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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 ).

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.

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.).

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.

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.

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.

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).

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.

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.

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.

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).

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.