacy and safety of piperacillin-tazobactam versus carbapenem therapy with or without amikacin in adult patients with febrile neutropenia.In this prospective, open, single-center study, 127 episodes were randomized to receive either piperacillin-tazobactam (4 x 4.5 g IV/day) or carbapenem [meropenem (3 x 1 g IV/day) or imipenem (4 x 500 mg IV/day)] with or without amikacin (1 g IV/day). Doses were adjusted according to renal function. Clinical response was determined during and at completion of therapy.One hundred and twenty episodes were assessable for efficacy (59 piperacillin-tazobactam, 61 carbapenem). Mean duration of treatment was 14.8 +/- 9.6 days in the piperacillin-tazobactam group and 14.7 +/- 8.8 days in the carbapenem group (P > 0.05). Mean days of fever resolution were 5.97 and 4.48 days for piperacillin-tazobactam and carbapenem groups, respectively (P > 0.05). Similar rates of success without modification were found in the piperacillin-tazobactam (87.9%) and in the carbapenem groups (75.4%; P > 0.05). Fungal infection occurrence rates were 30.5 and 18% in piperacillin-tazobactam and carbapenem groups, respectively (P = 0.05). Antibiotic modification rates were 30.5 and 13.1% (P = 0.02) and the addition of glycopeptides to empirical antibiotic regimens rates were 15.3 and 44.3% for piperacillin-tazobactam and carbapenem groups, respectively (P = 0.001). The rude mortality rates were 14% (6/43) and 29.3% (12/41) in piperacillin-tazobactam and carbapenem groups, respectively (P = 0.08).The effect of empirical regimen of piperacillin-tazobactam regimen is equivalent to carbapenem in adult febrile neutropenic patients."
1,"TITLE: Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial.ABSTRACT: Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (HNSCC) progressing after first-line platinum regimens have a poor prognosis and few treatment options. Afatinib, an irreversible ERBB family blocker, has shown efficacy in a phase 2 study in this setting. We aimed to assess the efficacy and safety of afatinib compared with methotrexate as second-line treatment in patients with recurrent or metastatic HNSCC progressing on or after platinum-based therapy.In this open-label, phase 3, randomised controlled trial conducted in 101 centres in 19 countries, we enrolled patients aged 18 years or older with histologically or cytologically confirmed HNSCC that was recurrent, metastatic, or both who had progressed on or after first-line platinum-based therapy, were not amenable for salvage surgery or radiotherapy, and who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Previous treatment with more than one systemic regimen in this setting was not allowed; previous treatment with EGFR-targeted antibody therapy (but not EGFR-targeted tyrosine-kinase inhibitors) was allowed. We randomly assigned eligible patients in a 2:1 ratio to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m(2) per week), stratified by ECOG performance status and previous EGFR-targeted antibody therapy for recurrent or metastatic disease. Randomisation was done centrally with an interactive voice or web-based response system. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. The primary endpoint was progression-free survival as assessed by an independent, central imaging review committee. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01345682.Between Jan 10, 2012, and Dec 12, 2013, we enrolled 483 patients and randomly assigned 322 to afatinib and 161 to methotrexate. After a median follow-up of 6·7 months (IQR 3·1-9·0), progression-free survival was longer in the afatinib group than in the methotrexate group (median 2·6 months [95% CI 2·0-2·7] for the afatinib group vs 1·7 months [1·5-2·4] for the methotrexate group; hazard ratio [HR] 0·80 [95% CI 0·65-0·98], p=0·030). The most frequent grade 3 or 4 drug-related adverse events were rash or acne (31 [10%] of 320 patients in the afatinib group vs none of 160 patients in the methotrexate group), diarrhoea (30 [9%] vs three [2%]), stomatitis (20 [6%] vs 13 [8%]), fatigue (18 [6%] vs five [3%]), and neutropenia (1 [<1%] vs 11 [7%]); serious adverse events occurred in 44 (14%) of afatinib-treated patients and 18 (11%) of methotrexate-treated patients.Afatinib was associated with significant improvements in progression-free survival and had a manageable safety profile. These findings provide important new insights into the treatment of this patient population and support further investigations with irreversible ERBB family blockers in HNSCC.Boehringer Ingelheim."
0,"TITLE: Change of insulin sensitivity in hepatitis C patients with normal insulin sensitivity: a 5-year prospective follow-up study variation of insulin sensitivity in HCV patients.ABSTRACT: Hepatitis C virus (HCV) infection is associated with a high prevalence of diabetes mellitus (DM). Insulin resistance (IR) is known to play a crucial role in the development of DM in chronic hepatitis C (CHC) patients. We prospectively investigated changes of insulin sensitivity in CHC patients during a 5-year period and analysed the factors significantly associated with IR.Sixty-two CHC patients with normal insulin sensitivity (CHC group), and a healthy control group of 172 subjects matched by age, gender, body mass index and lifestyles were studied. We compared the initial baseline insulin sensitivity, metabolic parameters and incidence of IR at the end of the follow-up period between the two groups. The changes in insulin sensitivity, metabolic parameters and the development of IR were analysed as well as factors associated with the development of IR.IR developed in 22.5% of 62 CHC patients and 5.2% of 172 normal individuals (P < 0.001). HCV infection per se and the genotype 1 were independent risk factors for the development of IR. The duration of infection > or = 120 months, initial fasting glucose 90-100 mg/dL, fasting insulin > or = 10 microIU/mL and the homeostasis model assessment (HOMA-IR) 2.3-2.7 were significantly associated with the development of IR in the CHC group.HCV infection was an independent risk factor for the development of IR. All CHC patients, even those with normal insulin sensitivity, require careful monitoring for the development of IR."
1,"TITLE: Improving contraceptive use among Latina adolescents: A cluster-randomized controlled trial evaluating an mHealth application, Health-E You/Salud iTu.ABSTRACT: To evaluate the effectiveness of Health-E You/Salud iTu, a mobile health application (app), on increasing knowledge, self-efficacy and contraception use among Latina adolescents, its impact on visit quality, and app satisfaction.This study used cluster-randomized controlled trial (CRCT) of 18 school-based health centers (SBHCs). Prior to the visit, intervention participants received the patient-centered contraceptive decision-making support app and controls answered sexual health questions on iPads. Participants completed a previsit questionnaire and 3 follow-up surveys (48 hours, 3-, and 6-months) after the recruitment visit (where intervention participants completed the app). Differences in adolescents' contraceptive knowledge, self-efficacy, and use over the 6-month follow-up were assessed by generalized mixed effects regression models.A total of 1,360 Latina adolescents participated; 57.2% responded to the 48-hour survey, 50.1% to the 3-month, 49.7% to the 6-month, and 42.3% to both the 3- and 6-month surveys. Health-E You users' demonstrated significant increases in pre-post knowledge (p < 0.001). Intervention participants who completed the follow-up survey reported greater increases in mean self-efficacy from baseline (23.2 intervention vs. 22.5 controls) to 6 months (26.1 vs. 23.4; b = 1.58, 95% CI 0.38-2.77, p = 0.01), and greater increases in non-barrier contraceptive use from baseline (29% intervention vs. 30% controls) to 3 months (63% vs. 45%; OR = 3.29, 95% CI 1.04-10.36, p = 0.04) and 6 months (63% vs. 44%; OR = 5.54, 95% CI 1.70-18.06, p = 0.005). Providers and adolescents reported high app satisfaction and stated it improved visit quality.While data suggest that Health-E You improved outcomes, findings must be interpreted cautiously. Intervention participants had higher baseline sexual activity rates, more recruitment visits for pregnancy testing, emergency contraception or birth control, and lower completion rates of follow-up surveys than controls.Despite declines in adolescent pregnancy in the United States, Latinas continue to have disproportionately high rates compared to white females. The Health-E You app may be an effective support tool for both adolescents and providers in SBHCs, and possibly other clinical settings, across the country to increase contraceptive use and thereby decrease unintended pregnancies. It could potentially reduce disparities in adolescent pregnancies and create more efficient visit time spent between clients and their providers."
1,"TITLE: Randomized Trial of a Vaccine Regimen to Prevent Chronic HCV Infection.ABSTRACT: A safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of efforts to eliminate the disease.In this phase 1-2 randomized, double-blind, placebo-controlled trial, we evaluated a recombinant chimpanzee adenovirus 3 vector priming vaccination followed by a recombinant modified vaccinia Ankara boost; both vaccines encode HCV nonstructural proteins. Adults who were considered to be at risk for HCV infection on the basis of a history of recent injection drug use were randomly assigned (in a 1:1 ratio) to receive vaccine or placebo on days 0 and 56. Vaccine-related serious adverse events, severe local or systemic adverse events, and laboratory adverse events were the primary safety end points. The primary efficacy end point was chronic HCV infection, defined as persistent viremia for 6 months.A total of 548 participants underwent randomization, with 274 assigned to each group. There was no significant difference in the incidence of chronic HCV infection between the groups. In the per-protocol population, chronic HCV infection developed in 14 participants in each group (hazard ratio [vaccine vs. placebo], 1.53; 95% confidence interval [CI], 0.66 to 3.55; vaccine efficacy, -53%; 95% CI, -255 to 34). In the modified intention-to-treat population, chronic HCV infection developed in 19 participants in the vaccine group and 17 in placebo group (hazard ratio, 1.66; 95% CI, 0.79 to 3.50; vaccine efficacy, -66%; 95% CI, -250 to 21). The geometric mean peak HCV RNA level after infection differed between the vaccine group and the placebo group (152.51×10 IU per milliliter and 1804.93×10 IU per milliliter, respectively). T-cell responses to HCV were detected in 78% of the participants in the vaccine group. The percentages of participants with serious adverse events were similar in the two groups.In this trial, the HCV vaccine regimen did not cause serious adverse events, produced HCV-specific T-cell responses, and lowered the peak HCV RNA level, but it did not prevent chronic HCV infection. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT01436357.)."
1,"TITLE: Evaluation of the gut microbiota after metformin intervention in children with obesity: A metagenomic study of a randomized controlled trial.ABSTRACT: Metformin, a first-line oral antidiabetic agent that has shown promising results in terms of treating childhood and adolescent obesity, might influence the composition of the gut microbiota. We aimed to evaluate whether the gut microbiota of non-diabetic children with obesity changes after a metformin intervention.The study was a multicenter and double-blind randomized controlled trial in 160 children with obesity. Children were randomly assigned to receive either metformin (1 g/day) or placebo for 6 months in combination with healthy lifestyle recommendations in both groups. Then, we conducted a metagenomic analysis in a subsample obtained from 33 children (15 metformin, 18 placebo). A linear mixed-effects model (LMM) was used to determine the abundance changes from baseline to six months according to treatment. To analyze the data by clusters, a principal component analysis was performed to understand whether lifestyle habits have a different influence on the microbiota depending on the treatment group.Actinobacteria abundance was higher after placebo treatment compared with metformin. However, the interaction time x treatment just showed a trend to be significant (4.6% to 8.1% after placebo vs. 3.8 % to 2.6 % after metformin treatment, p = 0.055). At genus level, only the abundance of Bacillus was significantly higher after the placebo intervention compared with metformin (2.5% to 5.7% after placebo vs. 1.5 % to 0.8 % after metformin treatment, p = 0.044). Furthermore, different ensembles formed by Firmicutes, Bacteroidetes, and Verrucomicrobia were found according to the interventions under a similar food consumption.Further studies with a large sample size controlled by lifestyle patterns are required in obese children and adolescents to clarify whether metformin might trigger gut microbiota alterations.Registered on the European Clinical Trials Database (EudraCT, ID: 2010-023061-21) on 14 November 2011."
1,"TITLE: Secukinumab in patients with psoriatic arthritis and axial manifestations: results from the double-blind, randomised, phase 3 MAXIMISE trial.ABSTRACT: MAXIMISE (Managing AXIal Manifestations in psorIatic arthritis with SEcukinumab) trial was designed to evaluate the efficacy of secukinumab in the management of axial manifestations of psoriatic arthritis (PsA).This phase 3b, double-blind, placebo-controlled, multi-centre 52-week trial included patients (≥18 years) diagnosed with PsA and classified by ClASsification criteria for Psoriatic Arthritis (CASPAR) criteria, with spinal pain Visual Analogue Score ≥40/100 and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥4 despite use of at least two non-steroidal anti-inflammatory drugs (NSAIDs). Patients were randomised (1:1:1) to secukinumab 300 mg, secukinumab 150 mg or placebo weekly for 4 weeks and every 4 weeks thereafter. At week 12, placebo patients were re-randomised to secukinumab 300/150 mg. Primary endpoint was ASAS20 (Assessment of SpondyloArthritis international Society) response with secukinumab 300 mg at week 12.Patients were randomly assigned; 167 to secukinumab 300 mg, 165 to secukinumab 150 mg and 166 to placebo. Secukinumab 300 mg and 150 mg significantly improved ASAS20 response versus placebo at week 12 (63% and 66% vs 31% placebo). The OR (95% CI) comparing secukinumab 300 mg and 150 mg versus placebo, using a logistic regression model after multiple imputation, was 3.8 (2.4 and 6.1) and 4.4 (2.7 and 7.0; p<0.0001).Secukinumab 300 mg and 150 mg provided significant improvement in signs and symptoms of axial disease compared with placebo in patients with PsA and axial manifestations with inadequate response to NSAIDs.NCT02721966."
1,"TITLE: Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial.ABSTRACT: Bortezomib and rituximab have shown additive activity in preclinical models of lymphoma, and have been shown to be active and generally well tolerated in a randomised phase 2 study in patients with follicular and marginal zone lymphoma. We compared the efficacy and safety of rituximab alone or combined with bortezomib in patients with relapsed or refractory follicular lymphoma in a phase 3 setting.In this multicentre phase 3 trial, rituximab-naive or rituximab-sensitive patients aged 18 years or older with relapsed grade 1 or 2 follicular lymphoma were randomly assigned (1:1) to receive five 35-day cycles consisting of intravenous infusions of rituximab 375 mg/m(2) on days 1, 8, 15, and 22 of cycle 1, and on day 1 of cycles 2-5, either alone or with bortezomib 1·6 mg/m(2), administered by intravenous injection on days 1, 8, 15, and 22 of all cycles. Randomisation was stratified by FLIPI score, previous use of rituximab, time since last therapy, and region. Treatment assignment was based on a computer-generated randomisation schedule prepared by the sponsor. Patients and treating physicians were not masked to treatment allocation. The primary endpoint was progression-free survival analysed by intention to treat. This trial has been completed and is registered with ClinicalTrials.gov, number NCT00312845.Between April 10, 2006, and Aug 12, 2008, 676 patients were randomised to receive rituximab (n=340) or bortezomib plus rituximab (n=336). After a median follow-up of 33·9 months (IQR 26·4-39·7), median progression-free survival was 11·0 months (95% CI 9·1-12·0) in the rituximab group and 12·8 months (11·5-15·0) in the bortezomib plus rituximab group (hazard ratio 0·82, 95% CI 0·68-0·99; p=0·039). The magnitude of clinical benefit was not as large as the anticipated prespecified improvement of 33% in progression-free survival. Patients in both groups received a median of five treatment cycles (range 1-5); 245 of 339 (72%) and 237 of 334 (71%) patients in the rituximab and bortezomib plus rituximab groups, respectively, completed five cycles. Of patients who did not complete five cycles, most discontinued early because of disease progression (77 [23%] patients in the rituximab group, and 56 [17%] patients in the bortezomib plus rituximab group). Rates of adverse events of grade 3 or higher (70 [21%] of 339 rituximab-treated patients vs 152 [46%] of 334 bortezomib plus rituximab treated patients), and serious adverse events (37 [11%] patients vs 59 [18%] patients) were lower in the rituximab group than in the combination group. The most common adverse events of grade 3 or higher were neutropenia (15 [4%] patients in the rituximab group and 37 [11%] patients in the bortezomib plus rituximab group), infection (15 [4%] patients and 36 [11%] patients, respectively), diarrhoea (no patients and 25 [7%] patients, respectively), herpes zoster (one [<1%] patient and 12 [4%] patients, respectively), nausea or vomiting (two [<1%] patients and 10 [3%] patients, respectively) and thrombocytopenia (two [<1%] patients and 10 [3%] patients, respectively). No individual serious adverse event was reported by more than three patients in the rituximab group; in the bortezomib plus rituximab group, only pneumonia (seven patients [2%]) and pyrexia (six patients [2%]) were reported in more than five patients. In the bortezomib plus rituximab group 57 (17%) of 334 patients had peripheral neuropathy (including sensory, motor, and sensorimotor neuropathy), including nine (3%) with grade 3 or higher, compared with three (1%) of 339 patients in the rituximab group (no events of grade ≥3). No patients in the rituximab group but three (1%) patients in the bortezomib plus rituximab group died of adverse events considered at least possibly related to treatment.Although a regimen of bortezomib plus rituximab is feasible, the improvement in progression-free survival provided by this regimen versus rituximab alone was not as great as expected. The regimen might represent a useful addition to the armamentarium, particularly for some subgroups of patients.Johnson & Johnson Pharmaceutical Research & Development and Millennium Pharmaceuticals, Inc."
1,"TITLE: Effect of the gonadotropin-releasing hormone analogue triptorelin on the occurrence of chemotherapy-induced early menopause in premenopausal women with breast cancer: a randomized trial.ABSTRACT: Premenopausal patients with breast cancer are at high risk of premature ovarian failure induced by systemic treatments, but no standard strategies for preventing this adverse effect are yet available.To determine the effect of the temporary ovarian suppression obtained by administering the gonadotropin-releasing hormone analogue triptorelin during chemotherapy on the incidence of early menopause in young patients with breast cancer undergoing adjuvant or neoadjuvant chemotherapy.The PROMISE-GIM6 (Prevention of Menopause Induced by Chemotherapy: A Study in Early Breast Cancer Patients-Gruppo Italiano Mammella 6) study, a parallel, randomized, open-label, phase 3 superiority trial, was conducted at 16 sites in Italy and enrolled 281 patients between October 2003 and January 2008. The patients were premenopausal women with stage I through III breast cancer who were candidates for adjuvant or neoadjuvant chemotherapy. Assuming a 60% rate of early menopause in the group treated with chemotherapy alone, it was estimated that 280 patients had to be enrolled to detect a 20% absolute reduction in early menopause in the group treated with chemotherapy plus triptorelin. The intention-to-treat analysis was performed by including all randomized patients and using imputed values for missing data.Before beginning chemotherapy, patients were randomly allocated to receive chemotherapy alone or combined with triptorelin. Triptorelin was administered intramuscularly at a dose of 3.75 mg at least 1 week before the start of chemotherapy and then every 4 weeks for the duration of chemotherapy.Incidence of early menopause (defined as no resumption of menstrual activity and postmenopausal levels of follicle-stimulating hormone and estradiol 1 year after the last cycle of chemotherapy).The clinical and tumor characteristics of the 133 patients randomized to chemotherapy alone and the 148 patients randomized to chemotherapy plus triptorelin were similar. Twelve months after the last cycle of chemotherapy (last follow-up, August 18, 2009), the rate of early menopause was 25.9% in the chemotherapy-alone group and 8.9% in the chemotherapy plus triptorelin group, an absolute difference of -17% (95% confidence interval, -26% to -7.9%; P < .001). The odds ratio for treatment-related early menopause was 0.28 (95% confidence interval, 0.14 to 0.59; P < .001).The use of triptorelin-induced temporary ovarian suppression during chemotherapy in premenopausal patients with early-stage breast cancer reduced the occurrence of chemotherapy-induced early menopause.clinicaltrials.gov Identifier: NCT00311636."
1,"TITLE: The impact of anesthesia on glycine absorption in operative hysteroscopy: a randomized controlled trial.ABSTRACT: Operative hysteroscopy requires the use of a distension medium and its absorption can lead to serious consequences from intravascular volume overload and water intoxication. We compared the impact of 2 types of anesthesia (general anesthesia and local anesthesia with sedation) on the absorption of glycine solution in operative hysteroscopy.A randomized controlled trial was conducted over a 17-month period. Eligible patients undergoing operative hysteroscopy for abnormal uterine bleeding were randomized in 2 groups: a general anesthesia group and a local anesthesia with sedation group. The primary outcome was the median absorption of the glycine solution (10th-90th percentile) measured with an automated tandem canister system. Secondary outcomes included incidence of absorption >1000 mL, discontinued surgery because of excessive absorption, median change in serum sodium, postoperative hyponatremia, and patients' postoperative quality of life at 24 hours (8-item Short Form Health Survey questionnaire). Nonparametric analyses (Mann-Whitney U test, χ(2) test, and Fisher exact test) were used.Of 142 eligible patients, 95 agreed to participate and were randomized. Women who underwent general anesthesia had a higher median absorption of the glycine solution (10th-90th percentile) compared with women who underwent local anesthesia with sedation (480 mL [76-1300 mL] vs 253 mL [70-728 mL]; P = 0.005). General anesthesia was also associated with a higher rate of glycine solution absorption (>1000 mL [20% vs 4%; P = 0.009]) and a more rapid rate of decrease in serum sodium (≥10 mEq/L [8% vs 0%; P = 0.005]) than local anesthesia with sedation. Postoperative quality of life measures as rated by the patients were comparable between the 2 groups.Compared with general anesthesia, local anesthesia with sedation is associated with less glycine absorption and should be considered the preferred method of anesthesia for operative hysteroscopy."
1,"TITLE: Acupuncture for 'frequent attenders' with medically unexplained symptoms: a randomised controlled trial (CACTUS study).ABSTRACT: Medically unexplained physical symptoms (MUPS) are common and difficult to treat.To investigate the effectiveness of adding five-element acupuncture to usual care in 'frequent attenders' with MUPS.Randomised controlled trial in four London general practices.Participants were 80 adults with MUPS, consulting GPs ≥8 times/year. The intervention was individualised five-element acupuncture, ≥12 sessions, immediately (acupuncture group) and after 26 weeks (control group). The primary outcome was 26-week Measure Yourself Medical Outcome Profile (MYMOP); secondary outcomes were wellbeing (W-BQ12), EQ-5D, and GP consultation rate. Intention-to-treat analysis was used, adjusting for baseline outcomes.Participants (80% female, mean age 50 years, mixed ethnicity) had high health-resource use. Problems were 59% musculoskeletal; 65% >1 year duration. The 26-week questionnaire response rate was 89%. Compared to baseline, the mean 26-week MYMOP improved by 1.0 (95% confidence interval [CI] = 0.4 to 1.5) in the acupuncture group and 0.6 (95% CI = 0.3 to 0.9) in the control group (adjusted mean difference: acupuncture versus control -0.6 [95% CI = -1.1 to 0] P = 0.05). Other between-group adjusted mean differences were: W-BQ12 4.4 (95% CI = 1.6 to 7.2) P = 0.002; EQ-5D index 0.03 (95% CI = -0.11 to 0.16) P = 0.70; consultation rate ratio 0.90 (95% CI = 0.70 to 1.15) P = 0.4; and number of medications 0.56 (95% CI = 0.47 to 1.6) P = 0.28. All differences favoured the acupuncture group. Imputation for missing values reduced the MYMOP adjusted mean difference to -0.4 (95% CI = -0.9 to 0.1) P = 0.12. Improvements in MYMOP and W-BQ12 were maintained at 52 weeks.The addition of 12 sessions of five-element acupuncture to usual care resulted in improved health status and wellbeing that was sustained for 12 months."
0,"TITLE: Obesity and COPD: associated symptoms, health-related quality of life, and medication use.ABSTRACT: There is little data about the combined effects of COPD and obesity. We compared dyspnea, health-related quality of life (HRQoL), exacerbations, and inhaled medication use among patients who are overweight and obese to those of normal weight with COPD.We performed secondary data analysis on 364 Veterans with COPD. We categorized subjects by body mass index (BMI). We assessed dyspnea using the Medical Research Council (MRC) dyspnea scale and HRQoL using the St. George's Respiratory Questionnaire. We identified treatment for an exacerbation and inhaled medication use in the past year. We used multiple logistic and linear regression models as appropriate, with adjustment for age, COPD severity, smoking status, and co-morbidities.The majority of our population was male (n = 355, 98%) and either overweight (n = 115, 32%) or obese (n = 138, 38%). Obese and overweight subjects had better lung function (obese: mean FEV(1) 55.4% ±19.9% predicted, overweight: mean FEV(1) 50.0% ±20.4% predicted) than normal weight subjects (mean FEV(1) 44.2% ±19.4% predicted), yet obese subjects reported increased dyspnea [adjusted OR of MRC score ≥2 = 4.91 (95% CI 1.80, 13.39], poorer HRQoL, and were prescribed more inhaled medications than normal weight subjects. There was no difference in any outcome between overweight and normal weight patients.Despite having less severe lung disease, obese patients reported increased dyspnea and poorer HRQoL than normal weight patients. The greater number of inhaled medications prescribed for obese patients may represent overuse. Obese patients with COPD likely need alternative strategies for symptom control in addition to those currently recommended."
1,"TITLE: Impact of stimulant pharmacotherapy on sleep quality: post hoc analyses of 2 large, double-blind, randomized, placebo-controlled trials.ABSTRACT: Sleep disturbances may cause distress among individuals with attention-deficit/hyperactivity disorder (ADHD), but few studies have examined the impact of stimulant pharmacotherapy for ADHD on sleep in adults.These post hoc analyses included sleep data collected with the Pittsburgh Sleep Quality Index (PSQI), a self-rated questionnaire, from 831 adults with DSM-IV-TR-defined ADHD in 2 large, randomized, double-blind, placebo-controlled, forced-dose titration studies of lisdexamfetamine (N = 420; conducted from May 25, 2006, to November 16, 2006) and triple-bead mixed amphetamine salts (MAS) (N = 411; conducted from April 25, 2005, to November 4, 2005). Change from baseline to endpoint in PSQI clinically meaningful change categories (ie, ""decrease,"" ""no change,"" or ""increase"") was analyzed by treatment group in each study using the χ² test. The Cochran-Mantel-Haenszel method was used (1) to determine whether there was a statistically significant difference in Clinical Global Impressions-Improvement (CGI-I) score of 1 or 2 (improved) versus > 2 (not improved) relative to a decrease or an increase in PSQI and (2) to analyze shifts from good sleep at baseline (PSQI ≤ 5) to poor sleep at endpoint (PSQI > 5).Impaired sleep (PSQI score > 5) relative to baseline was demonstrated in 8.3% and 9.7% of the treatment and placebo groups, respectively (P = .18), in the MAS study and 7.7% and 8.2%, respectively (P = .03), in the lisdexamfetamine study. Clinically meaningful change in baseline to endpoint PSQI was not statistically significantly different between treatment and placebo groups in either study. A significant difference in CGI-I 1 and 2 relative to an increase or decrease in PSQI was found in both the triple-bead MAS (P < .0001) and the lisdexamfetamine (P = .0008) trials. More subjects with improved CGI-I rating of 1 or 2 had improvement in PSQI than had worsening.Approximately one-third of subjects receiving treatment or placebo had clinically meaningful sleep improvement, emphasizing that change in sleep quality during treatment may not necessarily be related to stimulant therapy. When managing complaints of sleep difficulties in ADHD subjects, clinicians should undertake a broad assessment and consider underlying conditions that may contribute to sleep disruption.clinicaltrials.gov Identifiers: NCT00334880 and NCT00152022."
0,"TITLE: Central obesity and cardiovascular outcomes in patients with acute coronary syndrome: observations from the MERLIN-TIMI 36 trial.ABSTRACT: Despite the association of obesity with incident cardiovascular disease, obese patients with acute coronary syndrome (ACS) appear to have more favourable short-term outcomes. A study was undertaken to determine whether this 'obesity paradox' persists in the long term and to examine the specific relationship of central obesity with outcomes after ACS.The relationship was investigated between two measures of obesity-body mass index (BMI) and waist circumference (WC)-and 30-day and 1-year outcomes after ACS. 6560 patients with non-ST elevation ACS in the MERLIN-TIMI 36 trial were followed for 1 year. Patients were stratified into three BMI groups (<25, 25-30, ≥30 kg/m2) and gender-specific tertiles of WC. The primary endpoint was cardiovascular death, myocardial infarction or recurrent ischaemia.Patients with BMI ≥30 kg/m2 had a significantly lower risk of the primary endpoint than those with BMI <25 kg/m(2) (HR 0.64; 95% CI 0.51 to 0.81, p<0.0001) at 30 days. However, after the 30-day acute phase, landmark analysis from 30 days to 1 year showed no difference in risk between BMI groups (HR 1.09; 95% CI 0.92 to 1.29, p=0.34). WC tertiles demonstrated a similar relationship. When BMI groups were stratified by WC there was a trend towards more adverse outcomes in higher WC groups among those in lower BMI groups. The group with the lowest BMI and highest WC had the highest risk (HR 2.8; 95% CI 0.93 to 8.3; p=0.067).Obesity is associated with more favourable short-term outcomes after ACS. However, in the longer term the obesity paradox is no longer present and may reverse. Those with WC out of proportion to BMI suggestive of significant central adiposity may be at highest risk following ACS."
0,"TITLE: Oral prednisone use and risk of keratinocyte carcinoma in non-transplant population. The VATTC trial.ABSTRACT: Glucorticosteroids (GC) are potent anti-inflammatory medications with immunosuppressive property. Few retrospective studies have reported the increased risk of development of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) associated with GC use.We aimed to assess the effect of oral GC use on the risk of BCC and SCC using prospective data.We analysed data from the Veterans Affairs Topical Tretinoin Chemoprevention Trial, which followed up patients from 1998 to 2004. Exposure to oral GCs was defined as (1) use of any oral GCs at any point during follow-up and (2) use of GCs for a month or longer. Outcome was occurrence of new BCC or SCC. Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).Among the 1051 study participants, 148 patients (14%) had prednisone prescription filled during study period, and 63 (6%) used prednisone for over a month. A total of 472 patients (45%) developed at least one BCC during study: 394 (44%) among non-users of prednisone and 78 (53%) among any time users. The total number of new SCC was 309 (29%): 258 (29%) among non-users of prednisone and 51 (34%) among users. Among any time prednisone users, the adjusted HR was 1.11 (95% CI, 0.87-1.42) for BCC, and 1.05 (95% CI, 0.76-1.45) for SCC. Among those who used prednisone for 30 or more days, the HR was 1.26 (95% CI, 0.90-1.78) for BCC, and 1.03 (95% CI, 0.66-1.60) for SCC.This study does not support the existence of association between use of oral GCs and risk of BCC or SCC."
0,"TITLE: Carotid intima-media thickness, electrocardiographic left ventricular hypertrophy, and incidence of intracerebral hemorrhage.ABSTRACT: Carotid intima-media thickness and electrocardiographic left ventricular hypertrophy are 2 subclinical cardiovascular disease measures associated with increased risk of total and ischemic strokes. Increased intima-media thickness and electrocardiographic left ventricular hypertrophy also may reflect end-organ hypertensive effects. Information is scant on the associations of these subclinical measures with intracerebral hemorrhage (ICH). We hypothesized that greater carotid intima-media thickness and the presence of electrocardiographic left ventricular hypertrophy would be independently associated with increased ICH incidence.Among 18,155 participants initially free of stroke in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS), we assessed carotid intima-media thickness, carotid plaque, and electrocardiographic left ventricular hypertrophy. Over a median of 18 years of follow-up, 162 incident ICH events occurred.After adjustment for other ICH risk factors, carotid intima-media thickness was associated positively with incidence of ICH in both ARIC and CHS. The risk was lowest in study-specific Quartile 1, elevated 1.6- to 2.6-fold in Quartiles 2 to 3, and elevated 2.5 to 3.7-fold in Quartile 4 (P<0.05 for both studies). In CHS, having a carotid plaque was associated with a 2-fold (95% CI, 1.1-3.4) greater ICH risk than having no plaque, but only 1.2-fold (95% CI, 0.76-2.0) greater ICH risk in ARIC. Electrocardiographic left ventricular hypertrophy carried a hazard ratio of ICH of 1.7 (95% CI, 0.77-3.7) in CHS and 2.8 (95% CI, 1.2-6.4) in ARIC.Our data suggest that people with carotid atherosclerosis and possibly left ventricular hypertrophy are at increased risk not only of ischemic stroke, but also of ICH."
0,"TITLE: Assessing food appeal and desire to eat: the effects of portion size & energy density.ABSTRACT: Visual presentation of food provides considerable information such as its potential for palatability and availability, both of which can impact eating behavior.We investigated the subjective ratings for food appeal and desire to eat when exposed to food pictures in a fed sample (n=129) using the computer paradigm ImageRate. Food appeal and desire to eat were analyzed for the effects of food group, portion size and energy density of the foods presented as well as by participant characteristics.Food appeal ratings were significantly higher than those for desire to eat (57.9±11.6 v. 44.7±18.0; p<0.05). Body mass index was positively correlated to desire to eat (r=0.20; p<0.05), but not food appeal. Food category analyses revealed that fruit was the highest rated food category for both appeal and desire, followed by discretionary foods. Additionally, overweight individuals reported higher ratings of desire to eat large portions of food compared to smaller portions (p<0.001), although these effects were relatively small. Energy density of the foods was inversely correlated with ratings for both appeal and desire (r's=-0.27; p's<0.01).Results support the hypothesis that individuals differentiate between food appeal and desire to eat foods when assessing these ratings using the same type of metric. Additionally, relations among food appeal and desire to eat ratings and body mass show overweight individuals could be more responsive to visual foods cues in a manner that contributes to obesity."
1,"TITLE: Efficacy and tolerability of a 20-mg dose of methylphenidate for the treatment of daytime sleepiness in adult patients with myotonic dystrophy type 1: a 2-center, randomized, double-blind, placebo-controlled, 3-week crossover trial.ABSTRACT: Despite the fact that excessive daytime sleepiness (EDS) is one of the most common manifestations in patients with myotonic dystrophy type 1 (DM1), no treatment is yet available. Methylphenidate is being studied for prospective use in the treatment of EDS.The aim of this investigator-initiated study was to evaluate the efficacy and tolerability of a single 20-mg morning dose of methylphenidate for the treatment of EDS in adults with DM1.This randomized, double-blind, placebo-controlled, 3-week crossover trial was conducted at 2 sites in Quebec. French-Canadian patients with DM1 with an Epworth Sleepiness Scale score ≥10 were invited to participate in this crossover trial of 20 mg/d of methylphenidate versus placebo, with 3 weeks in each arm of the study separated by a 2-week washout period. The primary efficacy end points were the Daytime Sleepiness Scale and the Epworth Sleepiness Scale at week 3. Secondary end points included the energy/vitality scale of the RAND 36-Item Health Survey, the Profile of Mood States questionnaire, and the mean sleep latency test. Assessment of tolerability profile included a physical examination, measurement of blood pressure, standard 12-lead ECG, and laboratory tests. Adverse event assessments were recorded based on patient reporting at each visit on clinical report forms.In a total of 24 patients (12 men, 12 women; mean [SD] age, 46 [13] years), 17 completed the study. Treatment with methylphenidate showed a significant change in median scores on the Daytime Sleepiness Scale (-3.0 vs -0.5; P = 0.003) and the Epworth Sleepiness Scale (-3.0 vs -1.5; P = 0.039). The Profile of Mood States and the energy/vitality scale from the RAND 36-Item Health Survey showed no significant changes. Likewise, there was no significant change in mean sleep latency test results. One patient died during the trial, but the autopsy results eliminated methylphenidate as cause of death. Three patients discontinued methylphenidate due to treatment-emergent adverse events (1, diarrhea; 2, nervousness and irritability). Loss of appetite, nausea, and palpitations were the most common adverse events reported by more patients treated with methylphenidate than those receiving placebo.A single 20-mg dose of methylphenidate significantly reduced daytime sleepiness in this small selected population of patients with DM1. ClinicalTrials.gov identifier: NCT01421992."
1,"TITLE: Low-Sodium Versus Standard-Sodium Peritoneal Dialysis Solution in Hypertensive Patients: A Randomized Controlled Trial.ABSTRACT: Peritoneal dialysis (PD) solutions with reduced sodium content may have advantages for hypertensive patients; however, they have lower osmolarity and solvent drag, so the achieved Kt/Vurea may be lower. Furthermore, the increased transperitoneal membrane sodium gradient can influence sodium balance with consequences for blood pressure (BP) control.Prospective, randomized, double-blind clinical trial to prove the noninferiority of total weekly Kt/Vurea with low-sodium versus standard-sodium PD solution, with the lower confidence limit above the clinically accepted difference of -0.5.Hypertensive patients (≥ 1 antihypertensive drug, including diuretics, or office systolic BP ≥ 130 mmHg) on continuous ambulatory PD therapy from 17 sites.108 patients were randomly assigned (1:1) to 6-month treatments with either low-sodium (125 mmol/L of sodium; 1.5%, 2.3%, or 4.25% glucose; osmolarity, 338-491 mOsm/L) or standard-sodium (134 mmol/L of sodium; 1.5%, 2.3%, or 4.25% glucose; osmolarity, 356-509 mOsm/L) PD solution.Primary end point: weekly total Kt/Vurea; secondary outcomes: BP control, safety, and tolerability.Total Kt/Vurea was determined from 24-hour dialysate and urine collection; BP, by office measurement.Total Kt/Vurea after 12 weeks was 2.53 ± 0.89 in the low-sodium group (n = 40) and 2.97 ± 1.58 in the control group (n = 42). The noninferiority of total Kt/Vurea could not be confirmed. There was no difference for peritoneal Kt/Vurea (1.70 ± 0.38 with low sodium, 1.77 ± 0.44 with standard sodium), but there was a difference in renal Kt/Vurea (0.83 ± 0.80 with low sodium, 1.20 ± 1.54 with standard sodium). Mean daily sodium removal with dialysate at week 12 was 1.188 g higher in the low-sodium group (P < 0.001). BP changed marginally with standard-sodium solution, but decreased with low-sodium PD solution, resulting in less antihypertensive medication.Broader variability of study population than anticipated, particularly regarding residual kidney function.The noninferiority of the low-sodium PD solution for total Kt/Vurea could not be proved; however, it showed beneficial clinical effects on sodium removal and BP."
1,"TITLE: The impact of access blood flow surveillance on reduction of thrombosis in native arteriovenous fistula: a randomized clinical trial.ABSTRACT: The usefulness of access blood flow (QA) measurement is an ongoing controversy. Although all vascular access (VA) clinical guidelines recommend monitoring and surveillance protocols to prevent VA thrombosis, randomized clinical trials (RCTs) have failed to consistently show the benefits of QA-based surveillance protocols. We present a 3-year follow-up multicenter, prospective, open-label, controlled RCT, to evaluate the usefulness of QA measurement using Doppler ultrasound (DU) and ultrasound dilution method (UDM), in a prevalent hemodialysis population with native arteriovenous fistula (AVF).Classical monitoring and surveillance methods are applied in all patients, the control group (n = 98) and the QA group (n = 98). Besides this, DU and UDM are performed in the QA group every three months. When QA is under 500 ml/min or there is a >25% decrease in QA the patient goes for fistulography, surgery or close clinical/surveillance observation. Thrombosis rate, assisted primary patency rate, primary patency rate and secondary patency rate are measured.After one-year follow-up we found a significant reduction in thrombosis rate (0.022 thrombosis/patient/year at risk in the QA group compared to 0.099 thrombosis/patient/year at risk in the control group [p = 0.030]). Assisted primary patency rate was significantly higher in the QA group than in control AVF (hazard ratio [HR] 0.23, 95% confidence interval [CI] 0.05-0.99; p = 0.030). In the QA group, the numbers unddergoing angioplasty and surgery were higher but with no significant difference in non-assisted primary patency rate (HR 1.41, 95% CI 0.72-2.84; p = 0.293). There was a non-significant improvement in secondary patency rate in the QA group (HR 0.510, 95% CI 0.17-1.50; p = 0.207).The measurement of QA combining DU and UDM shows a reduction in thrombosis rate and an increased assisted primary patency rate in AVF after one-year follow-up.ClinicalTrials.gov Identifier: NCT02111655."
1,"TITLE: BRAzil magnesium (BRAMAG) trial: a double-masked randomized clinical trial of oral magnesium supplementation in pregnancy.ABSTRACT: There is conflicting evidence about the role of oral magnesium supplementation in the prevention of preterm birth and related adverse outcomes. The objective of this study was to compare magnesium citrate with placebo in the prevention of adverse perinatal and maternal outcomes among women at higher risk.This multicenter, double-masked, placebo-controlled randomized superiority clinical trial compared oral magnesium citrate 300 mg to matched placebo, from 12 to 20 weeks' gestation until delivery. This trial was completed in three centers in northeastern Brazil. Eligible women were those with a singleton pregnancy and ≥ 1 risk factor, such as prior preterm birth or preeclampsia, or current chronic hypertension or pre-pregnancy diabetes mellitus, age > 35 years or elevated body mass index. The primary perinatal composite outcome comprised preterm birth < 37 weeks' gestation, stillbirth > 20 weeks, neonatal death or NICU admission < 28 days after birth, or small for gestational age birthweight < 3rd percentile. The co-primary maternal composite outcome comprised preeclampsia or eclampsia < 37 weeks, severe gestational hypertension < 37 weeks, placental abruption, or maternal stroke or death during pregnancy or ≤ 7 days after delivery.Analyses comprised 407 women who received magnesium citrate and 422 who received placebo. The perinatal composite outcome occurred among 75 (18.4%) in the magnesium arm and 76 (18.0%) in the placebo group - an adjusted odds ratio (aOR) of 1.10 (95% CI 0.72-1.68). The maternal composite outcome occurred among 49 (12.0%) women in the magnesium arm and 41 women (9.7%) in the placebo group - an aOR of 1.29 (95% CI 0.83-2.00).Oral magnesium citrate supplementation did not appear to reduce adverse perinatal or maternal outcomes in high-risk singleton pregnancies.ClinicalTrials.gov NCT02032186, registered January 9, 2014."
1,"TITLE: FTY720 versus MMF with cyclosporine in de novo renal transplantation: a 1-year, randomized controlled trial in Europe and Australasia.ABSTRACT: FTY720 is a novel immunomodulator investigated in de novo renal transplantation and other therapeutic areas including multiple sclerosis. This 1-year multicenter, randomized, phase III study in 668 de novo renal transplant patients compared FTY720 2.5 mg plus full-dose cyclosporine (FDC) or FTY720 5.0 mg plus reduced-dose cyclosporine (RDC), with mycophenolate mofetil (MMF) plus FDC. The primary efficacy endpoint was the composite incidence of first treated biopsy-proven acute rejection (BPAR), graft loss, death or premature study discontinuation at month 12. Primary efficacy with FTY720 2.5 mg and MMF (32.4% and 30.2%; p = NS), plus mortality and BPAR incidence, were comparable. Patients receiving FTY720 5.0 mg plus RDC were discontinued from treatment due to increased risk of acute rejection (primary endpoint incidence 47.3%). FTY720 was associated with lower creatinine clearance (month 12: 53.1, 56.0 vs. 65.1 mL/min; p < 0.001) and more macular edema cases (2.2% and 1.3% vs. 0%), whereas cytomegalovirus infections were higher with MMF (6.2% and 10.6% vs. 18.1% p < 0.0001 and p = 0.0139, respectively). FTY720 2.5 mg provided comparable rejection prophylaxis over 12 months versus MMF; however, FTY720 5.0 mg did not support a 50% reduction in cyclosporine exposure. The cause of macular edema cases and lower creatinine clearance with FTY720 in de novo transplantation needs further investigation."
0,"TITLE: Prospective multicenter study of quality of life before and after lower extremity vein bypass in 1404 patients with critical limb ischemia.ABSTRACT: Patients with critical limb ischemia (CLI) have multiple comorbidities and limited life spans. The ability of infrainguinal vein bypass to improve quality of life (QoL) in patients with CLI has therefore been questioned. Prospective preoperative and postoperative QoL data for patients undergoing lower extremity vein bypass for CLI are presented.A validated, disease-specific QoL questionnaire (VascuQoL) with activity, symptom, pain, emotional, and social domains and responses scored 1 (lowest QoL) to 7 (best QoL) was administered before surgery and at 3 and 12 months after lower extremity vein bypass for CLI. Changes in QoL at 3 and 12 months after lower extremity vein bypass and multiple predetermined variables potentially influencing QoL after lower extremity vein bypass were analyzed to determine the effect of lower extremity vein bypass on QoL in CLI patients.A total of 1404 patients had lower extremity vein bypass for CLI at 83 centers in the United States and Canada as part of the PREVENT III clinical trial. Surveys were completed in 1296 patients at baseline, 862 patients at 3 months, and 732 patients at 12 months. The global QoL score (mean +/- SD) was 2.8 +/- 1.1 at baseline and was 4.7 +/- 1.4 and 5.1 +/- 1.4 at 3 and 12 months, respectively. Mean changes from baseline at 3 and 12 months were statistically significant (P < .0001). Improved QoL scores extended across all domains. Diabetes and the development of graft-related events were associated with decreased improvement in QoL scores, though the mean relative change from baseline remained positive.Patients with CLI have a low QoL at baseline that is improved at 3 and 12 months after lower extremity vein bypass. QoL improvements are lower in diabetic patients and those who develop graft-related events. Successful revascularization can be expected to improve QoL in patients with CLI, with benefits that are sustained to at least 1 year."
1,"TITLE: Randomized phase II trial of gemcitabine plus weekly versus three-weekly paclitaxel in previously untreated advanced non-small-cell lung cancer.ABSTRACT: Gemcitabine and paclitaxel (Taxol) each provides an efficacious non-platinum option for the treatment of advanced non-small-cell lung cancer (NSCLC), but the optimal dosage and schedule of the two agents used in combination are not well defined.Previously untreated patients with advanced NSCLC were randomized to receive gemcitabine-paclitaxel on a traditional three-weekly schedule (Arm A) or a novel weekly schedule (Arm B) as follows-Arm A (three-weekly): gemcitabine 1000 mg/m2 infused>30 min on days 1 and 8 and paclitaxel 200 mg/m2 infused>3 h on day 1 of a 21-day cycle or Arm B (weekly): gemcitabine 1000 mg/m2 infused>30 min and paclitaxel 100 mg/m2 infused>1 h, both administered on days 1 and 8 of a 21-day cycle.One hundred patients received at least one dose of treatment. The weekly schedule, Arm B, was more efficacious and less hematologically toxic than Arm A. Confirmed complete and partial response rates were 28.2% and 26.8%, respectively. Median survival was 10.3 months on Arm B and 7.9 months on Arm A (log-rank P=0.10); 1- and 2-year survival rates also favor Arm B: 42.0% versus 34.0% and 18.0% versus 6.0%. Progression-free survival was 5.8 versus 4.8 months, again favoring Arm B (log-rank P=0.06). There was a two-fold lower frequency of grade 3/4 hematologic events with Arm B as follows: neutropenia (16% versus 30%), thrombocytopenia (4% versus 8%), and anemia (2% versus 6%). One patient (2%) in each treatment group developed febrile neutropenia.In this trial, both schedules were efficacious and tolerable, although the weekly schedule resulted in improved survival and lower hematologic toxicity compared with a three-weekly schedule. The weekly schedule of gemcitabine-paclitaxel indicates an improved therapeutic index."
1,"TITLE: Effect of various diuretic treatments on rosiglitazone-induced fluid retention.ABSTRACT: The efficacy of diuretics in the management of rosiglitazone (RSG)-induced fluid retention was evaluated in a multicenter, randomized, open-label, parallel-group, proof-of-concept study. Of 381 patients who had type 2 diabetes and were on treatment with sulfonylurea or sulfonylurea plus metformin, 260 (63% male, 37% female) showed evidence of volume expansion as defined by an absolute reduction in hematocrit (Hct) of > or =0.5% after 12 wk of rosiglitazone 4 mg twice daily. They were randomly assigned to five treatments for 7 d: (1) Continuation of RSG (RSG-C), (2) RSG + furosemide (RSG+FRUS), (3) RSG + hydrochlorothiazide (RSG+HCTZ), (4) RSG + spironolactone (RSG+SPIRO), and (5) discontinuation of RSG. The primary end point was change in Hct at day 7 of diuretic treatment phase, powered to compare each diuretic group and the RSG discontinuation with the control group of RSG-C, with adjustments for multiple testing. After 12 wk on RSG, Hct fell by mean of 2.92% (95% confidence interval [CI] -3.10 to -2.63%; P < 0.001) and extracellular fluid volume increased by 0.62 L/1.73 m(2) (95% CI 0.26 to 0.90 L/1.73 m(2); P < 0.001). After treatment, the RSG+SPIRO group only showed a mean increase in Hct of 0.24%. The estimated mean difference in Hct reduction was significant: 1.14% (95% CI 0.29 to 1.98%) for RSG+SPIRO (P = 0.004) and 0.87% (95% CI 0.03 to 1.71%) for RSG+HCTZ (P = 0.041) only. In additional analyses of between-diuretic treatment effects SPIRO induced a greater Hct rescue at 0.88% (95% CI -0.12 to 1.87%; P = 0.095) and extracellular fluid volume reduction of -0.75 L/1.73 m(2) (95% CI -1.52 to 0.03 L/1.73 m(2); P = 0.06) compared with FRUS, suggesting superiority in the management of RSG-associated fluid retention. There were no significant differences between SPIRO and HCTZ. These findings are consistent with peroxisome proliferator-activated receptor-gamma agonist activation of the epithelial sodium channel in the distal collecting duct, a site of action of SPIRO and a potential target for thiazide diuretics."
1,"TITLE: Improving knowledge about mental illness through family-led education: the journey of hope.ABSTRACT: Families often do not receive the information that they need to care for their adult relatives with mental illness. This study examined the effectiveness of a family-led education intervention, the Journey of Hope, in improving participants' knowledge about mental illness and its treatment and decreasing their information needs.A total of 462 family members of adults with mental illness in Louisiana participated in the study; 231 were randomly assigned to immediate receipt of the Journey of Hope course (intervention group), and 231 were randomly assigned to a nine-month waiting list for the course (control group). Participants completed in-person, structured interviews assessing their knowledge of mental illness and problem-solving skills and their information needs at study enrollment (baseline), three months postbaseline, and eight months postbaseline.Random regression analyses indicate that at three and eight months postbaseline, compared with participants assigned to the control group, those in the intervention group reported greater knowledge gains (beta=.84, p< or =.01) and fewer needs for information on coping with positive symptoms (beta=-.63, p< or =.05), coping with negative symptoms (beta=-.80, p< or =.001), problem management (beta=-1.00, p< or =.001), basic facts about mental illness and its treatment (beta=-.73, p< or =.01), and community resources (beta=-.07, p< or =.05). These significant differences in knowledge and information needs were maintained over time and were significant even when controlling for participants' demographic characteristics and their relatives' clinical characteristics.Participation in family-led education interventions, such as the Journey of Hope, may provide families with the information they need to better cope with their relative's mental illness."
1,"TITLE: A 1-year safety and efficacy study of duloxetine in patients with fibromyalgia.ABSTRACT: Evaluate the efficacy and safety of duloxetine at doses up to 120 mg once daily in patients with fibromyalgia.This was a phase 3, 60-week study, which included an 8-week open-label period followed by a 52-week, randomized, double-blind period. Patients received duloxetine 30 mg daily for 1 week and duloxetine 60 mg daily for 7 weeks and were then randomized to receive either 60 or 120 mg daily (1:2 ratio).Enrolled patients (N=350, 95.7% female) exhibited moderate disease symptoms at study entry (Brief Pain Inventory average pain=6.7, Clinical Global Impression of Severity=4.1, and Patient's Global Impression of Severity=4.1). Significant pain reduction in patients was observed during the open-label study phase. This pain reduction continued during the 52-week double-blind study phase, as demonstrated by additional mean decreases in the Brief Pain Inventory average pain score within both duloxetine groups. The most common (> or =15%) treatment-emergent adverse events (overall phase) were nausea, headache, insomnia, dizziness, constipation, and dry mouth. Seventy-four (21.1%) patients reported adverse events as a reason for discontinuation [most common (>1%) were insomnia, vomiting, diarrhea, dizziness, and nausea]. The mean change (SD) in sitting systolic blood pressure (mm Hg) was -0.1 (14.4), in sitting diastolic blood pressure was -0.2 (9.6), in sitting pulse rate was 1.9 (10.4) bpm, and in weight was 0.7 (4.3) kg.The profile of duloxetine for the long-term treatment of fibromyalgia was consistent with that seen in other indications for which the drug is currently marketed."
1,"TITLE: Daclizumab versus antithymocyte globulin in high-immunological-risk renal transplant recipients.ABSTRACT: Nondepleting anti-CD25 monoclonal antibodies (daclizumab) and depleting polyclonal antithymocyte globulin (Thymoglobulin) both prevent acute rejection, but these therapies have not been directly compared in a high-risk, HLA-sensitized renal transplant population. We randomly assigned 227 patients, who were about to receive a kidney graft from a deceased donor, to either Thymoglobulin or daclizumab if they met one of the following risk factors: current panel reactive antibodies (PRA) >30%; peak PRA >50%; loss of a first kidney graft from rejection within 2 yr of transplantation; or two or three previous grafts. Maintenance immunosuppression comprised tacrolimus, mycophenolate mofetil, and steroids. Compared with the daclizumab group, patients treated with Thymoglobulin had a lower incidence of both biopsy-proven acute rejection (15.0% versus 27.2%; P = 0.016) and steroid-resistant rejection (2.7% versus 14.9%; P = 0.002) at one year. One-year graft and patient survival rates were similar between the two groups. In a comparison of rejectors and nonrejectors, overall graft survival was significantly higher in the rejection-free group (87.2% versus 75.0%; P = 0.037). In conclusion, among high-immunological-risk renal transplant recipients, Thymoglobulin is superior to daclizumab for the prevention of biopsy-proven acute rejection, but there is no significant benefit to one-year graft or patient survival."
1,"TITLE: Survival benefit with erlotinib maintenance therapy in patients with advanced non-small-cell lung cancer (NSCLC) according to response to first-line chemotherapy.ABSTRACT: In the placebo-controlled phase III SATURN study, maintenance erlotinib after first-line chemotherapy demonstrated significantly prolonged progression-free survival (PFS) and overall survival (OS) in the overall study population of patients with advanced non-small-cell lung cancer (NSCLC).After four cycles of platinum-based doublet chemotherapy, patients without progressive disease (PD) were randomised to erlotinib (150 mg/day) or placebo until PD or unacceptable toxicity. In this pre-planned analysis, data are assessed according to response to first-line chemotherapy (complete/partial response [CR/PR] or stable disease [SD]).Following first-line chemotherapy, 889 non-PD patients were included in the intention-to-treat population (55% SD; 44% CR/PR; <1% unknown response). Erlotinib maintenance therapy significantly prolonged PFS in both the SD (hazard ratio [HR] = 0.68; P < 0.0001) and CR/PR (HR = 0.74; P = 0.0059) groups, while OS was significantly prolonged in the SD group only (HR = 0.72; P = 0.0019). The erlotinib-related OS benefit in the SD group remained significant across subgroups, irrespective of tumour histology and/or EGFR mutation status. The incidence of adverse events was similar in the SD group and the overall population, and erlotinib treatment did not negatively impact quality of life.Patients with advanced NSCLC and SD following first-line platinum-based doublet chemotherapy derive a significant OS benefit from maintenance erlotinib therapy."
1,"TITLE: Efficient implementation of patient-specific simulated rehearsal for the carotid artery stenting procedure: part-task rehearsal.ABSTRACT: Patient-specific simulated rehearsal (PsR) is a technological advance within the domain of endovascular virtual reality (VR) simulation. It allows incorporation of patient-specific computed tomography Digital Imaging and Communications in Medicine (CT DICOM) data into the simulation and subsequent rehearsal of real patient cases. This study aimed to evaluate whether a part-task rehearsal (PTr) of a carotid artery stenting procedure (CAS) on a VR simulator is as effective as a full-task (FTr) preoperative run through.Medical trainees were trained in the CAS procedure and randomised to a PTr or FTr of a challenging CAS case (Type-II arch). PTr consisted of 30 min of repeated catheterisations of the common carotid artery (CCA). Thereafter, both groups performed the CAS procedure in a fully functional simulated operating suite (SOS) with an interventional team. Technical performances were assessed using simulator-based metrics and expert ratings. Other aspects of performance were assessed using the Non-Technical Skills for Surgeons (NOTSS) scoring.Twenty trainees were evenly randomised to either PTr or FTr. No differences in performance were seen except for the total time the embolic protection device (EPD) was deployed (9.4 min for the PT vs. 8.1 min for the FT, p = 0.02). Total time (26.3 vs. 25.5 min, p = 0.94), fluoroscopy time (15.8 vs. 14.4 min, p = 0.68), number of roadmaps (10.5 vs. 11.0, p = 0.54), amount of contrast (53.5 vs. 58.0 ml, p = 0.33), time to deploy the EPD (0.9 vs. 0.8 min, p = 0.31) and time to catheterise the CCA (9.2 vs. 8.9 min, p = 0.94) were similar. Qualitative performances as measured by expert ratings (score 24 vs. 24, p = 0.49) and NOTSS (p > 0.05 for all categories) were also comparable.Part- and full-task rehearsals are equally effective with respect to the operative performance of a simulated CAS intervention. This finding makes a patient-specific rehearsal more efficient and may increase the feasibility of implementation of this technology into medical practice."
0,"TITLE: Gambling and adverse life events among urban adolescents.ABSTRACT: This study explored the cross sectional association between adverse life events and gambling in a sample of 515 urban adolescents (average age 17, 55% male, 88% African American). Approximately half of the sample had gambled in the past year (51%); 78% of the gamblers gambled monthly and 39% had a gambling-related problem. On the other hand, 88% of the sample had experienced at least one life event in the past year, and those experiencing events tended to live in more disadvantaged neighborhoods. The mere acknowledgement of experiencing a stressful life event in the past year (yes/no) was not associated with an increase in odds of being a gambler, with gambling more frequently, or with having a gambling problem. However, when the context of the event was considered, an association was found between directly experiencing threatening and deviant/violent types of events and frequent gambling (OR > 2). Additionally, the probability of being a gambler increased as the number of events experienced increased (aOR = 1.07, 95% CI = 1.01, 1.13, P = 0.013), but problems among gamblers were not associated with the number of events experienced (aOR = 1.01, 95% CI = 0.92, 1.11, P = 0.876). During adolescence, life events appear to be connected more with the frequency of gambling rather than with problems related to gambling."
1,"TITLE: Outcome comparison of 600- and 300-mg loading doses of clopidogrel in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results from the ARMYDA-6 MI (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction) randomized study.ABSTRACT: The purpose of this study was to compare 600- and 300-mg clopidogrel loading doses in patients with ST-segment elevation myocardial infarction (STEMI).Given the high thrombotic risk of patients with STEMI, greater platelet inhibition may improve outcome in those patients receiving percutaneous coronary intervention (PCI). Although observational data suggest that pretreatment with a 600-mg clopidogrel loading dose may be more effective than the 300-mg regimen in primary PCI, this hypothesis has never been tested in a randomized study.A total of 201 patients undergoing primary PCI for STEMI randomly received a 600-mg (n = 103) or 300-mg (n = 98) clopidogrel loading dose before the procedure. The primary endpoint was the evaluation of the infarct size, defined as the area under the curve of cardiac markers.Infarct size was significantly lower in the high-dose regimen: median creatine kinase-myocardial band 2,070 ng/ml (interquartile range [IQR]: 815 to 2,847 ng/ml) versus 3,049 ng/ml (IQR: 1,050 to 7,031 ng/ml) in the 300-mg group, p = 0.0001; troponin-I 255 ng/ml (IQR: 130 to 461 ng/ml) versus 380 ng/ml (IQR: 134 to 1,406 ng/ml), p < 0.0001. In the 600-mg arm, Thrombolysis In Myocardial Infarction flow grade <3 after PCI was less frequent (5.8% vs. 16.3%, p = 0.031), left ventricular ejection fraction at discharge was improved (52.1 ± 9.5% vs. 48.8 ± 11.3%, p = 0.026), 30-day major adverse cardiovascular events were fewer (5.8% vs. 15%, p = 0.049), and bleeding/entry site complications were not increased (secondary endpoints).In STEMI patients, pre-treatment with a 600-mg clopidogrel loading dose before primary PCI was associated with a reduction of the infarct size compared with a 300-mg loading dose, as well as with improvement of angiographic results, residual cardiac function, and 30-day major adverse cardiovascular events; further studies are warranted to evaluate impact of such strategy on survival."
1,"TITLE: Integration of antiretroviral therapy with tuberculosis treatment.ABSTRACT: We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, the timing for the initiation of ART during tuberculosis treatment remains unresolved.We conducted a three-group, open-label, randomized, controlled trial in South Africa involving 642 ambulatory patients, all with tuberculosis (confirmed by a positive sputum smear for acid-fast bacilli), human immunodeficiency virus infection, and a CD4+ T-cell count of less than 500 per cubic millimeter. Findings in the earlier-ART group (ART initiated within 4 weeks after the start of tuberculosis treatment, 214 patients) and later-ART group (ART initiated during the first 4 weeks of the continuation phase of tuberculosis treatment, 215 patients) are presented here.At baseline, the median CD4+ T-cell count was 150 per cubic millimeter, and the median viral load was 161,000 copies per milliliter, with no significant differences between the two groups. The incidence rate of the acquired immunodeficiency syndrome (AIDS) or death was 6.9 cases per 100 person-years in the earlier-ART group (18 cases) as compared with 7.8 per 100 person-years in the later-ART group (19 cases) (incidence-rate ratio, 0.89; 95% confidence interval [CI], 0.44 to 1.79; P=0.73). However, among patients with CD4+ T-cell counts of less than 50 per cubic millimeter, the incidence rates of AIDS or death were 8.5 and 26.3 cases per 100 person-years, respectively (incidence-rate ratio, 0.32; 95% CI, 0.07 to 1.13; P=0.06). The incidence rates of the immune reconstitution inflammatory syndrome (IRIS) were 20.1 and 7.7 cases per 100 person-years, respectively (incidence-rate ratio, 2.62; 95% CI, 1.48 to 4.82; P<0.001). Adverse events requiring a switching of antiretroviral drugs occurred in 10 patients in the earlier-ART group and 1 patient in the later-ART group (P=0.006).Early initiation of ART in patients with CD4+ T-cell counts of less than 50 per cubic millimeter increased AIDS-free survival. Deferral of the initiation of ART to the first 4 weeks of the continuation phase of tuberculosis therapy in those with higher CD4+ T-cell counts reduced the risks of IRIS and other adverse events related to ART without increasing the risk of AIDS or death. (Funded by the U.S. President's Emergency Plan for AIDS Relief and others; SAPIT ClinicalTrials.gov number, NCT00398996.)."
1,"TITLE: Selective decontamination of the oral and digestive tract in surgical versus non-surgical patients in intensive care in a cluster-randomized trial.ABSTRACT: Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) are effective in improving survival in patients under intensive care. In this study possible differential effects in surgical and non-surgical patients were investigated.This was a post hoc subgroup analysis of data from a cluster-randomized multicentre trial comparing three groups (SDD, SOD or standard care) to quantify effects among surgical and non-surgical patients. The primary study outcome was 28-day mortality rate. Duration of mechanical ventilation, duration of intensive care unit (ICU) and hospital length of stay, and bacteraemia rates were secondary outcomes.The subgroup analyses included a total of 2762 surgical and 3165 non-surgical patients. Compared with standard care, adjusted odds ratios (ORs) for mortality were comparable in SDD-treated surgical and non-surgical patients: 0·86 (95 per cent confidence interval 0·69 to 1·09; P = 0·220) and 0·85 (0·70 to 1·03; P = 0·095) respectively. However, duration of mechanical ventilation, ICU stay and hospital stay were significantly reduced in surgical patients who had SDD. SOD did not reduce mortality compared with standard treatment in surgical patients (adjusted OR 0·97, 0·77 to 1·22; P = 0·801); in non-surgical patients it reduced mortality (adjusted OR 0·77, 0·63 to 0·94; P = 0·009) by 16·6 per cent, representing an absolute mortality reduction of 5·5 per cent with number needed to treat of 18.Subgroup analysis found similar effects of SDD in reducing mortality in surgical and non-surgical ICU patients, whereas SOD reduced mortality only in non-surgical patients. The hypothesis-generating findings mandate investigation into mechanisms between different ICU populations."
1,"TITLE: Usefulness of minimum stent cross sectional area as a predictor of angiographic restenosis after primary percutaneous coronary intervention in acute myocardial infarction (from the HORIZONS-AMI Trial IVUS substudy).ABSTRACT: HORIZONS-AMI was a prospective dual-arm randomized trial of different antithrombotic regimens and stent types in patients with ST-segment elevation myocardial infarction. A formal intravascular ultrasound (IVUS) substudy enrolled 464 patients with baseline and 13-month follow-up at 36 centers. Of them, 318 patients with 355 lesions were evaluated for this study. Angiographic restenosis occurred in 45 of 355 lesions (12.7%). Bare-metal stent use (45.5% vs 21.2%, p <0.001) and diabetes mellitus (29.5% vs 10.9%, p <0.001) were more prevalent in patients with versus without restenosis. Postprocedure IVUS minimum lumen area (5.6 mm(2), 5.0 to 6.1, vs 6.7 mm(2), 6.5 to 6.9, p <0.001), minimum stent area (5.7 mm(2), 5.1 to 6.3, vs 6.9 mm(2), 6.6 to 7.1, p <0.001), and reference average lumen area (7.7 mm(2), 6.8 to 8.6, vs 9.7 mm(2), 9.3 to 10.1, p <0.001) were smaller in restenotic versus nonrestenotic lesions. By multivariable analysis, minimum stent area was an independent predictor of angiographic restenosis (odds ratio 0.75, 95% confidence interval 0.61 to 0.93, p = 0.009) in addition to diabetes, bare-metal stent use, and longer stent length. Attenuated plaque behind the stent struts had a trend to predict less binary restenosis (p = 0.07). In conclusion, a smaller IVUS minimum stent area was an independent predictor of angiographic restenosis after primary percutaneous intervention in patients with ST-segment elevation myocardial infarction, similar to patients with stable coronary artery disease."
1,"TITLE: HIV-1 protease inhibitors and clinical malaria: a secondary analysis of the AIDS Clinical Trials Group A5208 study.ABSTRACT: HIV-1 protease inhibitors (PIs) have antimalarial activity in vitro and in murine models. The potential beneficial effect of HIV-1 PIs on malaria has not been studied in clinical settings. We used data from Adult AIDS Clinical Trials Group A5208 sites where malaria is endemic to compare the incidence of clinically diagnosed malaria among HIV-infected adult women randomized to either lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) or to nevirapine (NVP)-based ART. We calculated hazard ratios and 95% confidence intervals. We conducted a recurrent events analysis that included both first and second clinical malarial episodes and also conducted analyses to assess the sensitivity of results to outcome misclassification. Among the 445 women in this analysis, 137 (31%) received a clinical diagnosis of malaria at least once during follow-up. Of these 137, 72 (53%) were randomized to LPV/r-based ART. Assignment to the LPV/r treatment group (n = 226) was not consistent with a large decrease in the hazard of first clinical malarial episode (hazard ratio = 1.11 [0.79 to 1.56]). The results were similar in the recurrent events analysis. Sensitivity analyses indicated the results were robust to reasonable levels of outcome misclassification. In this study, the treatment with LPV/r compared to NVP had no apparent beneficial effect on the incidence of clinical malaria among HIV-infected adult women. Additional research concerning the effects of PI-based therapy on the incidence of malaria diagnosed by more specific criteria and among groups at a higher risk for severe disease is warranted."
1,"TITLE: Antiandrogen monotherapy in patients with localized or locally advanced prostate cancer: final results from the bicalutamide Early Prostate Cancer programme at a median follow-up of 9.7 years.ABSTRACT: To evaluate the efficacy and tolerability of bicalutamide 150 mg once-daily as immediate hormonal therapy in patients with prostate cancer or as adjuvant to radical prostatectomy or radiotherapy.In all, 8113 patients with localized (T1-2, N0/Nx) or locally advanced (T3-4, any N; or any T, N+) prostate cancer (all M0) were enrolled in three complementary, double-blind, placebo-controlled trials. Patients were randomized to receive standard care plus either oral bicalutamide 150 mg once-daily or oral placebo. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Data were collated from individual trials and evaluated in a combined analysis.Overall, at a median follow-up of 9.7 years, bicalutamide significantly improved PFS (hazard ratio 0.85, 95% confidence interval 0.79-0.91; P= 0.001). Compared with placebo there was no difference in OS (hazard ratio 1.01, P= 0.77). Patients who derived benefit from bicalutamide in terms of PFS were those with locally advanced disease, with OS significantly favouring bicalutamide in patients with locally advanced disease undergoing radiotherapy (P= 0.031). Patients with localized disease showed no clinically or statistically significant improvements in PFS; there was a survival trend in favour of placebo in patients with localized disease undergoing watchful waiting (P= 0.054). The overall tolerability of bicalutamide was consistent with previous analyses, with breast pain (73.7%) and gynaecomastia (68.8%) the most frequently reported adverse events in patients randomized to bicalutamide.Bicalutamide 150 mg, either as monotherapy or adjuvant to standard care, improved PFS in patients with locally advanced prostate cancer, but not in patients with localized disease. A pre-planned subset analysis showed a benefit for OS in patients with locally advanced disease undergoing radiotherapy. Bicalutamide 150 mg might represent an alternative for patients with locally advanced prostate cancer considering androgen-deprivation therapy."
1,"TITLE: Comparison of late results of percutaneous coronary intervention among stable patients ≤65 versus >65 years of age with an occluded infarct related artery (from the Occluded Artery Trial).ABSTRACT: Although opening an occluded infarct-related artery >24 hours after myocardial infarction in stable patients in the Occluded Artery Trial (OAT) did not reduce events over 7 years, there was a suggestion that the effect of treatment might differ by patient age. Baseline characteristics and outcomes by treatment with percutaneous coronary intervention (PCI) versus optimal medical therapy alone were compared by prespecified stratification at age 65 years. A p value <0.01 was prespecified as significant for OAT secondary analyses. The primary outcome was death, myocardial infarction, or New York Heart Association class IV heart failure. Patients aged >65 years (n = 641) were more likely to be female, to be nonsmokers, and to have hypertension, lower estimated glomerular filtration rates, and multivessel disease compared to younger patients (aged ≤65 years, n = 1,560) (p <0.001). There was no significant observed interaction between treatment assignment and age for the primary outcome after adjustment (p = 0.10), and there was no difference between PCI and optimal medical therapy observed in either age group. At 7-year follow-up, younger patients tended to have angina more often compared to the older group (hazard ratio 1.21, 99% confidence interval 1.00 to 1.46, p = 0.01). The 7-year composite primary outcome was more common in older patients (p <0.001), and age remained significant after covariate adjustment (hazard ratio 1.42, 99% confidence interval 1.09 to 1.84). The rate of early PCI complications was low in the 2 age groups. The trend toward a differential effect of PCI in the young versus the old for the primary outcome was likely driven by measured and unmeasured confounders and by chance. PCI reduces angina to a similar degree in the young and old. In conclusion, there is no indication for routine PCI to open a persistently occluded infarct-related artery in stable patients after myocardial infarction, regardless of age."
1,"TITLE: Six-month versus 12-month dual antiplatelet therapy after implantation of drug-eluting stents: the Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting (EXCELLENT) randomized, multicenter study.ABSTRACT: The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents.We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%; P=0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, 0.72-49.96; P=0.10), the risk of death or myocardial infarction did not differ in the 2 groups (2.4% versus 1.9%; hazard ratio, 1.21; 95% confidence interval, 0.60-2.47; P=0.58). In the prespecified subgroup analysis, target vessel failure occurred more frequently in the 6-month DAPT group than in the 12-month group (hazard ratio, 3.16; 95% confidence interval, 1.42-7.03; P=0.005) among diabetic patients.Six-month DAPT did not increase the risk of target vessel failure at 12 months after implantation of drug-eluting stents compared with 12-month DAPT. However, the noninferiority margin was wide, and the study was underpowered for death or myocardial infarction. Our results need to be confirmed in larger trials.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00698607."
1,"TITLE: Comparison of Lichtenstein and laparoscopic transabdominal preperitoneal repair of recurrent inguinal hernias.ABSTRACT: The aim of our study was the comparative analysis of the results of two surgical methods: tension-free repair by the Lichtenstein technique and laparoscopic transabdominal preperitoneal (TAPP) repair. In total 52 patients with recurrent inguinal hernia were randomly assigned to the two groups: Lichtenstein (28 patients) and TAPP (24 patients). Comparisons between these groups were done by several preoperative, intraoperative, and postoperative factors. For postoperative factors both short-term and long-term results were considered. Average operation time for Lichtenstein group was 59.6 +/- 9.9 minutes, compared with 64.4 +/- 8.4 minutes for TAPP patients (P = 0.068). In TAPP patients there was less pain in the postoperative period (P = 0.002) and fewer sick-leave days (13.4 +/- 1.7 versus 17.5 +/- 2.6 days; P < 0.001) and, correspondingly, faster recovery. In the Lichtenstein group a total of 4 postoperative complications (infection, hematoma, seroma, urinary retention) were observed, compared with 8 in the TAPP group (P = 0.19). Statistically significant difference was only by urinary retention (0 for Lichtenstein, 4 for TAPP; P = 0.039). There were no cases of hernia recurrence observed during the followup. Chronic pain developed in 5 patients from the Lichtenstein group (17.9%) and 2 patients from the TAPP group (8.3%; P = 0.28) more than 1 year after the operation; 4 Lichtenstein patients (14.3%) and 1 TAPP patient (4.2%; P = 0.23) more than 2 years after the operation; and 3 Lichtenstein patients (10.7%) and 1 TAPP patient (4.2%; P = 0.36) more than 3 years after the operation. For the treatment of recurrent inguinal hernias, which are developed after use of conventional (nonmesh) methods, the first choice should be given to the laparoscopic method, especially for young, physically active, nonobese patients, and if there are any contraindications for the laparoscopy, the Lichtenstein approach should be recommended."
1,"TITLE: Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial.ABSTRACT: The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM).ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction).This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without DM."
0,"TITLE: Long-term Survival Outcomes of 'Low Risk' Ductal Carcinoma in situ from a Territory-wide Cancer Registry.ABSTRACT: The LORIS trial is an ongoing phase III clinical trial on low risk ductal carcinoma in situ (DCIS). DCIS patients aged ≥46 years with screen-detected low/intermediate nuclear grade were considered low risk and were randomised into surveillance or standard surgery. Here we review the 10-year territory-wide breast cancer registry database and evaluate the clinical outcomes of low versus high risk DCIS patients.This was a retrospective study of a prospectively maintained territory-wide breast cancer registry in Hong Kong.Between 1997 and 2006, 1391 DCIS patients were identified from the Hong Kong cancer registry breast cancer database. The mean age at diagnosis was 49.2 years (range 30-70). In total, 372 patients were classified as 'low risk', whereas the remaining 777 patients were classified as 'high risk'. After a median follow-up of 11.6 years, the 10-year overall breast cancer-specific survival of the entire DCIS cohort was 1136/1149 (98.9%). Overall breast cancer-specific survival of low risk DCIS was 99.5%, whereas that in high risk DCIS was 98.6% (Log-rank test, P = 0.208). Forty-six (12.4%) patients in the LORIS low risk group did not receive surgery, whereas 93 (12%) patients in the LORIS high risk group did not receive surgery. The 10-year breast cancer-specific survival in the non-operated low risk DCIS group was 97.8%; that in the non-operated high risk DCIS group was 96.7% (P = 1).Long-term survival of DCIS was excellent, especially in low risk DCIS, regardless of surgical treatment."
1,"TITLE: Computerized clinical decision support during medication ordering for long-term care residents with renal insufficiency.ABSTRACT: OBJECTIVE To determine whether a computerized clinical decision support system providing patient-specific recommendations in real-time improves the quality of prescribing for long-term care residents with renal insufficiency. DESIGN Randomized trial within the long-stay units of a large long-term care facility. Randomization was within blocks by unit type. Alerts related to medication prescribing for residents with renal insufficiency were displayed to prescribers in the intervention units and hidden but tracked in control units. Measurement The proportions of final drug orders that were appropriate were compared between intervention and control units within alert categories: (1) recommended medication doses; (2) recommended administration frequencies; (3) recommendations to avoid the drug; (4) warnings of missing information. RESULTS The rates of alerts were nearly equal in the intervention and control units: 2.5 per 1,000 resident days in the intervention units and 2.4 in the control units. The proportions of dose alerts for which the final drug orders were appropriate were similar between the intervention and control units (relative risk 0.95, 95% confidence interval 0.83, 1.1) for the remaining alert categories significantly higher proportions of final drug orders were appropriate in the intervention units: relative risk 2.4 for maximum frequency (1.4, 4.4); 2.6 for drugs that should be avoided (1.4, 5.0); and 1.8 for alerts to acquire missing information (1.1, 3.4). Overall, final drug orders were appropriate significantly more often in the intervention units-relative risk 1.2 (1.0, 1.4). CONCLUSIONS Clinical decision support for physicians prescribing medications for long-term care residents with renal insufficiency can improve the quality of prescribing decisions.http://clinicaltrials.gov Identifier: NCT00599209."
1,"TITLE: Effect of trimetazidine on quality of life in elderly patients with ischemic dilated cardiomyopathy.ABSTRACT: Elderly patients have an increased incidence of ischemic dilated cardiomyopathy, often related to diffuse coronary artery disease. Data have been cumulated to suggest that trimetazidine improves myocardial ischemia in patients with ischemic heart disease and improves left ventricular function in elderly patients with ischemic cardiomyopathy. The purpose of the present study was to assess the effects of trimetazidine in addition to standard cardiovascular therapy on left ventricular function and quality of life (QOL) parameters in elderly patients with ischemic heart disease and reduced left ventricular function.Patients were randomized to receive either trimetazidine (twice daily) or placebo (twice daily) in addition to standard therapy, and were evaluated at baseline and after 6 months.Forty-seven patients completed the study (40 male, seven female; mean [+/-SD] age 78+/-3.4 years). Demographic data were comparable between the two groups with respect to sex, age, and race. At 6 months there was a significant improvement in the number of angina episodes per week in the trimetazidine group (-2.3+/-1, P=0.023). The overall assessment of QOL by a visual analog scale showed an improvement in patients randomized to trimetazidine at 6 months (from 4.1+/-0.6 to 6.4+/-0.8, P<0.01) and no changes in patients randomized to placebo (from 4.3+/-0.7 to 4.2+/-0.9, P>0.05). Physical QOL, evaluated by a MacNew Quality of Life After Myocardial Infarction questionnaire (MacNewQLMI), improved in patients randomized to trimetazidine but not in those allocated to placebo (32%+/-5% vs. -1%+/-3%, P<0.01). Similar results were obtained on social QOL evaluated by MacNewQLMI with trimetazidine compared with placebo (39%+/-4% vs. -2%+/-5%, P<0.01).In elderly patients with ischemic heart disease and reduced ventricular function, trimetazidine improves clinical condition and QOL."
1,"TITLE: Efficacy of gemfibrozil in the primary prevention of atrial fibrillation in a large randomized controlled trial.ABSTRACT: Peroxisome proliferator-activated receptor alpha (PPARalpha) activators reduce inflammation and oxidative stress. Inflammation plays an important role in the initiation and maintenance of atrial fibrillation (AF). It has been suggested that PPARalpha activators may have antiarrhythmic properties, but no clinical data exist. The objective of this study was to investigate whether the PPARalpha activator gemfibrozil prevents or delays the development of AF in patients with coronary heart disease.We retrospectively analyzed the electrocardiograms (ECGs) performed in the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial, a multicenter, randomized, double-blinded, secondary prevention trial of gemfibrozil and matching placebo. The ECGs were performed annually or biannually and when clinically indicated. Participants who were in AF on baseline ECG were excluded from the present analysis. Relative risk for AF was calculated from Cox regression with death as a competing risk factor.A total of 12,605 ECGs from 2,130 participants were interpreted (5.9 +/- 2.1 ECGs per participant, range 2-20). At baseline, the gemfibrozil (n = 1,070) and placebo (n = 1,060) groups were well matched. Mean age was 64.1 +/- 7.1 years. Over 4.4 +/- 1.5 years of follow-up, 123 (5.8%) participants developed new AF. There was no difference in AF incidence between the gemfibrozil and placebo groups (64/1,070 vs 59/1,060, respectively; P = .33). In Cox regression, the risk of AF was similar between the 2 study groups (hazard ratio 1.04, 95% CI 0.73-1.49, P = .82).In this post hoc analysis of a multicenter, double-blinded, randomized controlled trial, the PPARalpha activator gemfibrozil did not reduce the 4-year incidence of AF among men with coronary heart disease."
1,"TITLE: Long-term outcome of endovascular treatment versus medical care for carotid artery stenosis in patients not suitable for surgery and randomised in the Carotid and Vertebral Artery Transluminal Angioplasty study (CAVATAS).ABSTRACT: Optimal treatment of carotid stenosis in patients not suitable for surgery is unclear. The Carotid and Vertebral Artery Transluminal Angioplasty study contained a trial comparing medical and endovascular treatment in patients not suitable for surgery.Forty patients were randomised to medical or endovascular treatment in equal numbers, and patients were followed up for up to 10 years. The primary outcome measure was defined as stroke or death during follow-up, analysed by intention-to-treat. Secondary analyses included disabling stroke, death, any stroke, any stroke or transient ischemic attack (TIA), all during follow-up.Baseline characteristics were similar. The risk of stroke, retinal infarction or death within 30 days of endovascular treatment was 5% (95% CI: 0.1-24.9%). By the study end, >50% of patients had suffered a recurrent TIA, stroke or died. One third of events were non-stroke deaths. Overall, there was no significant difference between medical and endovascular treatment in the primary outcome rate of stroke or death after randomisation (hazard ratio: 0.98, 95% CI: 0.39-2.48) or the rate of any stroke or TIA (hazard ratio: 1.43, 95% CI: 0.54-3.75).We failed to show superiority of endovascular treatment above medical care alone for carotid stenosis in a very small group of patients not suitable for surgical treatment. However, the trial randomised only 40 patients, and was therefore severely underpowered to detect clinically relevant treatment differences. Ongoing trials of carotid stenting will need to demonstrate improved safety and efficacy before endovascular treatment should enter routine practice."
1,"TITLE: Safety and tolerability of duloxetine at 60 mg once daily in elderly patients with major depressive disorder.ABSTRACT: To compare the safety and tolerability profile of duloxetine versus placebo in elderly (> or = 65 years) patients with major depressive disorder (MDD).Patients were randomized (2:1) to duloxetine 60 mg/d (once daily) (n = 207) or placebo (n = 104) for 8 weeks. Safety and tolerability measures were analyzed in the total cohort of patients, as well as in subgroups defined by age and preexisting hypertension.Patients had a median age of 72 years (65-90 years). No deaths occurred in the study. Discontinuation rates due to adverse events were similar for duloxetine and placebo (9.7% vs 8.7%). Treatment-emergent dry mouth, nausea, and diarrhea occurred significantly (P < or = 0.05) more frequently with duloxetine compared with placebo. Changes in supine and standing blood pressure (BP) and pulse and in corrected QT (QTc) interval were not significantly different between duloxetine and placebo, except for change in orthostatic systolic BP (-2.45 vs 0.93 mm Hg; P = .017). Incidences of sustained elevation in BP and treatment-emergent orthostatic hypotension were similar for duloxetine compared with placebo (0.5% vs 1.0% and 15.6% vs 20.5%, respectively). The duloxetine group showed significant weight loss compared with the placebo group (-0.73 kg vs -0.13 kg; P = 0.009). Of 5 hepatic analytes, the only significant difference was an increase in alkaline phosphatase in duloxetine compared with placebo (P = 0.017); this difference was not considered clinically relevant. The incidence of 1 or more discontinuation-emergent adverse events was not significantly different between the duloxetine and placebo groups (17.3% vs 11.3%).This study suggests that duloxetine is safe and well tolerated in elderly patients with major depressive disorder."
1,"TITLE: Functional impact of high clopidogrel maintenance dosing in patients undergoing elective percutaneous coronary interventions. Results of a randomized study.ABSTRACT: The currently recommended maintenance dose of clopidogrel is often associated with inadequate platelet inhibition, suggesting the need for a higher dose. The aim of this pilot study was to assess the functional impact of a high (150 mg/day) maintenance dose of clopidogrel in patients undergoing elective percutaneous coronary intervention (PCI). This is a prospective, randomized, platelet function study which was performed in elective PCI patients assigned to treatment with either a 75 mg (n = 20) or 150 mg (n = 20) daily maintenance dose of clopidogrel for 30 days; afterwards, all patients resumed standard dosing. Platelet aggregation was performed using light transmittance aggregometry following 20 microM and 5 microM adenosine diphosphate (ADP) stimuli 30 days after randomization and 30 days after resuming standard dosing. Patients treated with 150 mg/day clopidogrel had lower 20 microM ADP-induced platelet aggregation compared to patients on 75 mg/day (52.1 +/- 9% vs. 64.0 +/- 8%; p < 0.001; primary endpoint). The dose-dependent effect was confirmed by the absolute and relative increase in platelet aggregation after resuming standard dosing (p < 0.001). No changes were observed in patients randomized to standard dosing. Parallel findings were observed following 5 microM ADP stimuli for all assessments. A broad variability in clopidogrel-induced antiplatelet effects was observed irrespective of dosing. In conclusion, a 150 mg/day maintenance dose regimen of clopidogrel is associated with reduced platelet reactivity and enhanced platelet inhibition compared to that achieved with the currently recommended 75 mg/day in patients undergoing elective PCI."
1,"TITLE: Tranexamic acid reduces perioperative blood loss in cervical laminoplasty: a prospective randomized study.ABSTRACT: A prospective randomized comparative study.To evaluate the effect of tranexamic acid (TXA) on decreasing perioperative blood loss in cervical laminoplasty, in which the surgical procedure is identical in all cases.TXA, an inhibitor of fibrinolysis, has proven to be effective in reducing perioperative blood loss in patients undergoing total hip and knee arthroplasty. However, only a limited number of well-controlled spinal surgery trials have been conducted due to heterogeneity in the performed surgical procedures.Forty consecutive patients with cervical compressive myelopathy were prospectively randomized into groups that received 15 mg/kg body weight of TXA or placebo intravenously before the skin incision was made. ""French-door"" cervical laminoplasty from C3 to C6 was performed for all patients by using a consistent procedure. Intraoperative and postoperative blood loss was compared between the groups. The surgery and follow-up were conducted at a single institution.There were no statistically significant differences between the TXA and control groups in terms of age, sex, body mass index, and operating time. Intraoperative blood loss in the TXA group (49.1 ± 30.6 mL) was not significantly different from that in the control group (63.4 ± 53.0 mL, P = 0.30). However, in the TXA group, postoperative blood loss during the first 16 hours was reduced by 37% as compared to the control group (132.0 ± 45.3 vs. 211.0 ± 41.5 mL; P < 0.01). The total blood loss (intraoperative plus postoperative blood loss during the first 40 hours) in the TXA group (264.1 ± 75.1 mL) was significantly lower than that in the control group (353.9 ± 60.8 mL, P < 0.01). No thromboembolic events or complications occurred in either group.TXA significantly reduced perioperative blood loss, primarily through a reduction in postoperative blood loss, in cervical laminoplasty."
1,"TITLE: Misoprostol vaginal insert for successful labor induction: a randomized controlled trial.ABSTRACT: To compare three doses of misoprostol vaginal insert for successful labor induction measured by the proportion of vaginal deliveries within 24 hours.A total of 374 women with modified Bishop scores of 4 or lower before induction of labor were randomly assigned to receive misoprostol vaginal insert (MVI) 100 (n=118), MVI 150 (n=125), or MVI 200 (n=131) micrograms. The insert was removed for onset of active labor or adverse event. The primary outcome was proportion of vaginal deliveries within 24 hours. The comparison group was MVI 100. Safety was assessed by comparing rates of cesarean deliveries and adverse events.Twenty-four percent of women receiving MVI 200 failed to achieve vaginal delivery within 24 hours compared with 36.3% of those receiving MVI 100 (P=.057, relative risk [RR] 0.66, 95% confidence interval [CI] 0.42-1.04). Compared with MVI 100, MVI 200 reduced median time to vaginal delivery (1,181 compared with 1,744 minutes, P=.02) and need for oxytocin (48.9% compared with 70.9%, P<.001, RR 0.70, 95% CI 0.56-0.85). The cesarean rates for women assigned to MVI 200 and 100 were 22.9% (30/131) and 31.4% (37/118) (P=.15, RR 0.73, 95% CI 0.48-1.10). Misoprostol vaginal insert 200 was associated with an increased rate of tachysystole (41.2%) compared with MVI 100 (19.5%) (P<.001, RR 2.11, 95% CI 1.39-3.22).Compared with MVI 100, MVI 200 was associated with a significant reduction in time to vaginal delivery, but did not improve proportion with vaginal delivery by 24 hours.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00828711."
1,"TITLE: Reduced darunavir dose is as effective in maintaining HIV suppression as the standard dose in virologically suppressed HIV-infected patients: a randomized clinical trial.ABSTRACT: Maximizing ART efficiency is of growing interest. This study assessed the efficacy, safety, pharmacokinetics and economics of a darunavir dose-reduction strategy.This was a multicentre, randomized, open-label clinical trial in HIV-infected patients with plasma HIV-1 RNA <50 copies/mL while receiving triple ART including 800 mg of darunavir once daily. Participants were randomized to continue 800 mg of darunavir (DRV800) or to 600 mg of darunavir (DRV600), both once daily. Treatment failure was defined as two consecutive HIV-1 RNA determinations >50 copies/mL or discontinuation of study treatment by week 48. The study was registered at https://www.clinicaltrialsregister.eu (trial number 2011-006272-39).Fifty participants were allocated to each arm. The mean (SD) CD4+ T cell count at baseline was 562 (303) cells/mm(3) and HIV-1 RNA had been <50 copies/mL for a median (IQR) of 106.9 (43.4-227.9) weeks before enrolment. At week 48 no treatment failure had occurred in 45/50 (90%) DRV600 patients and in 47/50 (94%) DRV800 patients (difference -4%; 95% CI lower limit, -12.9%). When only patients with virological data were considered, that endpoint was met by 45/48 (94%) in the DRV600 arm and 47/49 (96%) in the DRV800 arm (difference -2.2%; 95% CI lower limit, -9.6%). Darunavir exposure was similar in the two arms. The average reduction in annual cost per successfully treated DRV600-arm patient was US$7273.The efficacy of a darunavir daily dose of 600 mg seemed to be similar to the efficacy of the standard 800 mg dose in virologically suppressed HIV-infected patients on triple ART. This strategy can potentially translate to substantial savings in the cost of care of HIV-infected patients."
1,"TITLE: Efficacy and Safety of Varenicline for Adolescent Smoking Cessation: A Randomized Clinical Trial.ABSTRACT: Cigarette smoking is the leading cause of preventable morbidity and mortality in the United States and worldwide, and most tobacco users begin smoking in adolescence. Although advances have yielded efficacious pharmacotherapies to complement smoking cessation counseling in adults, far less progress has been made in addressing tobacco use in adolescence.To evaluate the efficacy and safety of varenicline tartrate for smoking cessation in adolescents and young adults.This 2-group randomized, placebo-controlled, double-blind intention-to-treat clinical trial enrolled a volunteer sample of treatment-seeking adolescent and young adult cigarette smokers (n = 157) aged 14 to 21 years at an outpatient clinical site in Charleston, South Carolina, from August 15, 2012, to October 20, 2017. Follow-up was completed on January 25, 2018. Data were analyzed from March 19, 2018, to August 11, 2018, with further revisions completed April 10, 2019.Participants were randomized in a 1:1 ratio to a 12-week course of varenicline (n = 77) or placebo (n = 80). All participants received weekly smoking cessation counseling.The preselected primary efficacy outcome was urine cotinine level-confirmed 7-day abstinence at the end of treatment. Secondary efficacy outcomes included weekly abstinence throughout active treatment, abstinence at posttreatment follow-up visits, and time to first 7-day abstinence. The primary safety outcome was the frequency of treatment-emergent adverse events.A total of 157 participants were enrolled (94 male [59.9%]; mean [SD] age, 19.1 [1.5] years). The varenicline and placebo groups did not differ in the primary outcome of cotinine-confirmed self-reported 7-day abstinence at the end of treatment (varenicline group, 4 of 45 [8.9%]; placebo group, 4 of 45 [8.9%]; risk ratio [RR], 0.97; 95% CI, 0.29-2.99; P = .96). However, among secondary outcomes, the varenicline group achieved self-reported earlier abstinence of at least 7 days (hazard ratio, 1.91; 95% CI, 1.12-3.27) and demonstrated higher rates of self-reported weekly abstinence during the full course of treatment (RR, 1.81; 95% CI, 1.09-2.99; P = .02) and at posttreatment follow-up (RR, 1.82; 95% CI, 1.01-3.28; P = .02). Study medication was generally well tolerated, and treatment-emergent adverse events did not differ between groups (any adverse events, 55 [71.4%] in the varenicline group vs 60 [75.0%] in the placebo group; RR, 0.95; 95% CI, 0.79-1.15; P = .61).When added to weekly cessation counseling for adolescent cigarette smokers, varenicline, compared with placebo, was well tolerated but did not improve end-of-treatment abstinence. However, varenicline may hasten abstinence and yield improvements in posttreatment abstinence outcomes.ClinicalTrials.gov identifier: NCT01509547."
1,"TITLE: Subgroup analysis of Japanese patients in a Phase 3 study of atezolizumab in advanced triple-negative breast cancer (IMpassion130).ABSTRACT: In the randomised Phase 3 IMpassion130 trial, atezolizumab combined with nab-paclitaxel (atezo + nab-P) in 902 patients with triple-negative breast cancer (TNBC) showed prolonged progression-free survival (PFS) in both the intention-to-treat (ITT) population and programmed death-ligand 1 (PD-L1)-positive subgroup compared with placebo plus nab-P (plac + nab-P). This study assessed the efficacy and safety of atezo + nab-P in the IMpassion130 Japanese subpopulation.Eligible patients had unresectable locally advanced or metastatic TNBC previously untreated with chemotherapy for metastatic disease. Patients were randomised 1:1 to receive either atezo + nab-P or plac + nab-P. Co-primary endpoints were investigator-assessed PFS and overall survival (ITT population and PD-L1-positive subgroup). These were also assessed in the Japanese subpopulation.There were 65 Japanese patients (34 atezo + nab-P; 31 plac + nab-P). The PD-L1-positive subgroup included 25 patients (12 atezo + nab-P; 13 plac + nab-P). Median PFS was 7.4 months (atezo + nab-P) versus 4.6 months (plac + nab-P; hazard ratio [HR], 0.47; 95% CI, 0.25-0.90). In the PD-L1-positive subgroup, median PFS was 10.8 months (atezo + nab-P) versus 3.8 months (plac + nab-P; HR, 0.04; 95% CI, <0.01-0.35). Safety results in the Japanese subgroup were consistent with those in the overall population. The Japanese subgroup had a lower incidence of adverse events leading to treatment withdrawal than the overall population. More patients in the atezo + nab-P arm had neutrophil count decreases and stomatitis than patients in the plac + nab-P arm.Atezo + nab-P efficacy in Japanese patients was consistent with the overall IMpassion130 population. No new safety signals were observed, and tolerability was consistent with that of the overall population."
1,"TITLE: Multicentre, controlled, randomised and blinded field study comparing efficacy of suxibuzone and phenylbutazone in lame horses.ABSTRACT: In horses, it has been demonstrated that suxibuzone (SBZ) has a lower gastric ulcerogenic effect than phenylbutazone (PBZ). However, no field trials have been reported comparing the efficacy of the drugs in alleviating lameness.To compare the therapeutic effect of SBZ to that of PBZ when administered orally in lame horses. Acceptability of both products was also compared.Lame horses (n = 155) were used in a multicentre, controlled, randomised and double-blinded clinical trial. Horses were treated orally with either SBZ or PBZ at equivalent therapeutic dosages. PBZ was given to 79 horses at a dose of 4.4 mg/kg bwt/12 h for 2 days, followed by 2.2 mg/kg bwt/12 h for 6 days. SBZ was given to 76 horses at 6.6 mg/kg bwt/12 h for 2 days, followed by 3.3 mg/kg bwt/ 12 h for 6 days. Efficacy of treatments was evaluated by clinicians in equine practices according to lameness progression throughout the study. Product ingestion was checked daily to evaluate product acceptability.Although SBZ showed a statistically significant tendency to have a better efficacy than PBZ (Odds ratio = 2.7; P = 0.016), significance dissipated once the analysis was adjusted for some imbalanced baseline covariates, confirming that they were actually related to the apparent advantage of SBZ over PBZ. Product acceptability was significantly higher in the SBZ group than in the PBZ group (96.1% vs. 77.2%; P = 0.001).SBZ and PBZ did not show significant differences in alleviating lameness in horses. However, SBZ had better product acceptability when administered orally with some food.SBZ is a good therapeutic alternative to PBZ in horses since there is no significant difference in alleviating lameness between the 2 therapies."
0,"TITLE: Effective removal of leptin via hemodiafiltration with on-line endogenous reinfusion therapy.ABSTRACT: Leptin is a middle-molecular weight uremic toxin. Hemodiafiltration with on-line endogenous reinfusion (HFR) is a novel dialytic method combining the processes of diffusion, convection and adsorption. We performed a prospective crossover study of patients with end-stage renal disease to investigate the effect of HFR therapy on the level of leptin as compared to conventional low flux hemodialysis (LHD).Eleven stable hemodialysis patients were treated with LHD for 12 weeks and then treated with HFR (SG30 Plus; Sorin Group Italia S.r.1, Mirandola, Italy) for 12 weeks.After 12 weeks of HFR treatment, serum leptin levels significantly decreased (17.1 (2.66 - 39.5) at Week 12 vs. 12.3 (1.80 - 24.3) ng/ml at Week 24, p = 0.014). Although serum adiponectin levels also decreased (1.66 (1.44 - 1.86) at Week 12 vs. 1.12 (0.79 - 1.34) g/ml at Week 24, p = 0.001), the ratio of leptin to adiponectin did not increase after HFR treatment. Serum beta2-microglobulin (beta2M) levels significantly decreased (37.7 (29.8 - 42.6) at Week 12 vs. 28.3 (26.5 - 32.2) mg/dl at Week 24, p = 0.002). Dry weight, Kt/V(urea), normalized protein equivalent of nitrogen appearance, subjective global assessment, and serum albumin levels of the patients were not changed after HFR treatment. There was no difference in the serum levels of C-reactive protein or interleukin-6 between Week 12 and Week 24.The results of our study indicate that HFR may be a better therapy than LHD for removal of middle-molecular-weight uremic toxins such as leptin and b2M."
1,"TITLE: Prostate-Only Versus Whole-Pelvic Radiation Therapy in High-Risk and Very High-Risk Prostate Cancer (POP-RT): Outcomes From Phase III Randomized Controlled Trial.ABSTRACT: We report the clinical outcomes of a randomized trial comparing prophylactic whole-pelvic nodal radiotherapy to prostate-only radiotherapy (PORT) in high-risk prostate cancer.This phase III, single center, randomized controlled trial enrolled eligible patients undergoing radical radiotherapy for node-negative prostate adenocarcinoma, with estimated nodal risk ≥ 20%. Randomization was 1:1 to PORT (68 Gy/25# to prostate) or whole-pelvic radiotherapy (WPRT, 68 Gy/25# to prostate, 50 Gy/25# to pelvic nodes, including common iliac) using computerized stratified block randomization, stratified by Gleason score, type of androgen deprivation, prostate-specific antigen at diagnosis, and prior transurethral resection of the prostate. All patients received image-guided, intensity-modulated radiotherapy and minimum 2 years of androgen deprivation therapy. The primary end point was 5-year biochemical failure-free survival (BFFS), and secondary end points were disease-free survival (DFS) and overall survival (OS).From November 2011 to August 2017, a total of 224 patients were randomly assigned (PORT = 114, WPRT = 110). At a median follow-up of 68 months, 36 biochemical failures (PORT = 25, WPRT = 7) and 24 deaths (PORT = 13, WPRT = 11) were recorded. Five-year BFFS was 95.0% (95% CI, 88.4 to 97.9) with WPRT versus 81.2% (95% CI, 71.6 to 87.8) with PORT, with an unadjusted hazard ratio (HR) of 0.23 (95% CI, 0.10 to 0.52;  < .0001). WPRT also showed higher 5-year DFS (89.5%  77.2%; HR, 0.40; 95% CI, 0.22 to 0.73;  = .002), but 5-year OS did not appear to differ (92.5%  90.8%; HR, 0.92; 95% CI, 0.41 to 2.05;  = .83). Distant metastasis-free survival was also higher with WPRT (95.9%  89.2%; HR, 0.35; 95% CI, 0.15 to 0.82;  = .01). Benefit in BFFS and DFS was maintained across prognostic subgroups.Prophylactic pelvic irradiation for high-risk, locally advanced prostate cancer improved BFFS and DFS as compared with PORT, but OS did not appear to differ."
1,"TITLE: Effects of oral clotrimazole troches on the pharmacokinetics of oral and intravenous midazolam.ABSTRACT: The aim of the study was to determine the effects of oral clotrimazole troches on the pharmacokinetics of oral and intravenous midazolam in the plasma.We conducted a randomized, open-label, four-way crossover study in 10 healthy volunteers. Each volunteer received oral midazolam 2 mg or intravenous midazolam 0.025 mg kg(-1) with and without oral clotrimazole troches 10 mg taken three times daily for 5 days. Each study period was separated by 14 days. Serial blood samples were collected up to 24 h after oral midazolam and 6 h after intravenous midazolam. Plasma concentrations for midazolam and its metabolite 1-hydroxymidazolam were measured and fitted to a noncompartmental model to estimate the pharmacokinetic parameters.Ten healthy volunteers aged 21-26 years provided written informed consent and were enrolled into the study. Clotrimazole decreased the apparent oral clearance of midazolam from 57 +/- 13 l h(-1)[95% confidence interval 48, 66] to 36 +/- 9.8 l h(-1) (95% confidence interval 29, 43) (P= 0.003). These changes were accompanied by a decrease in the area under the concentration-time curve (mean difference 22 microg h(-1) l(-1), P= 0.001) and bioavailability (mean difference 0.21, P= NS). There were no significant differences in the systemic clearance of midazolam with or without clotrimazole troches.Oral clotrimazole troches decreased the apparent oral clearance of midazolam; no significant differences in the systemic clearance of midazolam were found."
1,"TITLE: Predictors of embolization during protected renal artery angioplasty and stenting: Role of antiplatelet therapy.ABSTRACT: The objective of this study was to identify the predictors of distal embolization (DE) during protected renal artery angioplasty and stenting.DE may contribute to worsening renal function after renal artery stenting. The factors associated with DE, rates of platelet-rich emboli, and treatments that may prevent DE during renal stenting have not been evaluated.The current study evaluated patients randomized to receive an embolic protection device (EPD) in the RESIST trial. Forty-two patients were identified for inclusion in this study. These patients were further randomized to abciximab (N = 22) or placebo (N = 20). Modification in Diet in Renal Disease glomerular filtration rate (GFR) was used as the primary measure of renal function. Creatinine was measured by a modified Jaffe reaction using the IDMS-traceable assay. The primary endpoint was capture of platelet rich emboli in the angioguard basket.DE occurred in 15/42 (35%) of the patients and platelet rich DE in 10 (24%) of the patients who received an EPD. Of the angiographic characteristics only lesion length was significantly higher in patients with DE (16 +/- 7 mm vs. 10 +/- 5 mm, P = 0.04). Preprocedural abciximab reduced DE from 42 to 8% (P = 0.02). The rate of platelet rich emboli was 50% with neither abciximab nor a thienopyridine, 36% with thienopyridine only, 15% abciximab only, and 0% in patients who received both a thienopyridine and abciximab. Only Abciximab use was associated with improved renal function at 1-month, thienopyridine was not. Angiographic characteristics including percent stenosis, minimal luminal diameter (MLD), reference diameter, change in MLD, contrast volume, and procedure time were not predictors of DE during renal stenting.Capture of DE and specifically platelet DE are common during protected renal stenting using a filter-type EPD. Abciximab use, and potentially combined thienopyridine and abciximab use, decreased the rate of platelet rich DE; however, only abciximab improved renal function at 1-month."
1,"TITLE: Estradiol valerate plus dienogest versus ethinylestradiol plus levonorgestrel for the treatment of primary dysmenorrhea.ABSTRACT: To demonstrate the superiority of estradiol valerate plus dienogest (E(2)V/DNG) over ethinylestradiol plus levonorgestrel (EE/LNG) in reducing the number of days with dysmenorrheic pain among women with primary dysmenorrhea.In a phase IIIb trial conducted at 44 centers worldwide between April 2009 and November 2010, otherwise healthy women aged 14-50 years requesting contraception were randomized to daily oral administration of E(2)V/DNG (n = 253) or EE/LNG (n = 254) for three 28-daycycles. The primary efficacy variable was number of days with dysmenorrheic pain, the category of which (none, mild, moderate, severe) was self-assessed on a daily basis (irrespective of menstrual bleeding status) and recorded on diary cards. Notably, the women documented their pain as they experienced it before taking any (permitted) rescue medication.Overall, 217 and 209 women receiving E(2)V/DNG and EE/LNG, respectively, completed the study. The mean ± SD change from baseline in number of days with dysmenorrheic pain was -4.6 ± 4.6 days and -4.2 ± 4.2 days for the E(2)V/DNG and EE/LNG groups, respectively (P = 0.34).Both E(2)V/DNG and EE/LNG led to considerable relief of dysmenorrheic complaints among women with primary dysmenorrhea, decreasing the number of days with dysmenorrheic pain from baseline to a similar extent. ClinicalTrials.gov:NCT00909857."
1,"TITLE: Effect of repaglinide on endothelial dysfunction during a glucose tolerance test in subjects with impaired glucose tolerance.ABSTRACT: Impaired glucose tolerance (IGT) is associated with increased cardiovascular risk. The pathophysiological mechanisms linking post-challenge hyperglycemia to accelerated atherosclerosis, however remain to be elucidated.A prospective, open, randomised, cross-over study was performed to investigate the effect of 2 mg repaglinide on hyperglycemia and endothelial function during an oral glucose tolerance test (75 g glucose) in 12 subjects with diagnosed IGT. Blood samples for determination of plasma glucose were drawn fasting, 1 and 2 hours after glucose ingestion. Endothelial function was assessed by measuring flow-mediated dilatation (FMD) of the brachial artery with high-resolution ultrasound.Administration of repaglinide resulted in a significant reduction of plasma glucose at 2 hours (172.8+/-48.4 vs. 138.3+/-41.2 mg/dl; p < 0.001). The flow-mediated dilatation (FMD) 2 hours after the glucose-load was significantly reduced in comparison to fasting in the control group (6.21+/-2.69 vs. 7.98+/-2.24 %; p = 0.028), whereas after theadministration of repaglinide the FMD was not significantly different to fasting values (7.24+/-2.57 vs. 8.18+/-2.93 %; p = n.s.). Linear and logistic regression analysis revealed that only the change of glucose was significantly correlated to the change of FMD observed (p < 0.001). Regression analysis after grouping for treatment and time confirmed the strong negative association of the changes of plasma glucose and FMD and indicate that the effect of repaglinide observed is based on the reduction glycemia.In subjects with IGT, the endothelial dysfunction observed after a glucose challenge is related to the extent of hyperglycemia. Reduction of hyperglycemia by repaglinide reduces endothelial dysfunction in a glucose dependent manner."
1,"TITLE: Prevention of atrial fibrillation by bucindolol is dependent on the beta₁389 Arg/Gly adrenergic receptor polymorphism.ABSTRACT: This study assessed the impact of bucindolol, a beta-blocker/sympatholytic agent, on the development of atrial fibrillation (AF) in advanced chronic heart failure with reduced left ventricular ejection fraction (HFREF) patients enrolled in the BEST (Beta-Blocker Evaluation of Survival Trial).β-blockers have modest efficacy for AF prevention in HFREF patients. Bucindolol's effects on HF and ventricular arrhythmic endpoints are genetically modulated by β₁- and α(2c)-adrenergic receptor (AR) polymorphisms that can be used to subdivide HFREF populations into those with bucindolol effectiveness levels that are enhanced, unchanged, or lost.BEST enrolled 2,708 New York Heart Association (NYHA) class III to IV HFREF patients. A substudy in which 1,040 patients' DNA was genotyped for the β₁-AR position 389 Arg/Gly and the α(2c)322-325 wild type (Wt)/deletion (Del) polymorphisms, and new-onset AF was assessed from adverse event case report forms or electrocardiograms at baseline and at 3 and 12 months.In the entire cohort, bucindolol reduced the rate of new-onset AF compared to placebo by 41% (hazard ratio [HR]: 0.59 [95% confidence interval (CI): 0.44 to 0.79], p = 0.0004). In the 493 β₁389 arginine homozygotes (Arg/Arg) in the DNA substudy, bucindolol reduced new-onset AF by 74% (HR: 0.26 [95% CI: 0.12 to 0.57]), with no effect in β₁389 Gly carriers (HR: 1.01 [95% CI: 0.56 to 1.84], interaction test = 0.008). When β₁389 Gly carriers were subdivided by α(2c) Wt homozygotes (n = 413, HR: 0.94 [95% CI: 0.48 to 1.82], p = 0.84) or Del variant carriers (n = 134, HR: 1.33 [95% CI: 0.32 to 5.64], p = 0.70), there was a positive interaction test (p = 0.016) when analyzed with β₁389 Arg homozygotes.Bucindolol prevented new-onset AF; β₁ and α(2c) polymorphisms predicted therapeutic response; and the 47% of patients who were β₁389 Arg homozygotes had an enhanced effect size of 74%. (Beta-Blocker Evaluation in Survival Trial [BEST]; NCT00000560)"
0,"TITLE: Anthocyanin Intake and Physical Activity: Associations with the Lipid Profile of a US Working Population.ABSTRACT: While growing evidence exists on the independent associations between anthocyanins and physical activity on cardiovascular disease (CVD) risk determinants, the possible interaction between these exposures has not yet been studied. We aimed to study the potential synergism between anthocyanin intake and physical activity on lipid profile measures. This cross-sectional study was conducted among 249 US career firefighters participating in the  trial. Anthocyanin intake was calculated using a validated food frequency questionnaire (FFQ) and physical activity level by a validated questionnaire. Multivariable linear regression models determined the extent to which anthocyanin intake and physical activity predicted lipid parameters. Generalized linear models were used for joint effect and interaction analyses on the multiplicative and additive scales. Both anthocyanins and physical activity were independently inversely associated with total cholesterol:high density lipoprotein (HDL) cholesterol. Only physical activity was inversely associated with triglycerides, low density lipoprotein (LDL) cholesterol:HDL, and triglycerides (TG):HDL. Although the combined exposure of low anthocyanin intake and low physical activity was associated with lower (RR = 2.83; 95% CI: 1.42 to 5.67) HDL cholesterol <40 mg/dL, neither multiplicative ( = 0.72) nor additive interactions were detected (relative excess risk due to interaction (RERI): 0.02; 95% CI: -1.63 to 1.66;  = 0.98). Our findings provide insight on the potential synergism between anthocyanin intake and physical activity on the lipid profile."
1,"TITLE: Nifedipine plus candesartan combination increases blood pressure control regardless of race and improves the side effect profile: DISTINCT randomized trial results.ABSTRACT: DISTINCT (reDefining Intervention with Studies Testing Innovative Nifedipine GITS - Candesartan Therapy) aimed to determine the dose-response and tolerability of nifedipine GITS and/or candesartan cilexetil therapy in participants with hypertension.In this 8-week, multinational, multicentre, randomized, double-blind, placebo-controlled study, adults with mean seated DBP of at least 95 to less than 110 mmHg received combination or monotherapy with nifedipine GITS (N) 20, 30 or 60 mg and candesartan cilexetil (C) 4, 8, 16 or 32 mg, or placebo. The primary endpoint, change in DBP from baseline to Week 8, was analysed using the response surface model (RSM); this analysis was repeated for mean seated SBP.Overall, 1381 participants (mean baseline SBP/DBP: 156.5/99.6 mmHg) were randomized. Both N and C contributed independently to SBP/DBP reductions [P < 0.0001 (RSM)]. A positive dose-response was observed, with all combinations providing statistically better blood pressure (BP) reductions from baseline versus respective monotherapies (P < 0.05) and N60C32 achieving the greatest reduction [-23.8/-16.5 mmHg; P < 0.01 versus placebo (-5.3/-6.7 mmHg) and component monotherapies]. Even very low-dose (N20 and C4) therapy provided significant BP-lowering, and combination therapy was similarly effective in different racial groups. N/C combination demonstrated a lower incidence of vasodilatory adverse events than N monotherapy (18.3 versus 23.6%), including headache (5.5 versus 11.0%; P = 0.003, chi-square test) and peripheral oedema over time (3.6 versus 5.8%; n.s.).N/C combination was effective in participants with hypertension and showed an improved side effect profile compared with N monotherapy."
1,"TITLE: Efficacy of MPFF 1000 mg oral suspension on CVD C0s-C1-related symptoms and quality of life.ABSTRACT: To show the efficacy of micronized purified flavonoid fraction (MPFF) 1000 mg in the mild cases of chronic venous disorders (CVD), i.e. in C0s-C1 patients according to the CEAP classification.In an international, randomized, double-blind, parallel-group study, symptomatic C0s to C4 patients according to the Clinical Etiological Anatomic Pathophysiologic (CEAP) were treated for 8 weeks by either MPFF 1000 mg once daily or MPFF 500 mg twice daily. The present post-hoc analysis is focused on the efficacy of MPFF at the daily doses of 1000 mg in the population of mild cases of the CVD (C0s-C1 patients) on lower limb discomfort, leg pain and leg heaviness using a 10-cm Visual Analog Scale (VAS), and on quality of life (QoL) using CIVIQ-20.In the 256 patients of the C0s-C1 subset of the study patients, lower limb discomfort improvement measured on VAS was clinically and statistically significant: -2.87±2.38 cm in the MPFF 1000 mg group and -3.30±2.36 cm in the MPFF 500 mg group (P<0.001 in both groups). Leg pain and leg heaviness VAS improved similarly: -2.77±2.58 cm in the MPFF 1000 mg group and -3.45±2.38 cm in the MPFF 500 mg group (P<0.001 in both groups), and -2.91±2.47 cm in the MPFF 1000 mg group and -3.47±2.33 cm in the MPFF 500 mg group (P<0.001 in both groups). The quality of life assessed by the CIVIQ-20 questionnaire improved significantly in both treatment groups from baseline to W8 with a mean changes of global index score of -16.53±14.18 in the MPFF 1000 mg group and -18.78±18.14 in the MPFF 500 mg group (P<0.001).MPFF at the daily dose of 1000 mg was shown to have a similar efficacy in mild CVD cases (C0s-C1 patients) as in the whole spectrum of patients from the main study, with a very good safety profile. These result further illustrates the interest of MPFF in the management of the mild cases of the disease at a daily dose of 1000 mg."
1,"TITLE: A randomized controlled trial comparing concurrent chemoradiation versus concurrent chemoradiation followed by adjuvant chemotherapy in locally advanced cervical cancer patients: ACTLACC trial.ABSTRACT: To compare response rate and survivals of locally advanced stage cervical cancer patients who had standard concurrent chemoradiation therapy (CCRT) alone to those who had adjuvant chemotherapy (ACT) after CCRT.Patients aged 18-70 years who had International Federation of Gynecology and Obstetrics stage IIB-IVA without para-aortic lymph node enlargement, Eastern Cooperative Oncology Group scores 0-2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or by ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B).Data analysis of 259 patients showed no significant difference in complete responses at 4 months after treatment between arm A (n=129) and arm B (n=130): 94.1% vs. 87.0% (p=0.154) respectively. With the median follow-up of 27.4 months, 15.5% of patients in arm A and 10.8% in arm B experienced recurrences (p=0.123). There were no significant differences of overall or loco-regional failure. However, systemic recurrences were significantly lower in arm B than arm A: 5.4% vs. 10.1% (p=0.029). The 3-year progression-free survival (PFS) and 3-year overall survival (OS) of the patients in both arms were not significantly different. The hazard ratio of PFS and OS of arm B compared to arm A were 1.26 (95% CI=0.82-1.96; p=0.293) and 1.42 (95% CI=0.81-2.49; p=0.221) respectively.ACT with paclitaxel plus carboplatin after CCRT did not improve response rate and survival compared to CCRT alone. Only significant decrease of systemic recurrences with ACT was observed, but not overall or loco-regional failure.ClinicalTrials.gov Identifier: NCT02036164, Thai Clinical Trials Registry Identifier: TCTR 20140106001."
1,"TITLE: Efficacy and safety of plerixafor for the mobilization/collection of peripheral hematopoietic stem cells for autologous transplantation in Japanese patients with multiple myeloma.ABSTRACT: To evaluate the efficacy and safety of plerixafor for the mobilization/collection of peripheral hematopoietic stem cells (HSCs) for autologous transplantation in Japanese patients with multiple myeloma (MM). In a randomized study, patients received G-CSF (filgrastim, 400 µg/m/day) for 4 days prior to the first dose of plerixafor. Starting on Day 4 evening and for up to 4 days, patients received either plerixafor (240 µg/kg/day) + G-CSF group (PG group) or G-CSF alone (G group). Daily apheresis started on Day 5 for up to 4 days, or until ≥6 × 10 CD34+ cells/kg were collected. A total of 7 patients were randomized in each treatment group. Five patients in PG group and no patients in G group achieved a collection of ≥6 × 10 CD34+ cells/kg in ≤2 days of apheresis [difference of 71.4% (90%CI 29-100%)]. These results were supported by the shorter median time to collect ≥6 × 10 CD34+ cells/kg (2 days in PG group; no patient in G group). The incidence of treatment emergent adverse events (TEAEs) was higher in PG group than in G group. Plerixafor was well tolerated, and effective for the mobilization/collection of peripheral HSCs for autologous transplantation in Japanese patients with MM."
1,"TITLE: Midluteal Progesterone: A Marker of Treatment Outcomes in Couples With Unexplained Infertility.ABSTRACT: Adequate luteal phase progesterone exposure is necessary to induce endometrial changes required for a successful pregnancy outcome. The relationship between low midluteal progesterone concentration and the outcome of live birth in ovarian stimulation with intrauterine insemination (OS-IUI) treatments is not defined.To determine the level of midluteal progesterone portending a low chance of live birth after OS-IUI in couples with unexplained infertility.Secondary analyses of data from a prospective, randomized, multicenter clinical trial that determined pregnancy outcomes following OS-IUI with clomiphene citrate, letrozole, or gonadotropins for couples with unexplained infertility.Couples (n = 900) underwent 2376 OS-IUI cycles during the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation clinical trial.Live birth as it relates to midluteal progesterone level and thresholds below which no live births occur by treatment group.Thresholds for non-live birth cycles were similar for clomiphene (14.4 ng/mL) and letrozole (13.1 ng/mL) yet were lower for gonadotropin (4.3 ng/mL) treatments. A midluteal progesterone level >10th percentile specific for each treatment group independently was associated with greater odds for a live birth in all OS-IUI cycles (adjusted OR: 2.17; 95% CI: 1.05, 4.48).During OS-IUI, a low midluteal progesterone level was associated with a low probability of live birth. Thresholds differed by medication, with the lowest threshold for gonadotropin. Several pathophysiologic mechanisms may account for low progesterone levels. Refinement of the predictive range associated with particular ovarian stimulation medications during treatment of unexplained infertility may improve accuracy."
1,"TITLE: Differences between activities of coagulation factors after one month of therapy with different direct oral anticoagulant in pulmonary embolism patients.ABSTRACT: Direct oral anticoagulants (DOACs) are frequently used for the treatment of pulmonary embolism (PE), but both clinical and laboratory data comparing their efficacy and safety are conflicting. This study investigated and compared the impact of three DOACs (apixaban, rivaroxaban and dabigatran) on coagulation cascade in acute PE patients.After the initial treatment, acute PE patients were randomly allocated to one of three groups, and treatment continued using one of the three DOACs. Following 1 month of treatment, the activity of factors II, VII and VIII, as well as protein C, antithrombin, D-dimer and fibrinogen, were measured, and the values were compared between the groups.One hundred consecutive PE patients were included. The mean values for the activity of factors II and VII and protein C were higher in patients on apixaban than in patients on rivaroxaban (1.45 ± 1.12 (IU/mL) vs 1.13 ± 0.92 (IU/mL), P < 0.001; 1.24 ± 1.10 (IU/mL) vs 1.05 ± 0.98 (IU/mL), P = 0.024 and 1.15 ± 0.62 vs 1.02 ± 0.68 (IU/mL), P = 0.019, respectively). The mean of factor II activity and the median of factor VIII activity were also significantly higher in patients on apixaban than in patients on dabigatran (1.45 ± 1.12 vs 1.20 ± 0.96 (IU/mL), P = 0.003 and 2.9 (2.0-4.0) vs 2.1 (1.5-2.7) (IU/mL), P = 0.001, respectively). No difference was noticed in D-dimer concentrations, or in the activity of the other factors measured. Additionally, no difference was noticed between the rivaroxaban and dabigatran groups.Apixaban had a significantly higher thrombin activity, above the laboratory determined normal range, compared to patients on rivaroxaban and dabigatran. This higher thrombin activity in patients on apixaban may contribute to a better haemostatic response during the therapy or increased prothrombotic state after therapy interruption."
1,"TITLE: Effect of Meropenem-Vaborbactam vs Piperacillin-Tazobactam on Clinical Cure or Improvement and Microbial Eradication in Complicated Urinary Tract Infection: The TANGO I Randomized Clinical Trial.ABSTRACT: Meropenem-vaborbactam is a combination carbapenem/beta-lactamase inhibitor and a potential treatment for severe drug-resistant gram-negative infections.To evaluate efficacy and adverse events of meropenem-vaborbactam in complicated urinary tract infection (UTI), including acute pyelonephritis.Phase 3, multicenter, multinational, randomized clinical trial (TANGO I) conducted November 2014 to April 2016 and enrolling patients (≥18 years) with complicated UTI, stratified by infection type and geographic region.Eligible patients were randomized 1:1 to receive meropenem-vaborbactam (2g/2g over 3 hours; n = 274) or piperacillin-tazobactam (4g/0.5g over 30 minutes; n = 276) every 8 hours. After 15 or more doses, patients could be switched to oral levofloxacin if they met prespecified criteria for improvement, to complete 10 days of total treatment.Primary end point for FDA criteria was overall success (clinical cure or improvement and microbial eradication composite) at end of intravenous treatment in the microbiologic modified intent-to-treat (ITT) population. Primary end point for European Medicines Agency (EMA) criteria was microbial eradication at test-of-cure visit in the microbiologic modified ITT and microbiologic evaluable populations. Prespecified noninferiority margin was -15%. Because the protocol prespecified superiority testing in the event of noninferiority, 2-sided 95% CIs were calculated.Among 550 patients randomized, 545 received study drug (mean age, 52.8 years; 361 [66.2%] women; 374 [68.6%] in the microbiologic modified ITT population; 347 [63.7%] in the microbiologic evaluable population; 508 [93.2%] completed the trial). For the FDA primary end point, overall success occurred in 189 of 192 (98.4%) with meropenem-vaborbactam vs 171 of 182 (94.0%) with piperacillin-tazobactam (difference, 4.5% [95% CI, 0.7% to 9.1%]; P < .001 for noninferiority). For the EMA primary end point, microbial eradication in the microbiologic modified ITT population occurred in 128 of 192 (66.7%) with meropenem-vaborbactam vs 105 of 182 (57.7%) with piperacillin-tazobactam (difference, 9.0% [95% CI, -0.9% to 18.7%]; P < .001 for noninferiority); microbial eradication in the microbiologic evaluable population occurred in 118 of 178 (66.3%) vs 102 of 169 (60.4%) (difference, 5.9% [95% CI, -4.2% to 16.0%]; P < .001 for noninferiority). Adverse events were reported in 106 of 272 (39.0%) with meropenem-vaborbactam vs 97 of 273 (35.5%) with piperacillin-tazobactam.Among patients with complicated UTI, including acute pyelonephritis and growth of a baseline pathogen, meropenem-vaborbactam vs piperacillin-tazobactam resulted in a composite outcome of complete resolution or improvement of symptoms along with microbial eradication that met the noninferiority criterion. Further research is needed to understand the spectrum of patients in whom meropenem-vaborbactam offers a clinical advantage.clinicaltrials.gov Identifier: NCT02166476."
1,"TITLE: The effect of time to irrigation and debridement on the rate of reoperation in open fractures : a propensity score-based analysis of the Fluid Lavage of Open Wounds (FLOW) study.ABSTRACT: Despite long-standing dogma, a clear relationship between the timing of surgical irrigation and debridement (I&D) and the development of subsequent deep infection has not been established in the literature. Traditionally, I&D of an open fracture has been recommended within six hours of injury based on animal studies from the 1970s, however the clinical basis for this remains unclear. Using data from a multicentre randomized controlled trial of 2,447 open fracture patients, the primary objective of this secondary analysis is to determine if a relationship exists between timing of wound I&D (within six hours of injury vs beyond six hours) and subsequent reoperation rate for infection or healing complications within one year for patients with open limb fractures requiring surgical treatment.To adjust for the influence of patient and injury characteristics on the timing of I&D, a propensity score was developed from the dataset. Propensity-adjusted regression allowed for a matched cohort analysis within the study population to determine if early irrigation put patients independently at risk for reoperation, while controlling for confounding factors. Results were reported as odds ratios (ORs), 95% confidence intervals (CIs), and p-values. All analyses were conducted using STATA 14.In total, 2,286 of 2,447 patients randomized to the trial from 41 orthopaedic trauma centres across five countries had complete data regarding time to I&D. Prior to matching, the patients managed with early I&D had a higher proportion requiring reoperation for infection or healing complications (17% vs 13%; p = 0.019), however this does not account for selection bias of more severe injuries preferentially being treated earlier. When accounting for propensity matching, early irrigation was not associated with reoperation (OR 0.71 (95% CI 0.47 to 1.07); p = 0.73).When accounting for other variables, late irrigation does not independently increase risk of reoperation. Cite this article:  2021;103-B(6):1055-1062."
1,"TITLE: Repeated delivery of chlorhexidine chips for the treatment of peri-implantitis: A multicenter, randomized, comparative clinical trial.ABSTRACT: Peri-implantitis is a challenging condition to manage and is frequently treated using non-surgical debridement. The local delivery of antimicrobial agents has demonstrated benefit in mild to moderate cases of peri-implantitis. This study compared the safety and efficacy of chlorhexidine gluconate 2.5 mg chip (CHX chips) as an adjunctive treatment to subgingival debridement in patients afflicted with peri-implantitis.A multicenter, randomized, single-blind, two-arm, parallel Phase-3 study was conducted. Peri-implantitis patients with implant pocket depths (IPD) of 5-8 mm underwent subgingival implant surface debridement followed by repeated bi-weekly supragingival plaque removal and chlorhexidine chips application (ChxC group) for 12 weeks, or similar therapy but without application of ChxC (control group). All patients were followed for 24 weeks. Plaque and gingival indices were measured at every visit whereas IPD, recession, and bleeding on probing were assessed at 8, 12, 16, 24 week.A total of 290 patients were included: 146 in the ChxC group and 144 in the control. At 24 weeks, a significant reduction in IPD (P = 0.01) was measured in the ChxC group (1.76 ± 1.13 mm) compared with the control group (1.54 ± 1.13 mm). IPD reduction of ≥2 mm was found in 59% and 47.2% of the implants in the ChxC and control groups, respectively (P = 0.03). Changes in gingival recession (0.29 ± 0.68 mm versus 0.15 ± 0.55 mm, P = 0.015) and relative attachment gain (1.47 ± 1.32 mm and 1.39 ± 1.27 mm, P = 0.0017) were significantly larger in the ChxC group. Patients in the ChxC group that were < 65 years exhibited significantly better responses (P < 0.02); likewise, non-smokers had similarly better response (P < 0.02). Both protocols were well tolerated, and no severe treatment-related adverse events were recorded throughout the study.Patients with peri-implantitis that were treated with an intensive treatment protocol of bi-weekly supragingival plaque removal and local application of chlorhexidine chips had greater mean IPD reduction and greater percentile of sites with IPD reduction of ≥2 mm as compared with bi-weekly supra-gingival plaque removal."
1,"TITLE: The Impact of Erythropoietin on Short- and Long-Term Kidney-Related Outcomes in Neonates of Extremely Low Gestational Age. Results of a Multicenter, Double-Blind, Placebo-Controlled Randomized Clinical Trial.ABSTRACT: To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22-26 months of corrected gestational age (cGA) compared with those randomized to placebo.We performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs.The prevalence of severe (stage 2 or 3) acute kidney injury (AKI) was 18.2%. We did not find a statistically significant difference between those randomized to erythropoietin vs placebo for in-hospital primary (severe AKI) or secondary outcomes (any AKI and serum creatinine/cystatin C values at days 0, 7, 9, and 14). At 22-26 months of cGA, 16% of the cohort had an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m, 35.8% had urine albumin/creatinine ratio >30 mg/g, 23% had a systolic blood pressure (SBP) >95th percentile for age, and 40% had a diastolic blood pressure (DBP) >95th percentile for age. SBP >90th percentile occurred less often among recipients of erythropoietin (P < .04). This association remained even after controlling for gestational age, site, and sibship (aOR 0.6; 95% CI 0.39-0.92). We did not find statistically significant differences between treatment groups in eGFR, albumin/creatinine ratio, rates of SBP >95th percentile, or DBP >90th or >95th percentiles at the 2 year follow-up visit.ELGANs have high rates of in-hospital AKI and kidney-related problems at 22-26 months of cGA. Recombinant erythropoietin may protect ELGANs against long-term elevated SBP but does not appear to protect from AKI, low eGFR, albuminuria, or elevated DBP at 22-26 months of cGA."
1,"TITLE: Phase III study comparing amrubicin plus cisplatin with irinotecan plus cisplatin in the treatment of extensive-disease small-cell lung cancer: JCOG 0509.ABSTRACT: This randomized phase III trial was conducted to confirm noninferiority of amrubicin plus cisplatin (AP) compared with irinotecan plus cisplatin (IP) in terms of overall survival (OS) in chemotherapy-naive patients with extensive-disease (ED) small-cell lung cancer (SCLC).Chemotherapy-naive patients with ED-SCLC were randomly assigned to receive IP, composed of irinotecan 60 mg/m(2) on days 1, 8, and 15 and cisplatin 60 mg/m(2) on day 1 every 4 weeks, or AP, composed of amrubicin 40 mg/m(2) on days 1, 2, and 3 and cisplatin 60 mg/m(2) on day 1 every 3 weeks.A total of 284 patients were randomly assigned to IP (n = 142) and AP (n = 142) arms. The point estimate of OS hazard ratio (HR) for AP to IP in the second interim analysis exceeded the noninferior margin (HR, 1.31), resulting in early publication because of futility. In updated analysis, median survival time was 17.7 (IP) versus 15.0 months (AP; HR, 1.43; 95% CI, 1.10 to 1.85), median progression-free survival was 5.6 (IP) versus 5.1 months (AP; HR, 1.42; 95% CI, 1.16 to 1.73), and response rate was 72.3% (IP) versus 77.9% (AP; P = .33). Adverse events observed in IP and AP arms were grade 4 neutropenia (22.5% v 79.3%), grade 3 to 4 febrile neutropenia (10.6% v 32.1%), and grade 3 to 4 diarrhea (7.7% v 1.4%).AP proved inferior to IP in this trial, perhaps because the efficacy of amrubicin as a salvage therapy was differentially beneficial to IP. IP remains the standard treatment for extensive-stage SCLC in Japan."
1,"TITLE: Sustained inflation with 21% versus 100% oxygen during cardiopulmonary resuscitation of asphyxiated newborn piglets - A randomized controlled animal study.ABSTRACT: Current neonatal resuscitation guidelines recommend using 100% oxygen during chest compressions (CC), however the most effective oxygen concentration during cardiopulmonary resuscitation remains controversial.In term newborn piglets with asphyxia-induced cardiac arrest does 21% oxygen compared to 100% oxygen during resuscitation using CC during sustained inflation (SI; CC + SI) will have a reduced time to return of spontaneous circulation (ROSC).Twenty-two mixed breed piglets (1-3 days old, 1.7-2.4 kg), were obtained on the day of the experiment and anesthetized, intubated, instrumented, and exposed to 30-min normocapnic hypoxia followed by asphyxia. Piglets were resuscitated using CC + SI and randomized to 21% oxygen (n = 8) or 100% oxygen (n = 8). Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment.Baseline parameters were similar between 21% and 100% oxygen groups. There was no difference in asphyxiation (duration and degree) between groups. Time to ROSC was similar between 21% and 100% oxygen groups: median (interquartile range - IQR) 80 (70-190)sec vs. 90 (70-324)sec, (p = 0.56). There was no significant difference in the rate of ROSC between 21% and 100% oxygen groups: 7/8 (88%) vs. 5/8 (63%), (p = 0.569). All piglets that achieved ROSC survived to four hours post-resuscitation. Hemodynamics and regional perfusion were not significantly different between groups.In term newborn piglets resuscitated by CC + SI, the use of 21% oxygen resulted in a similar time to ROSC, short-term survival, and hemodynamic recovery compared to 100% oxygen."
1,"TITLE: Fusion Imaging to Guide Thoracic Endovascular Aortic Repair (TEVAR): A Randomized Comparison of Two Methods, 2D/3D Versus 3D/3D Image Fusion.ABSTRACT: To compare the accuracy of two-dimensional (2D) versus three-dimensional (3D) image fusion for thoracic endovascular aortic repair (TEVAR) image guidance.Between December 2016 and March 2018, all eligible patients who underwent TEVAR were prospectively included in a single-center study. Image fusion methods (2D/3D or 3D/3D) were randomly assigned to guide each TEVAR and compared in terms of accuracy, dose area product (DAP), volume of contrast medium injected, fluoroscopy time and procedure time.Thirty-two patients were prospectively included; 18 underwent 2D/3D and 14 underwent 3D/3D TEVAR. The 3D/3D method allowed more accurate positioning of the aortic mask on top of the fluoroscopic images (proximal landing zone error vector: 1.7 ± 3.3 mm) than was achieved by the 2D/3D method (6.1 ± 6.1 mm; p = 0.03). The 3D/3D image fusion method was associated with significantly lower DAP than the 2D/3D method (50.5 ± 30.1 Gy cm for 3D/3D vs. 99.5 ± 79.1 Gy cm for 2D/3D; p = 0.03). The volume of contrast medium injected was significantly lower for the 3D/3D method than for the 2D/3D method (50.6 ± 22.9 ml vs. 98.4 ± 47.9 ml; p = 0.002).Higher image fusion accuracy and lower contrast volume and irradiation dose were observed for 3D/3D image fusion than for 2D/3D during TEVAR.II, Randomized trial."
0,"TITLE: Duration of Heart Failure and Effect of Defibrillator Implantation in Patients With Nonischemic Systolic Heart Failure.ABSTRACT: Patients with nonischemic systolic heart failure (HF) have increased risk of sudden cardiac death (SCD) and death from progressive pump failure. Whether the risk of SCD changes over time is unknown. We seek here to investigate the relation between duration of HF, mode of death, and effect of implantable cardioverter-defibrillator implantation.We examined the risk of all-cause death and SCD according to the duration of HF among patients with nonischemic systolic HF enrolled in the DANISH (Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality). In all, 1116 patients were included. Patients were divided according to quartiles of HF duration (≤8, 9≤18, 19≤65, and ≥66 months). Patients with the longest duration of HF were older, more often men, had more comorbidity, and more often received a cardiac resynchronization therapy device. Doubling of HF duration was an independent predictor of both all-cause mortality (hazard ratio [HR], 1.27; 95% CI, 1.17-1.38; P<0.0001), and SCD (HR, 1.29; 95% CI, 1.11-1.50; P=0.0007). The proportion of deaths caused by SCD was not different between HF quartiles (P=0.91), and the effect of implantable cardioverter-defibrillator implantation on all-cause mortality was not modified by the duration of HF (P=0.59).Duration of HF predicted both all-cause mortality and risk of SCD independently of other risk indicators. However, the proportion of death caused by SCD did not change with longer duration of HF, and the effect of implantable cardioverter-defibrillator was not modified by the duration of HF.URL: https://www.clinicaltrials.gov. Unique identifier: NCT00542945."
1,"TITLE: Recombinant streptokinase vs phenylephrine-based suppositories in acute hemorrhoids, randomized, controlled trial (THERESA-3).ABSTRACT: To compare the efficacy and safety of recombinant streptokinase (rSK) and phenylephrine-based suppositories in acute hemorrhoidal disease.A multicenter (14 sites), randomized (1:1), open, parallel groups, active controlled trial was done. After inclusion, subjects with acute symptoms of hemorrhoids, who gave their written, informed consent to participate, were centrally randomized to receive, as outpatients, rSK (200000 IU) or 0.25% phenylephrine suppositories, which had different organoleptic characteristics. Treatment was administered by the rectal route, one unit every 6 h during 48 h for rSK, and up to a maximum of 5 d (20 suppositories) for phenylephrine. Evaluations were performed at 3, 5 and 10 d post-inclusion. The main end-point was the 5(th)-day complete clinical response (disappearance of pain and edema, and ≥ 70% reduction of the lesion size). Time to response and need for thrombectomy were secondary efficacy variables. Adverse events were evaluated too.5(th) day complete response rates were 83/110 (75.5%) and 36/110 (32.7%) with rSK and phenylephrine suppositories, respectively. This 42.7% difference (95%CI: 30.5-54.2) was highly significant (P < 0.001). The advantage was detected since the early 3(rd) day evaluation (37.3% vs 6.4% for the rSK and active control groups, respectively; P < 0.001) and was kept even at the late 10(th) day assessment (83.6% vs 58.2% for rSK and phenylephrine, respectively; P < 0.001). Time for complete response was significantly shorter (P = 0.031; log-rank test) in the rSK group (median: 4.9 d; 95%CI: 4.8-5.0) with respect to the active control (median: 9.8 d; 95%CI: 9.8-10.0). Thrombectomy was necessary in 1/59 and 8/57 patients with baseline thrombosis in the rSK and phenylephrine groups, respectively (P = 0.016). There were no adverse events attributable to the experimental treatment.rSK suppositories showed a significant advantage over a widely used over-the-counter phenylephrine preparation for the treatment of acute hemorrhoidal illness, with an adequate safety profile."
1,"TITLE: A Randomized Comparison of Chloroquine Versus Dihydroartemisinin-Piperaquine for the Treatment of Plasmodium vivax Infection in Vietnam.ABSTRACT: A total of 128 Vietnamese patients with symptomatic Plasmodium vivax mono-infections were enrolled in a prospective, open-label, randomized trial to receive either chloroquine or dihydroartemisinin-piperaquine (DHA-PPQ). The proportions of patients with adequate clinical and parasitological responses were 47% in the chloroquine arm (31 of 65 patients) and 66% in the DHA-PPQ arm (42 of 63 patients) in the Kaplan-Meier intention-to-treat analysis (absolute difference 19%, 95% confidence interval = 0-37%), thus establishing non-inferiority of DHA-PPQ. Fever clearance time (median 24 versus 12 hours,P= 0.02), parasite clearance time (median 36 versus 18 hours,P< 0.001), and parasite clearance half-life (mean 3.98 versus 1.80 hours,P< 0.001) were all significantly shorter in the DHA-PPQ arm. All cases of recurrent parasitemia in the chloroquine arm occurred from day 33 onward, with corresponding whole blood chloroquine concentration lower than 100 ng/mL in all patients. Chloroquine thus remains efficacious for the treatment of P. vivax malaria in southern Vietnam, but DHA-PPQ provides more rapid symptomatic and parasitological recovery."
0,"TITLE: Shock Index as a Predictor of Myocardial Damage and Clinical Outcome in ST-Elevation Myocardial Infarction.ABSTRACT: Data on the prognostic value of the shock index in patients with ST-elevation myocardial infarction (STEMI) are scarce. Furthermore, the relationship of the shock index with myocardial damage is unknown. The aim of this study was to evaluate the association of the shock index with markers of myocardial damage and clinical outcome in patients with STEMI.This multicenter study analyzed 791 patients. Patients were categorized in 2 groups according to the admission shock index (optimized cut-off=0.62). Infarct severity was determined by cardiac magnetic resonance (CMR) imaging. Patients with cardiogenic shock that were unable to undergo CMR acquisition were excluded. Major adverse cardiac events (MACE) were defined as a composite of death, reinfarction and congestive heart failure within 12 months. Patients with elevated admission shock index (n=321 [40.6%]) had a significantly larger area-at-risk (37.6 [27.8-50.4] % of left ventricular volume [LV] vs. 34.3 [24.5-46.0] % LV, P=0.02), larger infarct size (19.5 [10.7-28.0] % LV vs. 14.9 [7.7-22.3] % LV, P<0.001), lower myocardial salvage index (46.2 [27.9-64.5] vs. 53.5 [36.5-75.2], P<0.001), and a larger extent of microvascular obstruction (0.3 [0.0-2.2] % LV vs. 0.0 [0.0-1.4] % LV, P=0.01). An elevated shock index was associated with reduced MACE-free survival (P<0.001). Furthermore, the admission shock index was identified as an independent predictor of MACE (hazard ratio=2.92 [1.24-4.22], P<0.01).STEMI patients with an elevated admission shock index had more pronounced myocardial and microvascular damage. Moreover, the shock index was independently associated with MACE at 12 months."
1,"TITLE: A randomized clinical trial comparing ritonavir-boosted lopinavir versus raltegravir each with tenofovir plus emtricitabine for post-exposure prophylaxis for HIV infection.ABSTRACT: The objective of this study was to assess post-exposure prophylaxis (PEP) non-completion at day 28, comparing two regimens.A prospective, open, randomized clinical trial was conducted at a tertiary hospital in Barcelona, Spain. Individuals attending the emergency room because of potential sexual exposure to HIV were randomized to tenofovir disoproxil/emtricitabine (245/200 mg) plus either ritonavir-boosted lopinavir (400/100 mg) or raltegravir (400 mg). The primary endpoint was PEP non-completion at day 28. Secondary endpoints were adherence, adverse events and rate of seroconversions. This study was registered in ClinicalTrials.gov: NCT01576731.One-hundred-and-twenty-one individuals were randomized to receive ritonavir-boosted lopinavir and 122 to raltegravir (n = 243). PEP non-completion at day 28 was 43% with no significant difference between arms. We performed a modified ITT analysis including only those patients who attended on day 1 (n = 191). PEP non-completion in this subgroup was higher in the ritonavir-boosted lopinavir arm than in the raltegravir arm (34.6% versus 20.4%, P = 0.04), as was the number of patients lost to follow-up at day 28 (32.6% versus 21.6%, P = 0.08) and the proportion of patients with low adherence (49.2% versus 30.8%, P = 0.03). Adverse events were significantly more common in the ritonavir-boosted lopinavir arm (73.4% versus 60.2%, P = 0.007). There was an HIV seroconversion at day 90 in the raltegravir arm in a patient who had multiple potential sexual risk exposures before and after receiving PEP.Although we found no differences between arms regarding PEP non-completion, poor adherence and adverse events were significantly higher in patients allocated to tenofovir disoproxil/emtricitabine plus ritonavir-boosted lopinavir. These data support the use of raltegravir as the preferred third drug in current PEP recommendations."
1,"TITLE: Preventing Postpartum Smoking Relapse: A Randomized Clinical Trial.ABSTRACT: Most women who quit smoking during pregnancy will relapse postpartum. Previous efforts to prevent postpartum relapse have been unsuccessful at increasing rates of sustained abstinence.To evaluate the relative efficacy of 2 different approaches to prevent postpartum smoking relapse.Pregnant women who recently had quit smoking were recruited before the end of pregnancy. Intervention sessions were conducted through a combination of telephone calls and in-person visits beginning at delivery and continuing through 24 weeks postpartum. Participants completed assessments at the prenatal baseline and at 12, 24, and 52 weeks postpartum. Participants were recruited between March 2008 and December 2012. The dates of the analysis were April 2014 to February 2015.Women received postpartum-adapted, behavioral smoking relapse prevention intervention and were randomly assigned to an enhanced cognitive behavioral intervention that included additional specialized strategies and content focused on women's postpartum concerns about mood, stress, and weight (Strategies to Avoid Returning to Smoking [STARTS]) or a supportive, time and attention-controlled comparison (SUPPORT). Intervention began before delivery and continued through 24 weeks postpartum.The primary outcome was biochemically confirmed sustained tobacco abstinence at 52 weeks postpartum. Secondary outcomes were self-reported mood, levels of perceived stress, and degree of concern about smoking-related weight gain.The study cohort comprised 300 participants (150 randomly assigned to each group). Their mean (SD) age was 24.99 (5.65) years. Overall, 38.0% (114 of 300), 33.7% (101 of 300), and 24.0% (72 of 300) of the sample maintained abstinence at 12, 24, and 52 weeks' postpartum, respectively. There were no differences between the intervention groups in abstinence or time to relapse. Self-reported depressive symptoms and perceived stress significantly improved over time, and improvements were similar for both intervention groups. Women with more depressive symptoms and higher levels of perceived stress were more likely to relapse (hazard ratio, 1.02; 95% CI, 1.00-1.04; P = .04 for depressive symptoms and hazard ratio, 1.04; 95% CI, 1.01-1.07; P = .003 for stress).An intervention designed to address women's concerns about mood, stress, and weight did not differentially improve rates of sustained tobacco abstinence postpartum compared with a time and attention-controlled comparison. Women in STARTS and SUPPORT reported postpartum improvements in mood and stress, and the experience of fewer depressive symptoms and less perceived stress was related to sustained abstinence. Given that most pregnant quitters will relapse within 1 year postpartum and that postpartum smoking has negative health consequences for women and children, effective interventions that target postpartum mood and stress are needed.clinicaltrials.gov Identifier: NCT00757068."
1,"TITLE: Randomized Controlled Trial of Family Therapy in Advanced Cancer Continued Into Bereavement.ABSTRACT: Systematic family-centered cancer care is needed. We conducted a randomized controlled trial of family therapy, delivered to families identified by screening to be at risk from dysfunctional relationships when one of their relatives has advanced cancer.Eligible patients with advanced cancer and their family members screened above the cut-off on the Family Relationships Index. After screening 1,488 patients or relatives at Memorial Sloan Kettering Cancer Center or three related community hospice programs, 620 patients (42%) were recruited, which represented 170 families. Families were stratified by three levels of family dysfunction (low communicating, low involvement, and high conflict) and randomly assigned to one of three arms: standard care or 6 or 10 sessions of a manualized family intervention. Primary outcomes were the Complicated Grief Inventory-Abbreviated (CGI) and Beck Depression Inventory-II (BDI-II). Generalized estimating equations allowed for clustered data in an intention-to-treat analysis.On the CGI, a significant treatment effect (Wald χ(2) = 6.88; df = 2; P = .032) and treatment by family-type interaction was found (Wald χ(2) = 20.64; df = 4; P < .001), and better outcomes resulted from 10 sessions compared with standard care for low-communicating and high-conflict groups compared with low-involvement families. Low-communicating families improved by 6 months of bereavement. In the standard care arm, 15.5% of the bereaved developed a prolonged grief disorder at 13 months of bereavement compared with 3.3% of those who received 10 sessions of intervention (Wald χ(2) = 8.31; df = 2; P =.048). No significant treatment effects were found on the BDI-II.Family-focused therapy delivered to high-risk families during palliative care and continued into bereavement reduced the severity of complicated grief and the development of prolonged grief disorder."
0,"TITLE: Low Stroke Rate of Carotid Stenosis Under the Guideline-Oriented Medical Treatment Compared With Surgical Treatment.ABSTRACT: Medical treatment for asymptomatic carotid artery stenosis (ACAS) has advanced recently. The outcomes of medical treatment and surgical treatment were evaluated to clarify the optimal treatment for ACAS.Patients with ACAS of ≥ 50% luminal narrowing underwent serial follow-up carotid artery ultrasonography for one year or more at the Center for Cardiovascular Disease Prevention between November 2006 and October 2013. The incidence of cardiovascular events (stroke, myocardial infarction, cardiovascular death) was examined in 64 patients (medical treatment group), and in 47 patients (surgical group) who underwent surgical treatment (carotid endarterectomy or carotid artery stenting) during this same period at the Department of Neurosurgery.Annual cardiovascular event rate was 0.91% (2/219 person-year) in the group of guideline-oriented medical treatment with an annual check-up for disease management and 5.6% (6/107 person-year) in the surgical group (log-rank P = 0.027; HR in the medical treatment group, 0.19 [medical treatment/surgical]; 95% confidence interval [CI], 0.028 to 0.87). Annual stroke event rate was 0.46% (1/219 person-year) in the medical treatment group and 4.7% (5/107 personyear) in the surgical group (log-rank P = 0.016; HR in the medical treatment group, 0.11 [medical treatment/surgical]; 95% CI, 0.0057 to 0.70). Multivariate logistic analysis showed that the surgical group was an independent variable associated with cardiovascular events (P = 0.049).Annual cardiovascular and stroke event rates were low in patients receiving medical treatment for ACAS and better than surgical treatment. The present study shows that medical treatment is an important option for ACAS."
0,"TITLE: Angiotensin system inhibitors and survival in patients with metastatic renal cell carcinoma treated with VEGF-targeted therapy: A pooled secondary analysis of clinical trials.ABSTRACT: Use of angiotensin system inhibitors (ASIs; angiotensin receptor blockers or angiotensin-converting enzyme inhibitors) has been reported to be associated with improved survival in metastatic renal cell carcinoma (mRCC), particularly when used with vascular endothelial growth factor-targeted therapies. This study was a secondary pooled analysis of two Phase III randomized controlled trials (RCTs) of patients with mRCC: NCT00334282 comparing pazopanib to placebo and NCT00720941 comparing pazopanib to sunitinib. ASI users were defined as patients using an ASI at baseline. Association with overall survival (OS; primary outcome) and progression-free survival (PFS) was evaluated using Cox proportional hazards regression. The association was adjusted in multivariable analysis for baseline systolic blood pressure (SBP), use of other antihypertensive drugs and prognostic factors comprising the Heng risk criteria for mRCC. Of 1,545 patients pooled from the two RCTs, 649 (42%) were using one or more antihypertensive drugs at baseline, 385 (59%) of which were using an ASI. In the multivariable analysis of patients using pazopanib or sunitinib, no significant association was observed between baseline ASI use and OS (hazard ratio [HR] 0.97 [95% confidence interval (CI) 0.80-1.18], p = 0.80) or PFS (HR 0.88 [95% CI 0.73-1.06], p = 0.17). Exploratory subgroup analysis of NCT00720941 highlighted that the effect of baseline ASI use on OS may differ between patients treated with sunitinib and pazopanib. In conclusion, use of ASIs at baseline was not a significant independent prognostic factor for improved survival in a pooled analysis of mRCC patients treated with pazopanib or sunitinib."
0,"TITLE: BRCA1/2 mutations associated with progression-free survival in ovarian cancer patients in the AGO-OVAR 16 study.ABSTRACT: AGO-OVAR 16 demonstrated that pazopanib maintenance therapy significantly increased progression-free survival (PFS) in patients with ovarian cancer whose disease had not progressed after first-line therapy. In a sub-study, we evaluated the effect of clinically important germline BRCA1 and BRCA2 mutations on PFS.Of 940 AGO-OVAR 16 participants, 664 had BRCA1/2 exon sequencing data (pazopanib, n=335; placebo, n=329). A Cox model was used to test the association between genetic variants and PFS.Ninety-seven of 664 patients (15%) carried clinically important BRCA1/2 mutations (BRCA1/2 carriers: pazopanib 14%, placebo 16%). Median PFS was longer in BRCA1/2 mutation carriers than in BRCA1/2 non-carriers in the placebo arm (30.3 vs 14.1 months, hazard ratio, 0.48; 95% confidence interval [CI]: 0.29-0.78; P=0.0031); a similar non-significant trend was noted with pazopanib (30.2 vs 17.7 months, hazard ratio, 0.64; 95% CI: 0.40-1.03; P=0.069). Among BRCA1/2 non-carriers, PFS was longer for pazopanib-treated patients than placebo-treated patients (17.7 vs 14.1 months, hazard ratio, 0.77; 95% CI: 0.62-0.97; P=0.024). Among BRCA1/2 carriers, there was no significant PFS difference between treatments, although numbers were small (pazopanib, 46; placebo, 51), resulting in a wide CI (hazard ratio, 1.36; 95% CI: 0.66-2.82).Patients with clinically important BRCA1/2 mutations had better prognosis. BRCA1/2 mutation status might be added as strata in future trials in primary ovarian cancer."
1,"TITLE: Patient-Reported Outcomes and Long-Term Results of a Randomized Controlled Trial Comparing Single-Port Versus Conventional Laparoscopic Inguinal Hernia Repair.ABSTRACT: Surgical techniques for inguinal hernia repair have evolved rapidly from open methods to conventional laparoscopic totally extra-peritoneal (CTEP) and recently single-port TEP (STEP). As there is currently no randomized controlled trial (RCT) reporting long-term patient-reported outcomes between CTEP and STEP, we reviewed patients who were randomized to CTEP or STEP 5 years after surgery.Telephone interviews were administered to patients with primary unilateral inguinal hernia recruited for the RCT comparing CTEP and STEP in 2011. The modified Body Image Questionnaire was used to measure long-term patient-reported outcomes.Forty-two out of forty-nine of the STEP group and forty-one out of fifty of the CTEP group responded to phone interviews. Median follow-up time, demographic data and clinical outcomes were comparable between both groups. The Body Image Score (5-20: 5-least dissatisfied, 20-most dissatisfied; BIS score ± SD, STEP vs. CTEP, 5.33 ± 0.90 vs. 7.17 ± 1.87, p < 0.001) and Cosmetic Score (2-20: 2-least satisfied, 20-most satisfied; CS score ± SD, STEP vs. CTEP, 19.05 ± 1.31 vs. 15.87 ± 1.57, p < 0.001) were superior in the STEP group. Similarly, self-reported scar perception (1-cannot be seen, 2-can barely be seen, 3-visible; scar perception score ± SD, STEP vs. CTEP, 1.29 ± 0.51 vs. 2.55 ± 0.64, p < 0.001) and overall experience score (1-least satisfied, 10-most satisfied; overall satisfaction score ± SD, STEP vs. CTEP, 9.57 ± 0.67 vs. 8.22 ± 0.94, p < 0.001) were superior in the STEP group.Patients who underwent STEP reported superior cosmetic and satisfaction scores and comparable surgical outcomes 5 years after surgery compared to the CTEP group. STEP should be strongly considered in patients who are concerned about long-term cosmetic outcomes and should be offered if surgical expertise is available. Trial registration NCT02302937."
1,"TITLE: Family Integrated Care for Preterm Infants in China: A Cluster Randomized Controlled Trial.ABSTRACT: To explore whether family integrated care (FICare) is feasible and improves the outcomes of preterm infants in China.This was a multicenter prospective cluster-randomized controlled trial comparing FICare and standard care. The primary outcome was length of stay (LOS). Secondary outcomes were nosocomial infections, duration of supplemental oxygen, breastfeeding, and weight gain. Outcomes were compared using univariate and multivariable analyses adjusted for potential confounders and clustering.We enrolled 601 preterm infants from 11 neonatal intensive care units (FICare, n = 298; control, n = 303). The unadjusted LOS was 30.81 vs 30.26 days (mean ratio, 1.02; 95% CI, 0.85-1.22; P = .85). After adjustment, outcomes in the FICare group were improved compared with the control group, including LOS (28.26 vs 35.04 days; mean ratio, 0.81; 95% CI, 0.72-0.91), total medical expenditures (mean ratio, 0.69; 95% CI, 0.53-0.90), weight gain velocity (15.73 vs 10.30 g/day; mean difference, 5.43; 95% CI, 3.65-7.21), duration of supplemental oxygen (13.11 vs 21.42 days; mean difference, 0.71; 95% CI, 0.50-1.00), nosocomial infection rates (4.13 vs 5.84/1000 hospital days; mean ratio, 0.67; 95% CI, 0.47-0.96), antibiotic exposure (38.63 vs 57.32/100 hospital days; mean ratio, 0.67; 95% CI, 0.47-0.96), breastfeeding rates (87.25% vs 55.78%; OR, 5.42; 95% CI, 3.25-9.05), and rehospitalization rates (3.65% vs 7.48%; OR, 0.47; 95% CI, 0.28-0.77). At follow-up to 18 months, breastfeeding rates and weight were significantly (P < .05) higher over time in the FICare group.FICare was feasible in Chinese neonatal intensive care units and was associated with reduced hospital LOS, medical expenditures, and rates of adverse outcomes."
1,"TITLE: Effect of Progressive Weight Loss on Lactate Metabolism: A Randomized Controlled Trial.ABSTRACT: Lactate is an intermediate of glucose metabolism that has been implicated in the pathogenesis of insulin resistance. This study evaluated the relationship between glucose kinetics and plasma lactate concentration ([LAC]) before and after manipulating insulin sensitivity by progressive weight loss.Forty people with obesity (BMI = 37.9 ± 4.3 kg/m ) were randomized to weight maintenance (n = 14) or weight loss (n = 19). Subjects were studied before and after 6 months of weight maintenance and before and after 5%, 11%, and 16% weight loss. A hyperinsulinemic-euglycemic clamp procedure in conjunction with [6,6- H ]glucose tracer infusion was used to assess glucose kinetics.At baseline, fasting [LAC] correlated positively with endogenous glucose production rate (r = 0.532; P = 0.001) and negatively with insulin sensitivity, assessed as the insulin-stimulated glucose disposal (r = -0.361; P = 0.04). Progressive (5% through 16%) weight loss caused a progressive decrease in fasting [LAC], and the decrease in fasting [LAC] after 5% weight loss was correlated with the decrease in endogenous glucose production (r = 0.654; P = 0.002) and the increase in insulin sensitivity (r = -0.595; P = 0.007).This study demonstrates the interrelationships among weight loss, hepatic and muscle glucose kinetics, insulin sensitivity, and [LAC], and it suggests that [LAC] can serve as an additional biomarker of glucose-related insulin resistance."
1,"TITLE: Exenatide has a pronounced effect on energy intake but not energy expenditure in non-diabetic subjects with obesity: A randomized, double-blind, placebo-controlled trial.ABSTRACT: Exenatide is a glucagon-like peptide 1 (GLP-1) mimetic which induces weight loss predominantly, it is presumed, via decreased food intake. However, circulating GLP-1 is also a determinant of energy expenditure. We sought to quantify the effect of exenatide on energy expenditure (EE) and energy intake.In this single-center, randomized double-blind placebo controlled trial, we randomized 80 healthy, non-diabetic volunteers with obesity (46 women, age: 34.4 ± 8.7 y, body fat by DXA: 44.2 ± 7.8%) to subcutaneous exenatide 10 μg twice daily or placebo. Subjects were admitted to our clinical research unit for measurement of 24 h-EE in a whole-room indirect calorimeter and ad libitum food intake using an automated vending machine paradigm before and after randomization. Furthermore, energy expenditure and ad libitum food intake measures were repeated at 24-week after readmission for 7-day inpatient stay. Body weight was obtained weekly for up to 5 weeks and was recorded at each monthly follow up visit up to 24 weeks.Prior to randomization, participants over ate during the 3-day vending machine period in the whole study group (114.6 ± 35.2%), expressed as percentage of weight maintaining energy needs (WMEN) with those who were eventually randomized to exenatide overeating more (121.6 ± 37.7%) compared to placebo group (107.6 ± 31.5%). In the exenatide group, ad libitum absolute energy intake decreased by 1016.1 ± 724.5 kcal/day (95% CI: -1250.9 to -781.2) versus a 245.1 ± 710.5 kcal/day (95% CI: -475.4 to -14.7) decrease in placebo (Δ = -624.8 Kcal/day, p < 0.0001) whereas the reduction in ad libitum caloric intake relative to WMEN was a more modest 366.8 ± 752.1 kcal/day (95% CI: -614.0 to -119.6) decrease compared to 8.0 ± 860.1 kcal/day (95% CI: -286.8 to 270.8) reduction in placebo (Δ = -382.3 Kcal/day, p = 0.03). The decrease was uniform across all macronutrients groups. No differences in 24hEE or substrate oxidation rates were found. In the exenatide group, body weight decreased more over the 5 weeks (β = -0.039 kg/week, p = 0.02) and was lower compared to placebo at the end of fifth week (-1.48 ± 0.77 kg; 95% CI: -3.02 to 0.05, p = 0.06). At the 24-week follow up, there was no difference in energy intake between exenatide group and placebo group and the treatment group decreased 24-h EE more compared to placebo (β = -160.6 Kcal/day, 95% CI: -307.6 to 13.6, p = 0.03) compared to their pre-randomization measurement. However, this reduction was not present after adjustment for changes in FM and FFM (β = -87 kcal/day, p = 0.14). No difference was observed in body weight (Δ = -1.72 kg, 95% CI: -5.77 to 2.30, p = 0.39) in exenatide versus placebo over 24 weeks.Compared with placebo, exenatide decreased early ad libitum energy intake but did not change 24 h-EE. However, the reduction was more modest in relative versus absolute terms (i.e. below that needed for WMEN). Thus, although rate of weight change was greater in the exenatide treated subjects at 5 weeks, the absolute difference in weight was not significant. These findings indicate that although exenatide reduces food intake, it may be more beneficial in blunting overeating and thus may serve to more prevent weight regain following initial weight loss."
1,"TITLE: The effects of a dopamine agonist (apomorphine) on experimental and spontaneous pain in patients with chronic radicular pain: A randomized, double-blind, placebo-controlled, cross-over study.ABSTRACT: Although evidence suggests that dopaminergic systems are involved in pain processing, the effects of dopaminergic interventions on pain remains questionable. This randomized, double blinded, placebo-controlled, cross-over study was aimed at exploring the effect of the dopamine agonist apomorphine on experimental pain evoked by cold stimulation and on spontaneous pain in patients with lumbar radicular (neuropathic) pain.Data was collected from 35 patients with chronic lumbar radiculopathy (18 men, mean age 56.2±13 years). The following parameters were evaluated before (baseline) and 30, 75 and 120 minutes subsequent to a subcutaneous injection of 1.5 mg apomorphine or placebo: cold pain threshold and tolerance in the painful site (ice pack, affected leg) and in a remote non-painful site (12°C water bath, hand), and spontaneous (affected leg) pain intensity (NPS, 0-100).One-hundred and twenty minutes following apomorphine (but not placebo) injection, cold pain threshold and tolerance in the hand increased significantly compared to baseline (from a median of 8.0 seconds (IQR = 5.0) to 10 seconds (IQR = 9.0), p = 0.001 and from a median of 19.5 seconds (IQR = 30.2) to 27.0 seconds (IQR = 37.5), p<0.001, respectively). In addition, apomorphine prolonged cold pain tolerance but not threshold in the painful site (from a median of 43.0 seconds (IQR = 63.0) at baseline to 51.0 seconds (IQR = 78.0) at 120 min, p = 0.02). Apomorphine demonstrated no superiority over placebo in reducing spontaneous pain intensity.These findings are in line with previous results in healthy subjects, showing that apomorphine increases the ability to tolerate cold pain and therefore suggesting that dopaminergic interventions can have potential clinical relevance."
1,"TITLE: Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study.ABSTRACT: Glucocorticoid-induced osteoporosis is the most common form of secondary osteoporosis and is associated with an estimated annual fracture rate of 5%. We aimed to assess the efficacy and safety of denosumab compared with risedronate in glucocorticoid-induced osteoporosis.We did a 24-month, double-blind, active-controlled, double-dummy, non-inferiority study at 79 centres in Europe, Latin America, Asia, and North America. Eligible patients were aged 18 years or older and were receiving glucocorticoids (≥7·5 mg prednisone daily, or equivalent) for at least 3 months (glucocorticoid continuing) or less than 3 months (glucocorticoid initiating) before screening. Patients younger than 50 years needed to have a history of osteoporosis-related fracture; glucocorticoid-continuing patients aged 50 years or older needed a lumbar spine, total hip, or femoral neck bone mineral density T score of -2·0 or less, or -1·0 or less if they had a history of osteoporosis-related fracture. Participants were randomly assigned (1:1) to either 60 mg subcutaneous denosumab every 6 months and oral placebo daily for 24 months, or 5 mg oral risedronate daily and subcutaneous placebo every 6 months for 24 months. Randomisation was stratified by sex within each subpopulation, and was done with an interactive voice-response system. Active drugs and corresponding placebos had identical packaging, labels, and appearance. The primary outcome was non-inferiority of denosumab to risedronate in terms of percentage change from baseline in lumbar spine bone mineral density at 12 months based on non-inferiority margins (-0·7 and -1·1 percentage points for the glucocorticoid-continuing and glucocorticoid-initiating subpopulations, respectively). Superiority was also assessed as a secondary outcome. The primary efficacy set included all randomly assigned participants who had a baseline and postbaseline lumbar spine bone mineral density measurement, and was analysed according to randomised treatment assignment. The safety analysis set included all randomly assigned participants who received at least one dose of investigational product, and was analysed by actual treatment received. This study is registered with ClinicalTrials.gov (NCT01575873) and is completed.Between March 28, 2012, and June 30, 2015, 795 patients, 505 of whom were glucocorticoid continuing and 290 of whom were glucocorticoid initiating, were enrolled and randomly assigned (398 to denosumab, 397 to risedronate). Denosumab was both non-inferior and superior to risedronate at 12 months for effect on bone mineral density at the lumbar spine in both glucocorticoid-continuing (4·4% [95% CI 3·8-5·0] vs 2·3% [1·7-2·9]; p<0·0001) and glucocorticoid-initiating (3·8% [3·1-4·5] vs 0·8% [0·2-1·5]; p<0·0001) subpopulations. Incidence of adverse events, serious adverse events (including infections), and fractures was similar between treatment groups. The most common adverse events were back pain (17 [4%] patients in the risedronate group and 18 [5%] in the denosumab group) and arthralgia (21 [5%] patients in the risedronate group and 17 [4%] in the denosumab group). Serious infection occurred in 15 (4%) patients in the risedronate group and 17 (4%) patients in the denosumab group.Denosumab could be a useful treatment option for patients newly initiating or continuing glucocorticoids who are at risk of fractures.Amgen."
1,"TITLE: Efficacy of rimonabant in obese patients with binge eating disorder.ABSTRACT: In obesity, a dysregulation of the endocannabinoid system has been shown. The endocannabinoid receptor blockage by rimonabant demonstrated interesting metabolic effects. However, the role of rimonabant in weight loss of patients with binge eating disorder has not been investigated. Thus, our aim was to evaluate the effects of rimonabant on body weight in obese patients with binge eating disorders. This multicenter, randomized, double-blind, placebo-controlled study included 289 obese subjects (age 18-70 years, body mass index 30-45 kg/m(2)) with binge eating disorders. Subjects were randomized (1:1) to receive rimonabant 20 mg/day or placebo for 6 months. In total, 289 participants (age: 43.2±10.5 yrs, 91% of women) were randomized. The completer rate was similar (71%) in both treatment and placebo groups. Participants treated with rimonabant lost 4.7±5.2% of their initial body weight, vs. 0.4±4.5% in the placebo group (difference between both groups: 4.4±0.6 kg, p<0.0001). The rimonabant group showed a greater reduction on the binge eating scale total score (mean±SD  - 40.9±35.2%) vs. placebo ( - 29.9±34.6%, p=0.02). The incidence of treatment emergent adverse events was comparable in both the rimonabant (82.5%) and placebo (76.0%) group. Discontinuations due to treatment emergent adverse events occurred in 13.3% rimonabant-treated vs. 6.2% placebo-treated participants. In conclusion, this is the only randomised, placebo-controlled, double-blind trial having assessed the effect of rimonabant in patients with binge eating disorders. The rimonabant treatment reduced body weight significantly more than placebo in obese subjects with binge eating. Trial registration number (clinicaltrials.gov): NCT00481975."
1,"TITLE: Amylin Analog Pramlintide Induces Migraine-like Attacks in Patients.ABSTRACT: Migraine is a prevalent and disabling neurological disease. Its genesis is poorly understood, and there remains unmet clinical need. We aimed to identify mechanisms and thus novel therapeutic targets for migraine using human models of migraine and translational models in animals, with emphasis on amylin, a close relative of calcitonin gene-related peptide (CGRP).Thirty-six migraine without aura patients were enrolled in a randomized, double-blind, 2-way, crossover, positive-controlled clinical trial study to receive infusion of an amylin analogue pramlintide or human αCGRP on 2 different experimental days. Furthermore, translational studies in cells and mouse models, and rat, mouse and human tissue samples were conducted.Thirty patients (88%) developed headache after pramlintide infusion, compared to 33 (97%) after CGRP (p = 0.375). Fourteen patients (41%) developed migraine-like attacks after pramlintide infusion, compared to 19 patients (56%) after CGRP (p = 0.180). The pramlintide-induced migraine-like attacks had similar clinical characteristics to those induced by CGRP. There were differences between treatments in vascular parameters. Human receptor pharmacology studies showed that an amylin receptor likely mediates these pramlintide-provoked effects, rather than the canonical CGRP receptor. Supporting this, preclinical experiments investigating symptoms associated with migraine showed that amylin treatment, like CGRP, caused cutaneous hypersensitivity and light aversion in mice.Our findings propose amylin receptor agonism as a novel contributor to migraine pathogenesis. Greater therapeutic gains could therefore be made for migraine patients through dual amylin and CGRP receptor antagonism, rather than selectively targeting the canonical CGRP receptor. ANN NEUROL 2021;89:1157-1171."
1,"TITLE: Influence of Prednisone on Inflammatory Biomarkers in Community-Acquired Pneumonia: Secondary Analysis of a Randomized Trial.ABSTRACT: Glucocorticoids are frequently prescribed in inflammatory diseases and have recently experienced a boom in the treatment of COVID-19. Small studies have shown an effect of glucocorticoids on inflammatory marker levels, but definitive proof is lacking. We investigated the influence of prednisone on inflammatory biomarkers in a previous multicenter, randomized, placebo-controlled trial that compared a 7-day treatment course of 50-mg prednisone to placebo in patients hospitalized with community-acquired pneumonia. We compared levels of C-reactive protein (CRP), procalcitonin (PCT), leukocyte and neutrophil count between patients with and without glucocorticoid treatment at baseline and on days 3, 5, and 7 and at discharge by Wilcoxon tests and analysis of variance. A total of 356 patient data sets in the prednisone group and 355 in the placebo group were available for analysis. Compared to placebo, use of prednisone was associated with reductions in levels of CRP on days 3, 5, and 7 (mean difference of 46%, P < .001 for each time point). For PCT, no such difference was observed. Leukocyte and neutrophil count were higher in the prednisone group at all time points (mean difference of 27% for leukocytes and 33% for neutrophils, P <.001 for all time points). We conclude that after administration of glucocorticoids in community-acquired pneumonia, patients had lower CRP levels and increased leukocyte and neutrophil count as compared to the placebo group. PCT levels were not different between treatment groups. PCT levels thus may more appropriately mirror the resolution of infection compared to more traditional inflammatory markers."
1,"TITLE: Randomised clinical trial: gabapentin vs baclofen in the treatment of suspected refractory gastro-oesophageal reflux-induced chronic cough.ABSTRACT: Neuromodulators are considered potential therapeutic options for refractory gastro-oesophageal reflux-induced chronic cough.To compare the efficacy of gabapentin and baclofen in patients with suspected refractory gastro-oesophageal reflux-induced chronic cough.Two hundred and thirty-four patients with suspected refractory gastro-oesophageal reflux-induced chronic cough, who failed an 8-week course of omeprazole and domperidone, were recruited into the open-labelled study and randomly assigned to receive either gabapentin (maximum daily dose of 900 mg) or baclofen (maximum daily dose of 60 mg) for 8 weeks as add-on therapy to the previous treatment. The primary end point was the successful rate of cough resolution; and the secondary end-points included cough sensitivity to capsaicin and gastro-oesophageal reflux disease questionnaire score and reported side effects.One hundred and eleven patients in the gabapentin group and 106 in the baclofen group completed the study. The overall success rate for cough resolution was comparable (57.3% vs 53.0%, χ  = 0.357, P = 0.550) between the two groups. In parallel, cough sensitivity to capsaicin and gastro-oesophageal reflux disease questionnaire score decreased after treatment with either gabapentin or baclofen. However, gabapentin was associated with less frequent somnolence (20.5% vs 35.0%, χ = 6.156, P = 0.013) and dizziness (11.1% vs 23.9%, χ = 6.654, P = 0.010) than baclofen.Gabapentin and baclofen have similar therapeutic efficacy for suspected refractory gastro-oesophageal reflux-induced chronic cough. However, gabapentin may be preferable because of fewer side effects. Trial Register: http://www.chictr.org/; No.: ChiCTR-ONC-13003066."
0,"TITLE: Predictors of fasting serum insulin and glucose and the risk of pancreatic cancer in smokers.ABSTRACT: A history of type 2 diabetes is one of few consistent risk factors for pancreatic cancer. Potentially modifiable factors related to fasting insulin and glucose concentrations may influence pancreatic cancer risk.Multiple linear regression models were used to identify anthropometric, clinical, behavioral, and dietary factors associated with fasting insulin and glucose in a subcohort of non-diabetics in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (n = 366). Hazards ratios (HRs) and 95% confidence intervals (CIs) were calculated among the larger cohort (n = 27,035).During follow-up (median 16.1 years), 305 participants developed pancreatic cancer. Fasting insulin and/or glucose were positively associated with body mass index (BMI), height, and dietary total and saturated fat and inversely associated with serum high-density lipoprotein cholesterol (HDL) and dietary available carbohydrates, sucrose, and alcohol. Comparing highest to lowest quintiles, total fat (HR = 1.54, 95% CI 1.05-2.25, p-trend = 0.01) and saturated fat (HR = 1.38, 95% CI 0.97-1.98, p-trend = 0.06) were positively associated and available carbohydrates (HR = 0.63, 95% CI 0.44-0.90, p-trend = 0.01), particularly sucrose (HR = 0.62, 95% CI 0.43-0.89, p-trend = 0.09), were inversely associated with risk of pancreatic cancer. BMI, HDL, height, and alcohol were not associated with pancreatic cancer risk.Dietary fat is associated with higher fasting insulin concentrations and may increase pancreatic cancer risk in smokers."
1,"TITLE: Effect of calcium supplementation on blood lead levels in pregnancy: a randomized placebo-controlled trial.ABSTRACT: Prenatal lead exposure is associated with deficits in fetal growth and neurodevelopment. Calcium supplementation may attenuate fetal exposure by inhibiting mobilization of maternal bone lead and/or intestinal absorption of ingested lead.Our goal was to evaluate the effect of 1,200 mg dietary calcium supplementation on maternal blood lead levels during pregnancy.In a double-blind, randomized, placebo-controlled trial conducted from 2001 through 2003 in Mexico City, we randomly assigned 670 women in their first trimester of pregnancy to ingest calcium (n = 334) or placebo (n = 336). We followed subjects through pregnancy and evaluated the effect of supplementation on maternal blood lead, using an intent-to-treat analysis by a mixed-effects regression model with random intercept, in 557 participants (83%) who completed follow-up. We then conducted as-treated analyses using similar models stratified by treatment compliance.Adjusting for baseline lead level, age, trimester of pregnancy, and dietary energy and calcium intake, calcium was associated with an average 11% reduction (0.4 microg/dL) in blood lead level relative to placebo (p = 0.004). This reduction was more evident in the second trimester (-14%, p < 0.001) than in the third (-8%, p = 0.107) and was strongest in women who were most compliant (those who consumed > or = 75% calcium pills; -24%, p < 0.001), had baseline blood lead > 5 microg/dL (-17%, p < 0.01), or reported use of lead-glazed ceramics and high bone lead (-31%, p < 0.01).Calcium supplementation was associated with modest reductions in blood lead when administered during pregnancy and may constitute an important secondary prevention effort to reduce circulating maternal lead and, consequently, fetal exposure."
1,"TITLE: Romosozumab or alendronate for fracture prevention in East Asian patients: a subanalysis of the phase III, randomized ARCH study.ABSTRACT: Romosozumab, a sclerostin antibody, exerts dual effect to increase bone formation and decrease bone resorption. Among high-risk postmenopausal East Asian women, romosozumab followed by alendronate was associated with lower incidences of fractures vs alendronate alone. Romosozumab demonstrates potential to address an unmet need in osteoporosis management in Asia.Romosozumab, a sclerostin antibody, exerts dual effect to increase bone formation and decrease bone resorption. The global ARCH study demonstrated superiority of romosozumab followed by alendronate in reducing fracture risk in high-risk postmenopausal osteoporotic women vs alendronate alone. We report outcomes among ARCH East Asian patients.In ARCH, 4093 postmenopausal osteoporotic women with fragility fracture were randomized 1:1 to monthly romosozumab 210 mg or weekly alendronate 70 mg for 12 months, both followed by open-label alendronate. Primary endpoints were incidence of new vertebral fracture (VF) at 24 months and clinical fracture at primary analysis (confirmed fractures in ≥ 330 patients and all patients had opportunity to attend month 24 visit). This post hoc analysis was not powered to detect fracture-rate differences.This analysis included 275 patients from Hong Kong, Korea, and Taiwan. Romosozumab followed by alendronate reduced risk of new VFs at 24 months by 60% (P = 0.11) and clinical fractures at primary analysis by 44% (P = 0.15) vs alendronate alone. Romosozumab followed by alendronate significantly increased mean bone mineral density at 24 months from baseline by a further 9.0%, 3.3%, and 3.0% at the lumbar spine, total hip, and femoral neck vs alendronate alone. Adverse event (AE) rates, including positively adjudicated serious cardiovascular AEs (1.6% vs 1.4% at 12 months for romosozumab vs alendronate), were similar across treatment groups.Consistent with the global analysis, romosozumab followed by alendronate was associated with lower incidences of new vertebral, clinical, non-vertebral, and hip fractures vs alendronate alone among East Asian patients."
1,"TITLE: Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial.ABSTRACT: Preterm birth remains a common cause of neonatal mortality, with a disproportionately high burden in low-income and middle-income countries. Meta-analyses of low-dose aspirin to prevent pre-eclampsia suggest that the incidence of preterm birth might also be decreased, particularly if initiated before 16 weeks of gestation.ASPIRIN was a randomised, multicountry, double-masked, placebo-controlled trial of low-dose aspirin (81 mg daily) initiated between 6 weeks and 0 days of pregnancy, and 13 weeks and 6 days of pregnancy, in nulliparous women with an ultrasound confirming gestational age and a singleton viable pregnancy. Participants were enrolled at seven community sites in six countries (two sites in India and one site each in the Democratic Republic of the Congo, Guatemala, Kenya, Pakistan, and Zambia). Participants were randomly assigned (1:1, stratified by site) to receive aspirin or placebo tablets of identical appearance, via a sequence generated centrally by the data coordinating centre at Research Triangle Institute International (Research Triangle Park, NC, USA). Treatment was masked to research staff, health providers, and patients, and continued until 36 weeks and 7 days of gestation or delivery. The primary outcome of incidence of preterm birth, defined as the number of deliveries before 37 weeks' gestational age, was analysed in randomly assigned women with pregnancy outcomes at or after 20 weeks, according to a modified intention-to-treat (mITT) protocol. Analyses of our binary primary outcome involved a Cochran-Mantel-Haenszel test stratified by site, and generalised linear models to obtain relative risk (RR) estimates and associated confidence intervals. Serious adverse events were assessed in all women who received at least one dose of drug or placebo. This study is registered with ClinicalTrials.gov, NCT02409680, and the Clinical Trial Registry-India, CTRI/2016/05/006970.From March 23, 2016 to June 30, 2018, 14 361 women were screened for inclusion and 11 976 women aged 14-40 years were randomly assigned to receive low-dose aspirin (5990 women) or placebo (5986 women). 5780 women in the aspirin group and 5764 in the placebo group were evaluable for the primary outcome. Preterm birth before 37 weeks occurred in 668 (11·6%) of the women who took aspirin and 754 (13·1%) of those who took placebo (RR 0·89 [95% CI 0·81 to 0·98], p=0·012). In women taking aspirin, we also observed significant reductions in perinatal mortality (0·86 [0·73-1·00], p=0·048), fetal loss (infant death after 16 weeks' gestation and before 7 days post partum; 0·86 [0·74-1·00], p=0·039), early preterm delivery (<34 weeks; 0·75 [0·61-0·93], p=0·039), and the incidence of women who delivered before 34 weeks with hypertensive disorders of pregnancy (0·38 [0·17-0·85], p=0·015). Other adverse maternal and neonatal events were similar between the two groups.In populations of nulliparous women with singleton pregnancies from low-income and middle-income countries, low-dose aspirin initiated between 6 weeks and 0 days of gestation and 13 weeks and 6 days of gestation resulted in a reduced incidence of preterm delivery before 37 weeks, and reduced perinatal mortality.Eunice Kennedy Shriver National Institute of Child Health and Human Development."
1,"TITLE: Five-year follow up of a randomised controlled trial comparing subtotal with total abdominal hysterectomy.ABSTRACT: To compare the rates of urinary incontinence (UI) and other complications of subtotal abdominal hysterectomy (SAH) with total abdominal hysterectomy (TAH) at 5 years after surgery.Randomised clinical trial with central, computer-generated randomisation.Danish multi-centre trial performed in 11 departments of gynaecology.Women referred with benign uterine diseases scheduled for abdominal hysterectomy.Women were randomised to either SAH (n = 161) or TAH (n = 158). Follow-up data were collected from participants using postal questionnaires sent out 5 years after surgery. Complications of hysterectomy were further examined by scrutinising registered discharge summaries following hospitalisation. Intention-to-treat and per-protocol analyses were conducted. Potential bias caused by missing data was handled using multiple imputation.The primary outcome was UI. Secondary outcomes included constipation, prolapse of the vaginal vault or cervical stump, satisfaction with sexual life, pelvic pain, postoperative complications and vaginal bleeding.The response rate was 234/319 (73.4%). A significantly higher proportion of respondents had urinary incontinence 5 years after SAH 34/113 (30.1%) than TAH 21/119 (17.6%) (RR 1.71, 95% confidence interval 1.06-2.75, P = 0.026). This difference reduced after multiple imputation to account for missing data (RR 1.37, 95% confidence interval 0.99-1.89, P = 0.052). Eleven of the 101 women (11%) in the SAH group still experienced vaginal bleeding. No other differences were found between the two types of abdominal hysterectomy.A smaller proportion of women suffered from UI after TAH than after SAH 5 years postoperatively. Around one in ten women continued to experience vaginal bleeding 5 years after SAH."
1,"TITLE: Shielding Parenteral Nutrition Solutions From Light: A Randomized Controlled Trial.ABSTRACT: Oxidant stress is implicated in the pathogenesis of bronchopulmonary dysplasia (BPD). Light induces peroxide generation in parenteral nutrition (PN) solutions, creating an oxidant stress. Shielding PN from light decreases its peroxide content, which has nutrition and biochemical benefits in animals and humans. This study aims at determining whether full light protection of PN decreases the rate of bronchopulmonary dysplasia and/or death in very low-birth-weight infants.Multicenter randomized controlled trial of photoprotection, using amber bags and tubing initiated during compounding of PN and maintained throughout infusion in the light-protected (LP) group. The control group (light exposed [LE]) received PN exposed to ambient light. Depending on centers, lipids were infused either separately or as all-in-one PN.In total, 590 infants born <30 weeks gestational age were included. At randomization, LE and LP groups did not differ clinically except for maximal FiO2 before 12 hours. The rate of BPD/death was not different between groups at 28 days (77% LP vs 72% LE, P = .16) or at 36 weeks corrected age (30% LP vs 27% LE, P = .55). Multivariate analysis showed no significant effect of photoprotection on BPD and/or death. The rate of BPD/death was significantly lower (odds ratio, 0.54; 95% confidence interval, 0.32-0.93; P = .02) in infants receiving all-in-one PN vs those who received lipids separately.This study did not show significant beneficial effects of photoprotection. Since the decreased rate of BPD/death found with all-in-one PN relates to a center-dependent variable, this warrants further investigation."
1,"TITLE: Randomized clinical trial of isolated Roux-en-Y versus conventional reconstruction after pancreaticoduodenectomy.ABSTRACT: Pancreaticoduodenectomy (PD) is associated with a high incidence of postoperative complications including pancreatic fistula. This randomized clinical trial compared the incidence of pancreatic fistula between the isolated Roux-en-Y (IsoRY) and conventional reconstruction (CR) methods.Patients admitted for PD between June 2009 and September 2012 in a single centre were assigned randomly to CR or IsoRY. The primary endpoint was the incidence of pancreatic fistula (grade A-C) defined according to the International Study Group on Pancreatic Fistula. Secondary endpoints were complication rates, mortality and hospital stay. Multiple logistic regression analysis was performed to identify factors associated with pancreatic fistula.Some 153 patients were randomized, 76 to CR and 77 to IsoRY; two patients from the IsoRY group were excluded after randomization. Pancreatic fistula occurred in 26 patients (34 per cent) in the CR group and 25 (33 per cent) in the IsoRY group (P = 0·909). The number of patients with a clinically relevant pancreatic fistula (grade B or C) was similar in the two groups (10 and 11 patients respectively; P = 0·789), as were complication rates (42 versus 40 per cent; P = 0·793) and mortality (none in either group; P = 0·999). Soft pancreas was the only independent risk factor for pancreatic fistula (odds ratio 4·42, 95 per cent confidence interval 1·85 to 10·53; P <0·001).This study showed that IsoRY reconstruction does not reduce the incidence of pancreatic fistula compared with CR.NCT00915863 (http://www.clinicaltrials.gov/) and UMIN000001967 (http://www.umin.ac.jp/)."
1,"TITLE: Long-term follow-up of cyclophosphamide compared with azathioprine for initial maintenance therapy in ANCA-associated vasculitis.ABSTRACT: Treatment with azathioprine within 3 months of remission induction with cyclophosphamide is a common treatment strategy for patients with ANCA-associated vasculitis. This study comprised patients undergoing long-term follow-up who were randomly allocated to azathioprine after 3-6 months or after 12 months of cyclophosphamide treatment.Patients from 39 European centers between 1995 and 1997 with a new diagnosis of ANCA-associated vasculitis that involved the kidneys or another vital organ were eligible. At the time of diagnosis, participants were randomly allocated to convert to azathioprine after 3-6 months (the azathioprine group) or after 12 months of cyclophosphamide (the cyclophosphamide group). Patients who did not achieve a remission within 6 months were excluded. This study assessed relapses, ESRD, and death during long-term follow-up.Patients were allocated to the azathioprine group (n=71) and the cyclophosphamide group (n=73). Of these patients, 63 (43.8%) developed a relapse, 35 (24.3%) developed a renal relapse, 13 (9.0%) developed ESRD, and 21 (14.6%) died. Although there were worse outcomes in the azathioprine group, none were statistically significant. The subdistribution hazard ratio [sHR] for relapse was 1.63 (95% confidence interval [95% CI], 0.99 to 2.71), the composite of relapse or death hazard ratio [HR] was 1.59 (95% CI, 1.00 to 2.54), the ESRD sHR was 1.71 (95% CI, 0.56 to 5.19), and the death HR was 0.75 (95% CI, 0.32 to 1.79).It remains uncertain whether converting to azathioprine after 3-6 months of induction cyclophosphamide therapy is as effective as converting after 12 months. Outcomes are still poor for this group of patients and further research is required to determine the optimal timing of maintenance therapy."
1,"TITLE: Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease.ABSTRACT: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention.In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months.The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group.Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .)."
0,"TITLE: Association between selenium and lycopene supplementation and incidence of prostate cancer: Results from the post-hoc analysis of the procomb trial.ABSTRACT: Many potential chemopreventive agents have been used in PCa prevention, including selenium (Se) and lycopene (Ly). However, their role has been matter of debate over the years, due to potential of promotion of PCa.In this study we aimed at evaluating the incidence risk of prostate cancer (PCa) in a cohort of patients treated with Se and Ly.The Procomb trial design has been previously published (ISRCTN78639965). From April 2012 to April 2014 209 patients were followed and underwent prostate biopsy when PSA ≥4 ng/ml and/or suspicion of PCa. The all cohort was composed by patients treated with Se and Ly (Group A = 134 patients) and control (Group B = 75 patients).During the follow-up time of 2 years, a total of 24 patients (11.5%) underwent prostate biopsy, of which 9 (4.3%) where diagnosed with PCa and 15 (7.2%) where diagnosed with benign prostatic hyperplasia. We did not observe statistical differences in terms of mean changes of PSA between the two groups (p-value for trend = 0.33). The relative risk (RR) for PCa was 1.07 and 0.89 in group A and B, respectively (p = 0.95). At the multivariate Cox regression analysis supplementation with Se and Ly was not associated with greater risk of PCa (hazard ratio: 1.38; p = 0.67).In this analysis we did not show evidences supporting a detrimental role of Selenium and Lycopene supplementation in increasing PCa after 2 years of therapy, nor supporting a protective role."
1,"TITLE: Prevalent Herpes Simplex Virus-2 Increases the Risk of Incident Bacterial Vaginosis in Women from South Africa.ABSTRACT: Studies have shown that women diagnosed with herpes simplex virus-2 (HSV-2) have a higher risk for bacterial vaginosis (BV) infection. We investigated the presence of HSV-2 infections as a risk factor for incident BV infections in high risk, Human immunodeficiency virus (HIV) uninfected women enrolled in a HIV prevention trial in Durban, South Africa. The Vaginal and Oral Interventions to Control the Epidemic trial was a multicentre, double blinded, randomized controlled trial which was designed to estimate the effectiveness of daily treatment with vaginal tenofovir gel, oral tenofovir disoproxil fumarate and oral Truvada in preventing HIV-1 infection in women. Women provided samples for the diagnosis of HSV-2 and BV. The presence of HSV-2 antibodies was detected using HerpeSelect™ ELISA IgG. Bacterial vaginosis was diagnosed using the Nugent scoring system. To assess the risk of BV incidence, modelled as a time-dependent variable, we used the Andersen-Gill model with robust variance estimation and Efron methods for ties. Overall, 2750 women were enrolled in the VOICE trial at our study sites. Women who had a HSV-2 infection at enrolment were shown to be at increased risk for incident BV infections (adjusted hazard ratio 1.17, 95% CI 1.08, 1.27, p ≤ 0.001). In addition, being of a young age, being unmarried and having a partner that has other partners were significantly associated with subsequent BV infection. Our findings therefore advocate the need for strengthening STI prevention efforts among women in high burden STI settings."
1,"TITLE: Acetaminophen or Nonsteroidal Anti-Inflammatory Drugs in Acute Musculoskeletal Trauma: A Multicenter, Double-Blind, Randomized, Clinical Trial.ABSTRACT: We determine whether pain treatment with acetaminophen was not inferior to nonsteroidal anti-inflammatory drugs or the combination of both in minor musculoskeletal trauma.The Paracetamol or NSAIDs in Acute Musculoskeletal Trauma Study was a double-blind, randomized, clinical trial conducted in 2 general practices and 2 emergency departments in the Netherlands. A total of 547 adults, aged 18 years and older, with acute blunt minor musculoskeletal extremity trauma were randomly assigned in a 1:1:1 ratio to acetaminophen 4,000 mg/day, diclofenac 150 mg/day, or acetaminophen 4,000 mg/day+diclofenac 150 mg/day during 3 consecutive days. Patients, health care staff, and outcome assessors were blinded for treatment allocation. Follow-up for each patient was 30 days. Primary outcome measures were between-group differences in mean numeric rating scale (NRS) pain scores in rest and with movement at 90 minutes after initial drug administration compared with baseline pain scores with a predefined noninferiority margin of 0.75 NRS points. Secondary outcomes included NRS pain scores during 3 consecutive days and need for additional analgesia.One hundred eighty-two patients were treated with acetaminophen, 183 with diclofenac, and 182 with combination treatment. Intention-to-treat analysis revealed mean NRS reduction in rest -1.23 (95% confidence interval [CI] -1.50 to -0.95) and -1.72 (95% CI -2.01 to -1.44) with movement, both for acetaminophen at 90 minutes compared with baseline. Pairwise comparison in rest with diclofenac showed a difference of -0.027 (97.5% CI -0.45 to 0.39) and -0.052 (97.5% CI -0.46 to 0.36) for combination treatment. With movement, these numbers were -0.20 (97.5% CI -0.64 to 0.23) and -0.39 (97.5% CI -0.80 to 0.018), respectively. All differences were well below the predefined noninferiority margin.Pain treatment with acetaminophen was not inferior to that with diclofenac or the combination of acetaminophen and diclofenac in acute minor musculoskeletal extremity trauma, both in rest and with movement."
1,"TITLE: Baseline factors affecting closure of venous leg ulcers.ABSTRACT: The objective of this study was to characterize factors associated with closure of venous leg ulcers (VLUs) in a pooled analysis of subjects from three randomized clinical trials.Closure of VLUs after treatment with HP802-247, an allogeneic living cell therapy consisting of growth-arrested human keratinocytes and fibroblasts, vs standard therapy with compression bandaging was evaluated in three phase 3 clinical trials of similar design. Two trials enrolled subjects with VLUs ranging from 2 cm to 12 cm in area with 12-week treatment periods; the third trial enrolled subjects with VLUs between >12 cm and ≤36 cm with a 16-week treatment period. The first trial went to completion but failed to demonstrate a benefit to therapy with HP802-247 compared with placebo, and because of this, the remaining trials were terminated before completion. On the basis of no differences in outcomes between groups, subjects from both HP802-247 and control groups were pooled across all three studies. Cox proportional hazards regression analysis was employed to evaluate factors associated with VLU closure.This analysis included data from 716 subjects with VLU. Factors evaluated for association with healing included age, gender, race, diabetes, glycated hemoglobin level, body mass index, treatment (HP802-247 vs compression alone), and ulcer characteristics including location and area and duration at baseline. In an initial model including all of these putative factors, the following were significant at the P < .10 level: diagnosis of diabetes mellitus, gender, wound location (ankle or leg), baseline wound area, and wound duration at baseline. In a final model including only these factors, all but diabetes mellitus were significant at the P < .05 level. Effect sizes were as follows (hazard ratio [95% confidence interval]): female gender (1.384 [1.134-1.690]), wound location on the leg (1.490 [1.187-1.871]), smaller wound area at baseline (0.907 [0.887-0.927]), and shorter wound duration at baseline (0.971 [0.955-0.987]).Factors associated with VLU lesions including location, area, and duration were important predictors of healing. Women were more likely than men to achieve wound closure. Factors including body mass index, the presence of diabetes mellitus, and higher concentrations of glycated hemoglobin were not significant independent predictors of wound closure in this analysis."
1,"TITLE: A Comparison of 3 Videolaryngoscopes for Double-Lumen Tube Intubation in Humans by Users With Mixed Experience: A Randomized Controlled Study.ABSTRACT: To test the hypothesis that laryngoscopy using the Airtraq (Prodol Limited, Viscaya, Spain) or King Vision laryngoscope (KVL) (Ambu A/S, Ballerup, Denmark) would result in a shorter time for successful double-lumen endobronchial tube (DLT) intubation by users with mixed experience than the time required using the Macintosh or GlideScope (Verathon Inc., Bothell, WA) laryngoscopes.A randomized, prospective, blind study.A single university hospital.The study comprised 133 patients undergoing elective thoracic surgery.Patients were randomly allocated into the following 4 groups of DLTs: Macintosh (n = 32), GlideScope (n = 34), Airtraq (n = 35), or KVL (n = 32).The following data were recorded: time required for achieving successful DLT intubation; glottis visualization; optimization maneuvers; first-pass success rate; intubation difficulty; failure to intubate, defined as an attempt taking >150 seconds to perform or if peripheral oxygen saturation <92% was noted; and postoperative sore throat and hoarseness were recorded. Compared with GlideScope, the Airtraq resulted in shorter times for achieving successful DLT intubation (median times: 21 s [95% confidence interval 23.9-70.8 s] v 57.5 s [95% confidence interval 46.2-89.1 s], respectively; p = 0.021); a lower score for difficult intubations (p = 0.023); and fewer optimization maneuvers. The 4 laryngoscopes were associated with comparable glottis visualization; first-pass success rate (100%, 100%, 94.4%, and 100%, respectively; p = 0.522); incidence of oropharyngeal trauma; postoperative sore throat; and hoarseness of voice. There were 2 (5.7%) endobronchial intubation failures using the Airtraq due to the inability to advance the DLT through the glottis opening. The experience of the anesthesiologists in using the 4 devices had a statistically significant negative correlation with the time to confirmation of endobronchial intubation (Spearman r -0.392; p < 0.001).When used by operators with mixed experience, the channeled Airtraq required less time for DLT intubation and was easier to use than the GlideScope, although failures did occur with the Airtraq, whereas they did not occur with the other systems."
0,"TITLE: Adenosine-induced cardiac arrest as an alternative to temporary clipping during intracranial aneurysm surgery.ABSTRACT: OBJECTIVE The purpose of this study was to analyze the impact of adenosine-induced cardiac arrest (AiCA) on temporary clipping (TC) and the postoperative cerebral infarction rate among patients undergoing intracranial aneurysm surgery. METHODS In this retrospective matched-cohort study, 65 patients who received adenosine for decompression of aneurysms during microsurgical clipping were identified (Group A) and randomly matched with 65 selected patients who underwent clipping but did not receive adenosine during surgery (Group B). The matching criteria included age, Fisher grade, aneurysm size, rupture status, and location of aneurysms. The primary outcomes were TC time and the postoperative infarction rate. The secondary outcome was the incidence of intraoperative aneurysm rupture (IAR). RESULTS In Group A, 40 patients underwent clipping with AiCA alone and 25 patients (38%) received AiCA combined with TC, and in Group B, 60 patients (92%) underwent aneurysm clipping under the protection of TC (OR 0.052; 95% CI 0.018-0.147; p < 0.001). Group A required less TC time (2.04 minutes vs 4.46 minutes; p < 0.001). The incidence of postoperative lacunar infarction was equal in both groups (6.2%). There was an insignificant between-group difference in the incidence of IAR (1.5% in Group A vs 6.1% in Group B; OR 0.238; 95% CI 0.026-2.192; p = 0.171). CONCLUSIONS AiCA is a useful technique for microneurosurgical treatment of cerebral aneurysms. AiCA can minimize the use of TC and does not increase the risk of IAR and postoperative infarction."
1,"TITLE: Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2).ABSTRACT: Whether the route of early feeding affects outcomes of patients with severe critical illnesses is controversial. We hypothesised that outcomes were better with early first-line enteral nutrition than with early first-line parenteral nutrition.In this randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2 trial) done at 44 French intensive-care units (ICUs), adults (18 years or older) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned (1:1) to either parenteral nutrition or enteral nutrition, both targeting normocaloric goals (20-25 kcal/kg per day), within 24 h after intubation. Randomisation was stratified by centre using permutation blocks of variable sizes. Given that route of nutrition cannot be masked, blinding of the physicians and nurses was not feasible. Patients receiving parenteral nutrition could be switched to enteral nutrition after at least 72 h in the event of shock resolution (no vasopressor support for 24 consecutive hours and arterial lactate <2 mmol/L). The primary endpoint was mortality on day 28 after randomisation in the intention-to-treat-population. This study is registered with ClinicalTrials.gov, number NCT01802099.After the second interim analysis, the independent Data Safety and Monitoring Board deemed that completing patient enrolment was unlikely to significantly change the results of the trial and recommended stopping patient recruitment. Between March 22, 2013, and June 30, 2015, 2410 patients were enrolled and randomly assigned; 1202 to the enteral group and 1208 to the parenteral group. By day 28, 443 (37%) of 1202 patients in the enteral group and 422 (35%) of 1208 patients in the parenteral group had died (absolute difference estimate 2·0%; [95% CI -1·9 to 5·8]; p=0·33). Cumulative incidence of patients with ICU-acquired infections did not differ between the enteral group (173 [14%]) and the parenteral group (194 [16%]; hazard ratio [HR] 0·89 [95% CI 0·72-1·09]; p=0·25). Compared with the parenteral group, the enteral group had higher cumulative incidences of patients with vomiting (406 [34%] vs 246 [20%]; HR 1·89 [1·62-2·20]; p<0·0001), diarrhoea (432 [36%] vs 393 [33%]; 1·20 [1·05-1·37]; p=0·009), bowel ischaemia (19 [2%] vs five [<1%]; 3·84 [1·43-10·3]; p=0·007), and acute colonic pseudo-obstruction (11 [1%] vs three [<1%]; 3·7 [1·03-13·2; p=0·04).In critically ill adults with shock, early isocaloric enteral nutrition did not reduce mortality or the risk of secondary infections but was associated with a greater risk of digestive complications compared with early isocaloric parenteral nutrition.La Roche-sur-Yon Departmental Hospital and French Ministry of Health."
1,"TITLE: Trial of the route of early nutritional support in critically ill adults.ABSTRACT: Uncertainty exists about the most effective route for delivery of early nutritional support in critically ill adults. We hypothesized that delivery through the parenteral route is superior to that through the enteral route.We conducted a pragmatic, randomized trial involving adults with an unplanned admission to one of 33 English intensive care units. We randomly assigned patients who could be fed through either the parenteral or the enteral route to a delivery route, with nutritional support initiated within 36 hours after admission and continued for up to 5 days. The primary outcome was all-cause mortality at 30 days.We enrolled 2400 patients; 2388 (99.5%) were included in the analysis (1191 in the parenteral group and 1197 in the enteral group). By 30 days, 393 of 1188 patients (33.1%) in the parenteral group and 409 of 1195 patients (34.2%) in the enteral group had died (relative risk in parenteral group, 0.97; 95% confidence interval, 0.86 to 1.08; P=0.57). There were significant reductions in the parenteral group, as compared with the enteral group, in rates of hypoglycemia (44 patients [3.7%] vs. 74 patients [6.2%]; P=0.006) and vomiting (100 patients [8.4%] vs. 194 patients [16.2%]; P<0.001). There were no significant differences between the parenteral group and the enteral group in the mean number of treated infectious complications (0.22 vs. 0.21; P=0.72), 90-day mortality (442 of 1184 patients [37.3%] vs. 464 of 1188 patients [39.1%], P=0.40), in rates of 14 other secondary outcomes, or in rates of adverse events. Caloric intake was similar in the two groups, with the target intake not achieved in most patients.We found no significant difference in 30-day mortality associated with the route of delivery of early nutritional support in critically ill adults. (Funded by the United Kingdom National Institute for Health Research; CALORIES Current Controlled Trials number, ISRCTN17386141.)."
1,"TITLE: Prevention of electrocardiographic left ventricular remodeling by the angiotensin receptor blocker olmesartan in patients with type 2 diabetes.ABSTRACT: To assess the ability of olmesartan (OLM) to prevent or delay left ventricular remodeling and hypertrophy in patients with type 2 diabetes.This prespecified ECG substudy of Randomised OlmesArtan and Diabetes MicroAlbuminuria Prevention (ROADMAP), which compared OLM with placebo, assessed the signs of left ventricular remodeling in patients with a 12-lead ECG at baseline and after at least 2 years. Cornell voltage QRS duration product (primary objective), Cornell voltage index and Sokolow-Lyon index were assessed.In total, 9418 ECG recordings and 1513 patients from ROADMAP were analyzed (placebo, n = 736; OLM, n = 777). Quartiles defined by baseline Cornell voltage QRS duration product were assessed and the proportion of patients in the highest quartile (≥200 mVms) increased from 24.0 to 26.5% in the placebo group and decreased from 25.5 to 22.3% in the OLM group [odds ratio (OR) 0.598 (95% confidence interval [CI] 0.440-0.813); P = 0.0011]. The OR did not change after adjustment for baseline parameters. By the end of study, 38.7% of patients in the placebo group and 34.7% in the OLM group shifted from a lower to a higher quartile or remained in the highest quartile of Cornell voltage QRS duration product [OR 0.797 (95% CI 0.637-0.996); P = 0.0465]. This translated into a 20.3% risk reduction with OLM and suggested OLM attenuated the progression of left ventricular remodeling versus placebo.OLM substantially delayed the development of left ventricular remodeling in type 2 diabetes. This effect was not explained by the differences in blood pressure control. Thus, OLM delayed the onset of microalbuminuria, as well as the ECG signs of cardiac structural adaptation in type 2 diabetes."
1,"TITLE: Rectal indometacin dose escalation for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography in high-risk patients: a double-blind, randomised controlled trial.ABSTRACT: Although rectal indometacin 100 mg is effective in reducing the frequency and severity of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients, the optimal dose is unknown, and pancreatitis incidence remains high. The aim of this study was to compare the efficacy of two dose regimens of rectal indometacin on the frequency and severity of pancreatitis after ERCP in high-risk patients.In this randomised, double-blind, comparative effectiveness trial, we enrolled patients from six tertiary medical centres in the USA. Eligible patients were those at high risk for the development of pancreatitis after ERCP. We randomly assigned eligible patients (1:1) immediately after ERCP to receive either two 50 mg indometacin suppositories and a placebo suppository (standard-dose group) or three 50 mg indometacin suppositories (high-dose group). 4 h after the procedure, patients assigned to the high-dose group received an additional 50 mg indometacin suppository, whereas patients in the standard-dose group received an additional placebo suppository. The randomisation schedule, stratified according to study centre and with no other restrictions, was computer generated by an investigator who was uninvolved in the clinical care of any participants, distributed to the sites, and kept by personnel not directly involved with the study. These same personnel were responsible for packaging the drug and placebo in opaque envelopes. Patients, study personnel, and treating physicians were masked to study group assignment. The primary outcome of the study was the development of pancreatitis after ERCP. Analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01912716, and enrolment is complete.Between July 9, 2013, and March 22, 2018, 1037 eligible patients were enrolled and randomly assigned to receive either standard-dose (n=515) or high-dose indometacin (n=522). Pancreatitis after ERCP occurred in 141 (14%) of 1037 patients-76 (15%) of 515 patients in the standard-dose indometacin group and 65 (12%) of 522 patients in the high-dose indometacin group (risk ratio [RR] 1·19, 95% CI 0·87-1·61; p=0·32). We observed 19 adverse events that were potentially attributable to study drug. Clinically significant bleeding occurred in 14 (1%) of 1037 patients-six (1%) of 515 patients in the standard-dose indometacin group and eight (2%) of 522 patients in the high-dose indometacin group (p=0·79). Three (1%) of 522 patients in the high-dose indometacin group developed acute kidney injury versus none in the standard-dose group (p=0·25). A non-ST elevation myocardial infarction occurred in the standard-dose indometacin group 2 days after ERCP. A transient ischaemic attack occurred in the high-dose indometacin group 5 days after ERCP. All 19 adverse events, in addition to the 141 patients who developed pancreatitis after ERCP, were considered serious as all required admission to hospital. We observed no allergic reactions or deaths at 30 day follow-up.Dose escalation to rectal indometacin 200 mg did not confer any advantage compared with the standard 100 mg regimen, with pancreatitis incidence remaining high in high-risk patients. Current practice should continue unchanged. Further research should consider the pharmacokinetics of non-steroidal anti-inflammatory drugs to determine the optimal timing of their administration to prevent pancreatitis after ERCP.American College of Gastroenterology."
1,"TITLE: Daily Versus Weekly Prostate Cancer Image Guided Radiation Therapy: Phase 3 Multicenter Randomized Trial.ABSTRACT: The optimal frequency of prostate cancer image guided radiation therapy (IGRT) has not yet been clearly identified. This study sought to compare the safety and efficacy of daily versus weekly IGRT.This phase 3 randomized trial recruited patients with N0 localized prostate cancer. The total IGRT doses in the prostate ranged from 70 Gy to 80 Gy, sparing the lymph nodes. Patients were randomly assigned (1:1) to 2 prostate IGRT frequency groups: daily and weekly (ie, on days 1, 2, and 3 and then weekly). The primary outcome was 5-year recurrence-free survival. Secondary outcomes included overall survival and toxicity. Post hoc analyses included biochemical progression-free interval, clinical progression-free interval, and other cancer-free interval.Between June 2007 and November 2012, 470 men from 21 centers were randomized into the 2 groups. Median follow-up was 4.1 years. There was no statistically significant difference in recurrence-free survival between the groups (hazard ratio [HR] = 0.81; P = .330). Overall survival was worse in the daily group than in the weekly group (HR = 2.12 [95% confidence interval (CI), 1.03-4.37]; P = .042). Acute rectal bleeding (grade ≥1) was significantly lower in the daily group (6%) (n = 14) than in the weekly group (11%) (n = 26) (P = .014). Late rectal toxicity (grade ≥1) was significantly lower in the daily group (HR = 0.71 [95% CI, 0.53-0.96]; P = .027). Biochemical progression-free interval (HR = 0.45 [95% CI, 0.25 - 0.80]; P = .007) and clinical progression-free interval (HR = 0.50 [95% CI, 0.24-1.02]; P = .057) were better in the daily group, whereas other cancer-free interval was worse in the daily group (HR = 2.21 [95% CI, 1.10-4.44]; P = .026).Compared with weekly control, daily IGRT control in prostate cancer significantly improves biochemical progression-free and clinical progression-free interval, and rectal toxicity."
1,"TITLE: Phase III study of cisplatin with or without S-1 in patients with stage IVB, recurrent, or persistent cervical cancer.ABSTRACT: This open-label phase III trial evaluated efficacy and safety of S-1 plus cisplatin vs. cisplatin alone as first-line chemotherapy in patients with stage IVB, recurrent, or persistent cervical cancer.Patients were randomised (1:1) to S-1 plus cisplatin (study group) or cisplatin alone (control group). In each cycle, cisplatin 50 mg/m was administered on Day 1 in both groups. S-1 was administered orally at 80-120 mg daily on Days 1-14 of a 21-day cycle in the study group. The primary endpoint was overall survival (OS).A total of 375 patients were enrolled, of whom 364 (188, study group; 176, control group) received treatment. Median OS was 21.9 and 19.5 months in the study and control groups, respectively (log-rank P = 0.125; hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.67-1.05). Median progression-free survival (PFS) was 7.3 and 4.9 months in the study and control groups, respectively (HR 0.62, 95% CI 0.48-0.80, P < 0.001). The adverse event (AE) rate increased in the study group despite the absence of any unexpected AEs.S-1 plus cisplatin did not show superiority over cisplatin alone in OS but significantly increased PFS in patients with stage IVB, recurrent, or persistent cervical cancer. Since the standard therapy has changed in the course of this study, further studies are warranted to confirm the clinical positioning of S-1 combined with cisplatin for this population."
1,"TITLE: Randomized clinical trial of postoperative chewing gum versus standard care after colorectal resection.ABSTRACT: Chewing gum may stimulate gastrointestinal motility, with beneficial effects on postoperative ileus suggested in small studies. The primary aim of this trial was to determine whether chewing gum reduces length of hospital stay (LOS) after colorectal resection. Secondary aims included examining bowel habit symptoms, complications and healthcare costs.This clinical trial allocated patients randomly to standard postoperative care with or without chewing gum (sugar-free gum for at least 10 min, four times per day on days 1-5) in five UK hospitals. The primary outcome was LOS. Cox regression was used to calculate hazard ratios for LOS.Data from 402 of 412 patients, of whom 199 (49·5 per cent) were allocated to chewing gum, were available for analysis. Some 40 per cent of patients in both groups had laparoscopic surgery, and all study sites used enhanced recovery programmes. Median (i.q.r.) LOS was 7 (5-11) days in both groups (P = 0·962); the hazard ratio for use of gum was 0·94 (95 per cent c.i. 0·77 to 1·15; P = 0·557). Participants allocated to gum had worse quality of life, measured using the EuroQoL 5D-3L, than controls at 6 and 12 weeks after operation (but not on day 4). They also had more complications graded III or above according to the Dindo-Demartines-Clavien classification (16 versus 6 in the group that received standard care) and deaths (11 versus 0), but none was classed as related to gum. No other differences were observed.Chewing gum did not alter the return of bowel function or LOS after colorectal resection.ISRCTN55784442 (http://www.controlled-trials.com)."
1,"TITLE: Effect of Thyroid Hormone Therapy on Fatigability in Older Adults With Subclinical Hypothyroidism: A Nested Study Within a Randomized Placebo-Controlled Trial.ABSTRACT: Fatigue often triggers screening for and treatment of subclinical hypothyroidism. However, data on the impact of levothyroxine on fatigue is limited and previous studies might not have captured all aspects of fatigue.This study is nested within the randomized, placebo-controlled, multicenter TRUST trial, including community-dwelling participants aged ≥65 and older, with persistent subclinical hypothyroidism (TSH 4.60-19.99 mIU/L, normal free thyroxine levels) from Switzerland and Ireland. Interventions consisted of daily levothyroxine starting with 50 μg (25 μg if weight <50 kg or known coronary heart diseases) together with dose adjustments to achieve a normal TSH and mock titration in the placebo group. Main outcome was the change in physical and mental fatigability using the Pittsburgh Fatigability Scale over 1 year, assessed through multivariable linear regression with adjustment for country, sex, and levothyroxine starting dose.Among 230 participants, the mean ± standard deviation (SD) TSH was 6.2 ± 1.9 mIU/L at baseline and decreased to 3.1 ± 1.3 with LT4 (n = 119) versus 5.3 ± 2.3 with placebo (n = 111, p < .001) after 1 year. After adjustment we found no between-group difference at 1 year on perceived physical (0.2; 95% CI -1.8 to 2.1; p = .88), or mental fatigability (-1.0; 95% CI -2.8 to 0.8; p = .26). In participants with higher fatigability at baseline (≥15 points for the physical score [n = 88] or ≥13 points for the mental score [n = 41]), the adjusted between-group differences at 1 year were 0.4 (95% CI -3.6 to 2.8, p = .79) and -2.2 (95% CI -8.8 to 4.5, p = .51).Levothyroxine in older adults with mild subclinical hypothyroidism provides no change in physical or mental fatigability."
1,"TITLE: Effects of supplementation with curcuminoids on serum adipokines in critically ill patients: a randomized double-blind placebo-controlled trial.ABSTRACT: Previous studies have shown a beneficial effect of curcuminoids supplementation on serum concentrations of adipokines; however, there are no published studies that have examined this effect among critically ill patients. We aimed to assess the effects of supplementation with curcuminoids on serum concentrations of leptin and adiponectin in critically ill patients with traumatic brain injury (TBI). In this trial, 62 critically ill patients with TBI, aged 18-65 years, were randomly allocated to receive either 500 mg/day curcuminoids (co-administered with 5 mg/day piperine) or matched placebo for 7 days. Patients in both intervention groups received routine treatments for TBI as well as enteral nutrition. Serum concentrations of leptin and adiponectin were measured at baseline and at the end of trial. We found a significant reduction in serum levels of leptin in both curcuminoids (47.1%) and placebo (22.8%) groups; though the magnitude of reduction was greater in the former (p < .05). Supplementation with curcumioinds was not found to alter serum concentrations of adiponectin (p > .05). Supplementation with curcumioinds significantly reduced serum levels of leptin but had no significant effect on adiponectin levels in critically ill patients with TBI. Further clinical trials, particularly those with a long-term period, are needed to confirm our findings."
1,"TITLE: Residual Symptoms of Posttraumatic Stress Disorder and Alcohol Use Disorder Following Integrated Exposure Treatment Versus Coping Skills Treatment.ABSTRACT: Although some studies have demonstrated residual symptoms in patients who have participated in posttraumatic stress disorder (PTSD) treatment, no studies to date have assessed residual PTSD symptoms following treatment for comorbid alcohol use disorder (AUD) and PTSD (PTSD/AUD). We examined residual symptoms of PTSD and AUD in 73 veterans with PTSD/AUD who completed a posttreatment assessment after being randomized to receive either Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE) or Seeking Safety (SS). We used logistic regression to identify differences (a) in residual PTSD and AUD symptoms among participants randomized to COPE versus SS and (b) among those with versus without a posttreatment PTSD/AUD diagnosis within both treatment conditions. Participants randomized to SS were more likely to report persistent avoidance, inability to experience positive emotions, hypervigilance, difficulty concentrating, and difficulty sleeping, ORs = 3.74-6.21. There were no differences between COPE and SS regarding the likelihood of persistent AUD symptoms. Participants without a posttreatment PTSD diagnosis had lower conditional probabilities of most symptoms, although exaggerated startle, OR = 0.71, and irritability/aggression, OR = 0.58, were most likely to persist. Participants without a posttreatment AUD diagnosis had lower conditional probabilities of most symptoms, although withdrawal, OR = 0.21; unsuccessful quit attempts, OR = 0.04; and higher intake, OR = 0.01, were most likely to persist. Findings indicate hyperarousal may warrant additional intervention following PTSD treatment. Residual AUD symptoms may relate to the enduring nature of some AUD symptoms rather than a lack of treatment efficacy."
0,"TITLE: Prediction of incident hip fracture with the estimated femoral strength by finite element analysis of DXA Scans in the study of osteoporotic fractures.ABSTRACT: A bone fractures only when loaded beyond its strength. The purpose of this study was to determine the association of femoral strength, as estimated by finite element (FE) analysis of dual-energy X-ray absorptiometry (DXA) scans, with incident hip fracture in comparison to hip bone mineral density (BMD), Fracture Risk Assessment Tool (FRAX), and hip structure analysis (HSA) variables. This prospective case-cohort study included a random sample of 1941 women and 668 incident hip fracture cases (295 in the random sample) during a mean ± SD follow-up of 12.8 ± 5.7 years from the Study of Osteoporotic Fractures (n = 7860 community-dwelling women ≥67 years of age). We analyzed the baseline DXA scans (Hologic 1000) of the hip using a validated plane-stress, linear-elastic finite element (FE) model of the proximal femur and estimated the femoral strength during a simulated sideways fall. Cox regression accounting for the case-cohort design assessed the association of estimated femoral strength with hip fracture. The age-body mass index (BMI)-adjusted hazard ratio (HR) per SD decrease for estimated strength (2.21; 95% CI, 1.95-2.50) was greater than that for total hip (TH) BMD (1.86; 95% CI, 1.67-2.08; p < 0.05), FN BMD (2.04; 95% CI, 1.79-2.32; p > 0.05), FRAX scores (range, 1.32-1.68; p < 0.0005), and many HSA variables (range, 1.13-2.43; p < 0.005), and the association was still significant (p < 0.05) after further adjustment for hip BMD or FRAX scores. The association of estimated strength with incident hip fracture was strong (Harrell's C index 0.770), significantly better than TH BMD (0.759; p < 0.05) and FRAX scores (0.711-0.743; p < 0.0001), but not FN BMD (0.762; p > 0.05). Similar findings were obtained for intracapsular and extracapsular fractures. In conclusion, the estimated femoral strength from FE analysis of DXA scans is an independent predictor and performs at least as well as FN BMD in predicting incident hip fracture in postmenopausal women."
1,"TITLE: Mobile vs fixed-bearing total knee arthroplasty performed by a single surgeon: a 4- to 6.5-year randomized, prospective, controlled, double-blinded study.ABSTRACT: The superiority between posterior-stabilized mobile-bearing and fixed-bearing designs still remains controversial. Fifty-six consecutive patients undergoing primary, unilateral knee arthroplasty for osteoarthritis were randomly assigned to receive either a mobile-bearing (29 patients) or fixed-bearing (27 patients) prosthesis. We report the results at 4 to 6.5 years (mean, 5.5) follow-up. The Knee Society knee scores, pain scores, functional scores and Oxford knee scores were not statistically different (P > 0.05) between the two groups. Mean postoperative range-of-motion of mobile-bearing knees was significantly greater than that of fixed-bearing knees (127º versus 111º, P = 0.011). 72% of patients could sit cross legged, 48% could sit on the floor, and 17% could squat. Kaplan-Meier survival rate was 100%. No spin-out of mobile bearing was observed. The radiological analysis showed no osteolysis or implant loosening."
0,"TITLE: The association of gout with sleep disorders: a cross-sectional study in primary care.ABSTRACT: Both gout and sleep apnoea are associated with the metabolic syndrome. Hyperuricaemia is also prevalent in sleep apnoea syndrome. The objective of this study was to examine the association between gout and sleep apnoea and other sleep disorders.Data were taken from a validated database of general practice records from nine practices in the UK between 2001 and 2008. People consulting for gout were identified via Read codes and each matched with four controls for age, gender, practice and year of gout consultation. Sleep problems and confounding comorbidities were also identified via Read codes. Medications were identified through a linked database of prescription records. The association between gout and sleep disorders was assessed using a logistic regression model, adjusting for ischaemic heart disease, hypertension, diabetes mellitus and diuretic use.1689 individuals with gout were identified and each successfully matched to four controls. Amongst those with gout, the prevalence of any sleep problem was 4.9%, sleep problems other than sleep apnoea 4.2%, and sleep apnoea 0.7%, compared to 3.5%, 3.2% and 0.3% respectively in controls. Gout was associated with any sleep problem (odds ratio (OR) 1.44; 95% confidence interval (CI) 1.11, 1.87), sleep problems other than sleep apnoea (OR 1.36; 95% CI 1.03, 1.80), and sleep apnoea (OR 2.10; 95% CI 1.01, 4.39). On multivariable analysis, gout remained significantly associated with any sleep problem (OR 1.39; 95% CI 1.06, 1.81) and sleep problems other than sleep apnoea (OR 1.37; 95% CI 1.03, 1.82), however the association with sleep apnoea was attenuated (OR 1.48, 95% CI 0.70, 3.14).Gout and sleep problems appear to be associated and clinicians should be aware of the co-existence of these two conditions. Larger prospective epidemiological studies are required to explore causality."
1,"TITLE: A randomized clinical trial of the anti-caries efficacy of 5,000 compared to 1,450 ppm fluoridated toothpaste on root caries lesions in elderly disabled nursing home residents.ABSTRACT: Root caries is prevalent in elderly disabled nursing home residents in Denmark. This study aimed to compare the effectiveness of tooth brushing with 5,000 versus 1,450 ppm of fluoridated toothpaste (F-toothpaste) for controlling root caries in nursing home residents. The duration of the study was 8 months. Elderly disabled residents (n = 176) in 6 nursing homes in the Copenhagen area consented to take part in the study. They were randomly assigned to use one of the two toothpastes. Both groups had their teeth brushed twice a day by the nursing staff. A total of 125 residents completed the study. Baseline and follow-up clinical examinations were performed by one calibrated examiner. Texture, contour, location and colour of root caries lesions were used to evaluate lesion activity. No differences (p values >0.16) were noted in the baseline examination with regards to age, mouth dryness, wearing of partial or full dentures in one of the jaws, occurrence of plaque and active (2.61 vs. 2.67; SD, 1.7 vs.1.8) or arrested lesions (0.62 vs. 0.63; SD, 1.7 vs. 1.7) between the 5,000 and the 1,450 ppm fluoride groups, respectively. Mean numbers of active root caries lesions at the follow-up examination were 1.05 (2.76) versus 2.55 (1.91) and mean numbers of arrested caries lesions were 2.13 (1.68) versus 0.61 (1.76) in the 5,000 and the 1,450 ppm fluoride groups, respectively (p < 0.001). To conclude, 5,000 ppm F-toothpaste is significantly more effective for controlling root caries lesion progression and promoting remineralization compared to 1,450 ppm F-toothpaste."
1,"TITLE: Changes in blood pressure and cardiac output during cesarean delivery: the effects of oxytocin and carbetocin compared with placebo.ABSTRACT: Little is known about maternal hemodynamics after Cesarean delivery. Uterine contractions may increase cardiac output. Oxytocin is the first-line treatment for uterine atony, although the effects of the long-acting oxytocin analogue carbetocin are comparable with that of oxytocin. The authors analyzed the effects of i.v. oxytocin 5 U, carbetocin 100 µg, and placebo on hemodynamics, uterine tone, adverse events, and blood loss after Cesarean delivery.This was a randomized, double-blinded, placebo-controlled, parallel-group comparison of carbetocin and oxytocin after elective Cesarean delivery of singletons under spinal anesthesia (n = 76). Continuously measured invasive systolic arterial pressure was the primary outcome measure.The mean systolic arterial pressure decrease was 28 mmHg (95% CI, 22-34) after oxytocin and 26 mmHg (95% CI, 20-31) after carbetocin. The decrease was greatest after 80 (95% CI, 71-89) and 63 s (95% CI, 55-72), respectively (P = 0.006). The differences were nearly undetectable after 2.5 min, although the effect of carbetocin was slightly greater than placebo (P < 0.001). The group differences in systolic arterial pressure decreased over 5 min and were gone at 1 h. Heart rate and cardiac output increased in all three groups. Stroke volume increased after oxytocin and carbetocin but was unchanged after placebo.The hemodynamic side effects of oxytocin 5 U and carbetocin 100 µg were comparable. The lack of an increase in stroke volume in the placebo group challenges the theory that uterine contraction causes autotransfusion of uterine blood, leading to an increase in preload."
1,"TITLE: Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options.ABSTRACT: Patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3 for whom treatment with peginterferon is not an option, or who have not had a response to prior interferon treatment, currently have no approved treatment options. In phase 2 trials, regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection.We conducted two randomized, phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection. In one trial, patients for whom treatment with peginterferon was not an option received oral sofosbuvir and ribavirin (207 patients) or matching placebo (71) for 12 weeks. In a second trial, patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 weeks (103 patients) or 16 weeks (98). The primary end point was a sustained virologic response at 12 weeks after therapy.Among patients for whom treatment with peginterferon was not an option, the rate of a sustained virologic response was 78% (95% confidence interval [CI], 72 to 83) with sofosbuvir and ribavirin, as compared with 0% with placebo (P<0.001). Among previously treated patients, the rate of response was 50% with 12 weeks of treatment, as compared with 73% with 16 weeks of treatment (difference, -23 percentage points; 95% CI, -35 to -11; P<0.001). In both studies, response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection and, among patients with genotype 3 infection, lower among those with cirrhosis than among those without cirrhosis. The most common adverse events were headache, fatigue, nausea, and insomnia; the overall rate of discontinuation of sofosbuvir was low (1 to 2%).In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbuvir and ribavirin was effective. Efficacy was increased among patients with HCV genotype 2 infection and those without cirrhosis. In previously treated patients with genotype 3 infection, 16 weeks of therapy was significantly more effective than 12 weeks. (Funded by Gilead Sciences; POSITRON and FUSION ClinicalTrials.gov numbers, NCT01542788 and NCT01604850, respectively.)."
0,"TITLE: Mucosal IgG4 cell infiltration in ulcerative colitis is linked to disease activity and primary sclerosing cholangitis.ABSTRACT: The distribution of IgG4 plasma cells in colonic mucosa, its significance, and relation to disease activity in patients with inflammatory bowel disease (IBD) is unclear. We systematically evaluated IgG4 cell distribution in colonic mucosal biopsies of patients with IBD and correlated histological findings with disease pattern and mucosal inflammation.We reviewed clinical records and pathology specimens of 54 randomly selected patients with IBD (13 Crohn's colitis: 7 active, 6 inactive; 18 ulcerative colitis [UC]: 10 active, 8 inactive; 23 UC with primary sclerosing cholangitis: 11 active colitis, 12 inactive colitis), and 11 controls (3 nonspecific diarrhea, 8 collagenous/lymphocytic colitis) who had colonoscopy and biopsies performed at our institution from April 2003 to July 2010. Immunostains for IgG4 were performed on archived rectal biopsies. Presence of >10 IgG4 cells per high-power field (×40 field) on microscopic evaluation was considered significant.Overall, significant IgG4 plasma cell infiltration was seen in 24% of patients compared with none of the controls (P = 0.05). Within IBD groups, significant infiltration was limited to patients with UC with active colitis (30%), primary sclerosing cholangitis with inactive (25%) and active (64%) colitis. In contrast, patients with Crohn's colitis, UC with inactive colitis, and controls had rare IgG4 plasma cells. No correlation was observed between the number of IgG4 cells and degree of active inflammation. In 4 patients with UC and primary sclerosing cholangitis who had more than 1 colonoscopy and biopsies, the number of IgG4 cells fluctuated without correlation with colonic disease activity.IgG4 plasma cells are significantly increased in a subset of patients with IBD suggesting the possibility of a B-cell-mediated mechanism in these patients."
1,"TITLE: Echocardiographic assessment of cardiac valvular regurgitation with lorcaserin from analysis of 3 phase 3 clinical trials.ABSTRACT: Lorcaserin is a selective 5-HT2C agonist evaluated for weight management in clinical trials. Echocardiographic monitoring was conducted to test the hypothesis that selective 5-HT2C agonism would avoid valvular heart disease.Echocardiographic and weight change data from 5249 obese and overweight patients in 3 phase 3 trials were integrated. Treatment duration with 10 mg lorcaserin twice daily or placebo was 52 weeks. The proportions of patients who developed Food and Drug Administration-defined valvulopathy (≥ mild aortic or ≥ moderate mitral regurgitation) and changes in regurgitant grade at each heart valve were evaluated. Possible associations between weight or body mass index change and valvulopathy were explored. New valvulopathy was present in 2.04% of placebo and 2.37% of lorcaserin recipients at 52 weeks (risk difference, 0.33%; 95% confidence interval, -0.46 to 1.13; risk ratio, 1.16 [all patients with sufficient echocardiographic data, last-observation-carried-forward imputation] or 1.03 [patients who completed 52 weeks]). Changes in weight and body mass index were negatively associated with presence of valvulopathy at week 52 (P=0.02 and P=0.04, respectively); a 5% decrease in weight was associated with an odds ratio of 1.15 for Food and Drug Administration-defined valvulopathy. Most changes in regurgitation were ±1 grade in both treatment groups at all heart valves.In 3 prospective placebo-controlled trials with integrated data for 5249 patients, the rate of echocardiographic valvulopathy was similar with lorcaserin and placebo. Point estimates for risk ratios ranged from 1.03 to 1.16 and may be at least partially influenced by greater weight loss in the lorcaserin group than in the placebo group.URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00395135, NCT00603291, NCT00603902."
0,"TITLE: Axial elongation following cataract surgery during the first year of life in the infant Aphakia Treatment Study.ABSTRACT: To compare ocular axial elongation in infants after unilateral cataract surgery corrected with a contact lens (CL) or primary intraocular lens (IOL) implantation.Baseline axial length (AL) was measured at the time of cataract surgery (1-6 months) and at age 1 year. AL at baseline and age 1 year and the change in length/mo were analyzed in relation to treatment modality, cataractous versus fellow eye, and age at surgery using linear mixed models.Mean baseline AL did not differ between the CL and IOL groups for either cataractous or fellow eyes. Eyes with cataracts were shorter than fellow eyes by an average of 0.6 mm (95% confidence interval [CI], 0.4-0.8 mm; P < 0.0001). For the operated eyes, the mean change in AL/mo was smaller in the CL group (0.17 mm/mo) than in the IOL group (0.24 mm/mo) (P = 0.0006) and was independent of age at surgery (P = 0.19). In contrast, the change in AL/mo for fellow eyes decreased with older age at surgery (P < 0.0001). At age 1 year, operated eyes treated with a CL were 0.6 mm shorter on average than operated eyes treated with an IOL (P = 0.009).At baseline, eyes with cataracts were shorter than fellow eyes. The change in AL/mo was smaller in operated eyes treated with a CL than in operated eyes treated with an IOL, but was not significantly related to age at surgery. (ClinicalTrials.gov number, NCT00212134.)."
1,"TITLE: A prospective randomized multicenter comparison of balloon angioplasty and infrapopliteal stenting with the sirolimus-eluting stent in patients with ischemic peripheral arterial disease: 1-year results from the ACHILLES trial.ABSTRACT: The study investigated the efficacy and safety of a balloon expandable, sirolimus-eluting stent (SES) in patients with symptomatic infrapopliteal arterial disease.Results of infrapopliteal interventions using balloon angioplasty and/or bare stents are limited by a relatively high restenosis rate, which could be potentially improved by stabilizing the lesion with a SES.Two hundred patients (total lesion length 27 ± 21 mm) were randomized to infrapopliteal SES stenting or percutaneous transluminal balloon angioplasty (PTA). The primary endpoint was 1-year in-segment binary restenosis by quantitative angiography.Ninety-nine and 101 patients (mean age 73.4 years; 64% diabetics) were randomized to SES and PTA, respectively (8 crossover bailout cases to SES). At 1 year, there were lower angiographic restenosis rates (22.4% vs. 41.9%, p = 0.019), greater vessel patency (75.0% vs. 57.1%, p =0.025), and similar death, repeat revascularization, index-limb amputation rates, and proportions of patients with improved Rutherford class for SES versus PTA.SES implantation may offer a promising therapeutic alternative to PTA for treatment of infrapopliteal peripheral arterial disease."
0,"TITLE: Growth response to growth hormone treatment in patients with SHOX deficiency can be predicted by the Cologne prediction model.ABSTRACT: Background Growth hormone (GH) treatment in children with short stature homeobox-containing gene (SHOX) deficiency is recognized to increase height velocity (HV) and adult height. Prediction of growth response continues to be a challenge. A comparatively accurate method is the Cologne prediction model developed in children with GH deficiency. The aim was to investigate whether this model also applies to patients with SHOX deficiency. Methods Included were 48 patients with SHOX deficiency confirmed by DNA analysis and treated with 0.05 mg/kg/day of somatropin. Prediction by the Cologne model uses the following variables: relative bone age (BA) retardation, baseline insulin-like growth factor-I (IGF-I), urinary deoxypyridinoline (DPD) cross-links at 4 weeks and HV at 3 months. Results HV and height standard deviation scores (SDS) increased significantly during the first year of treatment. Predicted and observed HV (cm/year) showed a Pearson correlation coefficient of 0.50 (p<0.001; root-mean-square error=1.63) and for first-year change in height SDS a Pearson correlation coefficient of 0.751 (p<0.001; root-mean-square error=0.32). Poor response could be adequately predicted using SDS change, with sensitivity and specificity both above 70% for certain thresholds.The results demonstrate that the Cologne model can be used to predict growth response in patients with SHOX deficiency with reasonable precision in the first treatment year, comparable to prediction in patients with GH deficiency."
1,"TITLE: A randomised trial of hypertonic saline during hospitalisation for exacerbation of cystic fibrosis.ABSTRACT: The mucoactive effects of hypertonic saline should promote exacerbation resolution in people with cystic fibrosis (CF).To determine the effects of hypertonic saline inhalation during hospitalisation for exacerbation of CF on length of stay, lung function, symptoms, oxygenation, exercise tolerance, quality of life, bacterial load and time to next hospitalisation.132 adults with an exacerbation of CF were randomised to inhale three nebulised doses a day of either 4 mL 7% saline or a taste-masked control of 0.12% saline, throughout the hospital admission. The primary outcome measure was length of hospital stay.All participants tolerated their allocated saline solution. There was no significant difference in length of stay, which was 12 days in the hypertonic saline group and 13 days in controls, with a mean between-group difference (MD) of 1 day (95% CI 0 to 2). The likelihood of regaining pre-exacerbation FEV1 by discharge was significantly higher in the hypertonic saline group (75% vs 57%), and the number needed to treat was 6 (95% CI 3 to 65). On a 0-100 scale, the hypertonic saline group had significantly greater reduction in symptom severity than the control group at discharge in sleep (MD=13, 95% CI 4 to 23), congestion (MD=10, 95% CI 3 to 18) and dyspnoea (MD=8, 95% CI 1 to 16). No significant difference in time to next hospitalisation for a pulmonary exacerbation was detected between groups (HR=0.86 (CI 0.57 to 1.30), p=0.13). Other outcomes did not significantly differ.Addition of hypertonic saline to the management of a CF exacerbation did not reduce the length of hospital stay. Hypertonic saline speeds the resolution of exacerbation symptoms and allows patients to leave hospital with greater symptom resolution.ACTRN12605000780651."
1,"TITLE: Argon Laser Peripheral Iridoplasty for Primary Angle-Closure Glaucoma: A Randomized Controlled Trial.ABSTRACT: To determine the effectiveness of argon laser peripheral iridoplasty (ALPI) in primary angle closure (PAC) and primary angle-closure glaucoma (PACG).Randomized controlled trial.Eighty PAC or PACG subjects who underwent laser iridotomy (LI) and had at least 180° of persistent appositional angle closure and intraocular pressure (IOP) of more than 21 mmHg were enrolled.Subjects were randomized to receive either 360° ALPI (Visulas 532s; Carl Zeiss Meditec, Jena, Germany) or medical therapy (Travoprost 0.004%; Alcon-Couvreur, Puurs, Antwerp, Belgium). Repeat ALPI was performed if the IOP reduction was less than 20% from baseline along with inadequate angle widening at the month 1 or month 3 visit. Intraocular pressure was controlled with systematic addition of medications when required.The primary outcome measure was success rates after ALPI at 1 year. Complete success was defined as an IOP of 21 mmHg or less without medication, and qualified success was defined as an IOP of 21 mmHg or less with medication. Failure was defined as an IOP more than 21 mmHg despite additional medications or requiring glaucoma surgery.Forty subjects (51 eyes) were randomized to ALPI and 40 subjects (55 eyes) were randomized to medical therapy. Complete success (IOP ≤21 mmHg without medication) was achieved in 35.0% eyes of the ALPI group compared with 85.0% of eyes in the prostaglandin analog (PGA) group (P < 0.001), and qualified success (IOP ≤21 mmHg with medication) was achieved in 35.0% and 7.5%, respectively (P = 0.003). The IOP decreased by 4.9 mmHg (95% confidence interval [CI], 3.5-6.3 mmHg) in the ALPI group (P < 0.001) and by 6.1 mmHg (95% CI, 5.1-7.1 mmHg) in the medication group (P < 0.001). A failure rate of 30.0% was noted in the ALPI group compared with 7.5% in the medication group (P = 0.01). No treatment-related complications were recorded in either group.After 1 year, ALPI was associated with higher failure rates and lower IOP reduction compared with PGA therapy in eyes with persistent appositional angle closure and raised IOP after LI."
1,"TITLE: No significant difference in clinical outcome and knee stability between patellar tendon and semitendinosus tendon in anterior cruciate ligament reconstruction.ABSTRACT: ACL reconstruction with either patellar tendon or semitendinosus tendon autografts are standard procedures. Between these two grafts might be differences in stability, morbidity, or long-term changes. This study investigates outcomes of ACL reconstruction with patellar tendon versus semitendinosus tendon autografts. We hypothesize no significant differences in clinical outcome and knee stability between both groups.In a randomized prospective trial, we operated 62 ACL-deficient patients, 45 males and 17 females with a mean age of 29.8 years (min. 18, max. 44). We reconstructed the ligament using either autologous patellar tendon (n = 31) or semitendinosus tendon (n = 31). After 10 years of follow-up, we investigated 47 patients of the study. For evaluation we used a standard clinical examination including one-leg jump test and KT-1000 instrumental translation measure, visual analog pain scale, IKDC subjective knee form, Lysholm score, Tegner activity scale, and standard X-rays of the knee.The data did not show any significant differences between the two groups. Between 5 and 10 years after ACL reconstruction both groups started to develop degenerative arthritic changes, which were detectable in standard radiographs of the knee. At 10-year follow-up mean IKDC for the BPTB group was 1.8 (min. 1, max. 3) and for the ST group it was 2.2 (min 1, max. 4), p = 0.35. Regarding Tegner activity scale after 10 years, the BPTB group showed a mean score of 5.9 (min. 4, max. 9) versus 5.1 (min. 3, max. 7) in the ST group, p = 0.53. For the Lysholm score the BPTB group reached a mean of 92.0 (min. 63, max. 98) and the ST group 91.8 (min. 62, max. 98) points, p = 0.66. There is a tendency for higher donor site morbidity in the BPTB group than in the ST group, p = 0.07.Both, patellar tendon and semitendinosus tendon are safe autografts for ACL reconstruction. Regarding graft selection, individual patient-dependent factors should be considered. ACL reconstruction cannot fully restore pre-injury status of knee joint function in the majority of cases."
1,"TITLE: Acupuncture for Menopausal Hot Flashes: A Randomized Trial.ABSTRACT: Hot flashes (HFs) affect up to 75% of menopausal women and pose a considerable health and financial burden. Evidence of acupuncture efficacy as an HF treatment is conflicting.To assess the efficacy of Chinese medicine acupuncture against sham acupuncture for menopausal HFs.Stratified, blind (participants, outcome assessors, and investigators, but not treating acupuncturists), parallel, randomized, sham-controlled trial with equal allocation. (Australia New Zealand Clinical Trials Registry: ACTRN12611000393954).Community in Australia.Women older than 40 years in the late menopausal transition or postmenopause with at least 7 moderate HFs daily, meeting criteria for Chinese medicine diagnosis of kidney yin deficiency.10 treatments over 8 weeks of either standardized Chinese medicine needle acupuncture designed to treat kidney yin deficiency or noninsertive sham acupuncture.The primary outcome was HF score at the end of treatment. Secondary outcomes included quality of life, anxiety, depression, and adverse events. Participants were assessed at 4 weeks, the end of treatment, and then 3 and 6 months after the end of treatment. Intention-to-treat analysis was conducted with linear mixed-effects models.327 women were randomly assigned to acupuncture (n = 163) or sham acupuncture (n = 164). At the end of treatment, 16% of participants in the acupuncture group and 13% in the sham group were lost to follow-up. Mean HF scores at the end of treatment were 15.36 in the acupuncture group and 15.04 in the sham group (mean difference, 0.33 [95% CI, -1.87 to 2.52]; P = 0.77). No serious adverse events were reported.Participants were predominantly Caucasian and did not have breast cancer or surgical menopause.Chinese medicine acupuncture was not superior to noninsertive sham acupuncture for women with moderately severe menopausal HFs.National Health and Medical Research Council."
1,"TITLE: Shortened Antimicrobial Treatment for Acute Otitis Media in Young Children.ABSTRACT: Limiting the duration of antimicrobial treatment constitutes a potential strategy to reduce the risk of antimicrobial resistance among children with acute otitis media.We assigned 520 children, 6 to 23 months of age, with acute otitis media to receive amoxicillin-clavulanate either for a standard duration of 10 days or for a reduced duration of 5 days followed by placebo for 5 days. We measured rates of clinical response (in a systematic fashion, on the basis of signs and symptomatic response), recurrence, and nasopharyngeal colonization, and we analyzed episode outcomes using a noninferiority approach. Symptom scores ranged from 0 to 14, with higher numbers indicating more severe symptoms.Children who were treated with amoxicillin-clavulanate for 5 days were more likely than those who were treated for 10 days to have clinical failure (77 of 229 children [34%] vs. 39 of 238 [16%]; difference, 17 percentage points [based on unrounded data]; 95% confidence interval, 9 to 25). The mean symptom scores over the period from day 6 to day 14 were 1.61 in the 5-day group and 1.34 in the 10-day group (P=0.07); the mean scores at the day-12-to-14 assessment were 1.89 versus 1.20 (P=0.001). The percentage of children whose symptom scores decreased more than 50% (indicating less severe symptoms) from baseline to the end of treatment was lower in the 5-day group than in the 10-day group (181 of 227 children [80%] vs. 211 of 233 [91%], P=0.003). We found no significant between-group differences in rates of recurrence, adverse events, or nasopharyngeal colonization with penicillin-nonsusceptible pathogens. Clinical-failure rates were greater among children who had been exposed to three or more children for 10 or more hours per week than among those with less exposure (P=0.02) and were also greater among children with infection in both ears than among those with infection in one ear (P<0.001).Among children 6 to 23 months of age with acute otitis media, reduced-duration antimicrobial treatment resulted in less favorable outcomes than standard-duration treatment; in addition, neither the rate of adverse events nor the rate of emergence of antimicrobial resistance was lower with the shorter regimen. (Funded by the National Institute of Allergy and Infectious Diseases and the National Center for Research Resources; ClinicalTrials.gov number, NCT01511107 .)."
1,"TITLE: Randomized clinical trial of 24 versus 72 h antimicrobial prophylaxis in patients undergoing open total gastrectomy for gastric cancer.ABSTRACT: Open total gastrectomy carries a high risk of surgical-site infection (SSI). This study evaluated the non-inferiority of antimicrobial prophylaxis for 24 compared with 72 h after open total gastrectomy.An open-label, randomized, non-inferiority study was conducted at 57 institutions in Japan. Eligible patients were those who underwent open total gastrectomy for gastric cancer. Patients were assigned randomly to continued use of β-lactamase inhibitor for either 24 or 72 h after surgery. The primary endpoint was the incidence of SSI, with non-inferiority based on a margin of 9 percentage points and a 90 per cent c.i. The secondary endpoint was the incidence of remote infection.A total of 464 patients (24 h prophylaxis, 228; 72 h prophylaxis, 236) were analysed. SSI occurred in 20 patients (8·8 per cent) in the 24-h prophylaxis group and 26 (11·0 per cent) in the 72-h group (absolute difference -2·2 (90 per cent c.i. -6·8 to 2·4) per cent; P < 0·001 for non-inferiority). However, the incidence of remote infection was significantly higher in the 24-h prophylaxis group.Antimicrobial prophylaxis for 24 h after total gastrectomy is not inferior to 72 h prophylaxis for prevention of SSI. Shortened antimicrobial prophylaxis might increase the incidence of remote infection. Registration number: UMIN000001062 ( http://www.umin.ac.jp)."
1,"TITLE: Buparlisib and paclitaxel in patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck (BERIL-1): a randomised, double-blind, placebo-controlled phase 2 trial.ABSTRACT: Phosphatidylinositol 3-kinase (PI3K) pathway activation in squamous cell carcinoma of the head and neck contributes to treatment resistance and disease progression. Buparlisib, a pan-PI3K inhibitor, has shown preclinical antitumour activity and objective responses in patients with epithelial malignancies. We assessed whether the addition of buparlisib to paclitaxel improves clinical outcomes compared with paclitaxel and placebo in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.In this multicentre, randomised, double-blind, placebo-controlled phase 2 study (BERIL-1), we recruited patients aged 18 years and older with histologically or cytologically confirmed recurrent and metastatic squamous cell carcinoma of the head and neck after disease progression on or after one previous platinum-based chemotherapy regimen in the metastatic setting. Eligible patients were enrolled from 58 centres across 18 countries and randomly assigned (1:1) to receive second-line oral buparlisib (100 mg once daily) or placebo, plus intravenous paclitaxel (80 mg/m on days 1, 8, 15, and 22) in 28 day treatment cycles. Randomisation was done via a central patient screening and randomisation system with an interactive (voice and web) response system and stratification by number of previous lines of therapy in the recurrent and metastatic setting and study site. Patients and investigators (including local radiologists) were masked to treatment assignment from randomisation until the final overall survival analysis. The primary endpoint was progression-free survival by local investigator assessment per Response Evaluation Criteria In Solid Tumors (version 1.1) in all randomly assigned patients. Efficacy analyses were done on the intention-to-treat population, whereas safety was analysed in all patients who received at least one dose of study drug and had at least one post-baseline safety assessment according to the treatment they received. This trial is registered with ClinicalTrials.gov, number NCT01852292, and is ongoing but no longer enrolling patients.Between Nov 5, 2013, and May 5, 2015, 158 patients were enrolled and randomly assigned to receive either buparlisib plus paclitaxel (n=79) or placebo plus paclitaxel (n=79). Median progression-free survival was 4·6 months (95% CI 3·5-5·3) in the buparlisib group and 3·5 months (2·2-3·7) in the placebo group (hazard ratio 0·65 [95% CI 0·45-0·95], nominal one-sided p=0·011). Grade 3-4 adverse events were reported in 62 (82%) of 76 patients in the buparlisib group and 56 (72%) of 78 patients in the placebo group. The most common grade 3-4 adverse events (occurring in ≥10% of patients in the buparlisib group vs the placebo group) were hyperglycaemia (17 [22%] of 76 vs two [3%] of 78), anaemia (14 [18%] vs nine [12%]), neutropenia (13 [17%] vs four [5%]), and fatigue (six [8%] vs eight [10%]). Serious adverse events (regardless of relation to study treatment) were reported for 43 (57%) of 76 patients in the buparlisib group and 37 (47%) of 78 in the placebo group. On-treatment deaths occurred in 15 (20%) of 76 patients in the buparlisib group and 17 (22%) of 78 patients in the placebo group; most were caused by disease progression and none were judged to be related to study treatment.On the basis of the improved clinical efficacy with a manageable safety profile, the results of this randomised phase 2 study suggest that buparlisib in combination with paclitaxel could be an effective second-line treatment for patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck. Further phase 3 studies are warranted to confirm this phase 2 finding.Novartis Pharmaceuticals Corporation."
1,"TITLE: Phone-based intervention for blood pressure control among Ghanaian stroke survivors: A pilot randomized controlled trial.ABSTRACT: The potential of mobile-health (mHealth) technology for the management of hypertension among stroke survivors in Africa remains unexplored. We assessed whether an mHealth technology-enabled, nurse-guided intervention initiated among stroke patients within one month of symptom onset is effective in improving their blood pressure (BP) control.A two-arm pilot cluster randomized controlled trial involving 60 stroke survivors, ≥18 years, with BP ≥140/90 mmHg at screening/enrollment visit at a medical center in Ghana. Participants in the intervention arm (n = 30) received a Blue-toothed BP device and smartphone with an App for monitoring BP measurements and medication intake under nurse guidance for three months after which intervention was withdrawn. Control arm (n = 30) received usual care. Primary outcome measure was proportion with clinic BP < 140/90 mmHg at month 9; secondary outcomes included medication adherence.Mean ± SD age was 55 ± 13 years, 65% males. Two participants on intervention and three in control group were lost to follow-up. At month 9, proportion on the intervention versus controls with BP < 140/90 mmHg was 14/30 (46.7%) versus 12/30 (40.0%), p = 0.79 by intention-to-treat; systolic BP < 140 mmHg was 22/30 (73.3%) versus 13/30 (43.3%), p = 0.035. Mean ± SD medication possession ratio was 0.95 ± 0.16 on intervention versus 0.98 ± 0.24 in the control arm, p = 0.56.We demonstrate feasibility and signal of improvement in BP control among stroke survivors in a resource-limited setting via an mHealth intervention. Larger scale studies are warranted.NCT02568137. Registered on 13 July 2015 at ClinicalTrials.gov."
0,"TITLE: Fibroblast growth factor 21 as a circulating biomarker at various stages of colorectal carcinogenesis.ABSTRACT: Despite evidence that inflammation and metabolism play a crucial role in colorectal carcinogenesis, there have been few studies on the association of inflammatory and metabolic protein biomarkers in various stages of colorectal carcinogenesis.Ninety-two inflammatory and metabolic biomarkers were measured in plasma samples of participants of screening colonoscopy. Markers identified to be significantly associated with the presence of advanced colorectal neoplasia (ACN) in a discovery set (n = 204) were validated in an independent replication set (n = 422). Adjusted associations with the presence of non-advanced adenomas (NAA), advanced precancerous lesions (APL) and colorectal cancer (CRC) were quantified by multiple logistic regression.Out of the 92 inflammatory proteins, 72 markers were evaluable and 8 showed statistically significant associations with the odds of ACN after full adjustment for potential risk factors for CRC in the discovery set. One of these, fibroblast growth factor 21 (FGF-21), could be validated in the replication set. The multivariable-adjusted odds ratio (OR) reached 2.65 (95% CI, 1.50-4.81) for individuals with FGF-21 levels within the highest tertile, compared to those within the lowest tertile (P across tertiles = 0.001). Separate models revealed fully adjusted ORs for NAA, APL and CRC of 2.99 (95% CI, 1.45-6.58, P = 0.005), 2.24 (95% CI, 1.18-4.44, P = 0.021) and 3.92 (95% CI, 1.51-12.18, P = 0.003), respectively.Circulating FGF-21 level is associated with increased risk of early and late stages of colorectal carcinogenesis, supporting a role of inflammation and metabolism at all stages of colorectal carcinogenesis, and suggesting potential use of this biomarker for risk stratification in CRC screening."
1,"TITLE: Long-Term Effects of Intensive Glycemic and Blood Pressure Control and Fenofibrate Use on Kidney Outcomes.ABSTRACT: In people with type 2 diabetes, aggressive control of glycemia, BP, and lipids have resulted in conflicting short-term (<5 years) kidney outcomes. We aimed to determine the long-term kidney effects of these interventions.The Action to Control Cardiovascular Risk in Diabetes (ACCORD) was a multifactorial intervention study in people with type 2 diabetes at high risk for cardiovascular disease (=10,251), to examine the effects of intensive glycemic control (hemoglobin A1c <6.0% versus 7%-7.9%), BP control (systolic BP <120 mm Hg versus <140 mm Hg) or fenofibrate versus placebo added to simvastatin on cardiovascular events and death. The glycemia trial lasted 3.7 years and participants were followed for another 6.5 years in ACCORDION, the ACCORD Follow-On Study. The  primary composite kidney outcome was defined as incident macroalbuminuria, creatinine doubling, need for dialysis, or death by any cause. Cox proportional hazards regression estimated the effect of each intervention on the composite outcome and individual components. In secondary outcome analyses, competing risk regression was used to account for the risk of death in incident kidney outcomes. Analyses were adjusted for sociodemographics, randomization groups, and clinical factors.There were 988 cases of incident macroalbuminuria, 954 with doubling of creatinine, 351 requiring dialysis, and 1905 deaths. Hazard ratios (HRs) for the composite outcome with intensive glycemic, BP control, and fenofibrate use compared with standard therapy were 0.92 (95% confidence interval [95% CI], 0.86 to 0.98), 1.16 (95% CI, 1.05 to 1.28), and 1.16 (95% CI, 1.06 to 1.27). Multivariable, secondary outcome analyses showed that in the glycemia trial, only macroalbuminuria was significantly decreased (HR, 0.68; 95% CI, 0.59 to 0.77). In the BP and lipid trials, only creatinine doubling was affected (HR, 1.64; 95% CI, 1.30 to 2.06 and HR, 2.00; 95% CI, 1.61 to 2.49, respectively).In people with type 2 diabetes at high risk for cardiovascular disease, intensive glycemic control may result in a long-term reduction in macroalbuminuria; however, intensive BP control and fenofibrates may increase the risk for adverse kidney events."
1,"TITLE: Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: a multi-stage, randomised, double-blind, placebo-controlled trial.ABSTRACT: Glutamate excitotoxicity might contribute to the pathophysiology of amyotrophic lateral sclerosis. In animal models, decreased excitatory aminoacid transporter 2 (EAAT2) overexpression delays disease onset and prolongs survival, and ceftriaxone increases EAAT2 activity. We aimed to assess the safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis in a combined phase 1, 2, and 3 clinical trial.This three-stage randomised, double-blind, placebo-controlled study was done at 59 clinical sites in the USA and Canada between Sept 4, 2006, and July 30, 2012. Eligible adult patients had amyotrophic lateral sclerosis, a vital capacity of more than 60% of that predicted for age and height, and symptom duration of less than 3 years. In stages 1 (pharmacokinetics) and 2 (safety), participants were randomly allocated (2:1) to ceftriaxone (2 g or 4 g per day) or placebo. In stage 3 (efficacy), participants assigned to ceftriaxone in stage 2 received 4 g ceftriaxone, participants assigned to placebo in stage 2 received placebo, and new participants were randomly assigned (2:1) to 4 g ceftriaxone or placebo. Participants, family members, and site staff were masked to treatment assignment. Randomisation was done by a computerised randomisation sequence with permuted blocks of 3. Participants received 2 g ceftriaxone or placebo twice daily through a central venous catheter administered at home by a trained caregiver. To minimise biliary side-effects, participants assigned to ceftriaxone also received 300 mg ursodeoxycholic acid twice daily and those assigned to placebo received matched placebo capsules. The coprimary efficacy outcomes were survival and functional decline, measured as the slope of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00349622.Stage 3 included 66 participants from stages 1 and 2 and 448 new participants. In total, 340 participants were randomly allocated to ceftriaxone and 173 to placebo. During stages 1 and 2, mean ALSFRS-R declined more slowly in participants who received 4 g ceftriaxone than in those on placebo (difference 0·51 units per month, 95% CI 0·02 to 1·00; p=0·0416), but in stage 3 functional decline between the treatment groups did not differ (0·09, -0·06 to 0·24; p=0·2370). No significant differences in survival between the groups were recorded in stage 3 (HR 0·90, 95% CI 0·71 to 1·15; p=0·4146). Gastrointestinal adverse events and hepatobiliary adverse events were more common in the ceftriaxone group than in the placebo group (gastrointestinal, 245 of 340 [72%] ceftriaxone vs 97 of 173 [56%] placebo, p=0·0004; hepatobiliary, 211 [62%] vs 19 [11%], p<0·0001). Significantly more participants who received ceftriaxone had serious hepatobiliary serious adverse events (41 participants [12%]) than did those who received placebo (0 participants).Despite promising stage 2 data, stage 3 of this trial of ceftriaxone in amyotrophic lateral sclerosis did not show clinical efficacy. The adaptive design allowed for seamless transition from one phase to another, and central venous catheter use in the home setting was shown to be feasible.National Institute of Neurological Disorders and Stroke."
1,"TITLE: Propofol sedation with bispectral index monitoring is useful for endoscopic submucosal dissection: a randomized prospective phase II clinical trial.ABSTRACT: Endoscopic submucosal dissection (ESD) has become a standard treatment. However, the treatment time tends to be relatively long and insufflation and manipulation of the endoscope can increase pain and discomfort. We aimed to find an optimal method for sedation during ESD.Patients scheduled to undergo ESD for early gastric cancer or adenoma were randomly assigned to sedation with midazolam or propofol, and consciousness level was evaluated by bispectral index (BIS) monitoring. Primary end points of effectiveness (three parameters) and secondary end points of safety during ESD and after return to the ward were compared between the groups. Study registration was in the UMIN Clinical Trial Registry (UMIN 000001497), and the institutional trial number was KDOG 0801.From June 2008 through June 2009, we enrolled 178 patients (90 midazolam, 88 propofol). Regarding safety after ESD, recovery was significantly better in the propofol group immediately after and at 1 hour and 2 hours after return to the ward (P < 0.001). The number of patients who required a continuous supply of oxygen 2 hours after returning to the ward was significantly lower in the propofol group (midazolam 18; propofol 6; P = 0.010). Though propofol seemed to be better for effectiveness and safety, there were no statistically significant differences for all three primary end points and the safety parameters (hypotension, hypoxia, bradycardia).Propofol with BIS monitoring improved recovery of patients after ESD, though this study was underpowered to prove the effectiveness and safety of propofol."
1,"TITLE: Effectiveness of body wipes as an adjunct to reducing skin infections in high school wrestlers.ABSTRACT: To compare soap-and-water body wipes and 70% isopropyl alcohol (IPA) body wipes to a CONTROL (no treatment) in reducing skin infections in high school wrestlers competing in weekend tournaments.Repeated measures study evaluating a soap-and-water body wipe, a 70% IPA body wipe, and no-treatment CONTROL during 2 weekend tournaments.High school wrestling tournaments in Minneapolis-St Paul and surrounding communities of Minnesota.Each team was randomly assigned to use either wipe or serve as CONTROL during each tournament.Presence of skin infections that developed the following week after a weekend tournament.A total of 151 athletes competed in a total of 474 individual matches. Thirteen athletes tested positive afterward for skin infections. The odds of infection for the tested group compared with the CONTROL group were 0.089 [95% confidence interval (CI), 0.01-0.75; P = 0.026] for the soap-and-water group and 0.44 (95% CI, 0.11-1.69; P = 0.23) for 70% IPA group.Soap-and-water wipes seem to be more effective in reducing skin infections compared with the no-treatment group."
1,"TITLE: Randomized Teriparatide [human parathyroid hormone (PTH) 1-34] Once-Weekly Efficacy Research (TOWER) trial for examining the reduction in new vertebral fractures in subjects with primary osteoporosis and high fracture risk.ABSTRACT: Weekly teriparatide injection at a dose of 56.5 μg has been shown to increase bone mineral density.A phase 3 study was conducted to determine the efficacy of once-weekly teriparatide injection for reducing the incidence of vertebral fractures in patients with osteoporosis.In this randomized, multicenter, double-blind, placebo-controlled trial conducted in Japan, the incidence of morphological vertebral fractures by radiographs was assessed.Subjects were 578 Japanese patients between the ages of 65 and 95 yr who had prevalent vertebral fracture.Subjects were randomly assigned to receive once-weekly s.c. injections of teriparatide (56.5 μg) or placebo for 72 wk.The primary endpoint was the incidence of new vertebral fracture.Once-weekly injections of teriparatide reduced the risk of new vertebral fracture with a cumulative incidence of 3.1% in the teriparatide group, compared with 14.5% in the placebo group (P < 0.01), and a relative risk of 0.20 (95% confidence interval, 0.09 to 0.45). At 72 wk, teriparatide administration increased bone mineral density by 6.4, 3.0, and 2.3% at the lumbar spine, the total hip, and the femoral neck, respectively, compared with the placebo (P < 0.01). Adverse events (AE) and the dropout rates by AE were more frequently experienced in the teriparatide group, but AE were generally mild and tolerable.Weekly s.c. administration of teriparatide at a dose of 56.5 μg may provide another option of anabolic treatments in patients with osteoporosis at higher fracture risk."
1,"TITLE: Effect of adenosine-regulating agent acadesine on morbidity and mortality associated with coronary artery bypass grafting: the RED-CABG randomized controlled trial.ABSTRACT: Ischemia/reperfusion injury remains an important cause of morbidity and mortality after coronary artery bypass graft (CABG) surgery. In a meta-analysis of randomized controlled trials, perioperative and postoperative infusion of acadesine, a first-in-class adenosine-regulating agent, was associated with a reduction in early cardiac death, myocardial infarction, and combined adverse cardiac outcomes in participants undergoing on-pump CABG surgery.To assess the efficacy and safety of acadesine administered in the perioperative period in reducing all-cause mortality, nonfatal stroke, and severe left ventricular dysfunction (SLVD) through 28 days.The Reduction in Cardiovascular Events by Acadesine in Patients Undergoing CABG (RED-CABG) trial, a randomized, double-blind, placebo-controlled, parallel-group evaluation of intermediate- to high-risk patients (median age, 66 years) undergoing nonemergency, on-pump CABG surgery at 300 sites in 7 countries. Enrollment occurred from May 6, 2009, to July 30, 2010.Eligible participants were randomized 1:1 to receive acadesine (0.1 mg/kg per minute for 7 hours) or placebo (both also added to cardioplegic solutions) beginning just before anesthesia induction.Composite of all-cause mortality, nonfatal stroke, or need for mechanical support for SLVD during and following CABG surgery through postoperative day 28.Because results of a prespecified futility analysis indicated a very low likelihood of a statistically significant efficacious outcome, the trial was stopped after 3080 of the originally projected 7500 study participants were randomized. The primary outcome occurred in 75 of 1493 participants (5.0%) in the placebo group and 76 of 1493 (5.1%) in the acadesine group (odds ratio, 1.01 [95% CI, 0.73-1.41]). There were no differences in key secondary end points measured.In this population of intermediate- to high-risk patients undergoing CABG surgery, acadesine did not reduce the composite of all-cause mortality, nonfatal stroke, or SLVD.clinicaltrials.gov Identifier: NCT00872001."
1,"TITLE: Effect of intervention on decision making of treatment for disease progression, prostate-specific antigen biochemical failure and prostate cancer death.ABSTRACT: Patient preference for the choice of treatment modality for prostate cancer has increasingly gained attention.To assess the impact of client-oriented decision on long-term mortality, disease progression and biochemical failure compared with standard treatment protocol (TP).With data from a Finnish multicentre, randomized controlled trial with two arms [104 in the enhanced patient participation (EPP) arm and 106 in the TP arm], disease-specific and disease-free survival, biochemical failure with elevated prostate-specific antigen (PSA) level and disease progression were compared between the two arms using Wilcoxon test and also Cox proportional hazards regression model.Patients in the EPP arm had a higher risk of death by 37% [HR, 1.37 (0.87-2.17)] compared with those in the TP arm. Patients in the EPP arm were at increased risk of having biochemical failure by 14% [HR, 1.14 (0.72-1.79)] and for having disease progression by 2% [HR, 1.02 (0.61-1.70)] compared with those in the TP arm. All the differences were non-significant.Patients actively involved in the choice of treatment had higher risk of prostate cancer death but only slightly increased risk of biochemical failure and clinical disease progression. These findings would provide a good reference when patient autonomy for the choice of treatment modality is addressed."
1,"TITLE: Effects of hydroxychloroquine on immune activation and disease progression among HIV-infected patients not receiving antiretroviral therapy: a randomized controlled trial.ABSTRACT: Therapies to decrease immune activation might be of benefit in slowing HIV disease progression.To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline.Randomized, double-blind, placebo-controlled trial performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/μL.Hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks.The primary outcome measure was change in the proportion of activated CD8 cells (measured by the expression of CD38 and HLA-DR surface markers), with CD4 cell count and HIV viral load as secondary outcomes. Analysis was by intention to treat using mixed linear models.There was no significant difference in CD8 cell activation between the 2 groups (-4.8% and -4.2% in the hydroxychloroquine and placebo groups, respectively, at week 48; difference, -0.6%; 95% CI, -4.8% to 3.6%; P = .80). Decline in CD4 cell count was greater in the hydroxychloroquine than placebo group (-85 cells/μL vs -23 cells/μL at week 48; difference, -62 cells/μL; 95% CI, -115 to -8; P = .03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log10 copies/mL vs 0.23 log10 copies/mL at week 48; difference, 0.38 log10 copies/mL; 95% CI, 0.13 to 0.63; P = .003). Antiretroviral therapy was started in 9 patients in the hydroxychloroquine group and 1 in the placebo group. Trial medication was well tolerated, but more patients reported influenza-like illness in the hydroxychloroquine group compared with the placebo group (29% vs 10%; P = .03).Among HIV-infected patients not taking antiretroviral therapy, the use of hydroxychloroquine compared with placebo did not reduce CD8 cell activation but did result in a greater decline in CD4 cell count and increased viral replication.isrctn.org Identifier: ISRCTN30019040."
1,"TITLE: Correlation of adenosinergic activity with superior efficacy of clozapine for treatment of chronic schizophrenia: a double blind randomised trial.ABSTRACT: It has been proposed that a deficit of adenosinergic activity could contribute to the pathophysiology of schizophrenia. The authors undertook this study to further evaluate the level of adenosine deaminase (ADA) in patients with chronic schizophrenia treated with monotherapy of haloperidol, risperidone or clozapine and correlation between the ADA level with response to treatment.The trial was a prospective, 8-week, double blind study of parallel groups of patients with chronic schizophrenia. Eligible participants in the study were 51 patients with chronic schizophrenia with ages ranging from 20 to 45 years. All participants were inpatients, in the active phase of illness, and met DSM-IV-TR criteria for schizophrenia. Patients were randomly allocated (17 patients in each group) to risperidone (6 mg/day) or haloperidol 15 mg/day or clozapine (300 mg/day). Serum ADA activity was measured at baseline and week 8.The plasma levels of ADA in patients with chronic schizophrenia who received clozapine were significantly higher than patients who received haloperidol. In addition, response to treatment was positively correlated with plasma levels of ADA only in the clozapine group (r = 0.46 and p = 0.04).The results indicate an increased activity of the enzyme ADA in the serum of schizophrenic patients being treated with clozapine and this increase may be correlated with clozapine's superior antipsychotic efficacy."
1,"TITLE: Titration to target dose of bisoprolol vs. carvedilol in elderly patients with heart failure: the CIBIS-ELD trial.ABSTRACT: Various beta-blockers with distinct pharmacological profiles are approved in heart failure, yet they remain underused and underdosed. Although potentially of major public health importance, whether one agent is superior in terms of tolerability and optimal dosing has not been investigated. The aim of this study was therefore to compare the tolerability and clinical effects of two proven beta-blockers in elderly patients with heart failure.We performed a double-blind superiority trial of bisoprolol vs. carvedilol in 883 elderly heart failure patients with reduced or preserved left ventricular ejection fraction in 41 European centres. The primary endpoint was tolerability, defined as reaching and maintaining guideline-recommended target doses after 12 weeks treatment. Adverse events and clinical parameters of patient status were secondary endpoints. None of the beta-blockers was superior with regards to tolerability: 24% [95% confidence interval (CI) 20-28] of patients in the bisoprolol arm and 25% (95% CI 21-29) of patients in the carvedilol arm achieved the primary endpoint (P= 0.64). The use of bisoprolol resulted in greater reduction of heart rate (adjusted mean difference 2.1 b.p.m., 95% CI 0.5-3.6, P= 0.008) and more, dose-limiting, bradycardic adverse events (16 vs. 11%; P= 0.02). The use of carvedilol led to a reduction of forced expiratory volume (adjusted mean difference 50 mL, 95% CI 4-95, P= 0.03) and more, non-dose-limiting, pulmonary adverse events (10 vs. 4%; P < 0.001).Overall tolerability to target doses was comparable. The pattern of intolerance, however, was different: bradycardia occurred more often in the bisoprolol group, whereas pulmonary adverse events occurred more often in the carvedilol group. This study is registered with controlled-trials.com, number ISRCTN34827306."
1,"TITLE: Noble metal alloy-coated latex versus silicone Foley catheter in short-term catheterization: a randomized controlled study.ABSTRACT: The primary aim of this study was to compare the incidence of catheter-associated bacteriuria with a noble metal alloy-coated latex catheter or a non-coated silicone catheter in patients undergoing elective orthopaedic surgery with short-term catheterization. Secondary objectives included identifying risk factors for bacteriuria and catheter-associated urinary tract symptoms.The study compared 217 patients randomized to and receiving a silicone catheter with 222 patients treated with a coated latex catheter. Before removal of the catheter a sample for urinary culture was obtained. Bacteriuria was defined as the growth of ≥100 000 cfu/ml. A logistic regression model was used to identify risk groups for bacteriuria. Patients were interviewed about urinary tract symptoms during and after catheterization.The incidence of bacteriuria was 1.5% with the coated latex catheter and 5.5% with the silicone catheter (p = 0.027) after a mean period of 2 days' catheterization time. Female gender (odds ratio 6.02) and obesity (odds ratio 5.08) were significant risk factors for bacteriuria. A quarter of the patients reported at least one symptom from the urinary tract during and after catheterization. Most patients defined the symptoms as ""yes, a little"" and a few consulted a healthcare professional because of the symptoms.This study confirmed previous results that the noble metal alloy coating significantly reduces the risk of catheter-associated bacteriuria in short-term catheterization (1-3 days). Female gender and obesity were significant risk factors for developing bacteriuria, while the use of an open drainage system and insertion of the catheter on the ward were not."
1,"TITLE: Safety profile of tinzaparin versus subcutaneous unfractionated heparin in elderly patients with impaired renal function treated for acute deep vein thrombosis: the Innohep® in Renal Insufficiency Study (IRIS).ABSTRACT: Trials comparing the use of full dose unfractionated heparin (UFH) or low molecular weight heparins (LMWHs) in very elderly patients with impaired renal function are lacking. IRIS aimed to assess whether LMWH is at least as safe as UFH in this population.The study included renally impaired patients ≥70 years with acute symptomatic lower limb deep vein thrombosis (DVT). Patients were randomized to initial treatment with either tinzaparin 175 IU/kg once daily (n=269) or activated partial thromboplastin time-adjusted UFH twice daily (n=270). After acute management both groups received vitamin K antagonist to day 90.The trial was stopped prematurely due to a difference in mortality favoring the UFH group (11.5 vs. 6.3%; p=0.035). Rates of clinically relevant bleedings by day 90 were similar in the tinzaparin (11.9%) and UFH (11.9%) groups, as were rates of confirmed recurrent venous thromboembolism (VTE) (2.6 vs. 1.1%; p=0.34). As the mortality difference could not be explained by bleedings or recurrent VTE, a post-hoc analysis was performed. This identified six baseline characteristics significantly correlated with mortality, of which five were over-represented in the tinzaparin group.The IRIS study was a challenging study involving patients (mean age 83 years) usually excluded from clinical studies, but its early termination has left questions unanswered. The mortality difference observed with tinzaparin vs. UFH in elderly, renally-impaired patients with DVT cannot be explained on the basis of bleedings or recurrent VTE, and may reflect an imbalance of mortality risk factors at baseline."
1,"TITLE: Comparison of high protein and high fiber weight-loss diets in women with risk factors for the metabolic syndrome: a randomized trial.ABSTRACT: Studies have suggested that moderately high protein diets may be more appropriate than conventional low-fat high carbohydrate diets for individuals at risk of developing the metabolic syndrome and type 2 diabetes. However in most such studies sources of dietary carbohydrate may not have been appropriate and protein intakes may have been excessively high. Thus, in a proof-of-concept study we compared two relatively low-fat weight loss diets - one high in protein and the other high in fiber-rich, minimally processed cereals and legumes - to determine whether a relatively high protein diet has the potential to confer greater benefits.Eighty-three overweight or obese women, 18-65 years, were randomized to either a moderately high protein (30% protein, 40% carbohydrate) diet (HP) or to a high fiber, relatively high carbohydrate (50% carbohydrate, > 35 g total dietary fiber, 20% protein) diet (HFib) for 8 weeks. Energy intakes were reduced by 2000 - 4000 kJ per day in order to achieve weight loss of between 0.5 and 1 kg per week.Participants on both diets lost weight (HP: -4.5 kg [95% confidence interval (CI):-3.7, -5.4 kg] and HFib: -3.3 kg [95% CI: -4.2, -2.4 kg]), and reduced total body fat (HP: -4.0 kg [5% CI:-4.6, -3.4 kg] and HFib: -2.5 kg [95% CI: -3.5, -1.6 kg]), and waist circumference (HP: -5.4 cm [95% CI: -6.3, -4.5 cm] and HFib: -4.7 cm [95% CI: -5.8, -3.6 cm]), as well as total and LDL cholesterol, triglycerides, fasting plasma glucose and blood pressure. However participants on HP lost more body weight (-1.3 kg [95% CI: -2.5, -0.1 kg; p = 0.039]) and total body fat (-1.3 kg [95% CI: -2.4, -0.1; p = 0.029]). Diastolic blood pressure decreased more on HP (-3.7 mm Hg [95% CI: -6.2, -1.1; p = 0.005]).A realistic high protein weight-reducing diet was associated with greater fat loss and lower blood pressure when compared with a high carbohydrate, high fiber diet in high risk overweight and obese women."
0,"TITLE: Changes of ferritin and CRP levels in melanoma patients treated with adjuvant interferon-α (EORTC 18952) and prognostic value on treatment outcome.ABSTRACT: Adjuvant therapy with interferon-α (IFN) only benefits a small subgroup of melanoma patients and a predictive marker selecting responders does not exist. IFN induces increased ferritin and decreased C-reactive protein (CRP) levels; however, an association with treatment effect was not studied. Serum was collected from patients participating in the European Organization for Research and Treatment of Cancer 18 952 trial comparing adjuvant treatment with IFN to observation. Serial ferritin and CRP levels were determined using enzyme-linked immunosorbent assays, before treatment and up to 24 months. Ferritin levels are influenced by sex and age; therefore ratios of serial ferritin and CRP values with corresponding pretreatment values were calculated. Cox regression model and landmark method at end of induction and 6 months were used to evaluate the association between ferritin, CRP and distant metastasis-free survival (DMFS). Baseline ferritin levels were comparable in the two treatment groups (P=0.92). However, ferritin ratios were significantly higher in IFN-treated patients (N=96) compared with untreated patients (N=21) at end of induction (mean: 2.88 vs. 0.75; P=0.0003) and at 6 months (mean: 3.18 vs. 1.02; P=0.009). In the IFN arm, higher ferritin ratios at end of induction and at 6 months were not associated with improved outcome (respectively, P=0.66 and 0.86). Concerning CRP ratios, no differences between the treatment groups, neither an association with DMFS, were observed. Administration of IFN in melanoma patients induced increase in ferritin levels but not in CRP levels. Ferritin and CRP ratios have no prognostic value regarding DMFS."
1,"TITLE: Dynamics of circulating vascular endothelial growth factor-A predict benefit from antiangiogenic cediranib in metastatic or recurrent cervical cancer patients.ABSTRACT: There is a need for predictive and surrogate response biomarkers to support treatment with antiangiogenic vascular endothelial growth factor (VEGF) inhibitors. We aimed to identify a minimally-invasive biomarker predicting benefit from cediranib pretreatment or early during treatment in patients with recurrent or metastatic cervical cancer.Blood samples were collected before treatment, during treatment and upon disease progression where appropriate from patients enrolled in CIRCCa, a randomised phase II trial of carboplatin and paclitaxel with or without cediranib. Plasma concentrations of VEGF-A, VEGF-receptor 2, Ang1 and Tie2 were measured using multiplex enzyme-linked immunosorbent assay. Pretreatment and temporal changes of the biomarkers were investigated using proportional hazard regression and unsupervised clustering analysis.Samples (n = 556) from 52 patients were analysed. VEGF-receptor 2 (P = .0006) and Tie2 (P = .04) were downregulated following cediranib, while VEGF-A (P = .0025) was upregulated. High Eastern Cooperative Oncology Group performance status (P = .02, hazard ratio [HR] = 2.15, 95% confidence interval [CI] 1.13-4.09) and low pretreatment Tie2 concentrations (P = .003, HR = 0.57, 95%CI 0.39-0.83) were independent prognostic factors associated with reduced progression-free survival. Two patterns of changes in VEGF-A following cediranib were identified. Patients with elevated VEGF-A in the first 3 treatment cycles, regardless of magnitude, had reduced progression-free survival in the placebo arm but improved survival with the addition of cediranib (P = .019, HR = 0.13, 95% CI 0.02-0.71).Patterns of early elevation in plasma VEGF-A should be studied further as a potential biomarker to predict treatment benefit from cediranib."
1,"TITLE: Edoxaban in atrial fibrillation patients with established coronary artery disease: Insights from ENGAGE AF-TIMI 48.ABSTRACT: The relative efficacy and safety profile of the oral Factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation and established coronary artery disease (CAD) has not been analyzed.In the ENGAGE AF-TIMI 48 trial, two edoxaban regimens were compared with warfarin in 21,105 patients with atrial fibrillation and CHADS ⩾2. We analyzed the primary trial endpoints (efficacy: stroke or systemic embolic event, safety: International Society on Thrombosis and Haemostasis major bleeding) in patients with versus without CAD, and used interaction testing to assess for treatment effect modification.The 4510 patients (21.4%) with known CAD were older, more likely male, on aspirin, with lower creatinine clearance and higher CHADS and HAS-BLED scores ( p <0.001 for each). Treatment with the higher-dose edoxaban regimen (versus warfarin) in patients with known CAD tended to have a greater reduction in stroke/systemic embolic event compared with patients without CAD (CAD: hazard ratio 0.65 (0.46-0.92) versus no CAD: hazard ratio 0.94 (0.79-1.12), p-INT 0.062) and also in myocardial infarction (CAD: hazard ratio 0.69 (0.49-0.98) versus no CAD: hazard ratio 1.24 (0.89-1.72), p-INT 0.017), while there was a similar reduction in bleeding irrespective of CAD status (hazard ratio 0.81 and 0.80, p-INT 0.97). Presence or absence of CAD did not modify the efficacy or safety profile of the lower-dose edoxaban regimen (versus warfarin).The reduction in ischemic events with the higher-dose edoxaban regimen versus warfarin was greater in patients with CAD, while bleeding was significantly reduced with edoxaban regardless of CAD status. The efficacy and safety profile of the lower-dose edoxaban regimen relative to warfarin was unaffected by CAD status."
1,"TITLE: Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology-RTOG 1203.ABSTRACT: Purpose NRG Oncology/RTOG 1203 was designed to compare patient-reported acute toxicity and health-related quality of life during treatment with standard pelvic radiation or intensity-modulated radiation therapy (IMRT) in women with cervical and endometrial cancer. Methods Patients were randomly assigned to standard four-field radiation therapy (RT) or IMRT radiation treatment. The primary end point was change in patient-reported acute GI toxicity from baseline to the end of RT, measured with the bowel domain of the Expanded Prostate Cancer Index Composite (EPIC). Secondary end points included change in patient-reported urinary toxicity, change in GI toxicity measured with the Patient-Reported Outcome Common Terminology Criteria for Adverse Events, and quality of life measured with the Trial Outcome Index. Results From 2012 to 2015, 289 patients were enrolled, of whom 278 were eligible. Between baseline and end of RT, the mean EPIC bowel score declined 23.6 points in the standard RT group and 18.6 points in the IMRT group ( P = .048), the mean EPIC urinary score declined 10.4 points in the standard RT group and 5.6 points in the IMRT group ( P = .03), and the mean Trial Outcome Index score declined 12.8 points in the standard RT group and 8.8 points in the IMRT group ( P = .06). At the end of RT, 51.9% of women who received standard RT and 33.7% who received IMRT reported frequent or almost constant diarrhea ( P = .01), and more patients who received standard RT were taking antidiarrheal medications four or more times daily (20.4% v 7.8%; P = .04). Conclusion Pelvic IMRT was associated with significantly less GI and urinary toxicity than standard RT from the patient's perspective."
0,"TITLE: Are Husbands Involving in Their Spouses' Utilization of Maternal Care Services?: A Cross-Sectional Study in Yangon, Myanmar.ABSTRACT: Husbands can play a crucial role in pregnancy and childbirth, especially in patriarchal societies of developing countries. In Myanmar, despite the critical influence of husbands on the health of mothers and newborns, their roles in maternal health have not been well explored. Therefore, the aim of this study was to identify the factors associated with husbands' involvement in maternal health in Myanmar. This study also examined the associations between husbands' involvement and their spouses' utilization of maternal care services during antenatal, delivery and postnatal periods.A community-based, cross sectional study was conducted with 426 husbands in Thingangyun Township, Yangon, Myanmar. Participants were husbands aged 18 years or older who had at least one child within two years at the time of interview. Face to face interviews were conducted using a pretested structured questionnaire. Factors associated with the characteristics of husband's involvement as well as their spouses' utilization of maternal care services were analyzed by multivariable logistic regression models.Of 426 husbands, 64.8% accompanied their spouses for an antenatal visit more than once while 51.6% accompanied them for a postnatal visit. Husbands were major financial supporters for both antenatal (95.8%) and postnatal care (68.5%). Overall, 69.7% were involved in decision making about the place of delivery. Regarding birth preparedness, the majority of husbands prepared for skilled birth attendance (91.1%), delivery place (83.6%), and money saving (81.7%) before their spouses gave birth. In contrast, fewer planned for a potential blood donor (15.5%) and a safe delivery kit (21.1%). In the context of maternal health, predictors of husband's involvement were parity, educational level, type of marriage, decision making level in family, exposure to maternal health education and perception of risk during pregnancy and childbirth. Increased utilization of maternal health services was found among spouses of husbands who accompanied them to antenatal visits (AOR 5.82, 95% CI, 3.34-10.15) and those who had a well birth plan (AOR 2.42, 95% CI, 1.34-4.39 for antenatal visit and AOR 2.88, 95% CI, 1.52-5.47 for postnatal visit).The majority of husbands supported their spouses' maternal care services use financially; however, they were less involved in birth preparedness and postnatal care. Exposure to maternal health education and their maternal health knowledge were main predictors of their involvement. Women were more likely to use maternal care services when their husbands company them for ANC visits and had a well-birth plan in advance."
1,"TITLE: Inosine pranobex is safe and effective for the treatment of subjects with confirmed acute respiratory viral infections: analysis and subgroup analysis from a Phase 4, randomised, placebo-controlled, double-blind study.ABSTRACT: Inosine pranobex (Isoprinosine®) is an immunomodulatory drug approved in several countries for the treatment of viral infections. This study compared the efficacy and safety of inosine pranobex versus placebo in subjects with clinically diagnosed influenza-like illness, including subjects with laboratory-confirmed acute respiratory viral infections. Subgroup analyses evaluated the efficacy of inosine pranobex compared to placebo in otherwise healthy (without related ongoing disease) subjects that were less than 50 years of age and healthy subjects that were at least 50 years of age. The effect of body mass index (BMI) was evaluated in subjects less than 50 years of age.A total of 463 subjects were randomly assigned to receive inosine pranobex (n = 231) or placebo (n = 232) in this Phase 4, randomised, double-blind, multicentre study. The primary efficacy endpoint was time to resolution of all influenza-like symptoms present at baseline to none. Safety was evaluated through analysis of adverse events, vital signs, and physical examinations.The difference in time to resolution of all influenza-like symptoms between treatment groups was not statistically significant but showed a faster improvement in subjects in the inosine pranobex group versus those in the placebo group - Hazard Ratio = 1.175; (95 % CI: 0.806-1.714). P-value = 0.324. In the subgroup analysis for subjects less than 50 years of age, statistically significant differences in time to resolution of influenza-like symptoms that favoured the inosine pranobex group over the placebo group were observed in those without related ongoing disease and those who were non-obese (BMI <30 kg/m). The differences between the inosine pranobex and placebo groups in subjects at least 50 years of age without related ongoing disease and in subjects less than 50 years of age who were obese (BMI ≥30 kg/m) were not statistically significant. Inosine pranobex was generally well tolerated, and no deaths were reported.The study results indicate the safety of inosine pranobex for the treatment of subjects with confirmed acute respiratory viral infections and confirm the efficacy of inosine pranobex versus placebo in healthy non-obese subjects less than 50 years of age with clinically diagnosed influenza-like illnesses.EWO-ISO-2014/1, EudraCT 2014-001863-11 ; Date of registration: 29 APR 2014; Detail information web link: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001863-11/results."
1,"TITLE: Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial.ABSTRACT: Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke.In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0·9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants.Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7·3%, 95% CI -16·6 to 2·1, lower limit of one-sided 95% CI -15·1%, crossing the non-inferiority margin of -12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy (risk difference -1·0%, 95% CI -4·8 to 2·7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [91%] of 201 vs 199 [96%] of 207, risk difference -5·1%, 95% CI -10·2 to 0·0, p=0·047).Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients.Medtronic and University Hospital Bern."
1,"TITLE: Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial.ABSTRACT: Lynch syndrome is associated with an increased risk of colorectal cancer and with a broader spectrum of cancers, especially endometrial cancer. In 2011, our group reported long-term cancer outcomes (mean follow-up 55·7 months [SD 31·4]) for participants with Lynch syndrome enrolled into a randomised trial of daily aspirin versus placebo. This report completes the planned 10-year follow-up to allow a longer-term assessment of the effect of taking regular aspirin in this high-risk population.In the double-blind, randomised CAPP2 trial, 861 patients from 43 international centres worldwide (707 [82%] from Europe, 112 [13%] from Australasia, 38 [4%] from Africa, and four [<1%] from The Americas) with Lynch syndrome were randomly assigned to receive 600 mg aspirin daily or placebo. Cancer outcomes were monitored for at least 10 years from recruitment with English, Finnish, and Welsh participants being monitored for up to 20 years. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. The trial is registered with the ISRCTN registry, number ISRCTN59521990.Between January, 1999, and March, 2005, 937 eligible patients with Lynch syndrome, mean age 45 years, commenced treatment, of whom 861 agreed to be randomly assigned to the aspirin group or placebo; 427 (50%) participants received aspirin and 434 (50%) placebo. Participants were followed for a mean of 10 years approximating 8500 person-years. 40 (9%) of 427 participants who received aspirin developed colorectal cancer compared with 58 (13%) of 434 who received placebo. Intention-to-treat Cox proportional hazards analysis revealed a significantly reduced hazard ratio (HR) of 0·65 (95% CI 0·43-0·97; p=0·035) for aspirin versus placebo. Negative binomial regression to account for multiple primary events gave an incidence rate ratio of 0·58 (0·39-0·87; p=0·0085). Per-protocol analyses restricted to 509 who achieved 2 years' intervention gave an HR of 0·56 (0·34-0·91; p=0·019) and an incidence rate ratio of 0·50 (0·31-0·82; p=0·0057). Non-colorectal Lynch syndrome cancers were reported in 36 participants who received aspirin and 36 participants who received placebo. Intention-to-treat and per-protocol analyses showed no effect. For all Lynch syndrome cancers combined, the intention-to-treat analysis did not reach significance but per-protocol analysis showed significantly reduced overall risk for the aspirin group (HR=0·63, 0·43-0·92; p=0·018). Adverse events during the intervention phase between aspirin and placebo groups were similar, and no significant difference in compliance between intervention groups was observed for participants with complete intervention phase data; details reported previously.The case for prevention of colorectal cancer with aspirin in Lynch syndrome is supported by our results.Cancer Research UK, European Union, MRC, NIHR, Bayer Pharma AG, Barbour Foundation."
1,"TITLE: Otto Aufranc Award: A Multicenter, Randomized Study of Outpatient versus Inpatient Total Hip Arthroplasty.ABSTRACT: Length of stay after total hip arthroplasty (THA) has decreased over the last two decades. However, published studies that have examined same-day and early discharge protocols after THA have been done in highly selected patient groups operated on by senior surgeons in a nonrandomized fashion without control subjects.The purpose of this study was to evaluate and compare patients undergoing THA who are discharged on the same day as the surgery (""outpatient,"" less than 12-hour stay) with those who are discharged after an overnight hospital stay (""inpatient"") with regard to the following outcomes: (1) postoperative pain; (2) perioperative complications and healthcare provider visits (readmission, emergency department or physician office); and (3) relative work effort for the surgeon's office staff.A prospective, randomized study was conducted at two high-volume adult reconstruction centers between July 2014 and September 2015. Patients who were younger than 75 years of age at surgery, who could ambulate without a walker, who were not on chronic opioids, and whose body mass index was less than 40 kg/m were invited to participate. All patients had a primary THA performed by the direct anterior approach with spinal anesthesia at a hospital facility. Study data were evaluated using an intention-to-treat analysis. A total of 220 patients participated, of whom 112 were randomized to the outpatient group and 108 were randomized to the inpatient group. Of the 112 patients randomized to outpatient surgery, 85 (76%) were discharged as planned. Of the remaining 27 patients, 26 were discharged after one night in the hospital and one was discharged after two nights. Of the 108 patients randomized to inpatient surgery with an overnight hospital stay, 81 (75%) were discharged as planned. Of the remaining 27 patients, 18 met the discharge criteria on the day of their surgery and elected to leave the same day, whereas nine patients stayed two or more nights.On the day of surgery, there was no difference in visual analog scale (VAS) pain among patients who were randomized to discharge on the same day and those who were randomized to remain in the hospital overnight (outpatient 2.8 ± 2.5, inpatient 3.3 ± 2.3, mean difference -0.5, 95% confidence interval [CI], -1.1 to 0.1, p = 0.12). On the first day after surgery, outpatients had higher VAS pain (at home) than inpatients (3.7 ± 2.3 versus 2.8 ± 2.1, mean difference 0.9, 95% CI, 0.3-1.5, p = 0.005). With the numbers available, there was no difference in the number of reoperations, hospital readmissions without reoperation, emergency department visits without hospital readmission, or acute office visits. At 4-week followup, there was no difference in the number of phone calls and emails with the surgeon's office (outpatient: 2.4 ± 1.9, inpatient: 2.4 ± 2.2, mean difference 0, 95% CI, -0.5 to 0.6, p = 0.94).Outpatient THA can be implemented in a defined patient population without requiring additional work for the surgeon's office. Because 24% (27 of 112) of patients planning to have outpatient surgery were not able to be discharged the same day, facilities to accommodate an overnight stay should be available.Level I, therapeutic study."
1,"TITLE: Telemonitoring in heart failure patients treated by cardiac resynchronisation therapy with defibrillator (CRT-D): the TELECART Study.ABSTRACT: Telemonitoring (TM) is a safe and efficient monitoring system for internal cardioverter defibrillator device (ICD) recipients. TM has been used to track info on the clinical status of heart failure patients treated by ICD and/or cardiac resynchronisation therapy defibrillator (CRT-D). The aim of this study was to investigate the impact of TM on clinical outcomes in a population of CRT-D patients with heart failure.In a multicentre, randomised study, patients with chronic heart failure, New York Heart Association (NYHA) functional class II or III, left bundle branch block, severe left ventricle ejection fraction reduction (LVEF < 35%) have been identified and screened.One hundred and ninety-one patients have been randomised to receive either a CRT-D with TM or a CRT-D with traditional ambulatory monitoring (control group) and completed the 12-month study follow-up. Primary endpoints were all cause death, cardiac death and hospital admission for heart failure. Secondary endpoints were atrial fibrillation, sustained episodes, non-sustained and self terminated ventricular tachyarrhythmia, sustained ventricular tachycardia, and ventricular fibrillation, ICD shocks and percentage of CRT-D responder patients. Univariate analysis identified the following factors predicting hospitalisation: TM, age, chronic kidney disease, hypercholesterolaemia, LVEF and NYHA class. At multivariate analysis, TM was the only factor predicting heart failure hospitalisation (hazard ratio 0.6, 0.42-0.79, 95% CI, p = 0.002), without affecting overall mortality and cardiac deaths events.Taken together, our data indicate the importance of TM in predicting heart failure hospitalisation in patients treated with CRT-D."
1,"TITLE: Association Between Sitagliptin Use and Heart Failure Hospitalization and Related Outcomes in Type 2 Diabetes Mellitus: Secondary Analysis of a Randomized Clinical Trial.ABSTRACT: Previous trial results have suggested that dipeptidyl peptidase 4 inhibitor (DPP4i) use might increase heart failure (HF) risk in type 2 diabetes mellitus (T2DM). The DPP4i sitagliptin has been shown to be noninferior to placebo with regard to primary and secondary composite atherosclerotic cardiovascular (CV) outcomes in the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS).To assess the association of sitagliptin use with hospitalization for HF (hHF) and related outcomes.TECOS was a randomized, double-blind, placebo-controlled study evaluating the CV safety of sitagliptin vs placebo, each added to usual antihyperglycemic therapy and CV care among patients with T2DM and prevalent atherosclerotic vascular disease. The median follow-up was 2.9 years. The setting was 673 sites in 38 countries. Participants included 14 671 patients with T2DM and atherosclerotic vascular disease. The study dates were December 2008 through March 2015.Patients were randomized to sitagliptin vs placebo added to standard care.Prespecified secondary analyses compared the effect on hHF, hHF or CV death, and hHF or all-cause death composite outcomes overall and in prespecified subgroups. Supportive analyses included total hHF events (first plus recurrent) and post-hHF death. Meta-analyses evaluated DPP4i effects on hHF and on hHF or CV death.Of 14 671 patients, 7332 were randomized to sitagliptin and 7339 to placebo. Hospitalization for HF occurred in 3.1% (n = 228) and 3.1% (n = 229) of the sitagliptin and placebo groups, respectively (unadjusted hazard ratio, 1.00; 95% CI, 0.83-1.19). There was also no difference in total hHF events between the sitagliptin (n = 345) and placebo (n = 347) groups (unadjusted hazard ratio, 1.00; 95% CI, 0.80-1.25). Post-hHF all-cause death was similar in the sitagliptin and placebo groups (29.8% vs 28.8%, respectively), as was CV death (22.4% vs 23.1%, respectively). No heterogeneity for the effect of sitagliptin on hHF was observed in subgroup analyses across 21 factors (P > .10 for all interactions). Meta-analysis of the hHF results from the 3 reported DPP4i CV outcomes trials revealed moderate heterogeneity (I2 = 44.9, P = .16).Sitagliptin use does not affect the risk for hHF in T2DM, both overall and among high-risk patient subgroups.clinicaltrials.gov Identifier: NCT00790205."
1,"TITLE: Conditional survival and long-term efficacy with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma.ABSTRACT: Conditional survival estimates provide critical prognostic information for patients with advanced renal cell carcinoma (aRCC). Efficacy, safety, and conditional survival outcomes were assessed in CheckMate 214 (ClinicalTrials.gov identifier NCT02231749) with a minimum follow-up of 5 years.Patients with untreated aRCC were randomized to receive nivolumab (NIVO) (3 mg/kg) plus ipilimumab (IPI) (1 mg/kg) every 3 weeks for 4 cycles, then either NIVO monotherapy or sunitinib (SUN) (50 mg) daily (four 6-week cycles). Efficacy was assessed in intent-to-treat, International Metastatic Renal Cell Carcinoma Database Consortium intermediate-risk/poor-risk, and favorable-risk populations. Conditional survival outcomes (the probability of remaining alive, progression free, or in response 2 years beyond a specified landmark) were analyzed.The median follow-up was 67.7 months; overall survival (median, 55.7 vs 38.4 months; hazard ratio, 0.72), progression-free survival (median, 12.3 vs 12.3 months; hazard ratio, 0.86), and objective response (39.3% vs 32.4%) benefits were maintained with NIVO+IPI versus SUN, respectively, in intent-to-treat patients (N = 550 vs 546). Point estimates for 2-year conditional overall survival beyond the 3-year landmark were higher with NIVO+IPI versus SUN (intent-to-treat patients, 81% vs 72%; intermediate-risk/poor-risk patients, 79% vs 72%; favorable-risk patients, 85% vs 72%). Conditional progression-free survival and response point estimates were also higher beyond 3 years with NIVO+IPI. Point estimates for conditional overall survival were higher or remained steady at each subsequent year of survival with NIVO+IPI in patients stratified by tumor programmed death ligand 1 expression, grade ≥3 immune-mediated adverse event experience, body mass index, and age.Durable clinical benefits were observed with NIVO+IPI versus SUN at 5 years, the longest phase 3 follow-up for a first-line checkpoint inhibitor-based combination in patients with aRCC. Conditional estimates indicate that most patients who remained alive or in response with NIVO+IPI at 3 years remained so at 5 years."
0,"TITLE: Correlation between gastric residual volumes and markers of gastric emptying: A post hoc analysis of a randomized clinical trial.ABSTRACT: The correlation between gastric residual volumes (GRVs) and markers of gastric emptying (GE) in critically ill patients is unclear. This particularly applies to critically ill surgical patients, as they are underrepresented in previous studies.We conducted a post hoc analysis of a multicenter trial that investigated the effectiveness of a promotility drug. Pharmacokinetic markers of GE (3-O-methylglucose [3-OMG] and acetaminophen) were correlated with GRV measurements. High GRV was defined as one episode of >400 ml or two consecutive episodes of >250 ml, and delayed GE was defined as <20th percentile of the pharmacokinetic GE marker that had the strongest correlation with GE.Of 77 patients, 8 (10.4%) had high GRV, and 15 (19.5%) had delayed GE. The 3-OMG concentration at 60 min had the strongest correlation with GRV (ρ = -0.631), and high GRV had low sensitivity (46.7%) but high specificity (98.4%) in discriminating delayed GE. The positive (87.5%) and negative (88.4%) predictive values were similar. Compared with medical patients, surgical patients (n = 14, 18.2%), had a significantly higher incidence of high GRV (29% vs 6%, P = .032) and a trend toward delayed GE (36% vs 16%, P = .132).GRV reflects GE, and high GRV is an acceptable surrogate marker of delayed GE. From our preliminary observation, surgical patients may have a higher risk of high GRV and delayed GE. In summary, GRV should be monitored to determine whether complex investigations or therapeutic interventions are warranted."
1,"TITLE: Tolvaptan in hospitalized cancer patients with hyponatremia: a double-blind, randomized, placebo-controlled clinical trial on efficacy and safety.ABSTRACT: The rate of hyponatremia is higher in hospitalized cancer patients than in hospitalized patients without cancer and is associated with poor clinical outcomes. The availability of V2 receptor antagonists has been a major breakthrough in the management of hyponatremia, but its efficacy and safety in treating hyponatremia in patients with cancer is not known.Adult patients with cancer who were admitted to The University of Texas MD Anderson Cancer Center with nonhypovolemic hyponatremia (125-130 mmol/L) were randomized to receive either tolvaptan or placebo in a double-blind, placebo-controlled, adaptive, randomized trial. Both groups received the standard of care for hyponatremia, except that patients were allowed to drink to thirst.A preplanned Data Safety Monitoring Board analysis of 30 of 48 randomized patients who completed the study revealed that the primary endpoint of hyponatremia correction was met by 16 of 17 patients who received tolvaptan and by 1 of 13 patients who received placebo (94% vs 8%; P < .001), which met the study stopping rule for superiority. The secondary endpoints between the tolvaptan and placebo groups (mean ± standard deviation) for length of stay (21 ± 15 days vs 26 ± 15 days, respectively) and change in the Mini-Mental State Examination score (-0.35 ± 1.66 vs 0.31 ± 2.42, respectively) were not significantly different. No overcorrection of serum sodium (>12 mmol/L per day) was noted in the tolvaptan group, and the main adverse events noted were dry mouth, polydipsia, and polyuria, leading to 13% study withdrawal.Although tolvaptan was effective for correcting hyponatremia in patients with cancer, studies with a larger sample size will be required to confirm the current findings, including the outcomes of secondary endpoints."
1,"TITLE: Ingestion of a high-molecular-weight hydrothermally modified waxy maize starch alters metabolic responses to prolonged exercise in trained cyclists.ABSTRACT: We examined whether the ingestion of a hydrothermally modified starch (HMS) would alter metabolic and hormonal responses to prolonged cycling compared with maltodextrin (MAL).Nine male cyclists (30 ± 2 y, 79.2 ± 2.1 kg, 4.7 ± 0.1 L of O(2)/min, 7.5 ± 1.3 y training) fasted 10 h before cycling for 150 min at 70% peak oxygen consumption and completing a cycling-to-exhaustion trial at 100% peak oxygen consumption. Participants ingested 1g/kg of HMS or MAL 30 min before and within 10 min of completing the bout. Blood samples were provided every 15 min before, during, and 90 min after exercise. Expired gases were collected every 30 min during exercise. In a crossover, randomized, and double-blind fashion, identical testing was completed 1 wk later.Primary findings from this study were that 1) increases in serum glucose were greater during MAL (peak 9.5 mM) versus HMS (peak 7.4 mM, P ≤ 0.01), 2) insulin levels were significantly lower during HMS (peak 2.5 μIU/mL) versus MAL (peak 20.3 μIU/mL, P < 0.001), and 3) HMS was associated with greater fat breakdown as indicated by the increased serum non-esterified fatty acids (P < 0.01) and glycerol levels (P < 0.05).Ingestion of a low-glycemic HMS before prolonged cycling exercise blunted the initial spike in serum glucose and insulin and increased the breakdown in fat compared with MAL."
1,"TITLE: Laparoscopic versus open gastric resections for primary gastrointestinal stromal tumors (GISTs): a size-matched comparison.ABSTRACT: Laparoscopic resection of gastric GISTs appears technically feasible and associated with favorable outcomes. Tumor size however frequently plays a role in surgical approach with larger tumors tending toward laparotomy, raising concern that favorable outcomes reported for the laparoscopic approach may reflect this selection bias.From a prospectively collected sarcoma database, 155 primary gastric GIST resections were identified (1998-2009); 40 patients underwent successful laparoscopic resection for non-GE junction GIST and were randomly matched (1:1) by tumor size (±2.0 cm) to patients with open resection. Clinical and pathologic variables and surgical outcomes were associated with surgery type using conditional logistic regression analyses.The two surgical approaches were comparable for clinical and pathologic variables. Median operating room (OR) time was similar, although median length of stay postsurgery was lower in the laparoscopic versus open group (4 vs. 7 days, P = 0.002), as was estimated blood loss (EBL) (25 vs. 100 ml, P = 0.006). There was no operative mortality, and 30-day morbidity was similar. Oncologic outcomes were also similar with no positive microscopic margins, and 1 recurrence in each group with a median follow-up of 34 months. There were 13 conversions overall, 5 secondary to tumor location at the GE junction or lesser curve.When matched for tumor size, laparoscopic resection of primary gastric GISTs ≤8 cm results in shorter hospital stays with similar OR time while maintaining sound oncologic outcomes compared with open resection."
1,"TITLE: Melatonin decreases delirium in elderly patients: a randomized, placebo-controlled trial.ABSTRACT: Disturbance in the metabolism of tryptophan and tryptophan-derived compounds (e.g., melatonin) may have a role in the pathogenesis of delirium.To evaluate the efficacy of low dose exogenous melatonin in decreasing delirium.A randomized, double-blinded, placebo-controlled study.An Internal Medicine service in a tertiary care centre in London, Ontario, Canada.145 individuals aged 65 years or over admitted through the emergency department to a medical unit in a tertiary care hospital.Patients were randomized to receive either 0.5 mg of melatonin or placebo every night for 14 days or until discharge.The primary outcome was the occurrence of delirium as determined by Confusion Assessment Method (CAM) criteria.Of a total of 145 individuals (mean age (standard deviation): 84.5 (6.1) years) 72 were randomly assigned to the melatonin group and 73 to the placebo group. Melatonin was associated with a lower risk of delirium (12.0% vs. 31.0%, p = 0.014), with an odds ratio (OR), adjusted for dementia and co-morbidities of 0.19 (95% confidence intervals (CI): 0.06-0.62). Results were not different when patients with prevalent delirium were excluded.An intention to treat analysis was not possible due to loss to follow-up.Exogenous low dose melatonin administered nightly to elderly patients admitted to acute care may represent a potential protective agent against delirium."
1,"TITLE: Rosuvastatin for primary prevention in patients with European systematic coronary risk evaluation risk ≥ 5% or Framingham risk >20%: post hoc analyses of the JUPITER trial requested by European health authorities.ABSTRACT: On the basis of the JUPITER trial, European health authorities recently approved the use of rosuvastatin to reduce first major cardiovascular events among 'high' global risk primary prevention patients defined either by Framingham risk score >20% or European systematic coronary risk evaluation (SCORE) ≥5%. However, as these are post hoc analyses, data describing these subgroups have not previously been available to the clinical community.We randomized 17 802 apparently healthy men aged ≥50 and women ≥60 with low-density lipoprotein cholesterol (LDL-C) <3.4 mmol/L, who were at an increased vascular risk due to elevated levels of C-reactive protein measured with a high-sensitivity (hs) assay to rosuvastatin 20 mg daily or placebo. Patients with high global cardiovascular risk at baseline were identified by 10-year Framingham risk score >20% or SCORE risk ≥5%. During 1.8-year median follow-up (maximum 5 years) of patients with Framingham risk >20%, the rate of myocardial infarction/stroke/cardiovascular death was 9.4 and 18.2 per 1000 person-years in rosuvastatin and placebo-allocated patients, respectively [hazard ratio (HR): 0.50, 95% confidence interval (CI): 0.27-0.93, P = 0.028]. Among patients with SCORE risk ≥5%, the corresponding rates were 6.9 and 12.0 using a model extrapolating risk for age ≥65 years (HR: 0.57, 95% CI: 0.43-0.78, P = 0.0003) and rates were 5.9 and 12.7 when risk for age was capped at 65 years (HR: 0.47, 95% CI: 0.32-0.68, P < 0.0001).In primary prevention patients with elevated hs C-reactive protein who have high global cardiovascular risk (10-year Framingham risk score >20% or SCORE risk ≥5%), but LDL-C levels not requiring pharmacologic treatment, rosuvastatin 20 mg significantly reduced major cardiovascular events."
0,"TITLE: Safety and efficacy of gas-forced infusion (air pump) in coaxial phacoemulsification.ABSTRACT: To evaluate the safety and efficacy of gas-forced infusion (air pump) in uncomplicated coaxial phacoemulsification.Dr. Agarwal's Eye Hospital, Chennai, India.Comparative case series.Specular microscopy and optical coherence tomography were used to analyze the endothelium, central macular thickness (CMT), and peripapillary retinal nerve fiber layer (RNFL) thickness before and approximately 1, 7, 30, and 90 days after coaxial phacoemulsification with (infusion group) or without (control group) gas-forced infusion. Surgical time, surge, phaco energy, irrigation fluid volume, surgical ease, complications, and visual gain in the 2 groups were compared.The mean endothelial cell loss was lower in the infusion group than in the control group (6.98% ± 8.46% [SD] versus 10.54% ± 11.24%; P = .045) and the irrigation/aspiration time significantly shorter (54 ± 39 seconds versus 105 ± 84 seconds; P = .0001). The surgery was rated as easier with gas-forced infusion (scale 1 to 10: mean 8.3 ± 2.1 versus 6.6 ± 1.6; P = .00002). However, the amount of irrigating fluid volume was higher in the infusion group (117 ± 37 mL versus 94 ± 41 mL; P = .003). No surge occurred in the infusion group; it occurred a mean of 3.00 ± 4.16 times in the control group (P<.0001). The rate of visual gain, CMT, peripapillary RNFL thickness, phaco time, and amount of phaco energy were comparable in the 2 groups.Gas-forced infusion was safe and effective in controlling surge and increased the safety, ease, and speed of coaxial phacoemulsification."
0,"TITLE: Suicidality is associated with medication access problems in publicly insured psychiatric patients.ABSTRACT: Beginning January 1, 2006, the Medicare Part D prescription drug benefit shifted drug coverage from Medicaid to the new Medicare Part D program for patients who were eligible for both Medicare and Medicaid benefits (""dual-eligibles""). These patients were randomly assigned to a private Part D plan and came under specific formulary and utilization management procedures of the plan in which they were enrolled.To examine the relationship between physician-reported medication switches, discontinuations, and other access problems and suicidal ideation or behavior among ""dual-eligible"" psychiatric patients.Data were collected in 3 cross-sectional cycles in 2006 (January-April, May-August, and September-December) as part of the National Study of Medicaid and Medicare Psychopharmacologic Treatment Access and Continuity using through-the-mail, practice-based survey research methods. Data from the third cycle, representing all events since January 1, 2006, were used for these analyses. A national sample of psychiatrists randomly selected from the AMA Masterfile provided clinically detailed data on 1 systematically selected, dual-eligible psychiatric patient (N = 908). Propensity score analyses adjusted for patient sociodemographics, treatment setting, diagnoses, and psychiatric symptom severity.Patients who experienced medication switches, discontinuations, and other access problems had 3 times the rate of suicidal ideation or behavior compared with patients with no access problems (22.0% vs 7.4%, P < .0001). Mean odds ratios and excess probabilities were highest for patients who were clinically stable but were required to switch medications (31.8%; mean OR = 4.87, mean P = 8.92(-5), excess probability = 0.21). Patients who experienced discontinuations (26.4%; mean OR = 2.13, mean P = 2.12(-2), excess probability = 0.12), other access problems (18.7%; mean OR = 3.01, mean P = 1.03(-5), excess probability = 0.15), and multiple access problems (22.3%; mean OR = 2.88, mean P = 4.10(-5), excess probability = 0.14) also had significantly increased suicidal ideation or behavior.Increased occurrences of suicidal ideation or behavior appear to be associated with disruptions in patient medication access and continuity. Clinicians need to be aware of the possibility of increased suicidality when, for administrative reasons, a clinically stable patient's medication regimen is altered. Dual-eligible psychiatric patients represent a highly vulnerable group with a substantial burden of illness; these findings underscore the need to provide special protections for this population."
1,"TITLE: Hemodiafiltration with endogenous reinfusion with and without acetate-free dialysis solutions: effect on ESA requirement.ABSTRACT: Hemofiltrate reinfusion (HFR) is a form of hemodiafiltration (HDF) in which replacement fluid is constituted by ultrafiltrate from the patient 'regenerated' through a cartridge containing hydrophobic styrene resin. Bicarbonate-based dialysis solutions (DS) used in routine hemodialysis and HDF contain small quantities of acetate (3-5 mM) as a stabilizing agent, one of the major causes of intradialytic hypotension. Acetate-free (AF) DS have recently been made available, substituting acetate with hydrochloric acid. The impact of AF DS during HFR on Hb levels and erythropoietic-stimulating agent (ESA) requirement in chronic dialysis patients was assessed.After obtaining informed consent, 30 uremic patients treated by standard bicarbonate dialysis (BHD, DS with acetate) were randomized to treatment in 3-month cycles: first AF HFR, followed by HFR with acetate, and again AF HFR. At the beginning and end of each period, Hb and ESA requirements were evaluated.A significant increase in the Hb level was observed throughout all periods of HFR versus BHD (from 11.1 to 11.86 g/dl; p = 0.04), with a significant decrease of ESA requirements from 29,500 to 25,033 IU/month (p = 0.04).Regardless of the presence or absence of acetate in DS, HFR per se allows a significant lowering of ESA dosage versus BHD, while at the same time increasing Hb levels. Taking for granted the clinical impact produced, HFR seems to provide a relevant decrease in end-stage renal disease patient costs."
1,"TITLE: Pasireotide for postoperative pancreatic fistula.ABSTRACT: Postoperative pancreatic fistula is a major contributor to complications and death associated with pancreatic resection. Pasireotide, a somatostatin analogue that has a longer half-life than octreotide and a broader binding profile, decreases pancreatic exocrine secretions and may prevent postoperative pancreatic fistula.We conducted a single-center, randomized, double-blind trial of perioperative subcutaneous pasireotide in patients undergoing either pancreaticoduodenectomy or distal pancreatectomy. We randomly assigned 300 patients to receive 900 μg of subcutaneous pasireotide (152 patients) or placebo (148 patients) twice daily beginning preoperatively on the morning of the operation and continuing for 7 days (14 doses). Randomization was stratified according to the type of resection and whether the pancreatic duct was dilated at the site of transection. The primary end point was the development of pancreatic fistula, leak, or abscess of grade 3 or higher (i.e., requiring drainage).The primary end point occurred in 45 of the 300 patients (15%). The rate of grade 3 or higher postoperative pancreatic fistula, leak, or abscess was significantly lower among patients who received pasireotide than among patients who received placebo (9% vs. 21%; relative risk, 0.44; 95% confidence interval [CI], 0.24 to 0.78; P=0.006). This finding was consistent among 220 patients who underwent pancreaticoduodenectomy (10% vs. 21%; relative risk, 0.49; 95% CI, 0.25 to 0.95) and 80 patients who underwent distal pancreatectomy (7% vs. 23%; relative risk, 0.32; 95% CI, 0.10 to 0.99), as well as among 136 patients with a dilated pancreatic duct (2% vs. 15%; relative risk, 0.11; 95% CI, 0.02 to 0.60) and 164 patients with a nondilated pancreatic duct (15% vs. 27%; relative risk, 0.55; 95% CI, 0.29 to 1.01).Perioperative treatment with pasireotide decreased the rate of clinically significant postoperative pancreatic fistula, leak, or abscess. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT00994110.)."
0,"TITLE: Exaggerated blood pressure variability in patients with pneumoconiosis: a pilot study.ABSTRACT: Chronic hypoxia is a risk factor for cardiovascular disease, but its association with blood pressure (BP) remains unclear. We performed this study to clarify the hypothesis that chronic hypoxia is associated with abnormal BP variability in patients with pneumoconiosis.We recruited 19 patients with pneumoconiosis and 30 age- and BP level-matched control subjects. We used simultaneous pulse oximetry and ambulatory BP monitoring for all subjects. We evaluated their BP levels and variability by determining the SD and coefficient of variation (CV) of the BP data. The dipper pattern was defined as nocturnal BP fall ≥10%; the nondipper pattern was defined as nocturnal BP fall ≥0% but <10%; the riser pattern was defined as nocturnal BP fall <0%. Pearson and Spearman correlation coefficients were used to calculate the correlations between parameters.In patients with pneumoconiosis, the daytime systolic BP (SBP) level was lower, the CV in 24-hour SBP (P < 0.05) and diastolic BP (P < 0.001) were higher than that in control subjects. And although not statistically significant (P = 0.13), the odds ratio of riser pattern was 3.73 in patients with pneumoconiosis, and their nighttime pulse rate was significantly higher (P < 0.05) than that in control subjects. The median daytime pulse oximetry oxygen saturation was inversely associated with mean (r = -0.30; P < 0.01) and SD (r = -0.38; P < 0.001) in daytime SBP. The median nighttime pulse oximetry oxygen saturation was inversely associated (r = -0.55; P < 0.001) and the mean nighttime pulse rate was associated (r = 0.51; P < 0.001) with CV in nighttime SBP. Partial pressure of oxygen was inversely associated with CV in daytime SBP (r = -0.24; P < 0.05).Exaggerated BP variability was seen in patients with pneumoconiosis, and the measures of hypoxia were associated with large fluctuations in ambulatory BP. Chronic and intermittent hypoxia could be the contributing factors of these findings.Clinical Trial Number UMIN000000894 (University Hospital Medical Information Network Clinical Trials Registry website)."
1,"TITLE: Efficacy and safety of percutaneous nephrolithotomy (PCNL): a prospective and randomized study comparing regional epidural anesthesia with general anesthesia.ABSTRACT: To compare the efficacy and safety of regional epidural anesthesia and general anesthesia in patients who underwent PCNL.Fifty patients submitted to percutaneous nephrolithotomy (PCNL) were randomized into two groups: Group I (N = 26) received general anesthesia and Group II (N = 24) received regional epidural anesthesia. Demographic and operative data including age, BMI, stone position, stone size, postoperative pain, amount of postoperative analgesic usage, length of hospital stay, patient satisfaction, preoperative and postoperative hemoglobin and hematocrit, adverse effects and surgical complications were compared between both groups.Average pain score at 1 hour. was 6.88 in group I and 3.12 in group II (p < 0.001), at 4 hours. 5.07 in group I and 3.42 in group II (p = 0.025). Less morphine was required in the regional epidural anesthesia group compared to the general anesthesia group. Higher satisfaction was found in the regional epidural group. 6 (23.07 %) patients in Group I and 1 patient (4.19 %) in Group II had postoperative nausea and vomiting, respectively (p = 0.05). Pain score at 12 hours, 24 hours, 48 hours, 72 hours, preoperative and postoperative hemoglobin and hematocrit, length of hospital stay, and adverse effects were no different between the two groups.Regional epidural anesthesia is an alternative technique for PCNL which achieves more patient satisfaction, less early postoperative pain and less adverse effects from medication with the same efficacy and safety compared to general anesthesia."
1,"TITLE: Cognitive therapy versus fluvoxamine as a second-step treatment in obsessive-compulsive disorder nonresponsive to first-step behavior therapy.ABSTRACT: To compare the effectiveness of second-step treatment with cognitive therapy (CT) versus fluvoxamine in patients with obsessive-compulsive disorder (OCD) who are nonresponsive to exposure in vivo with response prevention (ERP).A 12-week randomized controlled trial at an outpatient clinic in the Netherlands comparing CT with fluvoxamine in OCD. Of 118 subjects with OCD treated with 12 weeks of ERP, 48 appeared to be nonresponders (Y-BOCS improvement score of less than one third). These nonresponders were randomized to CT (n = 22) or fluvoxamine (n = 26). The main outcome measure was the Y-BOCS severity scale. Statistical analyses were conducted in the intention-to-treat sample (n = 45) on an 'as randomized basis' and in the per-protocol sample (n = 30). Due to selective dropout in the fluvoxamine group, two additional sensitivity analyses were performed.Complete data could be obtained from 45 subjects (94%) after 12 weeks. Fifty percent of the patients refused fluvoxamine after randomization compared to 13% who refused CT [χ(2)(1) = 7.10; p = 0.01]. CT as a second-step treatment did not appear to be effective in this sample of nonresponders. Fluvoxamine was significantly superior to CT in the intention-to-treat sample, in the per-protocol sample and in the two separately defined samples in which the sensitivity analyses were performed.OCD patients who are nonresponsive to ERP may benefit more from a switch to treatment with an antidepressant instead of switching to CT. In clinical practice, it may be important to motivate this subgroup of patients to undergo psychopharmacological treatment, as this may improve their outcome considerably."
1,"TITLE: Vitamin E serum levels and controlled supplementation and risk of amyotrophic lateral sclerosis.ABSTRACT: There are no observational studies or controlled trials of amyotrophic lateral sclerosis (ALS) and circulating α-tocopherol (vitamin E) for prevention of ALS. This study addresses that gap. The study population comprised 29,127 Finnish male smokers, aged 50-69 years, who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, which is both a prospective cohort and a randomized, double-blind, placebo-controlled trial of α-tocopherol (50 mg/day) and β-carotene (20 mg/day). Serum α-tocopherol and β-carotene was assayed at baseline (1985 - 1988). Follow-up (median 16.7 years) continued through 2004. ALS cases were identified through the national Hospital Discharge Register with diagnostic verification by hospital records and death certificates. During 407,260 person-years of follow-up, 50 men were identified with ALS. For males with serum α-tocopherol concentration above the median (≥ 11.6 mg/l), the age-adjusted relative risk (RR) compared to α-tocopherol below the median, was 0.56 (95% confidence interval 0.32 - 0.99), p = 0.046. The RR among α-tocopherol supplement recipients was 0.75 (95% CI 0.32 - 1.79), p = 0.52. Neither serum β-carotene level nor β-carotene supplementation was associated with ALS. In conclusion, the results are consistent with a hypothesized protective effect of α-tocopherol on ALS risk. However, pooled analyses of cohorts with serum and controlled trials are needed to clarify the role of α-tocopherol in ALS risk."
1,"TITLE: Outpatient Foley catheter versus inpatient prostaglandin E2 gel for induction of labour: a randomised trial.ABSTRACT: Induction of labour (IOL) is one of the commonest obstetric interventions, with significant impact on both the individual woman and health service delivery. Outpatient IOL is an attractive option to reduce these impacts. To date there is little data comparing outpatient and inpatient IOL methods, and potential safety concerns (hyperstimulation) if prostaglandins, the standard inpatient IOL medications, are used in the outpatient setting. The purpose of this study was to assess feasibility, clinical effectiveness and patient acceptability of outpatient Foley catheter (OPC) vs. inpatient vaginal PGE2 (IP) for induction of labour (IOL) at term.Women with an unfavourable cervix requiring IOL at term (N=101) were randomised to outpatient care using Foley catheter (OPC, n=50) or inpatient care using vaginal PGE2 (IP, n=51). OPC group had Foley catheter inserted and were discharged overnight following a reassuring cardiotocograph. IP group received 2 mg/1 mg vaginal PGE2 if nulliparous or 1 mg/1 mg if multiparous. Main outcome measures were inpatient stay (prior to birth, in Birthing Unit, total), mode of birth, induction to delivery interval, adverse reactions and patient satisfaction.OPC group had shorter hospital stay prior to birth (21.3 vs. 32.4 hrs, p< .001), IP were more likely to achieve vaginal birth within 12 hours of presenting to Birthing Unit (53% vs. 28%, p= .01). Vaginal birth rates (66% OPC Vs. 71% IP), total induction to delivery time (33.5 hrs vs. 31.3 hrs) and total inpatient times (96 hrs OPC Vs. 105 hrs IP) were similar. OPC group felt less pain (significant discomfort 26% Vs 58%, p=.003), and had more sleep (5.8 Vs 3.4 hours, p< .001), during cervical preparation, but were more likely to require oxytocin IOL (88 Vs 59%, p=.001).OPC was feasible and acceptable for IOL of women with an unfavourable cervix at term compared to IP, however did not show a statistically significant reduction in total inpatient stay and was associated with increased oxytocin IOL.Australian New Zealand Clinical Trials Registry, ACTRN:12609000420246."
1,"TITLE: Bioidentical compounded hormones: a pharmacokinetic evaluation in a randomized clinical trial.ABSTRACT: Bioidentical compounded hormone therapy is popular among patients, but providers do not have pharmacokinetic information or dosing guidelines for these preparations. Our objective was to compare the pharmacokinetics of the commonly used compounded preparations with conventional hormonal preparations that are considered bioequivalent in practice.We conducted a randomized, blinded, four-arm 16-day clinical trial of forty postmenopausal women assigned to one of three doses of a compounded estrogen cream (Bi-est (80:20); 2.0, 2.5, or 3.0 mg)+compounded oral progesterone 100 mg, or to a conventional estradiol patch (Vivelle-Dot™ 0.05 mg)+Prometrium™ 100mg. Serum levels of estrone, estradiol, estriol, and progesterone were obtained at multiple time intervals during the first 24-h, and at steady-state.Results were analyzable for 37/40 women. Study medications were well tolerated. The AUC at 24h and at steady-state for estrogens remained consistently lower for all doses of Bi-est tested relative to the patch. The difference was statistically significant for Bi-est 2.0mg (AUC-estradiol=181 vs. 956; p<0.001) and 2.5mg (AUC-estradiol=286 vs. 917; p<0.001). Estriol levels remained low in all study arms. Serum progesterone levels were comparable in conventional vs. compounded groups.This pharmacokinetic trial showed that the currently used doses of compounded hormones yield lower levels of estrogen compared to the standard-dose estradiol patch. To find comparable doses, further studies are needed. This successfully conducted randomized controlled study attests to the feasibility of using a similar design in the setting of a larger clinical trial."
1,"TITLE: Reduced hepatotoxicity by total glucosides of paeony in combination treatment with leflunomide and methotrexate for patients with active rheumatoid arthritis.ABSTRACT: Combination use of methotrexate (MTX) and leflunomide (LEF) has been proved effective in the treatment of active rheumatoid arthritis (RA). However, previous trials have documented that both are associated with increased incidence of liver toxicity. As active compounds extracted from the roots of the traditional Chinese herb Paeonia lactiflora Pall, total glucosides of paeony (TGP) have been shown to have anti-inflammatory, hepatoprotective and immuno-regulatory activities, without evident toxicity or side effects. In this 24-week, open label, randomized multicenter clinical trial, we investigated the efficacy of TGP and the protective effect on hepatotoxicity in the combination treatment with LEF and MTX for patients with active RA. A total of 204 patients with active RA (DAS28>3.2) recruited from 3 regional referral centers were enrolled and received MTX and LEF combination therapy (MTX 10 mg/week plus LEF 20 mg/day) with or without TGP for up to 24 weeks by randomization. Hepatotoxicity was defined as an increase of at least 1.5-fold the upper limits of normal (ULN) of alanine aminotransferase (ALT) or aspartate aminotransferase (AST). Significantly less frequent hepatotoxicity was observed in patients with TGP than those without (9.5% vs 34.8%, p < 0.001) at 12 weeks. The proportion of patients whose ALT or AST levels were > 1.5 to ≤2 times and >2 to ≤3 times the ULN were lower in TGP group than the control (1.9% vs 10.1%, 2.9% vs 12.4%, p < 0.05 respectively). More patients in the TGP group achieved a European League Against Rheumatism (EULAR) good response or moderate response at 12 weeks, although there is no statistical significance. Similar results were observed at 24 weeks. Our preliminary study demonstrates the hepatoprotective and additive role of TGP in combination with MTX and LEF in the treatment of active RA."
1,"TITLE: Study of the use of antidepressants for depression in dementia: the HTA-SADD trial--a multicentre, randomised, double-blind, placebo-controlled trial of the clinical effectiveness and cost-effectiveness of sertraline and mirtazapine.ABSTRACT: Depression is common in dementia, causing considerable distress and other negative impacts. Treating it is a clinical priority, but the evidence base is sparse and equivocal. This trial aimed to determine clinical effectiveness of sertraline and mirtazapine in reducing depression 13 weeks post randomisation compared with placebo.Multicentre, parallel-group, double-blind placebo-controlled randomised controlled trial of the clinical effectiveness of sertraline and mirtazapine with 13- and 39-week follow-up.Nine English old-age psychiatry services.A pragmatic trial. Eligibility: probable or possible Alzheimer's disease (AD), depression (4+ weeks) and Cornell Scale for Depression in Dementia (CSDD) score of 8+.clinically too critical (e.g. suicide risk); contraindication to medication; taking antidepressants; in another trial; and having no carer.(1) Sertraline; (2) mirtazapine; and (3) placebo, all with normal care. Target doses: 150 mg of sertraline or 45 mg of mirtazapine daily.MAIN OUTCOME MEASURES METHODSCSDD score. Randomisation: Allocated 1 : 1 : 1 through Trials Unit, independently of trial team. Stratified block randomisation by centre, with randomly varying block sizes; computer-generated randomisation. Blinding: Double blind: medication and placebo identical for each antidepressant. Referring clinicians, research workers, participants and pharmacies were blind. Statisticians blind until analyses completed.Numbers randomised: 326 participants randomised (111 placebo, 107 sertraline and 108 mirtazapine).Differences in CSDD at 13 weeks from an adjusted linear-mixed model: mean difference (95% CI) placebo-sertraline 1.17 (-0.23 to 2.78; p = 0.102); placebo-mirtazapine 0.01 (-1.37 to 1.38; p = 0.991); and mirtazapine-sertraline 1.16 (-0.27 to 2.60; p = 0.112).Placebo group had fewer adverse reactions (29/111, 26%) than sertraline (46/107, 43%) or mirtazapine (44/108, 41%; p = 0.017); 39-week mortality equal, five deaths in each group.This is a trial with negative findings but important clinical implications. The data suggest that the antidepressants tested, given with normal care, are not clinically effective (compared with placebo) for clinically significant depression in AD. This implies a need to change current practice of antidepressants being the first-line treatment of depression in AD. From the data generated we formulated the following recommendations for future work. (1) The secondary analyses presented here suggest that there would be value in carrying out a placebo-controlled trial of the clinical effectiveness and cost-effectiveness of mirtazapine in the management of Behavioural and Psychological Symptoms of Dementia. (2) A conclusion from this study is that it remains both ethical and essential for trials of new medication for depression in dementia to have a placebo arm. (3) Further research is required to evaluate the impact that treatments for depression in people with dementia can have on their carers not only in terms of any impacts on their quality of life, but also the time they spend care-giving. (4) There is a need for research into alternative biological and psychological therapies for depression in dementia. These could include evaluations of new classes of antidepressants (such as venlafaxine) or antidementia medication (e.g. cholinesterase inhibitors). (5) Research is needed to investigate the natural history of depression in dementia in the community when patients are not referred to secondary care services. (6) Further work is needed to investigate the cost modelling results in this rich data set, investigating carer burden and possible moderators to the treatment effects. (7) There is scope for reanalysis of the primary outcome in terms of carer and participant CSDD results."
1,"TITLE: Clinical, angiographic, and intravascular ultrasound results of the VestSaync II trial.ABSTRACT: We sought to assess the long term efficacy of the novel VESTAsync™ Eluting Stent (VES) combining a Cro-Co platform with a nanothin-microporous hydroxyapatite surface coating impregnated with a polymer-free low-dose of Sirolimus (55 μg).The Vestasync II trial was a randomized (2:1), double-blinded, multicenter comparison of the VES to its platform, the Gen X stent, with microporous hydroxyapatite surface coating without sirolimus. Patients were eligible if they presented de novo lesions in native coronary arteries with 3.0-3.5 mm diameter and ≤ 14 mm in length. Primary endpoint was 8-month in-stent late loss and % of stent obstruction. Lifelong aspirin and 6-month clopidogrel were prescribed to all patients.Seventy-five patients were enrolled (VES = 50 pts). Baseline characteristics included mean age of 58 years and 29% of diabetics. Reference vessel diameter and lesion length were 2.8 ± 0.4 mm and 13.0 ± 2.0 mm, respectively. In-stent late loss (0.39 ± 0.20 vs. 0.74 ± 0.52, P = 0.03) and % of neointima hyperplasia (9.3 ± 6.6% vs. 17.6 ± 9.4%, P = 0.0016) were significantly reduced in the VES cohort. Up to 1 year, there was a single case of myocardial infarction and one target lesion revascularization (TLR) (2%) in the VES group while in the control cohort there were one TLR (4%) and one cardiac death (4%).The VestSync II trial is a proof-of-concept study and demonstrates the sustained efficacy of this novel polymer-free sirolimus drug-eluting stents. A larger trial, with more complex lesions, clinical endpoints and longer FU period is warranted. © 2013 Wiley Periodicals, Inc."
1,"TITLE: Body weight, plasma insulin, and coronary events with gemfibrozil in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT).ABSTRACT: The Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) showed that gemfibrozil significantly reduced major coronary events in men with known coronary heart disease (CHD). To better understand why therapy was especially effective with obesity, diabetes, and hyperinsulinemia, changes in body weight and plasma insulin were determined after 1 year of gemfibrozil or placebo therapy and related to changes in lipids and CHD events.With gemfibrozil significantly more subjects lost weight (51.7% versus 38.6%, P<0.0001) and significantly fewer subjects gained weight (42.5% versus 54.0%, P<0.0001) than with placebo. Both a greater loss and smaller gain in weight with gemfibrozil were age-related and significant in subjects > or =66 years (median age), but not in younger subjects. Weight change was paralleled by changes in insulin. With gemfibrozil, CHD events were significantly reduced with weight loss (hazard ratio [HR], 0.61; 95% CI, 0.44-0.84; P=0.002) and, particularly, with diabetes or hyperinsulinemia (HR, 0.53; 95% CI, 0.34-0.83; P=0.006). In contrast, CHD events were not significantly reduced without weight loss (HR, 0.83; 95% CI, 0.62-1.12; P=0.22).In VA-HIT, gemfibrozil resulted in weight loss associated with reductions in insulin. With weight loss gemfibrozil produced a significant reduction in CHD events that did not occur in the absence of weight loss."
1,"TITLE: Sexual function in nondepressed women using escitalopram for vasomotor symptoms: a randomized controlled trial.ABSTRACT: To evaluate sexual function in midlife women using selective serotonin reuptake inhibitors for vasomotor symptoms. Selective serotonin reuptake inhibitors effectively treat vasomotor symptoms but adversely affect sexual function in depressed populations. Information on sexual function in nondepressed midlife women using selective serotonin reuptake inhibitors for vasomotor symptoms is lacking; any treatments that might impair function are of concern.This was a randomized controlled trial comparing 8 weeks of escitalopram with placebo in women ages 40-62 years with 28 or more bothersome vasomotor symptoms per week. Change in Female Sexual Function Index composite score (ranges from 2 [not sexually active, no desire] to 36) and six sexual domains (desire, arousal, lubrication, orgasm, satisfaction, pain) and the Female Sexual Distress Scale, and a single-question of sexually-related personal distress from the Female Sexual Distress Scale, were compared between groups.Among all women, median composite baseline Female Sexual Function Index score was 18.1 (interquartile range 2.4-26.5, n=200) and among sexually active women was 22.8 (interquartile range 17.4-27.0, n=75) in the escitalopram group and 23.6 (interquartile range 14.9-31.0, n=70) in the placebo group. Treatment with escitalopram did not affect composite Female Sexual Function Index score at follow-up compared with placebo (P=.18 all women; P=.47 sexually active at baseline). Composite mean Female Sexual Function Index change from baseline to week 8 was 0.1 (95% confidence interval [CI] -1.5 to 1.7) for escitalopram and 2.0 (95% CI 0.2-3.8) for placebo. The Female Sexual Distress Scale results did not differ between groups (P=.73) nor did adverse reports of sexual function. At week 8, among those women sexually active at baseline, there was a small difference between groups in Female Sexual Function Index domain mean score change in lubrication (P=.02) and a marginal nonsignificant difference in orgasm (P=.07).Escitalopram, when used in the treatment of vasomotor symptoms, did not worsen overall sexual function among nondepressed midlife women."
1,"TITLE: Association Between Peritoneal Glucose Exposure and Peritonitis in Peritoneal Dialysis Patients: The balANZ Trial.ABSTRACT: Glucose is the primary osmotic medium used in most peritoneal dialysis (PD) solutions, and exposure to glucose has been shown to exert detrimental effects both locally, at the peritoneal membrane, and systemically. Moreover, high dialysate glucose exposure may predispose patients to an increased risk of peritonitis, perhaps as a result of impaired host defences, vascular disease, and damage to the peritoneal membrane.In this post-hoc analysis of a multicenter, multinational, open-label randomized controlled trial of neutral pH, low-glucose degradation product (GDP) versus conventional PD solutions (ANZ trial), the relationship between peritonitis rates of low (< 123.1 g/day) versus high (≥ 123.1 g/day) dialysate glucose exposure was evaluated in 177 incident PD patients over a 2-year study period.Peritonitis rates were 0.44 episodes per patient-year in the low-glucose exposure group and 0.31 episodes per patient-year in the high-glucose exposure group, (incidence rate ratio [IRR] 0.69,  = 0.09). There was no significant association between dialysate glucose exposure and peritonitis-free survival on univariable analysis (high glucose exposure hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.40 - 1.08) or on multivariable analysis (adjusted HR 0.64, 95% CI 0.39 - 1.05). Moreover, there was no relationship between peritoneal glucose exposure and type of organism causing peritonitis. Physician-rated severity of first peritonitis episodes was similar between groups, as was rate and duration of hospital admission.Overall, this study did not identify an association between peritoneal dialysate glucose exposure and peritonitis occurrence, severity, hospitalization, or outcomes. A further large-scale, prospective, randomized controlled trial evaluating patient-level outcomes is merited."
1,"TITLE: Effects of progressive resistance training in individuals with type 2 diabetic polyneuropathy: a randomised assessor-blinded controlled trial.ABSTRACT: The aim of this study was to evaluate the effects of progressive resistance training (PRT) on muscle strength, intraepidermal nerve fibre density (IENFD) and motor function in individuals with type 2 diabetic polyneuropathy (DPN) and to compare potential adaptations to those of individuals with type 2 diabetes without DPN and healthy controls.This was an assessor-blinded trial conducted at the Neurology department, Aarhus University Hospital. Adults with type 2 diabetes, with and without DPN and healthy control participants were randomised to either supervised PRT or non-PRT for 12 weeks. Allocation was concealed by a central office unrelated to the study. The co-primary outcomes were muscle strength in terms of the peak torque of the knee and ankle extensors and flexors, and IENFD. Secondary outcome measures included the 6 min walk test (6MWT), five-time sit-to-stand test (FTSST) and postural stability index obtained by static posturography.A total of 109 individuals were enrolled in three groups (type 2 diabetes with DPN [n = 42], type 2 diabetes without DPN [n = 32] and healthy control [n = 35]). PRT resulted in muscle strength gains of the knee extensors and flexors in all three groups using comparative analysis (DPN group, PRT 10.3 ± 9.6 Nm vs non-PRT -0.4 ± 8.2 Nm; non-DPN group, PRT 7.5 ± 5.8 Nm vs non-PRT 0.6 ± 8.8 Nm; healthy control group, PRT 6.3 ± 9.0 Nm vs non-PRT -0.4 ± 8.4 Nm; p<0.05, respectively). Following PRT the DPN group improved the 6MWT (PRT 34.6 ± 40.9 m vs non-PRT 2.7 ± 19.6 m; p=0.001) and the FTSST (PRT -1.5 ± 2.2 s vs non-PRT 1.5 ± 4.6 s; p=0.02). There was no change in IENFD following PRT in any of the groups.PRT improved muscle strength of the knee extensors and flexors and motor function in individuals with type 2 diabetic polyneuropathy at levels comparable with those seen in individuals with diabetes without DPN and healthy control individuals, while no effects were observed in IENFD.ClinicalTrials.gov NCT03252132 FUNDING: Research reported in this paper is part of the International Diabetic Neuropathy Consortium (IDNC) research programme, supported by a Novo Nordisk Foundation Challenge Program grant (grant no. NNF14OC0011633) and Aarhus University."
1,"TITLE: Differential effects of nebivolol vs. metoprolol on microvascular function in hypertensive humans.ABSTRACT: Use of β-adrenergic receptor (AR) blocker is associated with increased risk of fatigue and exercise intolerance. Nebivolol is a newer generation β-blocker, which is thought to avoid this side effect via its vasodilating property. However, the effects of nebivolol on skeletal muscle perfusion during exercise have not been determined in hypertensive patients. Accordingly, we performed contrast-enhanced ultrasound perfusion imaging of the forearm muscles in 25 untreated stage I hypertensive patients at rest and during handgrip exercise at baseline or after 12 wk of treatment with nebivolol (5-20 mg/day) or metoprolol succinate (100-300 mg/day), with a subsequent double crossover for 12 wk. Metoprolol and nebivolol each induced a reduction in the resting blood pressure and heart rate (130.9 ± 2.6/81.7 ± 1.8 vs. 131.6 ± 2.7/80.8 ± 1.5 mmHg and 63 ± 2 vs. 64 ± 2 beats/min) compared with baseline (142.1 ± 2.0/88.7 ± 1.4 mmHg and 75 ± 2 beats/min, respectively, both P < 0.01). Metoprolol significantly attenuated the increase in microvascular blood volume (MBV) during handgrip at 12 and 20 repetitions/min by 50% compared with baseline (mixed-model P < 0.05), which was not observed with nebivolol. Neither metoprolol nor nebivolol affected microvascular flow velocity (MFV). Similarly, metoprolol and nebivolol had no effect on the increase in the conduit brachial artery flow as determined by duplex Doppler ultrasound. Thus our study demonstrated a first direct evidence for metoprolol-induced impairment in the recruitment of microvascular units during exercise in hypertensive humans, which was avoided by nebivolol. This selective reduction in MBV without alteration in MFV by metoprolol suggested impaired vasodilation at the precapillary arteriolar level."
1,"TITLE: Long-Term Follow-Up of the Intergroup Exemestane Study.ABSTRACT: Purpose The Intergroup Exemestane Study, an investigator-led study of 4,724 postmenopausal patients with early breast cancer (clinical trial information: ISRCTN11883920), has previously demonstrated that a switch from adjuvant endocrine therapy after 2 to 3 years of tamoxifen to exemestane was associated with clinically relevant improvements in efficacy. Here, we report the final efficacy analyses of this cohort. Patients and Methods Patients who remained disease free after 2 to 3 years of adjuvant tamoxifen were randomly assigned to continue tamoxifen or switch to exemestane to complete a total of 5 years of adjuvant endocrine therapy. Given the large number of non-breast cancer-related deaths now reported, breast cancer-free survival (BCFS), with censorship of intercurrent deaths, was the primary survival end point of interest. Analyses focus on patients with estrogen receptor-positive or unknown tumors (n = 4,599). Results At the time of the data snapshot, median follow-up was 120 months. In the population that was estrogen receptor positive or had unknown estrogen receptor status, 1,111 BCFS events were observed with 508 (22.1%) of 2,294 patients in the exemestane group and 603 (26.2%) of 2,305 patients in the tamoxifen group. The data corresponded to an absolute difference (between exemestane and tamoxifen) at 10 years of 4.0% (95% CI, 1.2% to 6.7%), and the hazard ratio (HR) of 0.81 (95% CI, 0.72 to 0.92) favored exemestane. This difference remained in multivariable analysis that was adjusted for nodal status, prior use of hormone replacement therapy, and prior chemotherapy (HR, 0.80; 95% CI, 0.71 to 0.90; P < .001). A modest improvement in overall survival was seen with exemestane; the absolute difference (between exemestane and tamoxifen) at 10 years in the population that was estrogen receptor positive or had unknown estrogen receptor status was 2.1% (95% CI, -0.5% to 4.6%), and the HR was 0.89 (95% CI, 0.78 to 1.01; P = .08). For the intention-to-treat population, the absolute difference was 1.6% (95% CI, -0.9% to 4.1%); the HR was 0.91 (95% CI, 0.80 to 1.03, P = .15). No statistically significant difference was observed in the proportion of patients who reported a fracture event in the post-treatment period. Conclusion The Intergroup Exemestane Study and contemporaneous studies have established that a strategy of switching to an aromatase inhibitor after 2 to 3 years of tamoxifen can lead to sustained benefits in terms of reduction of disease recurrence and breast cancer mortality."
0,"TITLE: Ethnic differences in prevalence and barriers of HBV screening and vaccination among Asian Americans.ABSTRACT: Our study identifies the prevalence of HBV virus (HBV) screening and vaccination among Asian Americans, and ethnic differences for factors associated with screening and vaccination behaviors. In 2009-2010 we recruited 877 Korean, Chinese, and Vietnamese Americans 18 years of age and above through several community organizations, churches and local ethnic businesses in Maryland for a health education intervention and a self-administered survey. Prevalence of HBV screening, screening result and vaccinations were compared by each ethnic group. We used logistic regression analysis to understand how sociodemographics, familial factors, patient-, provider-, and resource-related barriers are associated with screening and vaccination behaviors, using the total sample and separate analysis for each ethnic group. Forty-seven percent of participants reported that they had received HBV screening and 38% had received vaccinations. Among the three groups, the Chinese participants had the highest screening prevalence, but lowest self-reported infection rate; Vietnamese has the lowest screening and vaccination prevalence. In multivariate analysis, having better knowledge of HBV, and family and physician recommendations was significantly associated with screening and vaccination behaviors. Immigrants who had lived in the US for more than a quarter of their lifetime were less likely to report ever having been screened (OR = 0.39, 95% CI: 0.28-0.55) or vaccinated (OR = 0.62, 95% CI: 0.44-0.88). In ethnic-specific analysis, having a regular physician (OR = 4.46, 95% CI: 1.62-12.25) and doctor's recommendation (OR = 2.11, 95% CI: 1.05-4.22) are significantly associated with Korean's vaccination behaviors. Health insurance was associated with vaccination behaviors only among Vietnamese (OR = 2.66, 95% CI: 1.21–5.83), but not among others."
1,"TITLE: A partially hydrolyzed formula with synbiotics supports adequate growth and is well tolerated in healthy, Chinese term infants: A double-blind, randomized controlled trial.ABSTRACT: The aim of this study was to evaluate growth and gastrointestinal tolerance in infants fed a partially hydrolyzed protein formula (pHF) with a synbiotic mixture of short-chain galacto-oligosaccharides and long-chain fructooligosaccharides (scGOS/lcFOS; 9:1) and Bifidobacterium breve M-16V (test formula) compared with an intact protein infant formula (IF) with scGOS/lcFOS (control formula).This randomized, double-blind, controlled, multicenter trial enrolled healthy, fully formula-fed Chinese infants (≤44 d) who received either the test (n = 112) or control formula (n = 112) until 17 wk of age. Fully breastfed infants served as a reference (n = 60). Anthropometrics, gastrointestinal symptoms, and adverse events were assessed monthly. Primary outcome was weight gain in grams per day from baseline to 17 wk of age.Equivalence in daily weight gain (primary outcome) was demonstrated between the test and control groups (estimated mean difference [SE]: -0.36 [0.93] g/d, 90% confidence interval [CI], -1.90 to 1.18) as well as between each IF group and the breastfed reference group (test: 0.02 [1.05] g/d, 90% CI, -1.71 to 1.75; control: 0.36 [1.04] g/d, 90% CI, -1.35 to 2.08). There were no clinically relevant differences in gastrointestinal tolerance or adverse events between the formula groups.A pHF with synbiotics supports adequate growth and is well tolerated in healthy, term-born Chinese infants. Additionally, infant growth and gastrointestinal tolerance measures of both IF groups were comparable to the breastfed group and can be considered suitable and well tolerated for use."
1,"TITLE: Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial.ABSTRACT: Inhibition of phosphatidylinositol 3-kinase (PI3K) is a promising approach to overcome resistance to endocrine therapy in breast cancer. Pictilisib is an oral inhibitor of multiple PI3K isoforms. The aim of this study is to establish if addition of pictilisib to fulvestrant can improve progression-free survival in oestrogen receptor-positive, endocrine-resistant breast cancer.In this two-part, randomised, double-blind, placebo-controlled, phase 2 study, we recruited postmenopausal women aged 18 years or older with oestrogen receptor-positive, HER2-negative breast cancer resistant to treatment with an aromatase inhibitor in the adjuvant or metastatic setting, from 123 medical centres across 21 countries. Part 1 included patients with or without PIK3CA mutations, whereas part 2 included only patients with PIK3CA mutations. Patients were randomly allocated (1:1 in part 1 and 2:1 in part 2) via a computer-generated hierarchical randomisation algorithm to daily oral pictilisib (340 mg in part 1 and 260 mg in part 2) or placebo starting on day 15 of cycle 1, plus intramuscular fulvestrant 500 mg on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles in both groups. In part 1, we stratified patients by presence or absence of PIK3CA mutation, primary or secondary aromatase inhibitor resistance, and measurable or non-measurable disease. In part 2, we stratified patients by previous aromatase inhibitor treatment for advanced or metastatic disease or relapse during or within 6 months of an aromatase inhibitor treatment in the adjuvant setting and measurable or non-measurable disease. All patients and those administering treatment and assessing outcomes were masked to treatment assignment. The primary endpoint was progression-free survival in the intention-to-treat population for both parts 1 and 2 and also separately in patients with PIK3CA-mutated tumours in part 1. Tumour assessment (physical examination and imaging scans) was investigator-assessed and done at screening and after 8 weeks, 16 weeks, 24 weeks, and 32 weeks of treatment from day 1 of cycle 1 and every 12 weeks thereafter. We assessed safety in as-treated patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT01437566.In part 1, between Sept 27, 2011, and Jan 11, 2013, we randomly allocated 168 patients to the pictilisib (89 [53%]) or placebo (79 [47%]) group. In part 2, between March 18, 2013, and Jan 2, 2014, we randomly allocated 61 patients to the pictilisib (41 [67%]) or placebo (20 [33%]) group. In part 1, we found no difference in median progression-free survival between the pictilisib (6·6 months [95% CI 3·9-9·8]) and placebo (5·1 months [3·6-7·3]) group (hazard ratio [HR] 0·74 [95% CI 0·52-1·06]; p=0·096). We also found no difference when patients were analysed according to presence (pictilisib 6·5 months [95% CI 3·7-9·8] vs placebo 5·1 months [2·6-10·4]; HR 0·73 [95% CI 0·42-1·28]; p=0·268) or absence (5·8 months [3·6-11·1] vs 3·6 months [2·8-7·3]; HR 0·72 [0·42-1·23]; p=0·23) of PIK3CA mutation. In part 2, we also found no difference in progression-free survival between groups (5·4 months [95% CI 3·8-8·3] vs 10·0 months [3·6-13·0]; HR 1·07 [95% CI 0·53-2·18]; p=0·84). In part 1, grade 3 or worse adverse events occurred in 54 (61%) of 89 patients in the pictilisib group and 22 (28%) of 79 in the placebo group. 19 serious adverse events related to pictilisib treatment were reported in 14 (16%) of 89 patients. Only one (1%) of 79 patients reported treatment-related serious adverse events in the placebo group. In part 2, grade 3 or worse adverse events occurred in 15 (36%) of 42 patients in the pictilisib group and seven (37%) of 19 patients in the placebo group. Four serious adverse events related to pictilisib treatment were reported in two (5%) of 42 patients. One treatment-related serious adverse event occurred in one (5%) of 19 patients in the placebo group.Although addition of pictilisib to fulvestrant did not significantly improve progression-free survival, dosing of pictilisib was limited by toxicity, potentially limiting its efficacy. For future assessment of PI3K inhibition as an approach to overcome resistance to hormonal therapy, inhibitors with greater selectivity than that of pictilisib might be needed to improve tolerability and potentially increase efficacy. No further investigation of pictilisib in this setting is ongoing.F Hoffmann-La Roche."
1,"TITLE: Cytochrome 2C19 polymorphism and response to adjunctive cilostazol versus high maintenance-dose clopidogrel in patients undergoing percutaneous coronary intervention.ABSTRACT: Among patients treated with clopidogrel, carriers of the cytochrome P450 (CYP) 2C19 loss-of-function allele have shown increased platelet reactivity and higher rates of ischemic events. Although adjunctive cilostazol to dual antiplatelet therapy (or ""triple antiplatelet therapy"") intensifies platelet inhibition, it remains unknown whether triple antiplatelet therapy after percutaneous coronary intervention can achieve adequate platelet inhibition in patients with the CYP2C19 mutant allele.CYP2C19 genotyping for *1, *2, and *3 was performed in 134 high-risk patients undergoing elective percutaneous coronary intervention. After measurement of preprocedural platelet reactivity, patients were randomly assigned to receive either adjunctive cilostazol 100 mg twice daily (triple group; n=69) or high maintenance-dose (MD) clopidogrel of 150 mg daily (high-MD group; n=65). Using light transmittance aggregometry and the VerifyNow P2Y(12) assay, platelet reactivity was assessed before the index procedure and at 30-day follow-up. The primary end point was absolute change in maximal platelet aggregation (ΔAgg(max)) according to CYP2C19 genotyping. High posttreatment platelet reactivity was defined as 5 μmol/L ADP-induced maximal platelet aggregation >50%. In noncarriers of the CYP2C19*2/*3 mutant allele, ΔAgg(max) values after 5 and 20 μmol/L ADP stimuli did not differ significantly between the triple (n=22) versus the high-MD group (n=22) (23.6±21.6% versus 16.6±15.4%, P=0.224 and 26.4±22.2% versus 18.6±14.9%, P=0.174, respectively). Absolute changes in late platelet aggregation and P2Y(12) reaction unit were not different between the groups. The rate of high posttreatment platelet reactivity at 30-day follow-up also was comparable between the triple versus the high-MD group (4.5% versus 13.6%, P=0.607). In carriers of at least 1 CYP2C19*2/*3 mutant allele, the triple group (n=47) showed greater values of ΔAgg(max) after addition of 5 μmol/L (25.8±16.8% versus 11.1±19.8%, P<0.001) and 20 μmol/L ADP (26.3±16.0% versus 11.5±16.3%, P<0.001) compared with the high-MD group (n=43). Likewise, absolute changes in late platelet aggregation and P2Y(12) reaction unit were consistently greater in the triple versus the high-MD group. Fewer patients in the triple group met the criteria of high posttreatment platelet reactivity at 30-day follow-up compared with the high-MD group (6.4% versus 37.2%, P<0.001).Among high-risk patients undergoing elective percutaneous coronary intervention, adjunctive cilostazol can achieve consistently intensified platelet inhibition and reduce the risk of high posttreatment platelet reactivity irrespective of CYP2C19 genotyping.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01012193."
1,"TITLE: Glomerular filtration rate reserve is reduced during mild passive heat stress in healthy young adults.ABSTRACT: We tested the hypothesis that, compared with normothermia, the increase in glomerular filtration rate (GFR) after an oral protein load (defined as the GFR reserve) is attenuated during moderate passive heat stress in young healthy adults. Sixteen participants (5 women; 26 ± 2 yr) completed two experimental visits, heat stress or a normothermic time-control, assigned in a block-randomized crossover design. During the heat stress trial, core temperature was increased by 0.6°C in the first hour before commencing a 2-min cold pressor test (CPT) to assess renal vasoconstrictor responses. One-hour post-CPT, subjects ingested a whey protein shake (1.2 g of protein/kg body wt), and measurements were taken pre-, 75, and 150 min postprotein. Segmental artery vascular resistance was calculated as the quotient of Doppler ultrasound-derived segmental artery blood velocity and mean arterial pressure and provided an estimate of renal vascular tone. GFR was estimated from creatinine clearance. The increase in segmental artery vascular resistance during the CPT was attenuated during heat stress (end CPT: 5.6 ± 0.9 vs. 4.7 ± 1.1 mmHg/cm/s,  = 0.024). However, the reduction in segmental artery vascular resistance in response to an oral protein load did not differ between heat stress (at 150 min: 1.9 ± 0.4 mmHg/cm/s) and normothermia (at 150 min: 1.8 ± 0.5 mmHg/cm/s;  = 0.979). The peak increase in creatinine clearance postprotein, independent of time, was attenuated during heat stress (+26 ± 19 vs. +16 ± 20 mL/min,  = 0.013,  = 13). GFR reserve is diminished by mild passive heat stress. Moreover, renal vasoconstrictor responses are attenuated by mild passive heat stress, but renal vasodilator responses are maintained."
1,"TITLE: Assessing race and ethnicity differences in outcomes based on GDMT and target NT-proBNP in patients with heart failure with reduced ejection fraction: An analysis of the GUIDE-IT study.ABSTRACT: The GUIDE-IT trial was, a multicenter, randomized, parallel group, unblinded study that randomized patients to having heart failure therapy titrated to achieve an NT-proBNP <1000 pg/mL or to usual clinical care.We performed pre-specified subgroup analysis to look for the race and ethnicity-based differences in clinical outcomes of patients who were able to achieve GDMT or target NT-proBNP concentration of ≤1000 pg/mL at 90 days of follow-up. There were 894 patients enrolled in GUIDE-IT study. Of these, 733 participants had available data on 90-day guideline directed triple therapy and 616 on NT-proBNP. 35% of the patients were Black and 6% were Hispanic. Black patients were younger, had more comorbidities, lower EF, and higher NYHA class compared with non-Black. Adjusting for 90-day NT-proBNP and important baseline covariates, Black patients were at a higher risk than non-Black patients for HF hospitalization [HR, 2.19; 95% CI, 1.51-3.17; p < 0.0001], but at a similar risk for mortality [HR, 0.85.; 95% CI, 0.44-1.66; p = 0.64]. Similar results were seen adjusting for 90-day GDMT [HF hospitalization: Black vs non-Black, HR: 1.97; 1.41-2.77, P < 0.0001; mortality: HR: 0.70; 0.39-1.26, p = 0.23]. There were no significant differences between Hispanic and non-Hispanic patients with respect to heart failure hospitalization, cardiovascular or all-cause mortality. Over the study period, Black and Hispanic patients experienced smaller changes in physical function and quality of life as measured by the Kansas City Cardiomyopathy Questionnaire overall score.Compared to non-Black patients, Black patients in GUIDE-IT study had a higher risk of heart failure hospitalization, but a comparable risk of mortality, despite improved use of GDMT and achievement of similar biomarker targets."
1,"TITLE: Early cryoprecipitate transfusion versus standard care in severe postpartum haemorrhage: a pilot cluster-randomised trial.ABSTRACT: There is a lack of evidence evaluating cryoprecipitate transfusion in severe postpartum haemorrhage. We performed a pilot cluster-randomised controlled trial to evaluate the feasibility of a trial on early cryoprecipitate delivery in severe postpartum haemorrhage. Pregnant women (>24 weeks gestation), actively bleeding within 24 h of delivery and who required at least one unit of red blood cells were eligible. Women declining transfusion in advance or with inherited clotting deficiencies were not eligible. Four UK hospitals were randomly allocated to deliver either the intervention (administration of two pools of cryoprecipitate within 90 min of first red blood cell unit requested plus standard care), or the control group treatment (standard care, where cryoprecipitate is administered later or not at all). The primary outcome was the proportion of women who received early cryoprecipitate (intervention) vs. standard care (control). Secondary outcomes included consent rates, acceptability of the intervention, safety outcomes and preliminary clinical outcome data to inform a definitive trial. Between March 2019 and January 2020, 199 participants were recruited; 19 refused consent, leaving 180 for analysis (110 in the intervention and 70 in the control group). Adherence to assigned treatment was 32% (95%CI 23-41%) in the intervention group vs. 81% (95%CI 70-90%) in the control group. The proportion of women receiving cryoprecipitate at any time-point was higher in the intervention (60%) vs. control (31%) groups; the former had fewer red blood cell transfusions at 24 h (mean difference -0.6 units, 95%CI -1.2 to 0); overall surgical procedures (odds ratio 0.6, 95%CI 0.3-1.1); and intensive care admissions (odds ratio 0.4, 95%CI 0.1-1.1). There was no increase in serious adverse or thrombotic events in the intervention group. Staff interviews showed that lack of awareness and uncertainty about study responsibilities contributed to lower adherence in the intervention group. We conclude that a full-scale trial may be feasible, provided that protocol revisions are put in place to establish clear lines of communication for ordering early cryoprecipitate in order to improve adherence. Preliminary clinical outcomes associated with cryoprecipitate administration are encouraging and merit further investigation."
1,"TITLE: Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study.ABSTRACT: Targeted inhibition of the PD-L1-PD-1 pathway might be further amplified through combination of PD-1 or PD-L1 inhibitors with novel anti-TIGIT inhibitory immune checkpoint agents, such as tiragolumab. In the CITYSCAPE trial, we aimed to assess the preliminary efficacy and safety of tiragolumab plus atezolizumab (anti-PD-L1) therapy as first-line treatment for non-small-cell lung cancer (NSCLC).CITYSCAPE is a phase 2, randomised, double-blind, placebo-controlled trial. Patients with chemotherapy-naive, PD-L1-positive (defined as a tumour proportion score of ≥1% by 22C3 immunohistochemistry pharmDx assay; Dako, Agilent Technologies, Santa Clara, CA, USA) recurrent or metastatic NSCLC with measurable disease, Eastern Cooperative Oncology Group performance status of 0 or 1, and no EGFR or ALK alterations were enrolled from 41 clinics in Europe, Asia, and the USA. Patients were randomly assigned (1:1), via an interactive voice or web-based response system, to receive tiragolumab (600 mg) plus atezolizumab (1200 mg) or placebo plus atezolizumab intravenously once every 3 weeks. Investigators and patients were masked to treatment assignment. The co-primary endpoints were investigator-assessed objective response rate and progression-free survival as per Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat population, analysed after approximately 80 progression-free survival events had been observed in the primary population. Safety was assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03563716, and is ongoing.Patients were enrolled between Aug 10, 2018, and March 20, 2019. At data cutoff for the primary analysis (June 30, 2019), 135 of 275 patients assessed for eligibility were randomly assigned to receive tiragolumab plus atezolizumab (67 [50%]) or placebo plus atezolizumab (68 [50%]). In this primary analysis, after a median follow-up of 5·9 months (4·6-7·6, in the intention-to-treat population, 21 patients (31·3% [95% CI 19·5-43·2]) in the tiragolumab plus atezolizumab group versus 11 patients (16·2% [6·7-25·7]) in the placebo plus atezolizumab group had an objective response (p=0·031). Median progression-free survival was 5·4 months (95% CI 4·2-not estimable) in the tiragolumab plus atezolizumab group versus 3·6 months (2·7-4·4) in the placebo plus atezolizumab group (stratified hazard ratio 0·57 [95% CI 0·37-0·90], p=0·015). 14 (21%) patients receiving tiragolumab plus atezolizumab and 12 (18%) patients receiving placebo plus atezolizumab had serious treatment-related adverse events. The most frequently reported grade 3 or worse treatment-related adverse event was lipase increase (in six [9%] patients in the tiragolumab plus atezolizumab group vs two [3%] in the placebo plus atezolizumab group). Two treatment-related deaths (of pyrexia and infection) occurred in the tiragolumab plus atezolizumab group.Tiragolumab plus atezolizumab showed a clinically meaningful improvement in objective response rate and progression-free survival compared with placebo plus atezolizumab in patients with chemotherapy-naive, PD-L1-positive, recurrent or metastatic NSCLC. Tiragolumab plus atezolizumab was well tolerated, with a safety profile generally similar to that of atezolizumab alone. These findings demonstrate that tiragolumab plus atezolizumab is a promising immunotherapy combination for the treatment of previously untreated, locally advanced unresectable or metastatic NSCLC.F Hoffmann-La Roche and Genentech."
1,"TITLE: Weight management and determinants of weight change in patients with coronary artery disease.ABSTRACT: To study the effects of a comprehensive secondary prevention programme on weight loss and to identify determinants of weight change in patients with coronary artery disease (CAD).We performed a secondary analysis focusing on the subgroup of overweight CAD patients (BMI ≥27 kg/m) in the Randomised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists-2 (RESPONSE-2) multicentre randomised trial. We evaluated weight change from baseline to 12-month follow-up; multivariable logistic regression with backward elimination was used to identify determinants of weight change.Intervention patients (n=280) lost significantly more weight than control patients (n=257) (-2.4±7.1 kg vs -0.2±4.6 kg; p<0.001). Individual weight change varied widely, with weight gain (≥1.0 kg) occurring in 36% of interventions versus 41% controls (p=0.21). In the intervention group, weight loss of ≥5% was associated with higher age (OR 2.94), lower educational level (OR 1.91), non-smoking status (OR 2.92), motivation to start with weight loss directly after the baseline visit (OR 2.31) and weight loss programme participation (OR 3.33), whereas weight gain (≥1 kg) was associated with smoking cessation ≤6 months before or during hospitalisation (OR 3.21), non-Caucasian ethnicity (OR 2.77), smoking at baseline (OR 2.70), lower age (<65 years) (OR 1.47) and weight loss programme participation (OR 0.59).The comprehensive secondary prevention programme was, on average, effective in achieving weight loss. However, wide variation was observed. As weight gain was observed in over one in three participants in both groups, prevention of weight gain may be as important as attempts to lose weight.NTR3937."
1,"TITLE: Suboptimal inhibition of platelet cyclooxygenase-1 by aspirin in metabolic syndrome.ABSTRACT: Interindividual variation in the ability of aspirin to inhibit platelet cyclooxygenase-1 (COX-1) could account for some on-treatment cardiovascular events. Here, we sought to determine whether there are clinical phenotypes that are associated with a suboptimal pharmacological effect of aspirin. In a prospective, 2-week study, we evaluated the effect of aspirin (81 mg) on platelet COX-1 in 135 patients with stable coronary artery disease by measuring serum thromboxane B(2) (sTxB(2)) as an indicator of inhibition of platelet COX-1. A nested randomized study compared enteric-coated with immediate-release formulations of aspirin. We found that sTxB(2) was systematically higher among the 83 patients with metabolic syndrome than among the 52 patients without (median: 4.0 versus 3.02 ng/mL; P=0.013). Twelve patients (14%) with metabolic syndrome, but none without metabolic syndrome, had sTxB(2) levels consistent with inadequate inhibition of COX (sTxB(2) ≥13 ng/mL). In linear regression models, metabolic syndrome (but none of its individual components) significantly associated with higher levels of log-transformed sTxB(2) (P=0.006). Higher levels of sTxB(2) associated with greater residual platelet function measured by aggregometry-based methods. Among the randomized subset, sTxB(2) levels were systematically higher among patients receiving enteric-coated aspirin. Last, urinary 11-dehydro thromboxane B(2) did not correlate with sTxB(2), suggesting that the former should not be used to quantitate aspirin's pharmacological effect on platelets. In conclusion, metabolic syndrome, which places patients at high risk for thrombotic cardiovascular events, strongly and uniquely associates with less effective inhibition of platelet COX-1 by aspirin."
1,"TITLE: Effects of probiotics supplementation on the hormone and body mass index in perimenopausal and postmenopausal women using the standardized diet. A 5-week double-blind, placebo-controlled, and randomized clinical study.ABSTRACT: The results of pioneering studies indicate that probiotics can alleviate menopausal symptoms (including cardiometabolic dysfunctions) and improve the quality of life of perimenopausal/postmenopausal women. However, the results of randomized control trials are scarce to evaluate whether the administration of probiotics could affect the balance of sex hormones during the menopause period.In this randomized, double-blind, and placebo-controlled study, 48 perimenopausal and postmenopausal women received multispecies probiotic Sanprobi Barrier in a dose of 2.5 × 109 (CFU) for five weeks. Dietary guidelines were introduced in both groups simultaneously (~1800 kcal/per day, whole grain, no-wheat meals). The study aimed to assess the variations in follicle-stimulating hormone (FSH), estradiol (E2), cortisol (as the hypothalamic-pituitary-ovarian axis hormone), and the body mass during the intervention.At the endpoint, FSH level has increased significantly concerning the baseline after the probiotic intake (31.91 vs. 42.00 mIU/ml; p < 0.009). Also, in the placebo group, a strong trend to elevate FSH was observed (22.31 vs. 41.99 mIU/ml; p = 0.055). Body mass has crucially decreased in reference to the baseline in both groups (PRO: 27.90 vs. 26.30 kg/m2, p<0.001; PBO: 25.90 to 24.60 kg/m2, p<0.001).Probiotics affect FSH levels in perimenopausal women while simultaneously representing a non-invasive strategy to impact hormonal homeostasis. They could potentially have an impact on cardiometabolic health."
1,"TITLE: Efficacy of Preoperative Oral Midodrine in Preventing Hypotension After Spinal Anesthesia in Young Adults: A Randomized Controlled Trial.ABSTRACT: Midodrine was effectively used for prophylaxis against hypotensive syndromes such as postural hypotension and intradialytic hypotension, and during the recovery phase of septic shock. In our study, we aimed to assess the efficacy of prophylactic administration of midodrine tablets before spinal anesthesia in reducing the occurrence of hypotension.This randomized placebo-controlled study embraced 67 patients aged 18 to 40 years undergoing elective knee surgery under spinal anesthesia. Patients were randomized to midodrine group (given 10-mg tablets of midodrine) or placebo group (given placebo tablets), and tablets were administered 1 hour before spinal anesthesia (intrathecal injection of 12.5-mg 0.5% hyperbaric bupivacaine and 15-μg fentanyl). The primary outcome was the occurrence of hypotension, defined as a systolic blood pressure <90 mm Hg or <80% of baseline. Secondary outcomes were hemodynamic characteristics (mean arterial pressure [MAP] and heart rate [HR]) after spinal anesthesia, ephedrine dose, and occurrence of complications including bradycardia, vasovagal attacks, reactive hypertension nausea, vomiting, and shivering.The number of patients who became hypotensive after spinal anesthesia was 5 (14.7%) in midodrine group versus 14 (42.4%) in the placebo group; relative risk (95% confidence interval) was 0.35 (0.14-0.85) ( P = .021). The median (interquartile range) total dose of ephedrine was significantly lower in midodrine group 0 (0-10) mg than in placebo group (0 (0-15) mg; the Hodges-Lehmann median difference (95% confidence interval) was 0 (0-5) mg ( P = .015). For MAP data, the group × time interaction was significant ( P = .038), and the MAP was significantly lower in the placebo group than in the midodrine group after intrathecal injection at 2 minutes ( P = .047), 10 minutes ( P = .045), 15 minutes ( P < .001), 20 minutes ( P = .007), 30 minutes ( P =.013), 45 minutes ( P = .029), 60 minutes ( P = .029), and at the end of surgery ( P < .001). For HR data, the group × time interaction was nonsignificant ( P = .807), and the difference in means (95% confidence interval) between groups collapsing over time was -1.4 (-3.1 to 0.2) beats/min ( P = .096). There was no significant difference between the 2 groups regarding the occurrence of complications.Prophylactic administration of 10-mg midodrine tablets before spinal anesthesia is an effective method in the prevention of hypotension in young adult patients undergoing elective orthopedic knee surgery."
1,"TITLE: A web-based self-care program to promote healthy lifestyles and control blood pressure in patients with primary hypertension: A randomized controlled trial.ABSTRACT: Hypertension is a major risk factor for cardiovascular diseases, which contributes to the worldwide mortality rate. Successful blood pressure control requires adherence to medications and lifestyle modifications. However, motivating patients with primary hypertension to change and sustain behaviors long-term is challenging. A web-based self-care program centered on self-efficacy theory could provide feedback for effective control of blood pressure.To examine the effect of a web-based self-care program for patients with primary hypertension on cardiovascular risk-factors (pulse pressure and lipids), self-efficacy, and self-care behaviors (medication adherence and lifestyle).A two-armed randomized controlled trial with 3-month and 6-month follow-ups.A total of 222 patients with primary hypertension were recruited between February 2017 and August 2018 at a cardiology clinic of a medical center in Taipei, Taiwan.Eligible patients were randomized by permuted block randomization into the intervention group (n = 111) and control group (n = 111). Patients in the intervention group received a 6-month web-based self-care program, based on the theory of self-efficacy, while patients in the control group received usual care. Baseline and outcome measures (3 and 6 months) included self-efficacy, evaluated with the Chinese version of the 6-item Self-Efficacy for Managing Chronic Diseases (SEMC6), self-care, using subscales of the Hypertension Self-Care Activity Level Effects Scale (H-SCALE) for lifestyle and medication adherence, and blood pressure and serum lipid data, collected through web-based self-reports and chart review. Generalized estimating equations evaluated the effects of the intervention.At baseline, the control group had higher scores on the SEMC6, and lower cholesterol (HDL) compared with the intervention group (t = -2.70, p < 0.05; and t = 1.76, p < 0.05, respectively). Pulse pressure decreased significantly (β = -20.30, 95% CI -23.76, -16.83), and serum triglycerides and low-density lipoprotein cholesterol levels were significantly lower compared with controls at 6 months (all p < 0.001). At 6 months, the intervention group had significantly higher mean scores for the SEMC6 compared with the control group (β = 21.84, 95% confidence interval [CI] 19.25, 24.42) and H-SCALE subscale for medication adherence, diet, weight management, and physical activity compared with controls at 6 months (all, p < 0.001).The greatest benefit of this program was allowing participants to immediately consult with the researchers about self-care issues via the website. Lifestyles vary from person to person; therefore, the individuality of each participant was considered when providing feedback. We provided devising interventions for participants that would increase their confidence in self-care for hypertension and ultimately achieve home blood pressure control. We encourage incorporating this program into standard clinical care for patients with hypertension."
1,"TITLE: Use of area under the curve to evaluate the effects of antimalarial drugs on malaria-associated anemia after treatment.ABSTRACT: To evaluate the effects of antimalarial drugs on Plasmodium falciparum malaria-associated anemia, we use the area under the curve (AUC) of anemia levels after treatment as an approach to combine their duration and magnitude. The method involves numeric estimation, by trapezoidal rule, of AUC from a plot of deficit in hematocrit levels from 30% (the lower threshold of normal) versus time in anemic children. Using the method, we evaluated, in randomized trials, the effects of artesunate-mefloquine versus mefloquine alone and artemether-lumefantrine versus amodiaquine-artesunate on the time course of recovery from malaria-associated anemia in 109 children. Anemia resolution times were similar (10.9 ± 6.2 [standard deviation] versus 13.3 ± 8.9 days, P = 0.2), but mean AUC was significantly lower in artesunate-mefloquine- compared with mefloquine-treated children (35.5 ± 7.1 [standard error of mean] versus 49.8 ± 11.3 %·h, P = 0.02) indicating larger exposure to anemia in mefloquine-treated children. In artemether-lumefantrine- and amodiaquine-artesunate-treated children, both anemia resolution times (8.6 ± 5.3 [standard deviation] versus 8.6 ± 4.8 days, P = 0.98) and mean AUC (57.1 ± 12.9 [standard error of mean] versus 46.3 ± 8.7 %·h, P = 0.74) were similar. Estimation of AUC appears more robust than estimation of anemia resolution time in evaluating antimalarial drug effects and can be used in both observational studies and clinical trials assessing the effects of therapies on malaria-associated anemia."
1,"TITLE: Effects of dapagliflozin, an SGLT2 inhibitor, on HbA(1c), body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy.ABSTRACT: To examine the safety and efficacy of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, added on to pioglitazone in type 2 diabetes inadequately controlled on pioglitazone.Treatment-naive patients or those receiving metformin, sulfonylurea, or thiazolidinedione entered a 10-week pioglitazone dose-optimization period with only pioglitazone. They were then randomized, along with patients previously receiving pioglitazone ≥30 mg, to 48 weeks of double-blind dapagliflozin 5 (n = 141) or 10 mg (n = 140) or placebo (n = 139) every day plus open-label pioglitazone. The primary objective compared HbA(1c) change from baseline with dapagliflozin plus pioglitazone versus placebo plus pioglitazone at week 24. Primary analysis was based on ANCOVA model using last observation carried forward; all remaining analyses used repeated-measures analysis.At week 24, the mean reduction from baseline in HbA(1c) was -0.42% for placebo versus -0.82 and -0.97% for dapagliflozin 5 and 10 mg groups, respectively (P = 0.0007 and P < 0.0001 versus placebo). Patients receiving pioglitazone alone had greater weight gain (3 kg) than those receiving dapagliflozin plus pioglitazone (0.7-1.4 kg) at week 48. Through 48 weeks: hypoglycemia was rare; more events suggestive of genital infection were reported with dapagliflozin (8.6-9.2%) than placebo (2.9%); events suggestive of urinary tract infection showed no clear drug effect (5.0-8.5% for dapagliflozin and 7.9% for placebo); dapagliflozin plus pioglitazone groups had less edema (2.1-4.3%) compared with placebo plus pioglitazone (6.5%); and congestive heart failure and fractures were rare.In patients with type 2 diabetes inadequately controlled on pioglitazone, the addition of dapagliflozin further reduced HbA(1c) levels and mitigated the pioglitazone-related weight gain without increasing hypoglycemia risk."
1,"TITLE: Effect of amlodipine + candesartan on cardiovascular events in hypertensive patients with coronary artery disease (from The Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease [HIJ-CREATE] Study).ABSTRACT: Combination therapy with calcium channel blockers and angiotensin II receptor blockers is recommended as one of the effective therapies for hypertension. However, it remains unclear whether this combination reduces major adverse cardiovascular events (MACEs) in patients with hypertension with coronary artery disease (CAD). The purpose of the present study was to examine the effects of amlodipine plus candesartan on MACEs in patients with hypertension with CAD. The study population was drawn from The Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease (HIJ-CREATE), which was a multicenter, prospective, randomized controlled trial including 2,049 patients with hypertension with angiographically documented CAD. Subgroup analysis was performed in patients treated with amlodipine at baseline (n = 388). The median follow-up period was 4.3 years. Treatment using amlodipine plus candesartan reduced the risk for MACEs by 39% (p = 0.015) compared to that using amlodipine without angiotensin II receptor blockers. Among the individual events constituting MACEs, the incidence of unstable angina pectoris requiring hospitalization was significantly lower, by 52% (p = 0.007). In conclusion, amlodipine plus candesartan demonstrated a more favorable effect on reducing cardiovascular events in patients with hypertension with CAD compared to amlodipine-based therapy without candesartan."
1,"TITLE: The alteration of aspart insulin pharmacodynamics when mixed with detemir insulin.ABSTRACT: Mixing rapid acting insulin analogs with detemir insulin to minimize daily injections has been adopted as a common regimen, especially for some children with type 1 diabetes, despite the manufacturing company's caution against mixing these analogs in the same syringe. The effect of this practice on the pharmacodynamics (PD) of rapid-acting insulin has not been widely studied. This crossover, randomized study was undertaken to determine whether mixing aspart with detemir insulin has an adverse effect on the early glucodynamic action of rapid-acting insulin analog in humans.Eight adolescents with type 1 diabetes (age 17.3 ± 0.6 years and A1C 7.3 ± 0.3%) had two euglycemic glucose clamps during which 0.2 units/kg aspart and 0.4 units/kg detemir insulin were injected either as a separate or single mixed injection in random order.Mixing the two insulins diminished the peak and overall early aspart insulin action with significantly lower maximum glucose infusion rate (GIR(max) separate 6.1 ± 0.7 mg/kg/min vs. mix 4.5 ± 0.5 mg/kg/min; P = 0.03) values and the area under curve for GIR during the first 3 h of the insulin action study (separate 757 ± 105 mg/kg vs. mix 491 ± 66 mg/kg; P = 0.04).These data demonstrate that mixing aspart with detemir insulin markedly lowers the early PD action of aspart and prolongs its time-action profile as compared with the separate injection of these analogs. These changes in insulin PD should be weighed against the added convenience of mixing when considering such unlicensed use of these insulins in youth with type 1 diabetes."
1,"TITLE: Laparoscopic versus open approach for aortobifemoral bypass for severe aorto-iliac occlusive disease--a multicentre randomised controlled trial.ABSTRACT: To investigate differences between open and laparoscopic aortobifemoral bypass surgery for aorto-iliac occlusive disease on postoperative morbidity and mortality.A multicentre randomised controlled trial.Between January 2007 and November 2009, 28 patients with severe aorto-iliac occlusive disease (TASC II C or D) were randomised between laparoscopic and open approach at one community hospital and one university hospital (TASC = Trans-Atlantic Inter-Society Consensus on the Management of Peripheral Arterial Disease).The operation time was longer for the laparoscopic approach (mean 4 h 19 min (2 h 00 min to 6 h 20 min) vs. 3 h 30 min (1 h 42 min to 5 h 11 min); p = 0.101)). Nevertheless, postoperative recovery and in-hospital stay were significantly shorter after laparoscopic surgery. Also oral intake could be restarted earlier (mean 20 h 34 min (6 h 00 min to 26 h 55 min) vs. 43 h 43 min (19 h 40 min to 77 h 30 min); p = 0.00014)) as well as postoperative mobilisation (walking) (mean 46 h 15 min (16 h 07 min to 112 h 40 min) vs. mean 94 h 14 min (66 h 10 min to 127 h 23 min); p = 0.00016)). Length of hospitalisation was shorter (mean 5.5 days (2.5-15) vs. mean 13.0 days (7-45); p = 0.0095)). Visual pain scores and visual discomfort scores were both lower after laparoscopic surgery. Also return to normal daily activities was achieved earlier. There were no major complications in both groups.Laparoscopic aortobifemoral bypass surgery for aorto-iliac occlusive disease is a safe procedure with a significant decrease in postoperative morbidity and in-hospital stay and earlier recovery."
1,"TITLE: Early statin treatment prior to primary PCI for acute myocardial infarction: REPERATOR, a randomized placebo-controlled pilot trial.ABSTRACT: The aim of this pilot study was to determine whether early atorvastatin treatment will reduce left ventricle (LV) remodeling, infarct size, and improve microvascular perfusion.In animal studies, early statin therapy reduces reperfusion injury after a percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI).Forty-two consecutive patients (82% male, mean age 61.2 ± 9.8) who underwent a primary PCI for a first ST-elevated AMI were randomized for pretreatment with atorvastatin 80 mg (n = 20) or placebo (n = 22) and continued with the same dosage daily for 1 week. All patients received atorvastatin 80 mg once daily 7 days after primary PCI. The LV function and infarct size were measured by magnetic resonance imaging within 1 day, at 1 week, and 3 months follow up. The primary endpoint was the end-systolic volume index (ESVI) at 3 months. Secondary endpoints were global LV function measurements, myocardial infarct size, biochemical cardiac markers, TIMI flow, and ST-T elevation resolution.ESVI 3 months after AMI was 25.1 mL/m(2) in the atorvastatin arm and 25.0 mL/m(2) in the placebo arm (P = 0.74). The differences in change from baseline to 3 months follow up in global LV function and myocardial infarct size did not differ between both treatment arms. Furthermore, biochemical markers, TIMI flow, and ST-T elevation resolution did not differ between atorvastatin and placebo arm.In this pilot study, pretreatment with atorvastatin in an acute myocardial infarction does not result in an improved cardiac function, microvascular perfusion, or decreased myocardial infarct size."
0,"TITLE: The powerful pre-treatment effect: placebo responses in restless legs syndrome trials.ABSTRACT: To investigate whether dopaminergic pre-treatment alters placebo and dopamine agonist responses in restless legs syndrome (RLS).Two large, multi-centre trials (SP790 and SP792; registration numbers NCT00136045 and NCT00135993) on the efficacy of rotigotine in RLS reported supplemental International RLS (IRLS) sum score data for pre-treated and drug-naïve patients, allowing for the estimation of the regression slope of the clinical response (change in the IRLS sum score) on baseline IRLS sum score.In both trials, patients pre-treated with dopaminergic medications tended to have blunted responses after placebo administration compared with drug-naïve patients. In the SP790 study, the pre-treated group had a negative slope (i.e. the response observed after placebo administration decreased as the baseline IRLS sum score increased), whereas the slope was positive in drug-naïve patients (slope, -0.43 vs. 0.28; P = 0.027). In the SP792 study, the two slopes were parallel (P = 0.84), but the magnitude of the response after placebo administration was smaller in the pre-treated group (6.31 vs. 10.49; P = 0.0089). Pre-treatment had no significant effect on rotigotine-group responses in either of the two studies.In RLS trials, dopaminergic pre-treatment tends to increase the apparent effect of new dopaminergic drugs by decreasing the placebo effect in the placebo arm without substantially modifying the placebo effect in the active treatment arm. This observation highlights that placebo-controlled trials are not necessarily placebo-effect controlled trials."
0,"TITLE: Red meat consumption and risk of heart failure in male physicians.ABSTRACT: Heart failure (HF) remains a major public health issue. Red meat and dietary heme iron have been associated with an increased risk of coronary heart disease and hypertension, two major risk factors for HF. However, it is not known whether red meat intake influences the risk of HF. We therefore examined the association between red meat consumption and incident HF.We prospectively studied 21,120 apparently healthy men (mean age 54.6 y) from the Physicians' Health Study (1982-2008). Red meat was assessed by an abbreviated food questionnaire and incident HF was ascertained through annual follow-up questionnaires. We used Cox proportional hazard models to estimate hazard ratios. In a multivariable model, there was a positive and graded relation between red meat consumption and HF [hazard ratio (95% CI) of 1.0 (reference), 1.02 (0.85-1.22), 1.08 (0.90-1.30), 1.17 (0.97-1.41), and 1.24 (1.03-1.48) from the lowest to the highest quintile of red meat, respectively (p for trend 0.007)]. This association was observed for HF with (p for trend 0.035) and without (p for trend 0.038) antecedent myocardial infarction.Our data suggest that higher intake of red meat is associated with an increased risk of HF."
1,"TITLE: Long-term effects of pioglitazone on carotid atherosclerosis in Japanese patients with type 2 diabetes without a recent history of macrovascular morbidity.ABSTRACT: No previous studies have evaluated the long-term anti-atherosclerotic effects of pioglitazone in Asian patients with type 2 diabetes. Therefore, the present study investigated the protective effects of pioglitazone on the progression of carotid intima-media thickness (IMT), an established surrogate marker of cardiovascular events in Japanese type 2 diabetic patients without a recent history of cardiovascular morbidity.This 2.5-4-year, randomized, open-label, blinded endpoint study was conducted in 6 centers across Japan. Patients received pioglitazone with or without other oral glucose-lowering drugs (excluding another thiazolidinedione) (n=89) or oral glucose-lowering drugs, excluding thiazolidinediones (n=97). Treatment was adjusted to achieve HbA(1c) <6.5%. The primary endpoints of the study were the absolute changes from the baseline to final visit in max- and mean-IMT in the average of bilateral common carotid arteries.Pioglitazone induced carotid IMT regression compared to baseline measurements (from 1.060 ± 0.2368 to 0.992 ± 0.1921 mm; p=0.0042 in max-IMT and from 0.839 ± 0.1873 to 0.780 ± 0.1571 mm; p=0.0019 in mean-IMT). Although the between-group difference did not reach statistical significance, the regression of carotid IMT values was greater in the pioglitazone-treatment group than in the non-pioglitazone group, (max-IMT: -0.069 ± 0.2199 mm vs -0.031 ± 0.2327 mm, respectively; p=NS, mean-IMT: -0.058 ± 0.1718 mm vs -0.043 ± 0.1644 mm, respectively; p=NS).Pioglitazone induced and maintained the long-term regression of carotid IMT in Japanese type 2 diabetic patients. This suggests that pioglitazone may inhibit the progression of atherosclerosis in this patient group. Further studies are required to verify these findings."
1,"TITLE: Quality of life in hormone receptor-positive HER-2+ metastatic breast cancer patients during treatment with letrozole alone or in combination with lapatinib.ABSTRACT: A phase III trial compared lapatinib plus letrozole (L + Let) with letrozole plus placebo (Let) as first-line therapy for hormone receptor (HR)(+) metastatic breast cancer (MBC) patients. The primary endpoint of progression-free survival (PFS) in patients whose tumors were human epidermal growth factor receptor (HER)-2(+) was significantly longer for L + Let than for Let (8.2 months versus 3 months; p = .019). This analysis focuses on quality of life (QOL) in the HER-2(+) population.QOL was assessed at screening, every 12 weeks, and at withdrawal using the Functional Assessment of Cancer Therapy-Breast (FACT-B). Changes from baseline were analyzed and the proportions of patients achieving minimally important differences in QOL scores were compared. Additional exploratory analyses evaluated how QOL changes reflected tumor progression status.Among the 1,286 patients randomized, 219 had HER-2(+) tumors. Baseline QOL scores were comparable in the two arms. Mean changes in QOL scores were generally stable over time for patients who stayed on study. The average change from baseline on the FACT-B total score in both arms was positive at all scheduled visits through week 48. There was no significant difference between the two treatment arms in the percentage of QOL responders.The addition of lapatinib to letrozole led to a significantly longer PFS interval while maintaining QOL during treatment, when compared with letrozole alone, thus confirming the clinical benefit of the combination therapy in the HR(+) HER-2(+) MBC patient population. This all oral regimen provides an effective option in this patient population, delaying the need for chemotherapy and its accompanying side effects."
1,"TITLE: Comparison of Vie Scope® and Macintosh laryngoscopes for intubation during resuscitation by paramedics wearing personal protective equipment.ABSTRACT: Endotracheal intubation (ETI) is still the gold standard of airway management, but in cases of sudden cardiac arrest in patients with suspected SARS-CoV-2 infection, ETI is associated with risks for both the patient and the medical personnel. We hypothesized that the Vie Scope® is more useful for endotracheal intubation of suspected or confirmed COVID-19 cardiac arrest patients than the conventional laryngoscope with Macintosh blade when operators are wearing personal protective equipment (PPE).Study was designed as a prospective, multicenter, randomized clinical trial performed by Emergency Medical Services in Poland. Patients with suspected or confirmed COVID-19 diagnosis who needed cardiopulmonary resuscitation in prehospital setting were included. Patients under 18 years old or with criteria predictive of impossible intubation under direct laryngoscopy, were excluded. Patients were randomly allocated 1:1 to Vie Scope® versus direct laryngoscopy with a Macintosh blade. Study groups were compared on success of intubation attempts, time to intubation, glottis visualization and number of optimization maneuvers.We enrolled 90 out-of-hospital cardiac arrest (OHCA) patients, aged 43-92 years. Compared to the VieScope® laryngoscope, use of the Macintosh laryngoscope required longer times for tracheal intubation with an estimated mean difference of -48 s (95%CI confidence interval [CI], -60.23, -35.77; p < 0.001). Moreover VieScope® improved first attempt success rate, 93.3% vs. 51.1% respectively (odds ratio [OR] = 13.39; 95%CI: 3.62, 49.58; p < 0.001).The use of the Vie Scope® laryngoscope in OHCA patients improved the first attempt success rate, and reduced intubation time compared to Macintosh laryngoscope in paramedics wearing PPE for against aerosol generating procedures.ClinicalTrials registration number NCT04365608."
1,"TITLE: Pansomatostatin Agonist Pasireotide Long-Acting Release for Patients with Autosomal Dominant Polycystic Kidney or Liver Disease with Severe Liver Involvement: A Randomized Clinical Trial.ABSTRACT: We assessed safety and efficacy of another somatostatin receptor analog, pasireotide long-acting release, in severe polycystic liver disease and autosomal dominant polycystic kidney disease. Pasireotide long-acting release, with its broader binding profile and higher affinity to known somatostatin receptors, has potential for greater efficacy.Individuals with severe polycystic liver disease were assigned in a 2:1 ratio in a 1-year, double-blind, randomized trial to receive pasireotide long-acting release or placebo. Primary outcome was change in total liver volume; secondary outcomes were change in total kidney volume, eGFR, and quality of life.Of 48 subjects randomized, 41 completed total liver volume measurements (=29 pasireotide long-acting release and =12 placebo). From baseline, there were -99±189 ml/m absolute and -3%±7% change in annualized change in height-adjusted total liver volume (from 2582±1381 to 2479±1317 ml/m) in the pasireotide long-acting release group compared with 136±117 ml/m absolute and 6%±7% increase (from 2387±759 to 2533±770 ml/m) in placebo (<0.001 for both). Total kidney volumes decreased by -12±34 ml/m and -1%±4% in pasireotide long-acting release compared with 21±21 ml/m and 4%±5% increase in the placebo group (=0.05 for both). Changes in eGFR were similar between groups. Among the =48 randomized, adverse events included hyperglycemia (26 of 33 [79%] in pasireotide long-acting release versus four of 15 [27%] in the placebo group; <0.001), and among the 47 without diabetes at baseline, 19 of 32 (59%) in the pasireotide long-acting release group versus one of 15 (7%) in the placebo group developed diabetes (=0.001).Another somatostatin analog, pasireotide long-acting release, slowed progressive increase in both total liver volume/total kidney volume growth rates without affecting GFR decline. Participants experienced higher frequency of adverse events (hyperglycemia and diabetes).Pasireotide LAR in Severe Polycystic Liver Disease, NCT01670110 PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_08_28_CJN13661119.mp3."
0,"TITLE: Comparative study of cisplatin-based definitive concurrent chemoradiotherapy with S-1 versus paclitaxel for unresectable locally advanced esophageal squamous cell carcinoma.ABSTRACT: This study compared the efficiency and safety of definitive concurrent chemoradiotherapy (CCRT) using Paclitaxel plus Cisplatin (TP) versus S-1 plus Cisplatin (CS) in unresectable locally advanced esophageal squamous cell carcinoma (LAESCC). Between January 2009 and December 2013, 203 LAESCC patients were retrospectively reviewed. We performed a propensity score matching analysis; 41 patients treated with the CS regimen were matched 1:1 to patients who received the TP regimen. Patient- and disease-related characteristics were well-balanced between the two groups. The CS group showed significantly better treatment compliance (90.2% vs. 70.7%, P = 0.026) and less hospital stay (48 days vs 49 days, P = 0.025) over the TP group during the CCRT course. The complete response rate was comparable between the two groups (51.2% vs. 48.8%, P = 0.825). The 1- and 3-year overall survival (OS) rates in the TP group were 63.4% and 32.4% compared to 62.8% and 32.1% in the CS group, respectively (P = 0.796). The 1- and 3-year progression-free survival (PFS) rates in the TP group were 51.2% and 24.9%, compared to 53.6% and 18.9% in the CS group, respectively (P = 0.630). The incidence of severe and total neutropenia in the TP group was significantly higher compared to the CS group (P = 0.011 and 0.046, respectively). Multivariate analysis revealed that T stage and the complete response rate were strong prognostic factors associated with OS and PFS. In conclusion, both treatment regimens yielded satisfactory survival outcomes, but the CS regimen could significantly improve treatment compliance, reduce hematological toxicities and lengths of hospital stay. Future prospective studies in large cohorts are highly warranted to confirm the findings in our report."
1,"TITLE: Pseudophakic cystoid macular edema prevention and risk factors; prospective study with adjunctive once daily topical nepafenac 0.3% versus placebo.ABSTRACT: Define the effectiveness of a topical non-steroidal anti-inflammatory drug (NSAID) added to topical steroid use after uncomplicated phacoemulsification for the prevention of pseudophakic cystoid macular edema (PCME) using a prospective, randomized, double-masked, placebo-controlled clinical study.Eyes (1000) were randomized to placebo (497) or nepafenac 0.3% (503) used once daily, post-operatively for 5 weeks at two ophthalmology clinics. Diagnosis of PCME was made by clinical, ocular coherence tomography (OCT), and with fluorescein angiography confirmation. Correlation of PCME to NSAID use and the presence of pre-operative risk factors for PCME were assessed including, contralateral PCME, diabetic retinopathy, retinal vein occlusion, macular hole, epiretinal membrane, macular degeneration, retinal detachment repair, and prostaglandin use.PCME was the most common complication associated with routine cataract surgery (4.2% with PCME risk factors, 2.0% with risk factors excluded). Topical nepafenac 0.3% significantly reduces the incidence of PCME compared to placebo when used after routine cataract surgery (p = .0001). When patients with pre-operative risk factors are excluded, the incidence of PCME between treatment and placebo groups is equivalent (p = 0.31). PCME relative risk (RR) was most significant in contralateral PCME (RR 19.5), diabetic retinopathy (RR 13.1), retinal vein occlusion (RR 12.9), macular hole (RR 7.7), and epiretinal membrane (RR 5.7). Prostaglandin use and previous retinal detachment were not shown to increase risk.Pseudophakic cystoid macular edema is common after phacoemulsification cataract surgery. Topical nepafenac 0.3% reduces PCME in patients with pre-operative risk factors for PCME compared to placebo but shows no benefit in patients without pre-operative risk factors.NIH ClincalTrials.gov retrospectively registered January 15, 2017, NCT03025945 ."
1,"TITLE: Simultaneous zinc and vitamin A supplementation in Bangladeshi children: randomised double blind controlled trial.ABSTRACT: To evaluate the effect of simultaneous zinc and vitamin A supplementation on diarrhoea and acute lower respiratory infections in children.Randomised double blind placebo controlled trial.Urban slums of Dhaka, Bangladesh.800 children aged 12-35 months were randomly assigned to one of four intervention groups: 20 mg zinc once daily for 14 days; 200 000 IU vitamin A, single dose on day 14; both zinc and vitamin A; placebo. The children were followed up once a week for six months, and morbidity information was collected.The incidence and prevalence of diarrhoea were lower in the zinc and vitamin A groups than in the placebo group. Zinc and vitamin A interaction had a rate ratio (95% confidence interval) of 0.79 (0.66 to 0.94) for the prevalence of persistent diarrhoea and 0.80 (0.67 to 0.95) for dysentery. Incidence (1.62; 1.16 to 2.25) and prevalence (2.07; 1.76 to 2.44) of acute lower respiratory infection were significantly higher in the zinc group than in the placebo group. The interaction term had rate ratios of 0.75 (0.46 to 1.20) for incidence and 0.58 (0.46 to 0.73) for prevalence of acute lower respiratory infection.Combined zinc and vitamin A synergistically reduced the prevalence of persistent diarrhoea and dysentery. Zinc was associated with a significant increase in acute lower respiratory infection, but this adverse effect was reduced by the interaction between zinc and vitamin A."
1,"TITLE: Follow-up Schedule for Patients With Sentinel Node-negative Cutaneous Melanoma (The MELFO Study): An International Phase III Randomized Clinical Trial.ABSTRACT: The MELFO (MELanoma FOllow-up) study is an international phase III randomized controlled trial comparing an experimental low-intensity schedule against current national guidelines.Evidence-based guidelines for the follow-up of sentinel node-negative melanoma patients are lacking.Overall, 388 adult patients diagnosed with sentinel node-negative primary melanoma patients were randomized in cancer centers in the Netherlands and United Kingdom between 2006 and 2016. The conventional schedule group (control: n=196) was reviewed as per current national guidelines. The experimental schedule group (n=192) was reviewed in a reduced-frequency schedule. Quality of life was the primary outcome measurement. Detection rates and survival outcomes were recorded. Patient satisfaction rates and compliance with allocated schedules were compared.At 5 years, both arms expressed high satisfaction with their regimens (>97%). This study found no significant group effect on any patient-reported outcome measure scores between the follow-up protocols. In total, 75/388 (19.4%) patients recurred, with no difference in incidence found between the 2 arms (hazard ratio=0.87, 95% confidence interval: 0.54-1.39, P =0.57). Self-examination was the method of detection for 25 experimental patients and 32 control patients (75.8% vs. 76.2%; P =0.41). This study found no difference in any survival outcomes between the 2 study arms (disease-free survival: hazard ratio=1.00, 95% confidence interval: 0.49-2.07, P =0.99).A reduced-intensity, American Joint Committee on Cancer (AJCC) stage-adjusted follow-up schedule for sentinel node-negative melanoma patients is a safe strategy, and patient self-examination is effective for recurrence detection with no evidence of diagnostic delay. Patients' acceptance is very high."
1,"TITLE: Effects of vatinoxan in dogs premedicated with medetomidine and butorphanol followed by sevoflurane anaesthesia: a randomized clinical study.ABSTRACT: To investigate effects of vatinoxan in dogs, when administered as intravenous (IV) premedication with medetomidine and butorphanol before anaesthesia for surgical castration.A randomized, controlled, blinded, clinical trial.A total of 28 client-owned dogs.Dogs were premedicated with medetomidine (0.125 mg m) and butorphanol (0.2 mg kg) (group MB; n = 14), or medetomidine (0.25 mg m), butorphanol (0.2 mg kg) and vatinoxan (5 mg m) (group MB-VATI; n = 14). Anaesthesia was induced 15 minutes later with propofol and maintained with sevoflurane in oxygen (targeting 1.3%). Before surgical incision, lidocaine (2 mg kg) was injected intratesticularly. At the end of the procedure, meloxicam (0.2 mg kg) was administered IV. The level of sedation, the qualities of induction, intubation and recovery, and Glasgow Composite Pain Scale short form (GCPS-SF) were assessed. Heart rate (HR), respiratory rate (f), mean arterial pressure (MAP), end-tidal concentration of sevoflurane (Fe'Sevo) and carbon dioxide (Pe'CO) were recorded. Blood samples were collected at 10 and 30 minutes after premedication for plasma medetomidine and butorphanol concentrations.At the beginning of surgery, HR was 61 ± 16 and 93 ± 23 beats minute (p = 0.001), and MAP was 78 ± 7 and 56 ± 7 mmHg (p = 0.001) in MB and MB-VATI groups, respectively. No differences were detected in f, Pe'CO, Fe'Sevo, the level of sedation, the qualities of induction, intubation and recovery, or in GCPS-SF. Plasma medetomidine concentrations were higher in group MB-VATI than in MB at 10 minutes (p = 0.002) and 30 minutes (p = 0.0001). Plasma butorphanol concentrations were not different between groups.In group MB, HR was significantly lower than in group MB-VATI. Hypotension detected in group MB-VATI during sevoflurane anaesthesia was clinically the most significant difference between groups."
1,"TITLE: Interactive Inpatient Asthma Education: A Randomized Controlled Trial.ABSTRACT: Inpatient asthma education interventions provide benefit compared with usual care, but evaluation of the most effective educational model is needed. We compared the impact of interactive versus didactic inpatient pediatric asthma education on subsequent emergency department (ED) visits and hospitalizations.Children (aged 2‒16) with asthma admitted to a tertiary care children's hospital with an asthma exacerbation between October 2016 and June 2017 were randomly assigned to interactive or didactic (control) asthma education. The primary outcome was asthma ED visits at 6 and 12 months; secondary outcomes included hospitalizations (6 and 12 months), inhaler technique, asthma knowledge, symptoms, quality of life, and parental management skills at baseline, discharge, and/or 12 months.One hundred forty participants (69 interactive, 71 control) completed the study. There were no differences in ED visits at 6 or 12 months. Compared to controls, the interactive group had fewer hospitalizations (10.1% vs 22.5%; P = .04) at 6 months. Inhaler technique in the interactive group improved at discharge (mean change 4.07 [95% confidence interval (CI): 3.21-4.94]) and remained increased at 12 months (P = .03). Patient-reported asthma symptoms and quality of life were similar in both groups at baseline (19.9 vs 20.62, best possible score 8) and significantly improved in the interactive group at 12 months (least square mean change, 3.52 vs -1.75; P < .01).There were no differences in ED visits; however, the interactive education reduced asthma hospitalizations over a 6-month period. These findings demonstrate that educational delivery methods can play a role in improving clinical outcomes for asthma."
1,"TITLE: Efficacy of 4.0 mg versus 0.4 mg Folic Acid Supplementation on the Reproductive Outcomes: A Randomized Controlled Trial.ABSTRACT: Folic acid (FA) supplementation prevents neural tube defects (NTDs), but the effects on other reproductive outcomes are unclear. While common recommendation is 0.4 mg/day in addition to regular nutrition, the most appropriate dose of FA is still under debate. We investigated the effects of a higher dose of periconception FA on reducing adverse reproductive outcomes. In this multicenter double-blind randomized controlled trial (RCT), 1060 women (aged 18-44 years and planning a pregnancy) were randomly assigned to receive 4.0 mg or 0.4 mg of FA daily. The primary outcome was the occurrence of congenital malformations (CMs). A composite outcome including one or more adverse pregnancy outcomes was also evaluated. A total of 431 women had a natural conception within 1 year. The primary outcome occurred in 8/227 (3.5%) women receiving 4.0 mg FA and 9/204 (4.4%) women receiving 0.4 mg FA (RR 0.80; 95%CI 0.31 to 2.03). The composite outcome occurred in 43/227 (18.9%) women receiving 4.0 mg FA and 75/204 (36.8%) women receiving 0.4 mg FA (RR 0.51; 95%CI 0.40 to 0.68). FA 4.0 mg supplementation was not associated with different occurrence of CMs, compared to FA 0.4 mg supplementation. However, FA 4.0 mg supplementation was associated with lower occurrence of other adverse pregnancy outcomes."
0,"TITLE: Incidence and predictors of surgical site infection in women who are obese and give birth by elective caesarean section: A secondary analysis.ABSTRACT: Surgical site infection (SSI) after a caesarean section is of concern (CS) is of concern to both clinicians and women themselves.The aim of this study is to identify the cumulative incidence and predictors of SSI in women who are obese and give birth by elective CS.The method used was planned secondary analysis of data from women with a pre-pregnancy body mass index (BMI) ≥30 kg/m giving birth by elective CS in a multicentre randomised controlled trial of a prophylactic closed-incision negative pressure wound therapy dressing. Data were collected from medical records, direct observations of the surgical site and self-reported signs and symptoms from October 2015 to December 2019. The Centers for Disease Control and Prevention definition was used to identify SSI. Women were followed up once in hospital just before discharge and then weekly for four weeks after discharge. Blinded outcome assessors determined SSI. After the cumulative incidence of SSI was calculated, multiple variable logistic regression models were used to identify independent risk factors for SSI.SSI incidence in 1459 women was 8.4% (122/1459). Multiple variable-adjusted odds ratios (OR) for SSI were BMI ≥40 kg/m (OR 1.55, 95% confidence interval (CI) 1.30-1.86) as compared to BMI 30-34.9 0 kg/m , ≥2 previous pregnancies (OR 1.38, 95% CI 1.00-1.80) as compared to no previous pregnancies and pre-CS vaginal cleansing (OR 0.55, 95% CI 0.33-0.99).Our findings may inform preoperative counselling and shared decision-making regarding planned elective CS for women with pre-pregnancy BMI ≥30 kg/m ."
1,"TITLE: Peanuts or an Isocaloric Lower Fat, Higher Carbohydrate Nighttime Snack Have Similar Effects on Fasting Glucose in Adults with Elevated Fasting Glucose Concentrations: a 6-Week Randomized Crossover Trial.ABSTRACT: The glycemic effects of peanuts are not well studied and no trials have been conducted in adults with elevated fasting plasma glucose (FPG). Furthermore, intake of peanuts as a nighttime snack, an eating occasion affecting FPG, has not been examined.The aim was to determine the effect of consuming 28 g/d of peanuts as a nighttime snack for 6 wk on glycemic control and cardiovascular disease risk factors, compared with an isocaloric lower fat, higher carbohydrate (LFHC) snack (whole grain crackers and low-fat cheese), in adults with elevated FPG.In a randomized crossover trial, 50 adults (FPG 100 ± 8 mg/dL) consumed dry roasted, unsalted peanuts [164 kcal; 11% energy (E) carbohydrate, 17% E protein, and 73% E fat] or a LFHC snack (164 kcal; 54% E carbohydrate, 17% E protein, and 33% E fat) in the evening (after dinner and before bedtime) for 6 wk with a 4-wk washout period. Primary (FPG) and secondary end points [Healthy Eating Index-2015 (HEI-2015), weight, insulin, fructosamine, lipids/lipoproteins, central and peripheral blood pressure, and pulse wave velocity] were evaluated at the beginning and end of each condition. Linear mixed models were used for data analysis.FPG was not different between the peanut and LFHC conditions (end point mean difference: -0.6 mg/dL; 95% CI: -2.7, 1.6; P = 0.67). There were no between-condition effects for secondary cardiometabolic endpoints. The HEI-2015 score was not different between the conditions (3.6 points; P = 0.19), although the seafood/plant protein (2.0 points; P < 0.01) and added sugar (0.8 points; P = 0.04) components were improved following peanut intake. The whole grain component was lower with peanuts compared with LFHC (-2.6 points; P < 0.01).In adults with elevated FPG, peanuts as a nighttime snack (28 g/d) did not affect FPG compared with an isocaloric LFHC snack after 6 wk.This trial was registered at clinicaltrials.gov as NCT03654651."
1,"TITLE: Brentuximab Vedotin with Chemotherapy in Pediatric High-Risk Hodgkin's Lymphoma.ABSTRACT: In adults with advanced-stage Hodgkin's lymphoma, the CD30-directed antibody-drug conjugate brentuximab vedotin combined with multiagent chemotherapy has been shown to have greater efficacy, but also more toxic effects, than chemotherapy alone. The efficacy of this targeted therapy approach in children and adolescents with Hodgkin's lymphoma is unclear.We conducted an open-label, multicenter, randomized, phase 3 trial involving patients 2 to 21 years of age with previously untreated Hodgkin's lymphoma of stage IIB with bulk tumor or stage IIIB, IVA, or IVB. Patients were assigned to receive five 21-day cycles of brentuximab vedotin with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide (brentuximab vedotin group) or the standard pediatric regimen of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (standard-care group). Slow-responding lesions, defined by a score of 4 or 5 (on a 5-point scale, with scores of 1 to 3 indicating rapid-responding lesions), were identified on centrally reviewed positron-emission tomography-computed tomography after two cycles. Involved-site radiation therapy was administered after the fifth cycle of therapy to slow-responding lesions and to large mediastinal adenopathy that was present at diagnosis. The primary end point was event-free survival, defined as the time until disease progression occurred, relapse occurred, a second malignant neoplasm developed, or the patient died. Safety and overall survival were assessed.Of 600 patients who were enrolled across 153 institutions, 587 were eligible. At a median follow-up of 42.1 months (range, 0.1 to 80.9), the 3-year event-free survival was 92.1% (95% confidence interval [CI], 88.4 to 94.7) in the brentuximab vedotin group, as compared with 82.5% (95% CI, 77.4 to 86.5) in the standard-care group (hazard ratio for event or death, 0.41; 95% CI, 0.25 to 0.67; P<0.001). The percentage of patients who received involved-site radiation therapy did not differ substantially between the brentuximab vedotin group and the standard-care group (53.4% and 56.8%, respectively). Toxic effects were similar in the two groups. Overall survival at 3 years was 99.3% (95% CI, 97.3 to 99.8) in the brentuximab vedotin group and 98.5% (95% CI, 96.0 to 99.4) in the standard-care group.The addition of brentuximab vedotin to standard chemotherapy resulted in superior efficacy, with a 59% lower risk of an event or death, and no increase in the incidence of toxic effects at 3 years. (Funded by the National Institutes of Health and others; AHOD1331 ClinicalTrials.gov number, NCT02166463.)."
1,"TITLE: Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma.ABSTRACT: A recombinant humanized anti-IgE mAb, omalizumab, forms complexes with free IgE, blocking its interaction with mast cells and basophils; as a consequence, it might be effective in the treatment of asthma.The purpose of this study was to evaluate the efficacy and safety of omalizumab in the treatment of inhaled corticosteroid-dependent asthma.In this phase III, double-blinded, placebo-controlled trial, 525 subjects with severe allergic asthma requiring daily inhaled corticosteroids were randomized to receive placebo or omalizumab subcutaneously every 2 or 4 weeks, depending on baseline IgE level and body weight. Inhaled corticosteroid doses were kept stable over the initial 16 weeks of treatment and tapered during a further 12-week treatment period.Omalizumab treatment resulted in significantly fewer asthma exacerbations per subject and in lower percentages of subjects experiencing an exacerbation than placebo treatment during the stable steroid phase (0.28 vs 0.54 [P =.006] and 14.6% vs 23.3% [P =.009], respectively) and during the steroid reduction phase (0.39 vs 0.66 [P =.003] and 21.3% vs 32.3% [P =.004], respectively). Beclomethasone dipropionate reduction was significantly greater with omalizumab treatment than with placebo (median 75% vs 50% [P <.001]), and beclomethasone dipropionate discontinuation was more likely with omalizumab (39.6% vs 19.1% [P <.001]). Improvements in asthma symptoms and pulmonary function occurred along with a reduction in rescue beta-agonist use. Omalizumab was well tolerated, with an adverse-events profile similar to that of placebo.The addition of omalizumab to standard asthma therapy reduces asthma exacerbations and decreases inhaled corticosteroid and rescue medication use."
1,"TITLE: Efficacy and Safety of Intensive Versus Nonintensive Supplemental Insulin With a Basal-Bolus Insulin Regimen in Hospitalized Patients With Type 2 Diabetes: A Randomized Clinical Study.ABSTRACT: Administration of supplemental sliding scale insulin for correction of hyperglycemia in non-intensive care unit (ICU) patients with type 2 diabetes is frequently used with basal-bolus insulin regimens. In this noninferiority randomized controlled trial we tested whether glycemic control is similar with and without aggressive sliding scale insulin treatment before meals and bedtime in patients treated with basal-bolus insulin regimens.Patients with type 2 diabetes with admission blood glucose (BG) 140-400 mg/dL treated with basal-bolus insulin were randomized to intensive (correction for BG >140 mg/dL, n = 108) or to nonintensive (correction for BG >260 mg/dL, n = 107) administration of rapid-acting sliding scale insulin before meals and bedtime. The groups received the same amount of sliding scale insulin for BG >260 mg/dL. Primary outcome was difference in mean daily BG levels between the groups during hospitalization.Mean daily BG in the nonintensive group was noninferior to BG in the intensive group with equivalence margin of 18 mg/dL (intensive 172 ± 38 mg/dL vs. nonintensive 173 ± 43 mg/dL, P = 0.001 for noninferiority). There were no differences in the proportion of target BG readings of 70-180 mg/dL, <70 or <54 mg/dL (hypoglycemia), or >350 mg/dL (severe hyperglycemia) or total, basal, or prandial insulin doses. Significantly fewer subjects received sliding scale insulin in the nonintensive (n = 36 [34%]) compared with the intensive (n = 98 [91%] [P < 0.0001]) group with no differences in sliding scale insulin doses between the groups among those who received sliding scale insulin (intensive 7 ± 4 units/day vs. nonintensive 8 ± 4 units/day, P = 0.34).Among non-ICU patients with type 2 diabetes on optimal basal-bolus insulin regimen with moderate hyperglycemia (BG <260 mg/dL), a less intensive sliding scale insulin treatment did not significantly affect glycemic control."
1,"TITLE: Effects of luseogliflozin on estimated plasma volume in patients with heart failure with preserved ejection fraction.ABSTRACT: Sodium glucose co-transporter 2 inhibitors have diuretic effects in both patients with glycosuria and with natriuresis. We sought to assess the effect of luseogliflozin on estimated plasma volume (ePV) in patients with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF).This study was a post-hoc analysis of the MUSCAT-HF trial (UMIN000018395), a multicentre, prospective, open-label, randomized controlled trial that assessed the effect of 12 weeks of luseogliflozin (2.5 mg, once daily, n = 83) as compared with voglibose (0.2 mg, three times daily, n = 82) on the reduction in brain natriuretic peptide (BNP) in patients with type 2 diabetes and HFpEF. The analysis compared the change in ePV calculated by the Straus formula from baseline to Weeks 4, 12, and 24, using a mixed-effects model for repeated measures. We also estimated the association between changes in ePV and changes in other clinical parameters, including BNP levels. Luseogliflozin significantly reduced ePV as compared to voglibose at Week 4 {adjusted mean group-difference -6.43% [95% confidence interval (CI): -9.11 to -3.74]}, at Week 12 [-8.73% (95%CI: -11.40 to -6.05)], and at Week 24 [-11.02% (95%CI: -13.71 to -8.33)]. The effect of luseogliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in ePV at Week 12 was significantly associated with log-transformed BNP (r = 0.197, P = 0.015) and left atrial volume index (r = 0.283, P = 0.019).Luseogliflozin significantly reduced ePV in patients with type 2 diabetes and HFpEF, as compared with voglibose. The reduction of intravascular volume by luseogliflozin may provide clinical benefits to patients with type 2 diabetes and HFpEF."
1,"TITLE: Misoprostol and oxytocin versus oxytocin alone in the active management of the third stage of labour: a randomised, double-blind, placebo-controlled trial.ABSTRACT: We investigated whether the use of misoprostol plus oxytocin in the active management of the third of stage of labour (AMTSL) would reduce the rate of primary postpartum haemorrhage (PPH) compared with intramuscular oxytocin alone. This was a multicentre, double-blind, placebo-controlled, randomised trial where 1036 pregnant women, in addition to intramuscular oxytocin (10 IU) in the third stage of labour, randomly received either 400 µg sublingual misoprostol (519 women) or a placebo (517 women). The primary outcome measure was the mean blood loss (MBL) within 1 h of delivery. The trial was registered with ClinicalTrials.gov (NCT02424201). The MBL in the oxytocin plus misoprostol group was 229.73 ± 108.12 compared to 274.58 ± 121.09 in the oxytocin plus placebo group ( = 6.289,  < .001). Twenty-eight (5.4%) women in the misoprostol group had a blood loss ≥500 ml  39 (7.5%) women in the placebo group (risk-ratio [RR] - 0·72, 95%CI 0.45-1.14;  = .1616). The combination of misoprostol with oxytocin in the AMTSL reduces MBL post-delivery but is not superior to oxytocin alone in the reduction of the rate of PPH.IMPACT STATEMENT The routine use of 10IU of intramuscular oxytocin in the active management of the third stage of labour reduces the rates of postpartum haemorrhage. The addition of 400ug of sublingual misoprostol to the routine use of 10IU of intramuscular oxytocin in the active management of the third stage of labour reduces mean blood loss when compared with intramuscular oxytocin alone, but is not better in reducing the rates of postpartum haemorrhage. Routine use of misoprostol as adjuncts to the active management of the third stage of labour does not reduce the rate of PPH."
1,"TITLE: Efficacy And Safety Of Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler (GFF MDI) Formulated Using Co-Suspension Delivery Technology In Chinese Patients With COPD.ABSTRACT: Glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI) is a long-acting muscarinic antagonist/long-acting β-agonist fixed-dose combination therapy delivered by MDI, formulated using innovative co-suspension delivery technology. The PINNACLE-4 study evaluated the efficacy and safety of GFF MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) from Asia, Europe, and the USA. This article presents the results from the China subpopulation of PINNACLE-4.In this randomized, double-blind, placebo-controlled, parallel-group Phase III study (NCT02343458), patients received GFF MDI 18/9.6 µg, glycopyrrolate (GP) MDI 18 µg, formoterol fumarate (FF) MDI 9.6 µg, or placebo MDI (all twice daily) for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 second at Week 24. Secondary lung function endpoints and patient-reported outcome measures were also assessed. Safety was monitored throughout the study.Overall, 466 patients from China were included in the intent-to-treat population (mean age 63.6 years, 95.7% male). Treatment with GFF MDI improved the primary endpoint compared to GP MDI, FF MDI, and placebo MDI (least squares mean differences: 98, 104, and 173 mL, respectively; all 0.0001). GFF MDI also improved daily total symptom scores and time to first clinically important deterioration versus monocomponents and placebo MDI, and Transition Dyspnea Index focal score versus placebo MDI. Rates of treatment-emergent adverse events were similar across the active treatment groups and slightly higher in the placebo MDI group.GFF MDI improved lung function and daily symptoms versus monocomponents and placebo MDI and improved dyspnea versus placebo MDI. All treatments were well tolerated with no unexpected safety findings. Efficacy and safety results were generally consistent with the global PINNACLE-4 population, supporting the use of GFF MDI in patients with COPD from China."
1,"TITLE: Occurrence of hypertension during third-line anlotinib is associated with progression-free survival in patients with squamous cell lung cancer (SCC): A post hoc analysis of the ALTER0303 trial.ABSTRACT: There is a lack of targeted therapeutic options for squamous cell lung cancer (SCC). Accelerated hypertension is an issue with many targeted therapies for lung cancer. This study aimed to analyze the efficacy of anlotinib, based on progression-free survival (PFS) and overall survival (OS) in patients with SCC, stratified by hypertension and Eastern Cooperative Oncology Group (ECOG) score.This was a post hoc analysis of a multicenter, double-blind, phase III ALTER0303 randomized controlled trial. Only patients with SCC were included. The occurrence of hypertension during the study period was defined according to CTCAE 4.03. OS and PFS were the primary and secondary endpoints, respectively. The patients were stratified according to hypertension and ECOG score, respectively.The median PFS in the patients who developed hypertension was longer than in those who did not (7.2 (95% CI: 3.5-11.0) versus 3.2 (95% CI: 1.2-5.3) months, p = 0.001; HR (95% CI), 0.4 (0.2-0.8)). In the ECOG 0 patients, the median PFS in the patients who developed hypertension versus those who did not was 5.6 vs. 1.8 months, respectively (Figure 2(d)). In the ECOG 1 patients, the median PFS in the patients who developed hypertension versus those who did not was 7.0 (95% CI: 3.0-11.0) vs. 4.8 (95% CI: 1.2-8.5) months (p = 0.043). No statistically significant differences were found in OS in the stratified analyses.The occurrence of hypertension might be a clinical indicator predicting the efficacy of third-line anlotinib treatment in patients with SCC."
1,"TITLE: Motivational Interviewing in Preventing Early Childhood Caries in Primary Healthcare: A Community-based Randomized Cluster Trial.ABSTRACT: To assess the effectiveness of motivational interviewing in preventing early childhood caries compared with conventional oral health education.Twelve health care units in southern Brazil were randomly allocated in 2 groups of 6 and professionals in 1 group were trained in motivational interviewing. The mothers/children and external examiners were blinded to the intervention. The data were collected by calibrated examiners using questionnaires and a clinical examination based on modified International Caries Detection and Assessment System criteria. Of the 674 children born in the catchment area in the year 2013, 469 received the intervention (224 in the conventional oral health education group, 245 in the motivational interviewing group), and 320 were examined by the end of the study (145 in the conventional oral health education group, 175 in the motivational interviewing group), with mean age of 30 months. The final follow-up was 68%, after 3 years.Mean of decayed, missing, and filled surfaces at the end of the study period for the whole sample was 1.34 (95% CI 0.97-1.71). The caries rate per 100 surface-year in the conventional oral health education group was 1.74 (95% CI 1.14-2.34) and in the motivational interviewing group, it was 0.92 (95% CI 0.63-1.20). To correct for clustering effect and unbalanced factors, multilevel Poisson regression was fitted and the effect of motivational interviewing on the incidence rate ratio was 0.40 (95% CI 0.21-0.79).An intervention based on the principles of motivational interviewing style was more effective in reducing the number of surfaces affected by early childhood caries compared with conventional oral health education intervention.ClinicalTrials.govNCT02578966, Brazilian Registry of Clinical Trials RBR-8fvwxq."
1,"TITLE: Effectiveness of the population-based 'check your health preventive programme' conducted in a primary care setting: a pragmatic randomised controlled trial.ABSTRACT: Health checks have been suggested as an early detection approach aiming at lowering the risk of chronic disease development. This study aimed to evaluate the effectiveness of a health check programme offered to the general population, aged 30-49 years.The entire population aged 30-49 years (N=26 216) living in the municipality of Randers, Denmark, was invited to a health check during 5 years. A pragmatic household cluster-randomised controlled trial was conducted in 10 505 citizens. The intervention group (IG, N=5250) included citizens randomised to the second year and reinvited in the 5th year. The comparison group (CG, N=5255) included citizens randomised to the 5th year. Outcomes were modelled cardiovascular disease (CVD) risk; self-reported physical activity (PA) and objectively measured cardio respiratory fitness (CRF); self-rated health (short-form 12 (SF-12)), self-rated mental health (SF-12_Mental Component Score (MCS)) and, registry information on sick-leave and employment. Due to low participation, we compared groups matched on propensity scores for participation when reinvited.Participation in the first health check was 51% (N=2698) in the IG and 40% (N=2120) in the CG. In the IG 26% (N=1340) participated in both the first and second health checks. No intervention effects were found comparing IG and CG. Mean differences were (95% CI): modelled CVD risk: -0.052 (95% CI -0.107 to 0.003)%, PA: -0.156 (-0.331 to 0.019) days/week with 30 min moderate PA, CRF: 0.133 (-0.560 to 0.826) mL O/min/kg, SF-12: -0.003 (-0.032 to 0.026), SF-12_MCS: 0.355 (-0.423 to 1.132), sick leave periods ≥3 weeks: -0.004 (-0.025 to 0.017), employment: -0.004 (-0.032 to 0.024).Preventive health checks offered to the general population, aged 30-49 years, had no effects on a wide range of indicators of chronic disease risk.NCT02028195."
0,"TITLE: Prognostic markers compared to CD3+TIL in locally advanced nasopharyngeal carcinoma.ABSTRACT: Locally advanced nasopharyngeal carcinoma (LA-NPC) is more prevalent in some geographic regions, including Saudi Arabia. Typically, Tumor-Node-Metastasis (TNM) staging is used in NPC. However, it is inadequate to assess the prognosis of LA-NPC.Therefore, we analyzed and compared several previously reported prognostic factors in LA-NPC patients, retrospectively, including CD3+tumor-infiltrating lymphocytes (TIL) and peripheral blood hemoglobin, EBV DNA copy number, ratios of albumin-to-alkaline phosphatase ratio (AAPR), neutrophils, or platelets-to-lymphocytes (NLR, PLR). The studied cohort was 83 LA-NPC patients previously recruited for a randomized phase II trial with a different aim.Univariate cox regression analysis showed no significant correlation between any of the tested variables with disease-free survival (DFS) or overall survival (OS) with the exception of low CD3+ TIL infiltration, which correlated significantly with DFS (HR = 6.7, P = <.001) and OS (HR = 9.1, P = .043). Similarly, in a validated multivariate cox regression analysis, only low CD3+ TIL correlated significantly with DFS (HR = 7.0, P < .001 for TIL) and OS (HR = 9.4, P = .040).Among tested parameters, CD3+ TIL was the only independent prognostic marker for DFS and OS in LA-NPC patients treated with CCRT. This study supports the use of CD3+TIL, over other factors, as an independent prognostic factor in LA-NPC."
1,"TITLE: Empagliflozin compared with glimepiride in metformin-treated patients with type 2 diabetes: 208-week data from a masked randomized controlled trial.ABSTRACT: To report results at week 208, including a 104-week masked extension, of the EMPA-REG H2H-SU trial in patients with type 2 diabetes with inadequate glycaemic control on metformin, in which empagliflozin 25 mg given for 104 weeks provided a sustained reduction in glycated haemoglobin (HbA1c) with a small but statistically significant benefit vs glimepiride, sustained reductions in weight and blood pressure, and low risk of hypoglycaemia.Patients with type 2 diabetes and HbA1c 53-86 mmol/mol (7% to 10%) were randomized to empagliflozin 25 mg or glimepiride 1 to 4 mg for 104 weeks as add-on to metformin. Patients who completed the randomized treatment period could participate in a 104-week extension in which they continued the double-blind treatment allocated at randomization.Of 765 and 780 patients treated with empagliflozin and glimepiride, 576 and 549 patients, respectively, entered the extension period of the study. At week 208, the adjusted mean difference in change from baseline in HbA1c with empagliflozin vs glimepiride was -1.96 mmol/mol, 95% CI -3.57, -0.35 (-0.18%, 95% CI -0.33, -0.03); P = 0.0172. Rescue therapy was given to 23% of patients on empagliflozin and 34% on glimepiride (odds ratio 0.56 [95% CI 0.45, 0.71]; P < 0.0001). Confirmed hypoglycaemic adverse events (plasma glucose ≤3.9 mmol/L and/or requiring assistance) occurred in 3% of patients on empagliflozin and 28% on glimepiride (odds ratio 0.08 [95% CI 0.05, 0.13]; P < 0.0001).In patients with type 2 diabetes, empagliflozin 25 mg as add-on to metformin for 208 weeks reduced HbA1c with a significantly lower risk of hypoglycaemia and a significantly smaller proportion of patients receiving rescue therapy compared with glimepiride."
1,"TITLE: Low-molecular-weight heparin alone versus a combination of unfractionated heparin and low-molecular-weight heparin.ABSTRACT: We analyzed the effect of the pharmacologic combination of 2 indirect antithrombin drugs--enoxaparin (low-molecular-weight heparin) and unfractionated heparin--versus enoxaparin alone on the recurrence of ischemia.Blocking some key factors of the coagulation cascade supports the concept that an antithrombin effect is needed during the acute phase of ischemia.This was a prospective, randomized, pilot trial in patients with an acute coronary ischemic event occurring within the previous 24 hours. A total of 126 patients were allocated to receive aspirin (200 mg/day orally) plus 1 mg/kg subcutaneous enoxaparin at 8 AM and 12.500 IU of subcutaneous unfractionated heparin at 8 PM (group A) or subcutaneous enoxaparin 1 mg/kg (group B).Severe recurrent ischemia provoking urgent coronary revascularization occurred in 12 patients (9.5%), 3 (5%) in group A and 9 (13%) in group B (P = .1). Refractory angina was present in 27 patients (21%), 10 (17%) in group A and 17 (25%) in group B (P = .45). The combination of severe recurrent ischemia and refractory angina occurred in 23% of group A, and 37% of group B (odds ratio 0.49; 95% confidence intervals, 0.21-1.15; P = .07). A total of 7 patients (5%) had acute nonfatal myocardial infarction develop, 3 (5%) in group A and 4 (6%) in group B. Two (1.6%) deaths were observed in the study, both in group B. The incidence of the double end point (death plus nonfatal myocardial infarction) was 5% in group A versus 9% in group B (P = .5) and the triple end point (death, nonfatal myocardial infarction, and severe recurrent ischemia) was 10.5% in group A vs 22% in group B (odds ratio 0.42, 95% confidence intervals, 0.13-1.29; P = .09).The combination of 2 indirect antithrombin drugs capable of intermittently blocking the coagulation system is not associated with a significant loss of safety."
1,"TITLE: Relation of oxidative biomarkers, vascular dysfunction, and progression of coronary artery calcium.ABSTRACT: The relation between oxidative stress and coronary artery calcium (CAC) progression is currently not well described. The present study evaluated the relation among the biomarkers of oxidative stress, vascular dysfunction, and CAC. Sixty asymptomatic subjects participated in a randomized trial evaluating the effect of aged garlic extract plus supplement versus placebo and underwent measurement of CAC. The postcuff deflation temperature-rebound index of vascular function was assessed using a reactive hyperemia procedure. The content of oxidized phospholipids (OxPL) on apolipoprotein B-100 (apoB) particles detected by antibody E06 (OxPL/apoB), lipoprotein(a), IgG and IgM autoantibodies to malondialdehyde-low-density lipoprotein and apoB-immune complexes were measured at baseline and after 12 months of treatment. CAC progression was defined as an annual increase in CAC >15%. Vascular dysfunction was defined according to the tertiles of temperature-rebound at 1 year of follow-up. From baseline to 12 months, a strong inverse correlation was noted between an increase in CAC scores and increases in temperature-rebound (r(2) = -0.90), OxPL/apoB (r(2) = -0.85), and lipoprotein(a) (r(2) = -0.81) levels (p <0.0001 for all). The improvement in temperature-rebound correlated positively with the increases in OxPL/apoB (r(2) = 0.81, p = 0.0008) and lipoprotein(a) (r(2) = 0.79, p = 0.0001) but inversely with autoantibodies to malondialdehyde-low-density lipoprotein and apoB-immune complexes. The greatest CAC progression was noted with the lowest tertiles of increases in temperature-rebound, OxPL/apoB and lipoprotein(a) and the highest tertiles of increases in IgG and IgM malondialdehyde-low-density lipoprotein. In conclusion, the present results have documented a strong relation among markers of oxidative stress, vascular dysfunction, and progression of coronary atherosclerosis. Increases in OxPL/apoB and lipoprotein(a) correlated strongly with increases in vascular function and predicted a lack of progression of CAC."
1,"TITLE: Pars plana vitrectomy and removal of the internal limiting membrane in diabetic macular edema unresponsive to grid laser photocoagulation.ABSTRACT: To evaluate the effectiveness of pars plana vitrectomy (PPV) with removal of the internal limiting membrane (ILM) in diabetic patients with macular edema unresponsive to grid laser photocoagulation.In this randomized controlled study, 20 eyes of 10 patients with diabetic macular edema unresponsive to grid laser photocoagulation were evaluated. PPV with ILM removal was performed randomly in one eye each of 10 patients and taken as the study group; the untreated fellow eyes were taken as the control group. Main outcome measures were foveal thickness changes measured with optical coherence tomography and preoperative and post-operative visual acuity. Mann-Whitney U, Wilcoxon, and chi-square tests were used in statistical analysis.The mean age of the patients was 61.5+/-6 years (range 51 to 71). All patients were followed up for 12 months. In the study group, mean foveal thickness was 391.3+/-91.6 microm preoperatively and 225.5+/-49.4 microm postoperatively (p=0.009). In the control group, mean foveal thickness was 356.2+/-140 microm at baseline and 318.4+/-111.1 microm at 12-month follow-up (p=0.138). Mean decrease in foveal thickness was 165.8+/-114.8 microm in the study group and 37.8+/-71.2 microm in the control group (p=0.016). In the study group, best-corrected log-MAR visual acuity was 0.71+/-0.43 preoperatively and 0.54+/-0.45 postoperatively (p=0.125). In the control group, best-corrected logMAR visual acuity was 0.43+/-0.44 at baseline and 0.59+/-0.55 at 12-month follow-up (p=0.235). In the study group, visual acuity improved by two or more lines in 4 eyes (40%) and remained stable in 6 eyes (60%). In the control group, visual acuity improved by two or more lines in 1 eye (10%) and decreased by two or more lines in 3 eyes (30%).PPV with ILM removal appears to be an effective procedure for reducing diabetic macular edema unresponsive to grid laser photocoagulation. A further study with a large number of patients is required to assess the effectiveness and safety of this procedure."
1,"TITLE: Nicorandil reduces the incidence of minor cardiac marker elevation after coronary stenting.ABSTRACT: Minor cardiac marker elevation after percutaneous coronary intervention has long-term prognostic significance. We examined whether nicorandil, a nicotinamide-nitrate ester, reduces the incidence of minor cardiac marker elevation after coronary stenting.Patients (n=192) undergoing coronary stenting were randomly assigned to receive nicorandil (nicorandil group, n=91) or vehicle (control group, n=101). Nicorandil (2 mug/kg/min, intravenously) was administered immediately after the patients were transferred into the catheterization laboratory and continued for 6 h. We measured the serum concentrations of creatine kinase isoenzyme MB (CK-MB) before, immediately after, and 6, 12, and 24 h after the procedure, and those of cardiac troponin T (cTnT) 24 h after the procedure.There was no significant difference in clinical background between the 2 groups. The nicorandil group showed a significantly lower incidence of CK-MB elevation (>1x upper limit of control range, 20 IU/l) than the control group (8.8% vs 21.8%, p<0.05). The levels of serum CK-MB in the nicorandil group were significantly lower than those in the control group (13.4+/-5.7 vs 16.5+/-9.7 IU/l, p<0.01). Similarly, the nicorandil group showed a significantly lower incidence of cTnT elevation [>1x (0.1 ng/ml) or >2x (0.2 ng/ml)] upper limit of control range than the control group (14.3% vs 26.7%, p<0.05, or 7.7% vs 17.8%, p<0.05). Serum cTnT levels were also significantly lower in the nicorandil group than in the control group (0.05+/-0.10 vs 0.15+/-0.36 ng/ml, p<0.05).The results demonstrated that nicorandil reduces minor cardiac marker elevation after coronary stenting."
0,"TITLE: Effect of telmisartan on forearm postischemic hyperemia and serum asymmetric dimethylarginine levels.ABSTRACT: Although telmisartan may be more beneficial for glucose metabolism than other angiotensin II receptor blockers (ARBs), it has not been determined whether telmisartan exerts more favorable effects on biological and functional parameters related to endothelial function than other ARBs.A study with a crossover design was conducted in 40 hypertensive patients (61 +/- 10 years old, mean +/- SD) who had previously been treated with ARBs other than telmisartan or valsartan (ie, ARBs were switched to either telmisartan 40 mg/day or valsartan 80 mg/day, administered alternately for 12 weeks each). Blood examinations were conducted, and the mean reactive hyperemia ratio (mRHR) was measured by plethysmography for each treatment regimen.There were no significant differences in either blood pressure or plasma levels of monocyte chemoattractant protein-1, C-reactive protein, 3-nitrotyrosine, or vascular cell adhesion molecule-1 between the two treatment regimens. The mRHR (2.7 +/- 1.0 v 2.4 +/- 1.0, mean +/- SD) was larger (P < .05), and the plasma levels of asymmetric dimethylarginine (ADMA) (0.45 +/- 0.08 v 0.50 +/- 0.17 micromol/L, mean +/- SD) and the homeostasis model assessment index of insulin resistance (HOMA-IR) (2.3 +/- 1.6 v 2.8 +/- 2.1, mean +/- SD) were lower (P < .05) in telmisartan-treated patients than in valsartan treated patients. The percent change in ADMA, but not in HOMA-IR, correlated significantly with that in the mRHR (beta = -0.33, t value = -2.00, P = .04).At doses producing equivalent hypotensive effects, telmisartan apparently had a more favorable effect on functional parameters related to endothelial function than did valsartan. The reduction in plasma ADMA levels may contribute to this more favorable effect of telmisartan."
0,"TITLE: Machine perfusion preservation improves renal allograft survival.ABSTRACT: Machine perfusion (MP) has been used as the kidney preservation method in our center for over 10 years. The first, small (n = 74) prospective, single-blinded randomized study comparing MP and Cold Storage (CS) showed that the incidence of delayed graft function was higher after CS. There have been no reports in the literature on the effect of storage modality on long-term function of renal allografts. This paper presents an analysis of long-term results of renal transplantation in 415 patients operated on between 1994 and 1999. Of those, 227 kidneys were MP-stored prior to KTx. The control group consisted of 188 CS kidney transplants. Kidneys were not randomized to MP or to CS. Donor demographics, medical and biochemical data, cold ischemia time, HLA match and recipient data were collected. Standard triple-drug immunosuppression was administered to both groups. Mortality, graft survival and incidence of return to hemodialysis treatment were analyzed. Despite longer cold ischemia time and poorer donor hemodynamics in MP group, 5-year Kaplan-Meier graft survival was better in MP-stored than in CS-stored kidneys (68.2% vs. 54.2%, p = 0.02).In this nonrandomized analysis, kidney storage by MP improved graft survival and reduced the number of patients who returned to dialysis."
1,"TITLE: Efficacy of real-time continuous glucose monitoring on glycaemic control and glucose variability in type 1 diabetic patients treated with either insulin pumps or multiple insulin injection therapy: a randomized controlled crossover trial.ABSTRACT: The aim of this study was to determine the efficacy of real-time continuous glucose monitoring in T1D patients treated with insulin pump therapy or multiple daily insulin therapy.Twenty adult patients (ten insulin pump therapy and ten multiple daily insulin) with poor glycaemic control (HbA1c  > 8.0%) were randomized into two groups for 6 months: the continuous glucose monitoring arm (using real-time continuous glucose monitoring) and the SMBG arm. After 2 months of wash-out, the participants crossed over. The primary outcome was HbA1c reduction. The secondary outcomes were hypoglycaemia and hyperglycaemia risk assessment (area under the curve < 70 mg/dL/day and AUC > 200 mg/dL/day, respectively) and glucose variability.Fourteen patients (eight multiple daily insulin, six insulin pump therapy) used continuous glucose monitoring appropriately (at least 40% of the time). In these patients, the improvement in glycaemic control was more evident during the real-time continuous glucose monitoring period (7.76% ± 0.4 vs 8.54% ± 0.4, p < 0.05) than during the self-monitoring of blood glucose period (8.42% ± 0.4 vs 8.56% ± 0.5, p = 0.2). Better results with continuous glucose monitoring were observed in patients using multiple daily insulin with greater improvement in both glycaemic control (7.71% ± 0.2 vs 8.58% ± 0.2, p < 0.05) and glucose variability and with a marked reduction in the risk of both hypoglycaemia and hyperglycaemia.Appropriate use of real-time continuous glucose monitoring improved glycometabolic control in T1D patients. The effects of continuous glucose monitoring were more evident in patients under multiple daily insulin treatment, compared with insulin pump therapy. Glucose variability, in addition to glycaemic control, was improved in compliant diabetic patients."
1,"TITLE: Growth hormone as concomitant treatment in severe fibromyalgia associated with low IGF-1 serum levels. A pilot study.ABSTRACT: There is evidence of functional growth hormone (GH) deficiency, expressed by means of low insulin-like growth factor 1 (IGF-1) serum levels, in a subset of fibromyalgia patients. The efficacy of GH versus placebo has been previously suggested in this population. We investigated the efficacy and safety of low dose GH as an adjunct to standard therapy in the treatment of severe, prolonged and well-treated fibromyalgia patients with low IGF-1 levels.Twenty-four patients were enrolled in a randomized, open-label, best available care-controlled study. Patients were randomly assigned to receive either 0.0125 mg/kg/d of GH subcutaneously (titrated depending on IGF-1) added to standard therapy or standard therapy alone during one year. The number of tender points, the Fibromyalgia Impact Questionnaire (FIQ) and the EuroQol 5D (EQ-5D), including a Quality of Life visual analogic scale (EQ-VAS) were assessed at different time-points.At the end of the study, the GH group showed a 60% reduction in the mean number of tender points (pairs) compared to the control group (p < 0.05; 3.25 +/- 0.8 vs. 8.25 +/- 0.9). Similar improvements were observed in FIQ score (p < 0.05) and EQ-VAS scale (p < 0.001). There was a prompt response to GH administration, with most patients showing improvement within the first months in most of the outcomes. The concomitant administration of GH and standard therapy was well tolerated, and no patients discontinued the study due to adverse events.The present findings indicate the advantage of adding a daily GH dose to the standard therapy in a subset of severe fibromyalgia patients with low IGF-1 serum levels.NCT00497562 (ClinicalTrials.gov)."
1,"TITLE: Patterns of disease progression and outcomes in a randomized trial testing ABVD alone for patients with limited-stage Hodgkin lymphoma.ABSTRACT: In the National Cancer Institute of Canada Clinical Trials Group/Eastern Cooperative Oncology Group HD.6 trial, progression-free survival was better in patients randomized to therapy that included radiation, compared to doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) alone. We now evaluate patterns of progression and subsequent outcomes of patients with progression.After a median of 4.2 years, 33 patients have progressed. Two radiation oncologists determined whether sites of progression were confined within radiation fields. Freedom from second progression (FF2P) and freedom from second progression or death (FF2P/D) were compared.Reviewers agreed for the extended (kappa = 0.87) and involved field (kappa = 1.0) analyses. Progression after ABVD alone was more frequently confined within both the extended (20/23 vs. 3/10; P = 0.002) and involved fields (16/23 vs. 2/10; P = 0.02). There was no difference in FF2P between groups [5-year estimate 99% (radiation) versus 96% (ABVD alone)] [hazard ratio (HR) = 3.14, 95% confidence interval (CI) 0.63-15.6; P = 0.14]; the 5-year estimates of FF2P/D were 94% in each group (HR = 1.04, 95% CI 0.41-2.63; P = 0.93).Treatment that includes radiation reduces the risk of progressive Hodgkin lymphoma in sites that receive this therapy, but we are unable to detect differences in FF2P or FF2P/D."
0,"TITLE: Compliance with joint commission measures in state-designated stroke centers.ABSTRACT: Comparison of state-designated primary and comprehensive stroke centers (PSCs and CSCs) with regard to adherence to nationally accepted performance standards are scarce. The objective of this study was to examine if a significant association exists between level of designation and fulfillment of Joint Commission (JC) stroke core measures.A retrospective comparative data analysis of the New Jersey acute stroke registry for the calendar years 2010 and 2011 was performed. JC core measures were compared by hospital level (PSCs vs CSCs). Adjusted odds ratios (aOR) were estimated for association between hospital levels and fulfillment of JC core measures. Median door-to-thrombolytic time was also compared.There were 36,892 acute stroke admissions. PSCs had 60% of the patients, whereas CSCs had 40%. Hemorrhagic stroke admissions were about 2 times more frequent at CSCs than PSCs (13.3% and 7.1%, respectively). CSCs adhered better to 6 of the 8 JC measures than PSCs. Of eligible patients, 19.5% received thrombolytic therapy at CSCs compared to 9.6% at PSCs, with a 44% difference in provision of thrombolytic therapy (aOR = 0.28, 95% confidence interval: 0.24-0.34). Median door-to-thrombolytic drug times was 65 minutes at CSCs compared to 74.0 minutes at PSCs (P < 0.0001).New Jersey state-designated CSCs are better at adhering to the JC core stroke measures and have shorter door-to-thrombolytic drug times."
1,"TITLE: Ketoconazole-tacrolimus coadministration in kidney transplant recipients: two-year results of a prospective randomized study.ABSTRACT: In developing countries, kidney transplantation is greatly hindered by financial problems, especially due to costly newer immunosuppressive medications. Ketoconazole increases blood levels of tacrolimus and cyclosporine through inhibition of cytochrome P450 microsomal enzymes. We previously reported on the 6-month safety and the outstanding impact on treatment costs of the ketoconazole-tacrolimus combination in kidney transplant recipients. Data of this combination are still lacking in the literature. We hereby report on the 2-year results of our trial.This prospective, randomized study included 70 live-donor kidney transplant recipients receiving tacrolimus (age 16-45 years, 54 males and 16 females). Patients were randomized into two equal groups: group 1, where ketoconazole 100 mg/day was added, and group 2 (control group).After 2 years, group 1 (ketoconazole) patients still showed a highly significant reduction of the tacrolimus dose (by 53.8%) and cost (by 52.9%) compared with the control group (p < 0.001) and a significant improvement in graft function in comparison to their own initial graft function (p = 0.002). Throughout the 2 years, no side effects of ketoconazole were noted.We conclude that the long-term ketoconazole-tacrolimus combination therapy in kidney transplant recipients during the 2 years is safe, has an outstanding impact on treatment costs and improves graft outcome."
1,"TITLE: The addition of fentanyl to local anesthetics affects the quality and duration of cervical plexus block: a randomized, controlled trial.ABSTRACT: Cervical plexus block is frequently associated with unsatisfactory sensory blockade. In this randomized, double-blind, placebo-controlled trial, we examined whether the addition of fentanyl to local anesthetics improves the quality of cervical plexus block in patients undergoing carotid endarterectomy (CEA).Seventy-seven consecutive adult patients scheduled for elective CEA were randomized to receive either fentanyl 1 mL (50 microg) or saline placebo 1 mL in a mixture of 10 mL bupivacaine 0.5% and 4 mL lidocaine 2% for deep cervical plexus block. Superficial cervical plexus block was performed using a mixture of 10 mL bupivacaine 0.5% and 5 mL lidocaine 2%. Pain was assessed using the verbal rating scale (0-10; 0 = no pain, 10 = worst pain imaginable), and propofol in 20-mg IV bolus doses was given to patients reporting verbal rating scale >3 during the procedure. Rescue medication consumption during surgery and analgesia requirements over the next 24 hours, as well as onset of sensory blockade, were recorded. A P value <0.05 was regarded as statistically significant.Fewer patients in the fentanyl group (4 of 38, 10.5%) required propofol compared with the placebo group (26 of 39, 66.7%; P < 0.001). In comparison with the placebo group, the fentanyl group consumed less propofol (median 0 [0-60] vs 60 [0-160] mg, respectively; P < 0.001), required postoperative analgesia less frequently (22 of 38 patients, 57.9% vs 35 of 39 patients, 89.7%, respectively; P = 0.002), and requested the first analgesic after surgery later (median 5.8 [1.9-15.6] vs 3.1 [1.0-11.7] hours, respectively; P < 0.001), whereas the onset time of sensory blockade was similar in both groups (median 12 [9-18] vs 15 [9-18] minutes, respectively; P = 0.18).The addition of fentanyl to local anesthetics improved the quality and prolonged the duration of cervical plexus block in patients undergoing CEA."
1,"TITLE: Barbed sutures reduce arthrotomy closure duration compared to interrupted conventional sutures for total knee arthroplasty: a randomized controlled trial.ABSTRACT: The broad aim of this study was to compare the safety and efficacy of using barbed sutures versus standard-of-care sutures for closure of arthrotomy during total knee arthroplasty. Specifically, we compared the duration of arthrotomy closure, the number of sutures utilized for arthrotomy closure, and 90-day outcomes, including wound-related readmission, reoperation, and complications.A total of 60 patients undergoing primary total knee arthroplasty were enrolled in a prospective, blinded trial and randomized to receive either running closure of the arthrotomy with barbed sutures (n = 30) or interrupted closure with standard-of-care sutures (n = 30).Arthrotomy closure time was significantly shorter in the barbed suture group (3 min ± 2 min) versus the standard-of-care group (13 min ± 5 min, p < 0.001). The average suture utilization for arthrotomy closure was 1 suture (range 1-2) versus 3 sutures (range 2-4) in the standard-of-care group (p < 0.001). The overall number of wound-related complications in the barbed suture group was 3/30 (10%) versus 3/30 (10%) in the standard-of-care group (p = 1.00). There was one dehiscence 1/30 (3%) in the standard-of-care group versus zero in the barbed suture group (p = 1.00). The rate of superficial surgical site infection was 1/30 (3%) in barbed suture versus zero in the standard-of-care groups (p = 1.00).These results suggest barbed suture utilization may be faster and more resource-efficient than the use of standard-of-care sutures for arthrotomy closure in primary total knee arthroplasty without increased complications. CLINICALTRIALS.NCT03285529."
1,"TITLE: Colour change of ceramic brackets with the use of coloured beverages in adolescent patients: A randomized clinical trial.ABSTRACT: To clinically evaluate colour change of ceramic orthodontic brackets with the use of coloured beverages as ceramic brackets' resistance to discoloration has become a major concern.A prospective two parallel groups-split mouth randomized trial with a 1:1 allocation ratio. Two equal groups including 40 adolescent patients from the orthodontic department (Faculty of Dentistry, Mansoura University, Egypt), scheduled for maxillary premolar extractions were bonded with 2 types of mono-crystalline ceramic brackets: Type 1 (Inspire ICETM) and Type 2 (Radiance PlusTM). Participants in each group were asked to rinse with either black tea or Cola. After extraction, the colour of the 80 debonded brackets was compared to that of 20 control brackets from each type by spectrophotometer according to the international standard CIELAB colour space (CIE L*a*b*). The latter consists of three coordinates: L* (lightness value), a* and b* (the colour channels). The total colour difference ΔE* is the distance between two colours in this three-dimensional colour space. The colour change was also assessed by digital image analysis according to the RGB model.Type 1 brackets showed mean ΔE* values of 2.24±0.25 in black tea and 1.76±0.1 in Cola groups (P<0.001), while Type 2 brackets showed means of 1.99±0.15 in black tea and 1.56±0.1 in Cola groups (P<0.001). The mean RGB values were 174.3±12.02 in black tea and 185.6±6.9 in the Cola groups of type 1 brackets (P<0.001), while were 166.5±17.8 in black tea and 190.8±8.9 in Cola groups of type 2 brackets (P<0.001).Black tea showed more significant effect than Cola on the two bracket types. Bracket type affected the colour change in each beverage group."
0,"TITLE: Can mean platelet component be used as an index of platelet activity in stable coronary artery disease?ABSTRACT: Acute coronary syndrome is associated with intracoronary thrombosis secondary to platelet activation. Previous groups have investigated platelet activation in both stable and unstable vascular disease. Most measures of platelet activation are not routinely available or easily adaptable to large scale clinical use. Recently, measurement of the mean platelet component (MPC) has become part of the routine data provided by an automated full blood count analyser, the Advia 120. MPC measures platelet density which changes on platelet activation. Our objectives were to determine if platelet activation, as measured by MPC, is increased in patients with stable coronary artery disease (CAD) and to determine if MPC could be useful in differentiating people with stable CAD from controls on an everyday clinical basis. Three hundred and forty-five consecutive patients attending for elective coronary angiography had full blood count analysis and MPC measurement performed using an ADVIA-120 analyser. Three hundred and twenty-four were analysed in our final dataset. Two hundred and fifty-three (78%) had CAD. Patients with CAD were significantly (p<0.001) older than those without (63.8 versus 56.0 years). Results failed to demonstrate a difference (p=0.467) in MPC between patients with CAD and those with normal coronary arteries (25.8 versus 26.0). Likewise, there was no correlation between MPC and the severity of CAD (Kendall's tau b=-0.086, p=0.04). MPC is not a useful index of platelet activity in stable CAD when used in everyday clinical practice."
1,"TITLE: Antibiotic prophylaxis at urinary catheter removal prevents urinary tract infections: a prospective randomized trial.ABSTRACT: To assess whether antibiotic prophylaxis at urinary catheter removal reduces the rate of urinary tract infections.Urinary tract infections are among the most common nosocomial infections. Antibiotic prophylaxis at urinary catheter removal is used as a measure to prevent them, albeit without supporting evidence.A prospective randomized study enrolled 239 patients undergoing elective abdominal surgery, who were randomized either for receiving 3 doses of trimethoprim-sulfamethoxazole at urinary catheter removal, or not. Urinary tract infections were diagnosed according to Center of Disease Control definitions. Urinary cultures were obtained before and 3 days after catheter removal. Subjective symptoms were assessed by an independent study-blind urologist.Patients who received antibiotic prophylaxis showed significantly fewer urinary tract infections (5/103, 4.9%) than those without prophylaxis (22/102, 21.6%), P < 0.001. The absolute risk reduction for the occurrence of a urinary tract infection was 16.7%; the relative risk reduction was 77.5%, and the number needed to treat was 6. Patients with antibiotic prophylaxis also had less significant bacteriuria 3 days after catheter removal (17/103, 16.5%) than those without (42/102, 41.2%), P < 0.001.Antibiotic prophylaxis with trimethoprim-sulfamethoxazole on urinary catheter removal significantly reduces the rate of symptomatic urinary tract infections and bacteriuria in patients undergoing abdominal surgery with perioperative transurethral urinary catheters."
1,"TITLE: Tension-free hernioplasty versus conventional hernioplasty for inguinal hernia repair.ABSTRACT: To show the effectiveness of tension-free hernioplasty for inguinal hernia repair.We studied 106 patients who underwent inguinal hernia repair, as conventional hernioplasty in 52 and as tension-free hernioplasty in 54. We analyzed the operation time, postoperative complications, pain, time to resume daily activities, and frequency of recurrence in the short and long term.The average age of the patients was 46.2 years. The operation time was significantly shorter in the tension-free group than in the conventional group, at 33 +/- 11.1 versus 49 +/- 8.8 min, respectively (P < 0.05). The overall complication rate was 10%, being 1.5% in the tension-free group and 13% in the conventional group (P = 0.4). The visual-analogue pain scores after surgery were lower in the tension-free group than in the conventional group (P = 0.01). Patients in the tension-free group returned to their normal activities sooner than those in the conventional group (P < 0.05).Tension-free hernioplasty resulted in less pain and allowed patients to return to their daily activities sooner than conventional hernioplasty."
1,"TITLE: Reduction of early postoperative morbidity in cardiac surgery patients treated with continuous veno-venous hemofiltration during cardiopulmonary bypass.ABSTRACT: Cardiac surgery with cardiopulmonary bypass is associated with a systemic inflammatory response syndrome. The major clinical features of this include a reduction of pulmonary compliance and increased extracellular fluids, with increased pulmonary shunt fraction similar to acute respiratory distress syndrome, thus resulting in prolonged mechanical ventilation time (VAM) and intensive care unit length of stay (ICU STAY). We evaluated the feasibility of an intraoperatory cardiopulmonary bypass (CPB) circuit connected with a monitor for continuous veno-venous hemofiltration (CVVH) to ameliorate pulmonary function after open heart surgery reducing VAM and ICU STAY. Forty patients undergoing elective coronary artery bypass grafting were randomized at the time of surgery into a control group (20 patients who received standard cardiopulmonary bypass) and a study group (20 patients who received CVVH during cardiopulmonary bypass). The analysis of postoperative variables showed a significative reduction of VAM in treated group (CVVH group mean 3.55 h +/- 0.85, control group 5.8 h +/- 0.94, P < 0.001) and ICU STAY (CVVH group mean 29.5 h +/- 6.7, control group 40.5 h +/- 6.67, P < 0.001). In our experience, the use of intraoperatory CVVH during cardiopulmonary bypass is associated with lower early postoperative morbidity."
1,"TITLE: Local anesthesia and pain perception during amniocentesis: a randomized double blind placebo-controlled trial.ABSTRACT: To determine the effect of local anesthesia on the maternal pain perception from amniocentesis.We conducted a randomized double blind placebo controlled trial comparing use of local anesthesia (1% lidocaine) with placebo with regards to maternal perception of pain among women undergoing genetic amniocentesis. The primary outcome was the intensity of perceived maternal pain as measured by the Visual Analogue Scale (VAS) as well a 101 point Numerical Rating Scale.Seventy six women participated in the trial. 36 (47.4%) women were randomized to lidocaine, whereas 40 (52.6%) were randomized to placebo. There were no statistically significant differences between the groups in terms of baseline sociodemographic and clinical characteristics. However, pain perception as characterized by the median 9.5 (2.1-21.0) VSA scores was significantly lower among women in the lidocaine group compared with among women in the placebo group [18.4 (12.9-31.3), P = 0.005]. Similarly the mean VSA scores was significantly lower in the lidocaine group (P = 0.02). A trend toward lower scores was also observed when maternal pain perception was measured by the Numerical Rating Scale.Local anesthetic lidocaine significantly lowers maternal perceived pain during genetic amniocentesis."
1,"TITLE: The necessity of using tenaculum for endometrial sampling procedure with pipelle: a randomized controlled study.ABSTRACT: To evaluate the use of tenaculum on pain perception of patients and on ease of endometrial sampling procedure with a pipelle.A randomized controlled trial was conducted in 118 patients for assessing pain perception and the ease of the procedure. Patients were randomly assigned to group 1 (without tenaculum) and group 2 (with tenaculum). Visual analog scale (VAS) was used to assess patients' pain at four different times during the process. VAS-3 reflected the pain during the procedure. Likert scale was employed by the surgeon to measure the ease of the procedure. Main outcome was VAS and the secondary outcomes were Likert scale and success rate in obtaining adequate samples of endometrial tissue for histopathological diagnosis.Endometrial sampling procedure could not be performed only on three patients who belonged to group 1. The VAS-3 scores were higher in group 2 than group 1 (p = 0.001). Nullipar patients had higher VAS-3 scores than multipars (p = 0.012). VAS-3 did not vary in pre-peri-postmenopausal women (p = 0.901). Likert scale was lower in postmenopausal women than peri- or pre-menopausal patients (p = 0.020, 0.017, respectively). Use of tenaculum was found by logistic regression analysis to be an independent risk factor for patients' pain perception (p = 0.0001, RR 31.8, 95 % CI 8.3-122.4). Inadequate endometrial sampling was reported in 12 patients who were all postmenopausal.Endometrial sampling procedure without tenaculum is feasible and yields less pain perception than with tenaculum."
1,"TITLE: Randomised controlled trial of a mobile phone infant resuscitation guide.ABSTRACT: The aim of this study was to develop a mobile phone resuscitation guide (MPRG) and to evaluate its use during simulated resuscitation of a mannequin.An MPRG was developed using EpiSurveyor. A randomised controlled trial was performed in school-going children aged 15-16 years. All subjects were taught infant CPR skills using the American Heart Association Infant CPR Anytime. Two weeks later, the students were randomised to use of MPRG or not, and their CPR skills were re-assessed. The assessment was conducted using previously validated checklists.Twenty-one students participated in this trial. The MPRG group performed notably better in the areas of calling emergency services (80% vs. 36.4%, P = 0.044), completing sufficient CPR cycles (90% vs. 45.5%, P = 0.047) and following the correct CPR sequence (60% vs. 9.1%, P = 0.013). No difference in resuscitation skills of participants was observed.We have shown that participants were more likely to call emergency services if they were using the MPRG. Further trials are needed to investigate the utility of mobile phone guides and whether or not they can reduce the time taken to contact emergency services as well as if they can sustain correct CPR sequence in an in-vivo setting."
0,"TITLE: Mechanical-ventilatory responses to peak and ventilation-matched upper- versus lower-body exercise in normal subjects.ABSTRACT: What is the central question of this study? To what extent are the mechanical-ventilatory responses to upper-body exercise influenced by task-specific locomotor mechanics? What is the main finding and its importance? When compared with lower-body exercise performed at similar ventilations, upper-body exercise was characterized by tidal volume constraint, dynamic lung hyperinflation and an increased propensity towards neuromechanical uncoupling of the respiratory system. Importantly, these responses were independent of respiratory dysfunction and flow limitation. Thus, the mechanical ventilatory responses to upper-body exercise are attributable, in part, to task-specific locomotor mechanics (i.e. non-respiratory loading of the thorax).The aim of this study was to determine the extent to which the mechanical ventilatory responses to upper-body exercise are influenced by task-specific locomotor mechanics. Eight healthy men (mean ± SD: age, 24 ± 5 years; mass, 74 ± 11 kg; and stature, 1.79 ± 0.07 m) completed two maximal exercise tests, on separate days, comprising 4 min stepwise increments of 15 W during upper-body exercise (arm-cranking) or 30 W during lower-body exercise (leg-cycling). The tests were repeated at work rates calculated to elicit 20, 40, 60, 80 and 100% of the peak ventilation achieved during arm-cranking (  ). Exercise measures included pulmonary ventilation and gas exchange, oesophageal pressure-derived indices of respiratory mechanics, operating lung volumes and expiratory flow limitation. Subjects exhibited normal resting pulmonary function. Arm-crank exercise elicited significantly lower peak values for work rate, O uptake, CO output, minute ventilation and tidal volume (p < 0.05). At matched ventilations, arm-crank exercise restricted tidal volume expansion relative to leg-cycling exercise at 60%  (1.74 ± 0.61 versus 2.27 ± 0.68 l, p < 0.001), 80%  (2.07 ± 0.70 versus 2.52 ± 0.67 l, p < 0.001) and 100%  (1.97 ± 0.85 versus 2.55 ± 0.72 l, p = 0.002). Despite minimal evidence of expiratory flow limitation, expiratory reserve volume was significantly higher during arm-cranking versus leg-cycling exercise at 100%  (39 ± 8 versus 29 ± 8% of vital capacity, p = 0.002). At any given ventilation, arm-cranking elicited greater inspiratory effort (oesophageal pressure) relative to thoracic displacement (tidal volume). Arm-cranking exercise is sufficient to provoke respiratory mechanical derangements (restricted tidal volume expansion, dynamic hyperinflation and neuromechanical uncoupling) in subjects with normal pulmonary function and expiratory flow reserve. These responses are likely to be attributable to task-specific locomotor mechanics (i.e. non-respiratory loading of the thorax)."
1,"TITLE: Pharmacodynamic effects of orally administered dexlipotam on endothelial function in type 2-diabetic patients.ABSTRACT: Diabetic endotheliopathy is the result of hyperglycemia and the production of oxygen-free radicals. In vitro and in vivo data have shown beneficial effects of dexlipotam (DEX), a tromethamine salt of R(+)-alpha-lipoic acid, on oxidative stress in hyperglycemic states, but no data are available on the effects of this agent on endothelial function. The purpose of this pilot study was to evaluate the impact of DEX on endothelial function in patients with type 2 diabetes (DM2) and to estimate the safety and tolerability of DEX.DEX 960 mg and DEX 1,920 mg were investigated in DM2 patients over a period of 4 weeks using a randomized, placebo- (PLA) controlled, double-blinded study with 3 parallel groups. The marker of arterial function after 4-week therapy with DEX was the maximum percentage change versus baseline in the flow-mediated dilation of the brachial artery (FMD) after reperfusion.A total of 114 diabetic patients were randomized to the three study groups. DEX was safe and well tolerated. Dyspepsia appeared to be the most relevant side effect of DEX treatment. Systolic (p = 0.078) and diastolic blood pressure (p = 0.059) tended to be lower in patients treated with DEX at a dose of 1,920 mg. There were no significant differences in FMD between the placebo- and the DEX-treated groups. In patients with poorer glucose control (HbA1c > 6.5% Hb), FMD increased significantly after 4-week treatment with DEX: PLA -1.51 +/- 2.98%, DEX 960 mg +1.22 +/- 3.22, p = 0.027, DEX 1,920 mg +1.47 +/- 3.78, p= 0.012. The magnitude of the mean change compared to placebo was 2.73% (DEX 920) and 2.98% (DEX 1,920) in patients with HbAlc > 7.5% Hb (DEX 960, p = 0.007, DEX 1,920, p = 0.032). The effects of treatment were usually statistically significant in subgroups with more severe vascular stress (longer duration of disease, pretreatment history, higher LDL-C, higher blood pressure).DEX therapy appears to reduce endothelial dysfunction in DM2, especially in men with long history of DM2 and having poor glucose control. These findings will be useful in patient selection in future prospective clinical trials with drugs to treat vascular stress."
1,"TITLE: Extending low-dose epidural analgesia in labour for emergency Caesarean section - a comparison of levobupivacaine with or without fentanyl.ABSTRACT: Women in labour receiving epidural analgesia with 15 ml bupivacaine 0.1% and 2 microg.ml(-1) fentanyl followed by 10-15-ml top-ups as required, who needed Caesarean section, were randomly allocated to receive 20 ml levobupivacaine 0.5% over 3 min with either 75 microg fentanyl (1.5 ml) or 1.5 ml saline. Further top-ups or inhaled or intravenous supplementation were given for breakthrough pain. Time to onset (loss of cold sensation to T4 and touch sensation to T5 bilaterally), quality of analgesia and side-effects were recorded. The study was stopped after 112 patients had been randomly assigned, due to a unit protocol change, from midwife-administered top-ups to patient-controlled epidural analgesia. Data from 51 patients given fentanyl and 54 given saline were available for analysis. There were no significant differences in onset times or supplementation between the groups, but there was more intra-operative nausea/vomiting with fentanyl (53%) than with saline (18%; p = 0.004). We found no advantage of adding fentanyl to epidural levobupivacaine when extending epidural analgesia in women already receiving epidural fentanyl during labour and there was an increased incidence of intra-operative nausea and vomiting. Power analysis suggested the same conclusion even had the study proceeded to completion."
1,"TITLE: Dry Needling Combined With Guideline-Based Physical Therapy Provides No Added Benefit in the Management of Chronic Neck Pain: A Randomized Controlled Trial.ABSTRACT: To determine the added benefit of combining dry needling with a guideline-based physical therapy treatment program consisting of exercise and manual therapy on pain and disability in people with chronic neck pain.Randomized controlled trial.Participants were randomized to receive either guideline-based physical therapy or guideline-based physical therapy plus dry needling. The primary outcomes, measured at 1 month post randomization, were average pain intensity in the previous 24 hours and previous week, measured with a numeric pain-rating scale (0-10), and disability, measured with the Neck Disability Index (0-100). The secondary outcomes were pain and disability measured at 3 and 6 months post randomization and global perceived effect, quality of sleep, pain catastrophizing, and self-efficacy measured at 1, 3, and 6 months post randomization.One hundred sixteen participants were recruited. At 1 month post randomization, people who received guideline-based physical therapy plus dry needling had a small reduction in average pain intensity in the previous 24 hours (mean difference, 1.56 points; 95% confidence interval [CI]: 1.11, 2.36) and in the previous week (mean difference, 1.20 points; 95% CI: 1.02, 2.21). There was no effect of adding dry needling to guideline-based physical therapy on disability at 1 month post randomization (mean difference, -2.08 points; 95% CI: -3.01, 5.07). There was no effect for any of the secondary outcomes.When combined with guideline-based physical therapy for neck pain, dry needling resulted in small improvements in pain only at 1 month post randomization. There was no effect on disability. ."
0,"TITLE: Defining the Most Informative Intermediate Clinical Endpoints for Patients Treated with Salvage Radiotherapy for Prostate-specific Antigen Rise After Radical Prostatectomy.ABSTRACT: Intermediate clinical endpoints (ICEs) might aid in trial design and potentially expedite study results. However, little is known about the most informative ICE for patients receiving salvage radiation therapy (sRT) after radical prostatectomy. To investigate the most informative ICE for patients receiving sRT, we used a multi-institutional database encompassing patients treated at eight tertiary centers. Overall, 1301 men with node-negative disease who had not received any form of androgen deprivation therapy were identified. Associations of biochemical (BCR) and clinical recurrence (CR) within 1, 3, 5, and 7yr after surgery with the risk of overall mortality were evaluated using multivariable Cox regression analyses fitted at the landmark points of 1, 3, 5, and 7yr after sRT. The discriminative ability of each model for predicting overall survival (OS) was assessed using Harrell's c index. Median follow-up for survivors was 5.6yr (interquartile range 2.0-8.8). On multivariable analysis, progression to CR within 3yr from sRT (hazard ratio 4.19, 95% confidence interval 1.44-11.2; p= 0.008) was the most informative ICE for predicting OS (c index 0.78) compared to CR within 1, 5, and 7yr (c index 0.72, 0.75, and 0.71). In conclusion, progression to CR within 3yr after sRT, irrespective of the time of surgery, was the most informative ICE for prediction of OS. Our study is hypothesis-generating. If these results are confirmed in future prospective studies and surrogacy is met, this information could be applied for study design and could potentially expedite earlier release of results from ongoing randomized controlled trials. PATIENT SUMMARY: Clinical recurrence of prostate cancer within 3yr after salvage radiation therapy, irrespective of the time of radical prostatectomy, represents the most informative intermediate clinical endpoint for the prediction of overall survival. This information could be applied in the design of future studies and could potentially expedite earlier release of results from ongoing randomized controlled trials."
1,"TITLE: The effects of nitrous oxide on recovery from isoflurane anaesthesia in dogs.ABSTRACT: To assess rate and quality of recovery from anaesthesia where isoflurane was delivered in oxygen or oxygen/nitrous oxide.Dogs anaesthetised with propofol were randomly allocated to receive isoflurane maintenance in either 100 per cent oxygen (group 1) or 66 per cent nitrous oxide (N(2)O)/34 per cent oxygen (group 2). Time from end of anaesthesia to achieving sternal recumbency was recorded. Incidence of adverse behaviours (vocalisation, uncontrolled head movement and restlessness) were assessed. Recovery quality was recorded on a visual analogue scale (VAS) (anchored at 0 with ""best possible"" recovery and ""did not recover"" at 100 mm). Age, weight, gender, anaesthetic duration, mean vaporiser setting, VAS scores, recovery times, postoperative temperature and behavioural scores were compared (chi-squared test, Mann-Whitney U test or t-test as appropriate, significance P< or =0.05).Objective data from 54 dogs were analysed, only VAS data where the observer was unaware of treatment group were used (n=33). Recovery was faster in group 2 dogs (median 10 min [range 4 to 31] compared with 14 minutes [3 to 43] in group 1, P=0.049) with less restlessness (0 [0 to 4] compared with 2 [0 to 4] in group 1, P=0.013) and uncontrolled head movement (0 [0 to 4] compared with 1 [0 to 3] in group 1, P<0.001). However, VAS scores were not statistically different between groups (group 1: mean 39.4 mm [s.d. 24.0)]; group 2: 30.1 mm [25.9]; P=0.303).Addition of N(2)O to isoflurane anaesthesia results in a lower incidence of adverse behaviour (for example restlessness) and marginally faster recovery."
1,"TITLE: A randomized, double-blind trial evaluating the efficacy of palonosetron with total intravenous anesthesia using propofol and remifentanil for the prevention of postoperative nausea and vomiting after gynecologic surgery.ABSTRACT: Palonosetron has potent and long-acting antiemetic effects for postoperative nausea and vomiting (PONV). The aim of this study was to prospectively evaluate the efficacy of palonosetron when used with total intravenous anesthesia (TIVA) using propofol and remifentanil for the prevention of PONV in patients undergoing laparoscopic gynecologic surgery.This prospective double-blind study comprised 100 female American Society of Anesthesiologist physical status I and II patients who were undergoing laparoscopic gynecologic surgery under TIVA. The patients were randomly assigned to two groups-the palonosetron plus TIVA group (palonosetron 0.075 mg i.v., n = 50) and the TIVA group (normal saline 1.5 ml i.v., n = 50). The treatments were given before the induction of anesthesia. The incidence of PONV, severity, number of rescue antiemetics, adverse effects, and patient satisfaction during the first 24 h after surgery were evaluated.The demographic profiles of the patients in the two groups were comparable. The overall incidence of PONV (0-24 h) was significantly lower in the TIVA plus palonosetron group than in the TIVA group (34 vs 58 %, p = 0.027). In particular, during the 6-24 h after surgery, the incidence of PONV (14 vs 30 %, p = 0.03) and the incidence of moderate to severe nausea (6 vs 22 %, p = 0.041) were significantly lower in the TIVA plus palonosetron group than in the TIVA group. There were no significant differences in adverse effects, use of rescue antiemetics or patient satisfaction.Combining palonosetron with TIVA can be considered as a good method to prevent PONV, not only during the short postoperative period but also especially during the 6-24-h period after anesthesia."
1,"TITLE: Changes in white spot lesions following post-orthodontic weekly application of 1.25 per cent fluoride gel over 6 months-a randomized placebo-controlled clinical trial. Part II: clinical data evaluation.ABSTRACT: White spot lesions (WSL) frequently occur as side-effect of multibracket appliance treatment. The clinical effects of local fluoridation on post-orthodontic WSL and oral health development are however inconclusive.In vivo monitoring of clinical WSL and oral health changes in response to weekly 1.25 per cent fluoride gel application after multibracket appliance treatment.Randomized, single-centre, double-blind, parallel-group, placebo-controlled study.Patients with not less than 1 WSL (modified score 1 or 2) on not less than 1 upper front teeth after debonding.Professional fluoride/placebo gel application during weeks 1-2; self-administered home application (weeks 3-24).Clinical evaluation of WSL index, lesion activity, plaque index, gingival bleeding index, and decayed, missing, and filled teeth index as well as saliva buffer capacity and stimulated salivary flow rate (T0-T5).Random assignment to test (n = 23) or placebo group (n = 23) using a sequentially numbered list (random allocation sequence generated for 50 subjects in 25 blocks of 2 subjects each).The clinical study duration lasted from March 2011 to September 2013.Unblinding was performed after complete data evaluation.Intention-to-treat analysis set comprised 39 participants (test: n = 21, placebo: n = 18).No clinical parameter except stimulated salivary flow rate (fluoride group: 1.1ml/min, placebo group: 0.74ml/min; P = 0.022) showed a statistically significant group difference after 24 weeks.Several adverse events occurred similarly frequent in both groups; none was classified as possibly related to the study product.The number of dropouts was higher than expected and the socio-economic status was not assessed. Furthermore, the unknown level of compliance during the home application phase must be considered as limitation.Based on the results of this study, no clinical effect of post-orthodontic high-dose fluoride treatment on WSL and oral health changes could be detected.The study was registered with ClinicalTrials.gov (Identifier: NCT01329731).The protocol wasn't published before trial commencement."
1,"TITLE: Regular Exercise to Prevent the Recurrence of Gestational Diabetes Mellitus: A Randomized Controlled Trial.ABSTRACT: To investigate the effect of a supervised home-based exercise program on the recurrence and severity of gestational diabetes mellitus (GDM) together with other aspects of maternal health and obstetric and neonatal outcomes.This randomized controlled trial allocated women with a history of GDM to an exercise intervention (14-week supervised home-based stationary cycling program) or to a control group (standard care) at 13±1 weeks of gestation. The primary outcome was a diagnosis of GDM. Secondary outcomes included maternal fitness, psychological well-being, and obstetric and neonatal outcomes. A sample size of 180 (90 in each group) was required to attain 80% power to detect a 40% reduction in the incidence of GDM.Between June 2011 and July 2014, 205 women provided written consent and completed baseline assessments. Of these, 33 (16%) were subsequently excluded as a result of an elevated baseline oral glucose tolerance test (OGTT), leaving 172 randomized to exercise (n=85) or control (n=87). Three women miscarried before the assessment of outcome measures (control=2; exercise=1). All remaining women completed the postintervention OGTT. The recurrence rate of GDM was similar between groups (control 40% [n=34]; exercise 40.5% [n=34]; P=.95) and the severity of GDM at diagnosis was unaffected by the exercise program with similar glucose and insulin responses to the OGTT (glucose 2 hours post-OGTT 7.7±1.5 compared with 7.6±1.6 mmol/L; P>.05). Maternal fitness was improved by the exercise program (P<.01) and psychological distress was reduced (P=.02). There were no differences in obstetric and neonatal outcomes between groups (P>.05).Supervised home-based exercise started at 14 weeks of gestation did not prevent the recurrence of GDM; however, it was associated with important benefits for maternal fitness and psychological well-being.ClinicalTrials.gov, https://clinicaltrials.gov, NCT01283854."
1,"TITLE: Vaginal misoprostol for cervical priming before hysteroscopy in perimenopausal and postmenopausal women.ABSTRACT: To evaluate the effectiveness and possible adverse effects of vaginal misoprostol for cervical priming before hysteroscopy in perimenopausal and postmenopausal women.A total of 105 women scheduled for hysteroscopy were randomly assigned to 2 groups. The study group (n=51) received 400 microg of vaginal misoprostol at least 12 h before the procedure and the control group (n=54) received no cervical priming agent. The primary outcome measure was the number of women who required cervical dilation. Secondary outcomes were cervical width (the largest size of Hegar dilator inserted without resistance) as well as complications and adverse effects.In the misoprostol group 27 women (52.9%) required cervical dilation vs. 53 (98.1%) in the control group (P<0.0001). The largest size of Hegar dilator inserted without resistance was 7.6+/-1.4 mm in the misoprostol group vs. 5.0+/-1.1 mm in the control group (P<0.0001). A similar effect of misoprostol on cervical dilation was also found in the subgroup of treated postmenopausal women. Only 2 women (3.9%) experienced mild lower abdominal pain after misoprostol application.Vaginal misoprostol applied before hysteroscopy reduced cervical resistance and the need for cervical dilation in perimenopausal and postmenopausal women, with only mild adverse effects."
1,"TITLE: Comparative study between clipless laparoscopic cholecystectomy by harmonic scalpel versus conventional method: a prospective randomized study.ABSTRACT: This study was planned to compare the traditional method of laparoscopic cholecystectomy (LC) versus LC using harmonic as regard the safety and efficacy.This study included group A (70 patients) in whom LC was conducted using the traditional method (TM) by clipping both cystic duct and artery and dissection of gallbladder from liver bed by diathermy, and group B (70 patients) LC was conducted using harmonic scalpel (HS) closure and division of both cystic duct and artery and dissection of gallbladder from liver bed by HS. The intraoperative and postoperative parameters were collected including duration of operation, postoperative pain, and complications.HS provides a shorter operative duration than TM (33.21 + 9.6 vs. 51.7 + 13.79, respectively, p = 0.001), with a significant less incidence of gallbladder peroration (7.1% vs. 18.6, p = 0.04) and less rate of conversion to open cholecystectomy but not reach a statistical significance. The amount of postoperative drainage is significantly less in HS (29 + 30 vs. 47.7 + 31, p = 0.001). No postoperative bile leak was encountered in HS, but it occurred in 2.9% of patients in TM. VAS in HS at 12 h postoperative was 3.25 + 1.84 vs 5.01 + 1.2 (p = 0.001) and at 24 h postoperative was 3.12 + 1.64 vs. 4.48 + 1.89 (p = 0.001).HS provides a complete hemobiliary stasis and is a safe alternative to stander clip of cystic duct and artery. It provides a shorter operative duration, less incidence of gallbladder perforation, less postoperative pain, and less rate of conversion to open cholecystectomy."
1,"TITLE: Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphate ratio in patients with heart failure.ABSTRACT: The addition of trimetazidine to standard treatment has been shown to improve left ventricular (LV) function in patients with heart failure. The aim of this study is to non-invasively assess, by means of in vivo 31P-magnetic resonance spectroscopy (31P-MRS), the effects of trimetazidine on LV cardiac phosphocreatine and adenosine triphosphate (PCr/ATP) ratio in patients with heart failure.Twelve heart failure patients were randomized in a double-blind, cross-over study to placebo or trimetazidine (20 mg t.i.d.) for two periods of 90 days. At the end of each period, all patients underwent exercise testing, 2D echocardiography, and MRS. New York Heart Association (NYHA) class, ejection fraction (EF), maximal rate-pressure product, and metabolic equivalent system (METS) were evaluated. Relative concentrations of PCr and ATP were determined by cardiac 31P-MRS. On trimetazidine, NYHA class decreased from 3.04+/-0.26 to 2.45+/-0.52 (P = 0.005), whereas EF (34+/-10 vs. 39+/-10%, P = 0.03) and METS (from 7.44+/-1.84 to 8.78+/-2.72, P = 0.03) increased. The mean cardiac PCr/ATP ratio was 1.35+/-0.33 with placebo, but was increased by 33% to 1.80+/-0.50 (P = 0.03) with trimetazidine.Trimetazidine improves functional class and LV function in patients with heart failure. These effects are associated to the observed trimetazidine-induced increase in the PCr/ATP ratio, indicating preservation of the myocardial high-energy phosphate levels."
1,"TITLE: Electronic monitoring-based counseling to enhance adherence among HIV-infected patients: a randomized controlled trial.ABSTRACT: To investigated the effectiveness of an adherence intervention (AIMS) designed to fit HIV-clinics' routine care procedures.Through block randomization, patients were allocated to the intervention or control group. The study included 2 months baseline measurement, 3 months intervention, and 4 months follow-up. HIV-nurses delivered a minimal intervention (""adherence sustaining"") to patients scoring >95% adherence at baseline, and an intensive intervention (""adherence improving"") to patients with <95% adherence. Control participants received high-quality usual care.Electronically monitored adherence and viral load.133 patients were included (67 control, 66 intervention), 60% had <95% adherence at baseline, and 87% (116/133) completed the trial. Intent-to-treat analyses showed that adherence improved significantly in the complete intervention sample. Subgroup analyses showed that this effect was caused by participants scoring <95% at baseline (mean difference = 15.20%; p < .001). These effects remained stable during follow-up. The number of patients with an undetectable viral load increased in the intervention group compared to the control group (OR = 2.96, p < .05). Treatments effects on viral load were mediated by the improvements in adherence.The AIMS-intervention was effective and can be integrated in routine clinical care for HIV-infected patients. Future research should study its (cost)effectiveness among more heterogeneous samples and in settings with variable levels of standard care."
1,"TITLE: The effect of low-volume high-intensity interval training on cardiovascular health outcomes in type 2 diabetes: A randomised controlled trial.ABSTRACT: Low-volume high-intensity interval training (HIIT) may be a time-efficient strategy that leads to similar or superior improvements in cardiorespiratory fitness (CRF) and cardiovascular disease (CVD) risk factors when compared with moderate-intensity continuous training (MICT). Our study investigated the effect of low-volume HIIT or MICT versus sham placebo-control (PLA) on central arterial stiffness, hemodynamic responses, and CVD risk factors in adults with obesity and type 2 diabetes (T2D).Eligible participants were previously inactive adults with obesity and T2D. Individuals were randomly allocated to: i) HIIT (1 × 4 min cycling at 90% peak oxygen consumption [V̇O]); ii) MICT (45 min of cycling at 60% VO); or PLA. Training groups exercised thrice weekly for 12 weeks. Central arterial stiffness, hemodynamics and CVD risk factors were assessed at baseline and post-intervention. Analysis of covariance (ANCOVA) was used to examine changes following HIIT, MICT and PLA.Thirty-five participants (age: 55.1 ± 1.4 years, BMI: 36.1 ± 0.8 kg/m) completed the study. A significant intervention effect was found for changes in pulse wave velocity (PWV) (p = .03), which reduced with HIIT (-0.3 ± 0.9 m/s) and MICT (-0.1 ± 1.1 m/s) but increased with PLA (0.8 ± 1.6 m/s). There was a significant intervention effect for changes in V̇O (p < .01), glycosylated hemoglobin (p = .03), systolic blood pressure (p < .01), and waist circumference (p = .03), which all improved following MICT or HIIT but not PLA; there was no difference between MICT and HIIT.Twelve minutes of low-volume HIIT per week leads to improvements in central arterial stiffness and cardiovascular health in inactive individuals with obesity and T2D."
1,"TITLE: Efficacy of a topical gel containing chitosan, chlorhexidine, allantoin and dexpanthenol for pain and inflammation control after third molar surgery: A randomized and placebo-controlled clinical trial.ABSTRACT: The aim of this study was to evaluate and compare the postoperative effect of a topic gel containing chlorhexidine, chitosan, allantoine and dexpanthenol versus a placebo for pain and inflammation control after third molar surgery.A gel combining 0.2% chlorhexdine, 0.5% chitosan, 5% dexpanthenol, 0.15% allantoin and 0.01% sodium saccharin was selected for this split mouth randomized controlled and double-blind trial including 36 patients with bilaterally and symmetrically impacted lower third molars. The teeth (n=72) were randomly divided into two groups before surgical removal: control group (CG; in which a placebo was given) and experimental group (EG). Swelling, trismus, postoperative pain, wound healing and complications were measured and recorded in order to evaluate differences between the placebo and experimental product.Five patients suffered from an alveolitis in the CG (13.9%), and none in the study group (0%), but no statistically significant difference was found (p=0.063). From day 0 to day 7, trismus and swelling were significantly less pronounced in the EG, and wound healing was considered 'good' in 22.2% for the CG and 97.2% for the EG (p<0.001). Mean VAS scores during the seven postoperative days were statistically lower in the study (2.56±1,19) compared to the placebo group (3.25±1.6) (p=0.002). The mean consumption of analgesic pills during the first 92 hours was also statistically lower in the EG (0.26±0.51) in comparison to the CG (0.56±0.67) (p=0.003).The use of an experimental gel containing chlorhexidine, chitosan, allantoine and dexpanthenol seems to significantly reduce postoperative pain, trismus and signs of inflammation. Future studies should further evaluate, if the gel is effective in dry socket preventing after third molar removal."
1,"TITLE: Capsaicin Supplementation during High-intensity Continuous Exercise: A Double-blind Study.ABSTRACT: To investigate the effect of acute capsaicin (CAP) supplementation on time to exhaustion, physiological responses and energy systems contribution during continuous high-intensity exercise session in runners. Fifteen recreationally-trained runners completed two randomized, double-blind continuous high-intensity exercises at the speed eliciting 90% V̇O (90% s V̇O), 45 minutes after consuming capsaicin or an isocaloric placebo. Time to exhaustion, blood lactate concentration, oxygen consumption during and 20-min post-exercise, energy systems contribution, time to reach V̇O, heart rate and the rate of perceived exertion (RPE) were evaluated. There was no significant difference between conditions for time to reach V̇O (CAP:391.71±221.8 vs. PLA:298.20±174.5 sec, ES:0.58, p=0.872), peak lactate (CAP:7.98±2.11 vs. PLA:8.58±2.15 µmol, ES:-0.28, p=0.257), time to exhaustion (CAP:654.28±195.44 vs. PLA:709.20±208.44 sec, ES:-0.28, p=0.462, end-of-exercise heart rate (CAP:177.6±14.9 vs. PLA:177.5±17.9 bpm, ES:-0.10, p=0.979) and end-of-exercise RPE (CAP: 19±0.8 vs. PLA: 18±2.4, ES: 0.89, p=0.623). In conclusion, acute CAP supplementation did not increase time to exhaustion during high-intensity continuous exercise nor alter physiological responses in runners."
1,"TITLE: Pharmacological Prophylaxis of Atrial Fibrillation After Surgical Myocardial Revascularization.ABSTRACT: Postoperative Atrial Fibrillation (POAF) is associated with a higher rate of postoperative complications and mortality, as well as with longer hospitalization and increased treatment costs. We have designed and performed a randomized, trial of pharmacological prophylaxis in which the event of interest is POAF.The aim of this study is to reduce the risk of postoperative, complications associated with this arrhythmia.We included 240 stable patients with a coronary heart disease, who were referred to elective surgical revascularization of the myocardium. The patients were assigned into three groups of 80 patients each: group A (BB, beta blocker, comparator), group B (BB+ Amiodarone) and group C (BB + Rosuvastatin). The goal was to establish whether intervention by combination therapy was more useful than a comparator.An event of interest (POAF) has occurred in 66 of the total 240 patients. Number of new POAF cases is the lowest in Group B, 14 (17.5%) compared to 25 (31.25%) new cases in the comparator group, and 27 new cases (33.75%) in group C. Absolute risk reduction was 13.75%, ≈14% less POAF in group B compared to comparator. Relative risk reduction was 56% (RR 0.56, p = 0.04). Number Needed to Treat was 7.27. In group C, 33.75% of patients developed POAF. Absolute risk was insignificantly higher in group C (2.5%, NS) compared to the comparator .The number needed to harm was high, 40.The results of our research show that prophylaxis of POAF with combined therapy BB + Amiodarone was the most efficient one."
1,"TITLE: Treatment with carvedilol improves survival of patients with acute-on-chronic liver failure: a randomized controlled trial.ABSTRACT: In addition to the portal pressure reducing effect, non-selective beta blockers (NSBBs) have possible immunomodulatory and effect in reducing bacterial translocation. Recently, it has been shown that patients who are already on NSBBs should be continued on them (if feasible), if acute-on-chronic liver failure (ACLF) develops. It, however, remains unknown if patients with ACLF and no or small esophageal varices at presentation will benefit from the use of NSBBs. We studied the efficacy and safety of carvedilol in patients with ACLF in reducing mortality, variceal bleeding and non-bleeding complications.136 patients with ACLF (with no or small esophageal varices and HVPG ≥ 12 mmHg) were randomized to either carvedilol (n = 66) or placebo arms (n = 70).Within 28 days, 7 (10.6%) of 66 patients in the carvedilol group and 17 (24.3%) of 70 in the placebo group died (p= 0.044). Fewer patients in the carvedilol compared to placebo group developed acute kidney injury (AKI) (13.6% vs 35.7%, p = 0.003 and spontaneous bacterial peritonitis (SBP) (6.1% vs 21.4%, p= 0.013). Significantly, more patients in the placebo group had increase in APASL ACLF Research Consortium-ACLF grade (22.9% vs 6.1%, p= 0.007). There was no significant difference in the 90-day transplant-free survival rate and development of AKI, SBP, non-SBP infections (including pneumonia) and variceal bleed within 90 days, between the two groups.In ACLF patients with either no or small esophageal varices and HVPG ≥ 12 mmHg, carvedilol leads to improved survival and fewer AKI and SBP events up to 28 days. CLINICALTRIALS.NCT02583698."
1,"TITLE: Spontaneous alveolar bone loss after 4NQO exposure in Wistar rats.ABSTRACT: This study evaluated the effect of an experimental carcinogenic, 4-Nitroquinoline 1-oxide (4NQO), in the spontaneous alveolar bone loss (ABL) in an animal model.Twenty-two male Wistar rats were included in this study. They were randomly divided into two groups: the control group (n = 10) received food and water ad libitum, and the test group (n = 12) receive the same food; however, 25 ppm of 4NQO was diluted in the drinking water. All animals were euthanized after 20 weeks, and the tongues were removed and analyzed macroscopically to determine the presence of oral mucosal lesions. All specimens were paraffin-embedded and histological sections were obtained. The microscopic analysis was based on routine procedure (haematoxylin and eosin stain). The analysis of spontaneous ABL was performed by a calibrated examiner using standardized photographs and imaging software. Differences in spontaneous ABL were assessed among the three resulting groups: control, 4NQO with oral squamous cell carcinoma (OSCC), and 4NQO without OSCC.In the 4NQO-treated group, nine animals developed OSCC. The animals in the 4NQO with OSCC group presented significantly more spontaneous ABL (0.65 ± 0.21 mm) than the control group (0.34 ± 0.05) (p < 0.001). The animals in the 4NQO without OSCC group showed a mean spontaneous ABL of 0.47 ± 0.13 mm, which was not statistically significant different when compared to the control group (p = 0.096).It was concluded that the presence of OSCC enhanced spontaneous ABL in Wistar rats when compared to control animals. Additionally, it was shown that, solely, administration of 4NQO may not be considered responsible for alveolar bone destruction."
1,"TITLE: The potential long-term neurological improvement of early hyperbaric oxygen therapy on hemorrhagic stroke in the diabetics.ABSTRACT: Although Hyperbaric oxygen therapy (HyperBOT) attract our attention successfully these days, it is still full of controversy on the treatment of acute stroke. The aim of this study is to assess the potential long-term neurological consequences and safety of using HyperBOT on intracerebral hemorrhage (ICH) in the diabetics.In this prospective, randomized controlled trial, 79 diabetes patients suffering from acute ICH were randomized to treat for 60 min in a monoplace hyperbaric chamber pressurized with pure oxygen to 2.5-atm absolute (ATA) in the HyperBOT group or 1.5 ATA in the normobaric oxygen therapy (NormBOT) group, which was performed as control. Both short-term and long-term neurological consequences were studied and compared in each group on National Institutes of Health Stroke Scale [NIHSS], Barthel Index, modified Rankin Scale [mRS] and Glasgow Outcome Scale [GOS]. The related complications or side-events of all patients were recorded as well at the final follow-up of six months after onset.No distinct difference was observed between each group at one month follow-up. However, in the long-term follow-up of six months, a higher frequency of patients in the HyperBOT group resulted into good outcome with a relative high neurological consequence compared with the NormBOT group (Barthel Index: 85.1% versus 65.6%, P = 0.080; mRS: 89.4% versus 68.8%, P = 0.045; GOS: 83.0% versus 62.5%, P = 0.073; NIHSS: 80.9% versus 56.2%, P = 0.035).Early HyperBOT was found to be safe and effective with regards to the long-term neurological outcome of diabetic patients suffering from ICH."
1,"TITLE: Hyoscine N-Butylbromide for Preventing Propofol Injection Pain: A Randomized, Placebo-Controlled and Double-Blind Study.ABSTRACT: In this study, the aim was to investigate the effect of hyoscine N-butylbromide (HnBB) pretreatment on pain during propofol injection.In this prospective, randomized, placebo-controlled and double-blind trial, 60 patients scheduled to undergo routine outpatient surgery under general anesthesia were randomly allocated to 2 groups, the HnBB (n = 30) and sodium chloride (n = 30) groups. Twenty seconds after the injection of 20 mg HnBB or 0.9 % sodium chloride, a 50-mg dose of propofol was injected in 2-3 s. Ten seconds later, the pain intensity was assessed using a 4-point scale: no pain (0), mild (1), moderate (2), and severe (3) pain. The Student t test was used for the analysis of parametric data and the Pearson χ2 test for categorical data.The occurrence of pain in the HnBB group (43.3%) was significantly lower than the control group (73.3%) (p < 0.018). Of the 30 patients in each group, 10 in the control group and 3 in the HnBB group experienced severe pain (p = 0.001).Pretreatment with 20 mg HnBB significantly reduced propofol injection pain compared to placebo."
1,"TITLE: Effects of anesthetics on early postoperative cognitive outcome and intraoperative cerebral oxygen balance in patients undergoing lung surgery: a randomized clinical trial.ABSTRACT: One-lung ventilation (OLV) may impair cerebral oxygen balance and induce postoperative cognitive dysfunction (POCD). It is unclear whether the type of anesthetic influences the incidence of POCD in patients undergoing OLV. This prospective study compared the incidence of POCD and intraoperative cerebral oxygen desaturation in OLV patients anesthetized with propofol vs sevoflurane during lung surgery.There were 148 participants enrolled in this study and randomized equally to either the propofol or the sevoflurane group. Anesthesia was maintained with either propofol or sevoflurane combined in both groups with fentanyl and epidural anesthesia. Regional cerebral oxygen saturation (rSO2), jugular bulb venous oxygen saturation (SjO2), and the incidence of cerebral oxygen desaturation (rSO2 or SjO2 < 50% or rSO2 < 80% of baseline) were measured during anesthesia. Cognitive function was assessed using seven neurocognitive tests two days preoperatively, five days postoperatively (primary outcome), and three months postoperatively. Bivariable and multivariable regression analyses were conducted to identify factors associated with POCD.Rates of POCD did not differ statistically between groups five days postoperatively (propofol, 16/72 patients; sevoflurane, 24/72 patients; RR, 0.67; 95% CI, 0.39 to 1.15; P = 0.14) or three months postoperatively (propofol, 9/60 patients; sevoflurane, 12/58 patients; RR, 0.73; 95% CI, 0.33 to 1.59; P = 0.42). Only three subjects per group showed intraoperative cerebral oxygen desaturation. Multivariable regression analysis revealed older age as an independent predictor of POCD.No statistically significant difference in the incidence of POCD could be detected between the sevoflurane and propofol anesthesia groups. Postoperative cognitive dysfunction was relatively frequent following OLV in both groups. (UMIN 000002826)."
1,"TITLE: Nurse-Delivered Screening and Brief Intervention Among College Students with Hazardous Alcohol Use: A Double-Blind Randomized Clinical Trial from India.ABSTRACT: To determine the effectiveness of individual-based, nurse-delivered, on-campus screening and brief intervention (SBI) for hazardous alcohol use among college students.It was a parallel-design, double-blind, randomized controlled trial. Out of 793 students screened, 130 met the selection criteria of hazardous alcohol use, defined by alcohol use disorder identification test (AUDIT) score 8-19. Participants were randomly allocated to either SBI or general advice group. Both interventions were delivered by one specially trained nurse. Outcome was assessed after 3 months. Primary outcome was the change in the mean AUDIT score and the secondary outcome was difference in the proportion of students transited from the high- to low-risk category of AUDIT. General linear model with repeated measures and logistic regression were used to determine the primary and secondary outcome, respectively.Majority (80.7%) of the participants were men. Among all the baseline demography and clinical characteristics, only family history of alcohol use was significantly different in the groups. Intention to treat analysis showed a significant but small effect (0.16) of SBI on the mean AUDIT score. Gender did not moderate the effect. SBI was also observed to have a significant effect (adjusted odds ratio 3.7 95% CI 1.529-8.850) on shifting the students from high- to low-risk AUDIT zone.SBI among college students is acceptable and has a small but significant effect on alcohol use. In countries like India, where despite the increasing magnitude of hazardous drinking in students no formal system exists to deal with the problem, SBI might be useful."
1,"TITLE: A randomized pilot trial of an integrated school-worksite weight control program.ABSTRACT: Worksite provision of paid time off for parent participation in a school-based healthy weight program may improve treatment adherence and outcomes. The current pilot study examined whether parents who received worksite support for attendance at a school-based healthy weight program would attend more sessions, lose more weight, and make healthier changes in home food environments than parents who did not receive worksite support.Thirty-eight urban, low-income African American and Mexican American mothers of kindergartners were randomized to an integrated school-parent-worksite program that targeted healthy home food environments and energy balance self-monitoring or the identical school-based program without worksite support. Ten sessions were delivered to parent participants during afterschool hours. Process measures included session attendance and energy balance log completion. Outcome measures included parent body mass index (BMI) change, child BMI z-score change, and home food inventory (HFI) score changes over 12 months.RESULTS showed better weight change for parents (i.e., BMI unit reduction of 1.4 vs. 0.3 in comparison group, p = .001), increased parental attendance, and improvements in the home food environment when parents received paid time off from their worksite for their participation in the healthy weight program. Child weight change was also observed despite no direct contact with children.The current pilot study provides support for the hypothesis that worksite support for school-based interventions may improve health outcomes that depend on parental involvement. Removing barriers to attendance in a healthy weight program resulted in improved treatment adherence and outcomes in low-income, minority parents and children."
1,"TITLE: Injection of intrathecal normal saline in decreasing postdural puncture headache.ABSTRACT: Postdural puncture headache (PDPH) is the most common and still unresolved postoperative complication of spinal anesthesia. Although there are several positive results of intrathecal saline injection for the treatment of PDPH and prophylaxis after accidental dural puncture, the effect of deliberate intrathecal saline injection before spinal anesthesia has not been examined. The objective of our study was to evaluate the effect of prophylactic administration of intrathecal normal saline in decreasing PDPH.One hundred healthy women (ASA physical status I) of age between 18 and 35 years scheduled for elective term cesarean delivery under spinal anesthesia were included. Patients were randomly divided into two equal groups. Group C received 2.5 ml (12.5 mg) hyperbaric bupivacaine 0.5 % as a control, and group S received intrathecal normal saline 5 ml before intrathecal injection of 2.5 ml (12.5 mg) hyperbaric bupivacaine 0.5%. The incidence and severity of PDPH were assessed after 48 h and again 3-7 days after operation.Basal characteristics were statistically similar in both groups (P > 0.05). The incidences of moderate and severe PDPH during first postoperative 48 h were not different between the groups (P = 0.24). However, the frequency of PDPH after 3-7 days was statistically higher in group C in compared with group S (16 vs. 2 %, P = 0.03). Totally the frequency of PDPH was higher in group C (24 vs. 2%, P = 0.002).Administration of normal saline (5 ml) before intrathecal administration of hyperbaric bupivacaine as a preventive approach is an effective and simple way to minimize PDPH in patients undergoing cesarean section."
1,"TITLE: Effectiveness of aerobic physical training for treatment of chronic asymptomatic bacteriuria in subjects with spinal cord injury: a randomized controlled trial.ABSTRACT: To evaluate the effectiveness and safety of aerobic physical training for treatment of chronic asymptomatic bacteriuria in subjects with spinal cord injury.Randomized controlled trial.University hospital.Forty-two participants with spinal cord injury between C8 and T12 segments were randomly assigned to intervention or control groups.In the intervention group, subjects received a risk evaluation, stress test and urinary culture before the start of the study and after 16 weeks. The study consisted of aerobic physical conditioning with moderate intensity for the intervention group while the control group was asked to maintain their daily life activities.Increase of estimated peak oxygen consumption and also if there was a decrease in the proportions of positive urinary culture.The intervention group showed an increase of estimated peak oxygen consumption of between 939 (714-1215) and 1154 (1005-1351) mL/min (P = 0.009) and a reduction of chronic asymptomatic bacteria of between 52.3% (29.8-74.3%) and 14.2% (3-36.3%) (P < 0.001). No adverse effects related to physical activity were recorded during the period of training.The regular practice of physical activity of moderate intensity applied to patients with spinal cord injury may be an effective and safe method for the treatment of chronic asymptomatic bacteriuria."
1,"TITLE: Osteoprotegerin levels decrease during testosterone therapy in aging men and are associated with changed distribution of regional fat.ABSTRACT: The cardiovascular effects of testosterone treatment are debated. Osteoprotegerin (OPG) is an independent marker of cardiovascular risk. We investigated the effect of testosterone therapy on OPG levels in aging men with low normal bioavailable testosterone levels. A randomized, double-blinded, placebo-controlled study of 6 months testosterone therapy (gel) in 38 men aged 60-78 years with bioavailable testosterone <7.3 nmol/l and waist circumference >94 cm was performed. Clinical evaluation, OPG, and C-reactive protein (CRP) measurements were carried out. Lean body mass (LBM), total fat mass, and bone mineral density (BMD) were established by dual X-ray absorptiometry. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured by magnetic resonance imaging. Power calculation was based on an increase in LBM during testosterone therapy and responders were defined as testosterone treated patients with increased LBM (Δ LBM positive), n=14. Data are presented as median (interquartile range). Testosterone therapy decreased total fat mass and SAT, whereas VAT was unchanged (n=38). OPG levels decreased during testosterone therapy (from 2.0 (1.9-2.5) to 1.9 (1.6-2.2) ng/ml, p<0.05 vs. placebo), whereas CRP levels were unchanged (n=38). In responders to testosterone therapy (n=14), ΔOPG levels were inversely associated with ΔSAT (r= - 0.60, p=0.03) and positively associated with ΔVAT (r=0.56, p=0.04). OPG levels decreased during testosterone therapy suggesting decreased cardiovascular risk. Decreased OPG levels were associated with changes in regional fat distribution and future studies are needed to further evaluate the association between OPG and regional fat mass distribution."
1,"TITLE: Terlipressin decreases vascular endothelial growth factor expression and improves oxygenation in patients with acute respiratory distress syndrome and shock.ABSTRACT: Recent clinical data suggest that treatment with terlipressin (TP) may be more advantageous for septic shock than catecholamines. However, it is unknown whether TP would be effective for acute respiratory distress syndrome (ARDS) patients with shock.The aim of this study was to compare the impact of TP vs. dopamine on hemodynamic variables and vascular endothelial growth factor (VEGF) in ARDS patients with shock.We studied 32 ARDS patients with shock despite fluid loading, who were randomized to receive TP (16 patients) or dopamine (16 patients). TP was administered as a continuous intravenous dose of 1.3 μg/kg/h and dopamine was administered in doses up to 20 μg/kg/min to maintain a mean arterial pressure of 70 ± 5 mm Hg for 48 h. Hemodynamic changes, ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO(2)/FiO(2)), and VEGF were recorded prospectively.There was a significant correlation between the plasma VEGF level and the lung injury score at baseline (r = 0.387, p < 0.01). VEGF concentrations significantly decreased from baseline levels in the TP group (p < 0.05) at 48 h; there was no difference in the dopamine group (p > 0.05) at 48 h vs. baseline. There was no significant difference in the tumor necrosis factor-α concentration between the groups.TP treatment has the potential to inhibit VEGF and improve oxygenation in patients with shock in the early stage of ARDS."
1,"TITLE: The effect of regular consumption of lupin-containing foods on glycaemic control and blood pressure in people with type 2 diabetes mellitus.ABSTRACT: Type 2 diabetes mellitus is a metabolic disorder characterized by high glucose and insulin resistance. It is strongly linked to lifestyle, including poor diet and physical inactivity. Lupin is a novel food ingredient, rich in protein and fibre with negligible sugar and starch, which can be incorporated into various foods to reduce glycaemic load. Regular consumption of lupin-enriched foods may be a novel and easily achievable means of reducing overall glycaemic load and improving glycaemic control in diabetes.To determine whether regular consumption of lupin-enriched foods can improve glycaemic control and lower blood pressure in people with type 2 diabetes mellitus.Fourteen men and 8 women (mean age 58.0 ± 6.6 years and BMI 29.0 ± 3.5 kg m-2) with type 2 diabetes mellitus were recruited from the general population to take part in a double-blind, randomised, controlled cross-over study. Participants consumed lupin or control foods for breakfast and lunch every day, and for dinner at least 3 days per week during the 8-week treatment periods. Lupin-enriched foods consisted of bread, pasta, Weetbix™ cereal and crumbs, with energy-matched control products. Treatments were completed in random order with an 8-week washout period. All participants monitored their blood glucose levels pre- and post-breakfast and lunch, and their blood pressure in the morning and evening, 3 days per week for the duration of each treatment period.Seventeen participants completed both treatment arms, with all 22 participants (14 males, 8 females) analysed on an intention-to-treat basis. Eight weeks consumption of lupin-enriched food had no significant effect on mean blood glucose levels (mean difference: -0.08 ± 0.06 mmol L-1, p = 0.214) or post-prandial blood glucose levels (-0.13 ± 0.10 mmol L-1, p = 0.196). There was no effect on home systolic (-0.4 ± 0.4 mmHg, p = 0.33) or diastolic (0.3 ± 0.3 mmHg, p = 0.321) blood pressure and heart rate (0.5 ± 0.3 bpm, p = 0.152), and no effect on body weight throughout the treatment periods.Regular consumption of lupin-enriched foods had no significant effect on glycaemic control or blood pressure in people with type 2 diabetes mellitus."
1,"TITLE: Lactobacillus GG in the prevention of nosocomial gastrointestinal and respiratory tract infections.ABSTRACT: The incidence of nosocomial infections, predominantly gastrointestinal and respiratory, in children in developed countries is high, ranging from 5% to 44%. There is no effective strategy for preventing these infections. The objective of our study was to investigate the role of Lactobacillus GG (LGG) in preventing nosocomial gastrointestinal and respiratory tract infections at a pediatric hospital.We conducted a randomized, double-blind, placebo-controlled trial of 742 hospitalized children. They were randomly allocated to receive for their hospitalization LGG at a dose of 10(9) colony-forming units in 100 mL of a fermented milk product (LGG group, n = 376) or placebo that was the same postpasteurized fermented milk product without LGG (placebo group, n = 366).In the LGG group, compared with the placebo group, we found a significantly reduced risk for gastrointestinal infections (relative risk [RR]: 0.40 [95% confidence interval (CI): 0.25-0.70]; number needed to treat: 15 [95% CI: 9-34)], respiratory tract infections (RR: 0.38 [95% CI: 0.18-0.85]; number needed to treat: 30 [95% CI: 16-159]), vomiting episodes (RR: 0.5 [95% CI: 0.3-0.9]), diarrheal episodes (RR: 0.24 [95% CI: 0.10-0.50]), episodes of gastrointestinal infections that lasted >2 days (RR: 0.40 [95% CI: 0.25-0.70]), and episodes of respiratory tract infections that lasted >3 days (RR: 0.4 [95% CI: 0.2-0.9]). Groups did not differ in hospitalization duration (P = .1).LGG administration can be recommended as a valid measure for decreasing the risk for nosocomial gastrointestinal and respiratory tract infections in pediatric facilities."
1,"TITLE: Effect of tiotropium in men and women with COPD: results of the 4-year UPLIFT trial.ABSTRACT: Gender differences may occur in many chronic diseases. We have examined the influence of gender in chronic obstructive pulmonary disease (COPD) on long-term responses to tiotropium.Subgroup analysis of data from the Understanding the Potential Long-term Impact of Tiotropium (UPLIFT) trial (4-year, randomized, double-blind, placebo-controlled trial of tiotropium in patients with COPD).Of 5992 patients, 75% were men and 25% women. Mean age was 65 and 63 years, respectively. Baseline post-bronchodilator forced expiratory volume in 1s (FEV(1))=47% predicted(men) and 49% predicted(women). St George's Respiratory Questionnaire (SGRQ) total score was 44.9 and 48.7units, respectively. At 48 months, improvement in trough FEV(1) over control was 92mL(men) and 77mL(women) (p<0.001 for both), with no differences in the rate of decline (trial primary endpoint). Hazard ratio (HR) (95% confidence interval [CI]) for first exacerbation (tiotropium/placebo) was 0.87(0.81, 0.93)(men) and 0.83(0.74, 0.94)(women). Number of exacerbations (per patient-year) was reduced with tiotropium in men (from 0.82 to 0.71) and women (from 0.92 to 0.77) (p<0.005 for both). HR (95% CI) for a hospitalized exacerbation was 0.89(0.79, 0.99) and 0.77(0.62, 0.94), respectively. HR (95% CI) for mortality during treatment was 0.85(0.72, 0.99)(men) and 0.85(0.62, 1.18)(women). Improvements in SGRQ total score (tiotropium-control) at 1, 2, 3 and 4 years were: -2.8, -2.3, -3.6, -2.4(men) and -2.7, -2.6, -2.6, -2.1(women) (p<0.05 for all).Long-term treatment of COPD with tiotropium improves lung function, exacerbations and health status in men and women, with similar magnitudes of benefit. Boehringer Ingelheim trial 205.235; ClinicalTrials.gov: NCT00144339."
1,"TITLE: Two per cent alcoholic chlorhexidine versus alcoholic five per cent povidone-iodine for the prevention of perineural catheter colonisation: The CHLOVEPI randomised, controlled trial.ABSTRACT: Multimodal analgesia, including a regional technique using perineural catheters (PNCs), is recommended for the treatment of moderate-to-severe acute postoperative pain. Perineural catheters are at risk of bacterial colonisation. In this study, we compared the cutaneous antiseptic efficacy of 2% alcoholic chlorhexidine and povidone-iodine-alcohol for preventing the bacterial colonisation of PNCs in orthopaedic surgery.We performed a randomised, controlled trial, comparing two cutaneous antisepsis strategies, one based on 2% alcoholic chlorhexidine and the other on povidone-iodine-5% alcohol, for placed PNCs before orthopaedic surgery. The primary endpoint was the incidence of catheter bacterial colonisation (threshold > 1000 colony-forming units/ml). The secondary endpoints were the incidence of catheter-related infections and the adverse effects of the antiseptic solutions.From November 2016 to May 2018, we included 113 patients in this study. The use of alcoholic chlorhexidine was associated with a lower incidence of catheter colonisation (15.5% (n = 9) versus 32.7% (n = 18); OR: 0.28 [0.09-0.77], p =  0.01). No catheter-related infections or adverse effects of antiseptic solutions were observed in either group. The risk factors associated with colonisation were a duration of catheter use ≥ 3 days (p =  0.04) and obesity (p = 0.005). The most frequently identified bacterium was Staphylococcus epidermidis.Skin disinfection with 2% alcoholic chlorhexidine decreases bacterial colonisation rates for placed perineural catheters."
0,"TITLE: Determination of isotretinoin in human plasma by high performance liquid chromatography-electrospray ionization mass spectrometry.ABSTRACT: A rapid, sensitive and specific high performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method for the quantification of 13-cis-retinoic acid (isotretinoin) in human plasma has been developed. Acitretin was employed as the internal standard (IS). The analytes were chromatographically separated on a Shimadzu Shim-pack VP-ODS C18 column (150 mm × 2.0 mm I.D.) with a mobile phase consisting of acetonitrile and water (90:10, v/v). Detection was performed on a single quadrupole mass spectrometer using an electrospray ionization interface with the selected-ion monitoring (SIM) mode. The method showed excellent linearity (r=0.9989) over the concentration range of 10-1500 ng/mL with good accuracy and precision. The intra- and inter-batch precisions were within 10% relative standard deviation. The recoveries were more than 80%. The validated method was successfully applied to a preliminary bioequivalence study of isotretinoin in 20 Chinese healthy male volunteers."
1,"TITLE: Children's familiarity with snack foods changes expectations about fullness.ABSTRACT: Palatability is regarded as a major determinant of children's energy intake. However, few studies have considered nonhedonic beliefs about foods. In adults, there is emerging evidence that expectations about the satiating properties of foods are an important determinant of meal size, and these beliefs are learned.We measured and quantified children's expected satiation across energy-dense snack foods by using a method of adjustment. Participants changed a comparison-food portion (pasta and tomato sauce) to match the satiation that they expected from a snack food. We predicted that children who were especially familiar with snack foods would expect the foods to generate greater satiation and that children who were unfamiliar with snack foods would match expected satiation on the basis of the physical characteristics (perceived volume) of the foods.Seventy 11- to 12-y-old children completed measures of expected satiation, perceived volume, familiarity, and liking across 6 snack foods.As anticipated, familiarity and expected satiation were positively related (r = 0.37, P = 0.002), and this association remained after liking was controlled for. Furthermore, expected-satiation and perceived-volume judgments were more dissimilar as familiarity with the foods increased.Our findings highlight the role of learning in shaping children's beliefs about the postingestive effects of the consumption of foods; children who ate the foods more often expected them to deliver greater satiation. Furthermore, our findings suggest that, in the absence of prior experience, children rely on a food's physical characteristics (a less-complex strategy) when they judge expected satiation. This trial was registered at clinicaltrials.gov as NCT01403753."
1,"TITLE: A single dose of a non-steroidal anti-inflammatory drug (NSAID) prevents severe pain after ureteric stent removal: a prospective, randomised, double-blind, placebo-controlled trial.ABSTRACT: To determine the incidence of severe pain after ureteric stent removal. To evaluate the efficacy of a single dose of a non-steroidal anti-inflammatory drug (NSAID) in preventing this complication.A prospective, randomised, double-blind, placebo-controlled trial was performed at our institution. Adults with an indwelling ureteric stent after ureteroscopy were randomised to receive either a single dose of placebo or an NSAID (rofecoxib 50 mg) before ureteric stent removal. Pain was measured using a visual analogue scale (VAS) just before and 24 h after stent removal Pain medication use after ureteric stent removal was measured using morphine equivalents.In all, 22 patients were enrolled and randomised into the study before ending the study after interim analysis showed significant decrease in pain level in the NSAID group. The most common indication for ureteroscopy was urolithiasis (14 patients). The proportion of patients with severe pain (VAS score of ≥7) during the 24 h after ureteric stent removal was six of 11 (55%) in the placebo group and it was zero of 10 in the NSAID group (P < 0.01). There were no complications related to the use of rofecoxib.We found a 55% incidence of severe pain after ureteric stent removal. A single dose of a NSAID before stent removal prevents severe pain after ureteric stent removal."
1,"TITLE: A randomized bilateral vehicle-controlled study of eflornithine cream combined with laser treatment versus laser treatment alone for facial hirsutism in women.ABSTRACT: Although there are a multitude of therapeutic modalities for removing unwanted facial hair in women, there is very little information on using the newer medical treatment approaches in combination. This study was designed to determine whether topical eflornithine can enhance the efficacy of laser hair removal.This was a randomized, double-blind, placebo-controlled, right-left comparison study of eflornithine cream combined with laser treatment versus laser alone for treating unwanted hair on the upper lip in women. All subjects underwent treatment to the entire upper lip with a long pulse alexandrite laser (10-40 ms pulse duration) at fluences of 7 to 40 J/cm(2). Laser treatments were performed every 4 weeks for up to 6 sessions. Each patient also applied either eflornithine or placebo cream twice daily to each side of the upper lip in a double-blinded manner. Subjects were evaluated for safety by recording adverse events and for efficacy via (1) investigator global scoring, (2) patient self assessment, and (3) hair count analysis.Both treatment modalities were well tolerated by the 31 evaluable patients. All 3 outcome measures showed significantly better results in favor of eflornithine plus laser versus laser treatment alone. At the end of the study, complete or almost complete hair removal was achieved in 29 of 31 (93.5%) of the eflornithine-laser-treated sites versus 21 of 31 (67.9%) for the placebo cream-laser-treated sites (P = .021, McNemar test). Statistically significant differences in favor of eflornithine were likewise demonstrated at the final assessment through blinded patient grading (13/31 patients [41.9%] thought that the eflornithine was superior to placebo, P = .029, Poisson regression) and hair count analysis (P < .01, paired t test).This is a single-center study that did not determine whether the differences noted above last beyond 6 months.On the basis of both investigator and patient assessments and hair count analysis, we have demonstrated that the addition of eflornithine to laser hair removal results in a more rapid and complete reduction of unwanted facial hair in women when the combination is used for up to 6 months."
1,"TITLE: Beneficial effects of a three-month structured exercise training program on cardiopulmonary functional capacity in young women with polycystic ovary syndrome.ABSTRACT: Polycystic ovary syndrome (PCOS) is an endocrine disease closely related to several risk factors for cardiovascular disease. An impaired cardiopulmonary functional capacity was previously demonstrated in PCOS women. No data regarding the effects of a structured exercise training (ET) program on cardiopulmonary functional capacity in PCOS women are available.Our objective was to evaluate the effects of a 3-month ET program on cardiopulmonary functional capacity in young PCOS women.A prospective baseline-randomized clinical study was conducted at the University ""Federico II"" of Naples, School of Medicine (Italy).Ninety young overweight PCOS women were enrolled.Ninety young PCOS women were randomly subdivided into two groups, each composed of 45 subjects. The PCOS-T (trained) group underwent a 3-month structured ET program, whereas the PCOS-UnT (untrained) group did not. Hormonal and metabolic profiles and cardiopulmonary and exercise parameters were evaluated.After 3-month ET, PCOS-T showed a significant improvement in peak oxygen consumption (+35.4%; P<0.001) and in maximal workload (+37.2%; P<0.001). In PCOS-T we also observed a significant reduction in body mass index (-4.5%; P<0.001) and in C-reactive protein (-10%; P<0.001), and a significant (P<0.001) improvement in insulin sensitivity indexes. After 3 months, no changes were observed in PCOS-UnT.A 3-month structured ET program improves cardiopulmonary functional capacity in young PCOS women."
1,"TITLE: Exercise performance during losartan- or atenolol-based treatment in hypertensive patients with electrocardiographic left ventricular hypertrophy (a LIFE substudy).ABSTRACT: The objective of the study was to assess the influence of left ventricular (LV) hypertrophy regression on exercise capacity in hypertensive patients. Doppler echocardiography was performed at rest and during exercise in 51 patients with electrocardiographic LV hypertrophy before and after 1 year of randomized blinded losartan- or atenolol-based antihypertensive treatment. After 1 year, blood pressure was comparably reduced by 32/14 and 27/13 mmHg, respectively, in the losartan and atenolol groups, but the atenolol group had higher mean LV mass index (118 vs 103 g/m2) and lower LV ejection fraction (61% vs 67%) and midwall shortening (15.8% vs 16.8%) (all p<0.05). Resting diastolic Doppler indices remained unchanged and did not differ between the groups. Peak oxygen uptake during exercise was virtually unchanged after 1 year and did not differ between the groups in spite of a lower peak exercise heart rate in atenolol-treated patients. In multivariate analysis, higher peak oxygen uptake at 1 year was associated with lower body mass index, and higher systolic blood pressure and shorter isovolumic relaxation time at peak exercise (multiple R2 = 0.51, p<0.01), while age, gender, heart rate increase during exercise, reduction in LV mass and study treatment did not enter. In conclusion, reduction in blood pressure and LV mass induced by losartan or atenolol treatment was not accompanied by improved exercise capacity after 1 year. The results may be explained by persistent impairment of myocardial relaxation influencing exercise capacity."
1,"TITLE: Efficacy of transcutaneous electrical nerve stimulation for pain relief in women undergoing office endometrial biopsy.ABSTRACT: To evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) for decreasing pain related with office endometrial biopsy.In this prospective study, 65 women undergoing office endometrial biopsy were randomly allocated to receive 550 mg oral naproxen sodium plus active TENS (Group I, n = 33) or 550 mg oral naproxen sodium plus placebo TENS (Group II, n = 32). The intensity of pain perceived by the patients was measured using a 10-cm visual analog scale (VAS) before insertion of the speculum, when the cervix grasped, immediately after biopsy, and 15 min after the procedure. The effect of anxiety (Spielberger's state anxiety inventory) on pain scores was also investigated.There were no statistical significant differences between groups in age, weight, body mass index, gravidity, parity, education, and menopausal status (p > 0.05). The pain scores before insertion of the speculum, when the cervix grasped, and immediately after biopsy were similar in both groups (p > 0.05). But at 15 min after the procedure, there was a significant reduction of the mean VAS pain score in naproxen sodium plus TENS group, compared with the naproxen sodium plus placebo TENS group (0.14 ± 0.47, 1.44 ± 1.37, respectively, p < 0.0001). The mean anxiety scores were 48.19 ± 6.71 and 45.85 ± 6.22 in Group I and Group II, respectively. We did not find any significant correlation between anxiety and VAS pain scores (p > 0.05).TENS appears to be successful in decreasing pain only after the procedure undergoing office endometrial biopsy. It can be used as a simple, cheap, safe, and effective pain relief method."
1,"TITLE: Prospective randomized trial of multiple micronutrients in subfertile women undergoing ovulation induction: a pilot study.ABSTRACT: This study investigated whether subfertile women undergoing ovulation induction using standard treatment regimens with clomiphene citrate/gonadotrophins have higher pregnancy rates when on an adjuvant multiple micronutrient (MMN) nutritional supplement compared with folic acid alone. A prospective randomized controlled trial was conducted in a teaching-hospital fertility clinic on 58 subfertile women, of which 56 women completed the study. Women undergoing ovulation induction were allocated to either receive adjuvant MMN supplementation or folic acid. Clinical pregnancy rates and blood nutrient concentrations were assessed after the third treatment attempt or as soon as the women achieved pregnancy. Using intention-to-treat analysis, it was observed that women on adjuvant MMN supplementation had a significantly higher cumulative clinical pregnancy rate (66.7%) compared with those on folic acid (39.3%; P = 0.013). The ongoing pregnancy rate in women on MMN supplementation was 60.0% versus 25.0% (P < 0.02) in the folic-acid group. Further, women who were on MMN supplementation had significantly fewer attempts to achieve pregnancy compared with women on folic acid (P < 0.001). The results of this pilot study suggest that women who take adjuvant MMN supplementation during ovulation induction have a higher chance of pregnancy compared with women on folic acid."
0,"TITLE: The relationship, structure and profiles of schizophrenia measurements: a post-hoc analysis of the baseline measures from a randomized clinical trial.ABSTRACT: To fully assess the various dimensions affected by schizophrenia, clinical trials often include multiple scales measuring various symptom profiles, cognition, quality of life, subjective well-being, and functional impairment. In this exploratory study, we characterized the relationships among six clinical, functional, cognitive, and quality-of-life measures, identifying a parsimonious set of measurements.We used baseline data from a randomized, multicenter study of patients diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder who were experiencing an acute symptom exacerbation (n = 628) to examine the relationship among several outcome measures. These measures included the Positive and Negative Syndrome Scale (PANSS), Montgomery-Asberg Depression Rating Scale (MADRS), Brief Assessment of Cognition in Schizophrenia Symbol Coding Test, Subjective Well-being Under Neuroleptics Scale Short Form (SWN-K), Schizophrenia Objective Functioning Instrument (SOFI), and Quality of Life Scale (QLS). Three analytic approaches were used: 1) path analysis; 2) factor analysis; and 3) categorical latent variable analysis. In the optimal path model, the SWN-K was selected as the final outcome, while the SOFI mediated the effect of the exogenous variables (PANSS, MADRS) on the QLS.The overall model explained 47% of variance in QLS and 17% of the variance in SOFI, but only 15% in SWN-K. Factor analysis suggested four factors: ""Functioning,"" ""Daily Living,"" ""Depression,"" and ""Psychopathology."" A strong positive correlation was observed between the SOFI and QLS (r = 0.669), and both the QLS and SOFI loaded on the ""Functioning"" factor, suggesting redundancy between these scales. The measurement profiles from the categorical latent variable analysis showed significant variation in functioning and quality of life despite similar levels of psychopathology.Researchers should consider collecting PANSS, SOFI, and SWN-K in their trials. This would allow a broad spectrum of assessments that would have the ability to capture a wide range of treatment outcomes and allow for a rich characterization of the subgroups involved. Additional research is needed to identify the critical cognitive measures.TRIALS REGISTRATION BACKGROUNDPredicting Response to Risperidone Treatment Through Identification of Early-onset of Antipsychotic Drug Action in SchizophreniaClinicalTrials.gov identifier: NCT00337662; http://www.clinicaltrials.gov/"
1,"TITLE: The Summit Score Stratifies Mortality and Morbidity in Chronic Obstructive Pulmonary Disease.ABSTRACT: Tobacco use and other cardiovascular risk factors often accompany chronic obstructive pulmonary disease (COPD). This study derived and validated the Summit Score to predict mortality in people with COPD and cardiovascular risks.SUMMIT trial subjects (N=16,485) ages 40-80 years with COPD were randomly assigned 50%/50% to derivation (N=8181) and internal validation (N=8304). Three external COPD validations from Intermountain Healthcare included outpatients with cardiovascular risks (N=9251), outpatients without cardiovascular risks (N=8551), and inpatients (N=26,170). Cox regression evaluated 40 predictors of all-cause mortality. SUMMIT treatments including combined fluticasone furoate (FF) 100μg/vilanterol 25μg (VI) were not included in the score.Mortality predictors were FEV, heart rate, systolic blood pressure, body mass index, age, smoking pack-years, prior COPD hospitalizations, myocardial infarction, heart failure, diabetes, anti-thrombotics, anti-arrhythmics, and xanthines. Combined in the Summit Score (derivation: c=0.668), quartile 4 vs 1 had HR=4.43 in SUMMIT validation (p<0.001, 95% CI=3.27, 6.01, c=0.662) and HR=8.15 in Intermountain cardiovascular risk COPD outpatients (p<0.001, 95% CI=5.86, 11.34, c=0.736), and strongly predicted mortality in the other Intermountain COPD populations. Among all SUMMIT subjects with scores 14-19, FF 100μg/VI 25μg vs placebo had HR=0.76 (p=0.0158, 95% CI=0.61, 0.95), but FF 100μg/VI 25μg was not different from placebo for scores <14 or >19.In this post hoc analysis of SUMMIT trial data, the Summit Score was derived and validated in multiple Intermountain COPD populations. The score was used to identify a subpopulation in which mortality risk was lower for FF 100μg/VI 25μg treatment.The SUMMIT trial is registered at ClinicalTrials.gov as number NCT01313676."
1,"TITLE: Effect of direct intramyocardial autologous stem cell grafting in the sub-acute phase after myocardial infarction.ABSTRACT: To assess the efficacy and safety of intramyocardial autologous bone marrow mononuclear stem cells (BMMNC) grafting combined with coronary artery bypass grafting (CABG) on ventricular remodeling and global and regional wall motion after acute transmural myocardial infarction (AMI).Randomized controlled trial including 20 patients with non-revascularized transmural AMI, left ventricular ejection fraction (LVEF) lower than 50% and surgical indication for CABG. The stem cell group was treated with BMMNC grafting by direct intramyocardial injection between the 10th and 15th days after AMI (subacute phase) combined with CABG under cardiopulmonary bypass; the control group was only treated with CABG. Magnetic resonance imaging with gadolinium and stress echocardiography were performed presurgery and 9 months postsurgery.Seventeen patients completed the follow-up. The baseline characteristics of both groups were homogeneous. No significant differences were found in the increase in LVEF (control: 6.99±4.60, cells: 7.47±6.61, P=0.876) or in the decrease in global (control: 0.28±0.39, cells: 0.22±0.28, P=0.759) or regional (control: 0.52±0.38, cells: 0.74±0.60, P=0.415) wall motion indices between the control and stem cell groups of AMI patients. No differences were found in the recovered non-viable segments (control: 1.29±1.11, cells: 2.50±1.41, P=0.091) or in the decrease in end-diastolic (control: 14.05±19.72, cells: 18.40±29.89, P=0.725) or end-systolic (control: 15.42±13.93, cells: 23.06±25.03, P=0.442) volumes. No complications from stem cell grafting were observed.The results from our study reported herein suggest that intramyocardial BMMNC administration during CABG in patients with AMI causes no medium- to long-term improvement in ventricular remodeling."
1,"TITLE: Nintedanib in Japanese patients with idiopathic pulmonary fibrosis: A subgroup analysis of the INPULSIS® randomized trials.ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia. Nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC) compared with placebo in patients with IPF in two replicate trials (INPULSIS®). We examined the efficacy and safety of nintedanib in Japanese patients.We conducted pre-specified subgroup analyses of the annual rate of decline in FVC, time to first acute exacerbation (AE), change from baseline in St George's Respiratory Questionnaire (SGRQ) total score and safety using pooled data from the INPULSIS® trials for Japanese patients.In the overall population, 76 of 638 and 50 of 423 patients in the nintedanib and placebo groups, respectively, were Japanese. Results in Japanese patients were consistent with those in the overall population. In Japanese patients, the adjusted annual rate of decline in FVC was -135.9 mL/year in the nintedanib group and -267.7 mL/year in the placebo group (difference (95% CI): 131.9 (50.7, 213.1) mL/year); the hazard ratio for the time to first AE was 0.25 (0.06, 1.02); and the adjusted mean change from baseline in SGRQ total score at week 52 was 5.81 in the nintedanib group and 9.68 in the placebo group (difference: -3.87 (-8.51, 0.76)). Diarrhoea and liver-related adverse events were the most common events in the nintedanib group, but were reversible following dose reduction, drug interruption or symptomatic therapy.The present results indicate that the efficacy and safety of nintedanib in Japanese patients are comparable with those in the overall population."
0,"TITLE: Determinants of delay in timely treatment seeking for diarrheal diseases among mothers with under-five children in central Ethiopia: A case control study.ABSTRACT: Delays in seeking timely appropriate care contributes to a large number of deaths from diarrhea in children. This study aimed to identify determinants of delays in seeking timely treatment by mothers/caregivers of under-five children with diarrheal diseases.We used an unmatched case-control study from February-March 2017 among 316 children: 158 cases and 158 controls. Cases were mothers/caregivers with under-five children who had signs/symptoms of diarrhea and sought treatment after 24 hours onset of symptom. Controls sought treatment within 24 hours. Field workers collected data using a pre-tested standardized questionnaire. Multivariate logistic regression was conducted to identify determinants of delay in timely diarrhea treatment seeking. Statistical significance was declared by using a p-value<0.05 and 95% of confidence interval (CI) for an adjusted-odds ratio (AOR).The determinants of delay in timely treatment seeking of mothers/caregivers of under-five children with diarrheal diseases were children <24months (AOR = 1.9,95%CI:1.1-3.4); fail to attend school (AOR = 2.4, 95%CI:1.2-4.6); being female children (AOR = 1.7,95%CI:1.05-2.9); preferring government health facility for the treatment of children with diarrheal diseases (AOR = 2.9, 95%CI, 1.3-6.7); lack of past history taking children to health facility and lack of counseling (AOR = 4.8, 95%CI:2.0-12.1); being in the15-25 years age (AOR = 1.7, 95%CI:1.1-3.0) and taking children to a health facility as a first response to diarrhea (AOR = 0.1, 95%CI:0.01-0.8).Age of the child, maternal age, and disease related determinants were determinants for seeking timely treatment to diarrheal diseases. Providing skilled based health education and counseling to mothers/caregivers on seeking timely treatment and taking children with diarrheal diseases to a health facility as a first response to diarrhea is a paramount intervention to reduce morbidity and mortality of children."
1,"TITLE: Effects of low- and high-pressure carbon dioxide pneumoperitoneum on intracranial pressure during laparoscopic cholecystectomy.ABSTRACT: Laparoscopic surgeries are a risk factor for raised intracranial **pressure and neurological complications. Even though rare, the consequences may be severe.One hundred and one patients of laparoscopic cholecystectomy were enrolled and were randomized into two groups: low-pressure 8 mm Hg (Group A) and high-pressure 14 mm Hg (Group B) carbon dioxide pneumoperitoneum during surgery. Fifty patients were in group A and 51 patients were in group B. Intracranial pressure was measured by measuring the optic nerve sheath diameter (ONSD) using ultrasound examination. Baseline ONSD was recorded followed by ONSD recording at various intervals: at the induction of anesthesia; 30 min, 45 min, at the end of surgery; and 30 min post surgery.The groups were comparable in terms of demographics and comorbidities. The mean age of group A was 45 years and for group B it was 45.75 years. Most common indication for surgery was symptomatic gall stone disease. Baseline ONSD in group A was 0.427 ± 0.0459 mm, whereas it was 0.412 ± 0.0412 mm in group B. There was a significant rise of ONSD (p < 0.05) 30 min after induction of pneumoperitoneum and up to 30 min post anesthesia. In the low-pressure group 7 (14%) patients had a significant rise of ICP, whereas in the high-pressure group 20 (39%) patients had a significant rise of ICP (p < 0.05).High-pressure pneumoperitoneum causes significant rise in intracranial pressure in comparison to low-pressure pneumoperitoneum during laparoscopic cholecystectomy, which can be monitored by ONSD measurement by ultrasound examination and is totally non-invasive."
1,"TITLE: Efficacy of oxycodone in intravenous patient-controlled analgesia with different infusion modes after laparoscopic radical surgery of cervical cancer a prospective, randomized, double-blind study.ABSTRACT: The aim of this study was to compare the analgesic and adverse effects of oxycodone with 3 different infusion modes on postoperative pain after laparoscopic radical surgery of cervical cancer.Ninety patients undergoing laparoscopic radical surgery of cervical cancer were randomly divided into 3 groups: Group A (continuous infusion with 0.01 mg/kg/h and a bolus dose with 0.03 mg/kg), Group B (a bolus dose with 0.03 mg/kg) and Group C (PCA was administered as a time-scheduled decremental continuous infusion based on lean body mass). A blinded observer recorded Visual Analogue Scale (VAS), Ramsay sedation score (RSS), infused cumulative dose of oxycodone and side effects at 1, 6, 12, 24, and 48 hours postoperatively, and satisfaction during the postoperative 48 hours.There were significant differences in the VAS pain score when resting or coughing among 3 groups at 1, 6 and 48 hours postoperatively (P <.05). VAS was significantly higher in Group B than in Group A and C until postoperative 1, 6, and 48 hours (P <.05). There were significant differences in cumulative PCA dose among the 3 groups at 1 and 48 hours postoperatively (P <.05). Group C showed significantly less amount of cumulative PCA dose compared to other 2 groups at 1 hour, whereas cumulative PCA dose of Group A at 48 hours was significantly more than other 2 groups (P <.05). There were no significant differences in postoperative nausea and vomiting, FAS, muscle chilling score and RSS among 3 groups at 1, 6, 12, 24 and 48 hours postoperatively. In addition, there was no difference in overall satisfaction during 48 hours postoperatively among 3 groups.Oxycodone provides significant analgesic effect in 3 different infusion modes over 48 hours after laparoscopic radical surgery of cervical cancer, and a time-scheduled decremental continuous infusion of oxycodone can become a better choice for patients after surgery of cervical cancer."
1,"TITLE: Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial.ABSTRACT: Multiple sclerosis (MS) is a chronic immune mediated disease and the progressive phase appears to have significant neurodegenerative mechanisms. The classification of the course of progressive MS (PMS) has been re-organized into categories of active vs. not active inflammatory disease and the presence vs. absence of gradual disease progression. Clinical trial experience to date in PMS with anti-inflammatory medications has shown limited effect. Andrographolide is a new class of anti-inflammatory agent, that has been proposed as a potential drug for autoimmune disorders, including MS. In the present trial, we perform an exploratory pilot study on the efficacy and safety of andrographolide (AP) compared to placebo in not active PMS.A pilot clinical trial using 140 mg oral AP or placebo twice daily for 24 months in patients with not active primary or secondary progressive MS was conducted. The primary efficacy endpoint was the mean percentage brain volume change (mPBVC). Secondary efficacy endpoints included 3-month confirmed disability progression (3-CDP) and mean EDSS change.Forty-four patients were randomized: 23 were assigned to the AP group, and 21 were assigned to the placebo group. The median baseline EDSS of both groups was 6.0. Annualized mPBVC was - 0.679% for the AP group and - 1.069% for the placebo group (mean difference: -0.39; 95% CI [- 0.836-0.055], p = 0.08, relative reduction: 36.5%). In the AP group, 30% had 3-CDP compared to 41% in the placebo group (HR: 0.596; 95% CI [0.200-1.777], p = 0.06). The mean EDSS change was - 0.025 in the AP group and + 0.352 in the placebo group (mean difference: 0.63, p = 0.042). Adverse events related to AP were mild rash and dysgeusia.AP was well tolerated and showed a potential effect in reducing brain atrophy and disability progression, that need to be further evaluated in a larger clinical trial.ClinicalTrials.gov NCT02273635 retrospectively registered on October 24th, 2014."
1,"TITLE: Is it necessary to insert a nasobiliary drainage tube routinely after endoscopic clearance of the common bile duct in patients with choledocholithiasis-induced cholangitis? A prospective, randomized trial.ABSTRACT: Little is known about whether a routinely inserted endoscopic nasobiliary drainage (ENBD) tube improves the clinical course in patients with choledocholithiasis-induced acute cholangitis after clearance of choledocholithiasis.The aim of this study was to investigate the need for ENBD on the clinical outcomes of patients with acute cholangitis undergoing endoscopic clearance of common bile duct (CBD) stones.Prospective, randomized study.Tertiary referral center.A total of 104 patients with choledocholithiasis-induced acute cholangitis who underwent primary endoscopic treatment were compared according to insertion of an ENBD tube (51 in the ENBD group and 53 in the no-ENBD group).Insertion of an ENBD tube after clearance of CBD stones.Recurrence of cholangitis and length of hospital stay after clearance of CBD stones.Baseline clinical characteristics were similar between both groups. There were no significant differences in the recurrence rate of cholangitis at 24 weeks (3.9% for the ENBD group vs 3.8% for the no-ENBD group at 24 weeks; P = .99) and length of hospital stay (7.9 days [standard error = 1.2] for the ENBD group vs 7.9 days [standard error = 0.7] for the no-ENBD group; P = .98). However, procedure time was longer (26.2 [SE = 1.8] minutes vs 22.7 [SE = 1.0] minutes, respectively; P = .01) and the discomfort score was higher (4.9 [SE = 0.4] vs 2.8 [SE = 0.3], respectively; P = .02) in the ENBD group than in the no-ENBD group.Single-center study.A routinely inserted ENBD tube did not improve the clinical course, despite patients having to endure increased procedure time and discomfort, and the insertion would therefore be unnecessary."
1,"TITLE: Prognosis of Behcet's syndrome among men with mucocutaneous involvement at disease onset: long-term outcome of patients enrolled in a controlled trial.ABSTRACT: To assess the influence of being free of major organ involvement during the early years of the disease on the prognosis of men with Behçet's syndrome (BS).Ninety-six men with BS, who had only active mucocutaneous manifestations when entering a controlled trial of thalidomide mean (s.d.) 11.7 (0.8) years ago, were re-evaluated for the use of immunosuppressives as an indication of major organ involvement during the post-trial period.Outcome information was obtained in 91 (95%) patients. Thirty-nine (43%) patients had to use immunosuppressives during the post-trial period. Immunosuppressive use was significantly more frequent among patients developing BS at younger age (76%; <or=24 years) than older age (30%; >or=25 years). Developing BS at young age (OR = 6.3; 95% CI 2.09, 19.04) and not using colchicine during the post-trial period (OR = 3.860; 95% CI 1.484, 10.034) were risk factors for immunosuppressive use. However, 82% of the patients using colchicine had onset during old age. Colchicine showed a significant effect in decreasing the use of immunosuppressives only among patients of old age at onset (Fisher's exact test = 5.026; P = 0.031) in the subgroup analysis. Eye disease (18 patients) and vascular involvement (14 patients) were the most frequent indications for immunosuppressive use.Being free of major organ involvement during the early years of BS does not indicate a mild prognosis for men developing BS at young age. Whether colchicine will reduce the need for immunosuppressive use among men developing BS at old age awaits formal studies."
1,"TITLE: Biomarkers for oxidative stress and organ injury during Transnasal Humidified Rapid-Insufflation Ventilatory Exchange compared to mechanical ventilation in adults undergoing microlaryngoscopy: A randomised controlled study.ABSTRACT: Apnoeic oxygenation using Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) during general anaesthesia prolongs the safe apnoeic period. However, there is a gap of knowledge how THRIVE-induced hyperoxia and hypercapnia impact vital organs. The primary aim of this randomised controlled trial was to characterise oxidative stress and, secondary, vital organ function biomarkers during THRIVE compared to mechanical ventilation (MV).Thirty adult patients, American Society of Anesthesiologists (ASA) 1-2, undergoing short laryngeal surgery under general anaesthesia were randomised to THRIVE, F O 1.0, 70 L min during apnoea or MV. Blood biomarkers for oxidative stress, malondialdehyde and TAC and vital organ function were collected (A) preoperatively, (B) at procedure completion and (C) at PACU discharge.Mean apnoea time was 17.9 (4.8) min and intubation to end-of-surgery time was 28.1 (12.8) min in the THRIVE and MV group, respectively. Malondialdehyde increased from 11.2 (3.1) to 12.7 (3.1) µM (P = .02) and from 9.5 (2.2) to 11.6 (2.6) µM (P = .003) (A to C) in the THRIVE and MV group, respectively. S100B increased from 0.05 (0.02) to 0.06 (0.02) µg L (P = .005) (A to C) in the THRIVE group. No increase in TAC, CRP, leukocyte count, troponin-T, NTproBNP, creatinine, eGFRcrea or NSE was demonstrated during THRIVE.While THRIVE and MV was associated with increased oxidative stress, we found no change in cardiac, inflammation or kidney biomarkers during THRIVE. Further evaluation of stress and inflammatory response and cerebral and cardiac function during THRIVE is needed."
1,"TITLE: Patient-centred innovation for multimorbidity care: a mixed-methods, randomised trial and qualitative study of the patients' experience.ABSTRACT: Patient-centred interventions to help patients with multimorbidity have had mixed results.To assess the effectiveness of a provider-created, patient-centred, multi-provider case conference with follow-up, and understand under what circumstances it worked, and did not work.Mixed-methods design with a pragmatic randomised trial and qualitative study, involving nine urban primary care sites in Ontario, Canada.Patients aged 18-80 years with ≥3 chronic conditions were referred to the Telemedicine IMPACT Plus intervention; a nurse and patient planned a multi-provider case conference during which a care plan could be created. The patients were randomised into an intervention or control group. Two subgroup analyses and a fidelity assessment were conducted, with the primary outcomes at 4 months being self-management and self-efficacy. Secondary outcomes were mental and physical health status, quality of life, and health behaviours. A thematic analysis explored the patients' experiences of the intervention.A total of 86 patients in the intervention group and 77 in the control group showed no differences, except that the intervention improved mental health status in the subgroup with an annual income of ≥C$50 000 (β-coefficient 11.003,  = 0.006). More providers and follow-up hours were associated with poorer outcomes. Five themes were identified in the qualitative study: valuing the team, patients feeling supported, receiving a follow-up plan, being offered new and helpful additions to their treatment regimen, and experiencing positive outcomes.Overall, the intervention showed improvements only for patients who had an annual income of ≥C$50 000, implying a need to address the costs of intervention components not covered by existing health policies. Findings suggest a need to optimise team composition by revising the number and type of providers according to patient preferences and to enhance the hours of nurse follow-up to better support the patient in carrying out the case conference's recommendations."
0,"TITLE: Impact of tylosin phosphate and distillers dried grains with solubles on energy and nutrient digestibility and flow through the gastrointestinal tract in growing pigs.ABSTRACT: The objective of this study was to evaluate the impact of tylosin phosphate (TP) on energy and nutrient digestibility and flow through the gastrointestinal tract in growing pigs fed corn-soybean meal or corn-soybean meal-distillers dried grains with solubles (DDGS) based diets. Eighteen barrows (initial BW = 32.6 ± 1.2 kg) were surgically fitted with a T-cannula in the distal ileum and allotted to a Youden square design with 6 diets and 3 replicate periods. Treatments were arranged in a 2 × 2 factorial: TP (0 vs. 44 mg/kg) and DDGS (0 vs. 25%). Two N-free dietary treatments (0 vs. 44 mg/kg TP) were also included for determining basal ileal endogenous AA losses (IAAend) and the effect of TP on basal IAAend. Replicate periods included 4 d of adaptation to treatments and 2 sampling periods. Fecal collection occurred on d 5 and 6 and ileal digesta collection occurred on d 7 and 8 for sampling period 1 whereas sampling period 2 included fecal collection on d 11 and 12 and ileal digesta collection on d 13 and 14. Apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) were calculated for DM, energy, and NDF. The AID and standardized ileal digestibility (SID) of AA were calculated. Inclusion of DDGS reduced AID (68.0 vs. 72.8%; P < 0.001) and ATTD (79.9 vs. 85.0%; P < 0.001) of energy. There were no effects of TP on energy digestibility. The DDGS inclusion increased the amount of GE (1.47 vs. 1.18 Mcal/kg DMI; P < 0.001) and NDF (94 vs. 60 g/kg DMI; P < 0.001) remaining at the terminal ileum; however, hindgut disappearance of energy (0.55 vs. 0.53 Mcal/kg DMI) and NDF (13 vs. 15 g/kg DMI) was similar between the corn-soybean meal-DDGS and corn-soybean meal based diets. There were no effects of TP on basal IAAend; therefore, SID AA values were calculated using means of the 2 N-free diets. The SID of Lys (79.6 vs. 84.1%; P < 0.001) and all other indispensible AA, except Leu, was lower in the DDGS diets. Inclusion of TP did not influence SID of AA. In conclusion, under the conditions of this experiment, TP did not affect digestibility of AA or the digestibility and gastrointestinal tract flow of energy and the inclusion of DDGS did not affect the response to TP."
1,"TITLE: Nutrition, Hygiene and Stimulation Education for Impoverished Mothers in Rural Uganda: Effect on Maternal Depression Symptoms and Their Associations to Child Development Outcomes.ABSTRACT: Optimal nutrition improves child development, and impaired development is associated with maternal depression symptoms, in particular in low resource settings. In this follow-up of an open cluster-randomized education trial, we examined its effects among mothers in rural Uganda on their depression symptoms and the association of these symptoms to child development. The education comprised complementary feeding, stimulation, and hygiene. We assessed 77 intervention mothers and 78 controls using Beck Depression Inventory-II (BDI-II) and Center for Epidemiologic Studies Depression Scale (CES-D) scores. Child development was assessed with Bayley Scales of Infant and Toddler Development-III (BSID-III) composite scores for cognitive, language and motor development. Compared to controls, the intervention reduced depression symptoms' scores with mean (95% CI) differences: -8.26 (-11.49 to -1.13,  = 0.0001) and -6.54; (-8.69 to -2.99,  = 0.004) for BDI II at 20-24 and 36 months, respectively. Similar results were obtained with CES-D. There was a negative association of BDI-II scores and BSID-III cognitive and language scores at 20-24 ( = 0.01 and 0.008, respectively) and 36 months ( = 0.017 and 0.001, respectively). CES-D associations with BSID-III cognitive and language scores showed similar trends. BSID-III motor scores were associated with depression scores at 36 months for both BDI-II and CES-D ( = 0.043 and 0.028, respectively). In conclusion, the group education was associated with reduced maternal depression scores. Moreover, the depression scores were inversely associated with child cognitive and language development outcomes."
1,"TITLE: The Influences of Chromium Supplementation on Metabolic Status in Patients with Type 2 Diabetes Mellitus and Coronary Heart Disease.ABSTRACT: This investigation was conducted to determine the effects of chromium supplementation on metabolic status in diabetic patients with coronary heart disease (CHD). This randomized, double-blind, placebo-controlled trial was performed in 64 diabetic patients with CHD between October 2017 and January 2018. Patients were randomly divided into two groups to obtain either 200 μg chromium (n = 32) or placebo (n = 32) for 12 weeks. Chromium supplementation significantly reduced body weight (- 0.9 ± 1.6 vs. + 0.1 ± 0.8 kg, P = 0.001), BMI (- 0.4 ± 0.7 vs. + 0.1 ± 0.3 kg/m, P = 0.002), fasting glucose (β - 11.03 mg/dL; 95% CI, - 18.97, - 3.09; P = 0.007), insulin (β - 1.33 μIU/mL; 95% CI, - 1.90, - 0.76; P < 0.001), and insulin resistance (β - 0.44; 95% CI, - 0.62, - 0.25; P < 0.001) and significantly increased insulin sensitivity (β 0.007; 95% CI, 0.003, 0.01; P < 0.001) compared with the placebo. In addition, taking chromium led to a significant reduction in serum high-sensitivity C-reactive protein (hs-CRP) (β - 0.49 mg/L; 95% CI, - 0.91, - 0.06; P = 0.02) and plasma malondialdehyde (MDA) levels (β - 0.22 μmol/L; 95% CI, - 0.35, - 0.10; P = 0.001); also, a significant rise in total antioxidant capacity (TAC) (β 84.54 mmol/L; 95% CI, 31.05, 138.02; P = 0.002) was observed in comparison with placebo. Additionally, chromium administration significantly reduced diastolic blood pressure (DBP) (β - 5.01 mmHg; 95% CI, - 9.04, - 0.97; P = 0.01) compared with the placebo. Overall, the 12-week supplementation of chromium to diabetic patients with CHD had beneficial impacts on weight, BMI, glycemic control, hs-CRP, TAC, MDA, and DBP.Trial Registration www.irct.ir: http://www.irct.ir: IRCT20170513033941N30."
1,"TITLE: Effect of a balance-training programme on postural balance, aerobic capacity and frequency of falls in women with osteoporosis: A randomized controlled trial.ABSTRACT: To investigate the effect of a 12-month complex balance-training programme on static and dynamic postural balance, aerobic capacity and frequency of falls in women with established osteoporosis.Randomized controlled trial in which the intervention group was assigned a 12-month exercise programme (3 times a week for 30 min) and the control group had no intervention.A total of 100 osteoporotic women with at least one previous fracture.Performance-based Timed Up and Go (TUG), Berg Balance Scale (BBS) and stabilometric platform tests were used to evaluate balance. Aerobic capacity was measured by bicycle ergometry. Frequency of falls was assessed using a falls diary.After 1 year, there was a statistically significant difference between the improvement achieved in the intervention and control groups on the performance-based TUG, BBS and stabilometric platform tests (p < 0.05). Mean metabolic equivalent (MET) value decreased in the intervention group, from 4.91 to 3.82 (a significant difference from the change achieved in the control group; p = 0.05). Relative risk of falls was 0.534 at 1 year (p = 0.17).The 12-month balance-training programme significantly improved postural balance and increased aerobic capacity in women with established osteoporosis."
1,"TITLE: Exercise and postprandial lipemia: effects on vascular health in inactive adults.ABSTRACT: There is evidence to suggest that postprandial lipemia are is linked to the impairment of endothelial function, which is characterized by an imbalance between the actions of vasodilators and vasoconstrictors. The aim of this study was to determine the effects of a 12-week high-intensity training (HIT) and moderate continuous training (MCT) protocol on postprandial lipemia, vascular function and arterial stiffness in inactive adults after high-fat meal (HFM) ingestion.A randomized clinical trial was conducted in 20 healthy, inactive adults (31.6 ± 7.1 years). Participants followed the two exercise protocols for 12 weeks. To induce a state of postprandial lipemia (PPL), all subjects received a HFM. Endothelial function was measured using flow-mediated vasodilation (FMD), normalized brachial artery FMD (nFMD), aortic pulse wave velocity (PWV) and augmentation index (AIx). Plasma total cholesterol, high-density lipoprotein cholesterol (HDL-c), triglycerides and glucose were also measured.The effects of a HFM were evaluated in a fasted state and 60, 120, 180, and 240 min postprandially. A significant decrease in serum glucose between 0 min (fasted state) and 120 min postprandially was found in the HIT group (P = 0.035). Likewise, FMD (%) was significantly different between the fasted state and 60 min after a HFM in the HIT group (P = 0.042). The total cholesterol response expressed as area under curve (AUC) was lower following HIT than following MCT, but no significant differences were observed (8%, P > 0.05). Similarly, triglycerides AUC was also lower after HIT compared with MCT, which trended towards significance (24%, P = 0.076). The AUC for the glucose response was significantly lower following HIT than MCT (10%, P = 0.008). FMD and nFMD AUC were significantly higher following HIT than following MCT (46.9%, P = 0.021 and 67.3%, P = 0.009, respectively). PWV AUC did not differ following between the two exercise groups (2.3%, P > 0.05).Supervised exercise training mitigates endothelial dysfunction and glucose response induced by PPL. Exercise intensity plays an important role in these protective effects, and medium-term HIT may be more effective than MCT in reducing postprandial glucose levels and attenuating vascular impairment.ClinicalTrials.gov ID: NCT02738385 Date of registration: April 14, 2016."
1,"TITLE: Sequential non-invasive following short-term invasive mechanical ventilation in the treatment of tuberculosis with respiratory failure: a randomized controlled study.ABSTRACT: Invasive and non-invasive mechanical ventilation (MV) have been combined as sequential MV in the treatment of respiratory failure. However, the effectiveness remains unclear. Here, we performed a randomized controlled study to assess the efficacy and safety of sequential MV in the treatment of tuberculosis with respiratory failure.Forty-four tuberculosis patients diagnosed with respiratory failure were randomly divided into sequential MV group (n = 24) and conventional MV group (n = 20). Initially, the patients in both groups received invasive positive pressure ventilation. When the patients' conditions were relieved, the ventilation modality in sequential MV group was switched to oronasal face mask continuous positive airway pressure until weaning.After treatment, the patients in sequential MV group had similar respiratory rate, heart rate, oxygenation index, alveolo-arterial oxygen partial pressure difference (A-aDO), blood pH, PaCO to those in conventional MV group (all P value > 0.05). There was no significant difference in ventilation time and ICU stay between the two groups (P > 0.05), but sequential MV group significantly reduced the time of invasive ventilation (mean difference (MD): - 36.2 h, 95% confidence interval (CI) - 53.6, - 18.8 h, P < 0.001). Sequential MV group also reduced the incidence of ventilator-associated pneumonia (VAP; relative risk (RR): 0.44, 95% CI 0.24, 0.83, P = 0.006) and atelectasis (RR:0.49, 95% CI 0.24,1.00, P = 0.040).Sequential MV was effective in treating tuberculosis with respiratory failure. It showed advantages in reducing invasive ventilation time and ventilator-associated adverse events.Chinese Clinical Trial Registry ChiCTR2000032311, April 21st, 2020."
1,"TITLE: The effect of stoma size on weight loss after laparoscopic gastric bypass surgery: results of a blinded randomized controlled trial.ABSTRACT: To determine the effect of different stoma sizes on the percent excess weight loss (%EWL) following laparoscopic Roux-en-Y gastric bypass surgery (LRYGBP).Blinded randomized prospective controlled study in two American Society for Bariatric Surgeons-designated Centers of Excellence hospitals. Two hundred gastric bypass patients between January 2005 and September 2005 were prospectively randomized into two groups of 100 patients each in the operating room, after the induction of anesthesia. Patients underwent LRYGBP with different stapler sizes of 21 and 25 mm for gastrojejunal (GJ) anastomosis from January 2005 to September 2005. Postoperative %EWL following LRYGBP in both patient groups were calculated using a multivariable linear mixed-effects model with an unstructured covariance matrix and a logistic regression was used to measure clinical comorbidities.Applying multivariable mixed models and logistical regression, circular stapler size of 21 and 25 mm, which predicted the need for dilations (odds ratio = 0.489), did not predict weight loss. The only predictors of weight loss were male gender and higher initial weight (p < 0.001). Follow-up at 2 years in the 21- and 25-mm groups was 68% and 66%, respectively. Both groups had > 80% EWL at 2 years.The level of restriction or the presence of stenosis achieved by different circular stapler sizes does not have a significant causative role in weight loss."
1,"TITLE: Management of Postoperative Pain after Elective Craniotomy: A Prospective Randomized Controlled Trial of a Neurosurgical Enhanced Recovery after Surgery (ERAS) Program.ABSTRACT: To prospectively evaluate the efficacy of a neurosurgical enhanced recovery after surgery (ERAS) protocol on the management of postoperative pain after elective craniotomies.  This randomized controlled trial was conducted in the neurosurgical center of Tangdu Hospital (Fourth Military Medical University, Xi'an, China). A total of 129 patients undergoing craniotomies between October 2016 and July 2017 were enrolled in a randomized clinical trial comparing an ERAS protocol to a conventional postoperative care regimen. The primary outcome was the postoperative pain score assessed by a verbal numerical rating scale (NRS).  Patients in the ERAS group had a significant reduction in their postoperative pain scores on POD 1 compared to patients in the control group (p < 0.05). More patients (n = 44, 68.8%) in the ERAS group experienced mild pain (NRS: 1 to 3) on POD1 compared with patients (n = 23, 35.4%) in the control group (p < 0.05). A further reduction in pain scores was also observed on POD 2 and maintained on POD 3 in the ERAS group compared with that in the control group. In addition, the median postoperative length of hospital stay was significantly decreased with the incorporation of the ERAS protocol compared to controls (ERAS: 4 days, control: 7 days, P<0.001).  The implementation of a neurosurgical ERAS protocol for elective craniotomy patients has significant benefits in alleviating postoperative pain and enhancing recovery leading to early discharge after surgery compared to conventional care. Further evaluation of this protocol in larger, multi-center studies is warranted."
0,"TITLE: An Open, Randomized, Single-Center, Crossover Pharmacokinetic Study of Meropenem after Intraperitoneal and Intravenous Administration in Patients Receiving Automated Peritoneal Dialysis.ABSTRACT: The objective of this study was to determine the pharmacokinetic profile of meropenem in automated peritoneal dialysis (APD) patients. In 6 patients without peritonitis, a single dose of 0.5 g of meropenem was applied intraperitoneally (i.p.) or intravenously (i.v.) and concentrations in serum and dialysate were measured at specified intervals over 24 h with high-performance liquid chromatography-mass spectrometry. The mean maximum concentrations of meropenem in serum (Cmax) were 27.2 mg/liter (standard deviation [SD], ±6.9) and 10.1 mg/liter (SD, ±2.5) and in dialysate were 3.6 mg/liter (SD, ±2.3) and 185.8 mg/liter (SD, ±18.7) after i.v. and i.p. administrations, respectively. The mean areas under the curve from 0 to 24 (AUC0-24) of meropenem in serum were 173.5 mg · h/liter (SD, ±29.7) and 141.4 mg · h/liter (SD, ±37.5) (P = 0.046) and in dialysate were 42.6 mg · h/liter (SD, ±20.0) and 623.4 mg · h/liter (SD, ±84.1) (P = 0.028) after i.v. and i.p. administrations, respectively. The ratios for dialysate exposure over plasma exposure after i.v. and i.p. treatments were 0.2 (SD, ±0.1) and 4.6 (SD, ±0.9), respectively (P = 0.031). A mean target value of 40% T>MIC (time for which the free meropenem concentration exceeds the MIC) for clinically relevant pathogens with EUCAST susceptibility breakpoints of 2 mg/liter was reached in serum after i.p. and i.v. administrations and in dialysate after i.p. but not after i.v. administration. The present data indicate that low i.p. exposure limits the i.v. use of meropenem for PD-associated peritonitis. In contrast, i.p. administration not only results in superior concentrations in dialysate but also might be used to treat systemic infections."
0,"TITLE: Association between Shammah Use and Oral Leukoplakia-like Lesions among Adult Males in Dawan Valley, Yemen.ABSTRACT: Shammah is a traditional form of snuff dipping tobacco (a smokeless tobacco form) that is commonly used in Yemen. Oral mucosal changes due to the use of shammah can usually be observed in the mucosal surfaces that the product touches. The aim of this study was to determine the association between shammah use and oral leukoplakia-like lesions. Other associated factors were also determined.A cross sectional study was conducted on 346 randomly selected adult males. Multi-stage random sampling was used to select the study location. After completing the structured questionnaire interviews, all the participants underwent clinical exanimation for screening of oral leukoplakia-like lesions Clinical features of oral leukoplakia-like lesion were characterized based on the grades of Axell et al (1976). Univariable logistic regression and multivariable logistic regression were used to assess the potential associated factors.Out of 346 male participants aged 18 years and older, 68 (19.7%) reported being current shammah users. The multivariable analysis revealed that age, non-formal or primary level of education, former shammah user, current shammah user, and frequency of shammah use per day were statistically associated with the presence of oral leukoplakia-like lesions [Adjusted odds ratio (AOR) = 1.03; 95% confidence interval (CI) : 1.01, 1.06; P= 0.006], (AOR= 8.65; 95% CI: 2.81, 26.57; P= 0.001), (AOR= 3.65; 95% CI: 1.40, 9.50; P= 0.008), (AOR= 12.99; 95% CI: 6.34, 26.59; P= 0.001), and (AOR= 1.17; 95% CI: 1.02, 1.36; P= 0.026), respectively.The results revealed oral leukoplakia-like lesions to be significantly associated with shammah use. Therefore, it is important to develop comprehensive shammah prevention programs in Yemen."
1,"TITLE: The benefit of adding a physiotherapy or occupational therapy intervention programme to a standardized group-based interdisciplinary rehabilitation programme for patients with chronic widespread pain: a randomized active-controlled non-blinded trial.ABSTRACT: To evaluate the benefit of adding occupational therapy or physiotherapy interventions to a standard rehabilitation programme targeted for chronic widespread pain.Randomized active-controlled non-blinded trial.Women with chronic widespread pain recruited in a tertiary outpatient clinic.Participants were randomized to a two-week, group-based standard rehabilitation programme followed by 16 weeks of group-based occupational therapy (Group B,  = 43) or 16 weeks of group-based physiotherapy (Group B,  = 42). Group A only received the two-week rehabilitation programme acting as comparator ( = 96).Primary outcomes were the Assessment of Motor and Process Skills and Short Form-36 (SF36) Mental Component Summary score.Mean changes in motor and process ability measures were clinically and statistically insignificant and without differences across the three groups assessed 88 weeks from baseline. Motor ability measures: -0.006 (95% confidence interval (CI): -0.244 to 0.233) in Group B; -0.045 (95% CI: -0.291 to 0.202) in Group B; and -0.017 (95% CI: -0.248 to 0.213) in Group A,  = 0.903. Process ability measures: 0.087 (95% CI: -0.056 to 0.231) in Group B; 0.075 (95% CI: -0.075 to 0.226) in Group B; and 0.072 (95% CI: -0.067 to 0.211) in Group A,  = 0.924. Mean changes in patient-reported outcomes were likewise small; clinically and statistically insignificant; and independent of group allocation, except for the SF36 mental component summary score in the B group: 8.58 (95% CI: 1.75 to 15.41).Participants were on average stable in observation-based measures of functional ability and patient-reported outcomes, except in overall mental well-being, favouring the enhanced intervention. Efficacy of additional interventions on functional ability remains uncertain."
1,"TITLE: A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy: Results of the Korean South West Oncology Group (KSWOG) Study.ABSTRACT: Data on the efficacy of olanzapine in patients receiving moderately emetogenic chemotherapy (MEC) are limited. This study aimed to evaluate and compare the efficacy of olanzapine versus placebo in controlling nausea and vomiting in patients receiving MEC.We conducted a randomized, double-blind, placebo-controlled study to determine whether olanzapine can reduce the frequency of chemotherapy-induced nausea and vomiting (CINV) and improve the quality of life (QOL) in patients receiving palonosetron and dexamethasone as prophylaxis for MEC-induced nausea and vomiting. The primary end point was complete response for the acute phase (0-24 hours after chemotherapy). The secondary end points were complete response for the delayed (24-120 hours) and overall phase (0-120 hours), proportion of significant nausea (visual analogue scale ≥ 25 mm), use ofrescue medications, and effect on QOL.Fifty-six patients were randomized to the olanzapine (n=29) and placebo (n=27) groups. Complete response rates were not significantly different between the olanzapine and placebo groups in the acute (96.5% vs. 88.0%, p=0.326), delayed (69.0% vs. 48.0%, p=0.118), and overall phases (69.0% vs. 48.0%, p=0.118). However, the percentage of patients with significant nausea (17.2% vs. 44.0%, p=0.032) and the use of rescue medications (0.03±0.19 vs. 1.88±2.88, p=0.002) were lower in the olanzapine group than in the placebo. Furthermore, the olanzapine group demonstrated better QOL (p=0.015).Olanzapine combined with palonosetron and dexamethasone significantly improved QOL and vomiting control among previously untreated patients receiving MEC, although the efficacy was limited to the reduction of the frequency of CINV."
1,"TITLE: Dutasteride is associated with reduced risk of transrectal prostate biopsy-associated urinary tract infection and related hospitalizations.ABSTRACT: To evaluate whether the use of dutasteride is associated with a lower risk of transrectal prostate biopsy-associated urinary tract infection (TPBA-UTI) among men in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study.Retrospective analysis of 6045 men undergoing 2-year repeat prostate biopsy in REDUCE. Participants were randomized to receive dutasteride 0.5 mg or placebo daily. TPBA-UTI was defined as the presence of urinary symptoms and the prescription of antibiotics by the treating physician within 30 days after biopsy. Severe TPBA-UTI was defined as TPBA-UTI requiring hospitalization. Comparison of TPBA-UTI between treatment arms was done using Chi-square test and logistic regression adjusting for participant characteristics.Of the subjects included in the study, 3067 (50.7%) were randomized to the placebo arm and 2978 (49.3%) to the dutasteride arm. A total 51 (0.8%) men had TPBA-UTI, including 38 (1.2%) in the placebo arm and 13 (0.4%) in the dutasteride arm (univariable relative risk [RR] = 0.35, P = 0.001; multivariable odds ratio [OR] = 0.34, P = 0.003). The number needed to treat (NNT) to prevent one TPBA-UTI was 125 subjects. Of these, 14 (28%) had severe TPBA-UTI, including 12 (0.4%) in the placebo arm and only 2 (0.07%) in the dutasteride arm (univariable RR = 0.17, P = 0.021; multivariable OR = 0.17, P = 0.031). The NNT to prevent one severe TPBA-UTI was 309 subjects.Among men undergoing a 2-year repeat prostate biopsy, the use of dutasteride for 2 years was associated with a reduced the risk of overall and severe TBPA-UTI. CLINICALTRIALS.NCT00056407."
1,"TITLE: The effect of foot reflexology massage on delirium and sleep quality following cardiac surgery: A randomized clinical trial.ABSTRACT: Delirium is the most common neurologic disorder after cardiac surgery and affects both short and long-term outcomes. This study was conducted to evaluate the effect of foot reflexology massage on the incidence of delirium and sleep quality in patients undergoing cardiac surgery.In this randomized clinical trial, 60 patients who were candidates for CABG surgery were randomly assigned into two equal groups (n = 30); intervention and control groups. In the intervention group, foot reflexology massage was done on each foot for 15 min, for two consecutive days. Delirium observation screening scale, the Richard Campbell sleep questionnaire (RSCQ), and pain intensity using VAS were compared.in the second postoperative day, delirium was observed in 8 (26.7 %) and 7 (23.3 %) of patients in the intervention and control groups, respectively (p > 0.05). The measured odds ratio for the effect of massage on delirium is 0.83 (95 %CI 0.71-2.69, p = 0.76). The difference in RSCQ scores was not significant between groups of intervention and control (68.32 ± 10.41 VS. 62.80 ± 11.86, P = 0.06). The pain intensity was lower in the intervention group (P < 0.001).Foot reflexology was not effective in reducing delirium and improving the sleep quality, but the pain intensity was decreased. It seems that the precise pathology and predicting model of delirium should be identified, and appropriate interventions should be planned accordingly."
1,"TITLE: Using a cane for one month does not improve walking or social participation in chronic stroke: An attention-controlled randomized trial.ABSTRACT: To examine the effects of the provision of a cane, delivered to ambulatory people with chronic stroke, for improving walking and social participation.Two-arm, randomized trial.Community-based.Ambulatory individuals with chronic stroke.The experimental intervention was the provision of a single-point cane during one month. The control group received a placebo intervention.Walking speed, step length, cadence, walking capacity, and walking confidence were measured without the cane to examine its rehabilitative effect. Walking speed was also measured with the cane for inclusiveness, and social participation was measured for examining carry over effects. Outcomes were measured at baseline, and after one and two months.Fifty individuals were included. In the experimental group, mean age was 69 years (SD 14), and walking speed was 0.58 m/s (SD 0.17). In the control group, mean age was 68 years (SD 13), and walking speed was 0.63 m/s (SD 0.15). When walking  the cane, after one and after two months, there were no between-group differences in any measures. When walking  the cane, after one month, the experimental group walked 0.14 m/s (95% CI 0.05-0.23) faster than the control group and after two months, they were still walking 0.18 m/s (95% CI 0.06-0.30) faster.Use of a cane improved walking speed, only when participants walked with the cane. Use of cane for one month did not improve walking outcomes, when walking without the cane. People with stroke would need to continue to use the cane to maintain any benefits in walking speed."
1,"TITLE: Vaginal Progesterone Supplementation in the Management of Preterm Labor: A Randomized Controlled Trial.ABSTRACT: The primary objective in this study was to evaluate the effects of vaginal progesterone supplementation for the prolongation of the latency period in preterm labor. The secondary objectives were to evaluate gestational age at delivery, rates of preterm birth less than 34 and 37 weeks, obstetric outcomes, maternal compliance with medication use, and side effects.A randomized controlled, unblinded trial was performed. Ninety women with preterm labor occurring at 24 to 34 weeks were either randomized to a vaginal progesterone group (44 women) receiving tocolytic and antenatal corticosteroids treatment combined with vaginal micronized progesterone (400 mg everyday) or to the no-progesterone group (46 women) receiving tocolytic and antenatal corticosteroids treatment only.Latency periods were more prolonged in the vaginal progesterone group than in the no-progesterone group (32.8 ± 18.7 vs. 25.8 ± 22.7 days, p = 0.045). Gestational age at delivery in the vaginal progesterone group was also higher than in the no-progesterone group (37 vs. 35 weeks, p = 0.027). There were significant reduction rates of preterm birth less than 34 weeks (13.6% vs. 39.1%, p = 0.012), low birth weight (29.5% vs. 50%, p = 0.048), neonatal respiratory distress syndrome (13.6% vs. 37%, p = 0.021), and neonatal intensive care unit admission (6.8% vs. 28.3%, p = 0.017).Combined treatment with vaginal progesterone 400 mg could prolong the latency period in preterm labor when compared with no progesterone."
0,"TITLE: Vancomycin-associated nephrotoxicity in adult medicine patients: incidence, outcomes, and risk factors.ABSTRACT: The prevalence of vancomycin-associated nephrotoxicity (VAN) is reported to vary from 1.0-42.6%, with most data from critically ill patients. Evaluation of VAN among internal medicine patients is lacking. Our objectives were to determine the incidence, time-course, outcomes, and risk factors of VAN in adult internal medicine patients.Retrospective cohort.Tertiary care academic medical center.A total of 125 adult internal medicine patients receiving vancomycin treatment with mean baseline creatinine clearance of 84.6 ± 27.6 ml/min.Vancomycin treatment for a minimum of 72 hours.Nephrotoxicity, defined as an increase in serum creatinine of 0.5 mg/dl or 50% above baseline (whichever was larger), occurred in 17 (13.6%) of 125 patients. No patients with VAN progressed to Loss or End stage as defined by the RIFLE criteria. The incidence rate of VAN was 0.02 cases/day of vancomycin treatment. Nephrotoxicity developed at a median of 4.5 days (interquartile range [IQR] 2.2-4.9) peaked at 5.7 days (IQR: 3.8-9.6), and resolved in 70.6% of the cases within 16.5 days (IQR: 6.0-17.8) after onset. On multivariable logistic regression analysis, after controlling for hypotensive episodes, Charlson Comorbidity Index, and baseline creatinine clearance, concomitant use of piperacillin-tazobactam was associated with increased VAN (adjusted odds ratio 5.36, 95% confidence interval 1.41-20.5).Vancomycin-associated nephrotoxicity is prevalent among internal medicine patients, with 5.36-fold higher odds if piperacillin-tazobactam is concomitantly administered."
1,"TITLE: Ropivacaine Intramuscular Paracervical Injections for Pediatric Headache: A Randomized Placebo-Controlled Trial.ABSTRACT: We seek to determine whether ropivacaine cervical paraspinal injections compared with normal saline solution injections provide headache relief to pediatric patients that is sufficient for emergency department (ED) discharge.We enrolled children aged 7 to 17 years in a double-blinded, randomized, controlled trial of patients presenting to a pediatric ED with headache. Subjects were randomized into 1 of 3 groups: bilateral cervical paraspinal injections of either (1) 0.5% ropivacaine or (2) normal saline solution, or (3) a natural history group (not blinded) receiving no headache therapy for the first 30 minutes. Pain scores were assessed at enrollment and at 10-, 20-, and 30-minute intervals after the administration of the injections. After the intervention period of 30 minutes, additional therapy was provided as needed. Primary outcome was the proportion of children discharged with adequate pain relief at 30 minutes without additional therapy. Secondary outcomes included reduction in pain scores, reoccurrence of headache, and re-presentation to health care with headache.One hundred fifty-three children were enrolled. The proportion discharged with adequate pain relief 30 minutes after the injections did not differ between the 2 intervention groups (32% in the ropivacaine group versus 28% in the saline solution group; effect difference 4%; 95% confidence interval -14% to 21%). In contrast, only 4% percent of patients in the natural history group were discharged without additional therapy after the 30-minute assessment. Reduction of pain scores (2.0 and 2.2 in ropivacaine versus saline solution), headache reoccurrence, and return to care was similar between the 2 treatment groups.Cervical paraspinal injections of either ropivacaine or saline solution were effective for approximately one third of patients."
1,"TITLE: Effect of magnesium supplementation on depression status in depressed patients with magnesium deficiency: A randomized, double-blind, placebo-controlled trial.ABSTRACT: The aim of this study was to determine the effect of magnesium supplementation on the depression status of depressed patients suffering from magnesium deficiency.Sixty depressed people suffering from hypomagnesemia participated in this trial. The individuals were randomly categorized into two groups of 30 members; one receiving two 250-mg tablets of magnesium oxide (MG) daily and the other receiving placebo (PG) for 8 wk. The Beck Depression Inventory-II was conducted and the concentration of serum magnesium was measured.At the end of intervention, 88.5% of the MG and 48.1% of the PG (P = 0.002) had a normal level of magnesium. The mean changes of serum magnesium were significantly different across the two groups. After the intervention, the mean Beck score significantly declined. However, in the MG, this reduction was more significant than in the PG (P = 0.02), so that the mean changes in this group experienced 15.65 ± 8.9 reduction, but in the PG, it declined by 10.40 ± 7.9.Daily consumption of 500 mg magnesium oxide tablets for ≥8 wk by depressed patients suffering from magnesium deficiency leads to improvements in depression status and magnesium levels. Therefore, assessment of the magnesium serum and resolving this deficiency positively influence the treatment of depressed patients."
1,"TITLE: The sex of the foetus affects maternal blood glucose concentrations in overweight and obese pregnant women.ABSTRACT: There is increasing evidence that the sex of the foetus may alter the maternal metabolic milieu during pregnancy. Following a randomized controlled trial of exercise in overweight and obese pregnant women, we assessed whether the sex of the foetus was associated with changes in maternal metabolism. Data were analysed on 74 randomized participants who completed the trial, including 38 mothers carrying males and 36 mothers carrying females. At 19 weeks of gestation, mothers carrying boys had higher blood glucose concentrations than those carrying girls (5.4 vs 4.9 mmol/l; p = .046). At 36 weeks of gestation, differences were more marked, with blood glucose concentrations 15% higher in mothers carrying females (5.7 vs 5.0 mmol/l; p = .004). In addition, mothers carrying girls had higher concentrations of hs-CRP across pregnancy (5.0 vs 3.6 mg/l; p = .029). Our findings provide further evidence that the sex of the foetus appears to influence maternal metabolism."
1,"TITLE: Letrozole and human menopausal gonadotropin for ovulation induction in clomiphene resistance polycystic ovary syndrome patients: A randomized controlled study.ABSTRACT: To compare the effects of letrozole and human menopausal gonadotropin (HMG) in the treatment of patients with polycystic ovary syndrome (PCOS) resistant to clomiphene citrate (CC).A total of 96 clomiphene resistance polycystic ovary syndrome patients infertility were randomly divided into an LE group, and HMG group (n = 48). LE group orally received letrozole at 5.0 mg/d on the 3rd-5th days of menstrual cycle for 5 consecutive days, and 75 U/d HMG was given through intramuscular injection for 5 days starting from the third day of menstrual cycle in HMG group. Number of growing and mature follicles, serum E2 (pg/mL), serum P (ng/mL), endometrial thickness, occurrence of pregnancy and miscarriage were observed.There was no significant difference in the number of ovulation cycles between the 2 groups (53.6% vs 64.7%, P > .05). The number of mature follicular cycles in the HMG group was higher than that of the letrozole group (P < .01). There were no significant differences in the clinical pregnancy rate (22.9% vs 27.1%, P > .05) and abortion rate (6.2% vs 10.4%, P > .05). There was no significant difference in the endometrial thickness between the 2 groups on the day of HCG injection [(9.1 ± 0.2) mm vs (10.7 ± 1.6) mm, P > .05]; the serum estradiol (E2) was lower in the letrozole group. The incidence of ovarian cysts was lower than that of HMG group (P < .05). There was2 ovarian hyperstimulation syndrome in the letrozole group; the incidence of ovarian hyperstimulation syndrome in the HMG group was 12.5%.Letrozole-induced ovulation can obtain ovulation rate and pregnancy rate similar to gonadotropin, but reduce the risk associated with treatment. It can be used as an effective ovulation option for patients with polycystic ovary syndrome who are resistant to clomiphene."
1,"TITLE: Eplerenone might affect atrial fibrosis in patients with hypertension.ABSTRACT: Eplerenone is reported to reduce the development of atrial fibrillation (AF). The aim of this study was to clarify the mechanism of eplerenone for AF prevention from the viewpoint of P wave morphology, which is reported to correlate with atrial fibrosis.Thirty-five patients with hypertension, who were randomized to receive eplerenone (n = 16) or amlodipine (n = 19) for 1 year, were evaluated. P wave signal-averaged electrocardiography was recorded at baseline and 1 year after entry, and P wave duration (Ad) and P wave dispersion (P-disp) were obtained. Serum levels of intact procollagen type I N-terminal propeptide (PINP) and N-terminal procollagen-III peptide (PIIIP) were also measured.There were no significant differences in baseline clinical characteristics including Ad, P-disp, and the decrease in blood pressure at 1-year follow-up between the two groups. Ad and P-disp (mean ± standard deviation) significantly increased in patients on amlodipine after 1 year (140 ± 21 ms to 139 ± 19 ms vs 132 ± 10 ms to 136 ± 12 ms, P < 0.01 and 14 ± 7 ms to 9 ± 4 ms vs 12 ± 5 to 16 ± 8, P < 0.01, respectively). PINP was significantly more decreased in patients with eplerenone than amlodipine (56.6 ± 30.4 μg/mL to 46.6 ± 19.4 μg/mL vs 41.5 ± 16.2 μg/L to 48.7 ± 21.3 μg/L, P < 0.01). Percent changes of Ad, P-disp, PINP, and PIIIP were significantly smaller in patients with eplerenone than amlodipine (0.0 ± 4.7% vs 3.2 ± 4.4%, P < 0.05, - 28.6 ± 31.0% vs 46.3 ± 73.0%, P < 0.01, - 5.6 ± 38.1% vs 22.7 ± 42.7%, P < 0.05, and - 9.2 ± 25.1% vs 7.4 ± 19.0%, P < 0.05, respectively).Eplerenone reduced the increase of Ad and P-disp with a decrease of PINP and PIIIP, which might translate into reduction of atrial fibrosis. This study showed that eplerenone may be useful as upstream therapy for AF in patients with hypertension."
1,"TITLE: ""She Gave Me the Confidence to Open Up"": Bridging Communication by Promotoras in a Childhood Obesity Intervention for Latino Families.ABSTRACT: Childhood obesity is a public health threat that disproportionally affects Latino youth in the United States. Active and Healthy Families (AHF) is a culturally tailored, family-based program for addressing obesity disparities in a predominantly immigrant Latino population. AHF was the first primary care, culturally tailored intervention for Latino children to significantly reduce BMI in a randomized controlled trial. The 10-week AHF intervention reduced BMI (kg/m) among overweight or obese children by 0.5, compared with an increase of 0.3 in the control group, yielding a -0.8 difference ( p < .01). A unique aspect of the program is its provider team: a physician, dietitian, and promotora. Because early feedback from families highlighted the importance of promotoras specifically, we sought to understand the unique mechanisms of promotora effectiveness in AHF. We conducted in-depth, semistructured interviews with the AHF providers ( n = 5) and parent participants ( n = 23) by phone between November 2012 and May 2013. In a grounded theory analysis, three main categories encompassing five themes emerged: (a) bridging communication by promotoras; (b) promotoras' personal qualities, including themes of kindness and caring and shared experiences with patients; and (c) impactful task performance, including themes of motivation, positive environment, and self-efficacy. Together, the themes serve as the basis of a conceptual model illustrating the process through which promotoras may enhance the impact of team-based obesity programs for the Latino community. Because this study identifies the specific ways through which promotoras can bridge cultural, linguistic, and other divides, it may inform development and dissemination of evidence-based approaches for obesity prevention in the Latino community."
1,"TITLE: Cecal intubation time between cap-assisted water exchange and water exchange colonoscopy: a randomized-controlled trial.ABSTRACT: The water exchange (WE) method can decrease the discomfort of the patients undergoing colonoscopy. It also provides salvage cleansing and improves adenoma detection, but a longer intubation time is required. Cap-assisted colonoscopy leads to a significant reduction in cecal intubation time compared with traditional colonoscopy with air insufflation. The aim of this study was to investigate whether combined cap-assisted colonoscopy and water exchange (CWE) could decrease the cecal intubation time compared with WE.A total of 120 patients undergoing fully sedated colonoscopy at a regional hospital in southern Taiwan were randomized to colonoscopy with either CWE (n=59) or WE (n=61). The primary endpoint was cecal intubation time.The mean cecal intubation time was significantly shorter in CWE (12.0 min) compared with WE (14.8 min) (P=0.004). The volume of infused water during insertion was lower in CWE (840 ml) compared with WE (1044 ml) (P=0.003). The adenoma detection rate was 50.8 and 47.5% for CWE and WE, respectively (P=0.472). The Boston Bowel Preparation Scale scores were comparable in the two groups. Results from the multiple linear regression analysis indicated that WE with a cap, a higher degree of endoscopist's experience, a higher Boston Bowel Preparation Scale score, and a lower volume of water infused during insertion, without abdominal compression, without change of position, and without chronic laxative use, were significantly associated with a shorter cecal intubation time.In comparison with WE, CWE could shorten the cecal intubation time and required lower volume of water infusion during insertion without compromising the cleansing effect of WE."
1,"TITLE: Methylprednisolone for prevention of ovarian hyperstimulation syndrome in patients with polycystic ovarian syndrome undergoing in-vitro fertilisation: a randomised controlled trial.ABSTRACT: This study aimed to evaluate the effect of methylprednisolone on prevention of ovarian hyperstimulation syndrome (OHSS) in polycystic ovarian syndrome (PCOS) patients undergoing in-vitro fertilisation (IVF). This randomised controlled trial was carried out between November 2009 and December 2013. A total of 219 eligible patients were randomly allocated for treatment (n = 108) or control groups (n = 111). The treatment group received oral methylprednisolone starting from the first day of stimulation. These patients also received an intravenous dose of methylprednisolone on the days of egg collection and embryo transfer. The control group received no glucocorticoid treatment to prevent OHSS. Nineteen percent of patients (18/93) who received methylprednisolone developed OHSS compared with 16.5% (15/91) in the control group and no significant difference was found (p = .61). There were no significant differences between treatment and control groups in the rates of implantation (10% versus 11%, p = .77) and clinical pregnancy (23.2% versus 17.7%, p = .46). Methylprednisolone did not reduce the incidence and severity of OHSS in PCOS patients undergoing IVF and no improvement in clinical outcomes was observed. Impact statement No significant differences were found in OHSS incidence and clinical outcomes between women who received methylprednisolone and control group. There seems to be no benefit for the routine use of glucocorticoids in IVF/ICSI treatments."
1,"TITLE: Effect of Tranexamic Acid on Prevention of Hemorrhagic Mass Growth in Patients with Traumatic Brain Injury.ABSTRACT: Intracranial hemorrhage is a common complication of traumatic brain injury (TBI). The purpose of this study is evaluation of the effect of tranexamic acid (TXA) on hemorrhagic mass growth in TBI patients.In this randomized, double-blind clinical trial, 149 patients with TBI and any kind of blood on their computed tomography scan enrolled in the study and were randomly allocated to receive TXA or placebo. After 24 hours, computed tomography scan was repeated for assessing the changes in hemorrhage, new bleeding, and mass effects of blood on brain tissue. The primary outcome was growth of the hemorrhagic lesion. Data were analyzed by SPSS software using Fisher exact, chi-square, and Mann-Whitney U tests, as well as linear and logistic regression models.The incidence of hemorrhagic lesion growth was 20.5% in the TXA group and 22.7% in the placebo group. The difference was not significant (P = 0.87, RR = 0.89). The mean (standard deviation) of hemorrhagic lesion growth was 9.4 (15.3) in the TXA group and 10.2 (10.1) in the placebo group without significant difference (P = 0.27). The frequency of deaths (2.7% vs. 4%), adverse outcome at discharge (10.8% vs. 17.3%), and 3 months later (6.8% vs. 14.7%) in the TXA group were lower than the placebo, but the difference was not statistically significant. No side effect was observed with the administration of TXA.Administration of a short dose of TXA does not lead to significant prevention of growth of posttraumatic hemorrhagic lesion or improvement of clinical outcomes."
1,"TITLE: A Randomized Trial of Incentives for Smoking Treatment in Medicaid Members.ABSTRACT: Low-income populations are especially likely to smoke and have difficulty quitting. This study evaluated a monetary incentive intended to increase smoking treatment engagement and abstinence among Medicaid recipients who smoke.Two-group randomized clinical trial of Incentive (n=948) and Control interventions (n=952) for smoking.Medicaid recipients recruited from primary care patients (n=920) and callers to the Wisconsin Tobacco Quit Line (n=980).Participants were offered five quitline cessation calls and were encouraged to obtain cessation medication (covered by Medicaid). All participants received payment for completing a baseline assessment and a 6-month smoking test. Only Incentive condition participants received compensation for taking counseling calls ($30 per call) and for biochemically verified abstinence at the 6-month visit ($40).Seven-day point-prevalence smoking abstinence 6-months post study entry and cost/quit.Incentive condition participants had significantly higher biochemically determined 7-day point-prevalence smoking abstinence rates 6 months after study induction than did Controls (21.6% vs 13.8%, respectively, p<0.0001). A positive treatment effect of incentives was present across other abstinence indices, but the size of effects and levels of abstinence varied considerably across indices. Incentive condition participants were also significantly more likely than non-incentivized Control participants to accept Wisconsin Tobacco Quit Line treatment calls and their acceptance of calls mediated their attainment of higher abstinence rates at 6-month follow-up. The cost/quit/participant averaged $4,268.26 for the Control participants and $3,601.37 for the Incentive participants.This study shows that fairly moderate levels of incentive payments for treatment engagement and abstinence (a total possible payment of $190) increased very low-income smokers' engagement and success in smoking cessation treatment.This study is registered at www.clinicaltrials.gov: NCT02713594."
0,"TITLE: Impact of continuation of metformin prior to elective coronary angiography on acute contrast nephropathy in patients with normal or mildly impaired renal functions.ABSTRACT: Discontinuation of metformin treatment in patients scheduled for elective coronary angiography (CAG) is controversial because of post-procedural risks including acute contrast-induced nephropathy (CIN) and lactic acidosis (LA). This study aims to discuss the safety of continuing metformin treatment in patients undergoing elective CAG with normal or mildly impaired renal functions.Our study was designed as a single-centered, randomized, and observational study including 268 patients undergoing elective CAG with an estimated glomerular filtration rate of >60 mL/min/1.73 m2. Of these patients, 134 continued metformin treatment during angiography, whereas 134 discontinued it 24 h before the procedure. CIN was defined as either a 25% relative increase in serum creatinine levels from the baseline or a 0.5 mg/dL increase in the absolute value that measured 48 h after CAG. Logistic regression analysis was performed to identify independent predictors of CIN and LA after CAG.Both groups were comparable in terms of demographics and laboratory values. CIN at 48 h was 8% (11/134) in the metformin continued group and 6% (8/134) in the metformin discontinued group (p=0.265). Patients in neither of the groups developed metformin-induced LA. Based on multiple regression analysis, the ejection fraction [p=0.029, OR: 0.760; 95% CI (0.590-0.970)] and contrast volume [p=0.016, OR: 0.022 95% CI (0.010-0.490)] were independent predictors of CIN.Patients scheduled for elective CAG with normal or mildly impaired renal functions and preserved left ventricular ejection fraction (>40%) may safely continue metformin treatment."
1,"TITLE: Adenosine stress perfusion cardiac magnetic resonance imaging in patients undergoing intracoronary bone marrow cell transfer after ST-elevation myocardial infarction: the BOOST-2 perfusion substudy.ABSTRACT: In the placebo-controlled, double-blind BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) 2 trial, intracoronary autologous bone marrow cell (BMC) transfer did not improve recovery of left ventricular ejection fraction (LVEF) at 6 months in patients with ST-elevation myocardial infarction (STEMI) and moderately reduced LVEF. Regional myocardial perfusion as determined by adenosine stress perfusion cardiac magnetic resonance imaging (S-CMR) may be more sensitive than global LVEF in detecting BMC treatment effects. Here, we sought to evaluate (i) the changes of myocardial perfusion in the infarct area over time (ii) the effects of BMC therapy on infarct perfusion, and (iii) the relation of infarct perfusion to LVEF recovery at 6 months.In 51 patients from BOOST-2 (placebo, n = 10; BMC, n = 41), S-CMR was performed 5.1 ± 2.9 days after PCI (before placebo/BMC treatment) and after 6 months. Infarct perfusion improved from baseline to 6 months in the overall patient cohort as reflected by the semi-quantitative parameters, perfusion defect-infarct size ratio (change from 0.54 ± 0.20 to 0.43 ± 0.22; P = 0.006) and perfusion defect-upslope ratio (0.54 ± 0.23 to 0.68 ± 0.22; P < 0.001), irrespective of randomised treatment. Perfusion defect-upslope ratio at baseline correlated with LVEF recovery (r = 0.62; P < 0.001) after 6 months, with a threshold of 0.54 providing the best sensitivity (79%) and specificity (74%) (area under the curve, 0.79; 95% confidence interval, 0.67-0.92).Infarct perfusion improves from baseline to 6 months and predicts LVEF recovery in STEMI patients undergoing early PCI. Intracoronary BMC therapy did not enhance infarct perfusion in the BOOST-2 trial."
1,"TITLE: Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study.ABSTRACT: Patients with distributive shock who require high dose vasopressors have a high mortality. Angiotensin II (ATII) may prove useful in patients who remain hypotensive despite catecholamine and vasopressin therapy. The appropriate dose of parenteral angiotensin II for shock is unknown.In total, 20 patients with distributive shock and a cardiovascular Sequential Organ Failure Assessment score of 4 were randomized to either ATII infusion (N =10) or placebo (N =10) plus standard of care. ATII was started at a dose of 20 ng/kg/min, and titrated for a goal of maintaining a mean arterial pressure (MAP) of 65 mmHg. The infusion (either ATII or placebo) was continued for 6 hours then titrated off. The primary endpoint was the effect of ATII on the standing dose of norepinephrine required to maintain a MAP of 65 mmHg.ATII resulted in marked reduction in norepinephrine dosing in all patients. The mean hour 1 norepinephrine dose for the placebo cohort was 27.6 ± 29.3 mcg/min versus 7.4 ± 12.4 mcg/min for the ATII cohort (P =0.06). The most common adverse event attributable to ATII was hypertension, which occurred in 20% of patients receiving ATII. 30-day mortality for the ATII cohort and the placebo cohort was similar (50% versus 60%, P =1.00).Angiotensin II is an effective rescue vasopressor agent in patients with distributive shock requiring multiple vasopressors. The initial dose range of ATII that appears to be appropriate for patients with distributive shock is 2 to 10 ng/kg/min.Clinicaltrials.gov NCT01393782. Registered 12 July 2011."
1,"TITLE: Effects of early treatment with zofenopril in patients with myocardial infarction and metabolic syndrome: the SMILE Study.ABSTRACT: To evaluate the clinical efficacy of the early administration of zofenopril in a group of patients with and without metabolic syndrome (MS+ and MS-) and anterior myocardial infarction enrolled in the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study.Patients were randomized double-blind to zofenopril (n=719) or placebo (n=699) for 6 weeks. The primary end point was the effect of treatment on the 6-week combined occurrence of death and severe congestive heart failure. The secondary end point was the 1-year mortality rate.Of the 1418 patients included in this post-hoc analysis, 686 (48.3%) had MS. After 6 weeks of treatment zofenopril significantly reduced the incidence of all-cause death and severe congestive failure (risk reduction: 69%, 95% CI: 7-78; 2p=0.002) in MS+ patients. This was the case for 1-year mortality, too (29%, 95% CI: 4-41; 2p=0.048). Zofenopril was effective also in MS- patients but the amount of relative risk reduction was less than in MS+ for both the primary (-11%; 2p=0.61) and secondary endpoint (-19%; 2p=0.025).Results of this post-hoc analysis of the SMILE Study demonstrate the striking benefit of early administration of zofenopril in MS+ patients with acute anterior myocardial infarction."
1,"TITLE: Do different culture intervals (2 × 24 hours) after thaw of cleavage stage embryos affect pregnancy rates? A randomized controlled trial.ABSTRACT: The aim of the study was to evaluate whether selecting embryos for transfer after prolonged culture after thaw (18-24 h) has better pregnancy rates than selecting embryos for transfer after short culture after thaw (2-5 h). We performed a double-blinded, randomized, controlled trial, evaluating 388 patients submitted to ART treatment who had embryos frozen on day-2 and subsequently transferred. All patients received the same endometrial priming with estradiol valerate followed by vaginal progesterone. Patients were randomized for Frozen embryo transfer 2-5 h after thaw (Group D2) or 18-24 h after thaw (Group D2/D3). The main Outcome Measure was ongoing pregnancy rate (OPR) at 20 weeks' gestation per embryo transfer. A total of 179 patients had embryos transferred 2-5 h after thaw and 209 patients had embryos transferred 18-24 h after thaw. The mean age in group D2 was 36 ± 4.4 and 36 ± 5.4 in group D2/D3. Ongoing pregnancy rate was 28% and 33.5% (p = 0.2) for groups D2 and D2/D3, respectively. These results suggest that increasing the culture time of embryos in one day to improve selection before transfer does not increase ongoing pregnancy rate. CLINICAL TRIAL REGISTRATION NUMBER: NCT03381001."
1,"TITLE: Metformin for prevention of cesarean delivery and large-for-gestational-age newborns in non-diabetic obese pregnant women: a randomized clinical trial.ABSTRACT: To evaluate the use of metformin for preventing cesarean deliveries and large-for-gestational-age (LGA) newborn (NB) outcomes in non-diabetic obese pregnant women.This is a randomized clinical trial with obese pregnant women, divided into 2 groups: metformin group and control group, with followed-up prenatal routine. The gestational age of participants was less than or equal to 20 weeks and were monitored throughout entire prenatal period. For outcomes of delivery and LGA newborns, absolute risk reduction (ARR) and the number needed to treat (NNT) were calculated with a 95% confidence interval (CI).357 pregnant women were evaluated. From the metformin group (n = 171), 68 (39.8%) subjects underwent cesarean delivery, and 117 (62.9%) subjects from the control group (n = 186) had intercurrence (p < 0.01). As for the mothers' general characteristics, there was significance for marital status (p < 0.01). Maternal-fetal results presented reduced preeclampsia (p < 0,01). Primary prophylactic results presented an ARR of 23.1 times (95% CI: 13.0-33.4) with NNT of 4 (95% CI: 3.0-7.7) and no significant values for LGA NB (p > 0.01). Secondary prophylactic outcomes presented decreased odds ratio for preeclampsia (OR = 0.17, 95% CI: 0.10-0.41).The use of metformin reduced cesarean section rates, resulted in a small number of patients to be treated, but it did not reduce LGA NB. Administering a lower dosage of metformin from the early stages to the end of treatment may yield significant results with fewer side effects. Arch Endocrinol Metab. 2020;64(3):290-7."
1,"TITLE: Effect of topical tranexamic acid in total hip arthroplasty patients who receive continuous aspirin for prevention of cardiovascular or cerebrovascular events: A prospective randomized study.ABSTRACT: Due to differences in pharmacological mechanism of action, the effect of tranexamic acid (TA) on aspirin-related bleeding remains unknown. We therefore conducted a prospective randomized study to elucidate: (1) the effect of topical TA administration on blood loss and transfusion rate in total hip arthroplasty (THA) patients receiving continuous aspirin for prevention of cardiovascular or cerebrovascular events; (2) 90-day complications of topical TA administration; (3) possible variables contributing to blood transfusion.Topical TA administration reduces blood loss and transfusion rate in THA patients receiving continuous aspirin.A total of 102 consecutive THA patients taking continuous aspirin were enrolled and randomized into two groups. In the topical TA (TTA) group (n=55), topical TA was administered at three points during THA; in the control group (n=47), the patients received saline solution as placebo. Based on drop in hemoglobin concentration, total estimated blood loss was calculated as the main assessment criterion. Secondary assessment criteria included transfusion rate and 90-day complications. Finally, a multivariate regression model was used to assess possible predictive factors for blood transfusion.(1) Significantly lower total blood loss was observed in the TTA group than in the control group (897±177ml vs. 1153±345ml, p<0.001). Furthermore, lower transfusion rate was observed in the TTA group than in the control group (10.9% vs. 34.0%, p=0.005). (2) No significant difference was observed between the two groups regarding 90-day complications. (3) We identified higher preoperative hemoglobin level (OR=0.675, p=0.002) and topical TA administration (OR=0.002, p=0.012) as negative predictive factors for blood transfusion.Topical application of TA was safe and beneficial in THA patients receiving continuous aspirin for prevention of cardiovascular or cerebrovascular events, to reduce blood loss and transfusion rate, without increasing the risk of 90-day complications."
1,"TITLE: Rivaroxaban Versus Warfarin in Patients with Mechanical Heart Valves: Open-Label, Proof-of-Concept trial-The RIWA study.ABSTRACT: To date, vitamin K antagonists are the only available oral anticoagulants in patients with mechanical heart valves. In this way, we developed a pilot trial with rivaroxaban.The RIWA study was a proof-of-concept, open-label, randomized clinical trial and was designed to assess the incidence of thromboembolic and bleeding events of the rivaroxaban-based strategy (15 mg twice daily) in comparison to dose-adjusted warfarin. Patients were randomly assigned in a 1:1 ratio and were followed prospectively for 90 days.A total of 72 patients were enrolled in the present study. Of these, 44 patients were randomized: 23 patients were allocated to the rivaroxaban group and 21 to the warfarin group. After 90 days of follow-up, the primary outcome occurred in one patient (4.3%) in the rivaroxaban group and three patients (14.3%) in the warfarin group (risk ratio [RR] 0.27; 95% confidence interval [CI] 0.02-2.85; P = 0.25). Minor bleeding (without discontinuation of medical therapy) occurred in six patients (26.1%) in the rivaroxaban group versus six patients (28.6%) in the warfarin group (RR 0.88; 95% CI 0.23-3.32; P = 0.85). One patient in the warfarin group died from myocardial infarction. No cases of hemorrhagic stroke, valve thrombosis, peripheral embolic events, or new intracardiac thrombus were related in both groups.In this pilot study, rivaroxaban 15 mg twice daily had thromboembolic and bleeding events similar to warfarin in patients with mechanical heart valves. These data confirm the authors' proof-of-concept and suggest that a larger trial with a similar design is not unreasonable. CLINICALTRIAL.NCT03566303."
1,"TITLE: Clinical value of tranexamic acid in unilateral and simultaneous bilateral TKAs under a contemporary blood-saving protocol: a randomized controlled trial.ABSTRACT: Despite the documented blood-saving effects of tranexamic acid (TNA) in total knee arthroplasty (TKA), the question whether clinical values of TNA are identical in unilateral and bilateral TKAs remains unclear. This study was undertaken to determine the clinical values of TNA in unilateral and simultaneous bilateral TKAs under a contemporary blood-saving protocol in terms of efficacy (total blood loss and transfusion rate) and safety (the incidences of symptomatic deep vein thrombosis and pulmonary embolism).One hundred and eighty unilateral and 146 bilateral TKA patients were randomized into TNA group or control group. In unilateral TKA patients, TNA (10 mg/kg) was administered intravenously 20 min before tourniquet deflation and repeated 3 h after surgery. In bilateral TKA patients, one more dose (10 mg/kg) was given before tourniquet deflation in the second TKA. A contemporary blood-saving protocol was applied to all patients. The TNA and control groups were compared separately in unilateral and bilateral TKA patients for the efficacy and safety variables.In unilateral TKA patients, the TNA group had less total blood loss (905 vs. 1,018 mL, p = 0.018) than the control group, but there was no difference in the allogenic transfusion rate (1 vs. 7 %, n.s.). In bilateral TKA patients, the TNA group showed no differences in total blood loss (1,282 vs. 1,379 mL, n.s.), but a significant reduction in the allogenic transfusion rate (7 vs. 27 %, p = 0.002). No symptomatic deep vein thrombosis or pulmonary embolism was found in all patients.This study demonstrates that the use of TNA reduces total blood loss, but the effects on the transfusion rate can differ depending on the type of TKAs (unilateral vs. bilateral) and the blood-saving protocols."
1,"TITLE: Economic evaluation of multisystemic therapy for young people at risk for continuing criminal activity in the UK.ABSTRACT: To evaluate whether multisystemic therapy (MST) is more cost-effective than statutory interventions that are currently available for young offenders in England.A cost-offset evaluation of MST based on data from a randomised controlled trial conducted in North London, England, comparing MST with usual services provided by two youth offending teams (YOT). Service costs were compared to cost savings in terms of rates of criminal re-offending.108 adolescents, aged 11-17 years, were randomly allocated to MST+YOT (n = 56) or YOT alone (n = 52). Reductions in offending were evident in both groups, but were higher in the MST+YOT group. At 18-month follow-up, the MST+YOT group cost less in terms of criminal activity (£9,425 versus £11,715, p = 0.456). The MST+YOT group were significantly cheaper in terms of YOT services than the YOT group (£3,402 versus £4,619, p = 0.006), but more expensive including the cost of MST, although not significantly so (£5,687 versus £4,619, p = 0.195). The net benefit per young person for the 18-month follow-up was estimated to be £1,222 (95% CI -£5,838 to £8,283).The results reported in this study support the finding that MST+YOT has scope for cost-savings when compared to YOT alone. However, the limitations of the study in terms of method of economic evaluation, outcome measures used and data quality support the need for further research."
1,"TITLE: Dronabinol increases pain threshold in patients with functional chest pain: a pilot double-blind placebo-controlled trial.ABSTRACT: Noncardiac chest pain is associated with poor quality of life and high care expenditure. The majority of noncardiac chest pain is either gastresophageal reflux disease related or due to esophageal motility disorders, and the rest are considered functional chest pain (FCP) due to central and peripheral hypersensitivity. Current treatment of FCP improves 40-50% of patients. Cannabinoid receptors 1 (CB1) and 2 (CB2) modulate release of neurotransmitters; CB1 is located in the esophageal epithelium and reduces excitatory enteric transmission and potentially could reduce esophageal hypersensitivity. We performed a prospective study to evaluate its effects on pain threshold, frequency, and intensity in FCP. Subjects with FCP received dronabinol (5 mg, twice daily; n = 7; average age, 44 years; mean body mass index, 26.7) or placebo (n = 6; average age, 42 years; mean body mass index, 25.9) for 28 days (4 weeks). Chest pain, general health, and anxiety/depression questionnaires were assessed at baseline and at 4 weeks. Subjects underwent an esophageal balloon distention test prior to treatment and on last day of the study. Dronabinol increased pain thresholds significantly (3.0 vs. 1.0; P = 0.03) and reduced pain intensity and odynophagia compared to placebo (0.18 vs. 0.01 and 0.12 vs. 0.01, respectively, P = 0.04). Depression and anxiety scores did not differ between the groups at baseline or after treatment. No significant adverse effects were observed. In this novel study, dronabinol increased pain threshold and reduced frequency and intensity of pain in FCP. Further, large scale studies are needed to substantiate these findings."
1,"TITLE: Effect of perioperative sodium bicarbonate administration on renal function following cardiac surgery for infective endocarditis: a randomized, placebo-controlled trial.ABSTRACT: Patients with infective endocarditis (IE) have an elevated risk of renal dysfunction because of extensive systemic inflammation and use of nephrotoxic antibiotics. In this randomized, placebo-controlled trial, we investigated whether perioperative sodium bicarbonate administration could attenuate postoperative renal dysfunction in patients with IE undergoing cardiac surgery.Seventy patients randomly received sodium chloride (n = 35) or sodium bicarbonate (n = 35). Sodium bicarbonate was administered as a 0.5 mmol/kg loading dose for 1 h commencing with anesthetic induction, followed by a 0.15 mmol/kg/h infusion for 23 h. The primary outcome was peak serum creatinine (SCr) level during the first 48 h postoperatively. The incidence of acute kidney injury, SCr level, estimated glomerular filtration rate, and major morbidity endpoints were assessed postoperatively.The peak SCr during the first 48 h postoperatively (bicarbonate vs.1.01 (0.74, 1.37) mg/dl vs. 0.88 (0.76, 1.27) mg/dl, P = 0.474) and the incidence of acute kidney injury (bicarbonate vs.29% vs. 23%, P = 0.584) were similar in both groups. The postoperative increase in SCr above baseline was greater in the bicarbonate group than in the control group on postoperative day 2 (0.21 (0.07, 0.33) mg/dl vs. 0.06 (0.00, 0.23) mg/dl, P = 0.028) and postoperative day 5 (0.23 (0.08, 0.36) mg/dl vs. 0.06 (0.00, 0.23) mg/dl, P = 0.017).Perioperative sodium bicarbonate administration had no favorable impact on postoperative renal function and outcomes in patients with IE undergoing cardiac surgery. Instead, it was associated with possibly harmful renal effects, illustrated by a greater increase in SCr postoperatively, compared to control.ClinicalTrials.gov, NCT01920126 . Registered on 31 July 2013."
1,"TITLE: Outcome of Unicondylar Knee Arthroplasty vs Total Knee Arthroplasty for Early Medial Compartment Arthritis: A Randomized Study.ABSTRACT: With increasing number of patients with early osteoarthritis of knee opting for total knee arthroplasty (TKA), there has been increase in patients dissatisfied with surgical outcomes. It is being presumed that offering unicondylar knee arthroplasty (UKA) to them would improve outcomes.Primary objective of our study was to look for any difference in patient-reported outcome and function at 2-year follow-up in patients undergoing UKA as compared to TKA. Our study was a randomized study with parallel assignment conducted at a high-volume specialized arthroplasty center. Eighty patients with bilateral isolated medial compartment knee arthritis were randomized into simultaneous 2-team bilateral TKA (n = 40) and UKA (n = 40) group. We finally analyzed 36 patients in each group. Main outcome measure was improvement in Knee Outcome Survey-Activities of Daily Living Scale (KOS-ADLS) and High Activity Arthroplasty Score (HAAS) obtained at 2-year follow-up.Improvement in KOS-ADLS and HAAS at 2 years was similar (P = .2143 and .2010) in both groups. Performance as assessed with Delaware index was also similar. Length of hospital stay was less in UKA group (6.6 days as against 5.4 days). Complications and readmission rates were more in TKA group (nil in UKA group; 08 in TKA group).At 2-year follow-up, UKA provides similar improvement in patient-reported outcomes, function, and performance as compared to TKA when performed in patients with early arthritis. However, UKA patients have shorter hospital stay and fewer complications."
1,"TITLE: Preoperative butorphanol and flurbiprofen axetil therapy attenuates remifentanil-induced hyperalgesia after laparoscopic gynaecological surgery: a randomized double-blind controlled trial.ABSTRACT: Several studies indicate that remifentanil exposure may engender opioid-induced hyperalgesia. Butorphanol and flurbiprofen axetil are proposed as adjunctive analgesics for postoperative pain control. This randomized double-blind controlled study was designed to investigate the antihyperalgesic effects of butorphanol combined with flurbiprofen axetil on opioid-induced hyperalgesia.One hundred and twenty patients undergoing elective laparoscopic gynaecological surgery with sevoflurane anaesthesia were randomized to one of four groups, as follows: intraoperative sufentanil 0.30 µg kg (Group S); remifentanil 0.30 µg kg min (Group R); intraoperative remifentanil and pre-anaesthesia butorphanol 20 µg kg (Group B); or intraoperative remifentanil and pre-anaesthesia butorphanol 10 µg kg combined with flurbiprofen axetil 0.5 mg kg (Group BF). Sufentanil was used to control postoperative pain. The threshold and area of postoperative mechanical hyperalgesia were measured with Von Frey filaments. Pain intensity, sufentanil consumption, and side-effects were recorded for 24 h after surgery.Compared with Group S, remifentanil anaesthesia increased the pain score, postoperative sufentanil consumption, and area of hyperalgesia [mean 49.9 (sd 8.6) vs 60.5 (10.0) cm, P<0.001] and reduced the hyperalgesia threshold on the dominant inner forearm [mean 89.5 (sd 23.4) vs 60.6 (22.6) g, P=0.004]. Compared with Group R, the pain score, sufentanil consumption, and area of hyperalgesia were reduced and hyperalgesia threshold was elevated likewise in Groups B and BF. However, the efficacy in Group BF was higher than in Group B (P=0.021).The preoperative combination of butorphanol and flurbiprofen axetil effectively ameliorated opioid-induced hyperalgesia in patients undergoing laparoscopic gynaecological surgery under sevoflurane-remifentanil anaesthesia.NCT02043366."
1,"TITLE: Efficacy of iron-supplement bars to reduce anemia in urban Indian women: a cluster-randomized controlled trial.ABSTRACT: India's high prevalence of iron-deficiency anemia has largely been attributed to the local diet consisting of nonheme iron, which has lower absorption than that of heme iron. We assessed the efficacy of the consumption of iron-supplement bars in raising hemoglobin concentrations and hematocrit percentages in anemic (hemoglobin concentration <12 g/dL) Indian women of reproductive age. The Let's be Well Red study was a 90-d, pair-matched, cluster-randomized controlled trial. A total of 361 nonpregnant women (age 18-35 y) were recruited from 10 sites within Mumbai and Navi Mumbai, India. All participants received anemia education and a complete blood count (CBC). Random assignment of anemic participants to intervention and control arms occurred within 5 matched site-pairs. Intervention participants received 1 iron-supplement bar (containing 14 mg Fe)/d for 90 d, whereas control subjects received nothing. CBC tests were given at days 15, 45, and 90. Primary outcomes were 90-d changes from baseline in hemoglobin concentrations and hematocrit percentages. Linear mixed models and generalized estimating equations were used to model continuous and binary outcomes, respectively. Of 179 anemic participants, 136 (76.0%) completed all follow-up assessments (65 intervention and 71 control participants). Baseline characteristics were comparable by arm. Mean hemoglobin and hematocrit increases after 90 d were greater for intervention than for control participants [1.4 g/dL (95% CI: 1.3, 1.6 g/dL) and 2.7% (95% CI: 2.2%, 3.2%), respectively]. The anemia prevalence at 90 d was lower for intervention (29.2%) than for control participants (98.6%) (OR: 0.007; 95% CI: 0.001, 0.04). The daily consumption of an iron-supplement bar leads to increased hemoglobin concentrations and hematocrit percentages and to a lower anemia prevalence in the target population with no reported side effects. This intervention is an attractive option to combat anemia in India. This trial was registered at clinicaltrials.gov as NCT02032615."
1,"TITLE: Clinical impact of pharmacogenetic profiling with a clinical decision support tool in polypharmacy home health patients: A prospective pilot randomized controlled trial.ABSTRACT: In polypharmacy patients under home health management, pharmacogenetic testing coupled with guidance from a clinical decision support tool (CDST) on reducing drug, gene, and cumulative interaction risk may provide valuable insights in prescription drug treatment, reducing re-hospitalization and emergency department (ED) visits. We assessed the clinical impact of pharmacogenetic profiling integrating binary and cumulative drug and gene interaction warnings on home health polypharmacy patients.This prospective, open-label, randomized controlled trial was conducted at one hospital-based home health agency between February 2015 and February 2016. Recruitment came from patient referrals to home health at hospital discharge. Eligible patients were aged 50 years and older and taking or initiating treatment with medications with potential or significant drug-gene-based interactions. Subjects (n = 110) were randomized to pharmacogenetic profiling (n = 57). The study pharmacist reviewed drug-drug, drug-gene, and cumulative drug and/or gene interactions using the YouScript® CDST to provide drug therapy recommendations to clinicians. The control group (n = 53) received treatment as usual including pharmacist guided medication management using a standard drug information resource. The primary outcome measure was the number of re-hospitalizations and ED visits at 30 and 60 days after discharge from the hospital. The mean number of re-hospitalizations per patient in the tested vs. untested group was 0.25 vs. 0.38 at 30 days (relative risk (RR), 0.65; 95% confidence interval (CI), 0.32-1.28; P = 0.21) and 0.33 vs. 0.70 at 60 days following enrollment (RR, 0.48; 95% CI, 0.27-0.82; P = 0.007). The mean number of ED visits per patient in the tested vs. untested group was 0.25 vs. 0.40 at 30 days (RR, 0.62; 95% CI, 0.31-1.21; P = 0.16) and 0.39 vs. 0.66 at 60 days (RR, 0.58; 95% CI, 0.34-0.99; P = 0.045). Differences in composite outcomes at 60 days (exploratory endpoints) were also found. Of the total 124 drug therapy recommendations passed on to clinicians, 96 (77%) were followed. These findings should be verified with additional prospective confirmatory studies involving real-world applications in larger populations to broaden acceptance in routine clinical practice.Pharmacogenetic testing of polypharmacy patients aged 50 and older, supported by an appropriate CDST, considerably reduced re-hospitalizations and ED visits at 60 days following enrollment resulting in potential health resource utilization savings and improved healthcare.ClinicalTrials.gov NCT02378220."
1,"TITLE: Topical Ketoprofen Versus Placebo in Children Presenting With Ankle Sprain to the Emergency Department: A Randomized Controlled Study.ABSTRACT: Despite the favorable data concerning topical agents use in outpatient clinics, they are not commonly in emergency departments (EDs). The present study aimed to compare the effect of 2.5% topical ketoprofen (gel form) to placebo in children presenting with ankle sprain to the ED.Children between 7 and 18 years old presenting with ankle sprain composed the study population. Study patients were randomized into 2 study arms: 2.5% ketoprofen gel and placebo administered in a 5-cm area locally. Pain improvements at 15 and 30 minutes were measured by visual analog scale.Median pain reductions at 15 minutes for ketoprofen and placebo groups were 27.5 (16-39) and 5 (4-10), respectively. Median changes in pain intensity at 30 minutes for ketoprofen and placebo gel groups were 48 (43-52) and 9 (6-16), respectively. When compared 2 arms for the pain improvement at 15 and 30 minutes, the differences between 2 study drugs were 20 (13-28) and 35 (29-41), respectively. There were 7 (12.7%) rescue drug needs in the placebo group and 1 (1.7%) in the ketoprofen group (difference, 10.9%; 95% confidence interval, -6% to 7%; P = 0.83). There were no adverse effects in either group.Ketoprofen gel is superior to placebo in ceasing pain in children presenting with ankle sprain to the ED with a high safety profile."
0,"TITLE: Electrocardiographic changes predict angiographic vasospasm after aneurysmal subarachnoid hemorrhage.ABSTRACT: Early identification of patients at risk of angiographic vasospasm after aneurysmal subarachnoid hemorrhage (SAH) may mitigate its sequelae. One mechanism that may contribute to angiographic vasospasm is increased central sympathetic activity, which is also thought to cause electrocardiographic (ECG) changes after SAH. Here, we perform the first study to determine the association between ECG changes and angiographic vasospasm after SAH.Exploratory analysis was performed on 413 patients from CONSCIOUS-1, a prospective randomized trial of clazosentan for the prevention of angiographic vasospasm. ECGs were obtained within 24 hours of aneurysm rupture and during the vasospasm risk period. Angiographic vasospasm was assessed using catheter angiography at baseline and 7 to 11 days after SAH. Multivariate logistic regression was used to identify significant associations.The most prevalent finding on ECG both immediately following SAH and during the vasospasm risk period was QT prolongation (42% and 25%, respectively). A prolonged QT interval and tachycardia on the baseline ECG were associated with angiographic vasospasm (OR, 1.86; 95% CI, 1.00-3.45; and OR, 10.83; 95% CI, 1.17-100.50, respectively). QT prolongation on ECG during the vasospasm risk period was also associated with angiographic vasospasm (OR, 3.53; 95% CI, 1.67-7.39). No ECG findings were associated with delayed ischemic neurological deficit, but tachycardia and ST changes were associated with worse clinical outcome.QT prolongation and tachycardia on ECG were independently associated with angiographic vasospasm after aneurysmal SAH on multivariate analysis.URL: http://clinicaltrials.gov. Unique Identifier: NCT00111085."
0,"TITLE: Effect of dietary mannan-oligosaccharides on in vivo performance, nutrient digestibility and caecal content characteristics of growing rabbits.ABSTRACT: To evaluate the effect of mannan-oligosaccharides (MOS) on in vivo performance, nutrient digestibility, fermentation characteristics and caecal microbial populations of rabbits, 144 thirty-five days old hybrid Hyla were equally divided into three groups, one of which was fed the same diet without additives (control group), one with antibiotics (colistin sulphate, 144 mg/kg; tylosin, 100 mg/kg; oxytetracyclin, 1000 mg/kg) and one with MOS (1 g/kg of diet). Mortality rate, live weight, feed intake and feed conversion ratio were recorded up to 62 days of age. At 60 days nutrient digestibility was measured by acid insoluble ash method. The caecal content of 10 rabbits per group was collected at 62 days and analysed for volatile fatty acids production, ammonia content and microbial count. Rabbits from the control group had a significantly (p < 0.01) lower body weight at 62 days (1638.9 g vs. 1779.4 g and 1862.5 g, respectively for the control, MOS and antibiotic groups) while the antibiotic group showed a higher (p < 0.05) feed intake than the control group (127.9 g/day vs. 109.3 g/day). Rabbits from the MOS group had a higher apparent digestibility of cellulose (34.27% vs. 29.61% and 27.49%, respectively for the MOS, control and antibiotic groups) and, as a consequence a higher level of acetate in the caecal content (39.93 mmol/l vs. 34.21 mmol/l and 23.09 mmol/l, respectively for the MOS, control and antibiotic groups). Caecal microflora of the MOS group rabbits also had a higher fermentative activity in respect of protein source, as demonstrated by the higher productions of branched chain fatty acids. MOS and antibiotics significantly reduced the colonies of Coliformis (2.32 vs. 3.20 vs. 2.40 logCFU/g, respectively for the MOS, control and antibiotic groups, p < 0.01). Mannan-oligosaccharides at 1 g/kg of diet can be used as an alternative to antibiotics during the rabbit's growth period."
1,"TITLE: Using Etomidate and Midazolam for Screening Colonoscopies Results in More Stable Hemodynamic Responses in Patients of All Ages.ABSTRACT: Recent studies have demonstrated that etomidate is a safe sedative drug with noninferior sedative effects. In our recent study, we revealed that etomidate/midazolam was more hemodynamically stable than propofol/midazolam in elderly patients undergoing colonoscopies. We aimed to investigate whether compared with propofol/midazolam, etomidate/midazolam causes fewer cardiopulmonary adverse events with noninferior efficacy for screening colonoscopies in patients of all ages.In this single-center, randomized, double-blind study, we prospectively enrolled 200 patients. The patients were divided into etomidate and propofol groups. The primary outcome was the occurrence of cardiopulmonary adverse events. The secondary outcomes were the proportion of patients with fluctuations in vital signs (oxygen desaturation and transient hypotension), adverse events interrupting the procedure, and sedation-related outcomes.Adverse cardiopulmonary events were more common in the propofol group than the etomidate group (65.0% vs 51.0%, respectively; p=0.045). Forty-six patients (46.0%) in the propofol group and 29 (29.0%) in the etomidate group experienced fluctuations in their vital signs (p=0.013). The proportions of patients experiencing adverse events that interrupted the procedure, including myoclonus, were not significantly different between the two groups (etomidate: 20.0% vs propofol: 11.0%; p=0.079). Both groups had similar sedation-related outcomes. Multivariate analysis revealed that compared with the propofol groups, the etomidate group had a significantly lower risk of fluctuations in vital signs (odds ratio, 0.427; 95% confidence interval, 0.230 to 0.792; p=0.007).Compared with using propofol/midazolam, using etomidate/midazolam for screening colonoscopies results in more stable hemodynamic responses in patients of all ages; therefore, we recommend using etomidate/midazolam for colonoscopies in patients with cardiovascular risk factors."
1,"TITLE: The Influence of Adding Diphenhydramine Before Initiation of Moderate Sedation with Midazolam and Pethidine for Improving Quality of Colonoscopy.ABSTRACT: Combination of Intravenous benzodiazepines with opiates appears to be essential in order to guarantee high quality of moderate sedation during colonoscopy. Diphenhydramine is recommended for endoscopic procedures in difficult-to-sedate patients However, the studies supporting its use have yielded conflicting results.To assess the value of adding diphenhydramine hydrochloride before initiation of moderate sedation with midazolam and pethidine for Improving Quality of Sedation during colonoscopy.We conducted a prospective, randomized, double-blind, placebo-controlled study of 150 Patients undergoing diagnostic colonoscopy. Of 150 patients, data were analyzed for 100 patients randomized into two groups: Diphenhydramine group (n = 53) received 50 mg of diphenhydramine intravenously before initiation of moderate sedation with pethidine and midazolam while in placebo group (n = 47) received placebo in addition to pethidine and midazolam. Amount of pethidine and midazolam used and Quality of sedation were assessed.The mean doses of pethidine was significantly higher in placebo group as compared to diphenhydramine group (69.9 ± 35.4 mg vs 61.2 ± 21.0 mg, p < 0.01) However, no significant difference between the two groups regarding midazolam mean dose (4.9.±2.1 mg vs 4.8 ± 2.0 mg,p = 0.786). More patients in diphenhydramine group were being very satisfied with the procedure as compared to those in placebo group (88.67% vs 59.57%,p < 0.001).Furthermore more endoscopist in diphenhydramine group were being very satisfied with the procedure as compared to those in placebo group (77.35% vs 51.06%,p < 0.001).Intravenous diphenhydramine hydrochloride given before initiation of midazolam and pethidine offers a significant Improvement of Quality of moderate Sedation during colonoscopy without increasing the number of sedation related complications."
1,"TITLE: Influence of High Polyphenol Beverage on Stress-Induced Platelet Activation.ABSTRACT: Platelets are playing a crucial role in acute cardiovascular events. We investigated if physical stress activates platelets and whether this activation can be inhibited by a polyphenol-enriched diet.Blood samples were taken from a total of 103 athletes three weeks before, one day before, immediately as well as 24 hours and 72 hours after a marathon run. Participants were randomized, double-blinded and divided into two groups. One group received a polyphenol-rich beverage the other the same beverage without polyphenols. Besides analysis of platelet counts and impedance-aggregometric-measurement of platelet activity, soluble P-selectin and Endothelin-A measurements were performed.In the control group, runners showed a 2.2-fold increased platelet aggregation directly after completing a marathon and within the following three days when compared with baseline values (p<0.01). In accordance, significant increases in sP-selectin (57.52ng/ml vs. 94.86ng/ml;p<0.01) were detectable. In contrast, for the group consuming a beverage with increased polyphenol content (upper quartile of study beverage intake) we did not find any increase of platelet aggregation.Physical stress causes a significant increase in platelet activity. Our results demonstrate that a diet enriched in polyphenols is capable of preventing platelet activation. These findings might indicate a diminished cardiovascular stress-reaction following pre-exposition to polyphenol-enriched diet."
1,"TITLE: Is structural hydroxyapatite tricalcium-phosphate graft or tricortical iliac crest autograft better for calcaneal lengthening osteotomy in childhood? interim results from a randomised, controlled non-inferiority study.ABSTRACT: To compare the structural durability of hydroxyapatite-tricalcium phosphate (HATCP) to autologous iliac crest bone graft in calcaneal lengthening osteotomy (CLO) for pes planovalgus in childhood.We present the interim results of ten patients (HATCP, n = 6 and autograft, n = 5) with a mean age of 11.5 years (8.2 to 14.2) from a randomised controlled non-inferiority trial with six months follow-up. The primary outcome was the stability of the osteotomy as measured by radiostereometric analysis. A non-inferiority margin of ≤ 2 mm osteotomy compression was set.At six months the data showed that the osteotomy had been compressed by a mean 1.97 mm (99.8% confidence interval -1.65 to 5.60) more in the HATCP group than in the autograft group. Migration of the CLO grafted with HATCP stabilised at six months rather than at six weeks with autograft.This is the first randomised trial to compare the efficacy of HATCP graft with autograft in terms of stability of CLO in children. Because of problems with the HATCP the trial was stopped. We do not recommend HATCP graft in its current structure for use in unfixed CLOs. Cite this article: Bone Joint J 2016;98-B:1554-62."
1,"TITLE: Self-perceived postural balance correlates with postural balance and anxiety during the first year after stroke: a part of the randomized controlled GOTVED study.ABSTRACT: Postural balance is an important rehabilitation outcome, and screening stroke patients for confidence in postural balance during rehabilitation and before hospital discharge is recommended. Early supported discharge could improve postural balance self-confidence. This study aimed to investigate associations between patient self-confidence in postural balance and observer-assessed postural balance and anxiety during the first year after stroke. Whether very early supported discharge (VESD) affects self-confidence in postural balance compared with standard discharge was also evaluated.A longitudinal trial for with data extracted from a randomized controlled study of 140 adults with confirmed stroke was conducted. The experimental group received VESD. The control group was discharged according to the standard routine. Postural balance was assessed with Berg Balance Scale (BBS), Timed Up and Go (TUG) test, and Falls Efficacy Scale. Anxiety was assessed with the Hospital Anxiety and Depression Scale. Spearman's rank correlation coefficient (rho) was used to test associations between independent variables. The Wilcoxon signed-rank test was used to examine differences over time. A single test, according to Eid, Gollwitzer, and Schmidt, was used to test temporal differences in correlation.The correlation between self-confidence in postural balance and observer-assessed postural balance was 0.62-0.78 in the first year after stroke. The correlation between self-confidence and anxiety was 0.22-0.41 in the first year after stroke. Correlations did not differ by group affiliation at any time point when the postural balance was assessed with BBS. The intervention group had a significantly higher correlation (r = - 0.709) than the control group (r = - 0.416) when postural balance was assessed with the TUG test 1 month after discharge. There were no significant differences in correlations between confidence in postural balance and anxiety between the two groups at any time point.Patients with mild stroke can accurately assess their confidence in performing daily activities without falling. VESD does not substantially affect the correlation between self-confidence in postural balance and observer assessed postural balance and is safe to use as an alternative to standard discharge. Assessment of self-confidence can provide important information for rehabilitation planning and supporting the physical activity of patients after discharge.Clinical Trials.gov: NCT01622205 . Registered 19 June 2012 (retrospectively registered)."
1,"TITLE: Postoperative analgesic efficacy of ear acupuncture in patients undergoing abdominal hysterectomy: a randomized controlled trial.ABSTRACT: Numerous studies have revealed that acupuncture can increase the somatic pain threshold. Electro-acupuncture (EA) can help pain-relieving with minimal physiologic disturbance. Various painful disorders, as well as pain following various surgeries, like cesarean section, gastrostomy, and enterectomy were managed properly with acupuncture. Therefore we studied the postoperative analgesic effect of EA in patients undergoing abdominal hysterectomy.A randomized, prospective clinical trial study was carried out on 56 women undergoing hysterectomy under spinal anesthesia. Patients were allocated randomly to receive either spinal anesthesia and electric ear acupuncture (EEA group) or spinal anesthesia alone (control group). EEA was done by fine needles to anatomically defined 4 points of the ear: Shen Men Point, thalamus Point 26, Analgesia Point 3, and Uterus Point 58, and connected to EA therapeutic apparatus. After finishing surgery, the fine needles were substituted by permanent press needles to be removed after 24 hours. The primary outcome was the postoperative 24 h morphine consumption by patient-controlled analgesia, while secondary outcomes included Post-operative pain scores and postoperative 1st request of analgesia.Total morphine consumption in the first 24 postoperative hours was obviously reduced in the EEA group versus the control group (mean ± SD:6.214± 2.1319 mg vs 15.714 ± 3.3428 mg, d = - 3.3886, 95% Confidence interval = - 4.2061,-2.5712, p-value =0.000). The postoperative pain scores were significantly reduced in the EEA group in comparison to the control group, with delayed 1st request of postoperative analgesia.Electric ear acupuncture provides postoperative analgesia, reducing morphine requirement and consequently its side effects.The trial was registered before enrolment of the first patient at the Pan African Clinical Trial Registry ( www.pactr.org ) database ( PACTR201903770607799 , Date of registration: 5th March 2019)."
0,"TITLE: Impaired beta cell sensitivity to incretins in type 2 diabetes is insufficiently compensated by higher incretin response.ABSTRACT: The incretin effect is impaired in type 2 diabetes (T2D), but the underlying mechanisms are only partially understood. We investigated the relationships between the time course of the incretin effect and that of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) during oral glucose tolerance tests (OGTTs), thereby estimating incretin sensitivity of the beta cell, and its associated factors.Eight patients with T2D and eight matched subjects with normal glucose tolerance (NGT) received 25, 75, and 125 g OGTTs and corresponding isoglycemic glucose infusions (IIGI). The time course of the incretin effect, representing potentiation of insulin secretion by incretins (P), was determined by mathematical modelling as the time-dependent fold increase in insulin secretion during OGTT compared to IIGI. The time course of P was correlated with that of both GIP and GLP-1 in each subject (median r = 0.67 in NGT and 0.45 in T2D). We calculated an individual beta cell sensitivity to incretins (S) using a weighted average of GIP and GLP-1 (pooled incretin concentration, PIC), as the slope of the relationship between P and PIC. S was reduced in T2D (p < 0.01). In the whole group, mean PIC, GIP and GLP-1 concentrations during the OGTT were inversely correlated with S, but T2D had lower PIC, GIP and GLP-1 levels at the same S (p < 0.05).Relative incretin insensitivity is partly compensated for by higher incretin secretory responses. However, T2D shows both impairment in incretin sensitivity and abnormal compensation by incretin secretion."
1,"TITLE: Happy Family Kitchen II: a cluster randomized controlled trial of a community-based positive psychology family intervention for subjective happiness and health-related quality of life in Hong Kong.ABSTRACT: Most positive psychology interventions conducted in the West have been focused on the individual. Family relationships are highly valued in the Chinese collectivist culture, and it is of interest to know whether family-focused interventions can improve the well-being of Chinese people. We have previously reported the effectiveness of a positive psychology family intervention in terms of family well-being. Based on the data derived from the Happy Family Kitchen II project, this paper examines the effectiveness of a community-based positive psychology family intervention on subjective happiness and health-related quality of life.Thirty-one social service units and schools organized intervention programs for 2070 participants in Hong Kong. In a cluster randomized controlled trial, participants were randomly assigned on the basis of computer-generated numbers into the intervention group or the control group. The intervention programs emphasized one of five positive psychology themes: joy, gratitude, flow, savoring, and listening. The control group engaged in activities unrelated to the intervention, such as arts and crafts workshops. Subjective happiness and mental and physical quality of life were assessed at baseline and at 4 weeks and 12 weeks postintervention.Data of 1261 participants were analyzed. The results showed that the intervention was more effective than the control condition in improving subjective happiness, with a small effect size, at 12 weeks postintervention (β = .15, p = .020, Cohen's d = .16). However, there were no improvements in mental and physical quality of life in the intervention group compared with the control group at 4 weeks (β = .39, p = .494, d = .05; β = -.10, p = 1.000, d = -.01, respectively) and 12 weeks postintervention (β = .71, p = .233, d = .08; β = -.05, p = 1.000, d = -.01, respectively). Furthermore, the booster session was no more effective than the tea gathering session in improving subjective happiness (β = .00, p = .990, d = .00) or mental (β = 1.20, p = 1.000, d = -.04) and physical quality of life (β = .15, p = 1.000, d = -.01).The analyses extend previous findings of salutary effects on family well-being by showing that positive psychology family interventions can improve subjective happiness. Suggestions for future research are proposed.ClinicalTrials.gov NCT01796275 . Retrospectively registered 19 February 2013."
1,"TITLE: Rapid molecular determination of methicillin resistance in staphylococcal bacteraemia improves early targeted antibiotic prescribing: a randomized clinical trial.ABSTRACT: Empiric therapy of methicillin-susceptible Staphylococcus aureus (MSSA) infections with vancomycin is associated with poorer outcome than targeted therapy with β-lactams. Our objective was to evaluate whether rapid determination of methicillin resistance shortens the time from Gram stain to targeted antimicrobial therapy in staphylococcal bacteraemia, thereby reducing vancomycin overuse. This was a single-centre open parallel RCT. Gram-positive cocci in clusters in positive blood culture underwent real-time PCR for rapid species and methicillin resistance determination parallel to conventional microbiology. Patients were randomized 1:1 so that clinicians would be informed of PCR results (intervention group) or not (control group). Eighty-nine patients (intervention 48, control 41) were analysed. MRSA was identified in seven patients, MSSA in 46, and CoNS in 36. PCR results were highly concordant (87/89) with standard microbiology. Median time (hours) from Gram stain to transmission of methicillin-susceptibility was 3.9 (2.8-4.3) vs. 25.4 (24.4-26-7) in intervention vs. control groups (p <0.001). Median time (hours) from Gram stain to targeted treatment was similar for 'all staphylococci' [6 (3.8-10) vs. 8 (1-36) p 0.13] but shorter in the intervention group when considering S. aureus only [5 (3-7) vs. 25.5 (3.8-54) p <0.001]. When standard susceptibility testing was complete, 41/48 (85.4%) patients in the intervention group were already receiving targeted therapy compared with 23/41 (56.1%) in the control group (p 0.004). There was no significant effect on clinical outcomes. Rapid determination of methicillin resistance in staphylococcal bacteraemia is accurate and reduces significantly the time to targeted antibiotic therapy in the subgroup of S. aureus, thereby avoiding unnecessary exposure to vancomycin."
1,"TITLE: Comparison of single-layer continues or two-layer interrupted pancreatojejunal suture in Frey procedure for treatment of chronic pancreatitis: a prospective randomized study.ABSTRACT: Many patients with chronic pancreatitis are elected for surgery when endoscopic interventions are ineffective. Duodenum preserving pancreatic head resection introduced by Charles F. Frey is the most common procedure used for surgical treatment of chronic pancreatitis. However, technical aspects of this procedure have not been studied extensively. Goal Our prospective randomized study is aimed to compare usage of single-layer continuous (I group) and two-layer interrupted sutures (II group) in constructing pancreatojejunostomy after Frey procedure.In a period between 2009 and 2016, a total of 103 patients, diagnosed with chronic pancreatitis and determined medical indications for surgical treatment were included into the study and randomized into group I (52 patients) and group II (51 patients). Preoperative, intraoperative patient characteristics and postoperative results were compared between both groups.Mean duration of surgery was statistically shorter in group I - 210 min, while in group II - 240 min (p = 0.004). Pancreatojejunoanastomosis construction time was shorter in group I - 19 (±6) min versus 51 (±18) min in group II, p &lt;0,001. No statistically relevant differences were observed in postoperative morbidity: group I - 51.9% and group II - 45,1% (p = 0.177) and mortality: group I - 3.8% and group II - 2% (p = 0.636).Frey procedure using single-layer continuous pancreatojejunostomy is safe, fast and less complex method in surgical treatment of chronic pancreatitis."
1,"TITLE: Clinical Study of Standard- vs Reduced-Dose Tacrolimus Combined With Generic Mycophenolate Mofetil in De Novo Kidney Transplantation: A Prospective Randomized Trial.ABSTRACT: The lowering of calcineurin inhibitor exposure is possibly considered as the proper strategy to prevent calcineurin inhibitor-induced nephrotoxicity in kidney transplant. This clinical study was designed to compare the efficacy and tolerability of reduced-dose tacrolimus with standard-dose mycophenolate mofetil (MMF) vs standard-dose tacrolimus with reduced-dose MMF.A prospective, multicenter, open-label, randomized, and parallel-group clinical trial was conducted at 4 transplant centers in Korea. A total sample size was 108, and eligible patients were randomly assigned in a 1:1 ratio to either reduced-dose tacrolimus with standard-dose MMF (the study group) or standard-dose tacrolimus with reduced-dose MMF (the control group) for 6 months in de novo kidney transplant recipients. Graft function, the incidence of efficacy failure, and adverse events were compared.The mean estimated glomerular filtration rate at 6 months post-transplantation was 69.83 ± 16.68 mL/min/1.73 m in the study group and 69.92 ± 17.55 mL/min/1.73 m in the control group (P > .05). The overall incidence of biopsy-proven acute rejection was 3.64% (n = 2) in the study group, compared to 3.77% (n = 2) in the control group (P > .05). There was no graft loss, death, or loss of follow-up in either group.In conclusion, the results suggest that tacrolimus minimization with standard-dose MMF provides adequate immunosuppression with proper renal function and similar rate of incidence of acute rejection compared with the regimen including standard-dose tacrolimus with reduced-dose MMF."
1,"TITLE: Clinical Outcome in Cerebral Vasospasm Patients Treated with and without Intra-Arterial Nimodipine Infusion.ABSTRACT: Cerebral vasospasm (CV) after aneurysmal subarachnoid hemorrhage (aSAH) is still a problem. Hypertension, hypervolemia, and hemodilution (triple-H) therapy and oral nimodipine only a modest effect on patients. Intra-arterial treatment, including nimodipine, has been studied, but only as retrospective and single-arm prospective studies. We compared the outcomes between CV patients who received an adjunct intra-arterial nimodipine infusion (IANI) and those who received the standard medical treatment alone in a prospective randomized controlled trial.In this study, patients between the age of 18 and 80 years, who underwent angiography within 14 days after aneurysm obliteration, were recruited and randomized to receive adjunct IANI or not, if they were identified with angiographic vasospasm. All the angiographic and neurologic data were recorded and analyzed during their admission, at the discharge date, and during the 6-month follow-up period.From June 2016 to December 2018, we enrolled 68 patients who were randomized into two groups, 36 in the intervention group and 32 in the control group. The patients' characteristics, aneurysm data, and modalities of treatment were similar between the two groups. Within 24 hours after IANI, Glasgow Coma Scale (GCS) score and motor strength revealed a significant improvement of 33.33 and 38.89%, respectively, in the intervention group versus 12.5 and 9.38%, respectively, in the control group. At discharge, the intervention group still had significant motor improvement (58.33 vs. 21.88%;  = 0.002).IANI could be considered an effective treatment for CV without significant complications. This is the first RCT demonstrating statistically significant motor strength improvement within 24 hours and at discharge."
1,"TITLE: The supportive effect of supplementation with α-keto acids on physical training in type 2 diabetes mellitus.ABSTRACT: The maintenance of physical activity is crucial for the prevention and management of type 2 diabetes (T2D), and exercise induced changes including production of metabolites like ammonia can result in fatigue and exercise intolerance. Nutritional supplements may serve as an effective measure in supporting patients undergoing physical training by acting on their metabolism. This study investigates the effects of supplementation with α-keto acids (KAS) on exercise tolerance and glucose control in T2D patients. In a double-blind, placebo-controlled, randomized study 28 T2D patients underwent 6 weeks training on a cycle ergometer while they were supplemented with either a placebo or KAS (0.2 g kg(-1) body weight each day). The weekly training volume, power output at maximum and lactic threshold, leg muscle torque, the plasma concentration and 8 h urinary discharge of glucose, ammonia and urea were determined before and after the training as well as after one week of recovery. With KAS the patients did significantly more voluntary exercise (213 vs. 62 min, P < 0.01), reached a higher VO2max (27.3 vs. 24.8 ml min(-1) kg(-1)), higher power output (224 vs. 193 watts, P < 0.05) and greater endurance capacity (108 vs. 96 watts at lactic threshold, P < 0.05). Although the patients without KAS improved their glucose control after the training (P < 0.05), this effect could not be maintained after recovery as it was in the KAS group, where there was a prolonged benefit in glucose control. KAS also affected the ammonia and urea metabolism. KAS delivered supportive effects on the physical training along with a prolonged benefit in glucose control in T2D patients."
1,"TITLE: Hypnosis Versus Placebo During Atrial Flutter Ablation: The PAINLESS Study: A Randomized Controlled Trial.ABSTRACT: The aim of this study was to assess the superiority of hypnosis versus placebo on pain perception and morphine consumption during typical atrial flutter (AFL) ablation.AFL ablation commonly requires intravenous opioid for analgesia, which can be associated with adverse outcomes. Hypnosis is an alternative technique with rising interest, but robust data in electrophysiological procedures are lacking.This single center, randomized controlled trial compared hypnosis and placebo during AFl ablation. In addition to the randomized intervention, all patients were treated according to the institution's standard of care analgesia protocol (administration of 1 mg of intravenous morphine in case of self-reported pain ≥5 on an 11-point numeric rating scale or on demand). The primary endpoint was perceived pain quantified by patients using a visual analog scale.Between October 2017 and September 2019, 113 patients (mean age 70 ± 12 years, 21% women) were randomized to hypnosis (n = 56) or placebo (n = 57). Mean pain score was 4.0 ± 2.2 in the hypnosis group versus 5.5 ± 1.8 in the placebo group (p < 0.001). Pain perception, assessed every 5 min during the whole procedure, was consistently lower in the hypnosis group. Patients' sedation scores were also better in the hypnosis group than in the placebo group (8.3 ± 2.2 vs. 5.4 ± 2.5; p < 0.001). Finally, morphine requirements were significantly lower in the hypnosis group (1.3 ± 1.3 mg) compared with the placebo group (3.6 ± 1.8 mg; p < 0.001).In this first randomized trial, hypnosis during AFL ablation was superior to placebo for alleviating pain and reducing morphine consumption."
0,"TITLE: The Clinical Risk Factors of Adenovirus Pneumonia in Children Based on the Logistic Regression Model: Correlation with Lactate Dehydrogenase.ABSTRACT: Children with bacterial pneumonia (41 cases) and adenovirus pneumonia (179 cases) hospitalized in Tianjin Children's Hospital from January to October 2020 were selected. The differences in baseline and clinical characteristics between children with two pneumonias, respectively, were compared via the chi-square test and Wilcox test. The Least Absolute Shrinkage and Selection Operator (LASSO) model was applied to screen the pneumonia type-related characteristics. Patients were randomly divided into the training set ( = 154) and test set ( = 66). The logistic model was constructed using the screened characteristics in the training set to predict whether the cases are bacterial pneumonia or adenovirus pneumonia. Finally, the model was validated by receiver operating characteristic (ROC) curve and area under curve (AUC) in the test set.The age ( < 0.001), hospital stay ( < 0.001), tonsil condition ( < 0.001), interleukin-6 (IL-6; =0.033), and lactate dehydrogenase (LDH;  < 0.001) between children with bacterial pneumonia and adenovirus pneumonia were significantly different. Sex, tonsil condition, age, hospital stay, r-glutamyltransferase (r-GT), and LDH levels were the factors associated with the types of pneumonia. Compared with bacterial pneumonia, children with adenovirus pneumonia were younger (OR = 0.207, 95% CI: 0.041-0.475), with longer hospital stay (OR = 7.974, 95% CI: 2.626-74.354) and higher LDH expression level (OR = 1.025, 95% CI: 1.006-1.060). 92.4% types of pneumonia were correctly predicted, and the AUC value of the model was 0.981.The LDH level was the associated factor to predict the types of pneumonia. Adenovirus pneumonia was associated with earlier age and longer hospital stay than bacterial pneumonia. The established model can well predict the types of pneumonia in children and provide clinical basis for guiding the individualized treatment of children."
1,"TITLE: FDA Approval Summary: Ivosidenib for the Treatment of Patients with Advanced Unresectable or Metastatic, Chemotherapy Refractory Cholangiocarcinoma with an IDH1 Mutation.ABSTRACT: On August 25, 2021, the FDA approved ivosidenib for the treatment of adult patients with unresectable locally advanced or metastatic hepatocellular isocitrate dehydrogenase 1 (IDH1) mutated cholangiocarcinoma (CCA) as detected by an FDA-approved test with disease progression after 1 to 2 prior lines of systemic therapy for advanced disease. The approval was based on data from Study AG120-C-005 (ClarIDHy), a double-blind placebo-controlled trial that randomly allocated (2:1) patients to receive either ivosidenib or placebo. Independently assessed progression-free survival (PFS) was the primary endpoint. With a median follow-up of 6.9 months, the HR for PFS was 0.37 [95% confidence interval (CI), 0.25-0.54; P < 0.0001). Overall survival (OS) was the key secondary endpoint. At the final analysis of OS, with 70.5% of patients in the placebo arm receiving ivosidenib post disease progression, a non-statistically significant improvement in the ivosidenib arm with an HR = 0.79 (95% CI, 0.56-1.12) and median OS of 10.3 months (95% CI, 7.8-12.4) and 7.5 months (95% CI, 4.8-11.1) in the ivosidenib and placebo arms, respectively, were reported. Adverse reactions occurring in >20% of patients receiving ivosidenib were fatigue/asthenia, nausea, diarrhea, abdominal pain, ascites, vomiting, cough, and decreased appetite. Adverse reactions occurring in >20% of patients receiving placebo were fatigue/asthenia, nausea, abdominal pain, and vomiting. This is the first approval for the subset of patients with CCA harboring an IDH1 mutation."
1,"TITLE: Rates of formal diagnosis in people screened positive for dementia in primary care: results of the DelpHi-Trial.ABSTRACT: Primary data about rates of formal diagnosis of dementia in the German primary care sector are widely lacking.Main objectives are to analyze the rate of syndrome diagnosis in primary care patients who screened positive for dementia, the distribution of differential diagnoses, and factors associated with undiagnosed dementia.DelpHi-MV (Dementia: life- and person-centered help in Mecklenburg-Western Pomerania) is an ongoing general practitioner (GP)-based, randomized, controlled intervention trial. A total of 4,064 patients (≥70 years, living at home) recruited from 108 participating GP practices were screened for dementia (DemTect < 9). Of 692 eligible patients (17%), a total of 406 subjects (59%) provided informed consent. Present analyses are based on the data of 243 patients with complete baseline assessment on January 1, 2014 (preliminary data). Formal diagnoses were retrieved from the medical records of the treating GPs. A conditional fixed effect regression analysis was performed to analyze factors associated with undiagnosed dementia.A total of 40% of patients who screened positive for dementia had been formally diagnosed with dementia. Unspecified dementia was diagnosed in 53%, vascular dementia in 24%, and Alzheimer's disease in 19% of these patients. Undiagnosed dementia was significantly associated with a higher mean score in the Mini-Mental State Examination (odds ratio, 1.11; p < 0.01, 95% confidence interval 1.04-1.18).The diagnosis rate of dementia in German primary care (40%) is well within the range of the international data (20-50%). The results emphasize the need for action to enhance recognition and differential diagnosis of dementia."
0,"TITLE: The 5352 A allele of the pro-inflammatory caspase-1 gene predicts late-acquired stent malapposition in STEMI patients treated with sirolimus stents.ABSTRACT: Late-acquired stent malapposition (LASM) is a common finding after sirolimus-eluting stent (SES) implantation and may be the cause for late stent thrombosis. Inflammation may play a pivotal role in LASM just as it plays in stent restenosis. We have therefore investigated seven polymorphisms involved in inflammatory processes, related in previous reports to restenosis, on the risk of LASM in SES patients. Patients with ST-elevation myocardial infarction who underwent SES implantation and had intravascular ultrasonography (IVUS) data available for both immediate post-intervention and 9-month follow-up were included in the present study. In total, 104 patients from the MISSION! Intervention Study were genotyped for the caspase-1 5352 G/A, eotaxin 1382 A/G, CD14 260 A/G, colony stimulating factor 2 1943 C/T, IL10 -1117 C/T, IL10 4251 C/T, and the tumor necrosis factor alpha 1211 C/T polymorphisms. LASM occurred in 26/104 (25%) of patients. We found a significantly higher risk for LASM in patients carrying the caspase-1 (CASP1) 5352 A allele (RR = 2.32; 95% CI 1.22-4.42). In addition, mean neointimal growth was significantly lower in patients carrying this LASM risk allele (1.6 vs. 4.1%, p = 0.014). The other six polymorphisms related to inflammation were not significantly related to the risk of LASM. In conclusion, carriers of the 5352 A allele in the caspase-1 gene are at increased risk of developing LASM after SES implantation. If this is confirmed in larger studies, then screening for this polymorphism in patients undergoing percutaneous coronary interventions could eventually help cardiologists to better select between commercially available stents."
1,"TITLE: Addition of atropine to submaximal exercise stress testing in patients evaluated for suspected ischaemia with SPECT imaging: a randomized, placebo-controlled trial.ABSTRACT: To evaluate the effects of the addition of atropine to exercise testing in patients who failed to achieve their target heart rate (HR) during stress myocardial perfusion imaging with single-photon emission computed tomography (SPECT).The study was a prospective, randomized, placebo-controlled design. Patients with suspected or known coronary artery disease who failed to achieve a target HR (≥85% of maximal predicted HR) during exercise SPECT imaging were randomized to receive intravenous atropine (n=100) or placebo (n=101).The two groups of patients did not differ with respect to demographic or clinical characteristics. A higher proportion of patients in the atropine group achieved the target HR compared to the placebo group (60% versus 3%, p<0.0001). SPECT imaging was abnormal in a higher proportion of patients in the atropine group as compared to the placebo group (57% versus 42%, p<0.05). Stress-induced myocardial ischaemia was present in more patients in the atropine group as compared to placebo (47% versus 29%, p<0.01). In both groups of patients, no major side effects occurred.The addition of atropine at the end of exercise testing is more effective than placebo in raising HR to adequate levels, without additional risks of complications. The use of atropine in patients who initially failed to achieve their maximal predicted HR is associated with a higher probability of achieving a diagnostic myocardial perfusion study."
1,"TITLE: Clinical benefits of methylprednisolone in off-pump coronary artery bypass surgery.ABSTRACT: It has not been established whether off-pump coronary artery bypass grafting (OPCABG) is less invasive than conventional CABG. In our experience, OPCABG has several advantages such as shorter operative duration, decreased requirement of blood transfusion and myocardial protection compared with conventional CABG. However, frequency of postoperative paroxysmal atrial fibrillation (PAF) is similar between these techniques and early postoperative C-reactive protein (CRP) levels have been shown to be significantly higher in OPCABG. We hypothesized that preoperative steroid administration, routinely used only in conventional CABG, may alleviate high postoperative PAF and CRP levels. Therefore, a prospective, double-blind, clinical trial was conducted in OPCABG patients to investigate the clinical effects of preoperative steroid administration.Thirty OPCABG patients were randomly divided into 2 groups: control (Group C: n = 15) and methylprednisolone (Group M: n = 15) groups. Group M patients were intravenously administered 1000 mg methylprednisolone during anesthesia induction.Hospital death and infectious complication such as mediastinitis were not observed in either group. Postoperative PAF occurred in 47 % (7/15) of patients in group C but in only 1 patient in group M (7 %, P = 0.013). Early postoperative CRP levels were significantly lower in group M than in group C (peak values on postoperative day 2: group M 15 ± 6 mg/dL vs. group C 23 ± 4 mg/dL; P = 0.0002).Preoperative steroid administration in OPCABG patients significantly suppresses CRP elevation and prevents postoperative PAF without increasing in-hospital mortality or infectious complications."
1,"TITLE: Does cow's milk protein elimination diet have a role on induction and maintenance of remission in children with ulcerative colitis?ABSTRACT: Aims of this study were to evaluate the efficacy of a cow's milk protein (CMP) elimination diet on induction and maintenance of remission and to define association with atopy in children with ulcerative colitis (UC).Twenty-nine consecutive patients (mean age: 11.2 years; range: 4.6-17 years; F/M: 15/14) with newly diagnosed UC were randomized either to receive a CMP elimination diet (n = 14) or to continue a free diet (n = 15) associated with concomitant steroid induction and mesalazine maintenance treatment. Children were prospectively evaluated at four time points: within 1 month, 6 months and 1 year after diagnosis or at the time of relapse.Twenty-five of the 29 enrolled patients responded to the UC induction therapy with a complete remission (86.2%), 13 belonging to CMP elimination diet group and 12 to free diet group (p = 0.59). Overall, our data showed that 7 of 13 (53.8%) patients treated with CMP elimination diet and 8 of 15 (53.3%) patients on free diet and UC therapy relapsed within 1 year of follow-up (p = 1).In conclusion, data of this paediatric, randomized trial suggest that CMP elimination has no role in the management of UC in non-sensitized children."
1,"TITLE: Simvastatin for secondary prevention of all-cause mortality and major coronary events in patients with mild chronic renal insufficiency.ABSTRACT: A potentially modifiable risk factor for cardiovascular disease in patients with mild chronic renal insufficiency is dyslipidemia. Few studies examined the effects of statins on all-cause mortality and major coronary events in patients with renal dysfunction.We performed a post hoc analysis from the Randomized Trial of Cholesterol Lowering in 4,444 Patients with Coronary Heart Disease: The Scandinavian Simvastatin Survival Study. Of 4,444 participants, 2,314 (52.1%) had mild chronic renal insufficiency defined as an estimated glomerular filtration rate less than 75 mL/min/1.73 m(2) (<1.25 mL/s), measured using the Modification of Diet in Renal Disease equation. The primary end point was all-cause mortality.During the follow-up period, simvastatin use was associated with decreased all-cause mortality (adjusted hazard ratio [HR], 0.69; confidence interval [CI], 0.54 to 0.89) in the 2,314 participants with mild chronic renal insufficiency. Rates of major coronary events (adjusted HR, 0.67; CI, 0.56 to 0.79) and coronary revascularization (adjusted HR, 0.62; CI, 0.49 to 0.77) also were significantly lower in the simvastatin group. No significant decreases in stroke incidence were observed in the simvastatin group (adjusted HR, 0.88; CI, 0.55 to 1.39). The side-effect profile was similar between the 2 treatment groups.Simvastatin therapy appears to be effective and safe for the secondary prevention of all-cause mortality and major coronary events in patients with mild chronic renal dysfunction."
1,"TITLE: Randomized controlled trial to assess the role of raised anal pressures in the pathogenesis of symptomatic early hemorrhoids.ABSTRACT: Increased maximum resting anal pressures (MRAP) have been found in patients with large prolapsed hemorrhoids undergoing hemorrhoidectomy, but their pathogenic role is controversial especially in view of the sphincteric damage that occurs with open and stapled procedures. This prospective randomized clinical trial was conducted to compare anal pressure changes in early symptomatic hemorrhoidal disease before and after successful treatment with band ligation or injection sclerotherapy, and to compare these pressures with those in normal asymptomatic controls.32 patients with symptomatic grade II hemorrhoids were randomized to treatment with either band ligation or injection sclerotherapy. Anal manometry was done before treatment and 8 weeks after completion of treatment, and compared with 20 normal age-matched controls.The pretreatment values in both study groups were similar to each other (69.38 cm H(2)O, 95% CI 58.67-80.08, vs. 67.75 cm H(2)O, 95% CI 56.86-78.64; p = 0.790), but were significantly higher (p = 0.0001 in both groups) than in the controls (45.25 cm H(2)O, 95% CI 38.36-52.14). After successful completion of treatment, there was a highly significant drop in the MRAP in both study groups (p = 0.0001 in group A, and p = 0.001 in group B) reaching normal values.Our study shows that even in early-stage hemorrhoids, the anal pressures are significantly raised, but after successful treatment with band ligation or injection sclerotherapy, these pressures return to normal, showing that they do not play a pathogenic role but are secondary to the congested hemorrhoidal cushions."
1,"TITLE: Effects of aerobic exercise on the circadian rhythm of heart rate and blood pressure.ABSTRACT: Although the effects of aerobic exercise on resting heart rate, heart rate variability, and blood pressure have been investigated, there are scant data on the effects of aerobic exercise on the circadian rhythm of such cardiovascular parameters. In this study, we investigated the effects of aerobic exercise on the 24 h rhythm of heart rate and ambulatory blood pressure in the morning, when cardiovascular events are more common. Thirty-five healthy young subjects were randomized to control and aerobic exercise groups. Subjects in the latter group participated in their respective exercise program for two months, while those in the former group did not exercise. Twenty-four-hour electrocardiogram and ambulatory blood pressure monitoring data were obtained at baseline and at the end of the exercise intervention. The control group showed no changes, while the aerobic exercise group showed a significant decrease in heart rate (73.7 +/- 6.6 bpm to 69.5 +/- 5.1 bpm, p < 0.005) and sympathetic activity such as LF/HF ratio (2.0 +/- 0.7 to 1.8 +/- 0.6, p < 0.05) throughout the 24 h period, particularly in the daytime. The decrease in the heart rate was most prominent in the morning. However, heart rate and LF/HF ratio showed no statistical changes during the night. No significant changes were observed in blood pressure. These findings suggest aerobic exercise exerts beneficial effects on the circadian rhythm of heart rate, especially in the morning."
1,"TITLE: Long-term safety and efficacy of perinatal probiotic intervention: Evidence from a follow-up study of four randomized, double-blind, placebo-controlled trials.ABSTRACT: Societies worldwide are faced with a progressive increase in immune-mediated health problems such as allergic, autoimmune, and inflammatory diseases, as well as obesity. Perinatal administration of specific probiotic bacteria is an attractive approach in reducing the risk of these conditions, but long-term efficacy and safety data are lacking. The aim here was to evaluate the clinical benefit and long-term safety of specific probiotics administered during the perinatal period.The probiotic strains used were Lactobacillus rhamnosus GG, Bifidobacterium lactis Bb-12, Lactobacillus paracasei ST11, and Bifidobacterium longum BL999. The children involved have subsequently undergone prospective long-term follow-up. In addition to physical examination, data were collected by structured questionnaires on non-communicable diseases and continued probiotic use, and growth data from welfare clinics and school nurses.Altogether 303 mother-infant pairs were included in the analysis. Seventy-six of 163 (47%) children receiving perinatal probiotics had developed allergic disease compared with 79 of 140 (56%) receiving placebo (OR 0.67, 95% confidence intervals [CI] 0.43-1.06, p = 0.09). Fifty-nine of 133 (44%) children receiving L. rhamnosus GG perinatally had developed allergic disease, OR 0.62, 95% CI 0.38-0.99, p = 0.047, as compared to placebo. We found no differences in growth or non-communicable disease prevalence between children receiving perinatally probiotics or placebo.Perinatal probiotic administration is safe in long-term follow-up. Children receiving L. rhamnosus GG perinatally tended to have decreased allergy prevalence."
1,"TITLE: Electronic Immunization Alerts and Spillover Effects on Other Preventive Care.ABSTRACT: The impact of electronic health record (EHR) immunization clinical alert systems on the delivery of other preventive services remains unknown. We assessed for spillover effects of an EHR immunization alert on delivery of 6 other preventive services, in children 18 to 30 months of age needing immunizations. We conducted a secondary data analysis, with additional primary data collection, of a randomized, historically controlled trial to improve immunization rates with EHR alerts, in an urban, primary care clinic. No significant differences were found in screening for anemia, lead, development, nutrition, and injury prevention counseling in children prompting EHR immunization alerts (n = 129), compared with controls (n = 135). Significant increases in oral health screening in patients prompting EHR alerts (odds ratio = 4.8, 95% CI = 1.8-13.0) were likely due to practice changes over time. An EHR clinical alert system targeting immunizations did not have a spillover effect on the delivery of other preventive services."
1,"TITLE: Open Radical Cystectomy versus Robot-Assisted Radical Cystectomy with Intracorporeal Urinary Diversion: Early Outcomes of a Single-Center Randomized Controlled Trial.ABSTRACT: Radical cystectomy (RC) with urinary diversion (UD) is still considered a complex surgery associated with significant morbidity. Open RC (ORC) remains the reference option of treatment, even if adoption of robot-assisted RC (RARC) is rapidly increasing. To date, all the available randomized controlled trials were characterized by an extracorporeal approach in performing UD, undermining potential benefits of a totally minimally invasive procedure. In this study, we aimed to report perioperative and 6-month outcomes from the first RCT comparing ORC and RARC with totally intracorporeal UD.Patients were eligible for randomization if they had a diagnostic transurethral resection of bladder tumor with cT2-4, cN0, cM0 or recurrent high-grade nonmuscle-invasive bladder cancer and no anesthesiological contraindications to robotic surgery. Patients were enrolled with a covariate adaptive randomization process based on the following variables: body mass index, American Society of Anesthesiologists® score, baseline hemoglobin, planned UD, neoadjuvant chemotherapy and cT stage. The primary end point was to demonstrate the superiority of RARC with intracorporeal UD in terms of a 50% transfusion rate reduction.Overall, 116 consecutive patients (58 RARC, 58 ORC) were enrolled. Among primary endpoint, overall perioperative transfusion rates were significantly lower in the RARC cohort (RARC: 22% vs ORC: 41%; p=0.046).This prospective randomized trial observed 22% and 41% overall perioperative transfusion rates in patients treated by RARC and ORC, respectively, confirming a significant benefit in favor of RARC with intracorporeal UD. However, perioperative complications, hospital stay and 6-month health-related quality of life were largely comparable between groups. Oncologic and functional outcomes will be assessed at longer followup to observe potential differences between arms."
1,"TITLE: Coming out under fire: The role of minority stress and emotion regulation in sexual orientation disclosure.ABSTRACT: Minority stress is hypothesized to interfere with sexual orientation disclosure and sexual minority wellbeing. In this study, we investigated whether minority stress is causally linked to reduced disclosure in sexual minorities, and whether emotion regulation, a potentially adaptive form of stigma coping, can intervene to promote disclosure even following exposure to minority stress. Sexual minority adults in the US (N = 168) were recruited online and randomized to a 2 x 2 between-subjects experimental design, where they: 1) received either emotion regulation instructions that asked them to either distance themselves from an emotionally evocative film clip or immerse themselves in the clip, and then 2) viewed either an affirming or a minority stress film clip. Following the film clip, participants completed a written reflection task in which they reflected on the film clip they viewed, which allowed research assistants to subsequently code for participants' spontaneous disclosures of sexual orientation. Participants who viewed the minority stress clip were significantly less likely to spontaneously disclose their sexual orientation in the written task compared to those who viewed the affirming film clip, OR = 3.21, 95% CI [1.14, 9.05], p = .03. Although the emotion regulation manipulation was successful, there was no effect on sexual orientation disclosure. To our knowledge, this is the first study to demonstrate a causal link between minority stress and disclosure in sexual minorities, and thus highlights an important mechanism underlying minority stress's effects on sexual minority wellbeing. Results demonstrate the importance of interventions that affirm marginalized identities and promote safe sexual orientation disclosure. Future research is needed to determine the circumstances under which effective emotion regulation can buffer against the negative emotional effects of minority stress to promote healthy approach behaviors like disclosure in safe contexts."
1,"TITLE: Bromelain and cardiovascular risk factors in diabetes: An exploratory randomized, placebo controlled, double blind clinical trial.ABSTRACT: To assess whether the dietary supplement (bromelain) has the potential to reduce plasma fibrinogen and other cardiovascular disease (CVD) risk factors in patients with diabetes.This randomized placebo controlled, double blind, parallel design, efficacy study was carried out in China and investigated the effect of 12 weeks of bromelain (1,050 mg/day) on plasma fibrinogen. This randomized controlled trial (RCT) recruited 68 Chinese diabetic patients [32 males and 36 females; Han origin, mean age of 61.26 years (standard deviation (SD), 12.62 years)] with at least one CVD risk factor. Patients were randomized into either bromelain or placebo group. While bromelain group received bromelain capsule, the placebo group received placebo capsule which consisted inert ingredient and has no treatment effect. Subjects were required to take 1,050 mg (3×350 mg) of either bromelain or starch-filled placebo capsules, two to be taken (2×350 mg) after breakfast and another (350 mg) after dinner, daily for 12 weeks. Plasma fibrinogen, CVD risk factors and anthropometric indicators were determined at baseline and at 12 weeks.The change in the fibrinogen level in the bromelain group at the end of the study showed a mean reduction of 0.13 g/L (standard deviation (SD) 0.86g/L) compared with the mean reduction of 0.36 g/L (SD 0.96 g/L) for the placebo group. However, there was no significant difference in the mean change in fibrinogen between the placebo and bromelain groups (mean difference=0.23g/L (SD 0.22 g/L), =0.291). Similarly, the difference in mean change in other CVD risk factors (blood lipids, blood pressure), blood glucose, C-reactive protein and anthropometric measures between the bromelain and placebo groups was also not statistically significant. Statistical differences in fibrinogen between bromelain and placebo groups before the trial despite randomization may have influenced the results of this study.This RCT failed to show a beneficial effect in reducing fibrinogen or influencing other selected CVD risk factors but suggests other avenues for subsequent research on bromelain."
1,"TITLE: Clinical and metabolic response to flaxseed oil omega-3 fatty acids supplementation in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial.ABSTRACT: Data on the effects of flaxseed oil omega-3 fatty acids supplementation on wound healing and metabolic status in subjects with diabetic foot ulcer (DFU) are scarce.This study was conducted to evaluate the effects of flaxseed oil omega-3 fatty acids supplementation on wound healing and metabolic status in subjects with DFU.The current randomized, double-blind, placebo-controlled trial was conducted among 60 subjects (aged 40-85years old) with grade 3 DFU. Subjects were randomly allocated into two groups (30 subjects each group) to receive either 1000mg omega-3 fatty acids from flaxseed oil supplements or placebo twice a day for 12weeks.After the 12-week intervention, compared with the placebo, omega-3 fatty acids supplementation resulted in significant decreases in ulcer length (-2.0±2.3 vs. -1.0±1.1cm, P=0.03), width (-1.8±1.7 vs. -1.0±1.0cm, P=0.02) and depth (-0.8±0.6 vs. -0.5±0.5cm, P=0.01). Additionally, significant reductions in serum insulin concentrations (-4.4±5.5 vs. +1.4±8.3 μIU/mL, P=0.002), homeostasis model of assessment-estimated insulin resistance (-2.1±3.0 vs. +1.0±5.0, P=0.005) and HbA1c (-0.9±1.5 vs. -0.1±0.4%, P=0.01), and a significant rise in the quantitative insulin sensitivity check index (+0.01±0.01 vs. -0.005±0.02, P=0.002) were seen following supplementation with omega-3 fatty acids compared with the placebo. In addition, omega-3 fatty acids supplementation significantly decreased serum high sensitivity C-reactive protein (hs-CRP) (-25.5±31.5 vs. -8.2±18.9μg/mL, P=0.01), and significantly increased plasma total antioxidant capacity (TAC) (+83.5±111.7 vs. -73.4±195.5mmol/L, P<0.001) and glutathione (GSH) concentrations (+60.7±140.2 vs. -15.5±129.7μmol/L, P=0.03) compared with the placebo.Overall, omega-3 fatty acids supplementation for 12weeks among subjects with DFU had beneficial effects on parameters of ulcer size, markers of insulin metabolism, serum hs-CRP, plasma TAC and GSH levels. In addition, flaxseed oil omega-3 fatty acids may have played an indirect role in wound healing due to its effects on improved metabolic profiles."
1,"TITLE: Effect of ultrasound-guided selective sensory nerve blockade of the knee on pain management compared with periarticular injection for patients undergoing total knee arthroplasty: A prospective randomized controlled trial.ABSTRACT: Ultrasound-guided selective sensory nerve blockade (SSNB) of the knee, including an adductor canal block (ACB), anterior femoral cutaneous nerve block, and infiltration between the popliteal artery and posterior capsule of the knee may provide effective motor-sparing knee analgesia for total knee arthroplasty (TKA). We hypothesized that the SSNB would manage pain better on ambulation 24 hours postoperatively compared to periarticular infiltration (PAI), when combined with postoperative continuous ACB.Seventy-two patients undergoing elective TKA under spinal anesthesia were randomly assigned to either SSNB (SSNB group) or intraoperative PAI (PAI group). All patients received postoperative multimodal analgesia, including continuous ACB. The primary outcome was pain on ambulation 24 hours postoperatively. Secondary outcomes included rest and dynamic numerical rating scale pain score, intravenous morphine requirement, functional performance measures, adverse events, satisfaction, and length of stay.There was no difference in pain score during movement between the groups (mean difference -0.48 [-1.38 to 0.42], p = 0.3) and other immediate overall pain scores 24 hours postoperatively. Patients in the SSNB group had significantly lower intravenous morphine requirement than the PAI group for 48 hours postoperatively (0 [0, 0] vs. 0 [0, 2]; p = 0.008). There was no intergroup difference in the performance-based measures, satisfaction, and length of stay.The SSNB did not provide superior postoperative analgesia, or improvement in immediate functional performance. However, it may result in lower opioid consumption postoperatively when compared with the intraoperative PAI."
1,"TITLE: A randomized controlled clinical trial on the impact of CCR5 blockade with maraviroc in early infection on T-cell dynamics.ABSTRACT: Initiation of antiretroviral therapy (ART) in early HIV infection demonstrates clinical benefits including enhanced CD4 T-lymphocyte recovery and minimization of the latent HIV reservoir. Whether ART intensification with CCR5 blockade provides additional benefits is unknown.This randomized controlled trial evaluated the impact of maraviroc (MVC) intensification in persons starting ART in acute and early HIV (AEH, within 3 months of estimated date of infection).Twenty persons in AEH in San Diego underwent double-blind randomization to receive either standard of care (SOC) ART or SOC + MVC to evaluate the hypothesis that early CCR5 blockage with a CCR5-containing ART regimen may provide immunologic and clinical benefit. The primary outcome of this study was the difference from baseline to week 48 in the proportion of CCR5 CD4 memory T cells. Blood was drawn at baseline and weeks 12, 24, and 48 to evaluate CCR5 CD4 and CD8 T-cell dynamics using multicolor flow cytometry.MVC intensification (n = 10) did not significantly alter CCR5 T-cell dynamics at week 48 of study compared to SOC (n = 9) in this fully recruited study (mean 1.12 vs 0.63, t = 0.36, df = 16, P = 0.727). Exploratory analyses of additional T-cell subsets suggest that MVC intensification in AEH trended to early greater increases in naïve and activated and proliferating CD4 T cells (P = 0.11, 0.19), and greater decreases in senescent memory CD4 T cells (P = 0.06), but these differences did not remain by week 48. CD8 T-cell evaluations did demonstrate trends to differences at week 48 with slower increases in naïve cells and slower decreases in activated memory cells (P = 0.16, 0.09). There were no reported harms or significantly different adverse events.We did observe a few trends, but did not find compelling evidence that MVC intensification during AEH significantly impacts CD4 and CD8 T-cell dynamics. Diagnosing and starting persons in AEH on ART may be of greater clinical importance than the regimen initiated."
1,"TITLE: The Prophylactic Use of Remifentanil for Delayed Extubation After Elective Intracranial Operations: a Prospective, Randomized, Double-Blinded Trial.ABSTRACT: Endotracheal extubation is a painful and stressful procedure. The authors hypothesized that the prophylactic use of remifentanil would attenuate the pain intensity and stress responses resulting from extubation in neurosurgical patients.In this prospective, randomized, double-blinded, controlled trial, 160 patients with planned delay extubation after elective intracranial operation were randomized 1:1 to receive either remifentanil or normal saline (control) before their extubation. The dose regime of remifentanil was a bolus of 0.5 μg/kg over 1 minute, followed by a continuous infusion of 0.05 μg/kg/min for 20 minutes. The primary outcome was the incidence of severe pain during the periextubation period. Secondary outcomes included changes in the pain intensity and vital signs, failing to pass an extubation evaluation after the study drug infusion, severe adverse events, postextubation complications, and clinical outcomes.Two patients in the remifentanil group did not pass the extubation evaluation. The incidence of severe pain during the periextubation period was significantly lower in the remifentanil group compared with the control group (25.0% vs. 41.3%, P=0.029). Compared with the control group, the visual analog scale in the remifentanil group was significantly lower after the bolus of remifentanil (12±18 vs. 25±27, P=0.001) and immediately after extubation (19±25 vs. 34±30, P=0.001). There were no significant differences in the vital signs immediately after extubation between the 2 groups (P>0.05).The prophylactic use of remifentanil decreases the incidence of severe pain. Our preliminary findings merit a larger trial to clarify the effect of the prophylactic use of remifentanil on clinical outcomes and adverse events."
1,"TITLE: Spontaneous versus mechanical ventilation during video-assisted thoracoscopic surgery for spontaneous pneumothorax: A randomized trial.ABSTRACT: Spontaneous ventilation video-assisted thoracic surgery (SV-VATS) is reported to have superior or equal efficacy on postoperative recovery to mechanical ventilation VATS (MV-VATS). However, perioperative safety of the SV-VATS blebectomy is not entirely demonstrated.We performed a noninferiority, randomized controlled trial (No. NCT03016858) for primary spontaneous pneumothorax patients aged 16 to 50 years undergoing a SV-VATS and the MV-VATS procedure. The trial was conducted at 10 centers in China from April 2017 to January 2019. The primary outcome was the comparison of intra- and postoperative complications between SV-VATS and MV-VATS procedures. Secondary outcomes included total analgesia dose, change of vital sign during surgery, procedural duration, recovery time, postoperative visual analog pain scores, and hospitalization length.In this study, 335 patients were included. There was no significant difference between the SV-VATS group and the MV-VATS group in the intra- and postoperative complication rates (17.90% vs 22.09%; relative risk, 0.81; 95% confidence interval, 0.52-1.26; P = .346). The SV-VATS group was associated with significantly decreased total dose of intraoperative opioid agents; that is, sufentanil (11.37 μg vs 20.92 μg; P < .001) and remifentanil (269.78 μg vs 404.96 μg; P < .001). The SV-VATS procedure was also associated with shorter extubation time (12.28 minutes vs 17.30 minutes; P < .001), postanesthesia care unit recovery time (25.43 minutes vs 30.67 minutes; P = .02) and food intake time (346.07 minute vs 404.02 minutes; P = .002). Moreover, the SV-VATS procedure deceased the anesthesia cost compared with the MV-VATS ($297.81 vs $399.81; P < .001).SV-VATS was shown to be noninferior to MV-VATS in term of complication rate and in selected patients undergoing blebectomy for primary spontaneous pneumothorax."
1,"TITLE: Is a Steroid Injection in Both Compartments More Effective than an Injection in the Extensor Pollicis Brevis Subcompartment Alone in Patients with de Quervain Disease? A Randomized, Controlled Trial.ABSTRACT: Ultrasonography (US)-guided steroid injections can improve the accuracy of injection in patients with de Quervain disease, especially in those with an intracompartmental septum. Although the main lesion of de Quervain disease in patients with a septum is a stenosing tenosynovitis of the extensor pollicis brevis (EPB), no report we know of has compared injection into the EPB subcompartment with an injection into both the abductor pollicis longus (APL) and EPB subcompartments. In this randomized trial, we compared the results of US-guided steroid injections targeting both subcompartments and the EPB subcompartment alone in patients with de Quervain disease.(1) Do patients who receive a steroid injection in the EPB subcompartment alone have lower pain scores at 6 weeks and at 3 months after US-guided injection compared with patients who receive an injection in both subcompartments? (2) Do patients who receive a steroid injection in the EPB subcompartment alone experience fewer steroid injection-related complications than patients who receive an injection in both subcompartments?A randomized controlled study was performed at a single center between August 2018 and March 2021. Patients with a diagnosis of de Quervain disease and with a complete intracompartmental septum between the APL and the EPB tendons were included. In total, 112 patients had a diagnosis of de Quervain disease during the study period. Definite, complete subcompartmentalization was seen in 50 patients. Patients were randomly assigned to US-guided injections targeting both subcompartments (n = 25) or the EPB subcompartment alone (n = 25). There were no between-group differences in age, gender, affected wrist, or disease duration, and all patients had US evidence of tendinosis of the EPB, with or without tendinosis of the APL. Although 33% of patients (16 of 48) showed tendinosis of the APL, no patient showed tendinosis of the APL alone. In all patients, a dorsal-to-palmar side injection of 0.5 mL of 2% lidocaine and 0.5 mL of triamcinolone acetonide (40 mg/mL) was administered by two experienced hand surgeons. In the both-subcompartments group, US-guided injections were performed in each of the APL and EPB subcompartments. In the EPB subcompartment group, US-guided injections were administered in the EPB subcompartment only. All patients underwent the same protocol after the procedure. Four percent (n = 2, 1 in each group) of patients were excluded after randomization because their pain level was not registered. Pre- and postinjection clinical outcome assessments were completed by orthopaedic surgery residents not involved in patient management. Patients were regularly examined at baseline, 6 weeks, and 3 months to evaluate the intensity of pain. We assessed pain by the VAS score, where 0 indicated no pain and 100 the most pain. At baseline, the VAS score was 67 ± 14 in the both-subcompartment group and 67 ± 16 in the EPB subcompartment group (mean difference 0.17 [95% CI -8.45 to 8.82]; p = 0.97). Complications related to the steroid injection, including numbness, tendon rupture, and skin hypopigmentation, were also recorded at final follow-up examinations. To determine statistical power, the VAS score for pain at 6 weeks after the injection was used as the primary outcome variable. The minimum clinically important difference for the VAS score was deemed to be 20 mm, and we estimated an SD of 23. A sample size calculation indicated that a sample of 21 patients per group would provide 80% power to detect an effect of this size between the groups at the p = 0.05 level using a t-test.There were no differences in the VAS scores between the both-subcompartment group and the EPB group at 6 weeks (10 ± 6 versus 10 ± 7, mean difference -0.08 [95% CI -4.08 to 3.91]; p = 0.97). The same was true at 12 weeks (12 ± 13 versus 11 ± 15, mean difference 0.38 [95% CI -7.74 to 8.49]; p = 0.09). No adverse events related to treatment (such as tendon rupture, infections, and numbness) occurred in either group. However, skin hypopigmentation occurred at the final follow-up examination in both groups. The proportion of patients experiencing skin hypopigmentation in the EPB subcompartment group was lower than in the both-subcompartment group (33% [8 of 24] versus 67% [16 of 24]; odds ratio 0.25 [95% CI 0.08 to 0.83]; p = 0.02).Our data suggest that a US-guided steroid injection targeting the EPB subcompartment alone is as effective in terms of pain reduction as targeting both subcompartments in patients with de Quervain disease who have complete septation. Furthermore, an injection targeting the EPB subcompartment alone can reduce the dose of steroids used, perhaps thereby decreasing complications related to steroid injections. We recommend using only single-compartment injections in this context, even among patients with an intracompartmental septum.Level I, therapeutic study."
1,"TITLE: Triggering with 1,500 IU of human chorionic gonadotropin plus follicle-stimulating hormone compared to a standard human chorionic gonadotropin trigger dose for oocyte competence in in vitro fertilization cycles: a randomized, double-blinded, controlled noninferiority trial.ABSTRACT: To assess if triggering with 1,500 IU of human chorionic gonadotropin (hCG) with 450 IU of follicle-stimulating hormone (FSH) induces noninferior oocyte competence to a standard dose of hCG trigger used in in vitro fertilization (IVF). The alternative trigger will be considered noninferior if it is at least 80% effective in promoting oocyte competence.Randomized, double-blinded, controlled noninferiority trial.Academic infertility practice.Women aged 18-41 undergoing IVF with antral follicle count ≥8, body mass index ≤30 kg/m, and no history of ≥2 IVF cycles canceled for poor response were enrolled. Participants with a serum estradiol >5,000 pg/mL on the day of trigger were excluded because of high risk of ovarian hyperstimulation syndrome.Participants were randomized to receive an alternative trigger of 1,500 IU of hCG plus 450 IU of FSH or a standard trigger dose of hCG (5,000 or 10,000 IU) for final oocyte maturation.The primary outcome was total competent proportion, defined as the probability of 2 pronuclei from an oocyte retrieved. The alternative trigger will be considered noninferior to the standard trigger if a 1-sided 95% confidence interval (CI) of the relative risk (RR) is not <0.8. Secondary outcomes included oocyte recovery and maturity, intracytoplasmic sperm injection fertilization, embryo quality, pregnancy rates, as well as serum and follicular hormones. Secondary outcomes were compared using a 2-sided superiority test. Outcomes were analyzed by intention-to-treat and per-protocol.A total of 105 women undergoing IVF were randomized from May 2015 to June 2018. The probability of the primary outcome was 0.59 with the alternative trigger and 0.65 with the standard trigger, with a RR of 0.91 and a 1-sided 95% CI of 0.83. Noninferiority of the alternative trigger was demonstrated. Live birthrate from all fresh transfers in the alternative trigger group vs. standard trigger was 46.9 vs. 46.4% (RR, 1.01; 95% CI, 0.62-1.62), respectively. Live birthrate per randomized participant was 48.1% in the alternative trigger group vs. 62.7% with the standard trigger (RR, 0.73; 95% CI, 0.48-1.11). No participants had a failed retrieval.Triggering with 1,500 IU of hCG plus 450 IU of FSH promoted noninferior oocyte competence compared to a standard hCG trigger dose.NCT02310919."
1,"TITLE: Vitamin D Supplementation on Carotid Remodeling and Stiffness in Obese Adolescents.ABSTRACT: Obesity is associated with vitamin D (VD) deficiency and arterial stiffness. This randomized control trial assessed the effects of VD supplementation during a weight-loss program on carotid intima-media thickness (IMT) and carotid compliance in obese adolescents. Participants were randomly assigned to receive either a 12-week lifestyle program with VD supplementation ( = 13), a lifestyle program without VD supplementation ( = 13) or a control group composed of normal-weight adolescents ( = 18). Serum total and free 25-hydroxyvitamin D (25(OH)D), IMT and carotid compliance were measured before and after the trial. Insufficiency in 25(OH)D concentration was found in 73% of obese participants compared to 22% among controls. Obese adolescents had lower free 25(OH)D and displayed higher IMT but lower carotid compliance than controls. Free 25(OH)D and IMT were negatively correlated in adolescents displaying VD insufficiency at baseline. After three months, total and free 25(OH)D increased in both groups. The changes of IMT and carotid compliance were similar between groups. The changes in IMT were correlated with the changes in total 25(OH)D in obese adolescents with VD insufficiency at baseline ( = -0.59,  = 0.03). While the lifestyle program with VD supplementation did not affect carotid compliance, IMT reduction was improved in obese adolescents."
1,"TITLE: Effects of capnometry monitoring during recovery in the post-anaesthesia care unit: a randomized controlled trial in adults (CAPNOSSPI).ABSTRACT: Continuous capnography should be used on patients admitted to post-anaesthesia care units (PACUs) with endotracheal tubes, but this monitoring is not always performed. Optimized ventilation in the PACU could be part of the global standards of practice to maintain the benefits of perioperative ventilation. The main objective was to study the rate of patients with alveolar hypoventilation before tracheal extubation or Laryngeal Mask Airway (LMA) removal upon the measurement of continuous capnography.In this prospective, parallel-group, randomized controlled study, we enrolled adult patients admitted to the PACU after general anaesthesia with an endotracheal tube or LMA in place. Patients were randomly assigned to two groups: in the Capno + group, nurses managed the patients with access to the capnometer and end-tidal carbon dioxide pressure (PETCO) measurements; in the Capno- group, nurses monitored the patients without seeing PETCO measurements. The primary outcome was the percentage of patients with PETCO measurements above 45 mm Hg during the minute before extubation. Secondary endpoints included the delay in recovering spontaneous breathing, rate of hypoxemia, delay before extubation, and length of stay in the PACU.Forty-eight patients were randomized into the two groups. The percentage of patients with PETCO > 45 mm Hg the minute before extubation was significantly decreased in the Capno + group (83.3% versus 54,1% in the Capno- and Capno + groups respectively, p = 0.029). There were no significant differences concerning secondary endpoints.The use of PETCO monitoring improves patient safety by decreasing the incidence of CO retention during recovery from general anaesthesia. This study suggests that this monitoring should be integrated in the PACU. The risk of hypoxemia can also be prevented through the early recognition of apnoea.clinicaltrial.gov. identifier: NCT03370081."
1,"TITLE: A randomized, double-blind, placebo-controlled pilot study of the comparative effects of dienogest and the combined oral contraceptive pill in women with endometriosis.ABSTRACT: To compare the effects of dienogest and a combined oral contraceptive pill (COCP) after laparoscopic surgery on pain and quality of life in women with severe endometriosis.A randomized double-blind pilot study was conducted from March 2018 to March 2020 in women with severe endometriosis confirmed by laparoscopic surgery. A total of 108 patients who had undergone laparoscopic surgery received dienogest, COCP, or placebo daily for 6 months. Primary and secondary outcomes were compared between the three groups.Treatment with dienogest or COCP was associated with improved self-reported pain after 6 months of treatment, as evidenced by significantly lower scores for pelvic pain and dyspareunia compared with placebo (P < 0.05). Significant differences in overall quality of life score were observed over 6 months in the dienogest, COCP, and placebo groups (mean difference 22.00, 23.45, and 6.45 points, respectively; P < 0.001). Post-hoc analysis revealed a significant difference in overall quality of life score between the placebo group and the dienogest (P < 0.001) and COCP groups (P = 0.004).Postoperative administration of dienogest or COCP reduced endometriosis-associated pain and improved quality of life in women with severe endometriosis.https://en.irct.ir/trial/43070."
1,"TITLE: Effect of dehydroepiandrosterone administration before in vitro fertilization on the live birth rate in poor ovarian responders according to the Bologna criteria: A randomised controlled trial.ABSTRACT: To evaluate the effect of dehydroepiandrosterone (DHEA) pre-treatment before in vitro fertilization and embryo transfer (IVF-ET) on the live birth rate in infertile women with poor ovarian response (POR) defined according to the Bologna criteria.A randomized, double-blind, placebo-controlled trial.Nine reproductive medical centers in China.A total of 821 participants with POR defined according to the Bologna criteria were enrolled in the study between April 2016 and December 2018.Eligible participants were randomly assigned to receive either DHEA (n = 410) or placebo (n = 411) treatments for 4-12 weeks prior to IVF-ET, in a 1:1 ratio.Live birth rate after the first embryo transfer.Thirty-six (8.8%) of 410 women in the DHEA group and 37 (9.0%) of 411 women in the placebo group had a live birth, with no significant difference observed between groups (relative risk, 0.98, 95% CI, 0.63-1.51; p = 0.911). There were no significant differences in the number of retrieved oocytes, and the rates of clinical pregnancy, pregnancy loss, and cumulative live births between the two groups.DHEA administration prior to IVF-ET had no beneficial effect on the live birth rate relative to placebo in women with POR defined according to the Bologna criteria.No benefit was found in poor ovarian responders who received DHEA administration prior to IVF."
0,"TITLE: Danger appraisal and pathogen-avoidance mechanisms in stigma towards severe mental illness: the mediating role of affective responses.ABSTRACT: Stereotypes of dangerousness are common predictors of stigmatising attitudes towards Severe Mental Illness (SMI). However less is known about pathogen avoidance mechanisms underlying stigma towards SMI, specially in samples of non-industrialised societies of Latin America and the Caribbean. The primary aim of this study was to examine pathogen-disgust sensitivity and danger appraisal mechanisms in responses of stigma towards SMI.Cross-sectional design with convenience sampling. Using an online survey, volunteers at the Universidad del Norte in Colombia (N = 271) provided their sociodemographic data and completed the Three-Domain Disgust Scale (TDDS). Participants were randomised to different descriptions of someone with SMI that varied in terms of aggressiveness (with and without danger) and causes of the SMI. Then, following the attribution questionnaire (AQ-27), respondents reported affective and discriminatory responses to the person in the description.Increased disgust sensitivity to pathogen stimuli resulted in stronger reports of anger (β = .14; p = .03), and fear (β = 0.27; p < 0.001). The relationship between disgust sensitivity and discriminatory responses was indirectly mediated by fear towards SMI (Bootstrapped CI =-.04,-.009). Dangerousness attributions in the description of SMI predicted stronger feelings of anger (β = .23; p = 0.001) and fear (β = .40; p < .001), as well increased support for coercion-segregation of SMI (β = .34; p = 0.04), but less intentions to help (β = -.26; p = 0.003). The relationship between dangerousness and support for coercion was mediated by fear (Bootstrapped CI = .72, 1.37) and anger (Bootstrapped CI = .06, .44), whereas pity (Bootstrapped CI = .03, .38) and fear (Bootstrapped CI = -1.39, -.69) mediated responses of support for coercion-segregation of SMI. Attributions about causes and personal responsibility were not significantly linked to stigma towards SMI (p > 0.05).Findings suggested that pathogen avoidance and danger appraisal systems interplay in the generation of discriminatory behaviour towards SMI. Anti-stigma programs and policy makers would benefit from introducing strategies that challenge stereotypes of dangerousness and unpredictability by promoting positive contact with people with SMI."
1,"TITLE: Outcome after percutaneous coronary intervention with contemporary stents in patients with concomitant peripheral arterial disease: A patient-level pooled analysis of four randomized trials.ABSTRACT: A considerable number of patients who undergo percutaneous coronary intervention (PCI) also have peripheral arterial disease (PAD) - a signal of more advanced atherosclerosis. After bare metal and early-generation drug-eluting coronary stent implantation, PAD patients showed inferior outcome. As stents and medical treatment were further improved, we aimed to assess the impact of PAD on outcome of PCI with contemporary new-generation stents.We analyzed 3-year pooled patient-level data from 4 large-scale randomized new-generation stent trials to compare all-comer patients with and without (core lab-verified) history of symptomatic PAD, defined as obstructive lesions in peripheral locations including lower and upper extremities, carotid, vertebral, mesenteric and renal arteries. Main endpoint was target vessel failure: cardiac death, target vessel-related myocardial infarction, or clinically indicated target vessel revascularization.Of all 9204 patients, 695 (7.6%) had a history of symptomatic PAD. They were older and had more often diabetes, renal failure, hypertension, hypercholesterolemia, and prior stroke. PAD was an independent risk factor for target vessel failure (adjusted-HR:1.42, 95%-CI:1.12-1.73, p = 0.001). Target vessel revascularization (adjusted-HR:1.37, 95%-CI:1.04-1.80, p = 0.026), death (adjusted-HR:1.52, 95%-CI:1.17-1.99, p = 0.002), and major adverse cardiovascular event risks (adjusted-HR:1.36, 95%-CI:1.13-1.64, p = 0.001) were also substantially higher.A history of symptomatic PAD still allows to simply identify patients with increased risk of unfavorable clinical outcome after PCI, including a higher risk of repeated coronary revascularization, despite using contemporary stents. In clinical practice, this knowledge about higher event risks of PAD patients is helpful both during Heart Team discussions and when informing patients about the procedural risk."
1,"TITLE: Effects of eicosapentaenoic acid on serum levels of selenoprotein P and organ-specific insulin sensitivity in humans with dyslipidemia and type 2 diabetes.ABSTRACT: Selenoprotein P (SeP, encoded by SELENOP in humans) is a hepatokine that causes insulin resistance in the liver and skeletal muscle. It was found that polyunsaturated fatty acid eicosapentaenoic acid (EPA) downregulates Selenop expression by inactivating SREBP-1c. The present study aimed to examine the effect of EPA for 12 weeks on circulating SeP levels and insulin sensitivity in humans with type 2 diabetes.A total of 20 participants with dyslipidemia and type 2 diabetes were randomly assigned to an EPA (900 mg, twice daily) group and a control group. The primary endpoint was a change in serum SeP levels. Organ-specific insulin sensitivity in the liver (HGP and %HGP), skeletal muscle (Rd), and adipose tissue (FFA and %FFA) were assessed using a hyperinsulinemic-euglycemic clamp study with stable isotope-labeled glucose infusion.Serum SeP levels were not changed in either group at the end of the study. In the EPA group, the changes in SeP levels were positively correlated with the change in serum EPA levels (r = 0.709, P = 0.022). Treatment with EPA significantly enhanced %FFA but not %HGP and Rd. The change in serum EPA levels was significantly positively correlated with the change in %HGP, and negatively correlated with changes in Rd.The change in serum EPA levels was positively correlated with serum SeP levels, hepatic insulin sensitivity, and negatively with skeletal muscle insulin sensitivity in humans with type 2 diabetes. The EPA-induced enhancement of hepatic insulin sensitivity might be associated with a mechanism independent of serum SeP levels."
0,"TITLE: Coronary revascularization strategy and outcomes according to blood pressure (from the International Verapamil SR-Trandolapril Study [INVEST]).ABSTRACT: The optimal blood pressure (BP) to prevent major adverse outcomes (death, myocardial infarction, and stroke) for patients with hypertension and coronary artery disease who have undergone previous revascularization is unknown but might be influenced by the type of revascularization procedure. We analyzed data from the INternational VErapamil SR-Trandolapril STudy, focusing on the relation between BP and the outcomes of 6,166 previously revascularized patients, using the 16,410 nonrevascularized patients as a reference group. The previous revascularization strategy consisted of coronary artery bypass grafting (CABG, 45.2%), percutaneous coronary intervention (PCI, 42.1%), or both (CABG+PCI, 12.8%). Patients who had undergone both CABG+PCI and CABG-only had a greater adverse outcome risk (adjusted hazard ratio 1.27% and 1.20%, 95% confidence interval 1.06 to 1.53 and 1.07 to 1.35, respectively). The risk was similar for PCI-only patients (adjusted hazard ratio 1.04, 95% confidence interval 0.92 to 1.19). The relations between the adjusted hazard ratio and on-treatment BP appeared J-shaped for each revascularization strategy, accentuated for PCI and diastolic BP (DBP), but excepting CABG only and DBP for which the relation was linear and positive. In conclusion, major adverse outcomes were more frequent in patients with coronary artery disease who had undergone previous CABG, with or without PCI, compared to those with previous PCI only. This likely reflected more severe vascular disease. The relation to systolic BP was J-shaped for each strategy. Among those patients with previous CABG only, the linear relation with DBP suggested that more complete revascularization might attenuate hypoperfusion at a low DBP. The management of BP might, therefore, require modification of targets according to the revascularization strategy to improve outcomes."
1,"TITLE: Equilibrium radionuclide angiography for evaluating the effect of facilitated percutaneous coronary intervention on ventricular synchrony in patients with acute myocardial infarction.ABSTRACT: It is unclear whether facilitated percutaneous coronary intervention (PCI) via a transradial approach therapy is preferable to primary PCI, with improved ventricular synchrony performance (VS), in Chinese patients.The 152 patients with their first anterior acute myocardial infarction (AMI) were randomized to a primary PCI group or facilitated PCI group. In the 1(st) week and 6(th) month after AMI onset, the parameters of VS were measured by equilibrium radionuclide angiography with ventricular phase analysis. The rate of TIMI grade-3 flow in the infarct-related artery pre-PCI in the facilitated PCI group was higher than that in the primary PCI group (30.56% vs. 8.45%, P=0.001). At the 6(th) month post-AMI, the parameters of time to peak ejection rate, phase shift and peak phase standard deviation were lower than in the primary PCI group (P<0.05, respectively). The incidence of recurrent ischemia and new or worsening congestive heart failure post-AMI in the facilitated PCI group was significantly lower than that in the primary PCI group (2.78% vs. 9.86%, P=0.043; 2.78% vs. 12.68%, P=0.028).Facilitated PCI via a transradial approach might significantly inhibit left ventricular remodeling and improve left ventricular function because of the complete, persistent patency of the infarct-related artery with few complications of vessel access and bleeding."
1,"TITLE: Pre-operative education and counselling are associated with reduced anxiety symptoms following carotid endarterectomy: a randomized and open-label study.ABSTRACT: Post-operative anxiety is common and may have significant impact on the post-operative recovery of the patients. Theatre nurse visits before surgery has been shown to reduce patient's anxiety levels following general surgery.To investigate the effect of pre-operative visits and counselling by intensive care unit (ICU) nurses on patient's anxiety levels following carotid endarterectomy.This is an open-label and randomized clinical trial. Patients undergoing carotid endarterectomy were divided into study (n=60) and control group (n=60). For the study group, in addition to routine pre-operational counselling by the surgeons, ICU nurses visited the patients and provided a structured counselling the day before surgery. For the control group, only routine pre-operative counselling was provided. Anxiety levels were assessed by Zung self-rating anxiety scale (SAS) the day before surgery and on the day after being discharged from ICU to the ward.The two groups were comparable in age, sex, surgical methods, and duration of ICU stays. Following the surgery, the mean SAS score in the control group increased from 50.5±5.4 to 58.5±7.3 (p=0.03), whereas the mean SAS score in the study group reduced from 51.5±4.3 to 45.1±6.5 (p=0.02). The proportion of patients with anxiety symptoms in the control group was higher than in the study group following the surgery (58.3% vs. 33.3%, p=0.001).Pre-operative visits and counselling by ICU nurses could reduce patient's anxiety levels following carotid endarterectomy."
1,"TITLE: Pre-emptive 600 mg oral gabapentin reduces morphine requirements and postoperative pain following non-obstetric lower abdominal surgery.ABSTRACT: Postoperative pain following lower abdominal surgery is one of the most common complications reported by patients. Gabapentin given two hours before surgery as pre-emptive analgesia has been reported to reduce postoperative pain and decrease postoperative analgesia requirements. The aim of this study was to determine the effectiveness of 600 mg oral gabapentin as a pre-emptive analgesia to reduce postoperative pain and morphine requirements following nonobstetric lower abdominal surgery.A double-blind randomized clinical trial was conducted with 72 subjects acquired by consecutive sampling from November 2019 to February 2020 at Tangerang District Hospital. Eligible subjects were randomized to two groups: placebo or 600 mg oral gabapentin two hours before skin incision. The total morphine requirements, visual analogue scale (VAS) score, first-time analgesic demand, and side effects were assessed during the first 24 hours postoperatively.The first 24-hour postoperative total morphine was higher in the placebo group (5.33 ± 1.97 mg vs. 2.47 ± 1.90 mg; P < 0.001). The pain scale at rest and movement during recovery, two hours postoperatively, and 24 hours postoperatively were significantly different between the two groups (P < 0.05). The Mann-Whitney test showed a significant difference in the first-time morphine required as rescue analgesia between the gabapentin group (161.5 [25-990] minutes) and placebo group (67.5 [10-371] minutes; P < 0.001). No significant difference was found in adverse events between the groups.Following nonobstetric lower abdominal surgery, 600 mg oral gabapentin as a pre-emptive analgesia attenuates postoperative pain and reduces morphine requirements."
0,"TITLE: Association of external cephalic version before term with late preterm birth.ABSTRACT: While evidence suggests that beginning an external cephalic version (ECV) before term (34 to 36 weeks) compared with after term may be associated with an increase in late preterm birth (34 to 36 weeks), it remains unknown what might account for this risk. The objective of the present study is to further investigate the association between ECV before term and late preterm birth.Secondary analysis of data collected from the international, multicenter Early ECV trials. We evaluated the relation between ECV exposure and late preterm birth (34 to 36 weeks), as well as whether additional risk factors for preterm birth (such as maternal age, height, body mass index, parity, placental location, and perinatal mortality rate) moderated this relation. Generalized linear mixed methods were used to account for center effect and adjust for covariates.Among 1765 women with breech pregnancies and without a prior preterm birth, 749 (42.4%) received at least one ECV before term. Exposure to an ECV before term was not associated significantly independently with odds of preterm birth. However, placenta location moderated the association between early ECV exposure and late preterm birth. The odds of preterm birth in women who were exposed to an ECV before term and who also had an anterior placenta were doubled (OR 2.05; 95% CI 1.12-3.71; p = 0.02).In a large cohort of women without known risks for preterm birth, those with an anterior placenta who undergo an ECV before term constitute a subgroup at particular risk for late preterm birth."
1,"TITLE: Herpes Simplex Virus Type 2 Acquisition Among HIV-1-Infected Adults Treated With Tenofovir Disoproxyl Fumarate as Part of Combination Antiretroviral Therapy: Results From the ACTG A5175 PEARLS Study.ABSTRACT: Tenofovir disoproxyl fumarate (TDF) disoproxyl fumarate (TDF) has in vitro activity against herpes simplex virus type 2 (HSV-2) and reduced HSV-2 acquisition as preexposure prophylaxis. Whether TDF-containing antiretroviral therapy (ART) reduces HSV-2 acquisition is unknown.Secondary analysis of AIDS Clinical Trials Group A5175, a randomized, open-label study of 3 ART regimens among 1571 participants.HSV-2 serostatus was assessed at baseline, at study exit, and before a change in ART regimen.Of 365 HSV-2-seronegative persons, 68 acquired HSV-2, with 24 receiving TDF-containing ART and 44 receiving ART without TDF (HSV-2 seroconversion incidence, 6.42 and 6.63 cases/100 person-years, respectively; hazard ratio, 0.89; 95% confidence interval, .55-1.44).HSV-2 acquisition was not reduced in HIV-infected, HSV-2-uninfected persons during TDF-containing ART."
1,"TITLE: Effect of an exercise intervention on global cognition after transient ischemic attack or minor stroke: the MoveIT randomized controlled trial.ABSTRACT: Patients with a transient ischemic attack (TIA) or ischemic stroke are at increased risk of developing cognitive impairment in the subacute phase. At present, the effects of exercise on cognitive functioning following a TIA or stroke are not fully known. The purpose of this trial was to investigate the effect of exercise on global cognition.The MoveIT trial is a single-centre, observer-blinded, randomized controlled trial involving a 1-year exercise intervention consisting of a 12-week group exercise program, combined with three counselling visits to the physiotherapists over a 9-month period. The control group received standard care. The primary outcome was global cognitive functioning, assessed at one year, using the Montreal Cognitive Assessment (MoCA). Secondary outcomes included cardiorespiratory fitness, the cardiovascular profile, and attainment of secondary prevention targets, anxiety, depression and fatigue at one and two years.The experimental group consisted of 60 patients, while the control group consisted of 59 patients. The mean age was 64.3 years and 41% were female. No between-group differences were found on global cognitive functioning (MD, 0.7 out of 30, 95% CI, - 0.2 to 1.6) or on secondary outcome measures at 12 months. The only significant between-group difference was found for fatigue, in favour of the experimental group at 12 months (MD, 0.6 out of 63, 95% CI, 0.1 to 1.1).No benefit of this exercise intervention was found regarding global cognition. Future studies need to focus on optimizing rehabilitation strategies for this vulnerable group of patients.http://www.trialregister.nl . Unique identifier: NL3721 . Date first registration: 06-03-2013."
1,"TITLE: Inverse relationship between body mass index and risk of venous thromboembolism among medically ill hospitalized patients: Observations from the APEX trial.ABSTRACT: Obesity is associated with cardiovascular complications such as diabetes and hypertension. However, obesity and high body mass index (BMI) can also be linked to improved clinical outcomes in certain patient populations. This counterintuitive observation is called the ""obesity paradox."" The effect of BMI on the risk of developing venous thromboembolism (VTE) in acutely ill medical patients remains unclear. In the Acute Medically Ill VTE Prevention with Extended Duration Betrixaban (APEX) trial, acutely ill hospitalized medical patients were randomized to receive either extended-duration betrixaban or shorter-duration enoxaparin and followed for 77 days. A total of 7372 patients with evaluable VTE endpoints had BMI measured at baseline. The association between BMI and VTE risk was assessed after adjusting for potential confounders. The multivariable adjusted ORs of VTE risk associated with BMI levels referencing the median BMI value (15, 18.5, 28.3 [reference], 35, 40, 45) were: 2.82 (95% CI, 1.32-6.04, [change from 28.3 to 15]), 1.85 (95% CI, 1.14-2.99, [change from 28.3 to 18.5]), 1.30 (95% CI, 1.04-1.63, [change from 28.3 to 35]), 1.13 (95% CI, 0.84-1.52, [change from 28.3 to 40]), and 0.91 (95% CI, 0.57-1.47, [change from 28.3 to 45]), respectively (p = 0.022). In conclusion, acutely ill hospitalized patients with lower BMI had a higher VTE risk through 77 days, which appears to be a manifestation of the BMI paradox."
1,"TITLE: The effectiveness of emotional freedom techniques (EFT) on depression of postmenopausal women: a randomized controlled trial.ABSTRACT: Postmenopausal women are at greater risk of depression. Depression may negatively affect the quality of life of women. An emotional freedom technique (EFT) is an evidence-based therapy combining cognitive and exposure components with acupressure. This study aimed to evaluate the effect of EFT on depression in postmenopausal women.This was a randomized controlled trial in which 88 women with mild to moderate depression recruited from a menopausal clinic in Ahvaz, Iran, and randomly assigned into two groups of EFT (n=44) and control for sham therapy (n=44). Women in the EFT group received two sessions of training and asked to continue EFT for 8 weeks, one time per day. The Beck Depression Inventory (BDI2) completed by women before and after the intervention. The control group received training on sham acupressure points similar to the intervention group. Data collected using a demographic and BDI2. Women requested to complete the BDI2 before and after the intervention. The independent t-test, chi-square, and ANCOVA were used to analyze data.The mean depression score in the intervention group reduced from 20.93 ± 4.6 to 10.96 ± 4.38 in comparison to the control group that reduced from 19.18 ± 2.79 to 17.01 ± 6.05 after intervention (p=0.001). After the 8 week intervention, the frequency of moderate depression decreased from 56.8 to 9.35% in the intervention and from 50 to 29.5% in the control group. In total, 63.4 and 34.15% in the intervention and control groups were free of depression respectively after the intervention (p<0.001).The results of this study showed that using EFT for 8 weeks could significantly reduce the mean score of depression in postmenopausal women. Using this method in public health centers for postmenopausal women is recommended."
1,"TITLE: Early Discontinuation of Cow's Milk Protein Ingestion Is Associated with the Development of Cow's Milk Allergy.ABSTRACT: Although early supplementation with cow's milk formula (CMF) reportedly increases the risk of cow's milk allergy (CMA) in breast-fed infants, little is known about the association between the timing of CMF discontinuation and subsequent CMA development.To elucidate the relationship between the timing of CMF discontinuation and CMA development in infants who received CMF in the early days of life.Using data from a randomized controlled trial of a birth cohort from 4 Japanese hospitals, we performed a subgroup analysis of participants who ingested CMF in the first 3 days of life. We compared the proportions of participants who developed CMA at age 6 months in those who discontinued CMF ingestion before age 1 month (""DISC <1-month group""), during age 1 to 2 months (""DISC 1-2-month group""), and during age 3 to 5 months (""DISC 3-5-month group"") with those who continued CMF ingestion until age 6 months (""continuous group""). The risk ratios (RRs) and 95% CIs for CMA development were calculated.CMA incidence was significantly higher in the DISC <1-month group (n = 7 of 17, 41.2%; RR, 65.7; 95% CI, 14.7-292.5; P < .001), DISC 1-2-month group (n = 3 of 26, 11.5%; RR, 18.4; 95% CI, 3.2-105.3; P = .003), and DISC 3-5-month group (n = 7 of 69, 10.1%; RR, 16.2; 95% CI, 3.4-76.2; P < .001) than in the continuous group (n = 2 of 319, 0.6%).Early CMF discontinuation, particularly in the first month of life, was associated with CMA development in infants who received CMF in the first 3 days of life."
1,"TITLE: LAW Trial - The Impact of Local Anesthetics Infiltration in Surgical Wound for Gastrointestinal Procedures (LAW): A Double-Blind, Randomized Controlled Trial.ABSTRACT: Prior studies have suggested that infiltration of local anesthetics reduce the rate of surgical site infections (SSIs). Opioid usage has become an epidemic. Some analgesic modalities, such as epidural analgesia and transversus abdominis plane block are associated with shorter length of stay and lower opioid use. The aim of our study was to assess the relationship between local infiltration of bupivacaine with rates of SSI and pain control.We conducted a prospective, double-blinded randomized controlled trial in patients who underwent open major gastrointestinal procedures from July 2016 to June 2017. Patients were divided into two groups based on administration of 0.5% bupivacaine ( = 30) (group 1) or placebo ( = 30) (control group). Outcomes evaluated were SSI, postoperative opioid requirements and pain scores.Patients in the bupivacaine group required a lower dose of epidural analgesia during the first 24 h (5.3 mcg/kg/h vs. 6.4 mcg/kg/h;  = 0.05). Opioid requirement was shorter in the bupivacaine group (3.5 ± 2.3 days vs. 5.7 ± 2.9 days;  = 0.01). No difference was found between groups in terms of SSI rates (0% vs. 6.7%,  = 0.49).There is no clear association between bupivacaine infiltration and reduction of SSI rate according to our study. Wound bupivacaine infiltration is associated with a lower dose of epidural infusion and opioid requirements."
0,"TITLE: Radiomics signature for predicting postoperative disease-free survival of patients with gastric cancer: development and validation of a predictive nomogram.ABSTRACT: PURPOSE Radiomics can be used to determine the prognosis of gastric cancer (GC). The objective of this study was to predict the disease-free survival (DFS) after GC surgery based on computed tomography-enhanced images combined with clinical features. METHODS Clinical, imaging, and pathological data of patients who underwent gastric adenocarcinoma resection from June 2015 to May 2019 were retrospectively analyzed. The primary outcome was DFS. Radiomics features were selected using Least Absolute Shrinkage and Selection Operator algorithm and converted into the Rad-score. A nomogram was constructed based on the Radscore and other clinical factors. The Rad-score and nomogram were validated in the training and validation groups. RESULTS Totally, 179 patients were randomly divided into the training (n=124) and validation (n=55) groups. In the training group, validation group, and overall population, the Rad-score could be divided into categories indicating low, moderate, and high risk of recurrence, metastasis, or death; all risk categories showed a significant difference between the training, validation, and overall population groups (all P < .001). Positive lymph nodes (hazard ratio (HR)=3.07, 95% CI: 1.52-6.23, P=.002), cancer antigen-125 (HR=3.24, 95% CI: 1.54-6.80, P=.002), and the Radscore (HR=0.73, 95% CI: 0.61-0.87, P < .001) were independently associated with DFS. These 3 variables were used to construct a nomogram. In the training group, the areas under the curve at 3 years were 0.758 and 0.776 for the Rad-score and the nomogram, respectively, while they were both 1.000 in the validation group. The net benefit rate was analyzed using a decision curve in the training and validation groups, and the nomogram was superior to the single Rad-score. CONCLUSION Rad-score is an independent factor for DFS after gastrectomy for GC. The nomogram established in this study could be an effective tool for the clinical prediction of DFS after gastrectomy."
1,"TITLE: Effectiveness of self-efficacy-enhancing interventions on rehabilitation following total hip replacement: a randomized controlled trial with six-month follow-up.ABSTRACT: As the world's population ages, hip replacement, a routine treatment for arthritis, has become more common. However, after surgery, rehabilitation has some limited effectiveness with postoperative complications and persistent impairments. This study aimed to explore the effect of a self-efficacy-enhancing intervention program following hip replacement on patients' rehabilitation outcomes (self-efficacy, functional exercise compliance, hip function, activity and social participation, anxiety and depression, and quality of life).A prospective randomized controlled trial with a repeated-measures, two-group design was conducted in a grade A general hospital in Guangdong Province, China. A total of 150 participants with a unilateral total hip replacement were recruited via convenience sampling. Participants were randomly assigned to either the self-efficacy enhancing intervention group (n = 76) or the control group (n = 74). The intervention encompassed a face-to-face education before discharge and four telephone-based follow-ups in six months after surgery. Researchers collected baseline data on one to three days after surgery, and outcomes data were collected one, three, and six months after surgery.Average age (deviation) in intervention and control group were 58 (10.32) and 59 (10.82), respectively. After six months, intervention group scored 86.83 ± 5.89 in rehabilitation self-efficacy, significantly higher than control group (72.16 ± 6.52, t = -10.820, p < 0.001) and their hip function has turned to ""excellent"" (90.52 ± 4.03), while that of the latter was limited to a ""middle"" level (78.47 ± 7.57). Statistically significant differences were found in secondary outcomes (p < 0.001). The advantage of intervention in improving quality of life was seen in the long term rather than in the early postoperative period.The self-efficacy-enhancing intervention performed by nurses induced better exercise compliance and physical, psychological, and social functions after hip replacement compared with routine care. We recommend such interventions to be combined with routine care soon after hip replacement. Further research should focus on the social participation of patients with hip replacement. Trial registration Retrospectively registered at Chinese Clinical Trial Registry (31/01/2020, No. ChiCTR2000029422, http://www.chictr.org.cn/index.aspx )."
0,"TITLE: Antidiabetic Treatment in Patients at High Risk for a Subsequent Keratinocyte Carcinoma.ABSTRACT: Metformin and sulfonylureas are the most commonly prescribed drugs used for the treatment of type II diabetes. Type II diabetes has been linked to the development of keratinocyte carcinoma (KC), consisting of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Previously we have demonstrated lower risk for a subsequent KC in metformin users. In this study, we aim to investigate the association between sulfonylureas use and the development of KC in patients with KC history. We performed a retrospective cohort study of the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial, which was a randomized double-blind vehicle-control cream originally investigating the effect of 5-fluorouracil on KC development. 932 patients with a history of KC were enrolled (98% male, 99% white, median age of 70 years) and followed for a median duration of 2.8 years. 153 patients were on metformin and 94 on sulfonylureas. We performed a survival analysis with cox regression and controlled for body mass index and known predictors: number of prior BCCs and age (for BCC) and for number of prior SCCs (invasive and in situ), number of actinic keratoses at baseline (for SCC). Sulfonylurea-users com-pared to non-users had a HR of 0.67 (CI: 0.40&ndash;1.56; P=0.49) and 0.94 (CI: 0.63&ndash;1.40; P= 0.77), for SCC and BCC, respectively. Diabetic patients at high risk for KC might benefit from the use of metformin versus sulfonylureas. J Drugs Dermatol. 2022;21(5):502-505. doi:10.36849/JDD.6087."
1,"TITLE: Effıcacy of cıtalopram on stroke recurrence: A randomızed clınıcal trıal.ABSTRACT: Post-stroke depression is one of the main causes of cerebrovascular and cardiovascular diseases. The aim of the present study was to investigate the efficacy of citalopram on stroke recurrence. A 52-week, randomized, double-blind, studyinvolved 440 ischemic stroke patients with depression. Patients with depression who met depression criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV and V) and Hamilton Depression Rating Scale ≥ 8 (HAM-DRS) were dichotomized into patients receiving citalopram (225 patients), titrated according to clinical response, and patients with placebo (215 patients) for 52 weeks. The primary outcome measure was stroke recurrence and the secondary outcome measures were cardiovascular events and mortality. Stroke recurrence (66% vs 34%; P = 0.001) and cardiovascular events (76% vs. 24%; P = o.oo1) were significantly higher in the placebo group compared to those treated with citalopram. Multivariable analysis showed that hypertension, atrial fibrillation, and large-artery disease were significantly associated with stroke recurrence. Executive processing disorder was more associated with stroke recurrence than other neuropsychological disorders (OR, 1.74; CI95%, 1.04-2.89; P = 0.035). Survival analysis showed that treatment for depression interacted with time to reduce stroke recurrence by nearly half (39% vs. 61%; P = 0.05). The current study supports the importance of depression treatment in protecting the patients from recurrent strokes. This result warrants further studies to demonstrate the efficacy of depression treatment on stroke recurrence."
0,"TITLE: Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease.ABSTRACT: Inflammation contributes to cardiovascular disease and is exacerbated with increased adiposity, particularly omental adiposity; however, the role of epicardial fat is poorly understood.For these studies the expression of inflammatory markers was assessed in epicardial fat biopsies from coronary artery bypass grafting (CABG) patients using quantitative RT-PCR. Further, the effects of chronic medications, including statins, as well as peri-operative glucose, insulin and potassium infusion, on gene expression were also assessed. Circulating resistin, CRP, adiponectin and leptin levels were determined to assess inflammation.The expression of adiponectin, resistin and other adipocytokine mRNAs were comparable to that in omental fat. Epicardial CD45 expression was significantly higher than control depots (p < 0.01) indicating significant infiltration of macrophages. Statin treated patients showed significantly lower epicardial expression of IL-6 mRNA, in comparison with the control abdominal depots (p < 0.001). The serum profile of CABG patients showed significantly higher levels of both CRP (control: 1.28 +/- 1.57 microg/mL vs CABG: 9.11 +/- 15.7 microg/mL; p < 0.001) and resistin (control: 10.53 +/- 0.81 ng/mL vs CABG: 16.8 +/- 1.69 ng/mL; p < 0.01) and significantly lower levels of adiponectin (control: 29.1 +/- 14.8 microg/mL vs CABG: 11.9 +/- 6.0 microg/mL; p < 0.05) when compared to BMI matched controls.Epicardial and omental fat exhibit a broadly comparable pathogenic mRNA profile, this may arise in part from macrophage infiltration into the epicardial fat. This study highlights that chronic inflammation occurs locally as well as systemically potentially contributing further to the pathogenesis of coronary artery disease."
1,"TITLE: Obstetric risk factors for urinary incontinence and preventative pelvic floor exercises: cohort study and nested randomized controlled trial.ABSTRACT: We conducted a cohort study assessing risk factors for developing urinary incontinence following childbirth, and a pilot randomized controlled trial of a physiotherapist-led intervention to reduce incidence of incontinence. A total of 723 women were recruited to the cohort study, of which 234 entered the nested trial and were randomized to intensive training in pelvic floor exercises or standard information. At 6 months post-partum, 45% of women reported some incontinence problems. A pre-existing incontinence problem was the best predictor of future incontinence (odds ratio 4.49, 95% confidence interval (CI) 3.09-6.53). Chronic constipation (1.86, 1.03-3.34) and episiotomy in at least one delivery (1.96, 1.25-3.07) were also independent risk factors, while an epidural or spinal (0.62, 0.42-0.92) was protective. The intervention as designed did not help in preventing future incontinence (relative risk 1.28, 95% CI 0.98-1.67), but this may be due to the failure to persuade the women to return for the classes. Any intervention aimed at promoting postnatal pelvic floor exercises should be limited to women who have already been experiencing incontinence problems."
0,"TITLE: Evidence for distinct effects of GH and IGF-I in the metabolic syndrome.ABSTRACT: The metabolic syndrome is a cluster of cardiovascular risk factors which include central obesity, dyslipidaemia, glucose intolerance and hypertension. These risk factors are common in patients with growth hormone (GH) deficiency, suggesting a role for the somatotropic axis in the development of metabolic syndrome.We used factor analysis to investigate the relationships linking serum levels of GH and insulin-like growth factor I (IGF-I) to metabolic syndrome variables (high-density lipoprotein cholesterol, triglycerides, fasting glucose, blood pressure and waist circumference). We studied 359 men and 388 women from the Data from an Epidemiological Study on the Insulin Resistance syndrome (DESIR). Their age range was 30-64 years.Three independent latent factors explained 61% of the total variance in women and four factors explained 73% in men. In both men and women, IGF-I showed a strong positive correlation with the lipid factor and a negative correlation with the obesity/glucose factor. In women, GH showed a strong negative correlation with the obesity/glucose factor but not the lipid factor. In men, GH was unrelated to the lipid and obesity/glucose factors. The blood pressure factor was not related to GH or IGF-I. In contrast with IGF-I, GH was significantly lower in women with metabolic syndrome (1575 +/- 449 pg/ml) than in the other women (2121 +/- 520 pg/ml, P = 0.002). No significant difference was observed in men for GH or IGF-I.Our results support a link between the somatotropic axis and several features of the metabolic syndrome, and suggest distinct effects of GH and IGF-I on these parameters."
1,"TITLE: A five-day gradual reduction regimen of chlormadinone reduces premenstrual anxiety and depression: a pilot study.ABSTRACT: Anxiety and depression commonly occur in premenstrual dysphoric disorder (PMDD). The PMDD symptomatology disappears once the menstrual cycle reinitiates, resembling a withdrawal syndrome.The present study is a pilot, controlled, double-blind study exploring the effectiveness of a premenstrual 5-day gradual reduction regimen of chlormadinone acetate on PMDD. Volunteers received an initial dose of 10 mg (five 2-mg tablets) on the 24(th) day of the menstrual cycle and one-fifth of the dose less (one tablet) each day until a dose of 2 mg (one 2-mg tablet) was reached on the 28(th) day of the menstrual cycle. The control group received placebo with a similar regimen.The 5-day gradual reduction regimen of chlormadinone significantly improved (F(3.76) = 3.29, p <0.02) the daily symptoms report (DSR) scores by the third month of treatment. The resulting relative risk was 4.09 (confidence interval: 1.15-14.57, p <0.005, 95% CI). Compared to placebo, chlormadinone clinically and statistically reduced the severity of depression, anxiety, food cravings, mood swings and cramps. A statistical reduction of symptoms such as poor coordination, irritability, feeling out of control, hopelessness, decreased interest and headache was detected but was not clinically relevant. No changes occurred in concentration difficulties, tiredness, insomnia, swelling, breast tenderness and aches. As side effects, 30% of the volunteers showed changes in the length of the menstrual cycle, and 15% experienced dyspepsia.A 5-day gradual reduction regimen of chlormadinone improves some of the discomforting ailments associated with PMDD, namely, depression and anxiety."
0,"TITLE: Vitamin B6 status improves in overweight/obese women following a hypocaloric diet rich in breakfast cereals, and may help in maintaining fat-free mass.ABSTRACT: To analyze the changes in vitamin B6 status in women following slightly hypocaloric diets based on the relative increase consumption of foods whose intakes are below those recommended, and to study how these changes influence the proportion of fat-free mass.Intervention study of two slightly hypocaloric diets: diet V (increased consumption of vegetables), or diet C (increased consumption of cereals, especially breakfast cereals).A total of 49 women with a body mass index (BMI) of 25-35 kg/m2.Dietetic, anthropometric and biochemical data were collected at the start of the study and at 2 and 6 weeks.Both the C and V subjects showed a reduction in their energy intake, body weight, BMI and fat mass. Pyridoxine intake increased in both groups and plasma pyridoxal phosphate (PLP) levels increased only with diet C. An association was found between the increase in plasma PLP at 6 weeks and the increase in pyridoxine intake (r=0.451; P<0.01). Multiple regression analysis showed a positive association between the increase in PLP at the end of the study and the increases in the pyridoxine intake, B6 density or B6/protein ratio. At the end of the study, and only in those women whose PLP levels were increased, the higher the increase in PLP level, the higher the increase in fat-free mass percentage (r=0.4426, P<0.05).Interventions aimed at weight control should also try to maintain or improve nutritional status. A diet rich in cereals (especially fortified breakfast cereals) appears to be useful in improving vitamin B6 status. Such an improvement could help maintain fat-free mass during periods of weight loss."
1,"TITLE: Dietary arginine supplementation speeds pulmonary VO2 kinetics during cycle exercise.ABSTRACT: To test the hypothesis that L-arginine (the substrate for nitric oxide synthase [NOS]) administration slows the VO2 kinetics at the onset of moderate-intensity exercise in humans.Seven physically active males were randomly assigned to receive either placebo (lactose) or L-arginine hydrochloride capsules (7.2 g x d(-1)) for 14 d in a double-blind crossover design, with a 7-d washout period between the two conditions. On day 11 and day 14 of each condition, the subjects completed two consecutive 6-min bouts of cycle exercise at 80% of the ventilatory threshold with a 12-min rest interval. VO2 was measured on a breath-by-breath basis, and VO2 kinetics were determined with a single exponential model from the averaged data derived from four repetitions. Capillary and venous blood samples were taken to determine plasma [La] and serum [arginine], respectively.There were no differences in circulating lactate either before or during exercise. However, serum [arginine] was higher (P < 0.05) in the arginine condition at rest (119.0 +/- 12.6 vs 103.6 +/- 15.7 micromol x L(-1) in the control condition) and after exercise (113.3 +/- 26.0 vs 103.8 +/- 12.6 micromol x L(-1) in the control condition). With regard to the pulmonary VO2 kinetics, no significant difference was observed in the time at which the phase II response emerged or in the phase II amplitude between the two conditions. However, contrary to our hypothesis, the time constant was significantly reduced after arginine administration (i.e., 13.9 +/- 3.1 vs 15.8 +/- 2.6 s in the control condition, P < or = 0.014).Exogenous L-arginine administration speeds the phase II pulmonary VO2 response by 12% at the onset of moderate-intensity exercise in humans."
0,"TITLE: Estimating the 10-year risk of cardiovascular disease and its economic consequences, by the level of adherence to the Mediterranean diet: the ATTICA study.ABSTRACT: In this study this traditional diet was assessed in relation to coronary heart disease risk and its economic consequences, in a cross-sectional study with economic analysis. From May 2001 to December 2002 we randomly enrolled 1,514 adult men and 1,528 women, without any clinical evidence of cardiovascular disease. Adherence to the Mediterranean diet was ascertained through a food-frequency questionnaire and a special diet score that incorporated the inherent characteristics of this dietary pattern. The 10-year absolute risk for coronary heart disease was derived from the Framingham equations. Persons with a 10-year risk greater than 10% were considered as potential hospitalized patients. The health care cost of hospitalization due to an event was estimated in 690euro per patient. Of the participants who were ""closer"" to the Mediterranean diet (i.e., above the median diet score) and of those ""away"" from this dietary pattern, 4.2% and 39.8%, respectively, had a 10-year coronary risk greater than 10% (P < .001). Moreover, participants ""closer"" to the Mediterranean diet had a 43% (odds ratio = 0.57, 95% confidence interval 0.38 to 0.86) lower likelihood of having a 10-year coronary risk greater than 10%, after adjusting for potential confounders. Total health care cost was estimated to be 336.720euro in those who were ""away"" and 35.880euro in those who were closer to this diet pattern. Life-years lost due to disability was 6.8 in those who were ""away"" and 0.9 in those ""close"" to this pattern. The incremental cost-effectiveness ratio was 50.989euro (i.e., the additive health care cost due to an unhealthy diet for each year lost). The implementation of the Mediterranean dietary pattern may lead to an improvement in life expectancy, a net gain to health, and a reduction in total lifetime costs."
0,"TITLE: Loneliness and health care consumption among older people.ABSTRACT: Few studies have investigated loneliness in relation to health care consumption among frail older people. The aim of this study was to examine loneliness, health-related quality of life (HRQoL), and health complaints in relation to health care consumption of in- and outpatient care among frail older people living at home. The study, with a cross-sectional design, comprised a sample of 153 respondents aged from 65 years (mean age 81.5 years) or older, who lived at home and were frail. Data was collected utilising structured interviews in the respondent's home assessing demographic data, loneliness, HRQoL and health complaints. Patient administrative registers were used to collect data on health care consumption. Loneliness was the dependent variable in the majority of the analyses and dichotomised. For group comparisons Student's t-test, Mann-Whitney U-test and Chi-square test were used. The results showed that 60% of the respondents had experienced loneliness during the previous year, at least occasionally. The study identified that lonely respondents had a lower HRQoL (p = 0.022), with a higher total number of reported health complaints (p = 0.001), and used more outpatient services including more acute visits at the emergency department, compared to not lonely respondents (p = 0.026). Multiple linear regression analysis showed that a depressed mood was independently associated to total use of outpatient care (B = 7.4, p < 0.001). Therefore, it might not be loneliness, per se, that is the reason for seeking health care. However, reasons for using health care services are difficult to determine due to the complex situation for the frail older person. To avoid emergency department visits and to benefit the well-being of the frail older person, interventions targeting the complex health situation, including loneliness, are suggested."
1,"TITLE: Village-randomized clinical trial of home distribution of zinc for treatment of childhood diarrhea in rural Western kenya.ABSTRACT: Zinc treatment shortens diarrhea episodes and can prevent future episodes. In rural Africa, most children with diarrhea are not brought to health facilities. In a village-randomized trial in rural Kenya, we assessed if zinc treatment might have a community-level preventive effect on diarrhea incidence if available at home versus only at health facilities.We randomized 16 Kenyan villages (1,903 eligible children) to receive a 10-day course of zinc and two oral rehydration solution (ORS) sachets every two months at home and 17 villages (2,241 eligible children) to receive ORS at home, but zinc at the health-facility only. Children's caretakers were educated in zinc/ORS use by village workers, both unblinded to intervention arm. We evaluated whether incidence of diarrhea and acute lower respiratory illness (ALRI) reported at biweekly home visits and presenting to clinic were lower in zinc villages, using poisson regression adjusting for baseline disease rates, distance to clinic, and children's age.There were no differences between village groups in diarrhea incidence either reported at the home or presenting to clinic. In zinc villages (1,440 children analyzed), 61.2% of diarrheal episodes were treated with zinc, compared to 5.4% in comparison villages (1,584 children analyzed, p<0.0001). There were no differences in ORS use between zinc (59.6%) and comparison villages (58.8%). Among children with fever or cough without diarrhea, zinc use was low (<0.5%). There was a lower incidence of reported ALRI in zinc villages (adjusted RR 0.68, 95% CI 0.46-0.99), but not presenting at clinic.In this study, home zinc use to treat diarrhea did not decrease disease rates in the community. However, with proper training, availability of zinc at home could lead to more episodes of pediatric diarrhea being treated with zinc in parts of rural Africa where healthcare utilization is low.ClinicalTrials.gov NCT00530829."
1,"TITLE: Use of oesophageal flap valvuloplasty and wrapping suturing technique in preventing postoperative complications after oesophagectomy for oesophageal cancer.ABSTRACT: Esophagogastrostomy for oesophageal cancer is the standard surgical treatment. However, traditional techniques have been associated with high frequency of anastomotic complications. The purpose of this study is to clarify the superiority of the oesophageal flap valvuloplasty and wrapping suturing technique in preventing postoperative complications after oesophagectomy for oesophageal cancer.A prospective, randomised study was performed on 394 patients treated for esophageal cancer between January 2006 and December 2010. The trial registry number is ChiCTR-TRC-13003817 in the Chinese Clinical Trial Registry.Anastomotic leaks occurred in four patients in group A (2.1%) and in twelve patients in group B (6.2%) with statistically significant (P = 0.038). During the evaluation of benign stricture seven patients were excluded for hospital mortality. Thirty three patients in group A (6.9%) and 25 patients in group B (13.2%) occurred anastomotic stricture respectively (P = 0.044). Furthermore, reflux oesophagitis and Barrett's epithelium were found in 105 patients (55.3%) of group B, and 54 (28.7%) patients in group A (P < 0.001).The oesophageal flap valvuloplasty and wrapping suturing technique decreased anastomotic leakage incidence and stricture rate thereby decreasing the morbidity and mortality. This procedure also prevented the occurrence of gastroesophageal reflux after esophagectomy."
1,"TITLE: A cluster randomized controlled trial to reduce childhood diarrhea using hollow fiber water filter and/or hygiene-sanitation educational interventions.ABSTRACT: Safe domestic potable water supplies are urgently needed to reduce childhood diarrheal disease. In periurban neighborhoods in Cochabamba, Bolivia, we conducted a cluster randomized controlled trial to evaluate the efficacy of a household-level hollow fiber filter and/or behavior change communication (BCC) on water, sanitation, and hygiene (WASH) to reduce the diarrheal disease in children less than 5 years of age. In total, 952 households were followed for a period of 12 weeks post-distribution of the study interventions. Households using Sawyer PointONE filters had significantly less diarrheal disease compared with the control arm during the intervention period, which was shown by diarrheal prevalence ratios of 0.21 (95% confidence interval [95% CI] = 0.15-0.30) for the filter arm and 0.27 (95% CI = 0.22-0.34) for the filter and WASH BCC arm. A non-significant reduction in diarrhea prevalence was reported in the WASH BCC study arm households (0.71, 95% CI = 0.59-0.86)."
1,"TITLE: Twenty-four hour ambulatory blood pressure for the management of antihypertensive treatment: a randomized controlled trial.ABSTRACT: The aim of this study was to assess whether the use of 24-h blood pressure (BP) measurement in the management of antihypertensive therapy improves BP in patients with sustained hypertension. Patients with sustained hypertension (office BP > or =140/90 mm Hg, and 24-h systolic BP > or =130/80 mm Hg) were randomly assigned to a strategy using 24-h BP to manage antihypertensive treatment (target <130/80 mm Hg) or to a standard strategy using office BP (target <140/90 mm Hg). The primary end point was change in 24-h systolic BP at 1 year of follow-up. We included 136 patients in the primary analysis. After 1 year of follow-up, the change in 24-h systolic BP was significantly greater in the ambulatory BP group compared with the office BP group (mean difference (95% confidence interval) -3.6 (-7.0, -0.3), P=0.03). Intention-to-treat analysis revealed essentially unchanged results. The mean number of antihypertensive drugs per participant at 1 year of follow-up was 1.76+/-1.1 and 1.95+/-0.9 in the ambulatory and office BP group, respectively (P=0.049). The benefit of ambulatory BP monitoring was mainly seen in patients with previously known hypertension (mean difference -7.2 (-11.6, -2.8), P=0.002), but not in those with newly detected hypertension (mean difference 0.2 (-4.9, 5.4), P=0.93). In conclusion, using 24-h BP for the management of antihypertensive therapy in patients with sustained hypertension leads to a greater BP reduction compared with a standard treatment strategy using office BP, although fewer antihypertensive drugs were used in the ambulatory BP group."
1,"TITLE: Liver dysfunction in paediatric obesity: a randomized, controlled trial of metformin.ABSTRACT: In a previous study we showed that metformin reduced BMI z-scores and fasting glucose and insulin concentrations, and increased whole body insulin sensitivity in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. We analyzed the data from this study to determine (a) if metformin reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations during the 6-month trial, and (b) if the response to pharmacotherapy varied along gender or ethnic lines.The 6-month trial was randomized, double blinded and placebo controlled; a total of 14 metformin-treated (500 mg bid) and 15 placebo-treated subjects completed the study. There were no dietary restrictions.In obese adolescents fed ad libitum, metformin (a) prevented the rise in ALT concentrations that were observed in placebo-treated subjects at the 3 to 5 month time-points (p < 0.05); (b) reduced (p < 0.01) the percentage of all ALT values exceeding 40 U/L; and (c) caused a modest (10%) but statistically significant (p < 0.05) reduction in serum ALT in Caucasian subjects. Metformin had no effect on ALT levels or the ALT to AST ratio in the five African American adolescents enrolled in the study but reduced their fasting insulin concentrations from 26.1 to 19.5 muU/mL (p < 0.05).Our findings suggest that metformin might reduce the rates or severity of liver dysfunction in selected high-risk adolescents."
1,"TITLE: Antiinflammatory effect of sevoflurane in open lung surgery with one-lung ventilation.ABSTRACT: To prospectively assess the antiinflammatory effect of volatile anesthetic sevoflurane in patients undergoing open lung surgery with one lung ventilation (OLV).This prospective, randomized study included 40 patients undergoing thoracic surgery with OLV (NCT02188407). The patients were randomly allocated into two equal groups that received either propofol or sevoflurane. Four patients were excluded from the study because after surgery they received blood transfusion or non-steroid antiinflammatory drugs. Inflammatory mediators (interleukins 6, 8, and 10, C-reactive protein [CRP], and procalcitonin) were measured perioperatively. The infiltration of the nonoperated lung was assessed on chest x-rays and the oxygenation index was calculated. The major postoperative complications were counted.Interleukin 6 levels were significantly higher in propofol than in sevoflurane group (P=0.014). Preoperative CRP levels did not differ between the groups (P=0.351) and in all patients they were lower than 20 mg/L, but postoperative CRP was significantly higher in propofol group (31±6 vs 15±7 ng/L; P=0.035); Pre- and postoperative procalcitonin was within the reference range (<0.04 µg/L) in both groups. The oxygenation index was significantly lower in propofol group (339±139 vs 465±140; P=0.021). There was no significant difference between the groups in lung infiltrates (P=0.5849). The number of postoperative adverse events was higher in propofol group, but the difference was not-significant (5 vs 1; P=0.115).The study suggests an antiinflammatory effect of sevoflurane in patients undergoing thoracotomy with OLV."
0,"TITLE: Choice stepping reaction time test using exergame technology for fall risk assessment in older people.ABSTRACT: Accidental falls remain an important problem in older people. Stepping is a common task to avoid a fall and requires good interplay between sensory functions, central processing and motor execution. Increased choice stepping reaction time has been associated with recurrent falls in older people. The aim of this study was to examine if a sensor-based Exergame Choice Stepping Reaction Time test can successfully discriminate older fallers from non-fallers. The stepping test was conducted in a cohort of 104 community-dwelling older people (mean age: 80.7 ± 7.0 years). Participants were asked to step laterally as quickly as possible after a light stimulus appeared on a TV screen. Spatial and temporal measurements of the lower and upper body were derived from a low-cost and portable 3D-depth sensor (i.e. Microsoft Kinect) and 3D-accelerometer. Fallers had a slower stepping reaction time (970 ± 228 ms vs. 858 ± 123 ms, P = 0.001) and a slower reaction of their upper body (719 ± 289 ms vs. 631 ± 166 ms, P = 0.052) compared to non-fallers. It took fallers significantly longer than non-fallers to recover their balance after initiating the step (2147 ± 800 ms vs. 1841 ± 591 ms, P = 0.029). This study demonstrated that a sensor-based, low-cost and easy to administer stepping test, with the potential to be used in clinical practice or regular unsupervised home assessments, was able to identify significant differences between performances by fallers and non-fallers."
1,"TITLE: Imbalance between nitric oxide generation and oxidative stress in patients with peripheral arterial disease: effect of an antioxidant treatment.ABSTRACT: Nitric oxide (NO), a potent vasodilator produced by endothelial cells, is reduced in patients with peripheral arterial disease (PAD), but the mechanism has not been fully elucidated. Because NO is rapidly inactivated by superoxide anion, we speculated that enhanced oxidative stress could lower NO generation. The aim of our study was to investigate if an imbalance between oxidative stress and NO does exist in patients with PAD and if an increase of NO formation could be achieved by an antioxidant treatment.In a first study, serum levels of nitrite and nitrate (NOx), markers of NO generation, and 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative stress and maximal walking distance (MWD), were measured in 40 PAD patients and 40 controls. In a second study, 10 PAD patients were randomly allocated in a crossover design to intravenous propionyl-L-carnitine (6 g/day) or placebo for 7 days, with a washout of 30 days between the two phases of the trial. Serum levels of NOx and 8-OHdG were measured before and after the study.Compared with controls, serum levels of 8-OHdG (mean +/- SD) were significantly increased in PAD patients (4.4 +/- 3.1 ng/mL vs 2.4 +/- 1.2 ng/mL; P < .001), and serum levels of NOx were significantly decreased (11.6 +/- 6 microM vs 17 +/- 6.1 microM; P < .001). Levels of 8-OHdG and NOx were inversely correlated (r = -0.879; P < .001). Serum levels 8-OHdG were inversely correlated with MWD (r = -0.48, P = .002). The interventional trial showed no changes in the patients given placebo. Patients treated with propionyl-L-carnitine showed a significant increase of MWD from 101 +/- 31 meters to 129 +/- 35 meters (P = .007) and in NOx from 14.5 +/- 4.5 microM to 17.1 +/- 3.8 microM (P = .007). A significant decrease of 8-OHdG from 3.6 +/- 1.1 ng/mL to 2.6 +/- 1 ng/mL was also found (P = .005.)This study suggests that in PAD patients, the reduction of NO generation could be dependent upon enhanced oxidative stress."
1,"TITLE: The effects of modified ultrafiltration on pulmonary function and transfusion requirements in patients underwent coronary artery bypass graft surgery.ABSTRACT: The inflammatory response after cardiac surgery increases vascular permeability leading to higher mortality and morbidity in the post operative time. The modified ultrafiltration (MUF) had shown benefits on respiratory, and hemodynamic in pediatric patients. This approach in adults is not well established yet. We hypothesize that modified ultrafiltration may improve respiratory, hemodynamic and coagulation function in adults after cardiac surgeries.A prospective randomized study was carried out with 37 patients who underwent coronary artery bypass graft surgery (CABG) were randomized either to MUF (n=20) at the end of bypass or to control (no MUF) (n=17). The anesthesia and ICU team were blinded for the group selection. The MUF were carried out for 15 minutes after the end of bypass. The patients data were taken at beginning of anesthesia, ending of bypass, ending MUF, 24 hours, and 48 hours after surgery. For clinical outcome the pulmonary, hemodynamic and coagulation function were evaluated.We observed lower drain loss in the MUF group compared to control group after 48 hours (598 +/- 123 ml vs. 848 +/- 455 ml; P=0.04) and required less red blood cells units transfusion compared to control group (0.6 +/- 0.6 units/patient vs.1.6 +/- 1.1 units/patient; P=0.03). The MUF group showed lower airway resistance (9.3 +/- 0.4 cmH2O.L-1s-1 vs. 12.1 +/- 0.8 cmH2O.L-1s-1; P=0.04). There were no deaths in both groups.The MUF reduces post operatory bleeding and red blood cells units transfusion, but with no differences on clinical outcome were observed. The routinely MUF employment was not associated with hemodynamic instability."
1,"TITLE: Evaluation of the haemodynamic characteristics of drug-eluting stents at implantation and at follow-up.ABSTRACT: The aim of this study was to investigate the physiologic parameters: fractional flow reserve (FFR), hyperaemic trans-stent gradient (HTG), and wall shear stress (WSS) at implantation and at 6-month follow-up in the drug-eluting sirolimus stent and in its bare metal counterpart implanted in pairs within the same patient.Twenty patients, accepted for percutaneous coronary intervention of at least two coronary arteries with comparable vessel and stenosis characteristics, received at random one sirolimus-eluting stent and one bare metal stent (BMS). Coronary pressure, FFR, HTG, and WSS were measured just after stent implantation and at 6-month follow-up. At 6-month follow-up, FFR was significantly higher in the sirolimus group compared with the bare metal group (0.91+/-0.05 vs. 0.83+/-0.10, P=0.027) and HTG was significantly lower (1.2+/-1.2 vs. 7.5+/-8.1 mmHg, P<0.001). In-stent WSS at 6 months remained normal in the sirolimus group but was elevated in the bare metal group (1.6+/-0.7 vs 3.9+/-3.1 Pa, respectively, P=0.003).The physiologic characteristics of the drug-eluting sirolimus stents were superior to those of the equivalent BMS. Six months after implantation, FFR was significantly higher, HTG was significantly lower in arteries treated by a sirolimus stent, and normal WSS was maintained within the drug-eluting stent."
1,"TITLE: Rates of luteolysis and pregnancy in dairy cows after treatment with cloprostenol or dinoprost.ABSTRACT: Our objective was to determine whether rates of luteolysis or pregnancy differed in lactating dairy cows of known progesterone status and either known or unknown luteal status after either cloprostenol or dinoprost was injected as part of a timed-insemination program. In Experiment 1, 2358 lactating dairy cows in six herds were given two injections of PGF(2 alpha) 14 d apart (Presynch), with the second injection given 12 to 14 d before the onset of a timed AI protocol (Ovsynch). Cows (n=1094) were inseminated when detected in estrus after the Presynch PGF(2 alpha) injections. Cows not inseminated (n=1264) were enrolled in the Ovsynch protocol and assigned randomly to be treated with either cloprostenol or dinoprost as part of the timed-AI protocol. In cows having pretreatment concentrations of progesterone >or= 1 ng/mL and potentially having a functional corpus luteum (CL) responsive to cloprostenol (n=558) or dinoprost (n=519), dinoprost increased (P<0.05) luteal regression from 86.6 to 91.3%. Despite a significant increase in luteolysis, pregnancies per AI did not differ between luteolytic agents (dinoprost=37.8% and cloprostenol=36.7%). Fertility was improved in cows of both treatments having reduced concentrations of progesterone at 72 h and in cows showing signs of estrus. In Experiment 2, an ovulation-resynchronization program was initiated with GnRH or saline in 427 previously inseminated lactating dairy cows of unknown pregnancy status in one herd. Seven days later, pregnancy was diagnosed and nonpregnant cows were blocked by number of CL and assigned randomly to be treated with cloprostenol or dinoprost. Compared with cloprostenol, dinoprost increased (P<0.05) luteal regression from 69.1 to 78.5%, regardless of the number of CL present or the total luteal volume per cow. Pregnancies per AI did not differ between dinoprost (32.8%) and cloprostenol (31.3%). Although dinoprost was more effective than cloprostenol at inducing luteolysis in lactating dairy cows exposed to an Ovsynch or ovulation-resynchronization protocol, resulting fertility did not differ between products."
1,"TITLE: Comparison of naproxen with placebo for the management of noncyclical breast pain: a randomized, double-blind, controlled trial.ABSTRACT: Breast pain is a common symptom in patients attending breast clinics. Although most patients experience mastalgia of mild to moderate severity, approximately 15% of patients suffer from severe pain that causes significant distress and some disturbance in their daily life that lead them to seek treatment. Despite a considerable number of drugs suggested for decreasing the severity of mastalgia, there is no standard treatment for the complaint. In this study, we investigated the effect of naproxen on reducing the complaint of breast pain compared with placebo.Eighty-one women suffering from noncyclic breast pain were recruited to a randomized, double-blind, clinical trial between January 2002 and September 2004. All patients were suffering from this complaint for at least 3 months before the study. Patients were randomly assigned to two groups. Patients in the case group received naproxen 250 mg BD. Patients in the placebo group took placebo in a similar manner. The intensity of mastalgia was assessed before and twice after intervention by using a Visual Analogue Scale.Forty-two of 81 patients were recruited randomly as cases and the remaining 39 were assigned placebo. Of these 24 and 22 patients fulfilled the study protocol respectively. The mean age of patients was 35 (SD = 7.5; range, 19-55) years. The mean pain severity at the beginning of the study was 5.8 and 6.1 in naproxen and placebo groups, respectively. The severity of pain was decreased significantly at the end of the study in both groups (3.9 in patients and 3.7 in controls (P = 0.005 and 0.0001)). Although the decrease in pain severity in each individual group was statistically significant, it was not significant compared with one another (P = 0.64).Breast pain is a complex symptom that can be relieved significantly with reassurance. According to the result of this study, naproxen has no superiority over placebo in reducing noncyclic breast pain."
1,"TITLE: Troponin levels after ICD implantation with and without defibrillation testing and their predictive value for outcomes: Insights from the SIMPLE trial.ABSTRACT: The Shockless IMPLant Evaluation trial randomized 2500 patients receiving a first implantable cardioverter-defibrillator (ICD)/cardiac resynchronization therapy-defibrillator device to have either defibrillation testing (DT) or no DT. It demonstrated that DT did not improve shock efficacy or reduce mortality.This prospective substudy evaluated the effect of DT on postoperative troponin levels and their predictive value for total and arrhythmic mortality.Troponin levels were measured between 6 and 24 hours after ICD implantation in 2200 of 2500 patients.A postoperative serum troponin level above the upper limit of normal (ULN) was more common in patients undergoing DT (n = 509 [46.4%]) than in those not subjected to DT (n = 456 [41.3%]; P = .02). After excluding patients with known preoperative troponin levels above the ULN, consistent findings were observed (42.1% vs 37.5%; P = .04). During a mean follow-up of 3.1 ± 1.0 years, the annual mortality rate was increased in patients with postoperative troponin levels above the ULN (adjusted hazard ratio [HR] 1.43; 95% confidence interval [CI] 1.15-1.76; P = .001) irrespective of DT or no DT. Likewise, patients with elevated troponin levels had a significantly higher risk of arrhythmic death (adjusted HR 1.80; 95% CI 1.23-2.63; P = .002). The rate of first appropriate ICD shock (adjusted HR 0.89; 95% CI 0.71-1.12; P = .32) or failed appropriate shock (adjusted HR 1.02; 95% CI 0.59-1.76; P = .95) was similar in patients with or without troponin elevation.DT at the time of ICD implantation is associated with increased troponin levels, indicating subclinical myocardial injury caused by the procedure. Elevated troponin levels but not DT seem to predict clinical outcomes in ICD recipients."
1,"TITLE: Efficacy and safety of intravenous theophylline administration for treatment of mild acute exacerbation of bronchial asthma.ABSTRACT: The present study was designed to evaluate the efficacy and safety of intravenously administered theophylline (IAT) for the treatment of an acute exacerbation of bronchial asthma. The theophylline was solubilized and not combined with ethylenediamine.The subjects were 22 asthmatic patients with mild acute exacerbation of bronchial asthma. All patients had been taking oral sustained-release theophylline and their serum concentrations of theophylline were measured. The 16 patients whose serum theophylline concentrations were <13 microg/mL were randomly selected and treated with IAT (200 mg theophylline in 200 mL saline) for 2 h. Six patients were randomly selected as controls and received 200 mL of saline. Pulmonary function and asthma severity (Borg scale) before and after treatment were measured.After IAT, both PEF (before IAT, 313+/-79 L/min; after IAT, 335+/-107; P<0.05) and FEV(1) (before IAT, 1.66+/-0.47 L; after IAT, 1.83+/-0.44; P<0.05) increased significantly. Furthermore, their severity of asthma as assessed by the Borg scale (before IAT, 2.5+/-1.2; after IAT, 1.3+/-1.0; P<0.05) improved significantly. In contrast, neither FEV(1), PEF, severity of asthma or Borg scale changed significantly in the group who only received saline. None of the patients treated in this study had any adverse effects.These results suggest that IAT is useful for patients with mild acute exacerbation of bronchial asthma and is safe if serum theophylline concentrations are measured."
1,"TITLE: Oral nutritional supplements containing (n-3) polyunsaturated fatty acids affect the nutritional status of patients with stage III non-small cell lung cancer during multimodality treatment.ABSTRACT: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), (n-3) fatty acids from fish oil, have immune-modulating effects and may improve nutritional status in cancer. The objective of this study was to investigate the effects of an oral nutritional supplement containing (n-3) fatty acids on nutritional status and inflammatory markers in patients with non-small cell lung cancer (NSCLC) undergoing multimodality treatment. In a double-blind experiment, 40 patients with stage III NSCLC were randomly assigned to receive 2 cans/d of a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids (2.0 g EPA + 0.9 g DHA/d) or an isocaloric control supplement. EPA in plasma phospholipids, energy intake, resting energy expenditure (REE), body weight, fat free mass (FFM), mid-upper arm circumference (MUAC), and inflammatory markers were assessed. Effects of intervention were analyzed by generalized estimating equations and expressed as regression coefficients (B). The intervention group (I) had a better weight maintenance than the control (C) group after 2 and 4 wk (B = 1.3 and 1.7 kg, respectively; P < 0.05), a better FFM maintenance after 3 and 5 wk (B = 1.5 and 1.9 kg, respectively; P < 0.05), a reduced REE (B = -16.7% of predicted; P = 0.01) after 3 wk, and a trend for a greater MUAC (B = 9.1; P = 0.06) and lower interleukin-6 production (B = -27.9; P = 0.08) after 5 wk. After 4 wk, the I group had a higher energy and protein intake than the C group (B = 2456 kJ/24 h, P = 0.03 and B = 25.0 g, P = 0.01, respectively). In conclusion, a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids beneficially affects nutritional status during multimodality treatment in patients with NSCLC."
1,"TITLE: Improvement in fibromyalgia symptoms with acupuncture: results of a randomized controlled trial.ABSTRACT: To test the hypothesis that acupuncture improves symptoms of fibromyalgia.We conducted a prospective, partially blinded, controlled, randomized clinical trial of patients receiving true acupuncture compared with a control group of patients who received simulated acupuncture. All patients met American College of Rheumatology criteria for fibromyalgia and had tried conservative symptomatic treatments other than acupuncture. We measured symptoms with the Fibromyalgia Impact Questionnaire (FIQ) and the Multidimensional Pain Inventory at baseline, immediately after treatment, and at 1 month and 7 months after treatment. The trial was conducted from May 28, 2002, to August 18, 2003.Fifty patients participated in the study: 25 in the acupuncture group and 25 in the control group. Total fibromyalgia symptoms, as measured by the FIQ, were significantly improved in the acupuncture group compared with the control group during the study period (P = .01). The largest difference in mean FIQ total scores was observed at 1 month (42.2 vs 34.8 in the control and acupuncture groups, respectively; P = .007). Fatigue and anxiety were the most significantly improved symptoms during the follow-up period. However, activity and physical function levels did not change. Acupuncture was well tolerated, with minimal adverse effects.This study paradigm allows for controlled and blinded clinical trials of acupuncture. We found that acupuncture significantly improved symptoms of fibromyalgia. Symptomatic improvement was not restricted to pain relief and was most significant for fatigue and anxiety."
1,"TITLE: Perioperative pregabalin improves pain and functional outcomes 3 months after lumbar discectomy.ABSTRACT: Patient outcome after lumbar discectomy for radicular low back pain is variable and the benefit is inconsistent. Many patients continue to experience pain 3 months after surgery. Pregabalin, a membrane stabilizer, may decrease perioperative central sensitization and subsequent persistent pain.Forty patients undergoing lumbar discectomy were randomly allocated to receive either pregabalin (300 mg at 90 minutes preoperatively and 150 mg at 12 and 24 hours postoperatively) or placebo at corresponding times in a double-blinded manner. Our primary outcome was the change in the present pain intensity (PPI) (visual analog scale [VAS], 0-100 mm [PPI-VAS, McGill Pain Questionnaire]) from preoperatively to 3 months postoperatively.The decrease in PPI-VAS score at 3 months was greater in patients who received pregabalin (37.6 +/- 19.6 mm) (mean +/- sd) than those who received placebo (25.3 +/- 21.9 mm) (P = 0.08). The Roland Morris disability score at 3 months was less in patients who received pregabalin (2.7 +/- 2.4) than in those who received placebo (5.6 +/- 4.8) (P = 0.032). Pregabalin administration was associated with greater pain tolerance thresholds in both lower limbs compared with placebo at 24 hours postoperatively.Perioperative pregabalin administration is associated with less pain intensity and improved functional outcomes 3 months after lumbar discectomy."
0,"TITLE: Urinary isoflavonoid excretion and soy consumption in three generations of Japanese women in Hawaii.ABSTRACT: To explore soy intake and urinary isoflavonoid excretion within several generations of American-Japanese women based on the hypothesis that earlier generations excrete higher levels of urinary isoflavonoids, in particular the metabolite equol, than later generations.A convenience sample of 43 women from 19 families aged 18-78 years, all of whom reported at least 50% Japanese ancestry.Each woman collected overnight urine samples at baseline and after consuming one serving of soymilk, both samples were analyzed for the isoflavonoids daidzein, genistein and equol using liquid chromatography-mass spectrometry.Median isoflavone intakes during the last year were 7.2 mg/day for the first generation, 7.3 mg/day for the second generation and 6.3 mg/day for the third generation (P=0.36). At baseline, the median isoflavonoid excretion for the first generation was nonsignificantly higher than for later generations (190, 86 and 42 nmol/h; P=0.20) but after intervention, the median urinary isoflavonoid excretion was very similar for the three groups: 2465, 1895 and 2775 nmol/h (P=0.70). Following intervention, a nonsignificantly higher proportion of older than younger women (53 vs 32 and 33%; P=0.41) excreted the metabolite equol. The respective median equol excretion rates by generation following intervention were 39.5, 4.2 and 3.5 nmol/h (P=0.04).This small investigation among three generations of Japanese-Americans detected a higher equol production among older women after a soy challenge, but no difference in the excretion of total isoflavonoids after a standardized dose of soymilk was observed."
1,"TITLE: A randomized trial in patients undergoing percutaneous coronary angioplasty: roxithromycin does not reduce clinical restenosis but angioplasty increases antibody concentrations against Chlamydia pneumoniae.ABSTRACT: Elevated antibodies against Chlamydia pneumoniae have been associated with coronary artery disease. In patients undergoing percutaneous coronary angioplasty, we therefore investigated the effect of roxithromycin on symptomatic restenosis and determined antichlamydial antibodies as well as inflammatory and immunological parameters.A total of 327 patients undergoing coronary angioplasty were randomized to roxithromycin or placebo and followed-up for 1 year. Antibodies were determined by microimmunofluorescence and enzyme-linked immunosorbent assay; C-reactive protein, interleukin-10, tumor necrosis factor-alpha (TNF-alpha), and eotaxin were determined by enzyme-linked immunosorbent assay.Although the frequency of restenosis was not affected by roxithromycin (25 restenoses vs 32 in the control group), antichlamydial antibodies increased during follow-up (anti-CP IgG +12 +/- 2%, P < .001). Concentrations of TNF-alpha and eotaxin increased as well (TNF-alpha +9 +/- 1% and eotaxin +10 +/- 2%) and correlated with antichlamydial antibody concentrations (TNF-alpha, r = 0.23, P = .02; eotaxin, r = 0.32, P = .002).Treatment with roxithromycin was not associated with a reduction of symptomatic restenoses. During follow-up, a marked increase in antichlamydial antibodies, TNF-alpha, and eotaxin was observed, suggesting that angioplasty-induced plaque rupture induces a specific immunological response without activation of inflammatory mechanisms as represented by C-reactive protein. Whether this mechanism occurs in all plaque ruptures remains to be determined."
1,"TITLE: Oral and Vaginal Tenofovir for Genital Herpes Simplex Virus Type 2 Shedding in Immunocompetent Women: A Double-Blind, Randomized, Cross-over Trial.ABSTRACT: Tenofovir is a potent anti-human immunodeficiency virus (HIV) agent that decreased risk of herpes simplex virus type 2 (HSV-2) acquisition in HIV pre-exposure prophylaxis trials. Whether tenofovir has utility in established HSV-2 disease is unclear.We randomized immunocompetent women with symptomatic HSV-2 infection to oral tenofovir disoproxil fumarate (TDF)/placebo vaginal gel, oral placebo/tenofovir (TFV) vaginal gel, or double placebo (ratio 2:2:1) in a one-way cross-over trial. Women collected genital swabs twice daily for HSV PCR during 4-week lead-in and 5-week treatment phases. The primary intent-to-treat end point was within-person comparison of genital HSV shedding and lesion rates.64 women completed the lead-in phase and were randomized. Neither TDF nor TFV gel decreased overall shedding or lesion rate in the primary analysis; TFV gel decreased quantity of HSV DNA by -0.50 (-0.86-0.13) log10 copies/mL. In the per-protocol analysis, TDF reduced shedding (relative risk [RR] = 0.74, P = .006) and lesion rates (RR = 0.75, P = .032); quantity of virus shed decreased by 0.41 log10 copies/mL.Oral TDF modestly decreased HSV shedding and lesion rate, and quantity of virus shed when used consistently. Vaginal TFV gel decreased quantity of virus shed by 60%. In contrast to effects on HSV-2 acquisition, tenofovir is unlikely to provide clinically meaningful reductions in the frequency of HSV shedding or genital lesions.NCT01448616."
0,"TITLE: A replicate designed bioequivalence study to compare two fixed-dose combination products of artesunate and amodiaquine in healthy chinese volunteers.ABSTRACT: Artesun-Plus is a fixed-dose combination antimalarial agent containing artesunate and amodiaquine. The current study was conducted to compare the pharmacokinetic and safety profiles of Artesun-Plus and the WHO-designated comparator product Artesunate Amodiaquine Winthrop. To overcome the high intrasubject variability of artesunate, the study applied a two-sequence and four-period crossover (2 by 4), replicate study design to assess bioequivalence between the two products in 31 healthy male Chinese volunteers under fasting conditions. The results showed that the values of the geometric mean ratios of maximum concentration of drug in plasma (Cmax) and area under the concentration-time curve from time zero to the last blood sample collection (AUC0-last) for the artesunate component in the test and reference products were 95.9% and 93.9%, respectively, and that the corresponding 90% confidence intervals were 84.5% to 108.7% and 87.2% to 101.1%, while the geometric mean ratios for the amodiaquine component in the test and reference products were 95.0% and 100.0%, respectively, and the corresponding 90% confidence intervals were 86.7% to 104.1% and 93.5% to 107.0%. In conclusion, bioequivalence between the two artesunate and amodiaquine fixed-dose combination products was demonstrated for both components. The study also confirmed high intrasubject variability, especially for artesunate: the coefficients of variation (CV) of Cmax values for the test and reference products were 39.2% and 43.7%, respectively, while those for amodiaquine were 30.6% and 30.2%, respectively."
1,"TITLE: Targeted temperature management at 33°C versus 36°C and impact on systemic vascular resistance and myocardial function after out-of-hospital cardiac arrest: a sub-study of the Target Temperature Management Trial.ABSTRACT: Cardiovascular dysfunction is common after out-of-hospital cardiac arrest as part of the postcardiac arrest syndrome, and hypothermia may pose additional impact on hemodynamics. The aim was to investigate systemic vascular resistance index (SVRI), cardiac index, and myocardial performance at a targeted temperature management of 33°C (TTM33) versus 36°C (TTM36).Single-center substudy of 171 patients included in the Target Temperature Management Trial (TTM Trial) randomly assigned to TTM33 or TTM36 for 24 hours after out-of-hospital cardiac arrest. Mean arterial pressure ≥65 mm Hg and central venous pressure of 10 to 15 mm Hg were hemodynamic treatment goals. Hemodynamic evaluation was performed by serial right heart catheterization and transthoracic echocardiography. Primary end point was SVRI after 24 hours of cooling and secondary end points included mean SVRI, cardiac index, systolic function, and lactate levels. The TTM33 group had a significant increase in SVRI compared with TTM36 (2595; 95% confidence interval, 2422-2767) versus 1960 (95% confidence interval, 1787-2134) dynes m(2)/s per cm(5); P<0.0001, respectively) after 24 hours of cooling with an overall difference of 556 dynes m(2)/s per cm(5) (P(group) <0.0001). TTM33 was associated with decreased cardiac index (-0.4 L/min per m(2); P(group) <0.0001), decreased heart rate (P(group)=0.01), and stroke volume index (P(group)=0.004) compared with TTM36. Left ventricular ejection fraction (P=0.39) and peak systolic myocardial velocity (P=0.62) did not differ between TTM groups. Lactate levels were significantly higher in the TTM33 group (P=0.0008).Targeted temperature management at 33°C with target mean arterial pressure ≥65 mm Hg is associated with increased SVRI and lower cardiac index because of lower heart rate with unaffected left ventricular systolic function compared with 36°C.http://www.clinicaltrials.gov. Unique identifier: NCT01020916."
1,"TITLE: A double-blind, randomized clinical trial of dietary supplementation on cognitive and immune functioning in healthy older adults.ABSTRACT: Declining cognitive function is relatively common and increasingly prevalent. Studies have shown that different nutrients (e.g., Ginkgo biloba and vitamin E) appear to be effective at improving memory and concentration, while less is known about their effect on immunity.This study investigated the effect of Ginkgo Synergy(®) plus Choline (n = 33) and OPC Synergy(®) plus Catalyn(®) (n = 31) versus placebo (n = 33) in a 6-month, randomized, double-blind trial on cognitive and immune functioning among English-speaking, non-smoking, healthy older adults. The Stroop Color and Word Test, Trail Making Test A and B, Controlled Oral Word Association, Hopkins Verbal Learning, Mini-Mental State Exam, and Digit Symbol were administered at baseline and 3 and 6 months follow-up to assess cognitive functioning. Cytokines and growth factors were measured at baseline and 6 months to assess inflammation and immune functioning. Data were analyzed with linear mixed modeling.No serious adverse events were noted in this study. According to time on the Trail Making Test-B, the Ginkgo Synergy(®) plus Choline arm showed improvement from baseline to 3 months follow-up (mean difference = 24.2; SE = 6.4; 95% CI: 8.6, 39.7; p = 0.01). On the Controlled Oral Word Association Trial-S, the scores significantly increased for the Ginkgo Synergy(®) plus Choline arm from baseline to 6 months follow-up (mean difference = 2.1; SE = 0.8; 95% CI: 0.2, 3.9; p < 0.05) and for the OPC Synergy(®) plus Catalyn(®) arm from baseline to 3 months follow-up (mean difference = 2.1; SE = 0.8; 95% CI: 0.2, 4.0; p < 0.05). Epidermal growth factor significantly decreased from baseline to 6 months follow-up for the Ginkgo Synergy(®) plus Choline arm (mean difference = 120.7; SE = 28.4; 95% CI: 62.6, 178.8; p < 0.001).Our study showed isolated and modest effects of a Ginkgo biloba plus choline-based formula on cognitive and immune functioning among healthy older adults with no history of significant cognitive deficits. Our trial was registered with clinicaltrials.gov (ID: NCT01672359). This study was supported by a grant from Standard Process, Inc."
1,"TITLE: Microwave endometrial ablation versus thermal balloon endometrial ablation (MEATBall): 5-year follow up of a randomised controlled trial.ABSTRACT: To compare long-term outcomes following microwave endometrial ablation (MEA™) and thermal balloon ablation (TBall).Follow up of a prospective, double-blind randomised controlled trial at 5 years.A teaching hospital in the UK.A total of 320 women eligible for and requesting endometrial ablation.Eligible women were randomised in a 1:1 ratio to undergo MEA or Tball. Postal questionnaires were sent to participants at a minimum of 5 years postoperatively to determine satisfaction with outcome, menstrual status, bleeding scores and quality of life measurement. Subsequent surgery was ascertained from the women and the hospital operative database.The primary outcome measure was overall satisfaction with treatment. Secondary outcomes included evaluation of menstrual loss, change in quality of life scores and subsequent surgery.Of the women originally randomised 217/314 (69.1%) returned questionnaires. Nonresponders were assumed to be treatment failures for data analysis. The primary outcome of satisfaction was similar in both groups (58% for MEA™ versus 53% for TBall, difference 5%; 95% CI -6 to 16%). Amenorrhoea rates were high following both techniques (51% versus 45%, difference 6%; 95% CI -5 to 17%). There was no significant difference in the hysterectomy rates between the two arms (9% versus 7%, difference 2%; 95% CI -5 to 9%).At 5 years post-treatment there were no significant clinical differences in patient satisfaction, menstrual status, quality of life scores or hysterectomy rates between MEA™ and Thermachoice 3, thermal balloon ablation."
1,"TITLE: Assessing the stability and safety of procedure during endoscopic submucosal dissection according to sedation methods: a randomized trial.ABSTRACT: Although endoscopic submucosal dissection (ESD) is routinely performed under sedation, the difference in ESD performance according to sedation method is not well known. This study attempted to prospectively assess and compare the satisfaction of the endoscopists and patient stability during ESD between two sedation methods.One hundred and fifty-four adult patients scheduled for ESD were sedated by either the IMIE (intermittent midazolam/propofol injection by endoscopist) or CPIA (continuous propofol infusion by anesthesiologist) method. The primary endpoint of this study was to compare the level of satisfaction of the endoscopists between the two groups. The secondary endpoints included level of satisfaction of the patients, patient's pain scores, events interfering with the procedure, incidence of unintended deep sedation, hemodynamic and respiratory events, and ESD outcomes and complications.Level of satisfaction of the endoscopists was significantly higher in the CPIA Group compared to the IMIE group (IMIE vs. CPIA; high satisfaction score; 63.2% vs. 87.2%, P=0.001). The incidence of unintended deep sedation was significantly higher in the IMIE Group compared to the CPIA Group (IMIE vs. CPIA; 17.1% vs. 5.1%, P=0.018) as well as the number of patients showing spontaneous movement or those requiring physical restraint (IMIE vs. CPIA; spontaneous movement; 60.5% vs. 42.3%, P=0.024, physical restraint; 27.6% vs. 10.3%, P=0.006, respectively). In contrast, level of satisfaction of the patients were found to be significantly higher in the IMIE Group (IMIE vs. CPIA; high satisfaction score; 85.5% vs. 67.9%, P=0.027). Pain scores of the patients, hemodynamic and respiratory events, and ESD outcomes and complications were not different between the two groups.Continuous propofol and remifentanil infusion by an anesthesiologist during ESD can increase the satisfaction levels of the endoscopists by providing a more stable state of sedation.ClinicalTrials.gov NCT01806753."
0,"TITLE: A possible alternative exercise test for youths with cystic fibrosis: the steep ramp test.ABSTRACT: The steep ramp test (SRT) can be used to provide an indication of exercise capacity when gas exchange measurements are not possible. This study evaluated the clinical usefulness of the SRT in adolescents with cystic fibrosis (CF) and compared the physiological responses of the SRT with the standard cardiopulmonary exercise test (CPET).Forty patients with CF (17 boys and 23 girls; mean ± SD age, 14.7 ± 1.7 years; forced expiratory volume in 1 s, 86% ± 18% of predicted) performed an SRT and a CPET with respiratory gas analysis in a randomized balanced design. Peak work rate (WRpeak), HRpeak, peak minute ventilation (V˙Epeak), and peak oxygen uptake (V˙O2peak) were the main outcome measures.Patients with CF attained values for absolute and relative WRpeak during the SRT of 82% ± 14% and 92% ± 14% of predicted. Nutritional status and degree of airway obstruction did not influence SRT performance. Significantly higher values were attained for WRpeak during the SRT compared with those during the CPET (252 ± 60 vs 174 ± 46 W; P < 0.001), whereas significantly lower values were achieved for HRpeak (168 ± 14 vs 182 ± 12 bpm; P < 0.001), V˙Epeak (59.2 ± 19.5 vs 72.0 ± 20.2 L·min(-1); P = 0.006), and V˙O2peak (36.9 ± 7.5 vs 41.5 ± 7.6 mL·kg(-1)·min(-1); P = 0.008). A strong correlation between WRpeak attained at the SRT and the V˙O2peak achieved during the CPET was found (r = 0.822, P < 0.001).The SRT seems to be a quick, convenient, and low-cost exercise test that is well-tolerated in patients with CF with mild-to-moderate airway obstruction. It provides an indication of exercise capacity and can potentially be used when exercise testing using gas exchange measurements is not possible."
1,"TITLE: Intravenous immunoglobulin treatment for secondary recurrent miscarriage: a randomised, double-blind, placebo-controlled trial.ABSTRACT: To determine whether infusions with intravenous immunoglobulin (IVIg) during early pregnancy increase live birth rate in women with secondary recurrent miscarriage compared with placebo.A single-centre, randomised, double-blind, placebo-controlled trial.A tertiary centre for recurrent miscarriage in Copenhagen, Denmark.A group of 82 women with unexplained secondary recurrent miscarriage and at least four miscarriages.Women were randomly assigned to repeated infusions with IVIg or placebo (albumin) from the time of positive pregnancy test to gestational week 15 or pregnancy loss.Primary outcome was birth with neonatal survival in all randomised women.In the intention-to-treat analyses, live birth rates were 23/42 (54.8%) in the IVIg and 20/40 (50.0%) in the placebo group, relative risk 1.11 (95% CI 0.70-1.74). In a per protocol analysis, almost identical results were found. The median gestational length at delivery was higher in the IVIg than the placebo group (282 versus 272 days, P = 0.02) but the mean birthweight was not significantly increased.In this trial, which is the largest so far, IVIg did not increase the live birth rate in patients with secondary recurrent miscarriage and the treatment cannot be recommended in clinical practice."
1,"TITLE: A randomized study of temperature-controlled versus bipolar radiofrequency for inferior turbinate reduction.ABSTRACT: The objective of this study is to compare outcomes of temperature-controlled radiofrequency (TCRF) and bipolar radiofrequency (BRF) for inferior turbinate reduction in patients with chronic rhinitis (CR). This was a prospective, randomized non-inferiority trial. Eighty-four adult patients with CR refractory to medication were randomized into two intervention groups: TCRF(42) or BRF(42). Primary outcomes consisted of patient-orientated visual analog scale (VAS; 0-10) of nasal obstruction at 4th postoperative week. Secondary subjective outcomes included VAS of nasal discharge, sneezing, hyposmia, and postnasal drip. Objective outcomes included crusting, mucociliary transportation time, minimal cross-sectional area, total nasal volume, and nasal airway resistance performed by blind assessors before and at 4th postoperative week and 1-year follow-up. Baseline and perioperative data showed no statistically significant difference between both groups, except for longer operative time in TCRF (481.5 ± 36.2 vs. 37.1 ± 3.0 s, p < 0.001) and slightly more crusts in BRF group (p = 0.04). Both intention-to-treat and per-protocol analyses, TCRF(39) versus BRF(41), revealed no significant difference among subjective and objective outcomes between two groups at 4th postoperative week. The 95% confidence intervals of mean differences of VAS scores of all subjective symptoms were within defined margin (-1.5 to 1.5), except for nasal discharge. At 1-year follow-up, there was still no significant difference in the outcomes. Minimal pain and minor bleeding without serious adverse effects from both interventions were reported. Both BRF and TCRF resulted in similar short-term outcomes, while less operative time was found in BRF group. Further studies, particularly, on cost-effectiveness should be conducted for better treatment selection.1b."
1,"TITLE: Use of cyclosporine 0.05% ophthalmic emulsion for contact lens-intolerant patients.ABSTRACT: To evaluate the effect of cyclosporine 0.05% ophthalmic emulsion (Restasis, Allergan, Inc., Irvine, CA) on contact lens comfort and reducing dry eye symptoms in patients with contact lens intolerance.A 5-week, randomized, investigator-masked study of 17 patients with self-reported contact lens-related dryness. Patients were randomized to cyclosporine twice per day or rewetting drops (carboxymethylcellulose 0.5%, Refresh Contacts) twice per day, to be used before and after lens wear. Changes from baseline in fluorescein staining of the cornea and conjunctiva and in tear breakup time were used to determine improvement of dry eye signs. Symptoms were assessed by lens wear time, use of rewetting drops during lens wear, subjective evaluation of dryness, and the completion of the Ocular Surface Disease Index questionnaire.Five weeks of cyclosporine treatment significantly improved dry eye symptoms (mean improvement of 0.88 +/- 0.64 with cyclosporine; no change of 0 +/- 0.58 [P = 0.01] with rewetting drops). Patients using cyclosporine decreased the use of rewetting drops by a mean 1.0 +/- 1.1 drops per day, and patients using rewetting drops increased their use (mean increase of 0.86 +/- 1.1 drops per day [P = 0.032]). Wearing time increased 1.9 +/- 2.1 hours per day with cyclosporine and 0.93 +/- 1.0 hours per day with rewetting drops (P = 0.258). There were no significant differences in mean corneal staining between groups. After 5 weeks, patients using cyclosporine showed statistically better improvements in temporal bulbar conjunctival fluorescein staining (decrease of 0.63 +/- 0.52 vs. increase of 0.57 +/- 0.67 [P = 0.002]) than patients using rewetting drops. Both treatments were tolerated well.The results of this pilot study indicate that cyclosporine 0.05% is beneficial for contact lens wearers with dry eye and reduces contact lens intolerance."
1,"TITLE: Antiplatelet Efficacy of Fixed-Dose Aspirin-Clopidogrel Combination in Patients with Stable Coronary Artery Disease Treated with Drug-Eluting Stent Implantation.ABSTRACT: A fixed-dose combination (FDC) of aspirin and clopidogrel bisulfate may improve medication adherence. However, the absence of data on the relative antiplatelet efficacy of FDC and separate dual pills (SDP) of aspirin and clopidogrel in real-world patients with stable coronary artery disease is a major factor retarding clinical introduction of such an FDC.This was a single-centre, randomized, open-label, parallel-group, non-inferiority trial. Patients who maintained a regimen of separate aspirin and clopidogrel pills for at least 1 year after drug-eluting stent implantation without adverse events were enrolled. Patients were randomly assigned to either the FDC group or the SDP group. Antiplatelet efficacy and tolerability were assessed at baseline and at 4 weeks.Of the 93 enrolled patients, 83 (FDC group: n = 42; SDP group: n = 41) completed the study. The difference in the changes in P2Y12 percentage inhibition did not exceed the predetermined value for inferiority [mean difference -1.7; 95 % confidence interval (CI) -6.9 to 4.5, p < 0.001 for non-inferiority]. The changes from baseline to 4 weeks in P2Y12 reaction units (PRU) (mean difference 9.7 PRU, p = 0.46), maximal platelet aggregation (mean difference 2.0 %, p = 0.44) and aspirin reaction units (ARU) (mean difference -2.3 ARU, p = 0.88) did not differ significantly between the treatment groups. The tolerability of the FDC formulation was similar to that of SDP therapy (p = 0.68).In patients with prior percutaneous coronary intervention, the antiplatelet efficacy of the aspirin/clopidogrel FDC was non-inferior to that of SDP and the tolerability of the two regimens was similar after 4 weeks of treatment."
1,"TITLE: A double blind randomised placebo controlled pilot study of oral co-trimoxazole in advanced fibrotic lung disease.ABSTRACT: In 1996, clinical improvement with oral co-trimoxazole was noted in a patient with biopsy proven advanced fibrotic lung disease who was awaiting a lung transplant. Subsequently, 14 patients with end stage fibrotic lung disease also responded to oral co-trimoxazole. This prompted a double blind randomised placebo controlled pilot study in patients with advanced stages of idiopathic interstitial pneumonias (IIP) to objectively measure benefit.Twenty patients (aged 49-84 years; 11 males) with progressive fibrotic lung disease who had differing subtype diagnosis from CT scans of progressive fibrotic IIP, and showed oxygen desaturation on exertion were selected.A detailed assessment of arterial gases, lung function, and progressive shuttle-walking tests combined with oxygen saturation monitoring. Quality of life data was recorded. Randomisation was to co-trimoxazole or identical placebo for 3 months followed by 6 weeks of pulmonary rehabilitation before decoding. Placebo patients received active treatment upon decoding with continued follow up of all patients.Primary 1. Shuttle walking test. Secondary 2. FVC and quality of life.Active treatment showed a significant improvement in shuttle walking test from 255 to 355 m (p=0.002) (95% CI 200-450) with reduced oxygen desaturations during exercise (p=0.003). FVC improved on treatment (+21%) from median 1.9 to 2.3 L (p=0.05) (95% CI 1.3-3.0) but TLC and DLCO were not significantly changed although stable at 12 months. The MRC 5 Point Dyspnoea Score showed improvement (p=0.05) at 3 months for the active group which was maintained at 12 months. The SGHRQ showed a significant reduction in symptom scores at 12 months (p=0.05). The placebo group showed no significant change in any parameters, but demonstrated identical improvement following oral co-trimoxazole. Serum vascular endothelial growth factor (VEGF) was reduced 50% in the active group at 3 months, but just failed to reach statistical significance. 'Out of study' HRCT scans in 12 patients showed significant reduction in ground glass changes (p=0.05) after 12 months of continuous co-trimoxazole treatment.The findings of the pilot study show significant improvements in objective and subjective parameters which fulfil the ATS/ERS (2000) criteria of 'a favourable response to treatment'."
1,"TITLE: Uric acid and other renal function parameters in patients with stable angina pectoris participating in the ACTION trial: impact of nifedipine GITS (gastro-intestinal therapeutic system) and relation to outcome.ABSTRACT: Little data is available concerning the prognostic implications of renal function abnormalities, their evolution over time and the effects of nifedipine on such abnormalities in patients with stable angina pectoris.The previously published ACTION trial compared long-acting nifedipine GITS 60 mg once daily to placebo among 7,665 patients. Standard laboratory tests including creatinine and uric acid were assessed at baseline, after 6 months, 2 and 4 years, and at the end of follow-up. We assessed the impact of nifedipine on markers of renal dysfunction and determined whether evidence of renal failure alters the impact of nifedipine on the clinical outcome of patients with stable angina.Uric acid was not while creatinine level and estimated creatinine clearance were potent conditionally independent predictors of total mortality and of cardiovascular clinical events. Relative to placebo, nifedipine reduced 6-month uric acid levels by 3% (P < 0.001) of the baseline value. This difference was maintained during long-term follow-up, was present both in normotensives and in hypertensives, and was not explained by differences in diuretic therapy or allopurinol use. Nifedipine had no effect on the occurrence of clinical renal failure. Relative to placebo, the effects of nifedipine on cardiovascular death or myocardial infarction [hazard ratio (HR) = 1.01, 95% confidence interval (CI) 0.88-1.17], any stroke or transient ischaemic attack (HR = 0.73, 95% CI 0.60-0.88), new overt heart failure (HR = 0.72, 95% CI 0.55-0.95), and the need for any coronary procedure (HR = 0.81, 95% CI 0.75-0.88) were consistent across strata of markers of renal dysfunction.We conclude that, in patients with stable angina, nifedipine reduces uric acid levels and does not affect other markers of renal dysfunction. Renal dysfunction does not alter the effects of nifedipine on clinical outcome."
1,"TITLE: A double-blind randomized controlled trial of mifepristone or placebo before buccal misoprostol for abortion at 14-21 weeks of pregnancy.ABSTRACT: To assess differences in outcomes of misoprostol with or without mifepristone for second-trimester abortion.A randomized, double-blind, placebo-controlled trial of buccal misoprostol following placebo or 200mg mifepristone was done in Tunisia among women presenting for abortions at 14-21 weeks of pregnancy between August 2009 and December 2011. Women with a live fetus, a closed cervical os, no cervical bleeding, and no contraindications to study drugs were eligible and underwent randomization (block size 10). Participants returned 24 hours later to receive 400 μg buccal misoprostol every 3 hours until complete fetal and placental expulsion (maximum 10 doses, five per 24-hour period). The primary outcomes were rates of complete uterine evacuation at 48 hours and time to expulsion.A total of 120 women were evenly randomized to treatment. Complete uterine evacuation at 48 hours was recorded in 55 (91.7%) women in the combined group versus 43 (71.7%) in the misoprostol alone group (relative risk 1.28; 95% confidence interval 1.07-1.53). Mean time to complete abortion was 10.4±6.6 hours in the group who received mifepristone versus 20.6±9.7 hours in the misoprostol alone group (P<0.001). Side effects were similar in both groups.Adding mifepristone before misoprostol can improve the quality of second-trimester abortion care by making the process faster."
1,"TITLE: Probiotic prophylaxis to prevent ventilator associated pneumonia (VAP) in children on mechanical ventilation: an open-label randomized controlled trial.ABSTRACT: Ventilator associated pneumonia (VAP) is one of the most common nosocomial infections in the pediatric intensive care unit (PICU). It is associated with increased mortality and prolonged hospital stay. Several preventive strategies have been introduced to reduce VAP. One novel intervention is prophylactic administration of probiotics. Studies on the effect of probiotics on VAP in pediatric populations are lacking.This was an open-label randomized controlled trial. A total of 150 children no older than 12 years admitted to the PICU were recruited from November 2011 to July 2013. Children who were likely to require ventilation for more than 48 h were eligible for inclusion in the study. Patients were randomized into two groups after stratification based on age groups. Children in the intervention group received probiotic preparation twice a day beginning from the day of ICU admission till 7 days or discharge from ICU, whichever was earlier. The control group did not receive any placebo. Children were examined daily for evidence of VAP and were followed up till discharge from hospital. Incidence of VAP, duration of hospital stay, and mortality were compared.Children who received prophylactic probiotics had a lower incidence of VAP compared to the control group (17.1 % in the probiotics group vs 48.6 % in the control group, p < 0.001; 22 per 1,000 ventilated days vs 39 per 1,000 ventilated days, p = 0.02). On multiple logistic regression analysis, use of prophylactic probiotics decreased the incidence of VAP by 77 % and reduced the duration of ICU and hospital stays by an average of 2.1 and 3.3 days, respectively, after adjusting for the other confounders. No complications due to administration of probiotics were observed in the study.Prophylactic probiotics administration resulted in reduction of the incidence of VAP in critically ill children in a setting where baseline VAP rates are high. The intervention was found to be safe."
1,"TITLE: Treatment for 24 months with recombinant human GH has a beneficial effect on bone mineral density in young adults with childhood-onset GH deficiency.ABSTRACT: Discontinuation of growth hormone (GH) therapy on completion of linear growth may adversely affect bone mineral density (BMD) in young adults with childhood-onset GH-deficiency (GHD). In the present study, we analyzed the impact of GH treatment on bone in young adults with GHD.BMD at the lumbar spine (L2-L4), total hip, and total body was measured at baseline and after 24 months in a cohort of young adults (18-25 years; n=160) with severe GHD treated with GH during childhood who were randomized to GH (n=109) or no treatment (n=51) in a multicenter, multinational, open-label study. GH starting doses (0.2 mg/day (males), 0.4 mg/day (females)) were increased after 1 month to 0.6 mg/day (males) and 0.9 mg/day (females) and then to 1.0 mg/day (males) and 1.4 mg/day (females) at 3 months for the remainder of the study.After 24 months, lumbar spine BMD had increased significantly more in GH-treated patients than in controls (6 vs 2%; estimated treatment difference; 3.5% (95% confidence interval, 1.52-5.51) P<0.001). GH also had a significant positive effect on total hip BMD (P=0.015). Total body BMD was unchanged from baseline (P=0.315).In young adults treated for childhood-onset GHD, there is a beneficial effect of continued GH treatment on BMD in adult life. Twenty-four months of GH treatment in these young adults was associated with an estimated 3.5% greater increase in BMD of the lumbar spine compared with controls."
1,"TITLE: Acute Effects of Brief Mindfulness Intervention Coupled with Carbohydrate Ingestion to Re-Energize Soccer Players: A Randomized Crossover Trial.ABSTRACT: This field experiment investigated the acute effects of brief mindfulness-based intervention (MBI) coupled with carbohydrate (CHO) intake on players' recovery from half-time break in a simulated soccer competition.  In a single-blinded randomized crossover experiment, 14 male players received 3 treatments (Control: non-carbohydrate solution + travelling introduction audio; CHO: CHO-electrolyte solution + travelling introduction audio; and CHO_M: CHO-electrolyte solution + MBI) during simulated half-time breaks. Vertical jump, sprint performance, mindfulness level, rate of perceived exertion, muscle pain, mental fatigue, blood glucose, and lactate were measured immediately before, during, and after the exercise.  (1) MBI significantly increased participants' mindfulness level (Control vs. CHO_M,  < 0.01; CHO vs. CHO_M,  < 0.01) and decreased mental fatigue for CHO_M condition (pre vs. post,  < 0.01); (2) participants in the CHO_M condition performed better in the repeated sprint tests than in the Control and CHO condition (Control vs. CHO_M,  = 0.02; CHO vs. CHO_M,  = 0.02).  Findings of this study provide preliminary evidence of the positive effect of MBI coupled with CHO ingestion on athletes' recovery from fatigue in the early stage of the second half of a game."
1,"TITLE: A 24-month randomized controlled trial on the success rates of restoring untreated and SDF-treated dentine caries lesions in primary teeth with the ART approach.ABSTRACT: To compare the success rates of restoring untreated and SDF-treated dentine caries lesions in primary teeth with atraumatic restorative treatment (ART) approach.Cavitated dentine caries lesions in preschool children were randomly allocated to two groups to be applied with either 38% silver diamine fluoride (SDF) solution or tonic water (control) ten weeks before being restored with the ART approach. Status of the restorations were assessed every six months by a blinded independent examiner. Multilevel logistic regression and multilevel survival analyses were conducted to assess the restoration success rates.A total of 194 children (SDF group, 101; control group, 93) were included, with 260 and 249 ART restorations placed in the SDF and the control groups, respectively. At 24-month follow-up, 88 (87 %) and 84 (90 %) children remained in the SDF and the control groups, respectively. There was no significant difference between the ART restoration success rates of the two study groups (p > 0.05). The success rate of ART restorations was associated with the class of restorations. Class I restorations had the highest success rate (∼50 %), followed by Class V (∼35 %), Class II (∼15 %) and Class III (<10 %). Besides, the mean time used to place an ART restoration in a SDF-treated caries lesion was shorter than that in untreated lesion (4.8 vs. 5.1 min, p = 0.006).Prior SDF application does not significantly affect the success rate of ART restorations placed in primary teeth. Besides, it is faster to place ART restorations in caries lesions that have been previously treated with SDF.Prior application of silver diamine fluoride solution on cavitated dentine caries lesions in primary teeth can shorten the average time required to place an ART restoration while not jeopardizing the success rate of the restorations."
1,"TITLE: Omitting fentanyl reduces nausea and vomiting, without increasing pain, after sevoflurane for day surgery.ABSTRACT: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia.This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl.Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia.As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery."
1,"TITLE: Consolidation radiotherapy in patients with advanced Hodgkin's lymphoma: survival data from the UKLG LY09 randomized controlled trial (ISRCTN97144519).ABSTRACT: This study analyzed the outcomes of nonrandomized consolidation radiotherapy (RT) given after chemotherapy in the initial treatment of advanced Hodgkin's lymphoma (HL). The results were collected prospectively within a randomized controlled trial of induction chemotherapy.Patients were randomly assigned between doxorubicin, bleomycin, vinblastine, and dacarbazine and one of two prespecified multidrug regimens. At least six cycles of chemotherapy were planned, with up to eight for patients showing slower response. Involved-field RT was recommended for incomplete response to chemotherapy or bulk disease at presentation. The primary outcome measure was progression-free survival (PFS), landmarked from the end of chemotherapy.Among 807 patients randomly assigned, 702 achieved objective response. Postchemotherapy RT for consolidation was reported in 300 (43%). With median follow-up of 6.9 years, 161 PFS events and 83 deaths were reported. Baseline characteristics showed more patients with bulk disease having RT (190 [63%] v 111 [28%]) and only partial response after chemotherapy (150 [50%] v 36 [9%]). Other baseline characteristics were similar. PFS was superior for patients having RT (hazard ratio [HR], 0.43; 95% CI, 0.30 to 0.60) with 5-year PFS 71% without RT, 86% with RT. A similar advantage was seen for overall survival (HR, 0.47; 95% CI, 0.29 to 0.77). There was no evidence of heterogeneity of treatment effect across subgroups.Patients who received consolidation RT apparently had better outcomes, consistently across all prognostic groups which persisted in multivariate analysis. This suggests that RT contributes significantly to the cure rate for advanced HL, although patient selection for combined modality treatment requires better definition in prospective trials."
1,"TITLE: Can postpartum pelvic floor muscle training reduce urinary and anal incontinence?: An assessor-blinded randomized controlled trial.ABSTRACT: Pelvic floor dysfunction, including urinary and anal incontinence, is a common postpartum complaint and likely to reduce quality of life.To study the effects of individualized physical therapist-guided pelvic floor muscle training in the early postpartum period on urinary and anal incontinence and related bother, as well as pelvic floor muscle strength and endurance.This was an assessor-blinded, parallel-group, randomized controlled trial evaluating effects of pelvic floor muscle training by a physical therapist on the rate of urinary and/or anal leakage (primary outcomes); related bother and muscle strength and endurance in the pelvic floor were secondary outcomes. Between 2016 and 2017, primiparous women giving birth at Landspitali University Hospital in Reykjavik, Iceland, were screened for eligibilty 6-10 weeks after childbirth. Of those identified as urinary incontinent, 95 were invited to participate, of whom 84 agreed. The intervention, starting at ∼9 weeks postpartum consisted of 12 weekly sessions with a physical therapist, after which the main outcomes were assessed (endpoint, ∼6 months postpartum). Additional follow-up was conducted at ∼12 months postpartum. The control group received no instructions after the initial assessment. The Fisher exact test was used to test differences in the proportion of women with urinary and anal incontinence between the intervention and control groups, and independent-sample t tests were used for mean differences in muscle strength and endurance. Significance levels were set as α = 0.05.A total of 41 and 43 women were randomized to the intervention and control groups, respectively. Three participants and 1 participant withdrew from these respective groups. Measurement variables and main delivery outcomes were not different at recruitment. At the endpoint, urinary incontinence was less frequent in the intervention group, with 21 participants (57%) still symptomatic, compared to 31 controls (82%) (P = .03), as was bladder-related bother with 10 participants (27%) in the intervention vs 23 (60%) in the control group (P = .005). Anal incontinence was not influenced by pelvic floor muscle training (P = .33), nor was bowel-related bother (P = .82). The mean differences between groups in measured pelvic floor muscle strength changes at endpoint was 5 hPa (95% confidence interval, 2-8; P = .003), and for pelvic floor muscle endurance changes, 50 hPa/s (95% confidence interval, 23-77; P = .001), both in favor of the intervention group. The mean between-group differences for anal sphincter strength changes was 10 hPa (95% confidence interval, 2-18; P = .01) and for anal sphincter endurance changes 95 hPa/s (95% confidence interval, 16-173; P = .02), both in favor of the intervention. At the follow-up visit 12 months postpartum, no differences were observed between the groups regarding rates of urinary and anal incontinence and related bother. Pelvic floor- and anal muscle strength and endurance favoring the intervention group were maintained.Postpartum pelvic floor mucle training decreased the rate of urinary incontinence and related bother 6 months postpartum and increased muscle strength and endurance."
1,"TITLE: The effects of vitamin D and probiotic co-supplementation on mental health parameters and metabolic status in type 2 diabetic patients with coronary heart disease: A randomized, double-blind, placebo-controlled trial.ABSTRACT: This study was carried out to evaluate the effects of vitamin D and probiotic co-supplementation on mental health parameters and metabolic status in diabetic people with coronary heart disease (CHD).This randomized, double-blind, placebo-controlled trial was carried out among 60 diabetic people with CHD, aged 45-85 years old. Subjects were randomly allocated into two groups to receive either 50,000 IU vitamin D every 2 weeks plus 8 × 10 CFU/g probiotic of Lactocare Zisttakhmir Co (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were obtained at baseline and after the 12-week intervention to determine metabolic profiles.After the 12-week intervention, compared with the placebo, vitamin D and probiotic co-supplementation resulted in significant improvements in beck depression inventory total score (-2.8 ± 3.8 vs. -0.9 ± 2.1, P = 0.01), beck anxiety inventory scores (-2.1 ± 2.3 vs. -0.8 ± 1.4, P = 0.009) and general health questionnaire scores (-3.9 ± 4.1 vs. -1.1 ± 3.4, P = 0.005). Compared with the placebo, vitamin D and probiotic co-supplementation resulted in significant reductions in serum insulin levels (-2.8 ± 3.8 vs. +0.2 ± 4.9 μIU/mL, P = 0.009), homeostasis model of assessment-estimated insulin resistance (-1.0 ± 1.6 vs. -0.1 ± 1.5, P = 0.02), and a significant increase in serum 25-OH-vitamin D (+11.8 ± 5.9 vs. +0.1 ± 1.4 ng/mL, P < 0.001), the quantitative insulin sensitivity check index (+0.03 ± 0.04 vs. -0.001 ± 0.01, P = 0.003) and serum HDL-cholesterol levels (+2.3 ± 3.5 vs. -0.5 ± 3.8 mg/dL, P = 0.004). In addition, changes in serum high sensitivity C-reactive protein (hs-CRP) (-950.0 ± 1811.2 vs. +260.5 ± 2298.2 ng/mL, P = 0.02), plasma nitric oxide (NO) (+1.7 ± 4.0 vs. -1.4 ± 6.7 μmol/L, P = 0.03) and plasma total antioxidant capacity (TAC) (+12.6 ± 41.6 vs. -116.9 ± 324.2 mmol/L, P = 0.03) in the supplemented group were significantly different from the changes in these indicators in the placebo group.Overall, vitamin D and probiotic co-supplementation after 12 weeks among diabetic people with CHD had beneficial effects on mental health parameters, serum hs-CRP, plasma NO, TAC, glycemic control and HDL-cholesterol levels.http://www.irct.ir: IRCT2017073033941N4."
0,"TITLE: A paradoxical difference in relationship between anxiety, depression and thyroid function in subjects on and not on T4: findings from the HUNT study.ABSTRACT: There have been conflicting reports on the relationship between thyroid function and mood between studies in subjects on T4 and the general population not on T4. We investigated this relationship in a large catchment area-based study.We analysed data on serum TSH levels and Hospital Anxiety and Depression Scale (HADS) scores from the HUNT 2 study (age > or = 40 years). Following a test for interaction, analyses were performed separately in females on T4 (n = 1265) and in people not on T4 (males n = 9319 and females n = 17 694).More females on T4 had high depression and anxiety scores than females not on T4 (depression 18.4%vs. 13.0%, P < 0.001, anxiety 23.4%vs. 18.7%, P < 0.001). In those not on T4, there was an inverse association between serum TSH and depression score in males (B coefficient = -0.61, 95% CI -0.91 to -0.24, P = 0.001) though not in females (B coefficient = -0.07, -0.33 to 0.19), and an inverse association between TSH and anxiety score in both genders (B coefficient for males = 0.68, 95% CI -1.04 to -0.32, P < 0.001; females -0.37, 95% CI -0.67 to -0.08, P = 0.01). In contrast, in females on T4, TSH was positively associated with both depression (B coefficient = +0.27, 95% CI 0.02 to 0.51, P < 0.05) and anxiety (B coefficient = +0.29, 95% CI 0.01 to 0.56, P < 0.05).There is a different relationship between thyroid function and depression and anxiety in females on T4 compared with individuals with no thyroid disease. This group also has a higher prevalence of depression and anxiety."
1,"TITLE: The effect of a short-term exercise programme on haemodynamic adaptability; a randomised controlled trial with newly diagnosed transient ischaemic attack patients.ABSTRACT: This study assessed the effect of a short-term, 8-week exercise programme on resting and exercise blood pressure (systolic (SBP); diastolic (DBP)), and other haemodynamic responses (heart rate (HR), pulse pressure (PP), double product (DP)), of newly diagnosed transient ischaemic attack (TIA) patients. Sixty-eight TIA patients completed a continuous and incremental exercise test within 2 weeks of symptom diagnosis. HR, SBP and DBP were regularly measured at rest, during exercise and in recovery. Participants were then randomised to either an 8-week exercise programme or to a usual care control group prior to completing an identical post-intervention (PI) re-assessment. Individuals randomised to the exercise condition experienced a significantly greater reduction in resting HR (-5.4±10.2%), SBP (-6.7±8.1%) and DBP (-2.8±7.2%) than the control group at the PI assessment (all P<0.05). Similar findings were demonstrated at the PI assessment when comparing haemodynamic responses during exercise (P<0.05), with significantly larger decrements observed for SBP and HR (both 10-14%), PP (17-24%) and DP (26-32%) for those randomised to the exercise intervention (all P<0.05). This study demonstrates that structured physical activity soon after TIA diagnosis will improve haemodynamic responses. The early implementation of exercise following TIA diagnosis may be an important secondary prevention strategy for this population."
1,"TITLE: Endovascular repair of type B aortic dissection: long-term results of the randomized investigation of stent grafts in aortic dissection trial.ABSTRACT: Thoracic endovascular aortic repair (TEVAR) represents a therapeutic concept for type B aortic dissection. Long-term outcomes and morphology after TEVAR for uncomplicated dissection are unknown.A total of 140 patients with stable type B aortic dissection previously randomized to optimal medical treatment and TEVAR (n=72) versus optimal medical treatment alone (n=68) were analyzed retrospectively for aorta-specific, all-cause outcomes, and disease progression using landmark statistical analysis of years 2 to 5 after index procedure. Cox regression was used to compare outcomes between groups; all analyses are based on intention to treat. The risk of all-cause mortality (11.1% versus 19.3%; P=0.13), aorta-specific mortality (6.9% versus 19.3%; P=0.04), and progression (27.0% versus 46.1%; P=0.04) after 5 years was lower with TEVAR than with optimal medical treatment alone. Landmark analysis suggested a benefit of TEVAR for all end points between 2 and 5 years; for example, for all-cause mortality (0% versus 16.9%; P=0.0003), aorta-specific mortality (0% versus 16.9%; P=0.0005), and for progression (4.1% versus 28.1%; P=0.004); Landmarking at 1 year and 1 month revealed consistent findings. Both improved survival and less progression of disease at 5 years after elective TEVAR were associated with stent graft induced false lumen thrombosis in 90.6% of cases (P<0.0001).In this study of survivors of type B aortic dissection, TEVAR in addition to optimal medical treatment is associated with improved 5-year aorta-specific survival and delayed disease progression. In stable type B dissection with suitable anatomy, preemptive TEVAR should be considered to improve late outcome.http://www.clinicaltrials.gov. Unique identifier: NCT01415804."
1,"TITLE: Interaction of serum vitamin B and folate with  genotypes on risk of ischemic stroke.ABSTRACT: We evaluated the interaction of serum folate and vitamin B with methylenetetrahydrofolate reductase () C677T genotypes on the risk of first ischemic stroke and on the efficacy of folic acid treatment in prevention of first ischemic stroke.A total of 20,702 hypertensive adults were randomized to a double-blind treatment of daily enalapril 10 mg and folic acid 0.8 mg or enalapril 10 mg alone. Participants were followed up every 3 months.Median values of folate and B concentrations at baseline were 8.1 ng/mL and 280.2 pmol/L, respectively. Over a median of 4.5 years, among those not receiving folic acid, participants with baseline serum B or serum folate above the median had a significantly lower risk of first ischemic stroke (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.57-0.96), especially in those with  677 CC genotype (wild-type) (HR, 0.49; 95% CI, 0.31-0.78). Folic acid treatment significantly reduced the risk of first ischemic stroke in participants with both folate and B below the median (2.3% in enalapril-folic acid group vs 3.6% in enalapril-only group; HR, 0.62; 95% CI, 0.46-0.86), particularly in  677 CC carriers (1.6% vs 4.9%; HR, 0.24; 95% CI, 0.11-0.55). However, TT homozygotes responded better with both folate and B levels above the median (HR, 0.28; 95% CI, 0.10-0.75).The risk of first ischemic stroke was significantly higher in hypertensive patients with low levels of both folate and B. Effect of folic acid treatment was greatest in patients with low folate and B with the CC genotype, and with high folate and B with the TT genotype."
1,"TITLE: A randomized, controlled, crossover trial to assess the acute appetitive and metabolic effects of sausage and egg-based convenience breakfast meals in overweight premenopausal women.ABSTRACT: Dietary protein at breakfast has been shown to enhance satiety and reduce subsequent energy intake more so than carbohydrate or fat. However, relatively few studies have assessed substitution of protein for carbohydrate on indicators of appetite and glucose homeostasis simultaneously.The acute appetitive and metabolic effects of commercially-prepared sausage and egg-based breakfast meals at two different protein levels (30 g and 39 g/serving), vs. a low-protein pancake breakfast (3 g protein) and no breakfast (water), were examined in premenopausal women (N = 35; age 32.5 ± 1.6 yr; BMI 24.8 ± 0.5 kg/m(2)). Test products provided ~280 kcal/serving and similar fat (12-14 g) and fiber contents (0-1 g). Visual Analog Scale ratings for appetite (hunger, fullness, prospective consumption, desire to eat) and repeated blood sampling for plasma glucose and insulin concentrations were assessed throughout each test day. Energy intake was recorded at an ad libitum lunch meal at 240 min.Results showed increased satiety ratings for both the 30 and 39 g protein meals vs. the low-protein and no breakfast conditions (p < 0.001 for all). Postprandial glucose and insulin excursions were lower following the 30 g and 39 g protein conditions vs. the low-protein condition, with smaller responses following the 39 g vs. 30 g protein condition (p < 0.05 for all). Energy intake at lunch was significantly less (p < 0.001) following the 39 g protein meal (692 kcal) vs. the low-protein and no breakfast conditions (789 and 810 kcal, respectively). Total energy intake from the test condition + lunch was higher (p < 0.01) for the 30 and 39 g meals (982 and 983 kcal, respectively) vs. no breakfast (810 kcal), and less than the low protein breakfast (1064 kcal; p < 0.01 vs. 39 g condition only).Results suggest that convenience meals providing 30 or 39 g protein/serving produce greater appetite control, lower postprandial glycemia and insulinemia, and reduced subsequent intake at lunch relative to a low-protein control, or no breakfast.NCT01713114."
1,"TITLE: Effect of vitamin E supplementation on HDL function by haptoglobin genotype in type 1 diabetes: results from the HapE randomized crossover pilot trial.ABSTRACT: Haptoglobin (Hp) genotype 2-2 increases cardiovascular diabetes complications. In type 2 diabetes, α-tocopherol was shown to lower cardiovascular risk in Hp 2-2, potentially through HDL function improvements. Similar type 1 diabetes data are lacking. We conducted a randomized crossover pilot of α-tocopherol supplementation on HDL function [i.e., cholesterol efflux (CE) and HDL-associated lipid peroxides (LP)] and lipoprotein subfractions in type 1 diabetes.Hp genotype was assessed in members of two Allegheny County, PA, type 1 diabetes registries and the CACTI cohort; 30 were randomly selected within Hp genotype, and 28 Hp 1-1, 31 Hp 2-1 and 30 Hp 2-2 were allocated to daily α-tocopherol or placebo for 8 weeks with a 4-week washout.Baseline CE decreased with the number of Hp 2 alleles (p-trend = 0.003). There were no differences in LP or lipoprotein subfractions. In intention-to-treat analysis stratified by Hp, α-tocopherol increased CE in Hp 2-2 (β = 0.79, p = 0.03) and LP in Hp 1 allele carriers (β Hp 1-1 = 0.18, p = 0.05; β Hp 2-1 = 0.21, p = 0.07); reduced HDL particle size (β = -0.07, p = 0.03) in Hp 1-1 carriers; increased LDL particle concentration in Hp 1-1; and decreased it in Hp 2-2 carriers. However, no significant interactions were observed by Hp.In this type 1 diabetes study, HDL function worsened with the number of Hp 2 alleles. α-Tocopherol improved HDL function in Hp 2-2 carriers and appeared to adversely affect lipid peroxides and lipoprotein subfractions among Hp 1 allele carriers. As no significant interactions were observed, findings require replication in larger studies."
1,"TITLE: School-based prevention of acute rheumatic fever: a group randomized trial in New Zealand.ABSTRACT: Acute rheumatic fever (ARF) and its sequela, rheumatic heart disease is the commonest cause of childhood cardiac morbidity globally. The current approach to the prevention of a primary attack of rheumatic fever in children using oral medication for streptococcal pharyngitis is poorly supported. The efficacy of injectable penicillin, in high rheumatic fever incidence military environments is indisputable.To evaluate school-based control of rheumatic fever in an endemic area.Fifty-three schools ( approximately 22,000 students) from a rheumatic fever high incidence setting ( approximately 60/100,000) in Auckland, New Zealand were randomized. The control group received routine general practice care. The intervention was a school-based sore throat clinic program with free nurse-observed oral penicillin treatment of group A streptococcal pharyngitis. The outcome measure was ARF in any child attending a study school. Analysis A defined ARF cases using criteria derived from Jones Criteria 1965 (definite) and 1956 (probable) with more precise definitions. Analysis B was based on 1992 Jones criteria but also included echocardiography to determine definite cases.In Analysis A, 24 (55/100,000) cases occurred in clinic schools and 29 (67/100,000) in nonclinic schools, a 21% reduction when adjusted for demography and study design (P = 0.47). Analysis B revealed a 28% reduction 26 (59/100,000) and 33 (77/100,000) cases, respectively (P = 0.27).This study involving 86,874 person-years showed a nonsignificant reduction in the school-based sore throat clinic programs."
1,"TITLE: Cost-effectiveness of a stepwise cardiometabolic disease prevention program: results of a randomized controlled trial in primary care.ABSTRACT: Cardiometabolic diseases (CMD) are the major cause of death worldwide and are associated with a lower quality of life and high healthcare costs. To prevent a further rise in CMD and related healthcare costs, early detection and adequate management of individuals at risk could be an effective preventive strategy. The objective of this study was to determine long-term cost-effectiveness of stepwise CMD risk assessment followed by individualized treatment if indicated compared to care as usual. A computer-based simulation model was used to project long-term health benefits and cost-effectiveness, assuming the prevention program was implemented in Dutch primary care.A randomized controlled trial in a primary care setting in which 1934 participants aged 45-70 years without recorded CMD or CMD risk factors participated. The intervention group was invited for stepwise CMD risk assessment through a risk score (step 1), additional risk assessment at the practice in case of increased risk (step 2) and individualized follow-up treatment if indicated (step 3). The control group was not invited for risk assessment, but completed a health questionnaire. Results of the effectiveness analysis on systolic blood pressure (- 2.26 mmHg; 95% CI - 4.01: - 0.51) and total cholesterol (- 0.15 mmol/l; 95% CI - 0.23: - 0.07) were used in this analysis. Outcome measures were the costs and benefits after 1-year follow-up and long-term (60 years) cost-effectiveness of stepwise CMD risk assessment compared to no assessment. A computer-based simulation model was used that included data on disability weights associated with age and disease outcomes related to CMD. Analyses were performed taking a healthcare perspective.After 1 year, the average costs in the intervention group were 260 Euro higher than in the control group and differences were mainly driven by healthcare costs. No meaningful change was found in EQ 5D-based quality of life between the intervention and control groups after 1-year follow-up (- 0.0154; 95% CI - 0.029: 0.004). After 60 years, cumulative costs of the intervention were 41.4 million Euro and 135 quality-adjusted life years (QALY) were gained. Despite improvements in blood pressure and cholesterol, the intervention was not cost-effective (ICER of 306,000 Euro/QALY after 60 years). Scenario analyses did not allow for a change in conclusions with regard to cost-effectiveness of the intervention.Implementation of this primary care-based CMD prevention program is not cost-effective in the long term. Implementation of this program in primary care cannot be recommended.Dutch Trial Register NTR4277 , registered on 26 November 2013."
1,"TITLE: WeChat-assisted dietary and exercise intervention for prevention of gestational diabetes mellitus in overweight/obese pregnant women: a two-arm randomized clinical trial.ABSTRACT: This study aimed to examine the influence of a WeChat-based dietary and exercise intervention on gestational diabetes mellitus (GDM) prevention in overweight/obese pregnant women in Beijing.Overweight/obese pregnant women were recruited in the early stages of pregnancy. After screening by include and exclude standards, eligible women were randomly divided into two groups, intervention and control groups. The control group received a general advice session about pregnancy nutrition and weight management. The intervention group received three face-to-face sessions about personalized dietary and exercise intervention, with the help of WeChat as a monitoring tool to promote treatment plan adherence. At 24-28 weeks of pregnancy, GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Gestational weight gain (GWG), maternal and neonatal outcomes were also collected.This study analyzed 215 participants. At the mid-trimester, 42 (37.8%) women in the control group were diagnosed with GDM (n = 111) versus 25 (24.5%) in the intervention group (n = 104; p < 0.05). The intervention group gained 11.2 ± 4.9 kg during the whole gestation period, with 4.9 ± 3.1 kg-weight increment in the first 25 weeks of pregnancy, versus 13.4 ± 5.0 kg and 6.9 ± 3.2 kg in the first 25 weeks in the control group (between groups: p < 0.001/p = 0.002). Incidence of macrosomia was not significantly lower in the intervention group than in the control group (8/7.9% vs 11/9.9%) (p > 0.05). No significant difference was found in the rate of natural labor and occurrence of perinatal complications (e.g., preterm birth, gestational hypertension, and preeclampsia) between the groups (p > 0.05).The WeChat-assisted dietary and exercise intervention was effective in reducing the occurrence of GDM and excessive weight gain in overweight/obese pregnant women. Disseminating knowledge of pregnancy and childbirth through social media platforms like WeChat could be an important part of antenatal care."
1,"TITLE: Metformin and carotid intima-media thickness in never-smokers with type 1 diabetes: The REMOVAL trial.ABSTRACT: To determine whether metformin's effects on carotid artery intima-media thickness (cIMT) in type 1 diabetes differ according to smoking status.Regression model effect estimates for the effect of metformin versus placebo (double-blind) on carotid IMT were calculated as a subgroup analysis of the REMOVAL trial.In 428 randomized participants (227 never-smokers, 201 ever-smokers), averaged mean carotid IMT progression (per year) was reduced by metformin versus placebo in never-smokers (-0.012 mm, 95% CI -0.021 to -0.002; p = .0137) but not in ever-smokers (0.003 mm, 95% CI -0.008 to 0.014; p = .5767); and similarly in non-current smokers (-0.008 mm, 95% CI -0.015 to -0.00001; p = .0497) but not in current smokers (0.013 mm, 95% CI -0.007 to 0.032; p = .1887). Three-way interaction terms (treatment*time*smoking status) were significant for never versus ever smoking (p = .0373, prespecified) and non-current versus current smoking (p = .0496, exploratory). Averaged maximal carotid IMT progression (per year) was reduced by metformin versus placebo in never-smokers (-0.020 mm, 95% CI -0.034 to -0.006; p = .0067) but not in ever-smokers (-0.006 mm, 95% CI -0.020 to 0.008; p = .4067), although this analysis was not supported by a significant three-way interaction term.This subgroup analysis of the REMOVAL trial provides additional support for a potentially wider role of adjunct metformin therapy in cardiovascular risk management in type 1 diabetes, particularly for individuals who have never smoked cigarettes."
1,"TITLE: Prophylactic Administration of Uterotonics to Prevent Postpartum Hemorrhage in Women Undergoing Cesarean Delivery for Arrest of Labor: A Randomized Controlled Trial.ABSTRACT: To evaluate whether prophylactic administration of oxytocin plus ergonovine or oxytocin plus carboprost is more effective than oxytocin alone in reducing the need for additional uterotonics among women undergoing cesarean delivery for labor arrest.In this double-blind, three-arm randomized controlled trial, participants were assigned to receive either oxytocin 5 units intravenous alone, or with ergonovine 0.25 mg intravenous or carboprost 0.25 mg intramuscular immediately after delivery, followed with maintenance infusion of oxytocin 40 milliunits/minute in all groups. Uterine tone was assessed at 3, 5, and 10 minutes after delivery, and additional uterotonics were administered if deemed necessary. The primary outcome was intraoperative need for additional uterotonics. Secondary outcomes included uterine tone, calculated blood loss, and side effects. A sample size of 34 per group (n=102), based on the null hypothesis that there is no association between treatment assignment and the need for additional uterotonics, permitted independent post hoc pairwise comparisons between oxytocin plus ergonovine, oxytocin plus carboprost, and oxytocin alone using an adjusted P-value of .025. The association between the need for additional uterotonics and treatment group was assessed using the χ2 test.From June 2013 through July 2019, 105 participants were randomized (35 per group) and data from 100 participants were analyzed: oxytocin (n=35), oxytocin plus ergonovine (n=33), and oxytocin plus carboprost (n=32). There was no difference in the requirement of additional intraoperative uterotonics across groups (oxytocin [37%] vs oxytocin plus ergonovine [33%] vs oxytocin plus carboprost [34%], P=.932). Uterine tone and calculated blood loss were similar across groups. Incidence of nausea or vomiting was higher in oxytocin plus ergonovine (85%; odds ratio [OR] 5.3, 95% CI 1.7-16.9, P=.003) and oxytocin plus carboprost (72%; OR 2.4, 95% CI 0.9-6.7, P=.086) compared with the oxytocin (51%) group.Compared with oxytocin alone, prophylactic use of a combination of uterotonic drugs did not reduce the need for additional uterotonics at cesarean delivery for labor arrest.ClinicalTrials.gov, NCT01869556."
1,"TITLE: Failure of oral DHEA treatment to increase local salivary androgen outputs of female patients with Sjögren's syndrome.ABSTRACT: Sjögren's syndrome (SS) is a female-dominant autoimmune disease characterized by androgen depletion and defective dehydroepiandrosterone (DHEA) processing enzymatic machinery in the salivary glands. We hypothesized that, because of these local failures, DHEA replacement therapy would be unable to improve the local androgen deficiency in SS salivary glands.DHEA-deficient female SS patients (n = 12) were treated with placebo for 4 months followed by DHEA 50 mg q.d. for 4 months. Serum and saliva, collected in the morning before the trial and after both periods, were analysed for pro-hormones, androgens, and androgen metabolite using an enzyme-linked immunosorbent assay (ELISA).DHEA treatment increased serum DHEA-sulfate from 1.3 ± 0.1 to 6.4 ± 1.3 µM (p = 0.005), DHEA from 16.5 ± 2.8 to 34.8 ± 8.2 nM (p = 0.012), androstenedione from 3.1 ± 0.3 to 17.2 ± 1.9 nM (p = 0.002), free testosterone from 2.2 ± 0.1 to 7.7 ± 1.1 pM (p = 0.002), DHT from 275.5 ± 24.4 to 834.6 ± 122.8 pM (p = 0.002) and 3-α-diol-G from 3.8 ± 0.6 to 13.6 ± 2.0 nM (p = 0.001). However, only salivary DHEA and DHT outputs increased significantly and 25% of the patients showed no increases, except for DHEA itself. Outputs of active androgens (T, DHT) and 3-α-diol-G metabolite correlated with salivation.The local androgen deficiency in SS salivary glands is not only caused by low serum DHEA(-S) because restoration of systemic androgen levels by DHEA treatment did not correct local androgen depletion. This could be explained by low or no capacity of DHEA-substituted patients to convert the pro-steroid to active androgen metabolites. Such intracrine failures affect women in particular, who must produce their salivary T and DHT locally from DHEA."
1,"TITLE: Mycophenolic acid-related diarrhea is not associated with polymorphisms in SLCO1B nor with ABCB1 in renal transplant recipients.ABSTRACT: We investigated the association between genetic polymorphisms in ABCB1 and SLCO1B and mycophenolic acid (MPA) pharmacokinetics, and MPA-related diarrhea and leukopenia in 338 kidney transplant recipients.A total of 338 patients participating in an international, randomized-controlled clinical trial were genotyped for ABCB1 and SLCO1B. Patients were all treated with mycophenolate mofetil and either cyclosporine or tacrolimus. MPA-area under the curve (AUCs), MPA-glucuronide AUCs and acylglucuronide-AUCs were measured on days 3 and 10, and months 1, 3, 6, and 12 after kidney transplantation.The risk of developing diarrhea was 1.8-fold higher in patients cotreated with tacrolimus compared with patients cotreated with cyclosporine (95% confidence interval: 1.03-3.13; P=0.038). ABCB1 and SLCO1B SNPs were not associated with dose-adjusted exposure to MPA, MPA-glucuronide, nor acylglucuronide-MPA nor with the incidence of diarrhea or leukopenia.Genotyping for ABCB1 or SLCO1B pretransplantation is unlikely to be of clinical value for individualization of MPA therapy."
1,"TITLE: The supplementation of acetyl-L-carnitine decreases fatigue and increases quality of life in patients with hepatitis C treated with pegylated interferon-α 2b plus ribavirin.ABSTRACT: The aim of this study was to evaluate whether supplementation of acetyl-L-carnitine (ALC) to pegylated-interferon-α 2b (Peg-IFN-α 2b) and ribavirin (RBV) improves the health-related quality of life during the treatment for chronic hepatitis C, thereby decreasing the risk of treatment discontinuation. Sixty patients with chronic hepatitis C underwent treatment with Peg-IFN-α 2b + RBV (group A; n = 29) or Peg-IFN-α 2b + RBV + ALC (group B; n = 31) for 12 months. At the end of the study, the comparison between group A and group B showed significant differences in aspartate aminotransferase (AST) (-80.9 versus -110.3; P < 0.001), alanine aminotransferase (-111.6 versus -134.7; P < 0.001), Viremia (-3.26 versus -3.82; P < 0.05), mental health (0 versus 11; P < 0.001), physical functioning (-1 versus 8; P < 0.001), role-physical (1 versus 13; P < 0.001), bodily pain (1 versus 12; P < 0.001), general health (3 versus 12; P < 0.001), vitality (3 versus 13; P < 0.001), social functioning (3 versus 10; P < 0.001), physical fatigue (2.1 versus -5.4; P < 0.001), mental fatigue (-0.7 versus -2.7; P < 0.001), and fatigue severity scale (-3.4 versus -12; P < 0.001). ALC supplementation reduced both mental and physical fatigue, improved health-related quality of life, and, therefore, has the potential to increase patient adherence to the combination regimen. This, in turn, may increase the percentage of patients achieving a sustained virological response."
1,"TITLE: Rosiglitazone and carotid IMT progression rate in a mixed cohort of patients with type 2 diabetes and the insulin resistance syndrome: main results from the Rosiglitazone Atherosclerosis Study.ABSTRACT: Insulin resistance is associated with progression of atherosclerosis. We assessed the effect of 12 months of treatment with rosiglitazone (RSG) on the progression of carotid intima-media thickness (IMT) in people with type 2 diabetes mellitus (T2DM) or the insulin resistance syndrome (IRS).Randomized, double-blind, placebo-controlled trial.Malmö University Hospital, Malmö, Sweden.555 subjects (200 with T2DM and 355 nondiabetics with IRS according to EGIR criteria), aged 35-80 years. 447 subjects (165 T2DM and 282 IRS) completed the study.Participants were allocated to placebo or RSG 4 mg for 2 months and then 8 mg daily.Change in composite IMT [mean IMT in the common carotid artery (CCA) and maximal IMT in the bulb] was the primary and various other IMT measures were secondary outcome variables.There was no effect of RSG treatment in the mixed population. In T2DM patients there was a reduced progression of the composite IMT (mean change: 0.041 vs. 0.070 mm, P = 0.07), and of the mean IMT CCA (mean change: -0.005 mm vs. 0.021 mm, P = 0.007). RSG treatment led to significant reductions of HOMA-IR, fasting plasma glucose, HbA1c, PAI-1 activity, fibrinogen, C-reactive protein and matrix metalloproteinase-9.In a mixed study population of patients with T2DM and IRS RSG treatment was not associated with a statistically significant reduction of carotid IMT progression rate. Separate analyses of these two patient groups indicated, however, a significant beneficial effect on CCA IMT in T2DM patients but no similar effect in subjects with IRS."
1,"TITLE: Comparison of midwife-led and consultant-led care of healthy women at low risk of childbirth complications in the Republic of Ireland: a randomised trial.ABSTRACT: No midwifery-led units existed in Ireland before 2004. The aim of this study was to compare midwife-led (MLU) versus consultant-led (CLU) care for healthy, pregnant women without risk factors for labour and delivery.An unblinded, pragmatic randomised trial was designed, funded by the Health Service Executive (Dublin North-East). Following ethical approval, all women booking prior to 24 weeks of pregnancy at two maternity hospitals with 1,300-3,200 births annually in Ireland were assessed for trial eligibility.1,653 consenting women were centrally randomised on a 2:1 ratio to MLU or CLU care, (1101:552). 'Intention-to-treat' analysis was used to compare 9 key neonatal and maternal outcomes.No statistically significant difference was found between MLU and CLU in the seven key outcomes: caesarean birth (163 [14.8%] vs 84 [15.2%]; relative risk (RR) 0.97 [95% CI 0.76 to 1.24]), induction (248 [22.5%] vs 138 [25.0%]; RR 0.90 [0.75 to 1.08]), episiotomy (126 [11.4%] vs 68 [12.3%]; RR 0.93 [0.70 to 1.23]), instrumental birth (139 [12.6%] vs 79 [14.3%]; RR 0.88 [0.68 to 1.14]), Apgar scores < 8 (10 [0.9%] vs 9 [1.6%]; RR 0.56 [0.23 to 1.36]), postpartum haemorrhage (144 [13.1%] vs 75 [13.6%]; RR 0.96 [0.74 to 1.25]); breastfeeding initiation (616 [55.9%] vs 317 [57.4%]; RR 0.97 [0.89 to 1.06]). MLU women were significantly less likely to have continuous electronic fetal monitoring (397 [36.1%] vs 313 [56.7%]; RR 0.64 [0.57 to 0.71]), or augmentation of labour (436 [39.6%] vs 314 [56.9%]; RR 0.50 [0.40 to 0.61]).Midwife-led care, as practised in this study, is as safe as consultant-led care and is associated with less intervention during labour and delivery."
1,"TITLE: Impact of a structured multidisciplinary intervention on quality of life of older adults with advanced cancer.ABSTRACT: Patients experience reductions in quality of life (QOL) while receiving cancer treatment and several approaches have been proposed to address QOL issues. In this project, the QOL differences between older adult (age 65+) and younger adult (age 18-64) advanced cancer patients in response to a multidisciplinary intervention designed to improve QOL were examined.This study was registered on ClinicalTrials.gov, NCT01360814. Newly diagnosed advanced cancer patients undergoing radiation therapy were randomized to active QOL intervention or control groups. Those in the intervention group received six multidisciplinary 90-minute sessions designed to address the five major domains of QOL. Outcomes measured at baseline and weeks 4, 27, and 52 included QOL (Linear Analogue Self-Assessment (LASA), Functional Assessment of Cancer Therapy-General (FACT-G)) and mood (Profile of Mood States (POMS)). Kruskall-Wallis methodology was used to compare scores between older and younger adult patients randomized to the intervention.Of 131 patients in the larger randomized controlled study, we report data on 54 evaluable patients (16 older adults and 38 younger adults) randomized to the intervention. Older adult patients reported better overall QOL (LASA 74.4 vs. 62.9, p = 0.040), higher social well-being (FACT-G 91.1 vs. 83.3, p = 0.045), and fewer problems with anger (POMS anger-hostility 95.0 vs. 86.4, p = 0.028). Long-term benefits for older patients were seen in the anger-hostility scale at week 27 (92.2 vs. 84.2, p = 0.027) and week 52 (96.3 vs. 85.9, p = 0.005).Older adult patients who received a multidisciplinary intervention to improve QOL while undergoing advanced cancer treatments benefited differently in some QOL domains, compared to younger adult patients. Future studies can provide further insight on how to tailor QOL interventions for these age groups."
0,"TITLE: Risk of recurrent stroke in patients with silent brain infarction in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) imaging substudy.ABSTRACT: Silent brain infarctions are associated with an increased risk of stroke in healthy individuals. Risk of recurrent stroke in patients with both symptomatic and silent brain infarction (SBI) has only been investigated in patients with cardioembolic stroke in the European Atrial Fibrillation Trial. We assessed whether patients with recent noncardioembolic stroke and SBI detected on MRI are at increased risk for recurrent stroke, other cardiovascular events, and mortality.The prevalence of SBI detected on MRI was assessed in 1014 patients enrolled in the imaging substudy of the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. The primary outcome was first recurrence of stroke in patients with both symptomatic stroke and SBI in comparison with age- and sex-matched patients with stroke without SBI. Secondary outcomes were a combined vascular end point, other vascular events, and mortality. The 2 groups were compared using conditional logistic regression.Silent brain infarction was detected in 207 (20.4%) of the 1014 patients. Twenty-seven (13.0%) patients with SBI and 19 (9.2%) without SBI had a recurrent stroke (OR, 1.42; 95% CI, 0.79-2.56; P=0.24) during a mean follow-up of 2.5 years. Similarly, there was no statistically significant difference for all secondary outcome parameters between patients with SBI and matched patients without SBI.The presence of SBI in patients with recent mild noncardioembolic ischemic stroke could not be shown to be an independent risk factor for recurrent stroke, other vascular events, or a higher mortality rate.URL: http://clinicaltrials.gov. Unique identifier: NCT00153062."
1,"TITLE: Ischemia detected on continuous electrocardiography after acute coronary syndrome: observations from the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction 36) trial.ABSTRACT: The purpose of this study was to assess the relationship between ischemia detected on continuous electrocardiographic (cECG) recording and cardiovascular outcomes after acute coronary syndrome (ACS).The small size of prior studies evaluating cECG prevented full evaluation of the risk associated with ischemia across subpopulations and compared with other methods of risk stratification. Ranolazine, a new antianginal agent, reduces ischemic symptoms in patients with chronic angina and after ACS but the anti-ischemic effect, as detected by cECG, is not known.In all, 6,560 patients hospitalized with non-ST-segment elevation ACS were randomly assigned to ranolazine or placebo in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction 36) trial. The cECG was performed for 7 days after randomization. Outcomes were followed for a median of 348 days. Clinical events that occurred during cECG recording were excluded from analysis.A total of 6,355 (97%) patients had cECG recordings evaluable for ischemia analysis. Patients with >or=1 episode of ischemia on cECG (n = 1,271, 20%) were at increased risk of cardiovascular death (7.7% vs. 2.7%, p < 0.001), MI (9.4% vs. 5.0%, p < 0.001), and recurrent ischemia (17.5% vs. 12.3%, p < 0.001). The relationship with cardiovascular death was independent of baseline characteristics or elevated biomarkers (adjusted hazard ratio: 2.46, p < 0.001). Ischemia on cECG was associated with significantly worse outcomes in several subgroups. Ranolazine did not reduce the rate of ischemia detected on cECG (19.9% vs. 21.0%, hazard ratio: 0.93, p = 0.21).In more than 6,300 patients with ACS, ischemia detected on cECG occurred frequently and was strongly and independently associated with poor cardiovascular outcomes, including cardiovascular death. Continuous ECG monitoring to detect ischemia after ACS may help to identify patients at increased risk. (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes [MERLIN]; NCT00099788)."
1,"TITLE: Rotigotine effects on early morning motor function and sleep in Parkinson's disease: a double-blind, randomized, placebo-controlled study (RECOVER).ABSTRACT: In a multinational, double-blind, placebo-controlled trial (NCT00474058), 287 subjects with Parkinson's disease (PD) and unsatisfactory early-morning motor symptom control were randomized 2:1 to receive rotigotine (2-16 mg/24 hr [n = 190]) or placebo (n = 97). Treatment was titrated to optimal dose over 1-8 weeks with subsequent dose maintenance for 4 weeks. Early-morning motor function and nocturnal sleep disturbance were assessed as coprimary efficacy endpoints using the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Examination) measured in the early morning prior to any medication intake and the modified Parkinson's Disease Sleep Scale (PDSS-2) (mean change from baseline to end of maintenance [EOM], last observation carried forward). At EOM, mean UPDRS Part III score had decreased by -7.0 points with rotigotine (from a baseline of 29.6 [standard deviation (SD) 12.3] and by -3.9 points with placebo (baseline 32.0 [13.3]). Mean PDSS-2 total score had decreased by -5.9 points with rotigotine (from a baseline of 19.3 [SD 9.3]) and by -1.9 points with placebo (baseline 20.5 [10.4]). This represented a significantly greater improvement with rotigotine compared with placebo on both the UPDRS Part III (treatment difference: -3.55 [95% confidence interval (CI) -5.37, -1.73]; P = 0.0002) and PDSS-2 (treatment difference: -4.26 [95% CI -6.08, -2.45]; P < 0.0001). The most frequently reported adverse events were nausea (placebo, 9%; rotigotine, 21%), application site reactions (placebo, 4%; rotigotine, 15%), and dizziness (placebo, 6%; rotigotine 10%). Twenty-four-hour transdermal delivery of rotigotine to PD patients with early-morning motor dysfunction resulted in significant benefits in control of both motor function and nocturnal sleep disturbances."
1,"TITLE: Reducing Elevated Heart Rates in Patients with Multiple Organ Dysfunction Syndrome with The If (Funny Channel Current) Inhibitor Ivabradine.ABSTRACT: A heart rate higher than 90 beats/min indicates an unfavorable prognosis for patients with multiple organ dysfunction syndrome (MODS). We sought to investigate the effect of the pacemaker current (If) inhibitor ivabradine on heart rate, hemodynamics, and disease severity among patients with MODS.In this prospective, controlled, randomized, open-label, two-arm phase II trial, 70 patients with MODS, a sinus rhythm of at least 90 beats/min, and contraindications to β-blocker therapy were randomly assigned to receive the standard treatment ± ivabradine (5 mg twice daily) for 96 h via the enteral route. The primary outcome was the percentage of patients with a heart rate reduction of at least 10 beats/min after 96 h. Secondary outcomes included the effect of ivabradine on hemodynamics, disease severity, vasopressor use, mortality, and adverse events.There were no significant differences in the primary outcome between the ivabradine and control groups (P = 0.147). After 96 h, the daily median heart rate was reduced by 7 beats/min in the control group and by 16 beats/min in the ivabradine group (P = 0.014). No differences in secondary outcomes were observed.The number of critically ill patients with MODS and a sinus rhythm of at least 90 beats/min that experienced a heart rate reduction of at least 10 beats/min after oral ivabradine treatment did not differ significantly between groups. The moderate but significant reduction of heart rate by 7 beats/min did not affect hemodynamics or disease severity."
1,"TITLE: Testing the efficacy of and parents' preferences for nutrition labels on children's menus from a full-service chain restaurant: results of an online experiment.ABSTRACT: Test the efficacy and perceived effectiveness of nutrition labels on children's menus from a full-service chain restaurant in an online study.Using a between-groups experiment, parents were randomised to view children's menus displaying one of five children's nutrition labelling conditions: (i) No Nutrition Information (control); (ii) Calories Only; (iii) Calories + Contextual Statement (CS); (iv) Calories, Sodium + CS; or (v) Calories and Sodium in Traffic Lights + CS. Parents hypothetically ordered up to one entrée, side, beverage and dessert for their child, then rated and ranked all five labelling conditions on the level of perceived effectiveness.Online survey.998 parents with a 3-12 year old child.Parents exposed to menus displaying 'Calories, Sodium + CS' selected significantly fewer calories 'overall' (entrées + side + dessert + beverage) compared to parents exposed to the control condition (-53·1 calories, P < 0·05). Parents selected 'entrees' with significantly fewer calories and lower sodium when exposed to menus with 'Calories + CS' (-24·3 calories, P < 0·05); 'Calories, Sodium + CS' (-25·4 calories, -56·1 mg sodium, P < 0·05 for both); and 'Calories and Sodium in Traffic Lights + CS' (-29·1 calories, -58·6 mg sodium, P < 0·05 for both). Parents exposed to menus with 'Calories, Sodium + CS' and 'Calories and Sodium in Traffic Lights + CS' were more likely to notice and understand nutrition information compared to other nuntrition labelling conditions. Parents perceived the menu with 'Calories and Sodium in Traffic Lights + CS' as most effective (P < 0·05).Menus disclosing calories, sodium and a contextual statement increased the proportion of parents who noticed and understood nutrition information, and resulted in parents selecting lower calorie and sodium entrées for their children in the hypothetical purchase task."
1,"TITLE: Longterm Effect on Leisure Time Physical Activity Level in Individuals with Axial Spondyloarthritis: Secondary Analysis of a Randomized Controlled Trial.ABSTRACT: To explore the longterm effect of a 3-month exercise program on leisure time physical activity level in individuals with axial spondyloarthritis (axSpA).A secondary analysis was performed on data from 100 individuals with axSpA who were included in a randomized controlled trial. The exercise group (EG) participated in a 3-month exercise program while the control group (CG) received no intervention. Physical activity during leisure time was measured with a questionnaire (physically active: ≥ 1 h/week with moderate/vigorous intensity physical activity). Disease activity was measured with the Ankylosing Spondylitis Disease Activity Scale (ASDAS; higher score = worst). Statistical analyses were performed on an intention-to-treat basis using chi-square tests, logistic regression, and mixed models.At the 12-month followup, significantly more individuals in the EG than in the CG were physically active [29 (67%) vs 13 (30%), p < 0.001] and exercised 2-3 times/week [25 (58%) vs 15 (34%), p = 0.02], and fewer exercised at light intensity [3 (8%) vs 14 (44%), p = 0.002]. ""Participation in the EG"" (OR 6.7, 95% CI 2.4-18.6, p < 0.001) and ""being physically active at baseline"" (OR 4.7, 95% CI 1.4-15.8, p = 0.01) were the factors most associated with being physically active. There were no differences between the groups in ASDAS (p = 0.79).A 3-month exercise program had a beneficial longterm effect on leisure time physical activity in individuals with axSpA, thus indicating a more beneficial health profile. Still, few individuals continued the intensive program, and there was no difference between the groups in disease activity after 12 months. (ClinicalTrials.gov: NCT02356874)."
1,"TITLE: Knowledge of and Intention to Participate in Physical Activity Programs and Their Associated Sociodemographic Factors in People with High Blood Pressure in a Rural Area of Bangladesh: Initial Investigation from a Cluster Randomized Controlled Trial.ABSTRACT: This initial investigation aimed to investigate the knowledge of the health benefits of physical activity (PA) and attitudes towards participation in PA. The study recruited 307 people aged 30-75 years with hypertension as part of a cluster randomized controlled trial from a rural area in Bangladesh. Of the 307 participants, 135 participated less than 2.5 h of physical activity per week, from which we collected data on attitudes toward PA. Regression analysis and Rasch analysis were used. More than 85% of homemakers, employees or businesspersons were willing to take part in PA. Based on the combined score from the knowledge and attitude items, 46% of people endorsed PA programs; proportions were higher in men than women (53% vs. 41%). After adjusting for covariates, men (odds ratio, 95% confidence interval (CI) 3.50, 1.72-7.11) compared to women and people with at least primary levels of schooling (OR 3.06, 95% CI, 1.27-7.38) compared with those with no education were more likely to organize or take part in any PA programs. People have positive attitudes towards PA but do not feel obligated to participate in PA programs. Future programs are needed to promote awareness and motivational interventions for PA, especially targeting women and people with low education levels, should be developed and implemented."
1,"TITLE: Cost-Effectiveness and Cost-Utility of a Home-Based Exercise Program in Geriatric Patients with Cognitive Impairment.ABSTRACT: There is a substantial lack of home-based exercise programs in the highly vulnerable group of geriatric patients with cognitive impairment (CI) after discharge from ward rehabilitation. Beyond clinical effectiveness, the cost-effectiveness of intervention programs to enhance physical performance is not well investigated in this target group.The aim of the study was to determine the cost-effectiveness of a 12-week home-based exercise intervention following discharge from ward rehabilitation compared to unspecified flexibility training for geriatric patients with CI from a societal perspective.This cost-effectiveness study was conducted alongside a randomized placebo-controlled trial. A total of 118 geriatric patients with CI (Mini-Mental State Examination score: 17-26) were randomized either to the intervention group (IG, n = 63) or control group (CG, n = 55). Participants in the IG received a home-based individually tailored exercise program to increase physical performance, while participants in the CG received unspecific flexibility training (placebo control). Healthcare service use, physical performance (Short Physical Performance Battery, SPPB), and quality of life (EQ-5D-3L) were measured over 24 weeks. The net monetary benefit (NMB) approach was applied to calculate incremental cost-effectiveness of the exercise intervention compared to the CG with respect to improvement of (a) physical performance on the SPPB and (b) quality-adjusted life years (QALYs).Physical performance was significantly improved in the IG compared to the CG (mean difference at 24 weeks: 1.3 points; 95% confidence interval [95% CI] = 0.5-2.2; p = 0.003), while health-related quality of life did not significantly differ between the groups at 24 weeks (mean difference: 0.08; 95% CI = -0.05 to 0.21; p = 0.218). Mean costs to implement the home-based exercise intervention were EUR 284 per patient. The probability of a positive incremental NMB of the intervention reached a maximum of 92% at a willingness to pay (WTP) of EUR 500 per point on the SPPB. The probability of cost-utility referring to QALYs was 85% at a WTP of EUR 5,000 per QALY.The home-based exercise intervention demonstrated high probability of cost-effectiveness in terms of improved physical performance in older adults with CI following discharge from ward rehabilitation, but not in terms of quality of life."
1,"TITLE: Effects of omega-3 fatty acids on resting heart rate, heart rate recovery after exercise, and heart rate variability in men with healed myocardial infarctions and depressed ejection fractions.ABSTRACT: We explored possible mechanisms by which recommended intakes of omega-3 fatty acids may decrease the risk for sudden cardiac death in patients with documented coronary heart disease. The cardioprotective effects of omega-3 fatty acids have been documented in epidemiologic and randomized controlled trials. These fatty acids are presumed to decrease susceptibility to fatal arrhythmias, but whether this is mediated by classic risk factors or direct cardiac mechanisms is not known. Eighteen white men with a history of myocardial infarction and ejection fractions <40% were randomized to placebo or omega-3 fatty acids (585 mg of docosahexaenoic acid and 225 mg of eicosapentaenoic acid) for two 4-month periods in a crossover design. At the end of each period, heart rate (HR), HR variability, and rate of HR recovery after exercise were determined, as were effects on arterial compliance, blood pressure, cardiac function, and fasting serum levels of lipids and inflammatory markers. Omega-3 fatty acids decreased HR at rest from 73 +/- 13 to 68 +/- 13 beats/min (p <0.0001) and improved 1-minute HR recovery after exercise (-27 +/- 10 to -32 +/- 12 beats/min, p <0.01). HR variability in the high-frequency band increased (p <0.02), but no change was noted in overall HR variability. There were no significant effects on blood pressure, arterial compliance, lipids, or inflammatory markers. These changes are consistent with an increase in vagal activity and may in part explain the observed decrease in risk for sudden cardiac death seen with omega-3 fatty acid supplementation."
1,"TITLE: A randomized controlled trial to isolate the effects of fasting and energy restriction on weight loss and metabolic health in lean adults.ABSTRACT: Intermittent fasting may impart metabolic benefits independent of energy balance by initiating fasting-mediated mechanisms. This randomized controlled trial examined 24-hour fasting with 150% energy intake on alternate days for 3 weeks in lean, healthy individuals (0:150;  = 12). Control groups involved a matched degree of energy restriction applied continuously without fasting (75% energy intake daily; 75:75;  = 12) or a matched pattern of fasting without net energy restriction (200% energy intake on alternate days; 0:200;  = 12). Primary outcomes were body composition, components of energy balance, and postprandial metabolism. Daily energy restriction (75:75) reduced body mass (-1.91 ± 0.99 kilograms) almost entirely due to fat loss (-1.75 ± 0.79 kilograms). Restricting energy intake via fasting (0:150) also decreased body mass (-1.60 ± 1.06 kilograms;  = 0.46 versus 75:75) but with attenuated reductions in body fat (-0.74 ± 1.32 kilograms;  = 0.01 versus 75:75), whereas fasting without energy restriction (0:200) did not significantly reduce either body mass (-0.52 ± 1.09 kilograms;  ≤ 0.04 versus 75:75 and 0:150) or fat mass (-0.12 ± 0.68 kilograms;  ≤ 0.05 versus 75:75 and 0:150). Postprandial indices of cardiometabolic health and gut hormones, along with the expression of key genes in subcutaneous adipose tissue, were not statistically different between groups ( > 0.05). Alternate-day fasting less effectively reduces body fat mass than a matched degree of daily energy restriction and without evidence of fasting-specific effects on metabolic regulation or cardiovascular health."
1,"TITLE: Long-term outcomes of ivermectin-albendazole versus albendazole alone against soil-transmitted helminths: Results from randomized controlled trials in Lao PDR and Pemba Island, Tanzania.ABSTRACT: Preventive chemotherapy is the cornerstone of soil-transmitted helminth (STH) control. Long-term outcomes and adequate treatment frequency of the recently recommended albendazole-ivermectin have not been studied to date.Double-blind randomized controlled trials were conducted in Lao PDR, Pemba Island, Tanzania and Côte d'Ivoire between 2018 and 2020 to evaluate the efficacy and safety of ivermectin-albendazole versus albendazole-placebo in Trichuris trichiura-infected individuals aged 6 to 60. In the framework of this study, in Lao PDR 466 and 413 participants and on Pemba Island, 558 and 515 participants were followed-up six and 12 months post-treatment, respectively. From each participant at least one stool sample was processed for Kato-Katz diagnosis and cure rates (CRs), egg reduction rates (ERRs) and apparent reinfection rates were calculated. If found helminth-positive at six months, participants were re-treated according to their allocated treatment. Long-term outcomes against T. trichiura based on CRs and ERRs of ivermectin-albendazole compared to albendazole were significantly higher at six months in Lao PDR (CR, 65.8 vs 13.4%, difference; 52.4; 95% CI 45.0-60.0; ERRs, 99.0 vs 79.6, difference 19.4; 95% CI 14.4-24.4) and Pemba Island (CR, 17.8 vs 1.4%, difference; 16.4; 95% CI 11.6-21.0; ERRs, 84.9 vs 21.2, difference 63.8; 95% CI 50.6-76.9) and also at 12 months in Lao PDR (CR, 74.0 vs 23.4%, difference; 50.6; 95% CI 42.6-61.0; ERRs, 99.6 vs 91.3, difference 8.3; 95% CI 5.7-10.8) and Pemba Island (CR, 19.5 vs 3.4%, difference; 16.1; 95% CI 10.7-21.5; ERRs, 92.9 vs 53.6, difference 39.3; 95% CI 31.2-47.4) respectively. Apparent reinfection rates with T. trichiura were considerably higher on Pemba Island (100.0%, 95% CI, 29.2-100.0) than in Lao PDR (10.0%, 95% CI, 0.2-44.5) at 12 months post-treatment for participants treated with albendazole alone.The long-term outcomes against T. trichiura of ivermectin-albendazole are superior to albendazole in terms of CRs and ERRs and in reducing infection intensities. Our results will help to guide decisions on how to best use ivermectin-albendazole in the context of large-scale PC programs tailored to the local context to sustainably control STH infections.ClinicalTrials.gov registered with clinicaltrials.gov, reference: NCT03527732, date assigned: 17 May 2018."
1,"TITLE: The impact of school uniforms on primary school student's physical activity at school: outcomes of a cluster randomized controlled trial.ABSTRACT: Many school-based physical activity (PA) interventions are complex and have modest effects when delivered in real world contexts. A commonly reported barrier to students' PA, particularly among girls, are uniforms that are impractical (e.g. tunic/dress and black leather shoes). Modifying student uniforms may represent a simple intervention to enhance student PA. The primary aim of this trial was to assess the impact of a PA enabling uniform intervention (shorts, polo shirt and sports shoes) on girls' moderate-to-vigorous physical activity (MVPA) and total PA i.e. counts per minute (cpm).A cluster randomized controlled trial was undertaken in 42 primary schools in New South Wales, Australia. Schools were randomized on one school day to the intervention group, where students wore a PA enabling uniform (their sports uniform) or a control group, where students wore their usual traditional uniform. Student PA was measured using wrist-worn Actigraph GT3X and GT9X accelerometers. Linear mixed models controlling for student characteristics were used to examine the effects of the intervention..Of the 3351 eligible students, 2315 (69.1%) had parental consent and 2180 of these consenting students participated (94.2%) of which 1847 (84.7%) were included in the analysis. For the primary aim the study found no significant differences between girls at schools allocated to the intervention relative to the control on change in MVPA (0.76 min, 95% CI - 0.47 to 1.99, p = 0.22) or cpm (36.99, 95% CI - 13.88 to 87.86, p = 0.15). Exploratory analysis revealed small effects for a number of findings, including significant reduction in sedentary activity (- 1.77, 95% CI - 3.40 to - 0.14, p = 0.035) among all students at schools allocated to the intervention, and non-significant improvements in girls' light intensity PA (1.47 min, 95% CI - 0.06 to 3.00, p = 0.059) and sedentary activity (- 2.23 min; 95% CI - 4.49 to 0.02, p = 0.052).The findings suggests that the intervention may yield small improvements in some measure of PA and require substantiation in a larger RCT with longer-term follow-up. The inclusion of additional intervention components may be required to achieve more meaningful effects.The trial was prospectively registered with Australian New Zealand Clinical Trials Register ACTRN12617001266358 1st September 2017."
1,"TITLE: Accumulated brisk walking reduces arterial stiffness in overweight adults: evidence from a randomized control trial.ABSTRACT: Arterial stiffness is a major contributor to the development of atherosclerosis and consequently cardiovascular disease. This study aimed to examine whether 6 months of accumulated (3 × 10 minutes, 5 days/week) brisk walking was sufficient to reduce arterial stiffness in sedentary, overweight individuals. Seventy-seven individuals (19 men, 58 women; age, 30-55 years) were randomly allocated to one of three groups; two groups completed 30 minutes of accumulated walking with either monthly or weekly telephone support; the third group (control) performed stretching exercises. The walking groups were combined and telephone support included as a covariate. Anthropometry, blood pressure (BP), blood lipids, pulse wave velocity (PWV), and NOx (surrogate marker for nitric oxide) were measured at baseline, post-intervention and 4 months post-intervention. No changes were observed for anthropometry, BP, or lipids. However, at the end of the intervention, there was a decrease in PWV (P < .001) accompanied by an increase in NOx (P < .001), with changes maintained 4 months post-intervention. A strong negative correlation between PWV and NOx was also observed (P < .001; r = -0.65). A lifestyle approach to meeting current physical activity guidelines results in favorable alterations in arterial function in overweight individuals."
1,"TITLE: Hyaluronic acid dressing (Healoderm) in the treatment of diabetic foot ulcer: A prospective, randomized, placebo-controlled, single-center study.ABSTRACT: Fast and complete healing of a diabetic foot ulcer (DFU) is challenging due to the hostile wound healing environment of the diabetic patients. As a part of a multimodal treatment approach, advanced dressing material using hyaluronic acid (HA) has been found to be effective. However, previous studies have used HA with additional biologics, which interferes in determining the true clinical effect of HA in DFU. To examine the sole effectiveness of HA in DFU treatment, a prospective, randomized, placebo-controlled, single-center study was conducted using an HA dressing without additional substances. Thus, 34 patients who met the inclusion criteria were randomized into two groups (the study group: HA dressing material; the control group: conventional dressing material). During the 12-week study period, complete ulcer healing rate was evaluated as a primary endpoint. Additionally, healing velocity and the mean duration for achieving a 50% ulcer size reduction was compared between the two groups as a secondary endpoint. At the end of the study, the study group presented a significantly higher complete healing rate as compared to that in the control group [84.6% (11/13), 41.6% (5/12), respectively, P = 0.041]. Additionally, faster ulcer healing velocity and shorter mean duration for achieving a 50% ulcer size reduction were observed in the study group (P = 0.022 and 0.004, respectively). The Kaplan-Meier survival analysis for the median time for 50% ulcer healing rate also showed a significantly shorter duration in the study group (21 days vs. 39 days, P = 0.0127). Finally, there were no adverse events related to the dressing materials used in the study. As a major component of the extracellular matrix, this study supports the safety and efficacy of a pure HA dressing without additional substances in treating DFU."
1,"TITLE: Nocturnal glucose metabolism after bedtime injection of insulin glargine or neutral protamine hagedorn insulin in patients with type 2 diabetes.ABSTRACT: Insulin glargine is a long-acting human insulin analog often administered at bedtime to patients with type 2 diabetes. It reduces fasting blood glucose levels more efficiently and with less nocturnal hypoglycemic events compared with human neutral protamine Hagedorn (NPH) insulin. Therefore, bedtime injections of insulin glargine and NPH insulin were compared overnight and in the morning.In 10 type 2 diabetic patients, euglycemic clamps were performed, including [6,6'](2)H(2) glucose, to study the rate of disappearance (Rd) and endogenous production (EGP) of glucose during the night. On separate days at bedtime (2200 h), patients received a sc injection of insulin glargine, NPH insulin, or saline in a randomized, double-blind fashion.Similar doses of both insulins had different metabolic profiles. NPH insulin had a greater effect on both Rd and EGP in the night compared with insulin glargine. By contrast, in the morning, insulin glargine was more effective, increasing Rd by 5.8 micromol/kg(-1).min(-1) (95% confidence interval 4.7-6.9) and reducing EGP -5.7 (-5.0 to -6.4) compared with NPH insulin. Nearly 80% of the glucose lowering effect in the morning was due to insulin glargine's reduction of EGP. Its injection was associated with one-third lower morning glucagon levels compared with NPH insulin (P = 0.021).Nocturnal variations of EGP and Rd explain the reduced incidence of hypoglycemia and lower fasting glucose levels reported for insulin glargine compared with human NPH insulin."
1,"TITLE: Randomised controlled trial of amoxycillin clavulanate in children with chronic wet cough.ABSTRACT: Despite guideline recommendations, there are no published randomised controlled trial data on the efficacy of antibiotics for chronic wet cough in children. The majority of children with chronic wet cough have protracted bacterial bronchitis (PBB), a recognised condition in multiple national guidelines. The authors conducted a parallel 1:1 placebo randomised controlled trial to test the hypothesis that a 2-week course of amoxycillin clavulanate is efficacious in the treatment of children with chronic wet cough.50 children (median age 1.9 years, IQR 0.9-5.1) with chronic (>3 weeks) wet cough were randomised to 2 weeks of twice daily oral amoxycillin clavulanate (22.5 mg/kg/dose) or placebo. The primary outcome was 'cough resolution' defined as a >75% reduction in the validated verbal category descriptive cough score within 14 days of treatment compared with baseline scores, or cessation of cough for >3 days. In selected children, flexible bronchoscopy and bronchoalveolar lavage (BAL) were undertaken at baseline.Cough resolution rates (48%) were significantly higher in children who received amoxycillin clavulanate compared with those who received placebo (16%), p=0.016. The observed difference between proportions was 0.32 (95% CI 0.08 to 0.56). Post treatment, median verbal category descriptive score in the amoxycillin clavulanate group of 0.5 (IQR 0.0-2.0) was significantly lower than in the placebo group, 2.25 (IQR 1.15-2.9) (p=0.02). Pre-treatment BAL data were consistent with PBB in the majority of children, with no significant difference between groups.A 2-week course of amoxycillin clavulanate will achieve cough resolution in a significant number of children with chronic wet cough. BAL data support the diagnosis of PBB in the majority of these children.ACTRN 12605000533695."
1,"TITLE: Trait dissociation as a predictor of induced dissociation by ketamine or esketamine in treatment-resistant depression: Secondary analysis from a randomized controlled trial.ABSTRACT: Dissociative symptoms are common, possibly severe, side effects associated with the use of ketamine and esketamine in depression. We investigated the relationship between trait dissociation and dissociation induced by ketamine and esketamine used as augmentation therapy in treatment-resistant depression (TRD). Adults with TRD were randomly assigned to receive a single intravenous infusion, with a duration of 40 min, of either esketamine 0.25 mg/kg or ketamine 0.5 mg/kg. We assessed trait dissociation with the Dissociative Experience Scale (DES) and, to evaluate induced dissociation, the Clinician-Administered Dissociative States Scale (CADSS) was used. Thirty-two subjects received esketamine and 29 received ketamine. The groups had similar median DES scores (p = 0.26). More than 30% of the patients in both groups had DES scores ≥30 points. The median CADSS score in the esketamine group was equivalent to that in the ketamine group (p = 0.40). Every 5 points increment in the DES was associated with a 10.9% (95% CI 4.5-17.8%) increase in the CADSS, in an exponential fashion when the two groups were pooled together. Subjects with high trait dissociation had a higher risk of induced dissociation state (relative risk [RR] 1.41, 95% CI 1.11-1.78) and very high induced dissociation (RR 3.05, 95% CI 1.14-8.15). Induced dissociation was not a serious adverse effect. The findings suggest that trait dissociation is a predictor of induced dissociation by Ketamine or Esketamine in TRD subjects. Screening for trait dissociation and counseling patients with high trait dissociation on the risks of dissociation by these drugs are recommended."
1,"TITLE: Steroids to reduce the impact on delirium (STRIDE): a double-blind, randomised, placebo-controlled feasibility trial of pre-operative dexamethasone in people with hip fracture.ABSTRACT: Neuro-inflammation may be important in the pathogenesis of postoperative delirium following hip fracture surgery. Studies have suggested a potential role for steroids in reducing postoperative delirium; however, the potential efficacy and safety of pre-operative high-dose dexamethasone in this specific population is largely unknown. Conducting such a study could be challenging, considering the multidisciplinary team involvement and the emergency nature of the surgery. The aim of this study was to assess feasibility and effectiveness of dexamethasone given as early as possible following hospital admission for hip fracture, to inform whether a full-scale trial is warranted. This single-centre, randomised, double-blind, placebo-controlled study randomly allocated 79 participants undergoing hip fracture surgery to dexamethasone 20 mg or placebo pre-operatively. Eligibility and recruitment rates, timing of the intervention and adverse events were recorded. Incidence and severity of postoperative delirium were assessed using the 4AT delirium screening tool and the Memorial Delirium Assessment Scale. Postoperative pain, length of stay and mortality were also assessed. The eligibility rate for inclusion was 178/527 (34%), and 57/178 (32%) of eligible patients presented to hospital when no researcher was available (e.g. after-hours, weekends, public holidays). Recruitment was limited mainly by ethical limitations (not including patients with impaired cognition) and lack of weekend staffing. Median (IQR [range]) time from emergency department admission to drug administration was 13.3 (5.9-17.6 [1.8-139.6]) hours. There was a significant difference in delirium severity scores, favouring the dexamethasone group: median (IQR [range]) 5 (3-6 [3-7]) vs. 9 (6-13 [5-14]) in the placebo group, with the probability of superiority effect size being 0.89, p = 0.010. Delirium incidence did not differ between groups: 6/40 (15%) in the dexamethasone group vs. 9/39 (23%) in the placebo group, relative risk (95%CI) 0.65 (0.22-1.65), p = 0.360). A larger randomised controlled trial is feasible and ideally this should include people with existing cognitive impairment, seven days-a-week cover and a multicentre design."
1,"TITLE: Trimethoprim and the CYP2C8*3 allele have opposite effects on the pharmacokinetics of pioglitazone.ABSTRACT: We studied the effects of the CYP2C8 inhibitor trimethoprim and CYP2C8 genotype on the pharmacokinetics of the antidiabetic pioglitazone. In a randomized crossover study, 16 healthy volunteers with the CYP2C8(*)1/(*)1 (n = 8), (*)1/(*)3 (n = 5), or (*)3/(*)3 (n = 3) genotype ingested 160 mg of trimethoprim or placebo twice daily for 6 days. On day 3, they ingested 15 mg of pioglitazone. The effects of trimethoprim on pioglitazone were characterized in vitro. Trimethoprim raised the area under the plasma pioglitazone concentration-time curve (AUC(0-infinity)) by 42% (p < 0.001) and decreased the formation rates of pioglitazone metabolites M-IV and M-III (p < 0.001). During the placebo phase, the weight-adjusted AUC(0-infinity) of pioglitazone was 34% smaller in the CYP2C8(*)3/(*)3 group and 26% smaller in the CYP2C8(*)1/(*)3 group than in the CYP2C8(*)1/(*)1 group (p < 0.05). Trimethoprim inhibited M-IV formation in vitro (inhibition constant 38.2 muM), predicting the in vivo interaction. In conclusion, drug interactions and pharmacogenetics affecting the CYP2C8 enzyme may change the safety of pioglitazone."
1,"TITLE: Rational selection of patients for antibacterial prophylaxis after chemotherapy.ABSTRACT: The SIGNIFICANT (Simple Investigation in Neutropenic Individuals of the Frequency of Infection after Chemotherapy +/- Antibiotic in a Number of Tumours) trial reported a reduction in febrile episodes (FEs) among 1,565 patients with solid cancers and lymphomas receiving cyclical, myelosuppressive chemotherapy (causing grade 4 neutropenia) in a randomized, placebo-controlled, double-blind trial of levofloxacin (P = .01). In response to concerns that increased antibacterial prescribing selects for microbial resistance, we examined our data to explore the rationale for more limited prophylaxis.The risk of FE was calculated for control patients on first versus nonfirst cycles, with or without first-cycle FE, and within subgroups defined by cancer type, performance status (PS), age, and treatment context (adjuvant v nonadjuvant). Using the randomized trial data, the prophylactic efficacy of levofloxacin was examined for the same subgroups.The per-cycle FE incidence was much lower on nonfirst (3.3%) versus first cycles (8.0%). Prophylaxis was less effective for nonfirst (odds ratio [OR] = 0.78; P = .16) compared with first cycles (OR = 0.42; P < .001). However, FE on cycle 1 predicted a much higher risk of FE and a trend to continued prophylactic efficacy on subsequent cycles. FE rate was greatest for testicular cancer (27.9%), then small-cell lung cancer (17.3%), and lowest for breast cancer (11.5%). Prophylactic efficacy was consistent across age, sex, PS, treatment context, and disease type (except possibly non-Hodgkin's lymphoma).Under pressure to limit antibacterial use, these exploratory data support offering prophylactic levofloxacin on cycle 1 only of myelosuppressive cancer chemotherapy and on subsequent cycles after a cycle-1 fever. Prophylactic levofloxacin is effective regardless of age, PS, or tumor type."
1,"TITLE: Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial.ABSTRACT: Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function.To evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI).Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013.Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months.The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure.At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L [IQR, 70-87 µmol/L] vs 79 µmol/L [IQR, 72-89 µmol/L], P = .61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed.Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting.clinicaltrials.gov Identifier: NCT01217307."
1,"TITLE: A behaviour change package to prevent hand dermatitis in nurses working in the National Health Service: results of a cluster randomized controlled trial.ABSTRACT: Occupational hand dermatitis poses a serious risk for nurses.To evaluate the clinical and cost-effectiveness of a complex intervention in reducing the prevalence of hand dermatitis in nurses METHODS: This was a cluster randomized controlled trial conducted at 35 hospital trusts, health boards or universities in the UK. Participants were (i) first-year student nurses with a history of atopic conditions or (ii) intensive care unit (ICU) nurses. Participants at intervention sites received access to a behavioural change programme plus moisturizing creams. Participants at control sites received usual care. The primary outcome was the change of prevalent dermatitis at follow-up (adjusted for baseline dermatitis) in the intervention vs. the control group. Randomization was blinded to everyone bar the trials unit to ensure allocation concealment. The trial was registered on the ISRCTN registry: ISRCTN53303171.Fourteen sites were allocated to the intervention arm and 21 to the control arm. In total 2040 (69·5%) nurses consented to participate and were included in the intention-to-treat analysis. The baseline questionnaire was completed by 1727 (84·7%) participants. Overall, 789 (91·6%) ICU nurses and 938 (84·0%) student nurses returned completed questionnaires. Of these, 994 (57·6%) had photographs taken at baseline and follow-up (12-15 months). When adjusted for baseline prevalence of dermatitis and follow-up interval, the odds ratios (95% confidence intervals) for hand dermatitis at follow-up in the intervention group relative to the controls were 0·72 (0·33-1·55) and 0·62 (0·35-1·10) for student and ICU nurses, respectively. No harms were reported.There was insufficient evidence to conclude whether our intervention was effective in reducing hand dermatitis in our populations. Linked Comment: Brans. Br J Dermatol 2020; 183:411-412."
1,"TITLE: ""Cool"" Topic: Feeding During Moderate Hypothermia After Intracranial Hemorrhage.ABSTRACT: Therapeutic moderate hypothermia (MH; T  33°C-34°C) is being studied for treatment of spontaneous intracerebral hemorrhage (ICH). Nutrition assessment begins with accurate basal metabolic rate (BMR) determination. Although early enteral nutrition (EN) is associated with improved outcomes, it is often deferred until rewarming. We sought to determine the accuracy of predictive BMR equations and the safety and tolerance of EN during MH after ICH.Patients were randomized to 72 hours of MH or normothermia (NT; T  36°C-37°C). Harris-Benedict (BMR-HB) and Penn-State equation (BMR-PS) calculations were compared with indirect calorimetry (IC) at day (D) 0 and D1-3. Patients with MH received trophic semi-elemental gastric EN. Occurrences of feeding intolerance, gastrointestinal (GI)-related adverse events, and ventilator-associated pneumonia (VAP) were analyzed with a double-sided matched pairs t test.Thirteen patients with ICH participated (6 MH, 7 NT). Mean time to initiate EN: 29.9 (MH) vs 18.4 (NT) hours ( P = .046). Average daily EN calories received D0-3: 398 (MH) vs 1006 (NT) ( P < .01). Three patients with MH experienced high gastric residuals prior to prokinetic agents, 1 had mild ileus, and 1 patient with NT vomited. No GI-related adverse events were reported. One patient with MH and 1 patient with NT had VAP. Two patients with MH received IC, and from D0 to D1-3, BMR-HB remained stable (1331 kcal), BMR-PS decreased (1511 vs 1145 kcal, P = .5), and IC decreased (1413 vs 985 kcal, P = .2).In patients with ICH undergoing MH, resting energy expenditure is decreased and predictive equations overestimate BMR. EN is feasible, although delayed EN initiation, high gastric residuals, and less EN provision are common. Future studies should focus on EN initiation within 24 hours, advanced EN rates, and postpyloric feeds during hypothermia."
1,"TITLE: Limited efficacy of antimicrobial metaphylaxis in finishing pigs: A randomized clinical trial.ABSTRACT: Pigs that die from pathogens associated with porcine respiratory disease complex (PRDC) in the late finishing period represent a significant economic wastage. While it is common to apply antimicrobial metaphylaxis (AM) to control PRDC, there are few studies exploring the potential cost-saving benefits of AM. In this study we examined the value of using AM in commercially reared, late finishing pigs, from farms with endemic PRDC. A total of 732 pigs from four AIAO wean to market sources, were blocked into 2 matching cohorts, based on enrollment body weight, sex, and rectal temperature. The cohorts received either control (C) or AM (Tulathromycin 2.5mg/kg IM, Zoetis, Florham Park, NJ, USA). Post treatment weight gain over the 21 day period was used as a measure of health and productivity. The AM treated pigs in the lowest weight quartile at enrollment, showed a significantly improved weight gain over controls (18.5 kg vs. 16.4 kg, mean difference=2.1 kg, CI 1.10-3.10, p=0.005) that was not evident in any other starting weight quartiles. These results indicate that the biological advantage and associated improvement in growth efficiency associated with the use of AM against PRDC, is only conferred to a specific sub-set of animals. The economic advantage of this strategy is therefore, only likely if the indicators of potential benefit (e.g., lighter weight cohort) can be reliably established. Further studies are needed to determine whether targeted AM could be effectively applied across the industry."
0,"TITLE: Triple antiviral therapy in hepatitis C virus infection with or without mixed cryoglobulinaemia: a prospective, controlled pilot study.ABSTRACT: Mixed cryoglobulinaemia is strongly related to hepatitis C virus infection. Treatment with peg-interferon and ribavirin has been indicated as first-line therapy for mild/moderate hepatitis C virus-related mixed cryoglobulinaemia.To evaluate the safety and efficacy of triple boceprevir-based antiviral therapy in patients with or without mixed cryoglobulinaemia previously treated with peg-interferon and ribavirin, and with advanced liver disease.Thirty-five hepatitis C virus-positive patients (17 with asymptomatic mixed cryoglobulinaemia, 5 with symptomatic mixed cryoglobulinaemia, and 11 without mixed cryoglobulinaemia) were treated with triple boceprevir-based antiviral therapy.In 19/22 cryoglobulinaemic subjects (86%), the addition of boceprevir induced cryocrit disappearance. Cryocrit behaviour was related to virological response, with improvement of symptoms upon undetectable viraemia and reappearance after virological breakthrough. The rate of sustained virological response was lower in cryoglobulinaemic patients than in patients without mixed cryoglobulinaemia (23.8% vs 70% respectively, p=0.01).Boceprevir-based therapy was safe and effective in cryoglobulinaemic patients. The correlation between direct inhibition of hepatitis C virus replication and clinical improvement in mixed cryoglobulinaemic patients is definitive proof of the key pathogenetic role played by viral replication. Further studies are needed to confirm and clarify the reduced virological response in patients with mixed cryoglobulinaemia."
1,"TITLE: Trauma-focused cognitive behavioral therapy or eye movement desensitization and reprocessing: what works in children with posttraumatic stress symptoms? A randomized controlled trial.ABSTRACT: To prevent adverse long-term effects, children who suffer from posttraumatic stress symptoms (PTSS) need treatment. Trauma-focused cognitive behavioral therapy (TF-CBT) is an established treatment for children with PTSS. However, alternatives are important for non-responders or if TF-CBT trained therapists are unavailable. Eye movement desensitization and reprocessing (EMDR) is a promising treatment for which sound comparative evidence is lacking. The current randomized controlled trial investigates the effectiveness and efficiency of both treatments. Forty-eight children (8-18 years) were randomly assigned to eight sessions of TF-CBT or EMDR. The primary outcome was PTSS as measured with the Clinician-Administered PTSD Scale for Children and Adolescents (CAPS-CA). Secondary outcomes included parental report of child PTSD diagnosis status and questionnaires on comorbid problems. The Children's Revised Impact of Event Scale was administered during the course of treatment. TF-CBT and EMDR showed large reductions from pre- to post-treatment on the CAPS-CA (-20.2; 95% CI -12.2 to -28.1 and -20.9; 95% CI -32.7 to -9.1). The difference in reduction was small and not statistically significant (mean difference of 0.69, 95% CI -13.4 to 14.8). Treatment duration was not significantly shorter for EMDR (p = 0.09). Mixed model analysis of monitored PTSS during treatment showed a significant effect for time (p < 0.001) but not for treatment (p = 0.44) or the interaction of time by treatment (p = 0.74). Parents of children treated with TF-CBT reported a significant reduction of comorbid depressive and hyperactive symptoms. TF-CBT and EMDR are effective and efficient in reducing PTSS in children."
1,"TITLE: Early Cognitive Impairment after Intracerebral Hemorrhage in the INTERACT1 Study.ABSTRACT: Data on cognitive impairment after acute intracerebral hemorrhage (ICH) are limited. This study is aimed at determining the frequency and predictors of cognitive impairment among participants of the pilot phase, Intensive Blood Pressure (BP) Reduction in Acute Cerebral Hemorrhage Trial (INTERACT1).INTERACT1 was an open randomized trial of early intensive (target systolic BP <140 mm Hg) compared with contemporaneous guideline-recommended BP lowering in 404 patients with elevated systolic BP (150-220 mm Hg) within 6 h of ICH onset. Cognitive impairment was defined by scores ≤24 on the Mini-Mental State Examination (MMSE) assessed by interview on follow-up at 90 days.A total of 231 (64.5%) of 358 90-day survivors had MMSE scores for analyses, and 75 (32.5%) had cognitive impairment. In multivariable analysis, older age (OR 2.48, 95% CI 1.73-3.56 per 10-year increase; p < 0.001), female sex (OR 2.06, 95% CI 1.00-4.23; p = 0.049), prior ICH (OR 2.87, 95% CI 1.08-7.65; p = 0.035), high baseline National Institute of Health Stroke Scale score (OR 1.06, 95% CI 1.00-1.13; p = 0.044), and high mean systolic BP over the first 24 h post-randomization (OR 1.34, 95% CI 1.07-1.68/10 mm Hg increase; p = 0.011) were independently associated with cognitive impairment.One third of patients have significant cognitive impairment early after ICH, which is more frequent in the elderly, females, those with prior ICH, and more severe initial neurological deficit and with persistently high early systolic BP."
1,"TITLE: Endoscopic versus laparoscopic drainage of pseudocyst and walled-off necrosis following acute pancreatitis: a randomized trial.ABSTRACT: Pancreatic fluid collections (PFC) may develop following acute pancreatitis (AP). Endoscopic and laparoscopic internal drainage are accepted modalities for drainage of PFCs but have not been compared in a randomized trial. Our objective was to compare endoscopic and laparoscopic internal drainage of pseudocyst/walled-off necrosis following AP.Patients with symptomatic pseudocysts or walled-off necrosis suitable for laparoscopic and endoscopic transmural internal drainage were randomized to either modality in a randomized controlled trial. Endoscopic drainage comprised of per-oral transluminal cystogastrostomy. Additionally, endoscopic lavage and necrosectomy were done following a step-up approach for infected collections. Surgical laparoscopic cystogastrostomy was done for drainage, lavage, and necrosectomy. Primary outcome was resolution of PFCs by the intended modality and secondary outcome was complications.Sixty patients were randomized, 30 each to laparoscopic and endoscopic drainage. Both groups were comparable for baseline characteristics. The initial success rate was 83.3% in the laparoscopic and 76.6% in the endoscopic group (p = 0.7) after the index intervention. The overall success rate of 93.3% (28/30) and 90% (27/30) in the laparoscopic and endoscopic groups respectively was also similar (p = 1.0). Two patients in the laparoscopic group required endoscopic cystogastrostomy for persistent collections. Similarly, two patients in the endoscopic group required laparoscopic drainage. Postoperative complications were comparable between the groups except for higher post-procedure infection in the endoscopic group (19 vs. 9; p = 0.01) requiring endoscopic re-intervention.Endoscopic and laparoscopic techniques have similar efficacy for internal drainage of suitable pancreatic fluid collections with < 30% debris. The choice of procedure should depend on available expertise and patient preference."
0,"TITLE: Enhancement of intragastric acid stability of a fat emulsion meal delays gastric emptying and increases cholecystokinin release and gallbladder contraction.ABSTRACT: Preprocessed fatty foods often contain calories added as a fat emulsion stabilized by emulsifiers. Emulsion stability in the acidic gastric environment can readily be manipulated by altering emulsifier chemistry. We tested the hypothesis that it would be possible to control gastric emptying, CCK release, and satiety by varying intragastric fat emulsion stability. Nine healthy volunteers received a test meal on two occasions, comprising a 500-ml 15% oil emulsion with 2.5% of one of two emulsifiers that produced emulsions that were either stable (meal A) or unstable (meal B) in the acid gastric environment. Gastric emptying and gallbladder volume changes were assessed by MRI. CCK plasma levels were measured and satiety scores were recorded. Meal B layered rapidly owing to fat emulsion breakdown. The gastric half-emptying time of the aqueous phase was faster for meal B (72 +/- 13 min) than for meal A (171 +/- 35 min, P < 0.008). Meal A released more CCK than meal B (integrated areas, respectively 1,095 +/- 244 and 531 +/- 111 pmol.min.l(-1), P < 0.02), induced a greater gallbladder contraction (P < 0.02), and decreased postprandial appetite (P < 0.05), although no significant differences were observed in fullness and hunger. We conclude that acid-stable emulsions delayed gastric emptying and increased postprandial CCK levels and gallbladder contraction, whereas acid-instability led to rapid layering of fat in the gastric lumen with accelerated gastric emptying, lower CCK levels, and reduced gallbladder contraction. Manipulation of the acid stability of fat emulsion added to preprocessed foods could maximize satiety signaling and, in turn, help to reduce overconsumption of calories."
1,"TITLE: Effect of seven-day atorvastatin pretreatment on the incidence of periprocedural myocardial infarction following percutaneous coronary intervention in patients receiving long-term statin therapy. A randomized study.ABSTRACT: The aim of this randomized study was to investigate the effect of seven-day high-dose atorvastatin therapy on the incidence of peri-procedural myocardial infarction (PMI) in patients receiving long-term statin therapy.The patients with stable angina receiving statin therapy and referred for percutaneous coronary intervention (PCI) were randomized (ratio 1:1) to a 7-day pre-treatment with atorvastatin of 80 mg daily and subsequent PCI (Atorvastatin group), or immediate PCI (Control group). The incidence of PMI was based on serum concentration of creatine kinase myocardial band (CK-MB) mass and troponin I (TnI), which were measured prior to and between 16 and 24h post PCI. The values were considered as positive if they were elevated ≥ 3 times the upper limit normal.We randomized 202 patients (male 67%, 65.5 ± 9.2 years; 100 vs. 102 pts.). There were no significant differences in the baseline characteristics among the randomized groups. The incidence of PMI, based on post-interventional release of TnI and/or CK-MB mass was 15% in the Atorvastatin group vs. 14% in the Control group (p=0.80). One patient (3%) in Atorvastatin group suffered from MI between randomization and PCI.These results suggest that 7-day pre-PCI therapy with high-dose atorvastatin did not reduce the occurrence of PMI in patients receiving chronic statin therapy."
1,"TITLE: Antiemetics added to phenylephrine infusion during cesarean delivery: a randomized controlled trial.ABSTRACT: To estimate whether the addition of metoclopramide or its combination with ondansetron to a prophylactic phenylephrine infusion provides improved intraoperative nausea and vomiting prophylaxis compared with phenylephrine infusion alone.Women scheduled for elective cesarean delivery were randomized to one of three groups: placebo (placebo plus placebo); metoclopramide (metoclopramide 10 mg plus placebo); or combination (metoclopramide 10 mg plus ondansetron 4 mg). The first study drug was administered before spinal placement and the second was administered after cord clamping. Spinal anesthesia was standardized. The primary outcome was intraoperative nausea and vomiting.Three-hundred patients completed the study in two centers. Intraoperative nausea and vomiting occurred in 49%, 31%, and 23% of patients in the placebo, metoclopramide, and combination groups, respectively (P<.001). There was a significant difference between the two centers in exteriorization of the uterus (93% compared with 39%; P<.001) and intraoperative nausea and vomiting rates (47% compared with 20%; P<.001). In a multivariable model adjusting for center, exteriorization of the uterus, age, and hypotension, intraoperative nausea and vomiting were significantly lower in the metoclopramide and combination groups compared with placebo (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.24--4.42; P=.001 and OR 4.06, 95% CI 2.06--7.97; P<.001, respectively). Postoperative nausea and vomiting were reduced with the combination compared with placebo at 2 hours (39% compared with 20%; P<.017), but not at 2-6 hours or at 6-24 hours.Metoclopramide with ondansetron reduced intraoperative nausea and vomiting and early postoperative nausea and vomiting compared with placebo. Metoclopramide alone also decreased intraoperative but not postoperative nausea and vomiting. Surgical factors contributed to a significant difference in intraoperative nausea and vomiting between the two centers."
0,"TITLE: Precursors of age-related macular degeneration: associations with physical activity, obesity, and serum lipids in the inter99 eye study.ABSTRACT: To investigate associations of small, hard macular drusen and larger macular drusen with obesity-related risk factors.Cross-sectional study of 888 subjects aged 30 to 60 years characterized using anthropometric measurements and blood sample analyses. Physical activity was assessed by questionnaire. Digital grayscale fundus photographs were recorded in red-free illumination and graded for the presence of macular drusen > 63 μm in either eye and the presence of 20 or more small, hard macular drusen as a mean of both eyes.Macular drusen > 63 μm were associated with the level of physical activity, the age- and sex-adjusted odds ratio being 0.33 (95% confidence interval 0.13-0.82, P = 0.016) for participants who were physically active more than 7 hours/week compared with participants active 0 to 2 hours/week. In women, macular drusen > 63 μm were associated with higher serum triglycerides (P = 0.0005). A waist circumference in the top quartile increased the odds for drusen > 63 μm in men whereas in women, having a waist circumference in the middle quartiles reduced these odds. The presence of 20 or more small, hard macular drusen was associated with lower levels of serum high-density lipoprotein cholesterol (HDL; P = 0.029) and with moderately elevated triglycerides.Precursors of AMD were associated with modifiable obesity-related risk factors; notably low physical activity with drusen > 63 μm; and lower serum HDL and moderately elevated serum triglycerides with 20 or more small, hard macular drusen per eye. These findings support that a physically active, heart-healthy lifestyle prevents the earliest manifestation of AMD. (ClinicalTrials.gov number, NCT00289237.)."
0,"TITLE: Use of viscoelastic coagulation testing to monitor low molecular weight heparin administration to healthy horses.ABSTRACT: To evaluate the utility of thromboelastography (TEG) and Sonoclot analyses to monitor the effects of low molecular weight heparin (LMWH) administration to healthy horses.Randomized crossover study.Large animal veterinary teaching hospital.Six adult mixed breed healthy mares.LMWH (dalteparin) was administered (50 U/kg subcutaneously) either every 12 or 24 h for 3 consecutive days. Blood samples were collected before LMWH administration and then at selected time points for analysis. Thromboelastography derived R-time (R), K-time (K), angle (ANG), and maximum amplitude (MA), and Sonoclot activated clot time (ACT), clot rate (CR), and platelet function (PF) were measured in whole blood 30 min after sample collection. Change (Δ) and percentage change (%Δ) from baseline of each TEG and Sonoclot variable were subsequently calculated. Anti-factor Xa activity and activated partial thromboplastin time (aPTT) were assayed in harvested plasma. The association between anti-factor Xa activity and TEG and Sonoclot (measured and calculated) variables was assessed by calculating correlation coefficients and multiple regression analysis. The ability of measured and calculated TEG and Sonoclot variables to predict when anti-factor Xa activity fell below suggested thromboprophylactic levels was assessed using receiver operating characteristic curve analysis.The correlation between aPTT and anti-factor Xa activity was weak (r = 0.343). Changes in TEG and Sonoclot variables following LMWH administration were consistent with hypocoagulation. All measured and calculated TEG variables were significantly correlated with anti-factor Xa activity. Sonoclot ACT, ΔACT, CR, ΔCR, and %ΔCR were also significantly correlated with anti-factor Xa activity. TEG ΔR and %ΔR best predicted anti-factor Xa activity below the suggested thromboprophylactic level.Although correlations were modest, serial measurement of TEG variables may be used to monitor LMWH therapy in horses; however, further research is required in sick horses."
0,"TITLE: Early neonatal feeding is common and associated with subsequent breastfeeding behavior in rural Bangladesh.ABSTRACT: Exclusive breastfeeding of newborns, a practice recommended by WHO, is hindered in many countries by practices such as prelacteal feeding (feeding other foods before breast milk is fed to infants). This paper describes maternal and infant characteristics and trends over time associated with early neonatal feeding (ENF) in Bangladesh. The analysis used data from 24,992 participants in a randomized controlled trial supplementing vitamin A and β-carotene to women in northwestern rural Bangladesh. A majority of newborns (89.2%) were fed substances other than breast milk in the first 3 d of life. Early neonatal feeding practices were found to be significantly associated with lower maternal education, higher gravidity, lower socioeconomic status, and younger maternal age. A perceived inability to suckle normally after birth was closely related to the risk of an infant being fed a food other than breast milk in the first 3 d of life [OR = 0.09 (95% CI: 0.08, 0.11)]. Only 18.8% of newborns fed an early neonatal food were exclusively breastfed between 3 d and 3 mo postpartum compared with 70.6% of those not fed an early neonatal food during this period (P < 0.05). Early neonatal feeding practices should be addressed when scaling-up exclusive breastfeeding in South Asia. Maternal education, antenatal care, and support during labor and delivery may help reduce ENF and promote exclusive breastfeeding."
1,"TITLE: Effect of discontinuation of antihypertensive medication on orthostatic hypotension in older persons with mild cognitive impairment: the DANTE Study Leiden.ABSTRACT: the relationship between antihypertensive medication and orthostatic hypotension in older persons remains ambiguous, due to conflicting observational evidence and lack of data of clinical trials.to assess the effect of discontinuation of antihypertensive medication on orthostatic hypotension in older persons with mild cognitive impairment.a total of 162 participants with orthostatic hypotension were selected from the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study. This randomised clinical trial included community-dwelling participants aged ≥75 years, with mild cognitive impairment, using antihypertensive medication and without serious cardiovascular disease. Participants were randomised to discontinuation or continuation of antihypertensive treatment (ratio 1:1). Orthostatic hypotension was defined as a drop of at least 20 mmHg in systolic blood pressure and/or 10 mmHg in diastolic blood pressure on standing from a seated position. Outcome was the absence of orthostatic hypotension at 4-month follow-up. Relative risks (RR) were calculated by intention-to-treat and per-protocol analyses.at follow-up, according to intention-to-treat analyses, of the 86 persons assigned to discontinuation of antihypertensive medication, 43 (50%) were free from orthostatic hypotension, compared with 29 (38%) of the 76 persons assigned to continuation of medication [RR 1.31 (95% confidence interval (CI) 0.92-1.87); P = 0.13]. Per-protocol analysis showed that recovery from orthostatic hypotension was significantly higher in persons who completely discontinued all antihypertensive medication (61%) compared with the continuation group (38%) [RR 1.60 (95% CI 1.10-2.31); P = 0.01].in older persons with mild cognitive impairment and orthostatic hypotension receiving antihypertensive medication, discontinuation of antihypertensive medication may increase the probability of recovery from orthostatic hypotension."
1,"TITLE: Oral nutritional supplements in a randomised trial are more effective than dietary advice at improving quality of life in malnourished care home residents.ABSTRACT: Few trials have explored the effect of nutrition support on quality of life (QoL). This study examined the effects of oral nutritional supplements (ONS) vs dietary advice on QoL in malnourished care home residents.104 malnourished, care home residents (medium + high risk), identified using the Malnutrition Universal Screening Tool ('MUST'), (mean age 88.5 ± 7.9y) were randomised to receive either oral nutritional supplements (ONS) (n = 53) or dietary advice (n = 51) for 12 weeks. Dietary intake was measured using 24 h dietary recall, and QoL assessed using EuroQol (EQ-5D), including time trade off (TTO) (range -0.59 to 1) and visual analogue scale (VAS) (score 0 to 100) for self-perceived health.QoL (adjusted for baseline QOL, malnutrition risk, type of care received (nursing or residential)) was significantly higher in the ONS than the dietary advice group (intention to treat analysis at week 12; n = 104 ). EQ-5D TTO scores (mean ± SE) were 0.50 ± 0.04 vs 0.36 ± 0.05 (P = 0.005), VAS rescaled scores were 0.54 + 0.03 vs 0.046 + 0.03 (P = 0.006) and VAS scores were 61.3 ± 4.5 vs 54.6 ± 6.3 (P = 0.533) for ONS vs dietary advice respectively. Total energy, protein and the majority of micronutrient intakes were significantly greater in the ONS group, with energy intake being 423 kcal greater in the ONS than the dietary advice group at week 12.This study in malnourished care home residents indicates that ONS can improve QoL and nutritional intake more effectively than dietary advice alone.This trial was registered with clinicaltrials.gov on 10th August 2007. Clinical trials identifier is NCT00515125http://www.clinicaltrials.gov/ct2/show/NCT00515125?term=nutrition+support&rank=60."
1,"TITLE: Effects of liraglutide on no-reflow in patients with acute ST-segment elevation myocardial infarction.ABSTRACT: The 'no-reflow' phenomenon after a percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) is a strong predictor of both short- and long-term mortality. Glucagon-like peptide-1 (GLP-1) exerts a cardioprotective effect during ischemia reperfusion injury. We planned to evaluate the effects of liraglutide on myocardial no-reflow after PCI for STEMI.A total of 284 patients with STEMI undergoing PCI were enrolled in this study between September 2013 and March 2015. Of these, 210 patients were randomized 1:1 to receive either liraglutide or placebo 30 min before PCI (1.8 mg).The primary end point, the prevalence of no-reflow, was significantly lower in the liraglutide group than in the control group (5% vs. 15%, P=0.01). Administration of liraglutide was consistently identified as a significant determinant for no-reflow ratio. There was a significant decrease in serum high-sensitivity C-reactive protein levels at 6-hour reperfusion in the liraglutide group compared to the control group (0.87 ± 0.09 mg/dL vs. 0.96 ± 0.10mg/dL, P<0.001). During a 3-month follow-up period, no difference was observed in the incidence of major adverse cardiovascular event.Liraglutide may be associated with less no-reflow in STEMI, which should be confirmed by larger-scale trials."
1,"TITLE: YAMATO Study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy).ABSTRACT: We investigated whether administration of edaravone, a free radical scavenger, before or during tissue-type plasminogen activator (tPA) can enhance early recanalization in a major arterial occlusion.The YAMATO study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy) is an investigator-initiated, multicenter (17 hospitals in Japan), prospective, randomized, and open-label study. Patients with stroke secondary to occlusion of the M1 or M2 portion of the middle cerebral artery and within 4.5 hours of the onset were studied. The subjects were randomly allocated to the early group (intravenous edaravone [30 mg] was started before or during tPA) and the late group (edaravone was started after tPA and the assessment of early recanalization).One-hundred sixty-five patients (96 men; median age [interquartile range], of 78 [69-85] years) were randomized 1:1 to either the early group (82 patients) or the late group (83 patients). Primary outcome, defined as an early recanalization 1.5 hour after tPA, was observed in 53% of the early group and in 53% of the late group (=1.000). About secondary outcomes, the rate of significant recanalization of ≥50% was not different between the 2 groups (28% versus 34%; =0.393). The symptomatic intracerebral hemorrhage has occurred in 4 patients (5%) in the early group and in 2 patients (2%) in the late group (=0.443). The favorable outcome (modified Rankin Scale score of 0-2) at 3 months was also similar between the groups (53% versus 57%; =0.738).The timing of edaravone infusion does not affect the rate of early recanalization, symptomatic intracerebral hemorrhage, or favorable outcome after tPA therapy.URL: http://www.umin.ac.jp/ctr/index-j.htm. Unique identifier: UMIN000006330."
0,"TITLE: Is abdominal obesity at baseline influencing weight changes in observational studies and during weight loss interventions?ABSTRACT: Body fat distribution is a marker of metabolic health independent of body size. Visceral fat accumulation has been suggested to result from a decreased expandability of the subcutaneous fat depots. Furthermore, the visceral fat may be easier to mobilize than the peripheral fat. We examined whether differences in abdominal obesity at baseline influenced prospective body-weight changes.In this study we examined whether body-fat distribution at baseline was associated with long-term and short-term weight changes.We included 3 observational studies (ntotal = 7271) with mean follow-up times of 5-9 y and two 8-10-wk weight loss intervention studies (ntotal = 1091). We examined the association between baseline waist circumference and weight changes in a substitution regression model, where body weight, height, and fat-free mass were fixed so that a difference in waist circumference would reflect a difference in body fat distribution alone. The results were summarized in meta-analyses.In the observational studies, we found no associations between baseline waist circumference and subsequent weight change in men (β: 0.03 kg; 95% CI: -0.01, 0.08 kg; P = 0.19), but a negligible inverse association in women (β: -0.05 kg; 95% CI: -0.08, -0.01 kg; P = 0.01). There was no association between baseline waist circumference and weight loss in the intervention studies (men: β: -0.05 kg; 95% CI: -0.13, 0.03 kg; P = 0.25; women: β: -0.00 kg; 95% CI: -0.03, 0.03 kg; P = 0.84). However, in all studies, the SDs of the weight change residuals were greater, the greater the waist circumference at baseline. This trend was statistically significant in women in most studies as well as in men in 1 of the studies.With narrow CIs in 3 observational studies and 2 weight loss interventions, we did not find any clinically or epidemiologically relevant association between baseline abdominal obesity and weight change. However, the present study suggests that a greater baseline abdominal obesity is a marker for greater weight fluctuations. The CCHS trial was registered at www.clinicaltrials.gov as NCT02993172. The Health2006 trial was registered at www.clinicaltrials.gov as NCT00316667. The ORG study was conducted before trial registration was required. The NUGENOB trial was registered at www.isrctn.com as ISRCTN25867281. The DiOGenes trial was registered atwww.clinicaltrials.gov as NCT00390637."
1,"TITLE: Long-term oncologic after robotic versus laparoscopic right colectomy: a prospective randomized study.ABSTRACT: The aim of this study was to compare the long-term outcomes of robot-assisted right colectomy (RAC) with those for conventional laparoscopy-assisted right surgery (LAC) for treating right-sided colon cancer.The enthusiasm for the robotic techniques has gained increasing interest in colorectal malignancies. However, the role of robotic surgery in the oncologic safety has not yet been defined.From September 2009 to July 2011, 71 patients with right-sided colonic cancer were randomized in the study. Adjuvant therapy and postoperative follow-up were similar in both groups. The primary and secondary endpoints of the study were hospital stay and survival, respectively. Data were analyzed by intention-to-treat principle.The RAC and LAC groups did not differ significantly in terms of baseline clinical characteristics. Compared with the LAC group, RAC was associated with longer operation times (195 min vs. 129 min, P < 0.001) and higher cost ($12,235 vs. $10,319, P = 0.013). The median follow-up was 49.23 months (interquartile range 40.63-56.20). The combined 5-year disease-free rate for all tumor stages was 77.4% (95% confidence interval [CI], 60.6-92.1%) in the RAC group and 83.6% (95% CI 72.1-0.97.0%) in the LAC group (P = 0.442). The combined 5-year overall survival rates for all stages were 91.1% (95% CI 78.8-100%) in the RAC group and 91.0% (95% CI 81.3-100%) in the LAC group (P = 0.678). Using multivariate analysis, RAC was not a predictor of recurrence.RAC appears to similar long-term survival as compared with LAC. However, we did not observe any clinical benefits of RAC which could translate to a decrease in expenditures.http://www.ClinicalTrials.gov , number NCT00470951."
1,"TITLE: Deterioration of glucose homeostasis in type 2 diabetic patients one year after beginning of statins therapy.ABSTRACT: We evaluated the long-term effects of rosuvastatin and simvastatin on insulin sensitivity and secretion in patients with well-controlled type 2 diabetes.After a 3 weeks run-in, 27 eligible patients were randomly assigned to receive either rosuvastatin 20 mg daily (Group 1) or simvastatin 20 mg daily (Group 2) for 6 months; thereafter they were switched to the other treatment for additional 6 months. Patients were recruited among individuals attending the outpatient service of the Diabetology Unit of the ""Policlinico Tor Vergata"" University Hospital, Rome, Italy. Serum lipids, glucose and insulin, glycated hemoglobin, C-reactive protein, TNF-α, leptin, adiponectin, insulin sensitivity by euglycemic-hyperinsulinemic clamp, β-cells function by HOMA-β were assessed at months 0, 6 and 12. Additionally, endothelial function was assessed by use of the brachial artery reactivity technique.Besides marked reduction in lipid levels, glycated hemoglobin significantly increased from baseline after 12 months in both Group 1 (+0.8 ± 0.2%, p < 0.001) and Group 2 (+0.9 ± 0.3%; p < 0.001). Similar trends were observed for fasting glucose in both groups. No changes in insulin sensitivity were detected throughout the study, whereas HOMA-β significantly decreased from baseline after 12 months in both Group 1 (-21.9%, p < 0.01) and Group 2 (-38.9%; p < 0.001). In addition, both treatments similarly decreased C-reactive protein and leptin, as well as improved endothelial function. No changes in anthropometric measures were observed.In well-controlled type 2 diabetic patients both rosuvastatin and simvastatin significantly impaired glycemic control and insulin secretion, without affecting insulin sensitivity."
1,"TITLE: Use of oxfendazole to control porcine cysticercosis in a high-endemic area of Mozambique.ABSTRACT: A randomized controlled field trial to evaluate the effectiveness of a single oral dose of 30 mg/kg of oxfendazole (OFZ) treatment for control of porcine cysticercosis was conducted in 4 rural villages of Angónia district, north-western Mozambique. Two hundred and sixteen piglets aged 4 months were selected and assigned randomly to OFZ treatment or control groups. Fifty-four piglets were treated at 4 months of age (T1), while another 54 piglets were treated at 9 months of age (T2) and these were matched with 108 control pigs from the same litters and raised under the same conditions. Baseline data were collected on the prevalence of porcine cysticercosis using antigen ELISA (Ag-ELISA), as well as knowledge and practices related to Taenia solium transmission based on questionnaire interviews and observations. All animals were followed and re-tested for porcine cysticercosis by Ag-ELISA at 9 and 12 months of age when the study was terminated. Overall prevalence at baseline was 5.1% with no significant difference between groups. At the end of the study, 66.7% of the controls were found positive, whereas 21.4% of the T1 and 9.1% of the T2 pigs were positive, respectively. Incidence rates of porcine cysticercosis were lower in treated pigs as compared to controls. Necropsy of 30 randomly selected animals revealed that viable cysts were present in none (0/8) of T2 pigs, 12.5% (1/8) of T1 pigs and 42.8% (6/14) of control pigs. There was a significant reduction in the risk of T. solium cysticercosis if pigs were treated with OFZ either at 4 months (OR = 0.14; 95% CI: 0.05-0.36) or at 9 months of age (OR = 0.05; 95% CI: 0.02-0.16). Strategic treatment of pigs in endemic areas should be further explored as a means to control T. solium cysticercosis/taeniosis."
0,"TITLE: Risk factors for reintubation in the post-anaesthetic care unit: a case-control study.ABSTRACT: Risk factors for reintubation in post-anaesthetic care units related to anaesthetic processes have not previously been reported. Our goal was to identify risk factors for reintubation in general surgical patients.A time-matched, case-control study was conducted on anaesthetic patients between 2001 and 2011. One hundred and sixty-four reintubated patients were compared with 656 randomly selected controls.Independent risk factors for reintubation were age <1 yr vs age 30-49 yr [odds ratio (OR)=16.4, 95% confidence interval (CI)=5.7-47.7], chronic pulmonary disease (OR=2.1, CI=1.1-4.0), preoperative hypoalbuminaemia (OR=4.9, CI=2.4-10), creatinine clearance <24 vs >60 (OR=4.1, CI=1.2-13.4), emergency case (OR=1.8, CI=1.0-3.1), operative time >3 vs <1 h (OR=3.0, CI=1.5-6.2), airway surgery (OR=32.2, CI=13.6-76), head and neck surgery (OR=3.4, CI=1.8-6.2), cardiac surgery (OR=3.8, CI=1.1-13.4), thoracic surgery (OR=6.3, CI=1.9-21.2), cardiac catheterization (OR=2.5, CI=1.1-5.5), ASA physical status III (OR=3.8, CI=1.4-10), and the use of certain types of neuromuscular blocking agent (P<0.001).Age <1 yr, chronic pulmonary disease, preoperative hypoalbuminaemia, and renal insufficiency were patient factors for reintubation. Emergency case, head and neck, cardiothoracic and airway surgery, and operative time >3 h were operative factors, while certain neuromuscular blocking agents and ASA physical status III were anaesthetic factors for reintubation."
1,"TITLE: Enteral and parenteral nutrition in the conservative treatment of pancreatic fistula: a randomized clinical trial.ABSTRACT: Postoperative pancreatic fistula is the most common and potentially life-threatening complication after pancreatic surgery. Although nutritional support is a key component of conservative therapy in such cases, there have been no well-designed clinical trials substantiating the superiority of either total parenteral nutrition or enteral nutrition. This study was conducted to compare the efficacy and safety of both routes of nutritional intervention.A randomized clinical trial was conducted in a tertiary surgical center of pancreatic and gastrointestinal surgery. Seventy-eight patients with postoperative pancreatic fistula were treated conservatively and randomly assigned to groups receiving for 30 days either enteral nutrition or total parenteral nutrition. The primary end point was the 30-day fistula closure rate.After 30 days, closure rates in patients receiving enteral and parenteral nutrition were 60% (24 of 40) and 37% (14 of 38), respectively (P=.043). The odds ratio for the probability that fistula closes on enteral nutrition compared to total parenteral nutrition was 2.571 (95% confidence interval [CI]: 1.031-6.411). Median time to closure was 27 days (95% CI: 21-33) for enteral nutrition, and no median time was reached in total parenteral nutrition (P=.047). A logistic regression analysis identified only 2 factors significantly associated with fistula closure, ie, enteral nutrition (odds ratio=6.136; 95% CI: 1.204-41.623; P=.043) and initial fistula output of ≤200 mL/day (odds ratio=12.701; 95% CI: 9.102-47.241; P<.001).Enteral nutrition is associated with significantly higher closure rates and shorter time to closure of postoperative pancreatic fistula."
1,"TITLE: Randomized Controlled Trial of Oropharyngeal Colostrum Administration in Very-low-birth-weight Preterm Infants.ABSTRACT: The purpose of this study was to evaluate the effects of oropharyngeal colostrum administration in the incidence of late-onset clinical and proven sepsis and in concentrations of immunoglobulin A (IgA) in very-low-birth-weight (VLBW) infants.We conducted a double-blinded, randomized, placebo-controlled trial and assigned 113 VLBW infants to receive 0.2 mL of maternal colostrum or sterile water (placebo) via oropharyngeal route every 2 hours for 48 hours, beginning in the first 48 to 72 hours of life. Neonates of both groups were fed breast milk from the first 3 days of life until a volume of at least 100 mL · kg · day. IgA was measured in serum and urine before and after treatment. Clinical data during hospitalization were collected.We found no statistically significant differences between colostrum and placebo groups in the incidence of late-onset clinical sepsis (odds ratio 0.7602; CI 95% 0.3-1.6) and proven sepsis (odds ratio 0.7028; CI 95% 0.3-1.6). The measurement of IgA was similar in serum before (P value 0.87) and after treatment (P value 0.26 day 4 and 0.77 day 18). No differences were also observed in IgA in urine before (P value 0.8) and after treatment (P value 0.73 day 4 and 0.52).This study could not confirm the hypothesis that oropharyngeal administration of maternal colostrum to VLBW could reduce the incidence of late-onset sepsis and increase the levels of IgA. We believe that this finding can be justified by the practice of feeding VLBW infants exclusively with breast milk in the first days of life and reinforces the prior knowledge of the importance of early nutrition, especially, with human milk. It also suggests that oropharyngeal administration of colostrum should be reserved for neonates who cannot be fed in first few days of life."
0,"TITLE: Cardiac and Inflammatory Biomarkers Are Associated with Worsening Renal Outcomes in Patients with Type 2 Diabetes Mellitus: Observations from SAVOR-TIMI 53.ABSTRACT: Cardiac and renal diseases commonly occur with bidirectional interactions. We hypothesized that cardiac and inflammatory biomarkers may assist in identification of patients with type 2 diabetes mellitus (T2DM) at high risk of worsening renal function.In this exploratory analysis from SAVOR-TIMI 53, concentrations of high-sensitivity cardiac troponin T (hs-TnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP) were measured in baseline serum samples of 12310 patients. The primary end point for this analysis was a ≥40% decrease in estimated glomerular filtration rate (eGFR) at end of treatment (EOT) at a median of 2.1 years. The relationships between biomarkers and the end point were modeled using adjusted logistic and Cox regression.After multivariable adjustment including baseline renal function, each biomarker was independently associated with an increased risk of ≥40% decrease in eGFR at EOT [Quartile (Q) Q4 vs Q1: hs-TnT adjusted odds ratio (OR), 5.63 (3.49-9.10); NT-proBNP adjusted OR, 3.53 (2.29-5.45); hs-CRP adjusted OR, 1.84 (95% CI, 1.27-2.68); all  values ≤0.001]. Furthermore, each biomarker was independently associated with higher risk of worsening of urinary albumin-to-creatinine ratio (UACR) category (all  values ≤0.002). Sensitivity analyses in patients without heart failure and eGFR >60 mL/min provided similar results. In an adjusted multimarker model, hs-TnT and NT-proBNP remained significantly associated with both renal outcomes (all  values <0.01).hs-TnT, NT-proBNP, and hs-CRP were each associated with worsening of renal function [reduction in eGFR (≥40%) and deterioration in UACR class] in high-risk patients with T2DM. Patients with high cardiac or inflammatory biomarkers should be treated not only for their risk of cardiovascular outcomes but also followed for renal deterioration."
1,"TITLE: Codeine delays gastric emptying through inhibition of gastric motility as assessed with a novel diagnostic intragastric balloon catheter.ABSTRACT: The use of opioids as analgesic is on the rise, despite their inhibitory effect on gastric emptying. A novel feeding catheter with integrated intragastric balloon was developed to continuously assess gastric motility, enabling to investigate the effect of opioids on motility and emptying simultaneously. We aimed to discriminate normal and pharmacologically impaired gastric motility and its impact on gastric emptying in healthy adults.The VIPUN Gastric Monitoring System comprises a nasogastric balloon catheter and a monitoring unit. In a four-way randomized, single-blinded, cross-over study, subjects received either placebo or 58.8 mg codeine phosphate in combination with either an uninflated or an inflated (180 mL) balloon catheter. Motility-induced pressure changes were recorded for 6 hours. During the first 2 hours, nutrients were infused (225 kcal, 75 mL/h). Gastric emptying was assessed with a  C-octanoate breath test and expressed as gastric half-emptying time (GET½). An algorithm, designed to detect phasic contractility, converted pressure changes to a gastric balloon motility index (GBMI). Results are presented as mean(SD).Eighteen subjects completed the investigation (32(13) years, 22(2) kg/m ). After codeine, GBMI was lower (0.31(0.16)) and GET½ was longer (233(57) minutes) compared with placebo (GBMI: 0.48(0.15), P < .01 and GET½: 172(12) minutes, P < .001). Within-subject ΔGET½ correlated significantly with ΔGBMI (r = -0.77 and P < .001).The VIPUN Gastric Monitoring System allowed to assess gastric motility safely and continuously. The correlation between pharmacologically decreased gastric emptying and motility indicates a strong link between both. Gastric motility, measured with this innovative device, can be an indicator for gastrointestinal intolerance."
1,"TITLE: Camelina sativa Oil, Fatty Fish, and Lean Fish Do Not Markedly Affect Urinary Prostanoids in Subjects with Impaired Glucose Metabolism.ABSTRACT: Dietary fatty acids are suggested to affect oxidative stress; however, results from interventions have been inconclusive. The aim was to examine if fatty fish, lean fish, and Camelina sativa oil (CSO) affect the urinary prostanoid levels in subjects with impaired glucose metabolism. Altogether 79 participants aged 43-72 years completed a randomized controlled study lasting 12 weeks. There were four parallel groups, fatty fish, lean fish (four fish meals/week in both), CSO providing 10 g/day alpha-linolenic acid (ALA), and control diet with limited fish and ALA containing oil consumption. Urinary prostanoids (prostaglandin F , 5-F -isoprostanes and 15-F -isoprostane metabolites, isofuran, 8-F -isoprostanes, and 4-(RS)-4-F -neuroprostane) of 72 participants (age: mean (±SD) 58.9 ± 6.5 years; body mass index: 29.3 ± 2.5 kg/m ) collected over 12-h were measured using liquid chromatography tandem-mass spectrometry. Plasma phospholipid fatty acids were determined using gas chromatography. Our study showed that the proportion of ALA in plasma phospholipids increased in the CSO group (overall difference among the groups p-value <0.001). In the fatty fish group, proportions of eicosapentaenoic and docosahexaenoic acids increased (overall p-value <0.001 for both). Prostaglandin F was higher in the CSO group than in the control group (p < 0.05), however, there were no other significant changes in urinary excretion of other prostanoids among the study groups. At baseline, arachidonic acid in plasma phospholipids was positively (r = 0.247, p < 0.05) and ALA negatively (r = -0.326, p < 0.05) associated with urinary total isoprostanes. In conclusion, CSO, fatty fish, and lean fish consumption do not cause major changes in oxidative stress markers in subjects with impaired glucose tolerance."
1,"TITLE: Adjuvant High-Flow Normobaric Oxygen After Mechanical Thrombectomy for Anterior Circulation Stroke: a Randomized Clinical Trial.ABSTRACT: Adjuvant neuroprotective therapies for acute ischemic stroke (AIS) have demonstrated benefit in animal studies, albeit without human translation. We investigated the safety and efficacy of high-flow normobaric oxygen (NBO) after endovascular recanalization in anterior circulation stroke. This is a prospective randomized controlled study. Eligible patients were randomized to receive high-flow NBO by a Venturi mask (FiO 50%, flow 15 L/min) or routine low-flow oxygen supplementation by nasal cannula (flow 3 L/min) after vessel recanalization for 6 h. Patient demographics, procedural metrics, complications, functional outcomes, symptomatic intracranial hemorrhage (sICH), and infarct volume were assessed. A total of 91 patients were treated with high-flow NBO. NBO treatment revealed a common odds ratio of 2.2 (95% CI, 1.26 to 3.87) favoring the distribution of global disability scores on the mRS at 90 days. The mortality at 90 days was significantly lower in the NBO group than in the control group, with an absolute difference of 13.86% (rate ratio, 0.35; 95% CI, 0.13-0.93). A significant reduction of infarct volume as determined by MRI was noted in the NBO group. The median infarct volume was 9.4 ml versus 20.5 ml in the control group (beta coefficient, - 20.24; 95% CI, - 35.93 to - 4.55). No significant differences were seen in the rate of sICH, pneumonia, urinary infection, and seizures between the 2 groups. This study suggests that high-flow NBO therapy after endovascular recanalization is safe and effective in improving functional outcomes, decreasing mortality, and reducing infarct volumes in anterior circulation stroke patients within 6 h from stroke onset."
1,"TITLE: High-Dose DHA Has More Profound Effects on LDL-Related Features Than High-Dose EPA: The ComparED Study.ABSTRACT: Supplementation with high-dose docosahexaenoic acid (DHA) increases serum low-density lipoprotein (LDL) cholesterol (LDL-C) concentrations more than high-dose eicosapentaenoic acid (EPA). The mechanisms underlying this difference are unknown.To examine the phenotypic change in LDL and mechanisms responsible for the differential LDL-C response to EPA and DHA supplementation in men and women at risk of cardiovascular disease.In a double-blind, controlled, crossover study, 48 men and 106 women with abdominal obesity and subclinical inflammation were randomized to a sequence of three treatment phases: phase 1, 2.7 g/d of EPA; phase 2, 2.7 g/d of DHA; and phase 3, 3 g/d of corn oil. All supplements were provided as three 1-g capsules for a total of 3 g/d. The 10-week treatment phases were separated by a 9-week washout period.In vivo kinetics of apolipoprotein (apo)B100-containing lipoproteins were assessed using primed-constant infusion of deuterated leucine at the end of each treatment in a subset of participants (n = 19).Compared with EPA, DHA increased LDL-C concentrations (+3.3%; P = 0.038) and mean LDL particle size (+0.7 Å; P < 0.001) and reduced the proportion of small LDL (-3.2%; P < 0.01). Both EPA and DHA decreased proprotein convertase subtilisin/kexin type 9 concentrations similarly (-18.2% vs -25.0%; P < 0.0001 vs control). Compared with EPA, DHA supplementation increased both the LDL apoB100 fractional catabolic rate (+11.4%; P = 0.008) and the production rate (+9.4%; P = 0.03).The results of the present study have shown that supplementation with high-dose DHA increases LDL turnover and contributes to larger LDL particles compared with EPA."
1,"TITLE: Effects of resistance training combined with moderate-intensity endurance or low-volume high-intensity interval exercise on cardiovascular risk factors in patients with coronary artery disease.ABSTRACT: To determine the effects of resistance training combined with either moderate-intensity endurance or low-volume high-intensity interval training on cardiovascular risk profiles in patients with coronary artery disease.Factorial repeated-measures study design.Nineteen patients were randomized into moderate-intensity endurance (n = 10) or high-intensity interval (n = 9) groups, and attended 2 supervised exercise sessions a week for 6-months. The first 3-months involved exclusive moderate-intensity endurance or high-intensity interval exercise, after which progressive resistance training was added to both groups for the remaining 3-months. Fitness (VO(2)peak), blood pressure and heart rate, lipid profiles and health related quality of life assessments were performed at pretraining, 3 and 6-months training.VO(2)peak increased from pretraining to 3-months in both groups (moderate-intensity endurance: 19.8 ± 7.3 vs. 23.2 ± 7.4 ml kg(-1)min(-1); high-intensity interval: 21.1 ± 3.3 vs. 26.4 ± 5.2 ml kg(-1)min(-1), p<0.001) with no further increase at 6-months. Self-evaluated health and high-density lipoprotein were increased following 6-months of moderate-intensity endurance exercise, while all remaining indices were unchanged. Low-volume high-intensity interval exercise did not elicit improvements in lipids or health related quality of life. Blood pressures and heart rates were unchanged with training in both groups.Findings from our pilot study suggest improvements in fitness occur within the first few months of training in patients with coronary artery disease, after which the addition of resistance training to moderate-intensity endurance and high-intensity interval exercise elicited no further improvements. Given the importance of resistance training in cardiac rehabilitation, additional research is required to determine its effectiveness when combined with high-intensity interval exercise."
1,"TITLE: A Worthy Finding: Decrease in Total Cholesterol and Low-Density Lipoprotein Cholesterol in Treated Mild Subclinical Hypothyroidism.ABSTRACT: Mild subclinical hypothyroidism (SCH) affects a large number of people and is known to be a risk factor for dyslipidemia. However, whether mild SCH patients should be treated with L-thyroxine to improve lipid profiles remains controversial. In addition, it is also unclear whether all mild SCH patients can benefit from L-thyroxine treatment, regardless of basal thyrotropin or lipid levels. This study aimed to assess the effects of L-thyroxine replacement therapy on the lipid profiles of mild SCH patients.This open-label randomized controlled trial was performed in Ningyang County, Shandong Province, China. A total of 378 mild SCH patients with diagnoses confirmed by two thyroid function tests were randomly assigned to either the intervention group (L-thyroxine replacement therapy) or the control group (no treatment). The primary outcome was a change in serum total cholesterol (TC) concentration.In all, 369 participants completed the 15-month follow-up period. Reduced TC concentrations were more prominent in the intervention group than they were in the control group (-0.41 mmol/L vs. -0.17 mmol/L; p = 0.012), and changes in low-density lipoprotein cholesterol levels exhibited the same trend. Subgroup analyses were performed to assess the effects of L-thyroxine in patients with different thyrotropin or TC levels. When the study population was stratified according to basal thyrotropin concentration, all patients who had received L-thyroxine showed reduced TC levels (p < 0.001). The treatment was similarly beneficial for all patients, regardless of basal TC level. Even for subjects with TC levels <5.18 mmol/L, serum TC concentrations remained unchanged in the intervention group (p = 0.936) but increased by 0.35 mmol/L in the control group (p = 0.004).The findings suggest that mild SCH patients could benefit from L-thyroxine treatment to improve lipid profiles, regardless of basal thyrotropin or TC concentrations."
0,"TITLE: Dynamic weight-bearing assessment of pain in knee osteoarthritis: construct validity, responsiveness, and interpretability in a research setting.ABSTRACT: The Osteoarthritis Research Society International (OARSI) has suggested to asses pain after specific activities consistently in clinical trials on knee OA. The Dynamic weight-bearing Assessment of Pain (DAP) assesses pain during activity (30 s of performing repeated deep knee-bends from a standing position). The purpose of this study is to evaluate the construct validity, responsiveness, and interpretability of the DAP for knee osteoarthritis (OA).One-hundred participants with knee OA were tested twice each with the DAP, the Knee injury and Osteoarthritis Outcome Score (KOOS), six-minute-walk-test (6MWT), and 6-min-walk-test with subsequent pain rating (6MWTpain), and once with a transition questionnaire (TRANS-Q) for the patient-reported change in pain after 12 weeks of exercise. Construct validity (baseline-scores) and responsiveness (change-scores) were estimated by Spearman Correlation Coefficients. We hypothesized that no correlations would be excellent (<0.7) (divergent validity), except for the 6MWTpain (convergent validity). The TRANS-Q was used for interpreting the DAP change-scores in terms of responsiveness and Minimal Important Change (MIC).Divergent validity with the KOOS subscales (r = -0.31 to-0.45) and the 6MWT (r = -0.25) was supported. Convergent validity with the 6MWTpain was not supported (r = 0.54). The DAP change-scores corresponded to patient-reported change in pain (TRANS-Q), while correlations with change-scores on the other instruments were <0.35. The MIC was 2.4 DAP points.The DAP possesses divergent validity compared to other instruments for knee OA, supporting the potential for this new way of assessing pain directly during activity. Importantly, the DAP change-scores correspond to patient-reported changes in pain, showing responsiveness. A change of 2.4 or more can be interpreted as clinically relevant. The DAP is a promising alternative to using 'pain on walking' as a clinical trial inclusion criterion/outcome."
1,"TITLE: The prophylactic use of fibrinogen concentrate in high-risk cardiac surgery.ABSTRACT: Perioperative blood loss is a major contributor to morbidity and mortality in cardiac surgery. Plasma fibrinogen levels play an essential role in hemostasis and deplete quickly during hemorrhage. The objective of this study was to determine whether prophylactic fibrinogen concentrate administration lowers overall blood product transfusion requirements in high-risk cardiac surgery in patients with low fibrinogen plasma levels.The study was performed in a prospective, randomized, and double-blinded design. The investigation included 62 patients undergoing elective, high-risk cardiac surgery. After weaning from cardiopulmonary bypass and reversal of heparin patients received either fibrinogen concentrate or placebo. The primary outcome variable was overall blood product usage 24 hours after intervention.The fibrinogen group received numerically fewer total units of blood products than the placebo group, but the difference was not statistically or clinically significant (for groups n = 27; n = 29 and 19 vs 37 units, respectively, P = .908). The overall transfusion rate in both groups was significantly lower than the institutional average suggested (fibrinogen group 26%, placebo group 28%). The fibrinogen group showed significantly higher fibrinogen levels (2.38 vs 1.83 g/L (end of surgery), P < .001; 3.33 vs 2.68 g/L (12 hours after intervention), P = .003) and improved viscoelastic coagulation parameters (FIBTEM MCF, 27 vs 23 mm, P = .022).This randomized, controlled trial demonstrates that point-of-care guided and prophylactic treatment with fibrinogen concentrate does not reduce transfusion of blood products in a setting of unexpectedly low transfusion rate as tested in this cohort, but may improve coagulation parameters in the setting of high-risk cardiac surgery."
1,"TITLE: Effects of the PRIMROSE prevention trial of childhood obesity on parental self-efficacy.ABSTRACT: Parental self-efficacy (PSE) has been suggested as a key factor for enabling parents to support children in the development of healthy dietary and physical activity behaviors and to prevent childhood obesity. However, studies of intervention effects on PSE are lacking. The present study involved a secondary analysis of data on PSE collected in a previous primary prevention trial of childhood obesity called the PRIMROSE trial. The trial involved a family-based intervention using motivational interviewing and principles of cognitive-behavioral therapy within a social-cognitive theory framework.In the PRIMROSE trial, parents and their children were randomly allocated to the intervention or usual care. In the present study, 928 mothers who responded to the Parental Self-Efficacy for Promoting Healthy Physical Activity and Dietary Behaviors in Children Scale (PSEPAD) at follow-up assessment were included. Data were analyzed using linear regression based on generalized estimating equations, with adjustment made for PSE at baseline.At follow-up assessment, there was a statistically significant difference of 1.4 units, 95% CI [0.4, 2.4], p = 0.009, between the intervention and control conditions on the subscale of the PSEPAD concerning PSE for promoting healthy dietary behaviors in children. However, this difference was deemed as without clinical importance. On the total scale or other subscales of the PSEPAD there were no statistically significant differences in PSE between conditions.There was a statistically significant, but not clinically meaningful, intervention effect on PSE. However, because previous research repeatedly has shown positive associations of PSE with dietary and physical activity behaviors in children and that self-efficacy mediates behaviors, the construct may be important for influencing dietary and physical behaviors in children. Therefore, more research is warranted evaluating the effects of interventions on PSE in the context of childhood obesity prevention.Retrospectively registered 9 October 2013 at ISRCTN (ISRCTN16991919 )."
0,"TITLE: Lipid-heparin infusion suppresses the IL-10 response to trauma in subcutaneous adipose tissue in humans.ABSTRACT: An imbalance between pro- and anti-inflammatory cytokine productions in adipose tissue is thought to contribute to chronic, systemic, low-grade inflammation and consequently to an increased risk of cardiovascular complications in obese and type 2 diabetic patients. Nonesterified fatty acids (NEFA), whose serum levels are elevated in such patients, have been shown to interfere with cytokine production in vitro. In order to evaluate the effects of elevated NEFA levels on cytokine production in adipose tissue in vivo we used an 18-gauge open-flow microperfusion (OFM) catheter to induce local inflammation in the subcutaneous adipose tissue (SAT) of healthy volunteers and to sample interstitial fluid (IF) specifically from the inflamed tissue. In two crossover studies, nine subjects received either an intravenous lipid-heparin infusion to elevate circulating NEFA levels or saline over a period of 28 h. The former increased the circulating levels of triglycerides (TGs), NEFA, glucose, and insulin over the study period. NEFA effects on locally induced inflammation were estimated by measuring the levels of a panel adipokines in the OFM probe effluent. Interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) levels increased during the study period but were not affected by lipid-heparin infusion. In contrast, the level of IL-10, an anti-inflammatory cytokine, was significantly reduced during the final hour of lipid-heparin infusion (saline: 449.2 ± 105.9 vs. lipid-heparin: 65.4 ± 15.4 pg/ml; P = 0.02). These data provide the first in vivo evidence that elevated NEFA can modulate cytokine production by adipose tissue."
1,"TITLE: Water exchange enhanced cecal intubation in potentially difficult colonoscopy. Unsedated patients with prior abdominal or pelvic surgery: a prospective, randomized, controlled trial.ABSTRACT: Colonoscopy is widely used for management of colorectal diseases. A history of abdominal or pelvic surgery is a well-recognized factor associated with difficult colonoscopy. Although water exchange colonoscopy (WEC) was effective in small groups of male U.S. veterans with such a history, its application in other cultural settings is uncertain.To investigate the application of WEC in such patients.Prospective, randomized, controlled, patient-blinded study.Tertiary-care referral center in China.Outpatients with prior abdominal or pelvic surgery undergoing unsedated diagnostic, screening, or surveillance colonoscopy.Patients were randomized to examination by either WEC or conventional air colonoscopy (AC).Cecal intubation rate.A total of 110 patients were randomized to the WEC (n = 55) or AC (n = 55) group. WEC significantly increased the cecal intubation rate (92.7% vs 76.4%; P = .033). The maximum pain scores (± standard deviation) were 2.1 ± 1.8 (WEC) and 4.6 ± 1.7 (AC), respectively (P < .001). Multivariate analysis showed that the colonoscopy method was the only independent predictor of failed colonoscopy (odds ratio 11.44, 95% confidence interval, 1.35-97.09). A higher proportion of patients examined by WEC would be willing to have a repeat unsedated colonoscopy (90.9% vs 72.7%, P = .013).Single center; unblinded but experienced endoscopists.This randomized, controlled trial confirms that the water exchange method significantly enhanced cecal intubation in potentially difficult colonoscopy in unsedated patients with prior abdominal or pelvic surgery. The lower pain scores and higher proportion accepting repeat of the unsedated option suggest that WEC is promising. It may enhances compliance with colonoscopy in specific populations. (NCT01485133.)."
1,"TITLE: Effects of a reduced-glycemic-load diet on body weight, body composition, and cardiovascular disease risk markers in overweight and obese adults.ABSTRACT: Lowering the dietary glycemic load and increasing protein intake may be advantageous for weight management.This randomized controlled trial was designed to evaluate the effects of an ad libitum reduced-glycemic-load (RGL) diet on body weight, body composition, and cardiovascular disease (CVD) risk markers in overweight and obese adults during an initial weight-loss phase (12 wk) and a weight-loss maintenance phase (weeks 24-36).Subjects were assigned to RGL (n = 43) or low-fat, portion-controlled (control; n = 43) diet groups. The RGL group was instructed to eat until satisfied, maintaining a low carbohydrate intake during weeks 0-2 and adding low-glycemic-index carbohydrate thereafter. Control subjects were instructed to reduce fat intake and decrease portion sizes, with a targeted energy deficit of 500 to 800 kcal/d.The RGL group had lost significantly more weight than did the control group at week 12 (-4.9 and -2.5 kg, respectively; P = 0.002), but the 2 groups did not differ significantly at week 36 (-4.5 and -2.6 kg, respectively; P = 0.085). Changes in fat mass differed between the groups at week 12 (-1.9 and -0.9 kg, respectively; P = 0.016) but not at week 36 (-2.0 and -1.3 kg, respectively; P = 0.333). At the end of the study, no differences were found in responses for CVD risk markers except a larger mean change in HDL cholesterol in the RGL group than in the control group (3.8 and 1.9 mg/dL, respectively; P = 0.037).These findings provide evidence that an ad libitum RGL diet is a reasonable alternative to a low-fat, portion-controlled eating plan for weight management."
0,"TITLE: Physical workload, leisure-time physical activity, obesity and smoking as predictors of multisite musculoskeletal pain. A 2-year prospective study of kitchen workers.ABSTRACT: The aim of this prospective study was to examine the role of physical workload, leisure-time physical activity, obesity and smoking in predicting the occurrence and course of multisite musculoskeletal pain (MSP).Data on physical and psychosocial workload, lifestyle factors and MSP were based on questionnaire surveys of 385 Finnish female kitchen workers. MSP (defined as pain at three or more of seven sites) during the past 3 months was measured repeatedly at 3-month intervals over 2 years. Four different patterns (trajectories) in the course of MSP were identified. The authors analysed whether the determinants at baseline predicted the occurrence of MSP (1) at the 2-year follow-up and (2) over the total of nine measurements during the 2 years by exploiting the MSP trajectories. Logistic regression was used.High physical workload at baseline was an independent predictor of MSP at the 2-year follow-up (OR 3.8, 95% CI 1.7 to 8.5) in a model allowing for age, psychosocial factors at work and lifestyle. High physical workload (OR 2.0, 95% CI 1.0 to 4.0) and moderate (OR 2.4, 95% CI 1.2 to 4.9) or low (OR 2.3, 95% CI 1.1 to 4.7) physical activity predicted persistent MSP. Obesity (OR 2.8, 95% CI 1.0 to 7.8) predicted an increased, and not being obese (OR 3.7, 95% CI 1.1 to 12.7) a decreased, prevalence of MSP in models similarly including all covariates. Smoking had no effect.The results emphasise the importance of high physical workload, low to moderate physical activity and obesity as potential modifiable risk factors for the occurrence and course of MSP over time."
1,"TITLE: Ketamine Alleviates Depressive Symptoms in Patients Undergoing Intracranial Tumor Resection: A Randomized Controlled Trial.ABSTRACT: Depressive symptoms occur in over 40% of neurosurgical patients during the perioperative period. However, no measure has been suggested to have a rapid effect on depressive surgical patients during increasingly shorter stays in the hospital. This study aimed to determine whether ketamine could improve depressive symptoms rapidly and safely during the hospital stay.This was a randomized, placebo-controlled, and double-blinded trial. Patients with moderate-to-severe depressive symptoms undergoing elective supratentorial brain tumor resection were randomized to intravenously receive either (1) 0.5 mg·kg-1 ketamine for 40 minutes or (2) an identical volume of normal saline. The primary outcome was treatment response on postoperative day 3, defined as a ≥50% reduction from the baseline depressive score. The secondary outcomes included the rate of remission and safety outcomes. The Montgomery-Åsberg Depression Rating Scale was applied by trained psychiatrists to evaluate depressive symptoms.A total of 84 neurosurgical patients were enrolled in the trial. The response rate was increased by the administration of ketamine (41.5% [17/41] vs 16.3% [7/43]; relative risk [RR]: 2.51, 95% confidence interval [CI], 1.18-5.50) relative to the administration of placebo at 3 days. Furthermore, the remission rate at discharge (29.3% [12/41] vs 7.0% [3/43]; RR: 4.20, 95% CI, 1.28-13.80) was also improved by ketamine. No psychotic symptoms or adverse events were reported to be substantially higher in the ketamine group.The trial indicates that the intraoperative administration of ketamine could alleviate moderate-to-severe depressive symptoms in neurosurgical patients without worsening safety."
1,"TITLE: Randomized Pragmatic Trial of Pacemaker Versus Implantable Cardiac Monitor in Syncope and Bifascicular Block.ABSTRACT: In this study, the authors tested whether a strategy of empiric permanent pacing reduces major composite events more effectively than acting on the results of an implantable cardiac monitor (ICM).Syncope may be caused by intermittent complete heart block in patients with bifascicular heart block, but competing diagnoses coexist. Whether empiric permanent pacing or acting on investigative results provides best care is unknown.This was a multinational, randomized, pragmatic clinical trial of patients ≥50 years of age with bifascicular block, preserved left ventricular function, and ≥1 syncope in the preceding year. The primary composite outcome measure comprised cardiovascular death, syncope, bradycardia resulting in pacemaker insertion, and device complications.There were 57 and 58 subjects randomized to receive a pacemaker or ICM. A total of 41 patients had left bundle branch block and 74 had right bundle branch block and a left fascicular block. Patients were followed for a median 33 months. There were fewer composite primary outcomes in patients randomized to pacemaker compared with ICM, respectively (20 [35%] vs 44 [76%]; chi square P < 0.0001), with lower actuarial probabilities of a primary outcome (0.45 and 1.00; P < 0.001). Syncope was as likely in the groups randomized to receive a pacemaker or ICM (29% vs 26%, chi-square P = 0.95).Empiric permanent pacing compared with ICM reduced major adverse events but not syncope in older patients with bifascicular block and recent syncope. There remains a substantial likelihood of syncope recurrence in patients who receive a permanent pacemaker likely caused by vasodepressor syncope. (Syncope: Pacing or Recording in the Later Years [SPRITELY]; NCT01423994)."
1,"TITLE: Evaluation of Daily Low-Dose Prednisolone During Upper Respiratory Tract Infection to Prevent Relapse in Children With Relapsing Steroid-Sensitive Nephrotic Syndrome: The PREDNOS 2 Randomized Clinical Trial.ABSTRACT: In children with corticosteroid-sensitive nephrotic syndrome, many relapses are triggered by upper respiratory tract infections. Four small studies found that administration of daily low-dose prednisolone for 5 to 7 days at the time of an upper respiratory tract infection reduced the risk of relapse, but the generalizability of their findings is limited by location of the studies and selection of study population.To investigate the use of daily low-dose prednisolone for the treatment of upper respiratory tract infection-related relapses.This double-blind, placebo-controlled randomized clinical trial (Prednisolone in Nephrotic Syndrome [PREDNOS] 2) evaluated 365 children with relapsing steroid-sensitive nephrotic syndrome with and without background immunosuppressive treatment at 122 pediatric departments in the UK from February 1, 2013, to January 31, 2020. Data from the modified intention-to-treat population were analyzed from July 1, 2020, to December 31, 2020.At the start of an upper respiratory tract infection, children received 6 days of prednisolone, 15 mg/m2 daily, or matching placebo preparation. Those already taking alternate-day prednisolone rounded their daily dose using trial medication to the equivalent of 15 mg/m2 daily or their alternate-day dose, whichever was greater.The primary outcome was the incidence of first upper respiratory tract infection-related relapse. Secondary outcomes included overall rate of relapse, changes in background immunosuppressive treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, and quality of life.The modified intention-to-treat analysis population comprised 271 children (mean [SD] age, 7.6 [3.5] years; 174 [64.2%] male), with 134 in the prednisolone arm and 137 in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 of 131 (42.7%) in the prednisolone arm and 58 of 131 (44.3%) in the placebo arm (adjusted risk difference, -0.02; 95% CI, -0.14 to 0.10; P = .70). No evidence was found that the treatment effect differed according to background immunosuppressive treatment. No significant differences were found in secondary outcomes between the treatment arms. A post hoc subgroup analysis assessing the primary outcome in 54 children of South Asian ethnicity (risk ratio, 0.66; 95% CI, 0.40-1.10) vs 208 children of other ethnicity (risk ratio, 1.11; 95% CI, 0.81-1.54) found no difference in efficacy of intervention in those of South Asian ethnicity (test for interaction P = .09).The results of PREDNOS 2 suggest that administering 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of nephrotic syndrome in children in the UK. Further work is needed to investigate interethnic differences in treatment response.isrctn.org Identifier: ISRCTN10900733; EudraCT 2012-003476-39."
1,"TITLE: Acetylcysteine has No Mechanistic Effect in Patients at Risk of Contrast-Induced Nephropathy: A Failure of Academic Clinical Science.ABSTRACT: Contrast-induced nephropathy (CIN) is a major complication of imaging in patients with chronic kidney disease (CKD). The publication of an academic randomized controlled trial (RCT; n = 83) reporting oral (N)-acetylcysteine (NAC) to reduce CIN led to > 70 clinical trials, 23 systematic reviews, and 2 large RCTs showing no benefit. However, no mechanistic studies were conducted to determine how NAC might work; proposed mechanisms included renal artery vasodilatation and antioxidant boosting. We evaluated the proposed mechanisms of NAC action in participants with healthy and diseased kidneys. Four substudies were performed. Two randomized, double-blind, placebo-controlled, three-period crossover studies (n = 8) assessed the effect of oral and intravenous (i.v.) NAC in healthy kidneys in the presence/absence of iso-osmolar contrast (iodixanol). A third crossover study in patients with CKD stage III (CKD3) (n = 8) assessed the effect of oral and i.v. NAC without contrast. A three-arm randomized, double-blind, placebo-controlled parallel-group study, recruiting patients with CKD3 (n = 66) undergoing coronary angiography, assessed the effect of oral and i.v. NAC in the presence of contrast. We recorded systemic (blood pressure and heart rate) and renal (renal blood flow (RBF) and glomerular filtration rate (GFR)) hemodynamics, and antioxidant status, plus biomarkers of renal injury in patients with CKD3 undergoing angiography. Primary outcome for all studies was RBF over 8 hours after the start of i.v. NAC/placebo. NAC at doses used in previous trials of renal prophylaxis was essentially undetectable in plasma after oral administration. In healthy volunteers, i.v. NAC, but not oral NAC, increased blood pressure (mean area under the curve (AUC) mean arterial pressure (MAP): mean difference 29 h⋅mmHg, P = 0.019 vs. placebo), heart rate (28 h⋅bpm, P < 0.001), and RBF (714 h⋅mL/min, 8.0% increase, P = 0.006). Renal vasodilatation also occurred in the presence of contrast (RBF 917 h⋅mL/min, 12% increase, P = 0.005). In patients with CKD3 without contrast, only a rise in heart rate (34 h⋅bpm, P = 0.010) and RBF (288 h⋅mL/min, 6.0% increase, P = 0.001) occurred with i.v. NAC, with no significant effect on blood pressure (MAP rise 26 h⋅mmHg, P = 0.156). Oral NAC showed no effect. In patients with CKD3 receiving contrast, i.v. NAC increased blood pressure (MAP rise 52 h⋅mmHg, P = 0.008) but had no effect on RBF (151 h⋅mL/min, 3.0% increase, P = 0.470), GFR (29 h⋅mL/min/1.73m², P = 0.122), or markers of renal injury. Neither i.v. nor oral NAC affected plasma antioxidant status. We found oral NAC to be poorly absorbed and have no reno-protective effects. Intravenous, not oral, NAC caused renal artery vasodilatation in healthy volunteers but offered no protection to patients with CKD3 at risk of CIN. These findings emphasize the importance of mechanistic clinical studies before progressing to RCTs for novel interventions. Thousands were recruited to academic clinical trials without the necessary mechanistic studies being performed to confirm the approach had any chance of working."
1,"TITLE: Assessment of cleaning methods on bacterial burden of hospital privacy curtains: a pilot randomized controlled trial.ABSTRACT: Healthcare-associated infections (HAIs) are an important global issue, leading to poor patient outcomes. A potential route of transmission of HAIs is through contact with hospital privacy curtains. The aim of this study is to evaluate cleaning on reduction of curtain bacterial burden. In this pilot cluster randomized controlled trial we compared the bacterial burden between three groups of 24 curtains on a regional burn/plastic surgery ward. A control group was not cleaned. Two groups were cleaned at 3-4 day intervals with either disinfectant spray or wipe. The primary outcome was the difference in mean CFU/cm between day 0 to day 21. The secondary outcome was the proportion of curtains contaminated with Methicillin-resistant Staphylococcus aureus (MRSA). By day 21, the control group was statistically higher (2.2 CFU/cm) than spray (1.3 CFU/cm) or wipe (1.5 CFU/cm) (p < 0.05). After each cleaning at 3-4 day intervals, the bacterial burden on the curtains reduced to near day 0 levels; however, the level increased again over the intervening 3-4 days. By day 21, 64% of control curtains were contaminated with MRSA compared to 10% (spray) and 5% (wipe) (p < 0.05). This study show that curtains start clean and progressively become contaminated with bacteria. Regularly cleaning curtains with disinfectant spray or wipes reduces bacterial burden and MRSA contamination."
1,"TITLE: Efficacy of FOLFIRI plus cetuximab vs FOLFIRI plus bevacizumab in 1st-line treatment of older patients with RAS wild-type metastatic colorectal cancer: an analysis of the randomised trial FIRE-3.ABSTRACT: The evidence on the efficacy of anticancer therapy is limited in older patients with metastatic colorectal cancer (mCRC). This retrospective analysis of phase III FIRE-3 trial assesses the efficacy of FOLFIRI plus either cetuximab or bevacizumab according to the patients' age and sidedness of primary tumour.The study endpoints overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were compared between younger (<65 years) and older (≥65 years) patients, followed by stratification according to primary tumour sidedness. ORR was compared using Fisher´s exact test, OS and PFS were estimated by the Kaplan-Meier method and compared using the log-rank test. Univariate Cox regression analyses assessed hazard ratios and 95% confidence intervals for OS and PFS.Overall, older patients with RAS WT tumours had a significantly shorter OS when compared to younger patients (25.9 months vs 29.3 months, HR 1.29; P = 0.02). Also the proportion of right-sided tumours was significantly greater in older patients (27.1% vs 17.9%; P = 0.029). Secondary resection rates were numerically higher in younger patients (25.4% vs. 17.6%, P = 0.068) than in older patients. This was primarily seen in the Cetuximab arm, where older patients underwent less likely resection (13.1% vs. 26%; P = 0.02). Older patients with left-sided tumours showed only a trend towards greater efficacy of cetuximab (HR 0.86; P = 0.38). In patients with right-sided primary tumours, older patients did not appear to benefit from cetuximab in contrast to younger patients (≥65 years: 16.6 months vs 23.6 months, HR 1.1; P = 0.87; <65 years: 21.9 months vs 16.4 months HR 1.5; P = 0.31).In FIRE-3, OS was generally shorter in older patients in comparison to younger patients. This could be explained by the overrepresentation of right-sided tumours and a lower secondary resection rate in older patients. The efficacy of targeted therapy was dependent on tumour sidedness in older patients with RAS WT mCRC.FIRE-3 (NCT00433927)."
1,"TITLE: Botulinum Toxin Type A for Lumbar Sympathetic Ganglion Block in Complex Regional Pain Syndrome: A Randomized Trial.ABSTRACT: The present study was designed to test the hypothesis that botulinum toxin would prolong the duration of a lumbar sympathetic block measured through a sustained increase in skin temperature. The authors performed a randomized, double-blind, controlled trial to investigate the clinical outcome of botulinum toxin type A for lumbar sympathetic ganglion block in patients with complex regional pain syndrome.Lumbar sympathetic ganglion block was conducted in patients with lower-extremity complex regional pain syndrome using 75 IU of botulinum toxin type A (botulinum toxin group) and local anesthetic (control group). The primary outcome was the change in the relative temperature difference on the blocked sole compared with the contralateral sole at 1 postoperative month. The secondary outcomes were the 3-month changes in relative temperature differences, as well as the pain intensity changes.A total of 48 participants (N = 24/group) were randomly assigned. The change in relative temperature increase was higher in the botulinum toxin group than in the control group (1.0°C ± 1.3 vs. 0.1°C ± 0.8, respectively; difference: 0.9°C [95% CI, 0.3 to 1.5]; P = 0.006), which was maintained at 3 months (1.1°C ± 0.8 vs. -0.2°C ± 1.2, respectively; P = 0.009). Moreover, pain intensity was greatly reduced in the botulinum toxin group compared with the control group at 1 month (-2.2 ± 1.0 vs. -1.0 ± 1.6, respectively; P = 0.003) and 3 months (-2.0 ± 1.0 vs. -0.6 ± 1.6, respectively; P = 0.003). There were no severe adverse events pertinent to botulinum toxin injection.In patients with complex regional pain syndrome, lumbar sympathetic ganglion block using botulinum toxin type A increased the temperature of the affected foot for 3 months and also reduced the pain.EDITOR’S PERSPECTIVE"
1,"TITLE: Effect of Feitai Capsule () on quality of life and progression-free survival of patients with unresectable non-small cell lung cancer.ABSTRACT: To examine the effect of a Chinese medicinal herbal formula (Feitai Capsule, ) on the quality of life (QOL) and progression-free survival (PFS) of patients with unresectable non-small cell lung cancer (NSCLC).Sixty-two patients were randomly divided into the treatment group (31 cases) and the control group (31 cases). For the treatment group, 4 capsules (1.2 g/capsule) of Feitai Capsule were administered 3 times a day after meals for 3 weeks; then no drug was administered for 1 week. This schedule was continued for at least 3 more cycles (12 weeks totally). If there were no obvious toxic reactions, the treatment was extended. The patients were evaluated at least once every 8 weeks until progressive disease (PD). For the control group, the regular follow-up and evaluation were performed at least once every 8 weeks until PD. Clinical symptoms, objective response, physical constitution and energy, QOL, and PFS were evaluated regularly. Analysis of variance (ANOVA), a non-parametric test, and analysis of covariance were used to compare clinical features, amelioration of clinical symptoms, physical constitution and energy, and QOL. Kaplan-Meier analysis was used to compare the two-group PFS.Sixty patients finished the final evaluation, with 30 patients in each group. Baseline characters between groups were not significantly different (P>0.05). The control group had a 36.7% improvement in clinical symptoms, while the treatment group had a 73.3% improvement. This difference was statistically significant (Z= -2.632, P=0.008). The control group had a 26.7% improvement in the Karnofsky performance status (KPS), while the treatment group had a 53.4% improvement. This was also significantly different (Z=-2.182, P=0.029). A comparative analysis indicated a positive correlation (r=0.917, P<0.001). Compared with the control group, QOL in the treatment group was significantly improved, except in the social/family condition and doctor-patient relationship indicators. The PFS of the treatment group and control group were 6.23 months and 4.67 months, respectively (P=0.048).Feitai Capsule, a Chinese medicinal herbal treatment could improve the QOL and extend the PFS of the unresectable NSCLC patients."
1,"TITLE: Rosuvastatin improves pulse wave reflection by restoring endothelial function.ABSTRACT: One of the major indicators of intact endothelial function is basal nitric oxide (NO) activity. Further, it seems to be likely that statin therapy exerts beneficial effects on vascular function, at least in part via an improvement of NO bioavailability. In the present double-blind crossover study 29 hypercholesterolemic patients were randomly assigned to receive rosuvastatin and placebo for 42days. Pulse wave analysis was assessed after 30min of rest (baseline) and after infusion of N(G)-monomethyl-l-arginine (l-NMMA) at the end of 42days treatment period. The magnitude of the increase in central augmentation index (cAIx) in response to inhibition of NO synthase (NOS) by l-NMMA is indicative of basal NO activity. CAIx was significantly lower (18.3±10 versus 21.9±12%, p=0.027) with rosuvastatin compared to placebo. There was no increment of cAIx in response to l-NMMA in placebo group. In contrast, cAIx increased significantly in response to l-NMMA (20.5±11 versus 25.7±10mm Hg, p=0.001) in rosuvastatin group. The percentage of increase of cAIx tended to be more pronounced after treatment with rosuvastatin compared to placebo (53.7±92 versus 14.1±36%, p=0.087). Pulse pressure amplification (PPA) improved (1.31±0.2 versus 1.26±0.2%, p=0.016) after rosuvastatin compared to placebo. Regression analyses revealed that both LDL-cholesterol and CRP-levels are independent determinants of basal NO activity improvement, which itself is an independent determinant of vascular function, expressed by an improvement of pulse wave reflection and PPA. In this placebo controlled study, treatment with rosuvastatin improved vascular and endothelial function. Determinants for improved NO production in patients with hypercholesterolemia were the achieved levels of LDL-cholesterol and CRP. Overall, in patients without CV disease, rosuvastatin exerted beneficially effect on vascular dysfunction, one of the earliest manifestation of atherosclerosis."
0,"TITLE: Psychiatric comorbidity of patients on methadone maintenance treatment with a history of sexual abuse.ABSTRACT: The aim of this study was to assess the prevalence of a history of sexual abuse and its relation to psychiatric comorbidity among former opiate addicts currently on methadone maintenance treatment (MMT). We evaluated the history of sexual abuse and current clinical obsessive compulsive disorder (OCD), dissociative identity disorder (DID), and complex posttraumatic distress disorder (cPTSD), and administered the Life Events Inventory Questionnaire among 125 MMT patients (76 females and 49 males). Eighty (64%) patients had experienced sexual abuse, 69 (55.2%) met the criteria for clinical OCD, 20 (16.0%) for cPTSD and 13 (10.4%) for DID. More females had clinical OCD than males (63.2% vs. 42.9%, respectively, p=0.03). Sexually abused patients had higher rates of clinical OCD than their non-abused counterparts (67.5% vs. 33.3%, respectively, p<0.0005) and a higher mean number of negative life events (8.0±2.0 vs. 7.1±1.8, p=0.01). Sexually abused patients showed a trend towards a higher Dissociative Experiences Scale score (17.6±10.1 vs. 14.6±8.1, p=0.08) and rate of DID (13.8% vs. 4.4%, p=0.1), but no significant difference in the rate of cPTSD (17.5% vs. 13.3%, p=0.6) compared to non-abused subjects. The 80 sexually abused patients were mostly female (85%), and 57.5% of them were abused by a family member. In summary, more sexually abused MMT patients were diagnosed with clinical OCD and fewer with cPTSD and DID. Those with cPTSD were characterized by more negative life events, higher dissociation scores, and assaults by a family member. We conclude that sexually abused MMT patients should be screened for clinical OCD."
1,"TITLE: Contrast Sensitivity and Lateral Inhibition Are Enhanced With Macular Carotenoid Supplementation.ABSTRACT: Once deposited in the retina, the so-called macular carotenoids lutein (L), zeaxanthin (Z), and mesozeaxanthin (MZ) have been shown to enhance visual performance. The purpose of our study was to investigate whether increasing macular pigment optical density (MPOD) could enhance lateral inhibitory processes, and thereby improve contrast sensitivity (CS).A total of 59 young (18-25 years), healthy individuals participated in this 1-year, double-masked, placebo-controlled study. MPOD was assessed via heterochromatic flicker photometry. Lateral inhibition sensitivity (LIS) was determined with a computer-based, user-adjustable Hermann grid. CS (at 8 cycles/degree) was determined with a two-alternative, forced-choice procedure. Subjects received either the placebo (n = 10), 12 mg total macular carotenoids (n = 24), or 24 mg total macular carotenoids (n = 25).MPOD, LIS, and CS increased significantly in treatment groups between baseline and 6 months, and between 6 and 12 months (P < 0.05 for all) versus placebo. The relationships between changes in MPOD and both LIS and CS were significant at 6 and 12 months (P < 0.05 for both). Changes in CS and LIS over the 12-month study period were found to be significantly related (r = 0.41; P = 0.0014).Increases in MPOD led to enhanced lateral inhibitory processes, which correspond to improved CS. Because optical filtering has the same net effect on dark versus light bars, it cannot explain these improvements. Improvement in CS with increases in MPOD therefore appears to involve enhancement of the fundamental physiological systems that give rise to edge detection."
1,"TITLE: The impact of a package of behaviour change interventions on breastfeeding practices in East Java Province, Indonesia.ABSTRACT: Suboptimal infant young child feeding practices are frequently reported globally, including in Indonesia. This analysis examined the impact of a package of behaviour change interventions on breastfeeding practices in Malang and Sidoarjo Districts, East Java Province, Indonesia. The BADUTA study (which in the Indonesian Language is an acronym for BAwah DUa TAhun, or children aged less than 2 years) was an impact evaluation using a cluster-randomized controlled trial with two parallel treatment arms. We conducted household surveys in 12 subdistricts from Malang and Sidoarjo. We collected information from 5175 mothers of children aged 0-23 months: 2435 mothers at baseline (February 2015) and 2740 mothers at endline (January to February 2017). This analysis used two indicators for fever and diarrhoea and seven breastfeeding indicators (early initiation of breastfeeding, prelacteal feeding, exclusive breastfeeding under 6 months, predominant breastfeeding, continued breastfeeding, age-appropriate breastfeeding and bottle-feeding). We used multilevel logistic regression analysis to assess the effect of the intervention. After 2 years of implementation of interventions, we observed an increased odds of exclusive breastfeeding under 6 months (adjusted odds ratio [aOR] = 1.85; 95% confidence interval [CI]: 1.35-2.53) and age-appropriate breastfeeding (aOR = 1.39; 95% CI: 1.07-1.79) in the intervention group than in the comparison group, at the endline survey. We found significantly lower odds for prelacteal feeding (aOR = 0.52; 95% CI: 0.41-0.65) in the intervention than in the comparison group. Our findings confirmed the benefits of integrated, multilayer behaviour change interventions to promote breastfeeding practices. Further research is required to develop effective interventions to reduce bottle use and improve other breastfeeding indicators that did not change with the BADUTA intervention."
1,"TITLE: The impact of mTOR inhibitors in the regression of left ventricular hypertrophy in elderly kidney transplant recipients.ABSTRACT: End-stage kidney disease is frequently associated with left ventricular hypertrophy (LVH), a condition more prevalent in the elderly, that may increase mortality after renal transplantation (RTx). Previous studies suggested that mTOR inhibitors (mTORi) can improve LVH, but this has never been tested in elderly kidney transplant recipients. In this prospective randomized clinical trial, we analyzed the impact of Everolimus (EVL) on the reversal of LVH after RTx in elderly recipients (≥60 years) submitted to different immunosuppressive regimens: EVL/lowTacrolimus (EVL group, n = 53) or mycophenolate sodium/regularTacrolimus (MPS group, n = 47). Patients performed echocardiograms (Echo) up to 3 months after RTx and then annually. At baseline, mean age was 65±3 years in both groups and LVH was observed in 63.6% of patients in EVL group and in 61.8% of MPS group. Last Echo was performed at mean time of 47 and 49 months after RTx in EVL and MPS groups, respectively (P = .34). LVH regression was observed in 23.8% (EVL group) and 19% (MPS group) of patients (P = 1.00). Mean eGFR, blood pressure, and use of RAS blockers were similar between groups throughout follow-up. EVL did not improve LVH in this cohort, and this lack of benefit may be attributed to concomitant use of TAC, senescence, or both."
1,"TITLE: Acute hyperglycaemia does not have a consistent adverse effect on exercise performance in recreationally active young people with type 1 diabetes: a randomised crossover in-clinic study.ABSTRACT: In individuals with type 1 diabetes, chronic hyperglycaemia impairs aerobic fitness. However, the effect of acute marked hyperglycaemia on aerobic fitness is unclear, and the impact of insulin level has not been examined. In this study, we explored if acute hyperglycaemia with higher or low insulin levels affects [Formula: see text] and other exercise performance indicators in individuals with type 1 diabetes.Eligible participants were aged 14 to 30 years, with complication-free, type 1 diabetes and HbA ≤ 75 mmol/mol (≤9%). Participants exercised in a clinical laboratory under three clamp (constant insulin, variable glucose infusion) conditions: euglycaemia (5 mmol/l) with 20 mU [m BSA] min insulin (where BSA is body surface area) (Eu20); hyperglycaemia (17 mmol/l) with 20 mU [m BSA] min insulin (Hyper20); and hyperglycaemia (17 mmol/l) with 5 mU [m BSA] min insulin (Hyper5) on separate days. Participants and the single testing assessor were blinded to condition, with participants allocated to randomised testing condition sequences as they were consecutively recruited. Standardised testing (in order) conducted on each of the three study days included: triplicate 6 second sprint cycling, grip strength, single leg static balance, vertical jump and modified Star Excursion Balance Test, ten simple and choice reaction times and one cycle ergometer [Formula: see text] test. The difference between conditions in the aforementioned testing measures was analysed, with the primary outcome being the difference in [Formula: see text].Twelve recreationally active individuals with type 1 diabetes (8 male, mean ± SD 17.9 ± 3.9 years, HbA 61 ± 11 mmol/mol [7.7 ± 1.0%], 7 ± 3 h exercise/week) were analysed. Compared with Eu20, [Formula: see text] was lower in Hyper20 (difference 0.17 l/min [95% CI 0.31, 0.04; p = 0.02] 6.6% of mean Eu20 level), but Hyper5 was not different (p = 0.39). Compared with Eu20, sprint cycling peak power was not different in Hyper20 (p = 0.20), but was higher in Hyper5 (64 W [95% CI 13, 115; p = 0.02] 13.1%). Hyper20 reaction times were not different (simple: p = 0.12) but Hyper5 reaction times were slower (simple: 11 milliseconds [95% CI 1, 22; p = 0.04] 4.7%) than Eu20. No differences between Eu20 and either hyperglycaemic condition were observed for the other testing measures (p > 0.05).Acute marked hyperglycaemia in the higher but not low insulin state impaired [Formula: see text] but to a small extent. Acute hyperglycaemia had an insulin-dependent effect on sprint cycling absolute power output and reaction time but with differing directionality (positive for sprint cycling and negative for reaction time) and no effect on the other indicators of exercise performance examined. We find that acute hyperglycaemia is not consistently adverse and does not impair overall exercise performance to an extent clinically relevant for recreationally active individuals with type 1 diabetes.This research was funded by Diabetes Research Western Australia and Australasian Paediatric Endocrine Group grants."
1,"TITLE: Exercise-induced amplification of mitogen-stimulated oxidative burst in whole blood is strongly influenced by neutrophil counts during and following exercise.ABSTRACT: This study characterized the effect of moderate- or vigorous-intensity exercise on leukocyte counts, using fingertip sampling, and mitogen-stimulated oxidative burst, measured in whole blood with a point-of-care test. In a randomized crossover design, 13 healthy adults (mean ± SD age: 22 ± 2 years; seven male, six female) cycled for 30-min, once at 52 ± 5%  O and on another occasion at 74 ± 9%  O . Blood was sampled at baseline, immediately post-exercise, and 15- and 60-min post-exercise. The leukocyte differential and mitogen-stimulated Reactive Oxygen Species (ROS) production were assessed. Lymphocytes increased immediately post-exercise and decreased below pre-exercise levels 15- and 60-min later. Lymphocyte mobilization immediately post-exercise was 59 ± 36% greater with vigorous- compared to moderate-intensity exercise (p < 0.01). Neutrophils increased immediately after exercise (38 ± 19%, p < 0.01) remaining elevated 60-min later (50 ± 34%, p < 0.01; averaged across intensities) and did not differ between intensities (p = 0.259). Mitogen-stimulated ROS production was amplified immediately (+32 ± 37%, p < 0.01) and 60-min post-exercise (+56 ± 57%, p < 0.01; averaged across intensities) compared to rest and did not differ with intensity (p = 0.739). Exercise-induced amplification of ROS production was abolished when correcting for neutrophil, monocyte and platelet counts and correlated most strongly with neutrophil mobilization immediately (r = 0.709, p < 0.01) and 60-min after vigorous exercise (r = 0.687, p < 0.01). Leukocyte kinetics can be assessed using fingertip blood sampling in exercise settings. Exercise-induced amplification of oxidative burst is detectable with a point-of-care test, but results are strongly influenced by neutrophil counts, which may not be routinely quantified."
1,"TITLE: Effects of canagliflozin on serum potassium in people with diabetes and chronic kidney disease: the CREDENCE trial.ABSTRACT: Hyperkalaemia is a common complication of type 2 diabetes mellitus (T2DM) and limits the optimal use of agents that block the renin-angiotensin-aldosterone system, particularly in patients with chronic kidney disease (CKD). In patients with CKD, sodium‒glucose cotransporter 2 (SGLT2) inhibitors provide cardiorenal protection, but whether they affect the risk of hyperkalaemia remains uncertain.The CREDENCE trial randomized 4401 participants with T2DM and CKD to the SGLT2 inhibitor canagliflozin or matching placebo. In this post hoc analysis using an intention-to-treat approach, we assessed the effect of canagliflozin on a composite outcome of time to either investigator-reported hyperkalaemia or the initiation of potassium binders. We also analysed effects on central laboratory-determined hyper- and hypokalaemia (serum potassium ≥6.0 and <3.5 mmol/L, respectively) and change in serum potassium. At baseline, the mean serum potassium in canagliflozin and placebo arms was 4.5 mmol/L; 4395 (99.9%) participants were receiving renin-angiotensin system blockade. The incidence of investigator-reported hyperkalaemia or initiation of potassium binders was lower with canagliflozin than with placebo [occurring in 32.7 vs. 41.9 participants per 1000 patient-years; hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.64-0.95, P = 0.014]. Canagliflozin similarly reduced the incidence of laboratory-determined hyperkalaemia (HR 0.77, 95% CI 0.61-0.98, P = 0.031), with no effect on the risk of hypokalaemia (HR 0.92, 95% CI 0.71-1.20, P = 0.53). The mean serum potassium over time with canagliflozin was similar to that of placebo.Among patients treated with renin-angiotensin-aldosterone system inhibitors, SGLT2 inhibition with canagliflozin may reduce the risk of hyperkalaemia in people with T2DM and CKD without increasing the risk of hypokalaemia."
1,"TITLE: Fentanyl versus placebo with ketamine and rocuronium for patients undergoing rapid sequence intubation in the emergency department: The FAKT study-A randomized clinical trial.ABSTRACT: The objective was to determine whether the use of fentanyl with ketamine for emergency department (ED) rapid sequence intubation (RSI) results in fewer patients with systolic blood pressure (SBP) measurements outside the pre-specified target range of 100-150 mm Hg following the induction of anesthesia. Methods This study was conducted in the ED of five Australian hospitals. A total of 290 participants were randomized to receive either fentanyl or 0.9% saline (placebo) in combination with ketamine and rocuronium, according to a weight-based dosing schedule. The primary outcome was the proportion of patients in each group with at least one SBP measurement outside the prespecified range of 100-150 mm Hg (with adjustment for baseline abnormality). Secondary outcomes included first-pass intubation success, hypotension, hypertension and hypoxia, mortality, and ventilator-free days 30 days following enrollment.A total of 142 in the fentanyl group and 148 in the placebo group commenced the protocol. A total of 66% of patients receiving fentanyl and 65% of patients receiving placebo met the primary outcome (difference = 1%, 95% CI = -10 to 12). Hypotension (SBP ≤ 99 mm Hg) was more common with fentanyl (29% vs. 16%; difference = 13%, 95% CI = 3% to 23%), while hypertension (≥150 mm Hg) occurred more with placebo (69% vs. 55%; difference = 14%, 95% CI = 3 to 24). First-pass success rate, 30 day mortality, and ventilator-free days were similar.There was no difference in the primary outcome between groups, although lower blood pressures were more common with fentanyl. Clinicians should consider baseline hemodynamics and postinduction targets when deciding whether to use fentanyl as a coinduction agent with ketamine."
1,"TITLE: Effects of treatment with SGLT-2 inhibitors on arginine-related cardiovascular and renal biomarkers.ABSTRACT: In patients with type 2 diabetes (T2D) sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve glycaemic control as well as cardiovascular and renal outcomes. Their effects on L-arginine (Arg) related risk markers asymmetric and symmetric dimethylarginine (ADMA and SDMA) and the protective biomarker L-homoarginine (hArg) linking T2D to cardiovascular and renal disease have not yet been reported.Plasma and 24-h urine samples taken before and after 6 weeks of treatment were available from two prospective, randomized, double-blind, placebo-controlled, cross-over trials with empagliflozin (71 patients analyzed, NCT02471963) and dapagliflozin (59 patients analyzed, NCT02383238). In these samples, concentrations of hArg, Arg, ADMA, SDMA, and creatinine were determined by liquid-chromatography coupled to tandem mass-spectrometry. Additionally, intraindividual changes of the biomarkers in plasma were correlated with intraindividual changes of clinical parameters.Treatment with empagliflozin and dapagliflozin was associated with a reduction of plasma hArg by 17.5% and 13.7% (both p < 0.001), respectively, and increase in plasma SDMA concentration of 6.7% and 3.6%, respectively (p < 0.001 and p < 0.05), while plasma Arg and ADMA concentrations were not significantly altered. 24-h urinary excretion of ADMA was reduced by 15.2% after treatment with empagliflozin (p < 0.001) but not after dapagliflozin treatment, while excretion of the other markers was not significantly altered. Renal clearance of SDMA was reduced by 9.1% and 3.9% for both drugs (both p < 0.05). A reduction in ADMA clearance was observable after empagliflozin treatment only (- 15.5%, p < 0.001), but not after dapagliflozin. Renal clearance of hArg and Arg was not significantly altered. Treatment effects on L-arginine related biomarkers were not constantly correlated with effects on glycated hemoglobin, fasting plasma glucose, body mass index, and systolic blood pressure.Treatment with SGLT-2 inhibitors has divergent effects on Arg-related biomarkers and could affect risk estimates associated with these markers. The observed effects are unlikely to explain the known cardiovascular and renal benefits of treatment with empagliflozin or dapagliflozin but still may indicate new therapeutic approaches in patients treated with SGLT-2 inhibitors. Trial registration http://www.clinicaltrials.gov : NCT02471963 (registered 15th June 2015, retrospectively registered) and NCT02383238."