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[ { "answer_id": 19288, "body": "<p>First of all, you have to be aware that most studies cited are on animals, not humans. Applicability of that data for humans is limited.</p>\n\n<p>Second, this molecule is interacting with all kinds of tissues thoughout the entire body. Its pharmacology is quite complicated, but it shows a lot of <a href=\"https://www.nytimes.com/interactive/2019/05/14/magazine/cbd-cannabis-cure.html\" rel=\"nofollow noreferrer\">potential</a>. In general. Its use for depression is not yet among the most promonent applications investigated.<br>\n_{Pisanti, S., et al., Cannabidiol: State of the art and new challenges for therapeutic applications, Pharmacology &amp; Therapeutics (2017), <a href=\"http://dx.doi.org/10.1016/j.pharmthera.2017.02.041\" rel=\"nofollow noreferrer\">DOI</a>}</p>\n\n<p>In the case of schizophrenia:</p>\n\n<blockquote>\n <p>Conclusions:</p>\n \n <p>These findings suggest that CBD has beneficial effects in patients with schizophrenia. As CBD’s effects do not appear to depend on dopamine receptor antagonism, this agent may represent a new class of treatment for the disorder.<br>\n _{Philip McGuire: \"Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial\", American Journal of Psychoiatry, Volume 175, Issue 3, March 01, 2018, Pages 225-231. <a href=\"https://doi.org/10.1176/appi.ajp.2017.17030325\" rel=\"nofollow noreferrer\">DOI</a>} </p>\n</blockquote>\n\n<p>The above should not read as \"it safe to experiment with this in schizophrenia\". But it is a significant finding as</p>\n\n<blockquote>\n <p>So far, much of the evidence regarding the antipsychotic effects of CBD has come from studies with animals or healthy participants.<br>\n There have only been a handful of double-blind trials so far reported that have included patients with psychosis.<br>\n The others (Leweke et al. 2012, Boggs et al. 2018) featured smaller sample sizes (N=42 and N=36 respectively) and lower doses (800mg and 600mg per day respectively).<br>\n Leweke et al. compared CBD to Amisulpride, and found both had a similar effect on psychotic symptoms but CBD had fewer side-effects.<br>\n Boggs et al. also tested CBD against placebo as an adjunct to existing antipsychotic treatment, but found no statistically significant effect after 6 weeks. </p>\n \n <p>Boggs D., Surti T., Gupta A., et al. (2018). The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial. Psychopharmacology. 235, 1923-1932. [<a href=\"https://link.springer.com/article/10.1007/s00213-018-4885-9\" rel=\"nofollow noreferrer\">Abstract</a>]</p>\n \n <p>Bridgeman M, Abazia D. (2017) <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312634/\" rel=\"nofollow noreferrer\">Medicinal cannabis: History, pharmacology, and implications for the acute care setting.</a> Pharm. Ther., 42, 180–188.</p>\n \n <p>Fakhoury, M. (2016) Could cannabidiol be used as an alternative to antipsychotics? Journal of Psychiatric Research , Volume 80 , 14 – 21. <a href=\"https://www.sciencedirect.com/science/article/pii/S0022395616301042\" rel=\"nofollow noreferrer\">[Abstract]</a></p>\n \n <p>Gage, S. H., Hickman, M., &amp; Zammit, S. (2016). <a href=\"https://research-information.bristol.ac.uk/files/54173362/Gage_accepteduncorrected.pdf\" rel=\"nofollow noreferrer\">Association Between Cannabis and Psychosis: Epidemiologic Evidence (PDF)</a>. Biological Psychiatry, 79(7), 549-556.</p>\n \n <p>Lim, K., See, Y.M., Lee, J. (2017) <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678490/\" rel=\"nofollow noreferrer\">A systematic review of the effectiveness of medical cannabis for psychiatric, movement and neurodegenerative disorders.</a> Clin Psychopharmacol Neurosci.; 15:301–312.</p>\n \n <p>Mücke M, Phillips T, Radbruch L, et al. (2018) <a href=\"https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012182.pub2/full\" rel=\"nofollow noreferrer\">Cannabis-based medicines for chronic neuropathic pain in adults.</a> Cochrane Database of Systematic Reviews, Issue 3. Art. No.: CD012182.</p>\n \n <p>Nielsen S., Germanos R., Weier M. et al. (2018). The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews. Current Neurology and Neuroscience Reports. 18: 8. <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/29442178\" rel=\"nofollow noreferrer\">[PubMed abstract]</a></p>\n \n <p>O’Connell, B. K., Gloss, D. &amp; Devinsky, O. (2017) Cannabinoids in treatment-resistant epilepsy: a review. Epilepsy Behav. 70, 341–348. <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/28188044\" rel=\"nofollow noreferrer\">[PubMed abstract]</a></p>\n \n <p>Rong C, Lee Y, Carmona NE, et al. Cannabidiol in medical marijuana: research vistas and potential opportunities. Pharmacol Res. 2017;121:213–8. <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/28501518\" rel=\"nofollow noreferrer\">[PubMed abstract]</a></p>\n \n <p>_{<a href=\"https://www.nationalelfservice.net/treatment/antipsychotics/cannabidiol-cbd-an-effective-antipsychotic/\" rel=\"nofollow noreferrer\">Luke Sheridan Rains: \"Is Cannabidiol (CBD) an effective antipsychotic?\", 24 Aug 2018</a>}</p>\n</blockquote>\n", "score": 3 } ]

[ "medications", "depression", "antidepressants" ]

[ { "answer_id": 19298, "body": "<p>Diffusion of water. </p>\n\n<p>Osmosis is movement of water <em>across a membrane</em> due to solute changes. In the case of diffusion tensor MRI, the whole point is that there is more diffusion along the same axis as white matter axons are traveling (either within or outside, but not across, those membranes), compared to a perpendicular axis. There isn't any net flow, it's just that water is more mobile in one axis because of the barriers that the membranes provide. We call this \"anisotropy\" because the diffusion is not \"isotropic\" which would mean the same in all directions. DWI is similar but we don't care about the direction, just the general ability of water to move freely in different parts of the brain. </p>\n\n<p>Le Bihan, D., Mangin, J. F., Poupon, C., Clark, C. A., Pappata, S., Molko, N., &amp; Chabriat, H. (2001). Diffusion tensor imaging: concepts and applications. Journal of Magnetic Resonance Imaging: An Official Journal of the International Society for Magnetic Resonance in Medicine, 13(4), 534-546.</p>\n", "score": 4 } ]

[ "brain", "mri" ]

[ { "answer_id": 19318, "body": "<p>Examples of books from four basic \"pre-clinical\" subjects:</p>\n\n<ul>\n<li><strong>Anatomy:</strong> Sobotta Atlas of Human Anatomy (<a href=\"https://archive.org/details/SobottaAtlasOfHumanAnatomyVolume1_201611\" rel=\"noreferrer\">entire book, page by page</a>)</li>\n<li><strong>Biology:</strong> Goodman: Medical Cell Biology (<a href=\"https://www.elsevier.com/books/medical-cell-biology/goodman/978-0-12-370458-0\" rel=\"noreferrer\">Google preview</a>)</li>\n<li><strong>Biochemistry:</strong> Lehninger: Principles of Biochemistry (<a href=\"https://www.macmillanlearning.com/catalog//samplechapters/1637_LehningerPreviewandCh5watermarked.pdf\" rel=\"noreferrer\">book overview with a sample chapter about proteins</a>)</li>\n<li><strong>Physiology:</strong> Berne &amp; Levy Physiology (<a href=\"https://www.elsevier.com/books/berne-and-levy-physiology/koeppen/978-0-323-39394-2\" rel=\"noreferrer\">Google preview</a>)</li>\n</ul>\n\n<p>These books are often a part of \"recommended literature\" for medical students at various universities. They are \"complete\" books. They should be easy to understand for everyone who has finished a high school with emphasis on natural sciences. I don't think it makes sense to read any short version of such books to \"get prepared.\"</p>\n\n<p>It is a good idea to get familiar with basic <strong>medical terms.</strong> Examples of online sources:</p>\n\n<ul>\n<li><a href=\"https://www.dmu.edu/medterms/basics/\" rel=\"noreferrer\">Des Moines University</a></li>\n<li><a href=\"https://www.aimseducation.edu/blog/all-essential-medical-terms/\" rel=\"noreferrer\">Aimseducation.edu</a></li>\n<li><a href=\"http://www.mb-guide.org/learn-basic-medical-terminology.html\" rel=\"noreferrer\">MB-Guide</a></li>\n<li><a href=\"https://www.medicinenet.com/medterms-medical-dictionary/article.htm\" rel=\"noreferrer\">Medterms</a> (a huge online medical dictionary)</li>\n</ul>\n", "score": 5 }, { "answer_id": 19314, "body": "<p>Medicine is challenging for many reasons. One major reason is that it takes multiple tiers of knowledge as a foundation prior to being able to even start studying the fundamentals.</p>\n<p>This is how it works in the USA for most schools:</p>\n<h2><strong>FIRST: College or University (after high school, before medical school)</strong></h2>\n<p><strong>Undergraduate level (usually 4 years):</strong></p>\n<ol>\n<li>Math: through advanced algebra and trigonometry, if not done in high school. Calculus may be required to enter med school, but its concepts are not really necessary for medicine unless you plan to do certain advanced research topics. I'd also recommend at least one course in statistics, if not biostatistics as well.</li>\n<li>Physics: minimum 2 semesters. Trig-based should be enough, not necessary for calculus-based.</li>\n<li>Biology: as much as you can get, usually multiple semesters are required. Especially focus on cellular, molecular, genetic. Consider taking mammalian physiology or an undergrad anatomy &amp; physiology class for a solid foundation.</li>\n<li>Chemistry: usually requires 2 semesters of inorganic, 2 of organic, and 1-2 of biochemistry. Biochemistry is the most useful.</li>\n</ol>\n<h2><strong>SECOND: Med school (4 years):</strong></h2>\n<p><strong>The first 2 years are basic sciences,</strong> extremely dense, fast classes:</p>\n<ol>\n<li>Anatomy and histology: goes in depth, including gross anatomy. Example textbooks: Grey's Anatomy, Moore's Clinical Anatomy, Netter's Atlas.</li>\n<li>Normal Physiology: including all systems (e.g. cardiology, pulmonology, endocrinology etc etc). Example textbooks: Boron and Boulpaep, West Pulmonology, Kablunde Cardiology, and other system-based textbooks.</li>\n<li>Pathology: including histopathology and the abnormal of all physiology topics. Example textbook: Robbins &amp; Cotran.</li>\n<li>Public health: usually just an overview, with lots of epidemiology and biostatistics.</li>\n</ol>\n<p><strong>The last 2 years of med school</strong> are clinical rotations plus lectures, reading, and exams on the application of all of the above to clinical situations. Examples of books used are Harrison's Internal Medicine, Case Files and Blueprints for each specialty rotation, etc.</p>\n<h2><strong>THIRD: Residency:</strong></h2>\n<p><strong>You'll do 3 to 7 years of residency in your specialty</strong>, where you practice medicine under supervision with additional lectures, reading, and exams. This is finally when things fully come together.</p>\n<h2><strong>In summary:</strong></h2>\n<p>It's hard to say &quot;read X to get started&quot; without a clear idea of how far into the fundamentals one has gone. There's a reason it takes so many years to study - it's like building a pyramid from the ground up. You can't skip to the top block without building a solid foundation.</p>\n", "score": 3 } ]

[ "physiology", "biochemistry" ]

[ { "answer_id": 19475, "body": "<p>\"Uppers\" and \"downers\" are colloquial terms for drugs with stimulant effects versus depressive effects, respectively.</p>\n\n<p>The primary acute health concern with either (i.e., what tends to kill people in an overdose) is overstimulation or oversuppression of the cardiovascular/respiratory systems.</p>\n\n<p>One recreational combination of upper/downer is a <a href=\"https://en.wikipedia.org/wiki/Speedball_(drug)\" rel=\"nofollow noreferrer\">\"speedball\" of cocaine and heroin/morphine</a>. The combination can provide a substantial euphoria, and a reduced perception of impairment and other side effects because of counteracting stimulant/depressive effects. Therefore, a drug user may underestimate how intoxicated they are and is more able to use more of each at the same time.</p>\n\n<p>However, these drugs do not have the same time course. When the immediate stimulant effects wear off, the respiratory depressive effects of the opioid persist, plus any rebound effect from withdrawal from the stimulant. The result is more respiratory depression than would be expected, leading to respiratory arrest and death.</p>\n\n<p>There have been many deaths of famous people (and many more not-so-famous) attributable to these drug combinations, including people who were long-time drug users beforehand.</p>\n\n<p>Ethanol (alcohol) can be even worse because of paradoxical drug reactions: alcohol is typically a depressant, but can also have dis-inhibitory effects as well. Simultaneous alcohol and cocaine use is also strongly associated with overdose death.</p>\n\n<p>More generally, combinations of stimulant and depressive drugs are likely to mask side effects that occur prior to the level at which the outcomes are dangerous, and individuals prescribed one category of drug likely have contraindications for the other. There is also increased potential for abuse due to larger combined euphoric effects and combined chronic effects depending on the specific drugs.</p>\n\n<hr>\n\n<p>Coffin, P. O., Galea, S., Ahern, J., Leon, A. C., Vlahov, D., &amp; Tardiff, K. (2003). Opiates, cocaine and alcohol combinations in accidental drug overdose deaths in New York City, 1990–98. Addiction, 98(6), 739-747.</p>\n\n<p>Ellinwood, E. H., Eibergen, R. D., &amp; Kilbey, M. M. (1976). Stimulants: interaction with clinically relevant drugs. Annals of the New York Academy of Sciences, 281(1), 393-408.</p>\n\n<p>Farré, M. A. G. I., De la Torre, R., Llorente, M., Lamas, X., Ugena, B., Segura, J., &amp; Camí, J. O. R. D. I. (1993). Alcohol and cocaine interactions in humans. Journal of Pharmacology and Experimental Therapeutics, 266(3), 1364-1373.</p>\n\n<p>O'Driscoll, P. T., McGough, J., Hagan, H., Thiede, H., Critchlow, C., &amp; Alexander, E. R. (2001). Predictors of accidental fatal drug overdose among a cohort of injection drug users. American Journal of Public Health, 91(6), 984.</p>\n\n<p>Ochoa, K. C., Hahn, J. A., Seal, K. H., &amp; Moss, A. R. (2001). Overdosing among young injection drug users in San Francisco. Addictive Behaviors, 26(3), 453-460.</p>\n", "score": 4 } ]

[ "mental-health", "practice-of-medicine" ]

[ { "answer_id": 19481, "body": "<p>The mentioned paper has been published in BMJ Open in 2015: <a href=\"https://bmjopen.bmj.com/content/bmjopen/6/6/e010401.draft-revisions.pdf\" rel=\"nofollow noreferrer\">The Association Between Low-Density Lipoprotein Cholesterol and Mortality in the Elderly. A systematic review</a>.</p>\n\n<p>The <a href=\"https://www.nhs.uk/news/heart-and-lungs/study-says-theres-no-link-between-cholesterol-and-heart-disease/\" rel=\"nofollow noreferrer\">NHS article</a> mentions the limitations of the review: only participants older than 60 years were included, only LDL (but not HDL) cholesterol was investigated, the effect of statins (cholesterol-lowering drugs) has been ignored and 9 of the authors are members of The International Network of Cholesterol Skeptics, so they may be biased in this regard. </p>\n\n<p>The conclusion of the review that high LDL levels have nothing to do with atherosclerosis is not presented convincingly. Still, there is a need for more precise evaluation of the effect of LDL cholesterol on the atherosclerosis risk. Two things to consider:</p>\n\n<ol>\n<li>\"<strong>Small dense LDL particles</strong>\" are more atherogenic than large LDL particles (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441126/\" rel=\"nofollow noreferrer\">Oxidative Medicine and Cellular Longevity, 2017</a> ; <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038964/\" rel=\"nofollow noreferrer\">Lipids in Health and Disease, 2011</a>), which suggests that \"total\" LDL may not be an accurate marker of the atherosclerosis risk.</li>\n<li><strong>Other factors,</strong> such as genetic predisposition, low HDL cholesterol, high blood pressure, high blood glucose, obesity, physical inactivity and smoking may greatly increase the risk of atherosclerosis at a given LDL level (<a href=\"https://www.nhlbi.nih.gov/health-topics/atherosclerosis\" rel=\"nofollow noreferrer\">National Heart, Lung and Blood Institute</a>).</li>\n</ol>\n", "score": 5 }, { "answer_id": 19482, "body": "<p>The NHS page you linked to does quite a good job of explaining why the study that puts forward the claim that there <em>isn't</em> a link doesn't actually quite say that with any degree of certainty. They are a bit wishy-washy about it and the British Heart Foundation takes a somewhat <a href=\"https://www.bhf.org.uk/informationsupport/heart-matters-magazine/news/behind-the-headlines/cholesterol-and-statins\" rel=\"nofollow noreferrer\">tougher stance</a></p>\n\n<p>LDL cholesterol (LDL-C), along with other types of cholesterol are widely upheld to be <strong>risk factors</strong> for cardiovascular disease as opposed to being the \"one true cause\" and there is very good evidence to suggest that reducing LDL-C levels in the bloodstream reduces the cardiovascular risk of an individual:</p>\n\n<p><a href=\"https://i.stack.imgur.com/gZznC.jpg\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/gZznC.jpg\" alt=\"Figure 3 from: Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis JAMA. 2016;316(12):1289-1297.\"></a></p>\n\n<p><a href=\"https://mfprac.com/web2018/07literature/literature/Cardiology/StatinsHead_Silverman.pdf\" rel=\"nofollow noreferrer\">Figure 3 from: Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis JAMA. 2016;316(12):1289-1297.</a></p>\n\n<p>The above graph shows a noticeable <em>decrease</em> in the risk of a cardiovascular event when the LDL-C levels are reduced - now it's important to note that correlation is not the same thing as causation. So we can't say for sure that lowering the LDL-C was definitively responsible for the reduction in risk, but it does indicate that as the LDL-C level lowers so does the risk.</p>\n\n<p>A <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988224/\" rel=\"nofollow noreferrer\">study carried out in 2013</a> also seems to indicate that as the level of reduction is increased the risk decreases further:</p>\n\n<blockquote>\n <p>… similar proportional reductions in major vascular events per 1·0 mmol/L LDL cholesterol reduction were found in all types of patient studied …</p>\n</blockquote>\n\n<p>This study was mainly looking at statin use vs. control but as per the <em>Silverman et al</em> paper shows the reduction in risk varies depending on the <em>mechanism</em> for reducing the LDL-C used – which suggests that LDL-C level alone doesn't control cardiovascular event risk but that there is an indication of a link.</p>\n\n<p>Crucially this correlation seems consistently to be in the opposite direction to what the <em>Rvanskov et al</em> study claims.</p>\n\n<p>It's generally accepted that there are of course <a href=\"https://www.nhs.uk/conditions/coronary-heart-disease/causes/\" rel=\"nofollow noreferrer\">other risk factors</a> besides LDL-C in determining the risk of a cardiac event – smoking, lack of exercise, diabetes, obesity, genetic predisposition etc. And of course it's quite feasible to have more than one of these factors working together to increase the risk levels to the point where a heart attack happens.</p>\n\n<p>For some reason the so-called \"cholesterol controversy\" seems to persist – and it's a particular hobby-horse of more than one of the authors of the paper in question. At least two of whom have written books about the theory (primary author <a href=\"https://en.wikipedia.org/wiki/Uffe_Ravnskov\" rel=\"nofollow noreferrer\">Uffe Rvanskov</a> and <a href=\"https://www.google.com/search?q=The%20Great%20Cholesterol%20Con%3A%20The%20Truth%20About%20What%20Really%20Causes%20Heart%20Disease%20and%20How%20to%20Avoid%20It%20Malcolm%20Kendrick\" rel=\"nofollow noreferrer\">Malcolm Kendrick</a>)\n and 9 are members of a lobbyist organisation on the subject – \"The International Network of Cholesterol Skeptics\" (\"THINCS\") which is a strong indicator of bias, and that the authors might be looking for results that supported the conclusion they already had.</p>\n\n<p>Bias alone does not necessarily mean a study is inherently bad or wrong but there's other warning signs as well, the paper is is what is called a <a href=\"https://www.nhs.uk/news/health-news-glossary/#narrativereview\" rel=\"nofollow noreferrer\">Narrative review</a> where the paper is structured as a narrative, in other words they are discussing and presenting a story rather than presenting a statistical analysis of the data (such as a meta-analysis).</p>\n\n<p>In this case they are describing what they found when they did a certain search on PubMed (an on-line searchable database of medical publications) – and they describe which keywords they used and what exclusions they made. One such search criteria was \"NOT trial\" – so clinical trials would be excluded from their search.</p>\n\n<p>This is worrying when the later in the paper they say the following:</p>\n\n<blockquote>\n <p>It is worth considering that some of the participants with high LDL-C may have started statin treatment during the observation period. Such treatment may have increased the lifespan for the group with high LDL-C. However, any beneficial effects of statins on mortality would have been minimal because most statin trials have had little effect on CVD and all-cause mortality, with a maximum reduction of mortality of two percentage points.</p>\n</blockquote>\n\n<p>Here the authors make an assertion regarding the efficacy of statins in reducing mortality and cite that they have \"little effect\" and a \"maximum reduction of mortality of two percentage points\", except they don't cite any such study, and they have <strong>explicitly</strong> excluded statin trials from their search criteria. We are expected to believe this statement simply because the authors say it is so.</p>\n\n<p>The closest the Rvanskov paper comes to directly addressing this is near the end where they state:</p>\n\n<blockquote>\n <p>Our review provides the basis for more research about the cause of atherosclerosis and CVD and also for a re-evaluation of the guidelines for cardiovascular prevention, in particular because the benefits from statin treatment have been exaggerated.</p>\n</blockquote>\n\n<p>And they list three citations for this statement - one is <em>another</em> Rvanskov paper (self-cites don't carry a great deal of weight IMO), a bombastic paper written by another member of THINCS and the <em>Kristensen et al</em> paper which analysed death postponement values during statin trials. The conclusion of that paper makes the fairly unequivocal statement that:</p>\n\n<blockquote>\n <p>Statins are usually inexpensive and safe, at least in a clinical trial setting, and the benefit in terms of mortality or non-fatal cardiovascular outcomes cannot reasonably be challenged.</p>\n</blockquote>\n\n<p>So in summary this paper from <em>Rvanskov el al</em> doesn't seem to offer much in the way of strong research and if anything shows strong indicators of bias and IMO it's hard to take it seriously. </p>\n", "score": 5 } ]

[ "heart-disease", "cardiovascular-disease", "cholesterol", "heart-attack", "hypertension" ]

[ { "answer_id": 19549, "body": "<p>Currently, there seems to be insufficient evidence for the carcinogenicity of coal tar for dermatological use and some evidence that coal-tar pitch fumes may increase the risk of lung cancer.</p>\n<p><strong>Coal tar for dermatological use</strong></p>\n<blockquote>\n<p>Conclusive evidence for the carcinogenicity of tar used in\ndermatologic practice is lacking (<a href=\"https://www.ncbi.nlm.nih.gov/pubmed/7712091\" rel=\"nofollow noreferrer\">Dermatologic Surgery, 1995</a>).</p>\n<p>This study [in 13,200 patients with psoriasis and eczema followed for 21 years] has sufficient power to show that coal tar treatment is not\nassociated with an increased risk of cancer. These results indicate\nthat coal tar can be maintained as a safe treatment in dermatological\npractice (<a href=\"https://www.sciencedirect.com/science/article/pii/S0022202X15347710?via%3Dihub\" rel=\"nofollow noreferrer\">The Journal of Investigative Dermatology, 2010</a>).</p>\n</blockquote>\n<p><strong>Coal-tar pitch fumes</strong></p>\n<p>Lung cancer:</p>\n<blockquote>\n<p>Except for lung cancer, evidence for increased cancer risks among\nbitumen-exposed workers was judged to be of low certainty (<a href=\"https://www.ncbi.nlm.nih.gov/pubmed/29111990\" rel=\"nofollow noreferrer\">Journal of\nOccupational and Environmental Medicine, 2018</a>).</p>\n<p>An increasing number of occupational studies demonstrate a positive\nexposure-response relationship with cumulative benzo[a]pyrene [a chemical in coal-tar fumes] exposure and lung cancer (<a href=\"https://cfpub.epa.gov/ncea/iris/iris_documents/documents/toxreviews/0136tr.pdf\" rel=\"nofollow noreferrer\">U.S. Environmental Protection Agency, 2017</a>).</p>\n</blockquote>\n<p>Skin cancer:</p>\n<blockquote>\n<p>Both coal tar and coal-tar pitch contain many chemical compounds,\nincluding carcinogens such as benzene. Occupational exposure to coal tar or coal-tar pitch increases the risk of <em>skin cancer</em> (<a href=\"https://www.cancer.gov/about-cancer/causes-prevention/risk/substances/coal-tar\" rel=\"nofollow noreferrer\">National Cancer Institute,\n2018</a>).</p>\n</blockquote>\n<p>According to a 2004 review of occupational carcinogens in <a href=\"http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.276.5235&amp;rep=rep1&amp;type=pdf\" rel=\"nofollow noreferrer\">Environmental Health Perspectives</a>, there is a strong evidence that the exposure to coal tar or coal-tar pitches increases the risk of <em>skin cancer</em> (see Table 7).</p>\n<p>Other:</p>\n<blockquote>\n<p>Coal tars and coal-tar pitches are known to be human carcinogens\nbased on sufficient evidence of carcinogenicity from studies in humans\n(<a href=\"https://ntp.niehs.nih.gov/ntp/roc/content/profiles/coaltars.pdf\" rel=\"nofollow noreferrer\">National Toxicology Program, Department of Health and Human\nServices, 2010</a>).</p>\n</blockquote>\n<p>It may take decades of exposure for a chemical to cause cancer. This and the fact that the chemical composition of coal tar has changed over time may partially explain the differences in estimations of carcinogenicity of coal tar among studies.</p>\n", "score": 2 } ]

[ "cancer", "safety" ]

[ { "answer_id": 19543, "body": "<p>The article you linked seems to be the best reference to answer your title question about mixing CBD and alcohol, and as pointed out by @CareyGregory in a comment:</p>\n\n<blockquote>\n <p>I think you misstated the 1979 study's findings. They found impairment with alcohol, but no difference between impairment with and without CBD. That agrees with the modern understanding that CBD has no psychoactive effects</p>\n</blockquote>\n\n<p>I'll focus on your last sentence \"<em>What is the scientific stance on addiction therapy with CBD?</em>\" with respect to alcohol use disorder.</p>\n\n<p>Currently there has not been sufficient clinical study to say anything about treating alcohol addiction with CBD specifically (the only existing studies included THC or studied effects of marijuana decriminalization). I can not find a single published clinical trial with CBD in the context of alcohol use disorder or measuring alcohol use more generally. This is consistent with limited or lacking clinical study for other indications of CBD besides epilepsy.</p>\n\n<p>A recent review (Nona et al 2019) discusses the lack of clinical research in this area, and summarizes existing preclinical research (all in rodents). The results overall are mixed but point to some potential anxiolytic effects that may contribute to reduced ethanol preference in CBD-treated rodents, as well as some results suggesting a reduction in ethanol toxicity. One recent mouse study (Viudez‐Martínez et al 2018) showed reduced ethanol self-administration and reduced relapse with CBD, but of course such models are only of limited predictive value for human outcomes.</p>\n\n<hr>\n\n<p>Nona, C. N., Hendershot, C. S., &amp; Le Foll, B. (2019). Effects of cannabidiol on alcohol-related outcomes: A review of preclinical and human research. Experimental and clinical psychopharmacology.</p>\n\n<p>Viudez‐Martínez, A., García‐Gutiérrez, M. S., Navarrón, C. M., Morales‐Calero, M. I., Navarrete, F., Torres‐Suárez, A. I., &amp; Manzanares, J. (2018). Cannabidiol reduces ethanol consumption, motivation and relapse in mice. Addiction biology, 23(1), 154-164.</p>\n", "score": 3 }, { "answer_id": 19547, "body": "<p>Jury still being out for an overall picture, it seems at least for a harm reduction perspective things are looking quite good. As an adjunct form of actual treatment it may have value as well. Specifically it seems as if neurologically and regarding the liver some of the worst outcomes of alcohol consumption are mitigated to a degree, but psychologically the state of drunkenness from a certain level of alcohol may not be lowered but motor impairments actually amy increase while the level of actual alcohol in the blood may slightly decrease.</p>\n\n<p>As a modulator for addictive behaviour it may have a tremendous effect on the positive side.</p>\n\n<blockquote>\n <p><strong>Results:</strong> Experimental studies find that CBD reduces the overall level of alcohol drinking in animal models of AUD by reducing ethanol intake, motivation for ethanol, relapse, anxiety, and impulsivity. Moreover, CBD reduces alcohol-related steatosis and fibrosis in the liver by reducing lipid accumulation, stimulating autophagy, modulating inflammation, reducing oxidative stress, and by inducing death of activated hepatic stellate cells. Finally, CBD reduces alcohol-related brain damage, preventing neuronal loss by its antioxidant and immunomodulatory properties.<br>\n <strong>Conclusions:</strong> CBD could directly reduce alcohol drinking in subjects with AUD. Any other applications warrant human trials in this population. By reducing alcohol-related steatosis processes in the liver, and alcohol-related brain damage, CBD could improve both hepatic and neurocognitive outcomes in subjects with AUD, regardless of the individual's drinking trajectory. This might pave the way for testing new harm reduction approaches in AUD, in order to protect the organs of subjects with an ongoing AUD.\n _{–– De Ternay J et al.: <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/31214036\" rel=\"nofollow noreferrer\">\"Therapeutic Prospects of Cannabidiol for Alcohol Use Disorder and Alcohol-Related Damages on the Liver and the Brain.\"</a>, Front Pharmacol. 2019 May 31;10:627. doi: 10.3389/fphar.2019.00627. eCollection 2019.}</p>\n \n <p>Substance use disorder is characterized by repeated use of a substance, leading to clinically significant distress, making it a serious public health concern. The endocannabinoid system plays an important role in common neurobiological processes underlying substance use disorder, in particular by mediating the rewarding and motivational effects of substances and substance-related cues. In turn, a number of cannabinoid drugs (e.g., rimonabant, nabiximols) have been suggested for potential pharmacological treatment for substance dependence. Recently, cannabidiol (CBD), a non-psychoactive phytocannabinoid found in the cannabis plant, has also been proposed as a potentially effective treatment for the management of substance use disorder. Animal and human studies suggest that these cannabinoids have the potential to reduce craving and relapse in abstinent substance users, by impairing reconsolidation of drug-reward memory, salience of drug cues, and inhibiting the reward-facilitating effect of drugs. Such functions likely arise through the targeting of the endocannabinoid and serotonergic systems, although the exact mechanism is yet to be elucidated. This article seeks to review the role of the endocannabinoid system in substance use disorder and the proposed pharmacological action supporting cannabinoid drugs' therapeutic potential in addictions, with a focus on CBD. Subsequently, this article will evaluate the underlying evidence for CBD as a potential treatment for substance use disorder, across a range of substances including nicotine, alcohol, psychostimulants, opioids, and cannabis. While early research supports CBD's promise, further investigation and validation of CBD's efficacy, across preclinical and clinical trials will be necessary.<br>\n _{–– Chye Y et al.: <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/30837904\" rel=\"nofollow noreferrer\">\"The Endocannabinoid System and Cannabidiol's Promise for the Treatment of Substance Use Disorder\"</a>, Front Psychiatry. 2019 Feb 19;10:63. doi: 10.3389/fpsyt.2019.00063.} </p>\n \n <p>Increased access to medicinal and recreational cannabis will be accompanied by greater exposure to its chemical constituents, including Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), the primary nonpsychoactive compound. Increasing attention has focused on CBD, in part, due to its potential therapeutic properties. Relatively little is known about how CBD might interact with other commonly used drugs. While a number of studies have explored the influence of cannabis or Δ9-THC on alcohol consumption and treatment outcomes, few have examined the effects of CBD on alcohol-related outcomes. This article reviews preclinical and human studies examining the effects of CBD administration on alcohol responses. Preliminary preclinical results suggest that CBD can attenuate alcohol consumption and potentially protect against certain harmful effects of alcohol, such as liver and brain damage. Also reviewed herein are the few existing studies involving CBD and alcohol coadministration in humans. The paucity of such studies precludes any definitive conclusions relating to CBD-alcohol interactions. Effects of CBD on alcohol use and potential therapeutic implications for alcohol use disorder are discussed.<br>\n _{–– Nona CN et al.: <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/31120285\" rel=\"nofollow noreferrer\">\"Effects of cannabidiol on alcohol-related outcomes: A review of preclinical and human research\"</a>, Exp Clin Psychopharmacol. 2019 May 23. doi: 10.1037/pha0000272.} </p>\n \n <p>There is substantial interest in the therapeutic potential of cannabidiol (CBD), a non-psychoactive cannabinoid found in plants of the genus Cannabis. The goal of the current systematic review was to characterize the existing literature on this topic and to evaluate the credibility of CBD as a candidate pharmacotherapy for alcohol use disorder (AUD). Using a comprehensive search strategy, 303 unique potential articles were identified and 12 ultimately met criteria for inclusion (8 using rodent models, 3 using healthy adult volunteers, and 1 using cell culture). In both rodent and cell culture models, CBD was found to exert a neuroprotective effect against adverse alcohol consequences on the hippocampus. In rodent models, CBD was found to attenuate alcohol-induced hepatotoxicity, specifically, alcohol-induced steatosis. Finally, findings from preclinical rodent models also indicate that CBD attenuates cue-elicited and stress-elicited alcohol-seeking, alcohol self-administration, withdrawal-induced convulsions, and impulsive discounting of delayed rewards. In human studies, CBD was well tolerated and did not interact with the subjective effects of alcohol. Collectively, given its favorable effects on alcohol-related harms and addiction phenotypes in preclinical models, CBD appears to have promise as a candidate AUD pharmacotherapy. This is further bolstered by the absence of abuse liability and its general tolerability. A clear limitation to the literature is the paucity of human investigations. Human preclinical and clinical studies are needed to determine whether these positive effects in model systems substantively translate into clinically-relevant outcomes.<br>\n _{–– Turna J et al.: <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/30698831\" rel=\"nofollow noreferrer\">\"Cannabidiol as a Novel Candidate Alcohol Use Disorder Pharmacotherapy: A Systematic Review\",</a> Alcohol Clin Exp Res. 2019 Apr;43(4):550-563. doi: 10.1111/acer.13964.} </p>\n</blockquote>\n\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pubmed/24398069\" rel=\"nofollow noreferrer\">Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy.</a></p>\n\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pubmed/24012796\" rel=\"nofollow noreferrer\">Transdermal delivery of cannabidiol attenuates binge alcohol-induced neurodegeneration in a rodent model of an alcohol use disorder.</a></p>\n\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444130/\" rel=\"nofollow noreferrer\">Cannabidiol as an Intervention for Addictive Behaviors: A Systematic Review of the Evidence</a></p>\n", "score": 3 } ]

[ "cannabidiol", "cannabinoids" ]

[ { "answer_id": 19565, "body": "<p>This answer is about the effect of NSAIDs and steroids on the resorption of disc herniation and pain.</p>\n\n<p>There seem to be no clinical trials in which NSAIDs or other drugs would slow down the resorption of disc herniation. Results of <em>in vitro</em> studies suggest that steroids may be able to delay resorption, but NSAIDs less likely.</p>\n\n<p><strong>STEROIDS</strong></p>\n\n<p>According to the study <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003509/\" rel=\"nofollow noreferrer\">Influence of cytokine inhibitors on concentration and activity of MMP-1 and MMP-3 in disc herniation (Arthritis Research &amp; Therapy, 2009)</a>, the resorption of a disc herniation is enabled by the enzymes called matrix metalloproteinases MMP-1 and MMP-3. In the study, a steroid dexamethasone and a tumor necrosis factor inhibitor infliximab reduced the activity of MMP-3, which suggests that...</p>\n\n<blockquote>\n <p>...at least under certain circumstances, the clinical use of these drugs may affect the resorption of disc herniation.</p>\n</blockquote>\n\n<p>BUT</p>\n\n<blockquote>\n <p>Such an effect was not reported after a foraminal injection of\n methylprednisolone [another steroid] in patients with sciatica, but\n was observed in a rabbit model using higher dosages.</p>\n</blockquote>\n\n<p>According to another study <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/12468973\" rel=\"nofollow noreferrer\">Lumbar disc herniation regression after successful epidural steroid injection (Journal of Spinal Disorders &amp; Techniques, 2002)</a>:</p>\n\n<blockquote>\n <p>In conclusion, epidural steroid injections do not alter ultimate\n herniated nucleus pulposus regression.</p>\n</blockquote>\n\n<p>According to this <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/16481946\" rel=\"nofollow noreferrer\">2006 trial</a>, <em>intravenous</em> steroids have a small and short effect on pain reduction. According to <a href=\"https://www.aafp.org/afp/2008/1001/p835.html\" rel=\"nofollow noreferrer\">American Family Physician, 2008</a>, <em>epidural</em> steroid injections can provide better short-term pain relief. </p>\n\n<p><strong>NSAIDS</strong> </p>\n\n<p>Here's one <a href=\"http://www.actaorthopaedica.be/acta/download/2013-6/20-Yu%20et%20al.pdf\" rel=\"nofollow noreferrer\">2013 study</a> about the effectiveness of physical therapy on the healing of the herniated discs. At the end of the article there is a recommendation that looks merely as an opinion:</p>\n\n<blockquote>\n <p>However, the use of NSAIDs (non-steroidal anti-inflammatory drugs)\n should be limited, as they inhibit the function of phagocytes and\n inflammatory cells, which initiate resorption of the hernia.</p>\n</blockquote>\n\n<p>But in a study <a href=\"https://www.sciencedirect.com/science/article/pii/S1063458406003220?via%3Dihub\" rel=\"nofollow noreferrer\">In vitro effects of non-steroidal anti-inflammatory drugs on cytokine, prostanoid and matrix metalloproteinase production by interface membranes from loose hip or knee endoprostheses (Science Direct, 2006)</a>, NSAIDs did not have any clear effect on the MMP synthesis, which suggests they should not delay the resorption of disc herniation.</p>\n\n<p>Anyway, according to several systematic reviews, NSAIDs are not very effective in treatment of spinal pain (<a href=\"https://ard.bmj.com/content/76/7/1269.short\" rel=\"nofollow noreferrer\">Annals of Rheumatic Disease, 2016</a> ; <a href=\"https://www.cochrane.org/CD012382/BACK_non-steroidal-anti-inflammatory-drugs-low-back-pain-sciatica\" rel=\"nofollow noreferrer\">Cochrane, 2016</a>).</p>\n\n<p>From a larger perspective, medications, other conservative therapy and surgery do not provide better long-term (1-2 year) results than no treatment at all (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895638/\" rel=\"nofollow noreferrer\">BMJ, 2007</a>).</p>\n", "score": 2 } ]

[ "immune-system", "back", "anti-inflammatory", "sciatic-nerve" ]

[ { "answer_id": 19651, "body": "<p>Homeopathy isn't a scientific thing, and sometimes it is very easily refuted\n<a href=\"https://www.livescience.com/31977-homeopathy.html\" rel=\"noreferrer\">https://www.livescience.com/31977-homeopathy.html</a>\nhomepathic \"remedies\" are compounds that are so diluted that there is a chance that the active molecule will appear only if the solution is as big as the solar system. There is no research that discovered how it works, so it is believed that it is a big fake and the only effect that it haves is the placebo.</p>\n", "score": 6 } ]

[ "practice-of-medicine" ]

[ { "answer_id": 19685, "body": "<p>Your back-of-the-envelope calculations seem to be off in estimating the extent of viral load reduction in a treated versus untreated person as well as the risk of transmission for unprotected, untreated sex (5% is much higher than any other number I have seen).</p>\n\n<blockquote>\n <p>Obviously the viral load is not zero because then they wouldn't be HIV positive</p>\n</blockquote>\n\n<p>is not accurate. Current antiretroviral therapies are able to reduce serum HIV concentrations to be below detectable limits. That doesn't make them HIV-negative, because they still have HIV infections in their cells and their serum would test positive if they stopped antiretroviral use (i.e., they are not cured).</p>\n\n<p>In 1238 couple-years, zero transmissions occurred with condomless sex (estimated 58,000 sexual interactions without a condom including both heterosexual couples and homosexual males) when the HIV-positive partner was on antiretroviral therapy <em>to the extent that they did not have detectable serum concentrations of virus</em> (Rodger et al, 2016). This is a sufficient observation period to make the upper limit of a 95% confidence interval =0.30/100.</p>\n\n<p>You are correct that this does not mean the risk is zero, but it is very low; several people involved in that study <em>did</em> become HIV-positive during the study but for all of them this was through sex with additional partners not part of the antiretroviral treatment.</p>\n\n<p>This study and others like it should not necessarily be interpreted as meaning that safer sex practices are unnecessary when HIV is suppressed to undetectable levels, but they speak to the efficacy of those drugs for prevention. One limitation the authors note is that because anal sex with ejaculation is associated with higher transmission rates than other types of sex, and since their study was not limited to that particular act:</p>\n\n<blockquote>\n <p>despite an observed transmission rate of zero for this risk behavior, a clinically important rate of less than 2.2 per 100 couple-years of follow-up cannot be excluded. This translates into an upper limit estimate of 20% risk over 10 years.</p>\n</blockquote>\n\n<p>(note this is still an upper limit estimate...further study may bring that upper limit downward; <em>edit: there is a further follow up from this study published June 2019, <a href=\"https://www.sciencedirect.com/science/article/pii/S0140673619304180\" rel=\"noreferrer\">Rodger et al</a>, focusing on condomless anal sex between men; they continued to not find any cases of partner to partner transmission with antiretroviral treatment allowing them to decrease the upper CI to 0.23 per 100 couple years</em> for the sex act known to be of highest risk for transmission without treatment)</p>\n\n<p>Serodiscordant couples will need to interpret for themselves how to respond to these risks, and from a broader standpoint other issues like the consistent use of prescribed drugs are also relevant. Cohen et al, 2016 used an intention-to-treat design to study a similar question, and found several partner transmissions (fewer when treatment was started earlier), but none of these where in cases where the positive partner had undetectable serum levels, which was likely because the person chose not to take the drug for whatever reason (and still the infection rates between partners were very low than without antiretroviral treatment).</p>\n\n<p>A meta analysis by LeMessurier et al, 2018 found \"no transmissions with antiretroviral therapy and a viral load of less than 200 copies/mL.\"</p>\n\n<hr>\n\n<p><a href=\"https://jamanetwork.com/journals/jama/fullarticle/2533066\" rel=\"noreferrer\">Rodger, A. J., Cambiano, V., Bruun, T., Vernazza, P., Collins, S., Van Lunzen, J., ... &amp; Asboe, D. (2016). Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy. Jama, 316(2), 171-181.</a></p>\n\n<p><a href=\"https://www.nejm.org/doi/full/10.1056/nejmoa1600693\" rel=\"noreferrer\">Cohen, M. S., Chen, Y. Q., McCauley, M., Gamble, T., Hosseinipour, M. C., Kumarasamy, N., ... &amp; Godbole, S. V. (2016). Antiretroviral therapy for the prevention of HIV-1 transmission. New England Journal of Medicine, 375(9), 830-839.</a></p>\n\n<p><a href=\"http://www.cmaj.ca/content/190/46/E1350.abstract\" rel=\"noreferrer\">LeMessurier, J., Traversy, G., Varsaneux, O., Weekes, M., Avey, M. T., Niragira, O., ... &amp; Rodin, R. (2018). Risk of sexual transmission of human immunodeficiency virus with antiretroviral therapy, suppressed viral load and condom use: a systematic review. CMAJ, 190(46), E1350-E1360.</a></p>\n", "score": 5 } ]

[ "sex", "disease-transmission", "statistics", "hiv" ]

[ { "answer_id": 19737, "body": "<p>In the context of your question, the <em>clinical context</em> is limited to a <em>patient's history</em> (symptoms and relevant circumstances) and signs discovered during a <em>physical examination,</em> which can include manual tests and tests using a stethoscope and other simple instruments. <em>Clinical context</em> here does not include laboratory tests and other tests that involve \"machines\" (ultrasound, CT, EKG, etc.).</p>\n\n<p>It may help if you imagine that the term <a href=\"https://www.medicinenet.com/script/main/art.asp?articlekey=21959\" rel=\"nofollow noreferrer\">clinical</a> originates from the Greek <em>kline,</em> which means <em>bed,</em> so <em>clinical</em> refers to what a doctor can do \"beside bed.\"</p>\n\n<p><em>(Outside of the context of your question, the term clinical can be used very broadly, for example, for everything what includes hospitals (clinics) and for pretty much all interactions between doctors and patients.)</em></p>\n\n<p>The process of diagnosing anemia includes the evaluation of:</p>\n\n<p><strong>1) Circumstances,</strong> for example, a vegan who does not eat a lot (and hence probably consumes only little iron), or a history of anemia in family members (genetic types of anemia).</p>\n\n<p><strong>2) Symptoms,</strong> such as tiredness</p>\n\n<p><strong>3) Signs,</strong> revealed during a physical examination, such as pallor and fast heart rate</p>\n\n<p><strong>4) Blood tests:</strong> low hemoglobin and ferritin, small erythrocite volume, etc.</p>\n\n<p>Sources:</p>\n\n<ul>\n<li><a href=\"https://www.aafp.org/afp/2013/0115/p98.html\" rel=\"nofollow noreferrer\">Iron Deficiency Anemia: Evaluation and Management (American Family Physician, 2013)</a></li>\n<li><a href=\"http://www.arup.utah.edu/media/anemia/Anemia%20Lecture%20for%20the%20MLT%20students.pdf\" rel=\"nofollow noreferrer\">Diagnostic approach to Anemia (University of Utah School of Medicine, 2014)</a></li>\n</ul>\n", "score": 5 } ]

[ "diagnosis", "hematology", "anemia" ]

[ { "answer_id": 19789, "body": "<p>Hydrocortisone is a steroid anti-inflammatory used by itself to treat dermatitis and other inflammatory symptoms.</p>\n\n<p>The combined treatment gives symptom relief at the same time as treating the underlying cause; hydrocortisone alone would be ineffective at treating the infection, and clotrimazole alone does not resolve symptoms as quickly. There may also be some synergistic effects on treating the actual infection:</p>\n\n<blockquote>\n <p>The addition of a corticosteroid to an antifungal agent at the initiation of treatment can attenuate the inflammatory symptoms of the infection and is thought to increase patient compliance, reduce the risk of bacterial superinfection and enhance the efficacy of the antifungal agent</p>\n</blockquote>\n\n<p>(Schaller et al 2016)</p>\n\n<hr>\n\n<p>Schaller, M., Friedrich, M., Papini, M., Pujol, R. M., &amp; Veraldi, S. (2016). Topical antifungal‐corticosteroid combination therapy for the treatment of superficial mycoses: conclusions of an expert panel meeting. Mycoses, 59(6), 365-373.</p>\n\n<p>Shankland, G. S., &amp; Richardson, M. D. (1990). Comparative in-vivo activity of clotrimazole and a clotrimazole/hydrocortisone combination in the treatment of experimental dennatophytosis in guinea pigs. Journal of Antimicrobial Chemotherapy, 25(5), 825-830.</p>\n", "score": 6 } ]

[ "medications", "prescription" ]

[ { "answer_id": 19969, "body": "<p>Isotretinoin works by reducing the production of the skin's natural oil (sebum) - <a href=\"https://www.netdoctor.co.uk/medicines/skin-hair/a7486/roaccutane-isotretinoin/\" rel=\"nofollow noreferrer\">Netdoctor UK</a>. \nThe half life of isotretinoin is 10-22 hours <a href=\"https://www.semanticscholar.org/paper/A-review-of-three-systemic-retinoids-in-dermatology-Mortazavi-Aghazadeh/5e1d7c4456fa24cff8dd4a87ef768c6fcd85d4ff\" rel=\"nofollow noreferrer\">(Mortazavis et al., 2014)</a>, so it would take about a 5 days to week for the drug to reach steady state. In the meantime as the sebum production reduces, the skin dryness will stimulate the sebum glands to increase production causing a period of short term deterioration due to sebum over-production, before sebum production drops by two to four weeks. Another factor could be is that isotretinoin causes an increase in increase in epidermal cell turnover <a href=\"https://www.researchgate.net/publication/7057374_Epidermal_effects_of_tretinoin_and_isotretinoin_Influence_of_isomerism\" rel=\"nofollow noreferrer\">(Tadini, Gaspar &amp; Campos, 2006)</a>. This can lead to sloughing, peeling, and redness that might make acne appear to be worsening when in fact it is a different skin process altogether.</p>\n\n<p>There is also a more serious complication of starting isotretinoin which is a flare of acne fulminans. Acne fulminans is a severe form of inflammatory acne which usually require steroids resolve. Younger age, male sex and sebaceous retention are significant risk factors for acne fulminans, more specificially if the acne was severe to start with, there is more than 44 facial comedones, 2 facial nodules and presence of truncal acne <a href=\"https://www.jle.com/en/revues/ejd/e-docs/predictive_factors_for_acne_flare_during_isotretinoin_treatment_278096/article.phtml?cle_doc=00043E50\" rel=\"nofollow noreferrer\">(Demircay, Kus &amp; Sur, 2008)</a>. However, now as isotretinoin is started at a lower dose and usually antibiotics and/or steroids are given for those at high risk making acne fulminans a far less common complication. </p>\n\n<p>*References:</p>\n\n<p>Demircay, Z., Sadiye, K., Haydar, S. (2008). <a href=\"https://www.jle.com/en/revues/ejd/e-docs/predictive_factors_for_acne_flare_during_isotretinoin_treatment_278096/article.phtml?cle_doc=00043E50\" rel=\"nofollow noreferrer\">Predictive factors for acne flare during isotretinoin treatment</a>. European Journal of Dermatology. pg 452-6. </p>\n\n<p>_{\nMortazavi, H., Aghazadeh, N., Ghiasi, M., &amp; Lajevardi, V. (2014). <a href=\"https://www.semanticscholar.org/paper/A-review-of-three-systemic-retinoids-in-dermatology-Mortazavi-Aghazadeh/5e1d7c4456fa24cff8dd4a87ef768c6fcd85d4ff\" rel=\"nofollow noreferrer\">A review of three systemic retinoids in dermatology: Acitretin , isotretinoin and bexarotene.</a> Iranian Journal of Dermatology.\n}</p>\n\n<p>Tadini, A., Gaspar, K., &amp; Campos, P. (2006). <a href=\"https://www.researchgate.net/publication/7057374_Epidermal_effects_of_tretinoin_and_isotretinoin_Influence_of_isomerism\" rel=\"nofollow noreferrer\">Epidermal effects of tretinoin and isotretinoin: Influence of isomerism</a>. Die Pharmazie, 61, 453–456.</p>\n", "score": 3 }, { "answer_id": 19907, "body": "<p>This is a concept not unique to <a href=\"https://en.wikipedia.org/wiki/Isotretinoin\" rel=\"nofollow noreferrer\">Isotretinoin</a>, which is that of either:</p>\n\n<ul>\n<li><a href=\"https://en.wikipedia.org/wiki/Desensitization_(medicine)\" rel=\"nofollow noreferrer\">drug sensitivity</a>.</li>\n<li><a href=\"https://en.wikipedia.org/wiki/Drug_allergy\" rel=\"nofollow noreferrer\">drug allergy</a></li>\n<li><a href=\"https://en.wikipedia.org/wiki/Drug_intolerance\" rel=\"nofollow noreferrer\">drug intolerance</a></li>\n</ul>\n\n<p>Drug sensitivity happens as the body reacts to an initial exposure to a drug, before it builds a <a href=\"https://en.wikipedia.org/wiki/Drug_tolerance\" rel=\"nofollow noreferrer\">tolerance</a> to it.</p>\n\n<blockquote>\n <p>A drug allergy is different from an intolerance. A drug intolerance, which is often a milder, non-immune-mediated reaction, does not depend on prior exposure. [WP:Drug Allergy]</p>\n</blockquote>\n", "score": 0 } ]

[ "medications", "dermatology", "side-effects", "acne" ]

[ { "answer_id": 19818, "body": "<p>That's a nice question. </p>\n\n<p>First of all, it is important to note that whenever a question of which drug to use arises, a number of factors should be taken into consideration, that is to say: prescribing a treatment is not simply a game of matching condition to drug (I am <strong>not</strong> saying that this is what the OP is saying or implying, this is just to illustrate that the process is complicated).</p>\n\n<p>The physician should take into account the patient's main complaint (current condition), age, weight, sex (particularly important for hair loss...), sensitivities (if any are known), physical condition, underlying diseases (if any), other concurrent drugs, and more. These are all \"filters\" of a sort that help the physician narrow down the list of possible drugs that may be suitable for the patient's current predicament (this question deals with two therapeutic options, but sometimes there are many more drugs to choose from, e.g. when starting treatment for hypertension).</p>\n\n<p>In addition, doctors also apply more subjective considerations to their decisions, such as their good judgement and experience, knowledge of drug prices (even if this is not a pure medical consideration, the doctor may apply it if he thinks that it's better for a patient to take a slightly less effective drug which is cheaper and the patient will be able to afford it, than if the patient will not be taking any treatment because the better option is more expensive/unavailable to the patient), and more.</p>\n\n<p>Now, on the topic of this question:<br>\nYour comparison between minoxidil and finasteride is quite on-spot. You could also say that minoxidil is even more available on account that is is an over-the-counter drug, while finasteride requires a doctor's prescription.\nIn that case, minoxidil would surely be preferred by most clinicians. The cases when finasteride would be preferable to minoxidil are more limited and may include the following:</p>\n\n<ol>\n<li>Hypersensitivity to minoxidil (as with any drug, probably rare but should be borne in mind). Even susceptibility for non-dangerous side effects may cause a patient to avoid using minoxidil.</li>\n<li>Minoxidil was tried and found to be ineffective - this is a common issue in drug therapy, and for that reason it is good to have first-line therapy, second-line therapy, third-line therapy and so on. \nAlso, according to a <a href=\"https://www.aafp.org/afp/2017/0915/p371.html\" rel=\"nofollow noreferrer\">publication of the AAFP</a> (American Academy of Family Physicians): <em>\"Finasteride (Propecia), 1 mg per day orally, is approved to treat androgenetic alopecia in men <strong>for whom topical minoxidil has been ineffective</strong>.\"</em></li>\n<li>Finasteride is available as a topical solution but also as a tablet. Minoxidil tablets are not used for treatment of hair loss, only for treatment of hypertension. Some patients may prefer to conveniently take a finasteride tablet than apply/rub a minoxidil solution/foam on their head, particularly if they are in a an environment where it would be less convenient to use the topical form.</li>\n</ol>\n\n<p>In conclusion, the selection of a treatment is based on both the doctor's and patient's preferences. These may not always be the same, but the final selection should be some average of both, so even when one alternative seems to shine above all others, it may not always be that way for all patients.</p>\n", "score": 1 }, { "answer_id": 19962, "body": "<p>Not the answer you would want to hear but have you considered combined therapy? </p>\n\n<blockquote>\n <p>combined treatment of male androgenetic alopecia with oral finasteride and topical minoxidil found that “the combined medication showed the best efficacy.</p>\n</blockquote>\n\n<p><a href=\"https://www.keeps.com/learn/finasteride-vs-minoxidil\" rel=\"nofollow noreferrer\">Hair loss article commenting on a 2015 study</a></p>\n\n<p>It really depends on how much hair loss you are getting. If you are getting a lot of hair loss, then probably finasteride is the better way to go. Apparently, minoxidil does not stop hair loss as effectively.</p>\n\n<p><a href=\"https://www.forhims.com/blog/minoxidil-vs-finasteride-do-either-really-work\" rel=\"nofollow noreferrer\">https://www.forhims.com/blog/minoxidil-vs-finasteride-do-either-really-work</a></p>\n", "score": 1 } ]

[ "hairloss" ]

[ { "answer_id": 19885, "body": "<p>Source 3 is a book sponsered by Cyanotech Corporation claiming beneficial effects for the human health using Astaxanthin. The author is employee of Cyanotech Corporation.\nThere is a small chapter regarding beneficial effects of Astaxanthin for the tennis elbow, but is is only referring to source 1.</p>\n\n<p>I did not find anymore studies referring to the effects of using Astaxanthin in the treatment of tennis elbow. But there is a <a href=\"https://www.google.com/url?sa=t&amp;source=web&amp;rct=j&amp;url=https://www.cyanotech.com/pdfs/bioastin/batl18.pdf&amp;ved=2ahUKEwjBpZz92fvjAhXBwsQBHSu5DM0QFjACegQIARAB&amp;usg=AOvVaw03Lg12cq8x4NKKAxHroM0y&amp;cshid=1565556981743\" rel=\"nofollow noreferrer\">study</a>(1) (sponsered by Cyanotech Corporation) regarding carpal tunnel syndrome claiming a beneficial effect of Astaxanthin while there is another <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280376/#__ffn_sectitle\" rel=\"nofollow noreferrer\">one</a>(2) stating that there is no significant effect. </p>\n\n<p>The European Food Saftey Authorizy gave their scientific opinion regarding health claims <a href=\"http://www.efsa.europa.eu/en/efsajournal/pub/1253\" rel=\"nofollow noreferrer\">here</a>(3):</p>\n\n<blockquote>\n <p>In addition, two unpublished reports on the effects of astaxanthin in the relief of pain and the improvement of performance in patients with carpal tunnel syndrome (Nir and Spiller, 2002a) and with tennis elbow (Spiller et al., 2006), and one intervention in patients with rheumatoid arthritis were \n presented to support the claimed effect (Nir and Spiller, 2002b). The Panel notes that the three studies above are pilot single-centre, double-blind placebo-controlled parallel studies conducted with a product containing high oleic safflower oil, Haematococcus extract, lutein, vitamin A, vitamin E, gelatine and rosemary oil in addition to astaxanthin, and therefore no conclusions can be drawn from these studies on the food that is the subject of the health claim, astaxanthin, in relation to the claimed \n effect. \n The Panel concludes that a cause and effect relationship has not been established between the \n consumption of astaxanthin and the maintenance of normal joints, tendons or connective tissue.</p>\n</blockquote>\n\n<p>So there is no evidence available supporting the use of Astaxanthin for the treatment of tennis elbow </p>\n\n<p>References:</p>\n\n<p>(1)</p>\n\n<p>BioAstin, a natural astaxanthin from microalge helps relieve pain and improves performance in patients with carpal tunnel syndrome\n <a href=\"https://www.google.com/url?sa=t&amp;source=web&amp;rct=j&amp;url=https://www.cyanotech.com/pdfs/bioastin/batl18.pdf&amp;ved=2ahUKEwjBpZz92fvjAhXBwsQBHSu5DM0QFjACegQIARAB&amp;usg=AOvVaw03Lg12cq8x4NKKAxHroM0y&amp;cshid=1565556981743\" rel=\"nofollow noreferrer\">https://www.google.com/url?sa=t&amp;source=web&amp;rct=j&amp;url=https://www.cyanotech.com/pdfs/bioastin/batl18.pdf&amp;ved=2ahUKEwjBpZz92fvjAhXBwsQBHSu5DM0QFjACegQIARAB&amp;usg=AOvVaw03Lg12cq8x4NKKAxHroM0y&amp;cshid=1565556981743</a></p>\n\n<p>(2)</p>\n\n<p>A blinded placebo-controlled randomized trial on the use of astaxanthin as an adjunct to splinting in the treatment of carpal tunnel syndrome\n <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280376/#__ffn_sectitle\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280376/#__ffn_sectitle</a></p>\n\n<p>(3)</p>\n\n<p>Scientific Opinion on the substantiation of health claims related to \nastaxanthin\n <a href=\"http://www.efsa.europa.eu/en/efsajournal/pub/1253\" rel=\"nofollow noreferrer\">http://www.efsa.europa.eu/en/efsajournal/pub/1253</a></p>\n", "score": 5 } ]

[ "tendinopathy", "treatment", "tendons" ]

[ { "answer_id": 31071, "body": "<p>The slice location can be easily computed by looking at the <code>(0020, 0032) ImagePosition</code> tag.</p>\n<p>This tag is described in the <a href=\"https://dicom.nema.org/medical/dicom/current/output/pdf/part03.pdf\" rel=\"nofollow noreferrer\">DICOM Documentation Part 3 (page 561)</a> and it's a type 1 attribute, i.e. it's required to be in the SOP (Service-Object Pair) Instance and must have a valid value, so you will always find this value within your DICOM sets.</p>\n<p>For your convenience I copy-paste here a table from the documentation above:\n<a href=\"https://i.stack.imgur.com/hF5ZW.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/hF5ZW.png\" alt=\"enter image description here\" /></a></p>\n<p>So the <code>ImagePosition</code> attribute gives you the <em>x</em>, <em>y</em>, and <em>z</em> coordinates of the upper left hand corner of the image, in mm. To compute the distance between two slices just compute the difference between the <em>z</em> coordinates of two contiguous images. Similarly, compute the difference between the <em>z</em> coordinates of the first and last slice to get the total height of the image set.</p>\n<p>Note that sometimes you can have an image set with variable slice spacing.</p>\n<p>Regarding the thickness, usually you can have overlapping slices, so the slice thickness and slice increment will be different as you can see in the image below (<a href=\"https://www.materialise.com/en/faq/what-difference-between-slice-thickness-and-slice-increment\" rel=\"nofollow noreferrer\">courtesy of Materialise</a>):\n<a href=\"https://i.stack.imgur.com/Gj6PO.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/Gj6PO.png\" alt=\"enter image description here\" /></a></p>\n", "score": 2 } ]

[ "medical-imaging", "radiology", "dicom" ]

[ { "answer_id": 19916, "body": "<p>Older paternal (and maternal) age in fact <em>is</em> associated with some increase in disease, though at fairly low rates.</p>\n\n<p>Cancer is largely a disease of probability. One does not need to have mutations in all of their cells to develop cancer, just one. But a parent does not pass on all their mutations in all their cells, they pass on just one, which need not have any deleterious mutations at all, even if the parent has cancer themselves in some other part of the body.</p>\n\n<p>If that one cell is defective in some way, it is less likely to be involved in creation of a successful pregnancy, and may lead to miscarriage. Therefore, the probabilistic process of reproduction tends to result in offspring from selection of healthier gametes.</p>\n\n<p>I grabbed a reference from <a href=\"https://biology.stackexchange.com/questions/77990/passing-on-the-dna-of-old-age/77993\">another StackExchange answer</a>, Cochran and Harpending 2013, which estimates that fathers pass on about <code>25+2(age−20)</code> novel mutations. Many of those mutations will have no effect at all; those that do will be more common with older fathers.</p>\n\n<hr>\n\n<p>Cochran, G., &amp; Harpending, H. (2013). Paternal age and genetic load. Human biology, 85(4), 515-529.</p>\n\n<p>de La Rochebrochard, E., &amp; Thonneau, P. (2002). Paternal age and maternal age are risk factors for miscarriage; results of a multicentre European study. Human reproduction, 17(6), 1649-1656.</p>\n\n<p>Jones, K. L., Smith, D. W., Harvey, M. A. S., Hall, B. D., &amp; Quan, L. (1975). Older paternal age and fresh gene mutation: data on additional disorders. The Journal of pediatrics, 86(1), 84-88.</p>\n\n<p>Sipos, A., Rasmussen, F., Harrison, G., Tynelius, P., Lewis, G., Leon, D. A., &amp; Gunnell, D. (2004). Paternal age and schizophrenia: a population based cohort study. Bmj, 329(7474), 1070.</p>\n", "score": 4 } ]

[ "sex", "reproduction", "dna" ]

[ { "answer_id": 19972, "body": "<p>Although the term \"contractility\" can refer to contraction of any muscle, including skeletal muscle (e.g. biceps) and smooth muscle (e.g. muscles in arterial walls), in medicine <strong>contractility usually refers to <a href=\"https://www.ncbi.nlm.nih.gov/books/NBK54085/\" rel=\"noreferrer\">cardiac contractility</strong></a>, which in most fundamental terms is the <strong>force with which the heart muscle squeezes.</strong></p>\n\n<p>According to the <a href=\"https://www.ncbi.nlm.nih.gov/books/NBK54078/\" rel=\"noreferrer\">textbook Regulation of Cardiac Contractility by Solaro</a>:</p>\n\n<blockquote>\n <p>Contractility describes the relative ability of the heart to eject a\n stroke volume (SV) at a given prevailing afterload (arterial pressure)\n and preload (end-diastolic volume; EDV).</p>\n</blockquote>\n\n<p><a href=\"https://medlineplus.gov/ency/article/002338.htm\" rel=\"noreferrer\">Vasoconstriction</a> is a specific term for the squeezing of smooth muscle within the walls of blood vessels (arteries, arteroiles, veins, venuoles, etc). Vasoconstriction of arteries increases arterial blood pressure and <a href=\"https://www.cvpharmacology.com/vasoconstrictor/vasoconstrictor\" rel=\"noreferrer\">cardiac afterload</a>. Vasoconstriction of veins increases venous return to the heart by reducing venous pooling, thus <a href=\"https://www.cvpharmacology.com/vasoconstrictor/vasoconstrictor\" rel=\"noreferrer\">increasing preload</a>. Of note, most often vasoconstriction is used to refer to <em>arterial</em> vasoconstriction. There is a lot of good information on the pharmacology of modulating blood pressure including vasopressors (norepinephrine, levophed) that vasoconstrict to raise blood pressure in septic or hemorrhagic shock, etc. </p>\n\n<p>Cortisol both <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568128/\" rel=\"noreferrer\">increases cardiac contractility</a> <em>as well as</em> <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/15320828\" rel=\"noreferrer\">increases arterial vasoconstriction</a>.</p>\n\n<p>Both increasing cardiac contractility (increased force of squeezing blood out of the heart) as well as increasing arterial vasoconstriction (decreasing diameter of arteries) will raise blood pressure. </p>\n", "score": 7 } ]

[ "terminology", "cardiovascular-disease", "cortisol", "vasoconstriction" ]

[ { "answer_id": 20045, "body": "<p><a href=\"https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&amp;Expert=1906\" rel=\"noreferrer\">Fetal valproate syndrome</a> (FVS) is now a well-known risk of using valproic acid in pregnancy. It is characterised by physical and intellectual developmental problems in the fetus, primarily with language and communication. </p>\n\n<h2>Teratogenicity</h2>\n\n<p>The general term for a drug that causes adverse developmental effects on a fetus is a <a href=\"https://en.m.wikipedia.org/wiki/Teratology\" rel=\"noreferrer\">teratogen</a>. It is thought that the teratogenicity of valproic acid is due to its action on folate (folic acid) metabolism. The risk of FVS is greatest when it is used in the first trimester of pregnancy.</p>\n\n<p>The drug is also known to increase the risk of neural tube defects like spina bifida and also autism spectrum disorder (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511955/\" rel=\"noreferrer\">Christensen et al, 2013</a>). Overlap of symptoms between FVS and ASD can complicate diagnosis.</p>\n\n<h2>Medical uses</h2>\n\n<p>Despite its teratogenicity in pregnancy, <a href=\"https://en.m.wikipedia.org/wiki/Valproate\" rel=\"noreferrer\">valproic acid</a> is widely used as an effective anti-epileptic drug and mood stabiliser.</p>\n\n<h2>Use in autism spectrum disorder</h2>\n\n<p>To answer your question, the teratogenic effect in pregnancy does not mean that people with ASD (or other groups of people) should not use valproic acid. They may be prescribed it for epilepsy or as a mood stabiliser. </p>\n\n<p>A study by <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846602/\" rel=\"noreferrer\">Hollander et al (2010)</a> shows the efficacy of valproic acid for the treatment of symptoms of irritability in people with autism spectrum disorder.</p>\n\n<hr>\n\n<p>See <a href=\"https://medicalsciences.stackexchange.com/a/20021/14056\">this excellent answer</a> for an in-depth analysis of current research on the causes of autism.</p>\n", "score": 5 } ]

[ "medications", "autism" ]

[ { "answer_id": 20059, "body": "<p>Hard stool that stays in the colon for more than a couple of days is called \"fecal impaction.\" Most <em>medical sources</em> recommend treating it with manually removing the stool (by a doctor, if necessary) and using <em>rectally</em> administrated enemas:</p>\n\n<blockquote>\n <p>Softening of hardened stool and stimulation of evacuation with enemas\n and suppositories is often helpful...Most enema solutions contain\n water and an osmotic agent. One such combination contains water,\n docusate sodium syrup...and sorbitol... <em>Rectally</em> administered\n solutions mechanically soften the impacted stool and the additional\n volume gently stimulates the rectum to evacuate <em>(<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348734/\" rel=\"nofollow noreferrer\">Clinics in Colon and Rectal Surgery</a>)</em>.</p>\n</blockquote>\n\n<p>You can also check the \"Fecal Impaction\" part on <a href=\"https://www.mayoclinicproceedings.org/article/s0025-6196(11)63796-8/fulltext\" rel=\"nofollow noreferrer\">Mayoclinicproceedings.org</a>.</p>\n\n<p>According to <a href=\"https://www.aafp.org/afp/2015/0915/p500.html\" rel=\"nofollow noreferrer\">American Family Physician</a>:</p>\n\n<blockquote>\n <p>Fecal impaction should be treated with <em>mineral oil or warm water\n enemas.</em></p>\n</blockquote>\n\n<p>According to some studies, <em>oral</em> stool softeners may also help to remove hard stool (<a href=\"https://www.sciencedirect.com/topics/medicine-and-dentistry/feces-impaction\" rel=\"nofollow noreferrer\">ScienceDirect</a>).</p>\n\n<blockquote>\n <p>Oral disimpaction can be accomplished by high doses of stimulant\n laxatives, docusate, mineral oil, and polyethylene glycol-electrolyte\n (PEG) solutions. Osmotic laxatives such as lactulose or sorbitol can\n be used in combination with other medication. <em>Oral disimpaction is\n often associated with abdominal pain and colic, as well as an initial\n increase in fecal soiling.</em></p>\n</blockquote>\n\n<p>The problem with <em>oral</em> softeners, stimulants and osmotic agents is that once you take them, you can't go back..They can cause severe bloating and abdominal or rectal pain, so one needs to judge carefully what to use. In fecal impaction, oral softeners can increase the amount of water in the intestine, but not necessary in the hard stool itself. This may cause pressure to push the hard stool out, which may not be successful and can be painful.</p>\n", "score": 5 } ]

[ "gastroenterology", "stools", "constipation", "laxative" ]

[ { "answer_id": 20230, "body": "<p>There are some data about possible causes of vaping-related lung damage, the type of the damage and symptoms, but not about the changes in medical history questionnaires, vaping habits or e-cigarette firmware.</p>\n<p>Most commonly associated substances were THC and nicotine containing oils. Most of the investigated samples contained very high amounts of vitamin E.</p>\n<h2>EVIDENCE:</h2>\n<p><strong>Tetrahydrocannabinol (THC)-containing oils</strong> (not smoking or vaping plant matter):</p>\n<p><a href=\"https://www.cdc.gov/mmwr/volumes/68/wr/mm6839e2.htm?s_cid=mm6839e2_w\" rel=\"nofollow noreferrer\">E-cigarette Product Use, or Vaping, Among Persons with Associated Lung Injury — Illinois and Wisconsin, April–September 2019 (CDC.gov, October 4th, 2019)</a>:</p>\n<blockquote>\n<p>Overall, 75 (87%) of 86 interviewed patients reported using\ne-cigarette products containing tetrahydrocannabinol (THC), and 61\n(71%) reported using nicotine-containing products.</p>\n</blockquote>\n<p><a href=\"https://i.stack.imgur.com/BlMEv.gif\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/BlMEv.gif\" alt=\"enter image description here\" /></a></p>\n<p><em>Image: Brands of tetrahydrocannabinol and nicotine products reported by patients with lung damage</em></p>\n<p><a href=\"https://newsnetwork.mayoclinic.org/discussion/vaping-associated-lung-injury-may-be-caused-by-toxic-chemical-fumes-study-fines/\" rel=\"nofollow noreferrer\">Mayo Clinic, October 2nd, 2019</a>:</p>\n<blockquote>\n<p>All of the patients (17) had vaped, and 71% had vaped with marijuana\nor cannabis oils.</p>\n</blockquote>\n<p><strong>Vitamin E acetate:</strong></p>\n<p><a href=\"https://www.health.ny.gov/press/releases/2019/2019-09-05_vaping.htm\" rel=\"nofollow noreferrer\">New York State Department of Health Announces Update on Investigation into Vaping-Associated Pulmonary Illnesses (September, 5th, 2019)</a>:</p>\n<blockquote>\n<p>Laboratory test results showed very high levels of vitamin E\nacetate in nearly all cannabis-containing samples analyzed by the\nWadsworth Center as part of this investigation.</p>\n</blockquote>\n<p>and, according to <a href=\"https://www.governor.ny.gov/news/governor-cuomo-takes-aggressive-action-protect-new-yorkers-harmful-and-addictive-vaping\" rel=\"nofollow noreferrer\">governor.ny.gov</a>:</p>\n<blockquote>\n<p>...The Wadsworth Center has obtained samples of thickeners from these\nthree companies and determined that they are nearly pure vitamin E\nacetate oil.</p>\n</blockquote>\n<p>So, they have found vitamin E acetate in the actual vaping liquids used by the patients and in the thickening agents sold by 3 commercial suppliers.</p>\n<p><strong>Chemical injury of the lungs:</strong></p>\n<p><a href=\"https://newsnetwork.mayoclinic.org/discussion/vaping-associated-lung-injury-may-be-caused-by-toxic-chemical-fumes-study-fines/\" rel=\"nofollow noreferrer\">Mayo Clinic, October 2nd, 2019</a>:</p>\n<blockquote>\n<p>it seems to be some kind of direct chemical injury, similar to\nwhat one might see with exposures to toxic chemical fumes, poisonous\ngases and toxic agents.</p>\n<p>Researchers found no evidence of tissue injury caused by accumulation\nof lipids — fatty substances such as mineral oils.</p>\n<p>We were not surprised by what we found, regarding toxicity,&quot; says Dr.\nLarsen, senior author of the study. &quot;We have seen a handful of cases,\nscattered individual cases, over the past two years where we've\nobserved the same thing, and now we are seeing a sudden spike in\ncases.</p>\n</blockquote>\n<p><strong>Symptoms:</strong></p>\n<p><a href=\"https://www.cdc.gov/media/releases/2019/s0821-cdc-fda-states-e-cigarettes.html\" rel=\"nofollow noreferrer\">CDC.gov, October, 3rd, 2019</a>:</p>\n<blockquote>\n<p>Patients in this investigation have reported symptoms such as: cough,\nshortness of breath, chest pain, nausea, vomiting, diarrhea, fatigue,\nfever, or abdominal pain that have developed over few days to several\nweeks.</p>\n<p>A lung infection does not appear to be causing the symptoms.</p>\n</blockquote>\n<p><strong>In summary,</strong> the cause of vaping-related lung damage is still not known; the only <em>unusual</em> thing they've found so far are high amounts of vitamin E acetate in vaping liquids that probably came from thickening agents.</p>\n", "score": 4 }, { "answer_id": 20388, "body": "<p>While it could still be a mixture of acute reasons: metals, dust, plainly unknown toxins; the underlying reason seems not to be that plant matter is vaped, nor that liquids are vaped.</p>\n\n<p>It also seems not to be causal whether THC or nicotine are in most cases \"associated\" with the disease.</p>\n\n<p>What the fast onset of this disease makes prudent: implicating either THC or nicotine is so highly unlikely as to be an irresponsible claim. It makes no sense to scare people into another moral panic when the exact same substances are tolerated for decades in anyone user when pyrolised (traditional smoking). Note though that adding anything, including THC, to stuff to be <em>inhaled</em> is not 'healthy' per se</p>\n\n<p>What is currently is known is that vaping liquids <em>can</em> be much more dangerous than ordinary smoking.<br>\n<em>But</em> this seems to be caused by additives in uncontrolled, unregulated, often even black-market and refill products. And in these the most likely suspect substance of the now leading theory is:</p>\n\n<blockquote>\n <ul>\n <li><p>Recent CDC laboratory testing of bronchoalveolar lavage (BAL) fluid samples (or samples of fluid collected from the lungs) from 29 patients with EVALI submitted to CDC from 10 states found <strong><em>vitamin E acetate in ALL of the BAL fluid samples.</em></strong> Vitamin E acetate is used as an additive in the production of e-cigarette, or vaping, products. This is the first time that we have detected a potential chemical of concern in biologic samples from patients with these lung injuries.</p></li>\n <li><p>CDC tested for a range of other chemicals that might be found in e-cigarette, or vaping, products, including plant oils, petroleum distillates like mineral oil, MCT oil, and terpenes (which are compounds found in or added to THC products). None of these potential chemicals of concern were detected in the BAL fluid samples tested.</p></li>\n <li><p>This is the first time that we have detected a potential chemical of concern in biologic samples from patients with these lung injuries. These findings provide direct evidence of vitamin E acetate at the primary site of injury within the lungs.</p></li>\n <li><p>These findings complement the <a href=\"https://www.fda.gov/news-events/public-health-focus/lung-illnesses-associated-use-vaping-products\" rel=\"nofollow noreferrer\">ongoing work of FDA</a> and some state public health laboratories to characterize e-liquid exposures and inform the ongoing multistate outbreak.</p></li>\n </ul>\n \n <p>Key Facts about Vitamin E Acetate</p>\n \n <ul>\n <li><p>Vitamin E is a vitamin found in many foods, including vegetable oils, cereals, meat, fruits, and vegetables. It is also available as a dietary supplement and in many cosmetic products, like skin creams.</p></li>\n <li><p>Vitamin E acetate usually does not cause harm when ingested as a vitamin supplement or applied to the skin. However, previous research suggests when vitamin E acetate is inhaled, it may interfere with normal lung functioning.</p></li>\n <li><p>Vitamin E acetate is used as an additive in the production of e-cigarette, or vaping, products, because it resembles THC oil. Vitamin E acetate is also used as a thickening ingredient in e-liquids.</p></li>\n </ul>\n \n <p>–– <a href=\"https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html#what-is-new\" rel=\"nofollow noreferrer\">CDC: Outbreak of Lung Injury Associated with the Use of E-Cigarette, or Vaping, Products (Updated November 8, 2019,)</a></p>\n</blockquote>\n", "score": 2 } ]

[ "lungs", "recreational-drugs", "epidemiology", "public-health" ]

[ { "answer_id": 20279, "body": "<p>I'm not familiar with using citrate or EDTA as an anticoagulant in medical care (i.e. as a drug). However, it is often used in blood sampling tubes so that the blood sample does not clot. </p>\n\n<p>As to their difference, EDTA works irreversibly while citrate is reversible. EDTA is used more often most notably to get the complete blood count. Citrate is mostly used to assess the bloods ability to clot (by reversing the anticoagulation). In rare cases we need to use citrate tubes to assess platelet numbers since EDTA makes the platelets cling together, this is called EDTA agglutination.</p>\n\n<p>Regarding the mechanisms behind the anticoagulation, EDTA irreversibly binds calcium ions which are essential for many enzymes in the coagulation cascade. Citrate also binds calcium ions but also seems to affect other parts of the coagulation cascade.</p>\n\n<p><strong>References:</strong></p>\n\n<p>Banfi et. al. (2007)The role of ethylenediamine tetraacetic acid (EDTA) as in vitro anticoagulant for diagnostic purposes. <em>Clin Chem &amp; Lab Med</em>; 45(5): p565-76</p>\n\n<p>Mann et. al. (2007) Citrate anticoagulation and the dynamics of thrombin generation.<em>J ThrombHaemost</em>;5: 2055–61</p>\n", "score": 6 } ]

[ "medications", "practice-of-medicine", "hematology", "biological-parameter", "biochemistry" ]

[ { "answer_id": 20503, "body": "<p>Yes, it is possible for topical Tacrolimus to cause systemic toxicity, in certain situations.</p>\n\n<p><strong>Evidence from a case series</strong></p>\n\n<p><a href=\"https://europepmc.org/abstract/med/24700567\" rel=\"nofollow noreferrer\">This paper</a> is a case report of two patients who were prescribed topical Tacrolimus (and other therapy) for post-transplant cutaneous <a href=\"https://en.wikipedia.org/wiki/Graft-versus-host_disease\" rel=\"nofollow noreferrer\">graft versus host disease</a> (GVHD).</p>\n\n<p>Their Tacrolimus trough levels (a way of measuring the blood level of the drug just prior to the next dose) rose sharply from 7.1ng/ml to 22.1ng/ml. Treatment with topical Tacrolimus was abandoned due to this unpredictable systemic absorption. There was no evidence of harm resulting.</p>\n\n<p>The authors note the following:</p>\n\n<blockquote>\n <p>These case reports suggest that substantial use of topical tacrolimus with occlusive dressings in patients with cutaneous GVHD may contribute to increased systemic absorption resulting in toxic tacrolimus levels.</p>\n</blockquote>\n\n<p>However, the are some factors that would predispose these patients to increased absorption; the use of occlusive dressings, skin barrier dysfunction (due to GVHD) etc.</p>\n\n<blockquote>\n <p>Based on the findings from our two patients as well as published case reports, systemic absorption appears to increase with greater skin permeability, skin barrier dysfunction, amount of body surface area applied, and use of occlusive dressings. When one or more of these factors are present, it may be prudent to monitor tacrolimus levels.</p>\n</blockquote>\n\n<p><strong>About tacrolimus</strong></p>\n\n<p><a href=\"https://bnf.nice.org.uk/drug/tacrolimus.html#indicationsAndDoses\" rel=\"nofollow noreferrer\">Tacrolimus</a> is a calcineurin-inhibitor immunosuppressant. It is used systemically to prevent or treat transplant rejection. It is used topically is psoriasis and eczema and other conditions. It is not currently licensed to treat vitiligo in the UK, but it is presumably being used as vitiligo is an autoimmune destruction of melanocytes in the skin.</p>\n\n<p>I cannot find any evidence so far on predicting what level of exposure to topical tacrolimus is likely to cause toxicity. It is recommended to monitor the levels if the risk factors above apply. In vitiligo the skin is intact and not inflamed, so toxicity in this setting would be less likely, especially if occlusive dressings are not being used.</p>\n\n<p>Source: <a href=\"https://europepmc.org/abstract/med/24700567\" rel=\"nofollow noreferrer\">Olsen et al. Pharmacotherapy, 2014. DOI: 10.1002/phar.1418</a></p>\n", "score": 5 } ]

[ "dermatology", "toxicity", "topical-cream-gel", "organ-transplant", "vitiligo" ]

[ { "answer_id": 20670, "body": "<p>A <strong>polyp</strong> is a broad term that is defined <em>only</em> by its <strong>macroscopic</strong> appearance. So, I'll just repeat the definition provided in the question:</p>\n\n<blockquote>\n <p>A polyp is a mass that projects above a mucosal surface... to form a\n macroscopically visible structure.</p>\n</blockquote>\n\n<p>Polyps can be categorized by their <strong>microscopic (type of cell)</strong> characteristics, for example:</p>\n\n<blockquote>\n <p><strong>Papillomas</strong> are benign <em>epithelial</em> neoplasms growing on any surface,\n that produce microscopic or macroscopic fingerlike fronds.</p>\n</blockquote>\n\n<p>Examples of other subtypes of <a href=\"https://en.wikipedia.org/wiki/Polyp_(medicine)\" rel=\"nofollow noreferrer\">polyps</a> (based on microscopic differences) are adenomas, inflammatory and hyperplastic polyps, hamarthomas, etc.</p>\n\n<p>So, papilloma is a type of polyp. </p>\n", "score": 4 } ]

[ "tumors" ]

[ { "answer_id": 20736, "body": "<p>In short, compared with complete fasting, intermittent fasting results only in a minimal increase in plasma cortisol levels.</p>\n\n<p><strong>Cortisol increase in INTERMITTENT FASTING:</strong></p>\n\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064803/\" rel=\"nofollow noreferrer\">Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males (Journal of Translational Medicine, 2016)</a>:</p>\n\n<p>In this small study in 34 males, intermittent fasting (16 h fasting/8 h feeding) was associated with an increase of plasma cortisol from 174 ng/mL at the beginning of the study to 186 ng/mL in average after 8 weeks (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064803/table/Tab3/?report=objectonly\" rel=\"nofollow noreferrer\">Table 3</a>), which is <strong>1.07-fold increase.</strong></p>\n\n<p><strong>Cortisol increase in COMPLETE (WATER) FASTING:</strong></p>\n\n<p><a href=\"https://watermark.silverchair.com/jcem0692.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAngwggJ0BgkqhkiG9w0BBwagggJlMIICYQIBADCCAloGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMLos1DpIrk78chMlNAgEQgIICKyJyZStrMa4JpCEZ4gLQW-ioDctEI8I126avX2ZbgGdOV9I5oiP4APLBfUWQDiIFV-CIJARMFQ85YDtJIbM18uZPPjg3TEYDTliYM6JfHiGrmqSI6dKbgr25p6naHJWU2-lw9pxBDomHfyyQofmiuhqS0pcKtQ7clEDnwI8T0Hyfvvq9fciQQz69boTXfHNRJ40X20lnwxe86AqB8Ob-agjgblG3KyoLVvjjSgO_8LF98EGa_hta2nSJjBuKGsRzR9WOqirHmjNw7_cW_KX3fOarAOXPVd07KI1nmcRT7Jd9XUwvXB4UcqwKwBG1CenIN0ptGoTmQ_N0iRG__KCRzEgB14rdfzm6S33nJmGJkBc_NKXXipPka-jsfRMCAk_gA9ZZQ9JBukeawFq-2MVxUwB0WbrUNl4VHYHMO95OQepaZIwQmTBIkFexvmAqzIPLb-gBi-1I_abUDKZCrQEFcbgheczgdJLvYWODEJ9jZy-RBtPOjpXjG2ZZ42YxnKVqhBsj2y1gueyEMy2V1p8QIwr9exU_wpp08zRXrrlu0pYILh-txgQ6FQuCA1iI7zzWy3MjKLcliJe0b94qZAnyph7v3BZVTK9sNAASsPMyaqr6i3IR5j5VOezMmpXmpkK8ksc7gDvCGVDwoPHQ4CstLFUSGb5x6huf4-SNVRYJoK9-XkhrMmjetT5T_isWfoSh2GL6xsrnd5OP-8oxTKGp1P0cBSRmh-KPyQ3ICA\" rel=\"nofollow noreferrer\">Fasting as a Metabolic Stress Paradigm Selectively Amplifies Cortisol Secretory Burst Mass and Delays the Time of Maximal Nyctohemeral Cortisol Concentrations in Healthy Men (Journal of Clinical Endocrinology and Metabolism, 1996)</a> </p>\n\n<p>In this study in 8 males, the 5-day fast resulted in a <strong>2.2-fold increase</strong> in 24-h mean serum cortisol concentrations.</p>\n\n<hr>\n\n<p>Elevated plasma cortisol level can be a part of normal stress response, so the presented studies alone do not suggest that either intermittent or complete fast is unhealthy.</p>\n", "score": 3 } ]

[ "fasting", "cortisol" ]

[ { "answer_id": 20761, "body": "<p>According to the following study in 9 <em>women,</em> <em>theoretically,</em> 16/8 hour intermittent fasting could increase the risk of gallstones (the risk increases with increased cholesterol content of bile): <a href=\"https://gut.bmj.com/content/gutjnl/21/12/1087.full.pdf\" rel=\"nofollow noreferrer\">Effects of fasting on the composition of gallbladder bile (Gut, 1980)</a>:</p>\n\n<blockquote>\n <p>Mean cholesterol saturation index was significantly greater after a 15\n hour fast (1.35+0.08) than after a 10 hour fast (1.05+0.10). However,\n after 20 hours of fasting, mean cholesterol saturation index had\n fallen to 1.13+0-10.</p>\n \n <p>In conclusion, our findings suggest that <strong>fasting for between 10 and\n 20 hours may indeed increase the risk of gallstone formation,</strong> but\n this effect is counteracted by a more prolonged fast.</p>\n</blockquote>\n\n<p>In another study mentioned in the above article, the cholesterol concentration after intermittent fasting increased only in women but not in men. To know, if intermittent fasting is <em>actually</em> associated with an increased risk of gallstones, clinical trials in which the increased incidence of stones would be observed, would be needed... </p>\n\n<p>In <a href=\"http://www.jlr.org/content/17/3/211.full.pdf\" rel=\"nofollow noreferrer\">another study</a> in 9 healthy adults, after fasting for <em>4-6 days,</em> the cholesterol content of bile has <em>decreased</em> by about 30%, but then again, from this study alone, it's not possible to conclude that such fasting regime can reduce the risk of gallstones.</p>\n\n<p>\"Prolonged fasting\" is still considered a risk factor for gallstones, according to several sources: <a href=\"https://www.sciencedirect.com/science/article/pii/S0140673606690442?via%3Dihub\" rel=\"nofollow noreferrer\">The Lancet, 2006</a>, <a href=\"https://www.uptodate.com/contents/gallstones-epidemiology-risk-factors-and-prevention\" rel=\"nofollow noreferrer\">UpToDate, 2018</a>, <a href=\"https://www.ijsurgery.com/index.php/isj/article/view/1748\" rel=\"nofollow noreferrer\">International Surgery Journal, 2017</a>, <a href=\"http://www.childrenshospital.org/conditions-and-treatments/conditions/g/gallstones-cholelithiasis\" rel=\"nofollow noreferrer\">Boston Children's Hospital</a>, etc.</p>\n", "score": 1 } ]

[ "fasting", "gallbladder" ]

[ { "answer_id": 20876, "body": "<p>A <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/3526085\" rel=\"nofollow noreferrer\">double-blind crossover study</a> of placebo and the antiestrogen tamoxifen in ten men with gynecomastia of diverse etiology showed that:</p>\n\n<blockquote>\n <p>The reduction of breast size was partial and may indicate the need for a longer course of therapy. A follow-up examination was performed in eight out of ten patients nine months to one year after discontinuing placebo and tamoxifen. There were no significant changes from the end of the initial study period except for one tamoxifen responder who developed a recurrence of breast tenderness after six months, and one nonresponder who demonstrated an increase in breast size and a new onset of tenderness after ten months. Therefore, antiestrogenic treatment with tamoxifen may represent a safe and effective mode of treatment for selected cases of cosmetically disturbing or painful gynecomastia.</p>\n</blockquote>\n\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pubmed/14759718\" rel=\"nofollow noreferrer\">Another study</a> conducted to explore the effectiveness of tamoxifen in physiological gynecomastia depicted that:</p>\n\n<blockquote>\n <p>It appears to confirm previous studies that tamoxifen is not only effective with a\n greater than 80% success rate but also safe. Furthermore, since only one case in our study\n recurred after stopping tamoxifen, it would indicate the permanent effect of tamoxifen on\n physiological gynecomastia. In conclusion, we have shown that physiological gynecomastia can be divided into two recognizable forms; fatty and lump gynaecomastia. The overall\n success rate of tamoxifen to reduce mass and tenderness is high at over 80% for both types, however, the lump form of gynecomastia appears to be completely responsive to this medication.\n <a href=\"https://i.stack.imgur.com/NG704.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/NG704.png\" alt=\"Source\"></a></p>\n</blockquote>\n\n<p>Supporting the promising therapeutic use of tamoxifen in gynecomastia, <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/6489180/\" rel=\"nofollow noreferrer\">a new study</a> concluded that:</p>\n\n<blockquote>\n <p>Tamoxifen, at a daily dose of 20 mg, was administered over 2-4 months to 16 patients with gynecomastia. Of twelve patients with painful gynecomastia ten became pain-free. Gynaecomastia regressed partially or completely in 14 patients, in only 2 was it unchanged. There was no recurrence of gynecomastia after discontinuing tamoxifen</p>\n</blockquote>\n\n<p>However, in case of management of Pubertal gynecomastia (it is defined as benign breast enlargement occurring during male puberty without evidence of endocrinopathy, underlying disease, or drug effect), better response to raloxifene than to tamoxifen was found in a <a href=\"https://www.ncbi.nlm.nih.gov/pubmed?term=15238910\" rel=\"nofollow noreferrer\">study</a></p>\n\n<blockquote>\n <p>A study reported that the real effect of clomiphene in reducing gynecomastia in 18 of 19 pubertal-adolescent patients is based on several grounds. It is rare to observe a measurable reduction in gynecomastia occurring spontaneously in a period as short as eight weeks, yet this phenomenon was noted in all 18 responders in this series. A recurrence within two months of stopping therapy in three responders implies a definite suppressive effect of the drug. It is noteworthy that no subject showed an increase in gynecomastia during clomiphene therapy. Spontaneous fluctuations in the size of untreated gynecomastia are occasionally seen, but the rapidity, extent, and consistency of the changes we observed with clomiphene treatment argue strongly against the operation of chance events.<a href=\"https://www.sciencedirect.com/science/article/abs/pii/S0022347677803946\" rel=\"nofollow noreferrer\">Link</a> </p>\n</blockquote>\n\n<p>However, another study concludes that Clomiphene citrate in a dose of 50 mg/day resulted in only small decreases in persistent pubertal gynecomastia and was not a satisfactory medical therapy for the condition.<a href=\"https://www.ncbi.nlm.nih.gov/pubmed/6637910\" rel=\"nofollow noreferrer\">Link</a></p>\n\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pubmed/3526085\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pubmed/3526085</a></p>\n\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pubmed/14759718\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pubmed/14759718</a></p>\n\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pubmed/6489180/\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pubmed/6489180/</a></p>\n\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pubmed?term=15238910\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pubmed?term=15238910</a></p>\n\n<p><a href=\"https://www.sciencedirect.com/science/article/abs/pii/S0022347677803946\" rel=\"nofollow noreferrer\">https://www.sciencedirect.com/science/article/abs/pii/S0022347677803946</a></p>\n\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pubmed/6637910\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pubmed/6637910</a></p>\n", "score": 3 } ]

[ "cancer", "breast", "estrogen", "gender-sex-identity", "gynecomastia-man-boobs" ]

[ { "answer_id": 20940, "body": "<p><strong>Young:</strong></p>\n\n<p><a href=\"https://www.ncbi.nlm.nih.gov/books/NBK13167/\" rel=\"nofollow noreferrer\">Definition of Older Adolescent and Young Adult</a>:</p>\n\n<blockquote>\n <p>For the purposes of this review, the older adolescent-young adult age\n range is considered to be <strong>15 to 29</strong> years of age. Most of the\n published analyses that have been performed on this age group were\n performed on subgroups in this age range, such as <strong>15 to 19, 20 to\n 29, and 16 to 21 years of age.</strong> When known, the age range is\n specified in this review.</p>\n</blockquote>\n\n<p><strong>Elderly:</strong></p>\n\n<p>The term elderly usually refers to those <strong>age 65 or older.</strong> \nExamples of the article titles:</p>\n\n<ul>\n<li><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573668/\" rel=\"nofollow noreferrer\">Polypharmacy Among Adults Aged 65 Years and Older in the United States: 1988–2010</a></li>\n<li><a href=\"https://www.cdc.gov/flu/highrisk/65over.htm\" rel=\"nofollow noreferrer\">People 65 Years and Older &amp; Influenza</a></li>\n</ul>\n\n<p><strong>Other age categories</strong> (<a href=\"https://www.healthychildren.org/English/ages-stages/Pages/default.aspx\" rel=\"nofollow noreferrer\">healthychildren.org</a>):</p>\n\n<ul>\n<li><a href=\"https://www.qualityindicators.ahrq.gov/Downloads/Modules/PQI/V60-ICD10/TechSpecs/PQI_Appendix_D.pdf\" rel=\"nofollow noreferrer\">Newborn (neonate)</a>: birth to 28 days</li>\n<li>Baby (infant): birth to 1 year</li>\n<li>Toddler: 1-3 years</li>\n<li><a href=\"https://myhealth.alberta.ca/Health/Pages/conditions.aspx?hwid=ta3612\" rel=\"nofollow noreferrer\">Preschool child</a>: 2-5 years</li>\n<li>School child 5-12 years</li>\n<li>Teen: 12-18 years</li>\n<li>Adult: 18 years and older</li>\n<li><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285482/\" rel=\"nofollow noreferrer\">Postmenopausal</a>: after cessation of menstruation: 45 years in average</li>\n</ul>\n", "score": 3 } ]

[ "disease" ]

[ { "answer_id": 20968, "body": "<blockquote>\n <p>If I get infected once with the virus which causes a common cold, does that mean I will not get infected with the same strain of the virus ever in my lifetime? </p>\n</blockquote>\n\n<p>It depends on quirks of your immune system and the viral load you're exposed to, but in theory (based on vaccination and other studies), presence of the virus will trigger a suppressive response, not to nasal mucosal invasion but to viral replication and cell destruction/inflammation to the degree that you clinically manifest \"a cold\". </p>\n\n<p>Regarding your quirks,</p>\n\n<blockquote>\n <p><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553670/\" rel=\"noreferrer\">The persistence of high-titer serotype-specific antibody is associated with protection from infection as well as reduced symptom severity following experimental challenge with the same serotype</a> (52). However, there is little cross-neutralization among serotypes, which presents a challenge to vaccine development, given that there are more than 100 different known HRV serotypes (53). Further support for the role of humoral immunity in the prevention and control of HRV infection was observed in a study of patients with primary hypogammaglobulinemia. These patients experienced more frequent and severe HRV infections than their healthy spouses despite the administration of replacement immunoglobulin therapy (54).</p>\n</blockquote>\n\n<p>That's only the beginning. Immunology is very complex.</p>\n\n<blockquote>\n <p>To what extent do you think creating a universal vaccine for the common cold could be successful...</p>\n</blockquote>\n\n<p>Close to, if not, zero.</p>\n\n<p>There are about 120 distinctly different serotypes of rhinovirus which cause the \"common cold\", which could require 120 separate vaccines. Also a significant percentage of \"colds\" are caused by other types of viruses (coronavirus - like tat in China right now, respiratory syncytial virus, influenza and parainfluenza viruses) as well as some bacteria.</p>\n\n<blockquote>\n <p>Human coronaviruses, members of the Coronaviridae family, were first identified in 1962 and have been <a href=\"https://academic.oup.com/cid/article/31/1/96/321510\" rel=\"noreferrer\">particularly difficult to isolate by use of standard cell culture techniques</a>.</p>\n</blockquote>\n\n<p>One needs to reliably grow a virus before making a vaccine.</p>\n\n<blockquote>\n <p>Efforts at vaccine development are hindered by the existence of more than <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553670/\" rel=\"noreferrer\">100 HRV serotypes with high-level sequence variability in the antigenic sites</a>.</p>\n</blockquote>\n\n<p>And</p>\n\n<blockquote>\n <p>Compared to patients with coronavirus-associated colds, there is no difference in respiratory symptom severity or duration.</p>\n</blockquote>\n\n<p>However, there is a light at the end of the tunnel: the older you get, the fewer new viruses you're exposed to (if you stay in one geograpical location), and the fewer colds you get. I haven't had a \"common cold\" in a few years now. If I move across the continent, I will have more colds.</p>\n", "score": 8 }, { "answer_id": 20969, "body": "<p>Edit: I'm new at this. In response to recommendations I received I've attempted to insert web citations. LMK if I did it wrong...</p>\n\n<p>Yes, your immune system can recognize and protect against viruses you've been infected with in the past. That's why folks typically only get the chickenpox once. But getting a cold does NOT protect you against future colds, largely for the same reasons that a vaccine is highly unlikely (read on...).</p>\n\n<p>There are multiple barriers to creating a successful vaccine against the common cold. First, as you noted, what we call 'the common cold' is really a constellation of symptoms that can be caused by over 200 different organisms <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355621/\" rel=\"nofollow noreferrer\">1</a>, most of them viruses (including rhinovirus, respiratory syncytial virus, coronavirus, adenovirus) but also some bacteria (haemophilus influenzae, mycoplasma pneumoniae, and a couple others named ___ pneumoniae)<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC104573/\" rel=\"nofollow noreferrer\">2</a>. A successful vaccine would need to protect against at least the most common ones (similar to the yearly flu vaccine which typically covers 3 strains of influenza) - a more difficult task than creating a vaccine for, say, polio (which only has 3 strains <a href=\"https://www.cdc.gov/cpr/polioviruscontainment/diseaseandvirus.htm\" rel=\"nofollow noreferrer\">3</a>). Second, the reason you have to get the flu shot every year is because the virus mutates. The same goes for cold viruses - they mutate, and rather frequently <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355621/\" rel=\"nofollow noreferrer\">1</a>, meaning a new vaccine would need to be developed at least annually.</p>\n\n<p>Additionally colds frankly just aren't a very high priority. While it is true that young babies, the very elderly, and those with certain health conditions can suffer serious complications from a cold, most of us just get an annoying cough &amp; nasal symptoms for a few days. Not a lot of investment is going to be made in preventing such a disease <a href=\"https://www.verywellhealth.com/why-there-will-never-be-a-vaccine-for-the-common-cold-770451#mild-illness\" rel=\"nofollow noreferrer\">4</a> (especially when there's so much money to be made in mitigating treatments).</p>\n\n<ul>\n<li>a pediatrician [all of the above is factual information except the $ made from cold treatments which represents my opinion ;) ]</li>\n</ul>\n", "score": 0 } ]

[ "immune-system", "vaccination", "virus", "common-cold", "epidemiology" ]

[ { "answer_id": 31076, "body": "<p>To tell from <a href=\"https://en.wikipedia.org/wiki/List_of_related_male_and_female_reproductive_organs\" rel=\"nofollow noreferrer\">Wikipedia's List of related male and female reproductive organs</a> the answer is in the affirmative.</p>\n<p>The medical community should not consider it as inappropriate to speak of Skene's glands as „female prostate“ as in in the year 1984</p>\n<p>Tepper, Jagirdar, Health and Geller found</p>\n<p>„Homology between the female paraurethral (Skene's) glands and the prostate&quot;, see  Archives of Pathology and Laboratory Medicine, 108(5), 423-425]<a href=\"https://scholars.uthscsa.edu/en/publications/homology-between-the-female-paraurethral-skenes-glands-and-the-pr\" rel=\"nofollow noreferrer\">2</a>:</p>\n<p>„(...)Homology between female paraurethral glands and the prostate has often been suggested. A means was developed that would lend histochemical support to this hypothesis.  (…) The tissue was stained with antibodies to prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAcPh) using the peroxidase-antiperoxidase method. Of those cases in which paraurethral glands were seen, 83% were positive for PSA and 67% for PSAcPh (...)“.</p>\n<p>There is a most recent paper that should answer your question if this point of view is still accepted:</p>\n<p><a href=\"https://www.sciencedirect.com/science/article/abs/pii/S2050052121001086?via%3Dihub\" rel=\"nofollow noreferrer\">Tomalty et al.</a>, Science Direct, April 2022,</p>\n<p>Should We Call It a Prostate?  </p>\n<p>„ (...) Whether this tissue should be called a prostate in women has been debated. (…) Gaps in knowledge relating to the functional anatomy, physiological roles, and embryological origins of this tissue have impeded the acceptance of a prostate in women. “ The scientists conducted a „literature review (...) using keywords including female prostate, Skene's/paraurethral glands, periurethral tissue, (…)&quot;, however came to the conclusions that</p>\n<p>„(c)ontinuing to advance our understanding of the morphology, histochemistry, and physiologic capacity of this glandular tissue will clarify the characterization of this tissue as the “prostate” involved in the (female periurethral tissue) (...)“</p>\n<p>Accordingly, and considering basic knowledge that the prostate organ is a male, not a female organ</p>\n<p><em><strong>the answer is:</strong></em> It is still a matter of debate within the medical community if periurethral glands (Skene's glands) are homologues of the male prostate.</p>\n<p>As breast cancer is as typical for women as prostate cancer for men the fact that <em>the PSA antigen</em> which the assumption of homology was based on is a known marker of prostate tumour may lead to further search about prostate-specific antigen circulating in the blood of (female) breast cancer patients.</p>\n<p>See\n<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033864/\" rel=\"nofollow noreferrer\">Prostate-specific antigen in serum of women with breast cancer</a> that recently found „prostate-specific antigen (PSA) (...) in 30% of female breast tumours.“ From this may be infered that Skene's glands should not be considered the only tissue in women that contain cell types (at least on the level of specific stem cell potential) equivalent to prostate tissue.</p>\n<p>For some easy reading on the issue see <a href=\"https://healthproblemsnews.com/health-news/female-prostate-cancer-do-women-have-a-prostate-and-is-cancer-possible/\" rel=\"nofollow noreferrer\">Health Problems News , 2018</a></p>\n<p>Female prostate cancer: Do women have a prostate and is cancer possible?</p>\n<p>&quot;(...) Researchers have discovered that the Skene's glands share some of the same properties as the male prostate, which is located between the bladder and the penis. For example, both the prostate and the Skene glands contain prostate-specific antigen (PSA) and PSA phosphatase (PSAP), which are enzymes that can indicate the health of the prostate in males.\nThe discovery that these glands have similarities has led to the use of the term “female prostate.”\nSo, in a sense, females do have prostates, and female prostate cancer is technically possible. It is, however, extremely rare.&quot;\nThis article refers to</p>\n<p>M. Goodwin in <a href=\"https://www.medicalnewstoday.com/articles/321801#female-prostate-cancer\" rel=\"nofollow noreferrer\">Medical news today, May 2021</a>, Can women get prostate cancer?\n(...) Doctors may find it difficult to recognize the signs and symptoms of Skene’s gland cancer because it is so rare (...). So refereing to the findings in 1984, see above, it may be infered that PSA is a natural occuring hormone of the Skine's glands.</p>\n<p>To this, see also Parise/Rezash, <a href=\"https://cjon.ons.org/cjon/13/3/do-women-have-prostate-specific-antigen-level\" rel=\"nofollow noreferrer\">Do Women Have a Prostate-Specific Antigen Level?</a></p>\n<p>Conversely, thinking of solely male or female tissue one might think of <a href=\"https://en.wikipedia.org/wiki/Seminal_vesicles\" rel=\"nofollow noreferrer\">Seminal vesicles</a> which are &quot;(...) also called vesicular glands, (...)  or seminal glands)&quot; and &quot;(...) are a pair of two convoluted tubular glands that lie behind the urinary bladder of some male mammals.(...) They &quot;(...) have been described as early as the second century AD by Galen, although the vesicles only received their name much later, as they were initially described using the term from which the word prostate is derived.'“. From this, the question may be infered if the female Skine's glands are (partly) homologue seminal vesicles.</p>\n<p>Interestingly, according to Britannica <a href=\"https://www.britannica.com\" rel=\"nofollow noreferrer\">Animal reproductive system</a> &quot;(t)he prostate, the most widely distributed mammalian accessory sex gland, is absent only in Echidna (a marsupial) and a few carnivores.&quot;, and according to Wikipedia, carnivores are animals that do not have a prostate.</p>\n<p>Further reading:</p>\n<p>Toivanen/Shen, Prostate organogenesis: tissue induction, hormonal regulation and cell type specification, <a href=\"https://journals.biologists.com/dev/article/144/8/1382/48435/Prostate-organogenesis-tissue-induction-hormonal\" rel=\"nofollow noreferrer\">Development 2017</a>:</p>\n<p>&quot;Interestingly, small paraurethral glands (sometimes termed Skene's glands) that resemble a rudimentary prostate are present in female rats and humans, but not mice (Mahoney, <em><strong>1940</strong></em>; Zaviacic and Ablin, 1998). Furthermore, these glands express PSA and prostatic acid phosphatase (PAP; also known as ACPP) (Dietrich et al., 2011; Zaviacic and Ablin, 2000), suggesting that at least some aspects of prostate development also occur in females. Although some reports suggest that Skene's glands <em><strong>might not be paralogous</strong></em> to the male prostate, as they are located caudally along the UGS, other studies have identified prostate-like epithelial buds in females that do emerge in regions analogous to prostatic buds in males (Huffman, 1948; Thomson et al., 2002; Timms et al., 1999). It is possible that low levels of androgens (...) could be sufficient for induction of prostate-like buds in females (Thomson, 2008). However, studies in rats have suggested that the presence of prostate-like buds in female embryos is more common when embryos are in proximity to other female embryos within the maternal uterus, raising the possibility that residual estrogens play a role in their induction (Timms et al., (...)&quot;</p>\n<p><a href=\"https://m.iliveok.com/health/paraurethral-cyst-signs-treatment-surgery_129862i15945.html\" rel=\"nofollow noreferrer\">This popular-scientific page</a> on paraurethral cysts says that &quot;(p)araurethral glands and ducts that are omitted in the female urethra are rudimentary analogues of the prostate gland in men&quot; without explaining the term &quot;omitted&quot;. From an evolutionary point of view this may insinuate that, counterintuitively, stem cells producing prostate type cells have been &quot;deleted&quot; in females, as other tissue that is not located in or at the urethra differentiated in prostate homology (having in mind that some mammal species do not have the prostate organ). This may speaks in favour of assuming female breast tissue partly being equivalent to prostate tissue, supported by the finding of PSA antigen in breast cancer tissue, see above. Mnemonical thesis, personal suggestion: near-urethra stem cells that would develop to &quot;prostate&quot; in females might be omitted, whereas in males those leading to &quot;urethral glands&quot; might be. Equivalents to presume: breast cells in females, seminal gland cells in males).</p>\n", "score": 3 } ]

[ "female", "prostate" ]

[ { "answer_id": 21100, "body": "<h2>In summary:</h2>\n\n<ul>\n<li>The first line of treatment of GERD <em>symptoms</em> are lifestyle changes: losing weight (if necessary), avoiding triggering foods and moderate physical activity. Eliminating all suspected foods until symptoms improve and then introducing them back one by one is a reasonable method.</li>\n<li>Even if you can control symptoms of GERD by lifestyle changes, GERD won't likely heal on its own until the <em>underlying causes</em> (obesity, hiatal hernia, delayed gastric emptying) persist.</li>\n</ul>\n\n<hr>\n\n<h2>Causes and risk factors of GERD</h2>\n\n<p><strong>1) Insufficiency of the lower esophageal sphincter (LES),</strong> a muscular valve that normally prevents reflux of food and acid from the stomach into the esophagus due to (<a href=\"https://www.mayoclinic.org/diseases-conditions/gerd/symptoms-causes/syc-20361940\" rel=\"nofollow noreferrer\">Mayo Clinic</a>):</p>\n\n<ul>\n<li>Obesity, pregnancy</li>\n<li><a href=\"https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2036.2006.03186.x\" rel=\"nofollow noreferrer\">Fructose malabsorption</a></li>\n<li>Hiatal hernia - a slip of the upper part of the stomach through an opening (hiatus) in the diaphragm muscle</li>\n<li><a href=\"https://www.mayoclinic.org/diseases-conditions/bile-reflux/symptoms-causes/syc-20370115\" rel=\"nofollow noreferrer\">Bile reflux</a> due to peptic ulcer or gallbladder removal</li>\n<li>Increased gastric acid secretion can be associated with reflux, but, in most cases, this is not the cause (<a href=\"https://www.nature.com/gimo/contents/pt1/full/gimo21.html\" rel=\"nofollow noreferrer\">GI Motility online, 2006</a>)</li>\n</ul>\n\n<p><strong>2) Delayed gastric emptying (gastroparesis),</strong> which can result from (<a href=\"https://www.webmd.com/digestive-disorders/digestive-disorders-gastroparesis#1\" rel=\"nofollow noreferrer\">WebMD</a>):</p>\n\n<ul>\n<li>A damage of the nerves due to <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356931/\" rel=\"nofollow noreferrer\">diabetes mellitus</a>, Parkinson's disease, multiple sclerosis, etc.</li>\n<li>Hypothyroidism</li>\n<li>Drugs, like narcotics and antidepressants</li>\n<li>Abnormal esophageal motility (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216628/\" rel=\"nofollow noreferrer\">achalasia</a>, <a href=\"https://www.mayoclinic.org/diseases-conditions/esophageal-spasms/symptoms-causes/syc-20372250\" rel=\"nofollow noreferrer\">esophageal spasms</a>)</li>\n<li>Connective tissue diseases, such as scleroderma</li>\n</ul>\n\n<h2>Triggers of GERD</h2>\n\n<p>In a person with established GERD, certain triggers can aggravate reflux:</p>\n\n<ul>\n<li>Certain foods and large meals</li>\n<li>Lying down shortly after a meal</li>\n<li>Medications: aspirin, antihistamines, narcotics (morphine, codeine, etc.), tricyclic antidepressants (amitriptyline, doxepin...), calcium channel blockers (amlodipine, diltiazem...), clonidine, drugs to treat Parkinson's disease, lithium and progesterone (<a href=\"https://www.medicinenet.com/gastroesophageal_reflux_disease_gerd/article.htm#what_are_the_symptoms_of_uncomplicated_gerd\" rel=\"nofollow noreferrer\">MedicineNet</a>).</li>\n<li>Smoking (nicotine)</li>\n</ul>\n\n<p>NOTE: Acidic foods may increase the feeling of esophageal irritation, but they don't actually increase the reflux:</p>\n\n<blockquote>\n <p>...some beverages with high acidity did not induce symptoms (i.e.,\n prune juice) and others with low acidity did (i.e., tomato juice)\n indicating other factors may play a role (18). Similar incongruencies\n between physiology and symptoms exist for carbonated beverages. <em>(<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702398/\" rel=\"nofollow noreferrer\">Journal of Thoracic Disease, 2019</a>)</em></p>\n</blockquote>\n\n<h2>Diagnosis of GERD</h2>\n\n<p>The investigations for diagnosis of GERD may include upper endoscopy, measurement of the acidity and pressure in the esophagus and an abdominal X-ray with barium swallow (<a href=\"https://www.mayoclinic.org/diseases-conditions/gerd/diagnosis-treatment/drc-20361959\" rel=\"nofollow noreferrer\">Mayo Clinic</a>). </p>\n\n<h2>Evidence-based approach to treatment of GERD</h2>\n\n<p><strong>1) Lifestyle changes</strong></p>\n\n<p>According to a systematic review of studies: <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668774/\" rel=\"nofollow noreferrer\">Body weight, lifestyle, dietary habits and gastroesophageal reflux disease (World Journal of Gastroenterology, 2009)</a>, weight loss (if overweight) and moderate physical activity can help to improve GERD symptoms, while the evidence about the effect of diet is inconclusive:</p>\n\n<blockquote>\n <p>There is sufficient evidence to support the relationship between being\n obese/overweight and GERD, expressed as specific symptoms and\n endoscopic features. Furthermore, available evidence suggests that\n controlled weight loss (by diet or surgery) is able to induce a\n significant improvement in GERD symptoms and/or in GERD\n clinical-endoscopic manifestations. Definitive data still do not exist\n regarding the association between dietary behavior, mainly in terms of\n specific dietary components and GERD manifestations. Moderate physical\n activity seems beneficial, while vigorous activity may be dangerous in\n predisposed individuals.</p>\n</blockquote>\n\n<p>The lack of strong evidence about the effect of diet on GERD symptoms on the <em>population</em> level should not discourage anyone to <em>personally</em> try and see what can help to him/her. The following lifestyle changes have been supported by some studies:</p>\n\n<ul>\n<li>Avoiding foods that are fatty (fried foods, chocolate), spicy or acidic (citrus fruits), carbonated beverages, sugars, tomato-based products, alcohol, caffeine (coffee, tea, cola), large meals and eating &lt;2 hours before bed (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326208/\" rel=\"nofollow noreferrer\">Journal of Neurogastroenterology and Motility, 2019</a>, <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702398/\" rel=\"nofollow noreferrer\">Journal of Thoracic Disease, 2019</a>)</li>\n<li>Weight loss, tobacco smoking cessation and head of the bed elevation (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636482/\" rel=\"nofollow noreferrer\">Clinical Gastroenterology and Hepatology, 2017</a>)</li>\n</ul>\n\n<p><strong>2) Medications and surgery</strong> </p>\n\n<p>Medications that reduce the stomach acid (antacids, H2 antagonists or proton pump inhibitors) can prevent symptoms and damage of the esophagus; hiatal hernia and certain other conditions may require surgery (<a href=\"https://www.aafp.org/afp/2005/0615/p2376.html\" rel=\"nofollow noreferrer\">American Family Physician, 2005</a>).</p>\n\n<p>Treatment of eventual <em>H. pylori</em> infection may improve or worsen GERD (<a href=\"https://www.nature.com/gimo/contents/pt1/full/gimo21.html\" rel=\"nofollow noreferrer\">GI Motility online, 2006</a>).</p>\n", "score": 3 } ]

[ "diet", "gerd-acid-reflux", "heartburn" ]

[ { "answer_id": 21143, "body": "<p>I somewhat agree that it's difficult to debunk conspiracy theories, as people that believe in them can and usually will reply to carefully crafted arguments with \"of course that's fabricated too\".</p>\n\n<p>Having said that, I came across this: <a href=\"http://virological.org/t/the-proximal-origin-of-sars-cov-2/398\" rel=\"nofollow noreferrer\">The Proximal Origin of SARS-CoV-2</a></p>\n\n<p>It discusses the origins for this virus. Hope you find it useful.</p>\n", "score": 3 } ]

[ "virus", "covid-19" ]

[ { "answer_id": 21683, "body": "<p>There has been at least one phylogenetic study of 48 near complete samples of the SARS-CoV-2 virus.</p>\n\n<p><a href=\"https://i.stack.imgur.com/3uvgy.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/3uvgy.png\" alt=\"sars-cov-2 phylogeny\"></a></p>\n\n<p>and a more up to date link at <a href=\"https://nextstrain.org/ncov\" rel=\"nofollow noreferrer\">Genomic epidemiology of novel coronavirus</a></p>\n\n<p><a href=\"https://arxiv.org/abs/2002.08802\" rel=\"nofollow noreferrer\">https://arxiv.org/abs/2002.08802</a></p>\n", "score": 2 } ]

[ "virus", "sars-cov-2", "microbiology" ]

[ { "answer_id": 21161, "body": "<p>“Acquisition in a single volume” means an image obtained by a single rotation of a scanner (\"single gantry rotation\"). It covers up to 16 cm of the body.</p>\n\n<p>\"Wide volume imaging\" includes repeated single volume imaging of adjacent areas and then combining them into a single image. So, two volumes would cover up to 32 cm, three volumes up to 48 cm, etc.</p>\n\n<p><em>Source: <a href=\"https://us.medical.canon/download/aq-one-vision-ctrp2019us\" rel=\"nofollow noreferrer\">Living in a Volume World: Applications for 320-detector row CT in a community-based hospital, Canon Medical Systems, USA</a></em></p>\n", "score": 3 } ]

[ "terminology", "medical-imaging", "ct-scans" ]

[ { "answer_id": 21167, "body": "<p>According to the standard blood compatibility chart:</p>\n\n<p><a href=\"https://i.stack.imgur.com/6HioY.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/6HioY.png\" alt=\"blood compatibility\"></a></p>\n\n<p>_{(image from <a href=\"https://owlcation.com/stem/All-about-Blood\" rel=\"nofollow noreferrer\">Owlcation: The Basics of Blood and Blood Typing</a> - <a href=\"https://en.wikipedia.org/wiki/File:Blood_Type_Compatability.png#file\" rel=\"nofollow noreferrer\">Wikipedia file</a>})</p>\n\n<p>AB blood types can only donate to other AB blood types, but AB blood types can receive from other blood types, so what is the point of being an AB donor.</p>\n\n<p>Well, the chart says that they are the only blood type that can do a full blood transfusion to other AB types.</p>\n\n<p>Also, organs aren't that easy to find - there are more people waiting for an organ than there are organs.</p>\n\n<p>Also, the Wikipedia article on <a href=\"https://en.wikipedia.org/wiki/Blood_donation#Blood_testing\" rel=\"nofollow noreferrer\">blood donation</a> says that this chart is only applicable to red blood cells. For plasma and platelets, the situation is reversed.</p>\n\n<blockquote>\n <p>Type O negative is often cited as the \"universal donor\" but this only refers to red cell and whole blood transfusions. For plasma and platelet transfusions the system is reversed: AB positive is the universal platelet donor type while both AB positive and AB negative are universal plasma donor types.</p>\n</blockquote>\n\n<p>As for what happens between an organ donor dying and their organs being transplanted, \n<a href=\"https://www.organdonor.gov/about/process/deceased-donation.html\" rel=\"nofollow noreferrer\">organDdonor.gov</a> has this lowdown:</p>\n\n<blockquote>\n <p>While the search for matching recipients is under way, the deceased donor's organs are maintained on artificial support. Machines keep blood containing oxygen flowing to the organs. The condition of each organ is carefully monitored by the hospital medical staff and the OPO procurement coordinator. </p>\n \n <p>A transplant surgical team replaces the medical team that treated the patient before death. (The medical team trying to save the patient’s life and the transplant team are never the same team.) </p>\n \n <p>The surgical team removes the organs and tissues from the donor's body in an operating room. First, organs are recovered, and then additional authorized tissues such as bone, cornea, and skin. All incisions are surgically closed. Organ donation does not interfere with open-casket funerals. </p>\n \n <p>Organs remain healthy only for a short period of time after removal from the donor, so minutes count. The OPO representative arranges the transportation of the organs to the hospitals of the intended recipients. Transportation depends on the distance involved, and can include ambulances, helicopters, and commercial airplanes.</p>\n</blockquote>\n", "score": 1 } ]

[ "blood", "blood-donation", "internal-organs", "organ-transplant" ]

[ { "answer_id": 24416, "body": "<p>It is a known fact that STDs are more easily transmitted by unprotected anal intercourse. As some STDs are known to (rarely) cause endocarditis, it seems plausible to me that unprotected anal intercourse increases the risk of an endocarditis.</p>\n<p>I could, however, find no statistical analysis on the relationship between (receptive) anal intercourses and endocarditis.</p>\n<p>The bacterium causing gonorrhoea is known to lead to endocarditis in rare cases:</p>\n<blockquote>\n<p>Untreated infection with gonococcus may lead to transient bacteremia, arthritis, or dermatitis. More severe sequelae such as endocarditis and meningitis are rare.</p>\n<p>^{<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780056/\" rel=\"nofollow noreferrer\">Whitlow CB. Bacterial sexually transmitted diseases. Clin Colon Rectal Surg. 2004;17(4):209-214. doi:10.1055/s-2004-836940</a>}</p>\n</blockquote>\n<blockquote>\n<p>In ascending infections, the posterior part of the urethra may become infected (posterior gonorrheal urethritis). Patients may also develop prostatitis, vesiculitis, funiculitis, epididymitis, Cowperitis, cavernitis, or even gonococcal sepsis, perihepatitis gonorrhoica, endocarditis, meningitis, or gonarthritis.</p>\n<p>^{<a href=\"https://onlinelibrary.wiley.com/doi/full/10.1111/ddg.12310\" rel=\"nofollow noreferrer\">Sexually Transmitted Infections</a>}</p>\n</blockquote>\n<p><a href=\"https://www.journalmc.org/index.php/JMC/article/view/1946/1414\" rel=\"nofollow noreferrer\">Here is a case report of a patient with HIV who got infected by\nEnterococci and developed an endocarditis.</a></p>\n<p>Bottom line: Be safe and <a href=\"https://www.nhs.uk/common-health-questions/sexual-health/does-anal-sex-have-any-health-risks/\" rel=\"nofollow noreferrer\">always use protection</a></p>\n", "score": 1 } ]

[ "research", "risks", "sex", "heart-disease" ]

[ { "answer_id": 21188, "body": "<p>It's better to use some guidelines from reputable sources rather than coming up with your own.</p>\n\n<p>The WHO does not recommend masks for healthy people in most circumstances, only <a href=\"https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public/when-and-how-to-use-masks\" rel=\"noreferrer\">when directly dealing with someone infected</a>, and in that case accompanied by careful hand washing.</p>\n\n<p>Their <a href=\"https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public\" rel=\"noreferrer\">advice for the general public</a> as of this posting (and this is good advice year-round anyways, not only when particular pathogens are present, because influenza and viruses that cause the common cold are always present) is to <strong>wash your hands</strong>, keep a distance from people who are sneezing/coughing, avoid touching your face, and cough or sneeze into a tissue or corner of the elbow rather than into the open or your hands.</p>\n", "score": 5 }, { "answer_id": 21663, "body": "<p>I think it's a great idea. It protects your eyes from respiratory droplets and keeps you from touching your face. I don't know how well it would work from keeping droplet from reaching your mouth, but probably pretty well, especially if you used it with an N95 respirator. It might be a little shocking/intimidating to people, so I would only use it in extremely infected areas. </p>\n", "score": 4 }, { "answer_id": 21664, "body": "<p>Now to address the whole debate about using respirators and masks. You absolutely want them. There has been a narrative throughout the western world that you don't need them, and they don't work. This is not the case. The CDC and WHO tell ordinary people to not wear respirators, but both organizations have political agendas and have frankly done a terrible job handling this public health crises. The truth is that there is a lack of respirators to go around when every single person should be wearing them. In Taiwan, their number one way to combat COVID19 is by having every single person in their population wear masks. Thus far, Tiawan has been one of the best countries in handling the COVID19 health crises. </p>\n\n<p>Now to address why N95/N99/N100/NIOSH respirators work. One of the leading pathways for transmitting this disease is through inhalation of respiratory droplets from other infected individuals. An immediate barrier that has been proven to be effective is having a mask/respirator to intercept these droplets before they reach your mucus membranes. The coronavirus is between 60 to 140 nm in diameter. Let's use the N95 mask for example. This mask captures all particulates at 300 nm at a rate of up to 95% or better. 300 nm is the particulate size that has the lowest capture efficiency. Anything smaller, including the coronavirus, will have an even higher capture efficiency. This virus is one of the most contagious pathogens we have had in recent human history. Any form of personal protection equipment is absolutely vital in keeping yourself from becoming infected. I would also recommend that when you are in a public areas you should wear eye protection, gloves and over coat that you leave outside your house. I do really think the motorcycle helmet is a very creative and potentially effective way to keep yourself protected. </p>\n", "score": 2 } ]

[ "infection", "virus", "infectious-diseases", "covid-19" ]

[ { "answer_id": 21249, "body": "<p>Yes, it does.</p>\n\n<p>According to the CDC, <a href=\"https://www.cdc.gov/coronavirus/2019-ncov/community/home/cleaning-disinfection.html\" rel=\"noreferrer\">this</a> is how surfaces should be disinfected:</p>\n\n<blockquote>\n <h2>Surfaces</h2>\n \n <ul>\n <li><p>Wear disposable gloves when cleaning and disinfecting surfaces. Gloves should be discarded after each cleaning. If reusable gloves are\n used, those gloves should be dedicated for cleaning and disinfection\n of surfaces for COVID-19 and should not be used for other purposes.\n Consult the manufacturer’s instructions for cleaning and disinfection\n products used. Clean hands immediately after gloves are removed.</p></li>\n <li><p>If surfaces are dirty, they should be cleaned using a detergent or soap and water prior to disinfection.</p></li>\n <li><p>For disinfection, diluted household bleach solutions, <strong>alcohol solutions with at least 70% alcohol</strong>, and most common EPA-registered\n household disinfectants should be effective.</p>\n \n <ul>\n <li><p>Diluted household bleach solutions can be used if appropriate for the surface. Follow manufacturer’s instructions for application\n and proper ventilation. Check to ensure the product is not past its\n expiration date. Never mix household bleach with ammonia or any other\n cleanser. Unexpired household bleach will be effective against\n coronaviruses when properly diluted.</p>\n \n <ul>\n <li>Prepare a bleach solution by mixing:\n \n <ul>\n <li>5 tablespoons (1/3rd cup) bleach per gallon of water or</li>\n <li>4 teaspoons bleach per quart of water</li>\n </ul></li>\n </ul></li>\n <li><p>A list of products with EPA-approved emerging viral pathogens claims, maintained by the American Chemistry Council Center for\n Biocide Chemistries (CBC), is available at:\n <a href=\"https://www.americanchemistry.com/Novel-Coronavirus-Fighting-Products-List.pdf\" rel=\"noreferrer\">https://www.americanchemistry.com/Novel-Coronavirus-Fighting-Products-List.pdf</a>.\n Products with EPA-approved emerging viral pathogens claims are\n expected to be effective against COVID-19 based on data for harder to\n kill viruses. Follow the manufacturer’s instructions for all cleaning\n and disinfection products (e.g., concentration, application method and\n contact time, etc.).</p></li>\n </ul></li>\n <li><p>For soft (porous) surfaces such as carpeted floor, rugs, and drapes, remove visible contamination if present and clean with\n appropriate cleaners indicated for use on these surfaces. After\n cleaning: Launder items as appropriate in accordance with the\n manufacturer’s instructions. If possible, launder items using the\n warmest appropriate water setting for the items and dry items\n completely, or Use products with the EPA-approved emerging viral\n pathogens claims (examples at this linkpdf iconexternal icon) that are\n suitable for porous surfaces.</p></li>\n </ul>\n</blockquote>\n", "score": 6 }, { "answer_id": 21710, "body": "<p>The List does mention Isopropyl Alcohol. It's sixth on the list, and it's listed by its other name--Isopropanol. </p>\n\n<p>Isopropanol=Isopropyl Alcohol. Just like Ethanol=Ethyl Alcohol.</p>\n", "score": 3 } ]

[ "infection", "disease-transmission", "microbiology" ]

[ { "answer_id": 21478, "body": "<p>I recommend this github project from the <a href=\"https://systems.jhu.edu/\" rel=\"nofollow noreferrer\">Johns Hopkins University Center for Systems Science and Engineering (JHU CSSE)</a>:</p>\n\n<p><a href=\"https://github.com/CSSEGISandData/COVID-19\" rel=\"nofollow noreferrer\">https://github.com/CSSEGISandData/COVID-19</a></p>\n\n<p>They collect the official numbers from different organizations and ministries from all over the world and update their repository every day.<br>\nThey don't provide information about the age of patients though.</p>\n\n<p>There is a Japanese project, however, which provides also some age information:<br>\n<a href=\"https://covid19japan.com/\" rel=\"nofollow noreferrer\">https://covid19japan.com/</a><br>\nBut the Japanese people seem to be very disciplined and have a very low infection rate at the moment.</p>\n\n<p><strong>Update:</strong><br>\nI found a database with German Covid-19 cases including age information:<br>\n<a href=\"https://npgeo-corona-npgeo-de.hub.arcgis.com/datasets/dd4580c810204019a7b8eb3e0b329dd6_0\" rel=\"nofollow noreferrer\">https://npgeo-corona-npgeo-de.hub.arcgis.com/datasets/dd4580c810204019a7b8eb3e0b329dd6_0</a></p>\n\n<p>From the same company (ESRI) there are a lot more data sets online also for Covid-19. One might have to search for age information, though.<br>\n<a href=\"https://coronavirus-resources.esri.com/\" rel=\"nofollow noreferrer\">https://coronavirus-resources.esri.com/</a></p>\n", "score": 3 }, { "answer_id": 21336, "body": "<p>You can find a collection of data that is updated on a daily basis on github. There is also included some code</p>\n\n<p><a href=\"https://github.com/globalcitizen/2019-wuhan-coronavirus-data\" rel=\"nofollow noreferrer\">https://github.com/globalcitizen/2019-wuhan-coronavirus-data</a></p>\n", "score": 1 }, { "answer_id": 21666, "body": "<p>Kaggle has an ongoing <a href=\"https://www.kaggle.com/allen-institute-for-ai/CORD-19-research-challenge\" rel=\"nofollow noreferrer\">competition analysing COVID-19 related medical literature</a>.\nThis competition provides a large dataset, as well as already published analysis tools and other assistance to get you started.</p>\n", "score": 1 }, { "answer_id": 21789, "body": "<p>Additionaly to Philipp Leitl's answer:\nOverview of cases in Italy, provided by Instituto Superiore Di Sanita, updated on a daily basis (just change the date in the url) with death distribution by age:\n<a href=\"https://www.epicentro.iss.it/coronavirus/bollettino/Infografica_27marzo%20ENG.pdf\" rel=\"nofollow noreferrer\">https://www.epicentro.iss.it/coronavirus/bollettino/Infografica_27marzo%20ENG.pdf</a>\nThe korean Korea Centers for Disease Control and Prevention also publish some data on a daly basis, including case distribution by gender and age:\n<a href=\"https://www.cdc.go.kr/board/board.es?mid=a30402000000&amp;bid=0030\" rel=\"nofollow noreferrer\">https://www.cdc.go.kr/board/board.es?mid=a30402000000&amp;bid=0030</a>\nFor example, press release No 215, 26.3.2020:\n<a href=\"https://www.cdc.go.kr/board/board.es?mid=a30402000000&amp;bid=0030&amp;act=view&amp;list_no=366650&amp;tag=&amp;nPage=1\" rel=\"nofollow noreferrer\">https://www.cdc.go.kr/board/board.es?mid=a30402000000&amp;bid=0030&amp;act=view&amp;list_no=366650&amp;tag=&amp;nPage=1</a></p>\n", "score": 1 }, { "answer_id": 21770, "body": "<p><a href=\"http://go.usa.gov/xdbuc\" rel=\"nofollow noreferrer\">http://go.usa.gov/xdbuc</a>\nSelect a dataset and click Download button.\nYou can choose Fasta format</p>\n", "score": 0 } ]

[ "covid-19", "reference-request", "covid-19-datasets" ]

[ { "answer_id": 21320, "body": "<p>Age is a red herring, only a secondary characteristic correlating to death rates.</p>\n\n<p>It's people that are already seriously ill or already have weak immune systems that are most likely to die soon after contracting Covid-19. And it's when people are clustered in a close community that they are most likely to contract the disease.</p>\n\n<p>In our society, the people in those circumstances tend to be old and in health-care facilities.\nAs a result, most of our deaths so far have involved people over 80 years old.</p>\n\n<p>In other societies, a lack of old people doesn't necessarily mean a lack people living in close quarters, that are weak or sick.</p>\n\n<p>There's certainly no shortage of such conditions in many parts of Africa.</p>\n\n<p>From <a href=\"https://ourworldindata.org/coronavirus\" rel=\"nofollow noreferrer\">Coronavirus Disease (COVID-19) - Our World in Data</a>:</p>\n\n<p><a href=\"https://i.stack.imgur.com/JUM5S.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/JUM5S.png\" alt=\"enter image description here\"></a></p>\n", "score": 4 }, { "answer_id": 21324, "body": "<p>Death risk from COVID-19 increases greatly with underlying diseases:</p>\n\n<blockquote>\n <p>Patients who reported no pre-existing (\"comorbid\") medical conditions\n had a case fatality rate of 0.9% <em>(<a href=\"https://www.worldometers.info/coronavirus/coronavirus-age-sex-demographics/\" rel=\"nofollow noreferrer\">Worldometer, Feb 29, 2020</a>).</em></p>\n</blockquote>\n\n<p>The most common underlying diseases in those who died from COVID-19 were: cardiovascular disease, diabetes, chronic respiratory disease, hypertension and cancer. So, it's not really age, but an underlying disease that increases the risk of death in COVID-19. </p>\n\n<p>The median age of those who died so far from COVID-19 in <strong>Italy</strong> with life expectancy 83.4 years was <strong>81 years:</strong></p>\n\n<blockquote>\n <p>Borrelli said the median age of the people who have died from the\n virus in Italy is 81 years of age <em>(<a href=\"https://edition.cnn.com/world/live-news/coronavirus-outbreak-03-06-20-intl-hnk/h_9ba4751542191c2e9408c3181ff6fbf1\" rel=\"nofollow noreferrer\">CNN, March 6, 2020</a>)</em>.</p>\n</blockquote>\n\n<p>and in <strong>China</strong> with life expectancy 74.6 years, it was <strong>75 years:</strong></p>\n\n<blockquote>\n <p>On 23 February 2020, the number of people diagnosed with COVID‐19 in\n China was 1879 times of that on 10 January 2020. They estimated the\n case fatality rate of COVID‐19 to be 2.84% based on their patient\n pool. The authors also found that the ratio of male to female deaths\n was 3.25:1, the median age of death was 75 years <em>(<a href=\"https://onlinelibrary.wiley.com/doi/10.1002/jmv.25722\" rel=\"nofollow noreferrer\">Journal of\n Medical Virology, Feb 25, 2020</a>).</em></p>\n</blockquote>\n\n<p>In the <a href=\"https://www.worldometers.info/coronavirus/\" rel=\"nofollow noreferrer\">US</a> with life expectancy 78.9 years, it was <strong>80 years</strong>.</p>\n\n<p>The risk of death from COVID-19 increases with chronic diseases and therefore with age. Moth deaths so far have been on Northern hemisphere in countries with life expectancy above 74 years. Moth countries with life expectancy lower than 65 years are on Southern hemisphere or around equator, where it is warm now, which is a likely reason for much fewer cases of infection there.</p>\n\n<p>In countries with low life expectancy, mainly in Africa, there are other potential risk factors for COVID-19: widespread parasitic diseases (malaria, intestinal parasites, etc.), malnutrition and less available health care, which are not associated with age. </p>\n\n<p><strong>In conclusion,</strong> even if in the countries with low <a href=\"https://en.wikipedia.org/wiki/List_of_countries_by_life_expectancy\" rel=\"nofollow noreferrer\">life expectancy</a>, lower average age (and hence less chronic diseases) can be a protective factor against COVID-19 <a href=\"https://www.worldometers.info/coronavirus/\" rel=\"nofollow noreferrer\">deaths</a> (Worldometer), we do not yet know the effects of other risk factors in these countries.</p>\n", "score": 2 }, { "answer_id": 25658, "body": "<p>The Accepted Answer by Ray Butterworth, while reasonable when it was written (March 2020), now appears to be <strong>wrong</strong>. Hardest hit countries have mainly been those with longest life expectancies (Europe, N. America) while Africa has had very low death rates from Covid (Europe 964 per million, Africa 70 per million, <a href=\"https://ourworldindata.org/coronavirus-data-explorer?zoomToSelection=true&amp;minPopulationFilter=1000000&amp;country=USA%7EAfrica%7EEurope&amp;region=World&amp;deathsMetric=true&amp;interval=total&amp;hideControls=true&amp;perCapita=true&amp;smoothing=0&amp;pickerMetric=location&amp;pickerSort=asc\" rel=\"nofollow noreferrer\">Our World In Data</a>, 2021 Feb 5). Multiple studies have found a high correlation between life expectancy and covid deaths, e.g. <a href=\"https://www.frontiersin.org/articles/10.3389/fpubh.2020.604339/full#SM6\" rel=\"nofollow noreferrer\">Frontiers | Covid-19 Mortality: A Matter of Vulnerability Among Nations Facing Limited Margins of Adaptation</a>,</p>\n<p><a href=\"https://bmjopen.bmj.com/content/10/11/e042750\" rel=\"nofollow noreferrer\">Factors associated with COVID-19 infections and mortality in Africa: a cross-sectional study using publicly available data | BMJ Open</a></p>\n", "score": 0 } ]

[ "covid-19" ]

[ { "answer_id": 23159, "body": "<p>The question boils down to does increasing the number of ACE2 receptors increase or lower your risk of severe disease with Covid-19. Increasing the number of receptors might increase the number of attack points for the virus, or, increasing the number of receptors might reduce the risk of lung damage as ACE2 acts to protect the lung. We know that the ACE2 receptor is encoded on the X chromosome and women, who have more ACE2 receptors, do better than men in the mortality statistics.</p>\n\n<p>We now have some observational data to suggest that ARBI help protect the lungs against SARS-CoV-2, approximately 34% less likely to have severe disease (OR=0.343, 95% CI 0.128-0.916, p=0.025). There wasn't enough data to inform about ACEI.</p>\n\n<blockquote>\n <p>Summary Background The novel coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 outbreak started at the end of 2019 in Wuhan, China, and spread over 100 countries. SARS-CoV-2 uses the membrane protein Angiotensin I converting enzyme 2(ACE2) as a cell entry receptor. Indeed, it was reported that the balance of Renin-Angiotensin System (RAS), regulated by both ACE and ACE2, was altered in COVID-19 patients. It is controversial, however, whether commonly used anti-hypertensive drugs Angiotensin I converting enzyme inhibitor (ACEI) and Angiotensin II receptor blocker (ARB) shall be continued in the confirmed COVID-19 patients. This study was designed to investigate any difference in disease severity between COVID-19 patients with hypertension comorbidity. The included COVID-19 patients used ACEI, ARB, calcium channel blockers (CCB), beta blockers (BB), or thiazide to treat preexisting hypertension prior to the hospital were compared to patients who did not take any of those drugs. Methods In this multicentre retrospective study, clinical data of 511 COVID-19 patients were analyzed. Patients were categorized into six sub-groups of hypertension comorbidity based on treatment using one of anti-hypertension drugs (ACEI, ARB, CCB, BB, thiazide), or none. A meta-analysis was performed to evaluate the use of ACEI and ARB associated with pneumonia using published studies. Findings Among the elderly (age>65) COVID-19 patients with hypertension comorbidity, the risk of COVID-19-S (severe disease) was significantly decreased in patients who took ARB drugs prior to hospitalization compared to patients who took no drugs (OR=0.343, 95% CI 0.128-0.916, p=0.025). The meta-analysis showed that ARB use has positive effects associated with morbidity and mortality of pneumonia. Interpretation Elderly (age>65) COVID-19 patients with hypertension comorbidity who are taking ARB anti-hypertension drugs may be less likely to develop severe lung disease compared to patients who take no anti-hypertension drugs. Funding National Natural Science Foundation of China, Chinese Academy of Medical Sciences</p>\n</blockquote>\n\n<p><strong>Update 7 May 2020</strong></p>\n\n<p>An observational study of 8,910 patients in hospitals in Asia, Europe, and North America who had either died in the hospital (5.8%) or survived to hospital discharge (94.2%). This showed an advantage with the use of ARBs but no ACEI</p>\n\n<blockquote>\n <p>No increased risk of in-hospital death was found to be associated with the use of ACE inhibitors (2.1% vs. 6.1%; odds ratio, 0.33; 95% CI, 0.20 to 0.54) or the use of ARBs (6.8% vs. 5.7%; odds ratio, 1.23; 95% CI, 0.87 to 1.74).</p>\n</blockquote>\n\n<p><strong>1 May 2020:</strong> Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19\n<a href=\"https://www.nejm.org/doi/full/10.1056/NEJMoa2007621\" rel=\"nofollow noreferrer\">https://www.nejm.org/doi/full/10.1056/NEJMoa2007621</a></p>\n\n<p>Anti-hypertensive Angiotensin II receptor blockers associated to mitigation of disease severity in elderly COVID-19 patients\n<a href=\"https://www.medrxiv.org/content/10.1101/2020.03.20.20039586v1\" rel=\"nofollow noreferrer\">https://www.medrxiv.org/content/10.1101/2020.03.20.20039586v1</a></p>\n", "score": 4 } ]

[ "covid-19", "sars-cov-2" ]

[ { "answer_id": 21507, "body": "<p>You should read the whole article: </p>\n\n<p><strong>Things You Should Never Microwave</strong><br>\n...<br>\n - Clothing and other large fabric items </p>\n\n<p>The problem with microwaves is that they are not heating any item put inside them homogeneously but create \"hot spots\" instead. The image shows a simulation of the electric field inside a microwave oven (taken from <a href=\"https://en.wikipedia.org/wiki/Microwave_oven\" rel=\"nofollow noreferrer\">wikipedia</a>).\nTherefore, microwave oven have a turning table and still it is advisable to stir your food in between of the heating process. \nA paper or cloth, however, could catch fire!</p>\n\n<p><a href=\"https://i.stack.imgur.com/4ntVd.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/4ntVd.png\" alt=\"Simulation of the electric field inside a microwave oven\"></a></p>\n\n<p>The better idea to clean cloth is obviously a washing machine. Those usually have also a program to wash at 60°C / 140°Fahrenheit, which should be sufficient, or even higher. This will not only kill most germs (denaturation of many proteins or nucleic acids starts already below 50°C) but also wash away contamination.</p>\n\n<p><strong>UPDATE</strong><br>\nDue to the current situation and the ongoing shortage of respirators the possibilities for decontamination are discussed broadly.\nThe best study on this topic seems to be from 2010:\n<a href=\"https://journals.sagepub.com/doi/abs/10.1177/155892501000500405\" rel=\"nofollow noreferrer\">Evaluation of Multiple (3-Cycle) Decontamination Processing for Filtering Facepiece Respirators</a><br>\nThey tried eight different methods including <strong>microwave-oven-generated steam</strong>.<br>\nSo it turns out, <strong>yes, it is possible</strong> to decontaminate respirators in a microwave. Two minutes with max power seem to be sufficient. But you should add a <strong>bowl with some water</strong> below the respirator. The generated steam ensures a more homogeneous temperature profile and prevents local hot spots.<br>\nBut be aware that some respirators have <strong>metal brackets</strong> at the nose part. Those can not be put in a microwave.<br>\nAnyhow, it is always stated that decontamination is not ideal and should only be an emergency solution.</p>\n", "score": 5 }, { "answer_id": 21608, "body": "<p>To add to Philipp Leitl's good and cautionary answer:</p>\n\n<p>Microwave ovens work by causing polar molecules in the food being cooked, e.g. water and fats, to rotate, according to: </p>\n\n<p><a href=\"https://chemistry.stackexchange.com/a/21780/65464\">Why does microwave heat up things so much more quickly than visible light?</a></p>\n\n<p>This rotational movement provides the heating effect. </p>\n\n<p>I would not be sure that the chemical make-up of clothing has equivalent properties such that it can be heated in the same way as food. Indeed as Philipp Leitl points out there is danger in this approach.</p>\n\n<p>However staying on the subject of photons/electromagentic radiation, what can kill pathogens, such as the coronavirus, is Ultra-Violet light, particular, UV-C: <a href=\"https://www.bbc.com/news/business-51914722\" rel=\"nofollow noreferrer\">Coronavirus: Robots use light beams to zap hospital viruses</a></p>\n\n<p>The UV radiation must be able to get to the target, so an obstructed or dirty surface will inhibit effectiveness.</p>\n", "score": 4 } ]

[ "covid-19", "virus", "coronavirus", "disinfection", "microwaves" ]

[ { "answer_id": 21580, "body": "<p>Here are studies on viability at different temperature for similar viruses</p>\n\n<p><a href=\"https://i.stack.imgur.com/lMNSL.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/lMNSL.png\" alt=\"enter image description here\"></a></p>\n\n<p><a href=\"https://www.journalofhospitalinfection.com/article/S0195-6701(20)30046-3/fulltext\" rel=\"nofollow noreferrer\">https://www.journalofhospitalinfection.com/article/S0195-6701(20)30046-3/fulltext</a></p>\n", "score": 3 }, { "answer_id": 21578, "body": "<p><strong>Casanova LM et al. 2010, \"Effects of air temperature and relative humidity on coronavirus survival on surfaces.\"</strong>\n This study on other similar viruses -- transmissible gastroenteritis virus and mouse hepatitis virus -- showed that those viruses persisted for as long as 28 days at 4 degrees C, and stayed activated at low humidity (20% RH). But inactivation was more rapid at warmer temperature, 20 deg C. At 40 degrees, both viurses were inactivated more rapidly. Humidity was different, as there was greater survival at high (80%).\n The Abstract: Assessment of the risks posed by severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) on surfaces requires data on survival of this virus on environmental surfaces and on how survival is affected by environmental variables, such as air temperature (AT) and relative humidity (RH). The use of surrogate viruses has the potential to overcome the challenges of working with SARS-CoV and to increase the available data on coronavirus survival on surfaces. Two potential surrogates were evaluated in this study; transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) were used to determine effects of AT and RH on the survival of coronaviruses on stainless steel. At 4 degrees C, infectious virus persisted for as long as 28 days, and the lowest level of inactivation occurred at 20% RH. Inactivation was more rapid at 20 degrees C than at 4 degrees C at all humidity levels; the viruses persisted for 5 to 28 days, and the slowest inactivation occurred at low RH. Both viruses were inactivated more rapidly at 40 degrees C than at 20 degrees C. The relationship between inactivation and RH was not monotonic, and there was greater survival or a greater protective effect at low RH (20%) and high RH (80%) than at moderate RH (50%). There was also evidence of an interaction between AT and RH. The results show that when high numbers of viruses are deposited, TGEV and MHV may survive for days on surfaces at ATs and RHs typical of indoor environments. TGEV and MHV could serve as conservative surrogates for modeling exposure, the risk of transmission, and control measures for pathogenic enveloped viruses, such as SARS-CoV and influenza virus, on health care surfaces.</p>\n\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pubmed/20228108\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pubmed/20228108</a></p>\n", "score": 2 }, { "answer_id": 21583, "body": "<p>For the sake of completeness:\n<strong>Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1</strong> (dated March 17 2020) from \n<a href=\"https://www.nejm.org/doi/full/10.1056/NEJMc2004973\" rel=\"nofollow noreferrer\">New England Journal of Medicine</a></p>\n\n<p>Begins: </p>\n\n<blockquote>\n <p>A novel human coronavirus that is now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (formerly called HCoV-19) emerged in Wuhan, China, in late 2019 and is now causing a pandemic.1 We analyzed the aerosol and surface stability of SARS-CoV-2 and compared it with SARS-CoV-1, the most closely related human coronavirus.2</p>\n \n <p>We evaluated the stability of SARS-CoV-2 and SARS-CoV-1 in aerosols and on various surfaces</p>\n</blockquote>\n", "score": 2 }, { "answer_id": 23078, "body": "<p>UPDATE:\nAccording to:<a href=\"https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(20)30003-3/fulltext\" rel=\"nofollow noreferrer\">Lancet April 2 2020</a></p>\n\n<p>The concentration of SARS-COV-2 decayed thusly:<a href=\"https://i.stack.imgur.com/mqeK0.jpg\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/mqeK0.jpg\" alt=\"enter image description here\"></a></p>\n\n<p>To my non-professional eye it appears that at 72F the concentration of SARS-COV-2 decayed by (approximately) 50% after 72 hours.</p>\n\n<p>When the same experiment was carried at at 99F the concentration decayed by 50% in 24 hours.</p>\n\n<p>The same experiment when carried out at 133 F, the concentration decayed by 50% in 10 minutes.</p>\n\n<p>The layperson's conclusion: Extraordinary heating conditions (greater than 100 F) will be required to decay the virus in a reasonable time period (less than 24 hours). </p>\n", "score": 2 } ]

[ "covid-19", "sars-cov-2" ]

[ { "answer_id": 21562, "body": "<p><strong>Update Apr 2</strong>: Pooled tests are under development now (<a href=\"https://www.faz.net/aktuell/rhein-main/frankfurter-forscher-entwickeln-schnelleren-corona-test-16704912.html\" rel=\"nofollow noreferrer\">newspaper in German</a>), the plan is to pool 5 samples and to use the usual amount of each sample (and presumably dilute less) so that sensitivity is not an issue. </p>\n\n<p><strong>Update Apr 9</strong> <a href=\"https://www.nytimes.com/2020/04/04/world/europe/germany-coronavirus-death-rate.html\" rel=\"nofollow noreferrer\">NYT article</a> mentioning a pooled procedure for routine tests for health care workers (pooling 10 samples) in Germany.</p>\n\n<hr>\n\n<p>In general, pooled tests help in screening situations, that is, when very few samples are positive, so that 10+ samples can be pooled and still only a small fraction of pooled samples is positive. They require good sensitivity. </p>\n\n<p>We're <em>not</em> in a screening situation with the current SARS-CoV-2 testing, and pooling wouldn't help much right now - it would probably not be worth while the effort to develop and implment pooled tests. </p>\n\n<hr>\n\n<p>Long version:</p>\n\n<p>(update: deleted newspaper hints that logistics may be the bottleneck:)</p>\n\n<blockquote>\n <p>What is the bottle neck in the testign process?</p>\n</blockquote>\n\n<p>According to <a href=\"https://www.mdr.de/nachrichten/podcast/kekule-corona/mundschutz-besser-als-zu-hause-bleiben100.html\" rel=\"nofollow noreferrer\">Kekulé (10 min or so into the interview)</a> the \"lab machinery\" in Germany has a capacity of several 100k tests per day, but right now there are shortages in reagents but also e.g. in the swabs for taking samples (so, comparably low tech parts of the test). Pooled tests of course need just as many swabs (if not more: false negatives due to the sampling not picking up virus material is a concern, and the usual remedy is to take more swabs.)</p>\n\n<hr>\n\n<p>Anything that comes now are my guesses as a professional from a neighbouring field: analytical chemistry). I don't have any first hand experience with PCR. </p>\n\n<blockquote>\n <p>Does the amount of material needed to test for COVID-19 scale rather with the number of performed tests, or with the amount of tested material?</p>\n</blockquote>\n\n<p>I expect the reagent needs to scale (mostly) with the number of performed tests. I also expect the amount of tested material to be the same (prescribed by the method/protocol) for each run. <strike>That is, when you pool n samples, you'd take only 1/n of material from each (In practice it may be better to pool and then take out 1/n of the pooled sample). </strike> Update: The test described in the newspaper goes the opposite direction: they take n times the sample material in order to avoid trouble with low sensitivity. In consequence, this cannot be considered a \"derived\" \"variety\" of the 1-sample tests, it must be newly developed almost from scratch.</p>\n\n<blockquote>\n <p>Does the amount of time needed to test for COVID-19 scale rather with the number of performed tests, or with the amount of tested material?</p>\n</blockquote>\n\n<p>Again: the tests, mor precisely the number of batches of tests since multiple tests can be processed in parallel. </p>\n\n<blockquote>\n <p>Is the the nucleic acid amplification test still reliable enough, if the Virus RNA to be detected is dilluded among multiple samples?</p>\n</blockquote>\n\n<p>(From here on, we're back inside my professional experience)</p>\n\n<p>This I cannot answer since I don't know the typical concentration range of virus RNA in the samples of positive cases. </p>\n\n<p>The lowest concentration of virus RNA that can reliably be detected is called the limit of detection (LoD). In this context, reliably is 19 out of 20 validation samples at that concentration according to the emergency/\"shortcut\" validation procedure of the FDA (I expect other parts of the world to have similar validation procedures right now). The rFDA has a page with tests that have this emergency approval](<a href=\"https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations#covid19ivd\" rel=\"nofollow noreferrer\">https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations#covid19ivd</a>), and the Manufacturer information lists the LoD. </p>\n\n<p>One would relate the lower end of the typical concentration range to the LoD to calculate how many samples could be pooled without the test becoming unreliable. \n<strike>The linked news article hints that this may actually be a limiting factor.</strike> The test under development avoids this problem by using more sample material.</p>\n\n<hr>\n\n<p>There's another limitation to how many samples one can sensibly pool. The aim of the procedure is to save tests. Thus, we need to set up the pooling so that only a small proportion of pooled tests is positive and a large fraction of cases can be \"closed\" as negative. </p>\n\n<p>Here's the fraction of pooled samples that is positive depending on the prevalence = fraction of positive samples and the number of samples that are pooled n:</p>\n\n<p><a href=\"https://i.stack.imgur.com/gjB0v.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/gjB0v.png\" alt=\"proportion of positive pooled cases\"></a> </p>\n\n<p>Contours are every 10 %points. Dashed and dotted lines are the current fractions of positive samples for Germany and Italy.</p>\n\n<p>From that, we can calculate how many samples we need to run (for every positive pooled sample, additional n tests) and from that the fraction of tests we save compared to testing each sample separately:</p>\n\n<p><a href=\"https://i.stack.imgur.com/qE797.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/qE797.png\" alt=\"fraction of samples saved by pooling\"></a></p>\n\n<p>Contours here are right to left: 0, 25 %, 50 % and 75 % \"savings\".</p>\n\n<p>So, at the current testing situation in Germany, pooling 4 samples would allow to save almost 60 % of tests. In Italy, pooling 3 samples would save less than 15 % of tests.</p>\n\n<p>A pooled test would need its own validation and one would also do some additional development to get the required sensitivity (LoD) for the desired number of pooled samples, meaning more delay until pooled tests would be available. </p>\n\n<p>In addition, pooled tests alongside the single tests that are anyways needed would mean additional logistic burden in the labs. </p>\n\n<p>I don't think developing a pooled test would be worth while right now, the more so, as other measures would give similar or better relief:</p>\n\n<p>Doing only 1 test per household would save about 50 % since the <a href=\"https://de.statista.com/statistik/daten/studie/200374/umfrage/anzahl-der-haushalte-in-deutschland-im-jahr-2010-nach-bundeslaendern/\" rel=\"nofollow noreferrer\">average size of a household in Germany is 2</a> without the need of any new test development.</p>\n\n<p>The same is true for further concentrating the tests on the vulnerable/high risk population. </p>\n\n<p>Thus, pooled tests may help in the containment phase when they'd allow to test a larger number of possible contacts. </p>\n\n<p><strong>Update:</strong> Getting back into containment phase is the aim of the current lockdown. </p>\n\n<p>We'd still have high requirements for sensitivity and specificity. This means, pooled tests would have helped most right at the beginning of the epidemic - but they always mean additional R&amp;D and also additional validation needs to be done (and part of the validation work btw. must be done in every single lab that wants to use the test) since they need to be implemented in addition to the single sample method. This means, they'll always be available only after the single sample method is established.</p>\n", "score": 5 }, { "answer_id": 23164, "body": "<p>Israel now have the capacity to pool 64 tests in one</p>\n\n<blockquote>\n <p>“According to the new pooling approach that we have currently tested, molecular testing can be performed on a “combined sample,” taken from 32 or 64 patients. This way we can significantly accelerate the testing rate. Only in those rare cases, where the joint sample is found to be positive, will we conduct an individual test for each of the specific samples,” said Dr. Yuval Gefen, director of the Rambam Clinical Microbiology Laboratory.</p>\n</blockquote>\n\n<p><a href=\"https://www.hospimedica.com/coronavirus/articles/294781273/israeli-researchers-introduce-pooling-method-for-covid-19-testing-of-over-60-patients-simultaneously.html\" rel=\"nofollow noreferrer\">https://www.hospimedica.com/coronavirus/articles/294781273/israeli-researchers-introduce-pooling-method-for-covid-19-testing-of-over-60-patients-simultaneously.html</a></p>\n\n<p>which might be useful if there is a person who contacted many hundreds of people. Eg. We have a supermarket worker who tested positive and they were working during their infectious period.</p>\n", "score": 1 } ]

[ "covid-19", "test", "public-health" ]

[ { "answer_id": 21692, "body": "<blockquote>\n <p>Protecting the majority with the minority (old people, people with bad immune systems, etc) doesn't seem to be an ethical thing to do. (Think of this case. It's kind of like putting the pain of everybody onto a single innocent person. )</p>\n</blockquote>\n\n<p>Essentially the idea was to do the <em>reverse</em> i.e. if the majority get infected -> gain immunity then if you can keep the (vulnerable) minority from being exposed while the infection->immunity process happens they won't <em>need</em> to get immunity because they will then be protected by the immunity of the majority (i.e. the herd).</p>\n\n<p>In the same way that there are always going to be people who can't be vaccinated for a disease like measles (immunocompromised, too young, etc) but if a sufficient majority are vaccinated that prevents the disease ever getting an opportunity to get to them in the first place.</p>\n\n<blockquote>\n <p>That means that there will be more people who are infected, so there will be more deaths.</p>\n</blockquote>\n\n<p>If more people <em>total</em> get infected but less <em>vulnerable</em> people then you can still see less overall deaths.</p>\n\n<blockquote>\n <p>Maybe do they mean to attempt to social-distance vulnerable people like old people but let other healthy people get an infection? Wouldn't that also overflow the hospital?</p>\n</blockquote>\n\n<p>That was basically the initial UK plan - the idea being that if you could keep the spread amongst \"healthy\" people slow enough you'd \"flatten the peak\" and while the same eventual number would get the virus less would have it any one time, therefore (hopefully) avoiding an overload on the health infrastructure. This has sort of (although not entirely) gone out of the window now as it wasn't slow enough - and too many vulnerable people were getting infected.</p>\n\n<p>The difference between this so-called \"mitigation\" approach and the China-style \"suppression\" approach is that in a suppression you're aiming to reduce the number of people that each infected person can subsequently infect to less than 1.</p>\n\n<p>The change in tack to more intensive measures was driven mainly by modelling done by a team at <a href=\"https://www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gida-fellowships/Imperial-College-COVID19-NPI-modelling-16-03-2020.pdf\" rel=\"nofollow noreferrer\">Imperial College London</a>, where they predicted that at the rate the virus was spreading the NHS would be overwhelmed and concluded:</p>\n\n<blockquote>\n <p>We therefore conclude that epidemic suppression is the only viable strategy at the current time.</p>\n</blockquote>\n\n<p>Hence why more drastic lockdown measures are now being implemented. Suppression brings its own challenges - namely that if it is successful the population at large remains non-immune and when you ease the suppression measures off too soon and you get any new cases introduced into the population it can spread very quickly again and you're back where you started.</p>\n", "score": 3 }, { "answer_id": 21743, "body": "<p>Unfortunately the ideas about herd-immunity have become a populist term to down-play serious diseases, by many people who do not understand the conditions where this can be applied. Just straight off, it can only <em>work</em> within western ethical standards when:</p>\n\n<ol>\n<li>The disease doesn't kill a large percentage of the infected.</li>\n<li>The infected are not infectious for a long time.</li>\n<li>The incubation time is very short.</li>\n<li>The virus causing the disease does not mutate fast.</li>\n</ol>\n\n<p>Unfortunately <strong>none</strong> of the above are true for COVID-19. Which make the arguments for applying <em>herd-immunity</em>, in that case, macabre.</p>\n\n<hr>\n\n<p>PS. For those who will immediately scream for references, please google and search here or in the <a href=\"https://biology.stackexchange.com/\">biology SE</a>, where you will find hundreds of answers to the above statements. </p>\n", "score": 0 } ]

[ "covid-19", "immune-system", "medical-ethics" ]

[ { "answer_id": 21751, "body": "<p>Well this is a guess because there is no published data that I am aware of in the english literature to be able to answer the question.</p>\n\n<p>A small percentage of people who have presented with covid-19 pneumonia have also had diarrhoea, it is thought that the faecal-oral route is also an important mode of transmission. </p>\n\n<p>If the person develops a respiratory infection the affected cells will eventually spill virus into the circulation, a condition called viraemia. This allows the virus to reach distant cells that bear the ACE2 surface receptor and these cells are also in the heart, kidneys and gut as well as monocytes. One would also expect that intestinal cells affected primarily by ingestion of virus particles would also do the same, and produce a viraemia leading to the virus spreading to the lungs, heart and kidneys. But they may present initially with diarrhoea before getting respiratory symptoms.</p>\n", "score": 3 } ]

[ "covid-19", "virus", "food-poisoning", "diarrhea" ]

[ { "answer_id": 21787, "body": "<p>We know that early CT scan of patients, even asymptomatic ones, show ground glass opacities and histology of resected lung segments in asymptomatic patients taken for lung cancer resection show alveloli filling with proteinaceous material. Patchy changes progress with time and if it were haematogenous spread then we would expect military like spread through the lung which is not what is being described.</p>\n\n<p>The disease is spread by droplets full of virus, and it is likely that the patient in coughing is spreading the virus to other parts of the lung.</p>\n\n<p>But this is speculative as the disease progression has not yet been fully characterised.</p>\n\n<p>Pulmonary Pathology of Early-Phase 2019 Novel\nCoronavirus (COVID-19) Pneumonia in Two Patients\nWith Lung Cancer\n<a href=\"https://www.jto.org/article/S1556-0864(20)30132-5/pdf\" rel=\"nofollow noreferrer\">https://www.jto.org/article/S1556-0864(20)30132-5/pdf</a></p>\n\n<p>Temporal Changes of CT Findings in 90 Patients with COVID-19 Pneumonia: A Longitudinal Study\n<a href=\"https://pubs.rsna.org/doi/10.1148/radiol.2020200843\" rel=\"nofollow noreferrer\">https://pubs.rsna.org/doi/10.1148/radiol.2020200843</a></p>\n", "score": 2 } ]

[ "coronavirus" ]

[ { "answer_id": 22879, "body": "<p>Because we know its genomic sequence.</p>\n\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720273/\" rel=\"noreferrer\">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720273/</a>:</p>\n\n<blockquote>\n <p>Using fixed and frozen lung tissue of 1918 influenza victims, the complete genomic sequence of the 1918 influenza virus has been deduced. Sequence and phylogenetic analysis of the completed 1918 influenza virus genes shows them to be the most avian-like among the mammalian-adapted viruses. This finding supports the hypotheses that (1) the pandemic virus contains genes derived from avian-like influenza virus strains and that (2) the 1918 virus is the common ancestor of human and classical swine H1N1 influenza viruses</p>\n</blockquote>\n", "score": 6 } ]

[ "virus", "influenza", "medical-history" ]

[ { "answer_id": 22918, "body": "<p>TL;DR: Factors such as UV light and heat causes the mix of RNA, fatty membrane, and protein making up the viruses to steadily break down.</p>\n\n<hr>\n\n<p>More details:</p>\n\n<p><a href=\"https://www.sciencefocus.com/nature/do-viruses-die/\" rel=\"nofollow noreferrer\">https://www.sciencefocus.com/nature/do-viruses-die/</a>:</p>\n\n<blockquote>\n <p>Strictly speaking, viruses can’t die, for the simple reason that they aren’t alive in the first place. Although they contain genetic instructions in the form of DNA (or the related molecule, RNA), viruses can’t thrive independently. Instead, they must invade a host organism and hijack its genetic instructions.</p>\n</blockquote>\n\n<p><a href=\"https://www.sciencealert.com/how-long-does-coronavirus-last-on-surfaces\" rel=\"nofollow noreferrer\">https://www.sciencealert.com/how-long-does-coronavirus-last-on-surfaces</a>:</p>\n\n<blockquote>\n <p>Just hanging about in the atmosphere, the effect of factors such as UV light and heat causes the mix of RNA, fatty membrane, and protein making up the [viruses] to steadily break down in a few hours [or less/more].</p>\n</blockquote>\n\n<p><a href=\"https://www.statnews.com/2020/03/19/coronavirus-survives-on-surfaces-how-to-protect-yourself/\" rel=\"nofollow noreferrer\">https://www.statnews.com/2020/03/19/coronavirus-survives-on-surfaces-how-to-protect-yourself/</a> (<a href=\"https://web.archive.org/web/20200401153344/https://www.statnews.com/2020/03/19/coronavirus-survives-on-surfaces-how-to-protect-yourself/\" rel=\"nofollow noreferrer\">mirror</a>):</p>\n\n<blockquote>\n <p>Viruses covered in “envelopes” have the most trouble surviving outside a living cell. On surfaces, the surrounding light, heat, and dryness break down the envelope, killing the virus. (Porous surfaces pull moisture away from viruses that land on them, accelerating the destruction of the envelope.) Most rhinoviruses have such envelopes; so do some influenza viruses. Norovirus doesn’t, enabling it to last longer in the environment.</p>\n</blockquote>\n", "score": 4 } ]

[ "virus" ]

[ { "answer_id": 23179, "body": "<p>The early data from the symptom tracker at Kings College, London</p>\n\n<blockquote>\n <p>Since then, researchers at Kings College London have developed an app, called the COVID-19 Symptom Tracker, for British citizens to document their Coronavirus Experience. It now has around 2 million users, Hopkins says, as Britons are encouraged to map their symptoms on a daily basis, even if they're feeling well. The goal is to learn more about the onset of the infection and \"identify which symptoms occur at which stage of the disease.\" When Hopkins first put out the organization's statement, loss of smell was not included among the app's options. But she got in contact with the development team and convinced them to add it.</p>\n</blockquote>\n\n<p>While anosmia was not initially in the symptom tracker, it was added later on and </p>\n\n<blockquote>\n <p>The app team released a statement this week announcing that sense of smell is \"actually the strongest symptom to predict infection,\" according to Hopkins, including when compared to fever. They found 60 percent of patients who tested positive had lost their sense of smell, while in those that tested negative, only 18 percent had anosmia symptoms. This offers more specificity than a fever, which was commonly found in those who tested negatively. The takeaway, Hopkins says, was that \"anyone with new onset loss of sense of smell should be self-isolating, and ideally tested.\" It's an early warning sign. Hopkins has developed a cohort of around 2,500 patients she's monitoring, and while the exact timeline of when anosmia occurs still isn't clear, she says around one-in-four lost their sense of smell before developing any other symptoms. Another one-in-four develop it around the same time as other symptoms, and for the other half, it comes after.</p>\n</blockquote>\n\n<p>The damage is thought to be neuronal rather than just blocking the path for molecules to reach the olfactory receptors</p>\n\n<blockquote>\n <p>Unlike with smell loss due to the common cold, there's no physical blockage in most COVID-19 patients. The odor is getting back there, but the receptors are damaged. \"Coronavirus in particular can damage the nerve and then travel along the olfactory nerve to the olfactory bulb, which is the more simple processing part, and of course damage that as well,\" Hopkins adds. \"Now fortunately, the olfactory nerves have the ability to recover, which is why they're being used in research for spinal cord injury. So they can regenerate and your sense of smell can return.\"</p>\n</blockquote>\n\n<p>There are stem cells which allow the nerves to regenerate</p>\n\n<p>The early data from the app suggests that you can recover the sense of smell in a couple of weeks</p>\n\n<blockquote>\n <p>\"There are certainly people who have persistent, severe anosmia after post-viral infections,\" Hopkins says. \"We know you can get persistent loss. Coronaviruses are known to cause long-term loss. Obviously, it's too early to tell what proportion of patients with COVID-19 will have long-term loss, but if you look at studies with post-viral loss in general, at least two thirds will make a good recovery. But that means that as many as one in three may not fully get their sense of smell back. In our cohort, at least 60 percent of people were seeing improvement within two weeks, and I just sent out a follow-up again today to try and see people beyond that.\"</p>\n</blockquote>\n\n<p>And more recent data from a French April 2020 paper of 417 patients:</p>\n\n<p><img src=\"https://media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs00405-020-05965-1/MediaObjects/405_2020_5965_Fig3_HTML.png\" alt=\"\"></p>\n\n<blockquote>\n <p>Pattern of recovery time for patients with olfactory dysfunction. The ordinate axis consists of percentages of patients. The patients with hyposmia or anosmia had the following recovery times a 1–4 days (33.0%), 5–8 days (39.6%), 9–14 days (24.2%), and more than 15 days (3.3%). The patients with anosmia had the following recovery times b 1–4 days (20.3%), 5–8 days (47.5%), 9–14 days (28.8%), and more than 15 days (3.4%)</p>\n</blockquote>\n\n<p><a href=\"https://www.esquire.com/news-politics/a32030330/coronavirus-sense-of-smell-covid-19/\" rel=\"nofollow noreferrer\">https://www.esquire.com/news-politics/a32030330/coronavirus-sense-of-smell-covid-19/</a></p>\n\n<p><a href=\"https://link.springer.com/article/10.1007/s00405-020-05965-1\" rel=\"nofollow noreferrer\">https://link.springer.com/article/10.1007/s00405-020-05965-1</a></p>\n", "score": 4 } ]

[ "covid-19", "anosmia" ]

[ { "answer_id": 23183, "body": "<p>From <a href=\"https://www.businessinsider.com/us-coronavirus-hospitalizations-underlying-health-conditions-cdc-2020-3\" rel=\"nofollow noreferrer\">https://www.businessinsider.com/us-coronavirus-hospitalizations-underlying-health-conditions-cdc-2020-3</a> (<a href=\"https://web.archive.org/web/20200412111344/https://www.businessinsider.com/us-coronavirus-hospitalizations-underlying-health-conditions-cdc-2020-3\" rel=\"nofollow noreferrer\">mirror 1</a>, <a href=\"http://archive.is/WJsGC\" rel=\"nofollow noreferrer\">mirror 2</a>):</p>\n\n<p><a href=\"https://i.stack.imgur.com/OTEHZ.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/OTEHZ.png\" alt=\"enter image description here\"></a></p>\n\n<p>Transcription... </p>\n\n<blockquote>\n <p>Counts are among the 7162 cases with completed information on pre-existing conditions:</p>\n \n <ul>\n <li>Chronic liver disease</li>\n <li>Current smoker </li>\n <li>Former smoker </li>\n <li>Chronic renal disease</li>\n <li>Immunocompromised </li>\n <li>Cardiovascular disease </li>\n <li>Chronic lung disease</li>\n <li>Diabetes mellitus</li>\n <li>Other chronic disease </li>\n </ul>\n</blockquote>\n\n<p>Source: CDC Data as of March 28, 2020 at 12 pm EST. </p>\n\n<p>Also: <a href=\"https://medicalsciences.stackexchange.com/q/23128/43\">What are the genetic predispositions, if any, for covid-19?</a></p>\n", "score": 3 }, { "answer_id": 23189, "body": "<p>A pre-publication study at NYU in New York City looked at the risk factors for more severe COVID-19 disease. </p>\n\n<p>These risks included older age, especially age over 75, as well as obesity (BMI>40), and congestive heart failure, which conferred dramatically higher odds of being hospitalized for COVID-19. </p>\n\n<p>The strongest risk factor was low oxygen levels upon presentation in the E.R. </p>\n\n<p><a href=\"https://www.medrxiv.org/content/10.1101/2020.04.08.20057794v1\" rel=\"nofollow noreferrer\">https://www.medrxiv.org/content/10.1101/2020.04.08.20057794v1</a></p>\n\n<p>According to the authors’ abstract:</p>\n\n<blockquote>\n <p>Strongest hospitalization risks were age ≥75 years (OR 66.8, 95% CI,\n 44.7-102.6), age 65-74 (OR 10.9, 95% CI, 8.35-14.34), BMI>40 (OR 6.2, 95% CI, 4.2-9.3), and heart failure (OR 4.3 95% CI, 1.9-11.2).\n Strongest critical illness risks were admission oxygen saturation &lt;88%\n (OR 6.99, 95% CI 4.5-11.0), d-dimer>2500 (OR 6.9, 95% CI, 3.2-15.2),\n ferritin >2500 (OR 6.9, 95% CI, 3.2-15.2), and C-reactive protein\n (CRP) >200 (OR 5.78, 95% CI, 2.6-13.8). In the decision tree for\n admission, the most important features were age >65 and obesity; for\n critical illness, the most important was SpO2&lt;88, followed by\n procalcitonin >0.5, troponin &lt;0.1 (protective), age >64 and CRP>200.\n Conclusions: Age and comorbidities are powerful predictors of\n hospitalization; however, admission oxygen impairment and markers of\n inflammation are most strongly associated with critical illness.</p>\n</blockquote>\n", "score": 3 } ]

[ "covid-19" ]

[ { "answer_id": 23233, "body": "<p>We now have some data from randomized studies that provide some indications of safety considerations when using Hydroxychloroquine/Chloroquine in the management of Covid-19. The first study (non-peer reviewed) from Renmin Hospital of Wuhan University</p>\n\n<blockquote>\n <p>Main methods: From February 4 to February 28, 2020, 62 patients suffering from COVID-19 were diagnosed and admitted to Renmin Hospital of Wuhan University. All participants were randomized in a parallel-group trial, 31 patients were assigned to receive an additional 5-day HCQ (400 mg/d) treatment, Time to clinical recovery (TTCR), clinical characteristics, and radiological results were assessed at baseline and 5 days after treatment to evaluate the effect of HCQ</p>\n</blockquote>\n\n<p>So, these were 62 patients half of whom were only given 5 days of 400 mg of Hydroxychloroquine, which is a standard dose used in the management of rheumatic disease at approximately 5 mg/Kg, 400 mg/d (200 mg/bid) between days 1 and 5.</p>\n\n<p>It's important to note the inclusion criteria here in particular</p>\n\n<blockquote>\n <ol start=\"4\">\n <li>SaO2/SPO2 ratio > 93% or PaO2/FIO2 ratio > 300 mmHg under the condition in the hospital room (mild illness); </li>\n </ol>\n</blockquote>\n\n<p>So, these were mildly affected patients who would have been expected to have a good outcome. Average age was 44.7 years (sd 15.3 years) with approximately even split in gender, so again a group expected to do well. Excluded were:</p>\n\n<blockquote>\n <ol>\n <li>Severe and critical illness patients </li>\n </ol>\n</blockquote>\n\n<p>among other criteria.</p>\n\n<p>Although this was an efficacy study, there were minor side effects noted in the treatment arm</p>\n\n<blockquote>\n <p>Notably, a total of 4 of the 62 patients progressed to severe illness, all of which occurred in the control\n group not receiving HCQ treatment. For adverse effects, it should be noted that there were two patients\n with mild adverse reactions in the HCQ treatment group, one patient developed a rash, and one patient\n experienced a headache, none severe side effects appeared among them. </p>\n</blockquote>\n\n<p>The next large study we have is from Brazilian Hospital <em>Hospital e Pronto-Socorro Delphina Rinaldi Abdel Aziz</em> and is a</p>\n\n<blockquote>\n <p>double-blinded, randomized clinical trial addressing different dosages of Chloroquine for the treatment of severe patients with COVID-19 in the absence of a control group using placebo. </p>\n</blockquote>\n\n<p>The inclusion criteria included</p>\n\n<blockquote>\n <p>Hospitalized patients aged 18 years or older at the time of inclusion, with respiratory rate\n higher than 24 rpm AND/OR heart rate higher than 125 bpm (in the absence of fever)\n AND/OR peripheral oxygen saturation lower than 90% in ambient air AND/OR shock\n (defined as mean arterial pressure lower than 65 mmHg, with the need for vasopressors\n medicines or oliguria or a lower level of consciousness) were included.</p>\n</blockquote>\n\n<p>So, these were very sick patients. Their age was slightly higher at average of 51.1 years (sd 13.9) </p>\n\n<p>Annoyingly there is no placebo controlled arm due to \"ethical\" considerations, and we note that this study is very different from the Wuhan study in that it looks at <strong>severe</strong> patients.</p>\n\n<p>The high dose arm intended to give 12 g of Chloroquine over 12 days (Wuhan used 2 g over 5 days), and their low dose arm used 2.7 g over 5 days. Both arms also used ceftriaxone and azithromycin as well, and their preliminary data used 81 patients from a predefined population size of 440.</p>\n\n<p>Given the toxicity of hydroxychloroquine/chloroquine at high dose with Qtc prolongation, and theoretically compounded with the co-administration of azithromycin, not unexpectedly Qtc prolongation was observed:</p>\n\n<blockquote>\n <p>Regarding cardiotoxicity and\n QTc over time, the variation in the QTc as compared to the baseline ECG increased more on\n days 2 and 3 in the high dose CQ arm, with both arms (low and high CQ) showing more\n similar QTc variations in the last three days of follow-up (Figure 2). Two patients in the high\n dose CQ arm evolved with ventricular tachycardia before death. This severe type of arrythmia\n is usually facilitated when QTc is prolonged. </p>\n</blockquote>\n\n<p>There was also evidence of myocardial injury in both arms</p>\n\n<blockquote>\n <p>Occurrence of myocarditis (defined as CKMB higher than 2x the upper normal\n limit), which may be a final complication of severe sepsis or a lesion triggered by the virus\n itself, was seen in 2/24 (8.3%) patients (1 patient/arm). No echocardiogram was performed. </p>\n</blockquote>\n\n<p>By day 6, 4 of the low dose arm had died, and 7 of the high dose arm. Ventricular tachycardia was observed in 2 of the high dose arm deaths at total dose of 7.2 g of Chloroquine. However, more patients with heart disease were randomized to the high dose arm, and there were 5 people over age 75 in the high dose arm, and none in the low dose.</p>\n\n<p>Given the appearance of a cardiotoxicity signal as well as excess deaths, enrollment in the high dose arm was ceased and all patients were moved to the low dose arm. However, there is no comparator arm going forwards.</p>\n\n<p>Their table 3 also has a mistake in that they state 4/41 died in the High Dose arm, and 7/40 in the low dose which is not what the conclusions state.</p>\n\n<p><strong>Update: 16 April 2020</strong></p>\n\n<p>A review has just been pre-published looking at the safety of Hydroxychloroqine in combination with other drugs that points to the possible lethality of combination of hydroxychloroquine with azithromycin.</p>\n\n<blockquote>\n <p>Results: Overall, 956,374 and 310,350 users of hydroxychloroquine and sulfasalazine, and 323,122 and 351,956 users of hydroxychloroquine-azithromycin and hydroxychloroquine-amoxicillin were included. No excess risk of SAEs was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. SCCS confirmed these findings. However, <strong>when azithromycin was added to hydroxychloroquine, we observed an increased risk of 30-day cardiovascular mortality (CalHR2.19 [1.22-3.94]), chest pain/angina (CalHR 1.15 [95% CI 1.05-1.26]), and heart failure (CalHR 1.22 [95% CI 1.02-1.45])</strong> Conclusions: Short-term hydroxychloroquine treatment is safe, but addition of azithromycin may induce heart failure and cardiovascular mortality, potentially due to synergistic effects on QT length. We call for caution if such combination is to be used in the management of Covid-19.</p>\n</blockquote>\n\n<p><strong>Update: 22 April 2020</strong> </p>\n\n<p>A VA review looked at 386 VA patients treated with Hydroxychloroquine with or without Azithromycin vs with neither until 11th April 2020</p>\n\n<blockquote>\n <p>performed a retrospective analysis of data from patients hospitalized with confirmed SARS-CoV-2 infection in all United States Veterans Health Administration medical centers until April 11, 2020. Patients were categorized based on their exposure to hydroxychloroquine alone (HC) or with azithromycin (HC+AZ) as treatments in addition to standard supportive management for Covid-19. The two primary outcomes were death and the need for mechanical ventilation.</p>\n</blockquote>\n\n<p>And there appeared to be worse outcomes for those on HC</p>\n\n<blockquote>\n <p>RESULTS: A total of 368 patients were evaluated (HC, n=97; HC+AZ, n=113; no HC, n=158). Rates of death in the HC, HC+AZ, and no HC groups were 27.8%, 22.1%, 11.4%, respectively</p>\n</blockquote>\n\n<p>A weakness of the study was that it was retrospective review of outcomes.</p>\n\n<p>Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study\n<a href=\"https://www.medrxiv.org/content/10.1101/2020.04.08.20054551v1\" rel=\"nofollow noreferrer\">https://www.medrxiv.org/content/10.1101/2020.04.08.20054551v1</a></p>\n\n<p><a href=\"https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v3.full.pdf\" rel=\"nofollow noreferrer\">https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v3.full.pdf</a></p>\n\n<p><a href=\"https://www.medrxiv.org/content/10.1101/2020.04.07.20056424v1.full.pdf\" rel=\"nofollow noreferrer\">https://www.medrxiv.org/content/10.1101/2020.04.07.20056424v1.full.pdf</a></p>\n\n<p><a href=\"https://www.medrxiv.org/content/10.1101/2020.04.16.20065920v1\" rel=\"nofollow noreferrer\">https://www.medrxiv.org/content/10.1101/2020.04.16.20065920v1</a></p>\n", "score": 4 }, { "answer_id": 23229, "body": "<p>And June news: that large study <a href=\"https://www.bbc.com/news/health-52929916\" rel=\"nofollow noreferrer\">was withdrawn</a>. And there are some <a href=\"https://www.theguardian.com/world/2020/jun/03/covid-19-surgisphere-who-world-health-organization-hydroxychloroquine\" rel=\"nofollow noreferrer\">real questions</a> if their data was real! </p>\n\n<p>May <a href=\"https://finance.yahoo.com/news/hydroxychloroquine-shows-no-coronavirus-benefit-raises-death-risk-144240073.html\" rel=\"nofollow noreferrer\">23 news (AFP)</a> of a large study found no benefits and an increased risk of dying from treatment of Covid-19 with hydroxychloroquine and chloroquine:</p>\n\n<blockquote>\n <p>A study of nearly 100,000 coronavirus patients has shown no benefit in treating them with anti-viral drugs hydroxychloroquine and chloroquine and even increased the likelihood of them dying in hospital.</p>\n \n <p>Chloroquine is an anti-malarial. Both drugs can produce potentially serious side effects, particularly heart arrhythmia. </p>\n \n <p>And neither drug benefitted patients hospitalised with COVID-19, according to a study published on Friday in The Lancet. </p>\n \n <p>Looking at the records of 96,000 patients across hundreds of hospitals, they found that administering the drugs actually increased the risk of dying.</p>\n \n <p>They compared outcomes from four groups: those treated with hydroxychloroquine alone, with chloroquine alone, and then two groups given the respective drugs in combination with antibiotics. </p>\n \n <p>There was also a control group of patients not given these treatments. </p>\n \n <p>At the end of the study period around nine per cent of those in the control group had died. </p>\n \n <p>Of those treated with hydroxychloroquine or chloroquine alone, 18 per cent and 16.4 per cent respectively had died. </p>\n \n <p>And those given each drug in combination with antibiotics were even more likely to die: 22.8 per cent with chloroquine and 23.8 per cent with hydroxychloroquine. </p>\n \n <p>The authors estimated that the drugs put patients at up to 45 per cent higher risk of dying from COVID-19 compared with underlying health issues. </p>\n</blockquote>\n\n<p>Some additional expert commentary on this study on <a href=\"https://www.statnews.com/2020/05/22/what-a-big-new-study-on-malaria-drugs-as-covid-19-treatments-tells-us-and-what-it-doesnt/\" rel=\"nofollow noreferrer\">Stat news</a>.</p>\n\n<blockquote>\n <p>The study is the largest observational study so far on the use of chloroquine and hydroxychloroquine to treat Covid-19; it combined data from 15,000 Covid-19 patients at 671 hospitals on six continents who were treated with the drugs. Those patients were compared to 81,000 patients who had Covid-19 but did not receive the drugs.</p>\n \n <p>Other observational studies have made comparisons in smaller populations. A study of 368 U.S. veterans also showed that the drugs might be potentially harmful. But two different studies each including 1,400 patients treated in New York during the Covid-19 pandemic showed no impact on mortality at all. [...]</p>\n \n <p>Adding more patients helps. But the problem is that, while researchers can control for risk factors that they know about, they can’t rule out that patients getting chloroquine and hydroxychloroquine are dying for reasons they don’t understand that have nothing to do with the drugs.</p>\n \n <p>Still, the results don’t bode well for the malaria drugs as Covid-19 treatments. After controlling for risks such as weight, heart disease, and lung disease, the mortality rate in the control group was 9%. For those who received hydroxychloroquine, it was 18%; when an antibiotic was added, it was more than 20%. That’s not what would be expected if the drugs were highly effective treatments.</p>\n</blockquote>\n\n<p>(And thankfully, this latter piece of news has a <a href=\"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31180-6/fulltext\" rel=\"nofollow noreferrer\">link to the actual study</a>.)</p>\n\n<hr>\n\n<p>Old (April) answer below</p>\n\n<p>This is a pretty partial answer since several studies (including <a href=\"https://www.nih.gov/news-events/news-releases/nih-clinical-trial-hydroxychloroquine-potential-therapy-covid-19-begins\" rel=\"nofollow noreferrer\">a NIH one</a>) are ongoing on CQ and HCQ (I'm assuming you'll accept answers about the latter too, as related enough).</p>\n\n<p>The NYT and various medical blogs have reported <a href=\"https://www.medrxiv.org/content/10.1101/2020.04.07.20056424v1.full.pdf\" rel=\"nofollow noreferrer\">on a draft paper</a> of Brazilian researchers highlighting that they stopped one (high-dose) arm of their trial. Quoting from the conclusions:</p>\n\n<blockquote>\n <p>CQ, despite being a safe drug used for more than 70 years for malaria,\n might be toxic in the dosages recommended by Chinese authorities (high dosage 10g, for 10\n days). Our study raises enough red flags to stop the use of such dosage (12g of CQ in total [...]</p>\n</blockquote>\n\n<p>As for safety details:</p>\n\n<blockquote>\n <p>One patient developed severe rhabdomyolysis, and causality could be attributed to the virus\n or to CQ, which is already known to cause myolysis. Regarding cardiotoxicity and\n QTc over time, the variation in the QTc as compared to the baseline ECG increased more on\n days 2 and 3 in the high dose CQ arm, with both arms (low and high CQ) showing more\n similar QTc variations in the last three days of follow-up. Two patients in the high\n dose CQ arm evolved with ventricular tachycardia before death. This severe type of arrythmia is usually facilitated when QTc is prolonged.</p>\n</blockquote>\n\n<p>And they did a Kaplan-Meier analysis too:</p>\n\n<blockquote>\n <p><a href=\"https://i.stack.imgur.com/pz1wz.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/pz1wz.png\" alt=\"enter image description here\"></a></p>\n \n <p>Time (in days) from randomization to death, in patients treated with each\n chloroquine dosage. The gray band represents the upper and lower limits of the confidence\n interval for lethality in hospitalized patients not receiving CQ obtained by the meta-analysis\n of the studies by Zhou et al. (Lancet, 2020) and Chen et al. (BMJ, 2020) (167/990 = 16.9%;\n 95% CI 14.5-19.2). </p>\n</blockquote>\n\n<p>In term of efficacy (which I won't detail here) they've concluded that (up to day 6):</p>\n\n<blockquote>\n <p>Major presented outcomes were not different between the arms.</p>\n</blockquote>\n\n<p>It might also be useful to quote a bit more from their related-research section:</p>\n\n<blockquote>\n <p>Before the CloroCovid-19 trial began, to our knowledge, there were no published reports of\n robust clinical studies on the safety and/or efficacy of chloroquine (CQ) and/or\n hydroxychloroquine (HCQ) for the treatment of COVID-19 during the recent 2020 pandemic.\n [...] We found three non-randomized studies with limited sample\n sizes in which (1) HCQ use led to a decrease in SARS-Cov-2 detected in respiratory\n secretions five days after treatment, together with azithromycin (France, 36 patients); (2)\n HCQ use shortened time to clinical recovery (China, 62 patients); and (3) CQ was superior to\n control treatment in inhibiting the exacerbation of pneumonia, improving lung imaging\n findings, and promoting virus-negative conversion and shortening the disease course (China,\n 100 patients). We found no published studies comparing different dosages of CQ/HCQ and\n their thorough safety assessment. </p>\n</blockquote>\n\n<p>There's also a <a href=\"https://www.cmaj.ca/content/cmaj/early/2020/04/08/cmaj.200528.full.pdf\" rel=\"nofollow noreferrer\">CMAJ review</a> posted a few days before that Brazilian paper came out. It mentions the same studies from China and France, as far as I can tell, and discusses the safety concerns from the general knowledge/perspective of CQ use in malaria etc.</p>\n\n<p>Of the Chinese studies, the <a href=\"https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v3.full.pdf\" rel=\"nofollow noreferrer\">Wuhan one</a> reported as adverse events (on 31 HCQ-treated patients) only</p>\n\n<blockquote>\n <p>2 patients with mild adverse reactions in the HCQ treatment group [...] one patient developed a rash, and one patient experienced a headache</p>\n</blockquote>\n\n<p>but this was with</p>\n\n<blockquote>\n <p>5-day HCQ (400 mg/d) treatment</p>\n</blockquote>\n\n<p>There's a much shorter <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/32074550\" rel=\"nofollow noreferrer\">\"Breakthrough\"</a> (yeah, that's a word from its title) paper on the Chinese studies, which alas covers a lot more of them, but it's pretty contrieved in just annoucing:</p>\n\n<blockquote>\n <p>A number of subsequent clinical trials [ChiCTR ids list] have\n been quickly conducted in China to test the efficacy\n and safety of chloroquine or hydroxychloroquine in the\n treatment of COVID-19 associated pneumonia in more\n than 10 hospitals in Wuhan, Jingzhou, Guangzhou,\n Beijing, Shanghai, Chongqing, and Ningbo</p>\n \n <p>Thus far,\n results from more than <strong>100 patients</strong> have demonstrated\n that chloroquine phosphate is superior to the control\n treatment in inhibiting the exacerbation of pneumonia,\n improving lung imaging findings, promoting a virus negative\n conversion, and shortening the disease\n course according to the news briefing. <strong>Severe adverse\n reactions to chloroquine phosphate were not noted in\n the aforementioned patients.</strong></p>\n</blockquote>\n\n<p>More annoyingly, it says absolutely nothing about dosage.</p>\n\n<p>And as far as I can tell the <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102549/\" rel=\"nofollow noreferrer\">French study</a> does not mention any adverse reactions either. The dose administered was 600mg/day.</p>\n\n<p>On the other hand, a <a href=\"https://www.bmj.com/content/369/bmj.m1335.full\" rel=\"nofollow noreferrer\">BMJ news/review</a> (Apr 1) of this French paper says:</p>\n\n<blockquote>\n <p>Although Raoult reported the results as positive, he excluded from the analysis six patients in the hydroxychloroquine arm because they had not remained in the study for six days. The reasons for non-completion were that one patient died, three were transferred to the intensive care unit (ICU), and two withdrew. None of the 16 patients in the control group died, withdrew, or needed care in an ICU. [...]</p>\n \n <p>Eight days after his initial study, Raoult posted the results of an uncontrolled observational study of 80 patients. In that study one patient died and one remained in the ICU at the time of the report, putting the case fatality rate at 1.3% or 2.5%, depending on the outcome of the ICU patient. This compares with case fatality rates in Germany and the US of 0.9% and 1.8%, respectively.</p>\n \n <p>Raoult did not respond to requests for an interview by <em>The BMJ</em>.</p>\n</blockquote>\n\n<p>Another BMJ <a href=\"https://www.bmj.com/content/369/bmj.m1432\" rel=\"nofollow noreferrer\">editorial</a> published a week later is also quite critical of the CQ studies published thus far.</p>\n\n<p>Apparently the protest/questions directed at the French paper have resulted in a <a href=\"https://www.isac.world/news-and-publications/official-isac-statement\" rel=\"nofollow noreferrer\">official reaction</a> from the journal board (this was mentioned in \"quick reactions\" the later BMJ piece)</p>\n\n<blockquote>\n <p>Official Statement from International Society of Antimicrobial Chemotherapy (ISAC)</p>\n \n <p>Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial (Gautret P et al. PMID 32205204)</p>\n \n <p>ISAC shares the concerns regarding the above article published recently in the International Journal of Antimicrobial Agents (IJAA). <strong>The ISAC Board believes the article does not meet the Society’s expected standard, especially relating to the lack of better explanations of the inclusion criteria and the triage of patients to ensure patient safety.</strong></p>\n \n <p>Despite some suggestions online as to the reliability of the article's peer review process, the process did adhere to the industry's peer review rules. Given his role as Editor in Chief of this journal, Jean-Marc Rolain had no involvement in the peer review of the manuscript and has no access to information regarding its peer review. Full responsibility for the manuscript's peer review process was delegated to an Associate Editor.</p>\n \n <p>Although ISAC recognises it is important to help the scientific community by publishing new data fast, this cannot be at the cost of reducing scientific scrutiny and best practices. Both Editors in Chief of our journals (IJAA and Journal of Global Antimicrobial Resistance) are in full agreement.</p>\n \n <p>Andreas Voss\n ISAC President</p>\n \n <p>April 3rd-2020</p>\n</blockquote>\n\n<p><em>The Lancet</em> <a href=\"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30817-5/fulltext\" rel=\"nofollow noreferrer\">noted (on Apr 11)</a> that contra France (and US/FDA), based on current data, the European Medicines Agency is not convinced CQ/HCQ has any role in treating Covid-19.</p>\n\n<p>See also, <a href=\"https://annals.org/aim/fullarticle/2764587/annals-call-covid-19-chloroquine-answer\" rel=\"nofollow noreferrer\">podcast discussion</a> on Annals of Internal Medicine and <em>Science Translational Medicine</em> <a href=\"https://blogs.sciencemag.org/pipeline/archives/2020/03/29/more-on-cloroquine-azithromycin-and-on-dr-raoult\" rel=\"nofollow noreferrer\">blog</a> critical of the 2nd (draft) French study. The latter piece notes that at one point:</p>\n\n<blockquote>\n <p>Raoult and several of his co-authors were banned from publishing in any ASM (American Society for Microbiology) journals for a year.</p>\n</blockquote>\n\n<hr>\n\n<p>A more recent <a href=\"https://www.medrxiv.org/content/10.1101/2020.04.10.20060699v1.full.pdf\" rel=\"nofollow noreferrer\">French study</a> (not from the Raoult group) found that HCQ wasn't effective (or more precisely that the effect wasn't statistically significant--although just a preprint it was also <a href=\"https://edition.cnn.com/2020/04/15/health/new-french-study-hydroxychloroquine/index.html\" rel=\"nofollow noreferrer\">covered by CNN</a> on April 15). The study also found some patients had to discontinue HCQ due to ECG changes:</p>\n\n<blockquote>\n <p>This study included 181 patients with SARS-CoV-2 pneumonia; 84 received HCQ within\n 48 hours of admission (HCQ group) and 97 did not (no-HCQ group). Initial severity was well\n balanced between the groups. In the weighted analysis, 20.2% patients in the HCQ group\n were transferred to the ICU or died within 7 days vs 22.1% in the no-HCQ group (16 vs 21\n events, relative risk [RR] 0.91, 95% CI 0.47–1.80). In the HCQ group, 2.8% of the patients\n died within 7 days vs 4.6% in the no-HCQ group (3 vs 4 events, RR 0.61, 95% CI 0.13–2.89),\n and 27.4% and 24.1%, respectively, developed acute respiratory distress syndrome within 7\n days (24 vs 23 events, RR 1.14, 95% CI 0.65–2.00). <strong>Eight patients receiving HCQ (9.5%)\n experienced electrocardiogram modifications requiring HCQ discontinuation.</strong></p>\n \n <p>Interpretation: These results do not support the use of HCQ in patients hospitalised for documented SARSCoV-2-positive hypoxic pneumonia. </p>\n</blockquote>\n\n<p>(The HCQ dose was 600 mg daily.)</p>\n", "score": 3 } ]

[ "covid-19", "treatment", "hydroxychloroquine" ]

[ { "answer_id": 23231, "body": "<p>To clarify there are different types of ventilation where ventilation means to assist the delivery of oxygen to a patient.</p>\n\n<h2>Non-invasive Ventilation (NIV)</h2>\n\n<ul>\n<li><p>Without significantly increasing pressure in the airways</p>\n\n<ul>\n<li><p>Masks</p></li>\n<li><p>high flow nasal cannula </p></li>\n</ul></li>\n<li><p>Positive airways pressure </p>\n\n<ul>\n<li><p>CPAP</p></li>\n<li><p>BPAP</p></li>\n</ul></li>\n<li><p>Negative Pressure Ventilation</p>\n\n<ul>\n<li>Iron lungs</li>\n</ul></li>\n</ul>\n\n<h2>Invasive Ventilation</h2>\n\n<ul>\n<li>intubation or tracheostomy delivered</li>\n</ul>\n\n<p>It sounds like you're asking when treating a case of ARDS when does one switch from using a mask/cannula to using CPAP/BPAP.</p>\n\n<p><img src=\"https://www.uptodate.com/contents/images/PULM/108315/Helmetinterface.jpg\" alt=\"\"></p>\n\n<blockquote>\n <p>Several types of helmets are commercially available in Europe, each with different features. There are no helmets commercially available for use with NIV in the US, but one helmet is approved for use in bariatric chambers to protect against excessively high oxygen tensions. This graphic shows a representative image of helmet interface used to deliver noninvasive ventilation. Shown are ventilation ports for the administration and removal of gas flow and a rubber seal at the neck, while others have additional optional features including ports for the introduction of catheters and under-arm straps for extra security to ensure a tight seal.</p>\n</blockquote>\n\n<p>ARDS is by definition a severe illness and it's usually only at the very early stages that a patient can be managed using NIV positive airways pressure ventilation. </p>\n\n<blockquote>\n <p>Noninvasive ventilation (NIV; ie, ventilation via a mask or nasal prongs with breaths delivered by a NIV device) may be reserved for the <strong>occasional patient with mild ARDS who is hemodynamically stable, is easily oxygenated, does not need immediate intubation, and has no contraindications to its use.</strong> This approach is based upon our experience and conflicting data regarding the benefit of NIV (eg, prevention of intubation, improved mortality) in this population. Importantly, when NIV is implemented, frequent evaluation is necessary and clinicians should have a low threshold for intubation.</p>\n</blockquote>\n\n<p>However, there are risks from such an approach</p>\n\n<blockquote>\n <p>In contrast, a study of patients with hypoxemic respiratory failure, many of whom had ARDS, reported increased mortality in association with NIV when compared with patients treated with high flow nasal cannula (HFNC)</p>\n</blockquote>\n\n<p>So, at least some studies suggest that switching from masks/cannula to using positive airways pressure could increase mortality. Whereas other studies suggest using a helmet may reduce the mortality and increase the number of days free of intubation.</p>\n\n<p><a href=\"https://www.uptodate.com/contents/ventilator-management-strategies-for-adults-with-acute-respiratory-distress-syndrome\" rel=\"nofollow noreferrer\">https://www.uptodate.com/contents/ventilator-management-strategies-for-adults-with-acute-respiratory-distress-syndrome</a></p>\n", "score": 5 }, { "answer_id": 23230, "body": "<p>Obviously depends on the exact case at hand, but from what I know, non mechanical ventilation (ie. Venti mask, etc.) Is only used for very mild ARDS where there is fairly good oxygenation and the patient is hemodynamically stable (good blood pressure and heart rate), able to keep their airway open, no copious secretions, etc. (<a href=\"https://www.ncbi.nlm.nih.gov/pubmed?term=22020236\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pubmed?term=22020236</a>). In moderate or severe ARDS, intubation is usually used (most cases end up requiring at least some form of ventilation). </p>\n\n<p>Yes, you are absolutely correct. Mechanical ventilation is when there is pressure forcing air in, while non mechanical is not forcing any air in and rather providing more oxygen flow. </p>\n", "score": 3 }, { "answer_id": 23234, "body": "<p>note- I won't accept my own answer, as discussion with others here has helped contribute to it.</p>\n\n<p>I'm a lay person.</p>\n\n<p>Having discussed this with people, I now see there is some confusion in the question, which if cleared up, would make for a clearer question. To address the confusion, the question asks.</p>\n\n<blockquote>\n <p>\"When somebody has ARDS, when is non-mechanical ventilation used, vs\n mechanical ventilation? (I'm talking no intubation, no sedation)\"</p>\n</blockquote>\n\n<p>One person I spoke to has said</p>\n\n<p>All ventilators are mechanical. And when people say mechanical, hands-free is meant - not manual. Machine operated. And a ventilator would be forcing air in at set intervals. (Note- there are CPAP machines that give a continuous supply of air, but they are not ventilators. <a href=\"https://geekymedics.com/cpap-vs-niv-bipap\" rel=\"nofollow noreferrer\">https://geekymedics.com/cpap-vs-niv-bipap</a> ) </p>\n\n<p>Masks being fed a steady air supply wouldn't be ventilators. </p>\n\n<p>HFNC - not a ventilator. (it doesn't force air in at set intervals). </p>\n\n<p>NRB - not a ventilator</p>\n\n<p>NIV e.g.(NIPPV/NPPV or NPV) - are ventilators </p>\n\n<p>BVM <a href=\"https://www.redcross.org/store/disposable-bvm-bag-valve-mask-adult-size/760002.html\" rel=\"nofollow noreferrer\">https://www.redcross.org/store/disposable-bvm-bag-valve-mask-adult-size/760002.html</a> wouldn't be considered a ventilator 'cos it's hand operated.</p>\n\n<p>Also, regarding the term \"mechanical ventilator\" I think it's not really used much as the qualifier doesn't add anything, as when somebody says ventilator, they mean that hands free machine device forcing air in in a timed manner, it's a machine, hands free, not manual. The term \"mechanical ventilator\" gets 523K results on google. The term \"mechanical ventilation\" gets 6.6 million results. </p>\n\n<p>The term ventilation is not particular to medicine and means supplying air to some enclosed space. Medicine does have non-mechanical ventilation. A Bag Valve Mask <a href=\"https://en.wikipedia.org/wiki/Bag_valve_mask\" rel=\"nofollow noreferrer\">https://en.wikipedia.org/wiki/Bag_valve_mask</a> would be a form of manual ventilation. And as that link mentions, you also have \"mouth to mouth ventilation\", whicj would also be manual. </p>\n\n<p>In terms of English, machines that don't force air e.g. HFNC would not be ventilation devices 'cos it helps get oxygen in, rather than helps with breathing(getting air in/out). </p>\n\n<p>A BPAP or CPAP machine for sleep apnea machine that does a bit of the work of breathing, could perhaps be a ventiation device. But not a ventilator. A ventilator is capable of handling a person's breathing completely. Like a sleep apnea BPAP machine but with more power.</p>\n\n<p>Specific to medicine, is the term \"mechanical ventilation\", a form of respiratory therapy, with ventilators. <a href=\"https://www.resmed.co.uk/healthcare-professional/respiratory-care/respiratory-therapy/\" rel=\"nofollow noreferrer\">https://www.resmed.co.uk/healthcare-professional/respiratory-care/respiratory-therapy/</a> And when they speak of non-invasive ventilation, they talk of non-invasive ventilators.</p>\n\n<p>So the question could be split into the question about mechanical ventilators, and a question of, when somebody has ARDS, when are they moved from HFNC or NRB, to NPPV and eventually perhaps to an (invasive) ventilator(i.e. ventilator with intubation). </p>\n", "score": 0 } ]

[ "covid-19", "mechanical-ventilation" ]

[ { "answer_id": 23227, "body": "<p><strong>Hemophagocytic lymphohistiocytosis</strong> (HLH) syndrome is a life-threatening condition commonly triggered by viral illness. It is caused by over-activated macrophages and low NK cell/cytotoxic T-cell activity, leading to increased cytokine release (cytokine storm) and organ failure. A non-exhaustive list of clinical features of this syndrome includes:</p>\n\n<ul>\n<li>fever</li>\n<li>splenomegaly</li>\n<li>cytopenia</li>\n<li>hypertriglyceridemia/hypofibrinogenemia</li>\n<li>increased ferritin</li>\n<li>macrophage phagocytosis of red blood cells in bone marrow, spleen, lymph node, or liver</li>\n</ul>\n\n<p>COVID-19 infection seems to trigger a similar cytokine storm as HLH, as according to a Lancet paper[1]</p>\n\n<blockquote>\n <p>A cytokine profile resembling sHLH is associated with COVID-19 disease severity, characterised by increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumour necrosis factor-α.</p>\n</blockquote>\n\n<p>Cytokine storm is classically treated with IL-6 receptor inhibitors such as tocilizumab.</p>\n\n<p>A preliminary study from China[2] has also shown that in a sample size 21 severe or critical COVID-19 patients treated with tocilizumab, 75% of patients needed oxygen therapy and there were no mortalities after 2 weeks of the study. Due to a low sample size and lack of control group, this is just an initial finding, but has prompted larger clinical trials on the efficacy of il-6 inhibitors for COVID-19.</p>\n\n<p>Currently, two major U.S. clinical trials are being done on il-6 receptor inhibitors:</p>\n\n<ol>\n<li>Sanofi and Regeneron Pharmaceuticals is evaluating <strong>sarilumab</strong>[3]</li>\n<li>Genentech (of Roche Group) is evaluating <strong>tocilizumab</strong> in the COVACTA trial[4]</li>\n</ol>\n\n<p>Source:</p>\n\n<ol>\n<li><a href=\"https://doi.org/10.1016/S0140-6736(20)30628-0\" rel=\"nofollow noreferrer\">COVID-19: consider cytokine storm syndromes and immunosuppression</a></li>\n<li><a href=\"http://www.chinaxiv.org/abs/202003.00026\" rel=\"nofollow noreferrer\">Effective Treatment of Severe COVID-19 Patients with Tocilizumab</a></li>\n<li><a href=\"http://www.news.sanofi.us/2020-03-16-Sanofi-and-Regeneron-begin-global-Kevzara-R-sarilumab-clinical-trial-program-in-patients-with-severe-COVID-19\" rel=\"nofollow noreferrer\">http://www.news.sanofi.us/2020-03-16-Sanofi-and-Regeneron-begin-global-Kevzara-R-sarilumab-clinical-trial-program-in-patients-with-severe-COVID-19</a></li>\n<li><a href=\"https://www.genengnews.com/virology/coronavirus/genentech-launches-phase-iii-trial-of-actemra-as-coronavirus-treatment/\" rel=\"nofollow noreferrer\">https://www.genengnews.com/virology/coronavirus/genentech-launches-phase-iii-trial-of-actemra-as-coronavirus-treatment/</a></li>\n</ol>\n", "score": 2 } ]

[ "covid-19", "treatment", "treatment-options", "cytokines" ]

[ { "answer_id": 23260, "body": "<p><a href=\"https://www.beiresources.org/Portals/2/PDFS/Long-Term%20and%20Short-Term%20Stability%20of%20Viruses.pdf\" rel=\"nofollow noreferrer\">It's true</a> for practically every virus that they are viable for longer at lower temperatures. Unless they are cultured, storing [freeze dried] viruses below -20C is the only way to keep them viable for decades. (More typically they are held below -70C as a safety margin.)</p>\n\n<blockquote>\n <p>The ability to store viruses for long periods of time with minimal loss of viability is critical [well, for research]. Even more than most organisms, many\n viruses are fragile and degrade quickly unless stored at low temperatures. The ATCC® and BEI Resources collections offer a\n unique opportunity to study the stability of various viruses under different conditions. The ATCC® Virology Collection, which\n celebrates 50 years of operation in 2008, contains more than 2,500 different holdings spanning decades of storage time using\n many different storage methods. A retrospective study was performed to evaluate the short and long-term viability of various\n holdings of influenza virus within the ATCC® collection, using virus stocks that had been grown and titered as long ago as 1968 (40\n years) up to as recently as 2007 (3 months). Influenza and parainfluenza viruses prepared from 1968 to 1992 were either in liquid\n form or were lyophilized, while preparations after 1992, were only stored in liquid form at -70°C or in vapor phase of liquid nitrogen\n (approximately -125°C). In addition, a prospective study was performed by holding viruses at -80°C, -20°C, 4°C, room temperature\n (~20°C) and 37°C for various lengths of time with periodic re-titration. All testing was performed in specific pathogen free\n embryonated chicken eggs in order to obtain the 50% chicken egg infectious dose (CEID50 ). Titers were then plotted and rate of\n decay (log of titer loss per unit time - D10 values) was calculated. When stored at -20°C, -70°C or in liquid nitrogen, most influenza\n and parainfluenza viruses maintained viability with no significant loss of titer over the study period. One influenza isolate was seen\n to lose approximately 1 log of titer over a 16 year period when stored at -70°C. This drop in viability opens the possibility of strain-to-strain differences in storage. <strong>Viruses stored at temperatures above -20°C showed a direct correlation between temperature and\n decay rate, with the virus stored at 37°C having the highest rate of decay.</strong> From these data, we conclude that of the various\n methods employed at ATCC® and BEI Resources for the storage of virus preparations, storage in liquid form in the vapor phase of\n liquid nitrogen offers the benefits of simple, safe storage and excellent recovery [...]</p>\n</blockquote>\n\n<p>An ancient giant virus was <a href=\"https://www.nature.com/news/giant-virus-resurrected-from-30-000-year-old-ice-1.14801\" rel=\"nofollow noreferrer\">discovered</a> in permafrost in 2014; it's estimated it had remained viable for 30,000 years.</p>\n\n<blockquote>\n <p>Two years ago, Claverie and Abergel's team learned that scientists in Russia had resurrected an ancient plant from fruits buried in 30,000-year-old Siberian permafrost. “If it was possible to revive a plant, I wondered if it was possible to revive a virus,” says Claverie. Using permafrost samples provided by the Russian team, they fished for giant viruses by using amoebae — the typical targets of these pathogens — as bait. The amoebae started dying, and the team found giant-virus particles inside them.</p>\n</blockquote>\n\n<p>More relevantly, there have been such cases of viruses dangerous to us, like hepatitis or norovirus being found <a href=\"https://www.fda.gov/food/cfsan-constituent-updates/fda-sampling-frozen-berries-harmful-viruses\" rel=\"nofollow noreferrer\">e.g. in frozen berries</a>.</p>\n\n<blockquote>\n <p>Frozen berries are used as ingredients in many foods and like other produce can be an important part of a healthy eating pattern. While frozen berries are used in pies and other baked goods, they are also used raw in fruit salads or smoothies and have been associated with outbreaks of foodborne illness. <strong>The FDA reported three hepatitis A virus outbreaks and one norovirus outbreak linked to frozen berries in the United States from 1997 to 2016.</strong></p>\n</blockquote>\n\n<p>But note that we didn't abandon using fridges for our food for this reason (that viruses are viable for a long time once frozen)...</p>\n\n<p>In particular, since you mentioned Covid-19 outbreaks at meat factories, we usually cook meat before eating it, so most dagner is probably to factory workers rather than consumers. So far the FDA has not reported any outbreaks/clusters of Covid-19 as being caused by food sources. Additionally, they mention <a href=\"https://www.fda.gov/food/food-safety-during-emergencies/food-safety-and-coronavirus-disease-2019-covid-19\" rel=\"nofollow noreferrer\">that</a></p>\n\n<blockquote>\n <p>Unlike foodborne gastrointestinal (GI) viruses like norovirus and hepatitis A that often make people ill through contaminated food, SARS-CoV-2, which causes COVID-19, is a virus that causes respiratory, not gastrointestinal, illness. <strong>Foodborne exposure to this virus is not known to be a route of transmission.</strong></p>\n</blockquote>\n", "score": 3 } ]

[ "covid-19", "coronavirus" ]

[ { "answer_id": 23282, "body": "<p>Regarding calcium transport in the kidney:</p>\n\n<blockquote>\n <p>In contrast with the proximal tubule and the thick ascending limb of\n the loop of Henle, the distal tubule reabsorbs calcium exclusively via\n the transcellular route.</p>\n</blockquote>\n\n<p><a href=\"https://i.stack.imgur.com/j2XNY.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/j2XNY.png\" alt=\"enter image description here\"></a></p>\n\n<p>See also: <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491294/\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491294/</a></p>\n\n<p>Also, calcium availability in blood (and hence for filtration in the kidney) is dependent on pH - higher pH will increase binding of calcium to albumine (this is happens e. g. in plasmapheresis when EDTA is added to your blood to prevent coagulation outside of your body); see also: <a href=\"https://www.kidney-international.org/article/S0085-2538(15)57007-5/pdf\" rel=\"nofollow noreferrer\">https://www.kidney-international.org/article/S0085-2538(15)57007-5/pdf</a></p>\n\n<blockquote>\n <p>In the distal convoluted tubule (DCT) and connecting tubule (CNT),\n acidosis effects the expression of TRPV5, but also the luminal H+\n concentration has direct effects on TRPV5 activity (H+ inhibits). </p>\n \n <p>Consequently, bicarbonaturia, by increasing luminal pH increases TRPV5\n activity. There is debate as to whether there is significant calcium\n reabsorption from the collecting duct. However, α intercalated cells\n in this segment, when unable to secrete protons such as with dRTA,\n will fail to acidify the urine altering the solubility of calcium\n salts. In the proximal tubule, a high pH inhibits citrate reabsorption\n (as observed in pRTA).</p>\n \n <p>Patients with dRTA have long been appreciated to also have a disorder\n of sodium wasting.73 The molecular details of how the vacuolar\n H+-ATPase in the collecting duct contributes to sodium reabsorption\n were recently described. In combination with pendrin and Slc4A8, the\n H+-ATPase mediates thiazide-sensitive sodium reabsorption through the\n β-intercalated cell under situations of volume depletion.72,88,89\n Mutations in either disease causing subunits would therefore prevent\n transcellular sodium reabsorption via this mechanism. Consequently,\n patients with mutations in the H+-ATPase would be prone to volume\n contraction and, as has been suggested for mutations in NCC, have\n increased proximal tubular sodium and consequently calcium\n reabsorption. Thus, if volume contracted, these patients would further\n attenuate hypercalciuria induced by metabolic acidosis. However, it\n should also be noted that volume contraction could exacerbate\n nephrocalcinosis and nephrolithiasis by decreasing urinary flow\n resulting in increased urine supersaturation of calcium, phosphate, or\n oxalate.</p>\n</blockquote>\n\n<p>Source: <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118493/\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118493/</a></p>\n", "score": 2 } ]

[ "side-effects", "renal", "diuretics", "mechanism-of-action" ]

[ { "answer_id": 23336, "body": "<p>Almost every single person in the entire USA has been sick in their lifetime. And the vast majority of everyone has gotten the flu or the common cold. <a href=\"https://www.cdc.gov/flu/about/burden/index.html\" rel=\"nofollow noreferrer\">1</a> <a href=\"https://www.cdc.gov/dotw/common-cold/index.html\" rel=\"nofollow noreferrer\">2</a> This is because they are pretty contagious and there is almost no way of stopping the spread if everyone is out and about. <a href=\"https://www.cdc.gov/coronavirus/2019-ncov/downloads/2019-ncov-factsheet.pdf\" rel=\"nofollow noreferrer\">3</a> </p>\n\n<p>So in the quote above, Ben Shapiro is explaining that the same will happen with COVID-19. And that makes total sense because the country can not and will not stay in lockdown. <a href=\"https://www.politico.com/news/2020/03/23/trump-coronavirus-lockdown-skepticism-143800\" rel=\"nofollow noreferrer\">4</a> Thus it will spread person to person when in close contact. <a href=\"https://www.cdc.gov/coronavirus/2019-ncov/downloads/2019-ncov-factsheet.pdf\" rel=\"nofollow noreferrer\">3</a> The whole point of a lockdown is to not overwhelm the health care system. <a href=\"https://www.npr.org/sections/goatsandsoda/2020/04/15/834021103/who-sets-6-conditions-for-ending-a-coronavirus-lockdown\" rel=\"nofollow noreferrer\">5</a> So answering your second question, the percentage of people that will NOT get COVID-19 over the next few decades is very very low. </p>\n", "score": 3 } ]

[ "covid-19", "disease-transmission", "epidemiology", "coronavirus", "infectious-diseases" ]

[ { "answer_id": 23416, "body": "<p>I don't see that we can have that data yet, nor can it be answered simply. In Wuhan, Italy and New York when ICUs were being overwhelmed with patients, and there was a ventilator shortage, then only the most sick were being invasively ventilated, and others were left to die. Or, ventilators were split so that each patient shared the same settings which is not ideal. Or, patients were not being ventilated early enough after a failure of (high flow nasal cannulae) HFNC and were switched to CPAP/BiPAP. And there is controversy whether HFNC should be used in an ideal situation as COVID-19 patient can crash easily requiring urgent intubation so it may be better to switch to IV early.</p>\n\n<p>Then you have to look at the patient demographics. Italian patients tended to be older with more co-morbid conditions whereas younger patients needing ventilation were more likely to survive. In an elderly population needing invasive ventilation the mortality rate was higher than 90%</p>\n\n<p>The most recent data is from New York and given the constraints above</p>\n\n<blockquote>\n <p>Mortality rates for those who received mechanical ventilation in the 18-to-65 and older-than-65 age groups were 76.4% and 97.2%, respectively. Mortality rates for those in the 18-to-65 and older-than-65 age groups who did not receive mechanical ventilation were 19.8% and 26.6%, respectively.²</p>\n</blockquote>\n\n<p>Settings are fairly standard and include standardized ventilator protocols and proning.</p>\n\n<p><strong>Update from New York study 27 April 2020</strong></p>\n\n<blockquote>\n <p>It found that, overall, about 20% of Covid-19 patients treated at Northwell Health died, and 25% of those placed on ventilators died. A ventilator is a device that forces air into the lungs of patients who cannot breathe on their own because of severe pneumonia or acute respiratory distress syndrome.³</p>\n</blockquote>\n\n<ol>\n<li><strong>April 7, 2020</strong>: <a href=\"https://www.medscape.com/viewarticle/928259\" rel=\"nofollow noreferrer\">https://www.medscape.com/viewarticle/928259</a></li>\n<li><strong>April 22, 2020</strong>: Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area\n<a href=\"https://jamanetwork.com/journals/jama/fullarticle/2765184\" rel=\"nofollow noreferrer\">https://jamanetwork.com/journals/jama/fullarticle/2765184</a></li>\n<li><a href=\"https://edition.cnn.com/2020/04/22/health/coronavirus-ventilator-patients-die/index.html\" rel=\"nofollow noreferrer\">https://edition.cnn.com/2020/04/22/health/coronavirus-ventilator-patients-die/index.html</a></li>\n</ol>\n", "score": 3 } ]

[ "covid-19", "mechanical-ventilation", "icu-intensive-care-unit", "mortality-rate" ]

[ { "answer_id": 23436, "body": "<p>Definitive proof would be by challenge by live virus as might have to be done with possible vaccine trials</p>\n<blockquote>\n<p>As a result, some scientists have proposed a way to speed up the process – by deliberately exposing volunteers to the virus to determine a vaccine’s efficacy. “This approach is not without risks but has the potential to expedite candidate vaccine testing by many months,” says Nir Eyal, a professor of bioethics at Rutgers University.</p>\n<p>Volunteers would have to be young and healthy, he stresses: “Their health would also be closely monitored, and they would have access to intensive care and any available medicines.” The result could be a vaccine that would save millions of lives by being ready for use in a much shorter time than one that went through standard phase three trials.</p>\n<p>But deliberately infecting people – in particular volunteers who would be given a placebo vaccine as part of the trial – is controversial. “This will have to be thought through very carefully,” says Prof Adam Finn of Bristol University. “Young people might jump at the opportunity to join such a trial but this is a virus that does kill the odd young person. We don’t know why yet. However, phase-three trials are still some way off, so we have time to consider the idea carefully.”</p>\n</blockquote>\n<p>One would hope that they had immune sera and other facilities available if the trials go badly, and that might happen considering the virus can rapidly mutate so immunity to one strain might not at all protect against another.</p>\n<p><a href=\"https://www.theguardian.com/world/2020/apr/24/coronavirus-what-have-scientists-learned-about-covid-19-so-far\" rel=\"nofollow noreferrer\">https://www.theguardian.com/world/2020/apr/24/coronavirus-what-have-scientists-learned-about-covid-19-so-far</a></p>\n", "score": 4 } ]

[ "covid-19", "immune-system" ]

[ { "answer_id": 23768, "body": "<p>The virus has actually continued to spread during the lockdowns, just at a slower pace than if no lockdown had been imposed. See for example <a href=\"https://www.doh.wa.gov/Emergencies/NovelCoronavirusOutbreak2020COVID19/DataDashboard\" rel=\"nofollow noreferrer\">Washington state in the USA</a>.</p>\n\n<p>The hope is that the lockdowns have reduced the spread of infections to <a href=\"https://en.wikipedia.org/wiki/Exponential_growth\" rel=\"nofollow noreferrer\">linear or sub-linear rather than exponential growth</a>. Linear or sub-linear growth provides an opportunity for other measures to be effective, like wide spread testing followed by <a href=\"https://www.cdc.gov/coronavirus/2019-ncov/php/open-america/contact-tracing-resources.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fphp%2Fopen-america%2Fcontact-tracing.html\" rel=\"nofollow noreferrer\">contact tracing</a>. If test and trace works, this would allow quarantine of only those who actually have the virus, or are known to have been exposed, rather than asking that <em>everyone</em> stay in lockdown preemptively.</p>\n\n<p><a href=\"https://www.cnn.com/2020/04/16/world/coronavirus-response-lessons-learned-intl/index.html\" rel=\"nofollow noreferrer\">It is argued that extensive contact tracing followed by targeted quarantine is what has allowed Germany, Taiwan, and South Korea</a> to avoid the massive outbreaks seen in Italy, Spain, and the Americas. However, if the number of new infections was doubling every few days, no testing and tracing system would be able to keep up.</p>\n", "score": 4 }, { "answer_id": 23434, "body": "<p><a href=\"https://edition.cnn.com/2020/03/12/world/coronavirus-covid-19-update-intl-hnk/index.html\" rel=\"nofollow noreferrer\">China</a> and <a href=\"https://www.reuters.com/article/us-health-coronavirus-newzealand/new-zealand-orders-quarantine-for-returning-citizens-in-coronavirus-battle-idUSKCN21R0D4\" rel=\"nofollow noreferrer\">New Zealand</a> are quarantining all returning citizens for 14 days.</p>\n\n<p>That could be beefed up by antibody testing and rt-PCR if those become readily available.</p>\n\n<p>That should halt the importation of the virus. And continued social distancing may be necessary for a couple of years yet.</p>\n\n<p>NZ is on target to <strong>completely eliminate the virus</strong> with no new cases for some days now, current cases no longer considered infectious and the only risk being from imported cases.</p>\n\n<p><a href=\"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31097-7/fulltext\" rel=\"nofollow noreferrer\">https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31097-7/fulltext</a></p>\n", "score": 2 } ]

[ "covid-19", "disease-transmission" ]

[ { "answer_id": 23476, "body": "<p>The story for these \"common cold\" coronaviruses is a slightly complicated. <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456285/\" rel=\"nofollow noreferrer\">Mostly</a>, these target different receptors (than the SARS family), except for NL63.</p>\n\n<p><a href=\"https://i.stack.imgur.com/rU3Rz.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/rU3Rz.png\" alt=\"enter image description here\"></a></p>\n\n<blockquote>\n <p>The host receptor is a major determinant of pathogenicity, tissue tropism and host range of the\n virus. The S protein comprises of two domains: S1 and S2. The interaction between the S1 domain and\n its cognate receptor triggers a conformational change in the S protein, which then promotes membrane\n fusion between the viral and cell membrane through the S2 domain. Today, the main host cell receptors\n utilised by all HCoVs are known: <strong>aminopeptidase N by HCoV-229E, angiotensin-converting\n enzyme 2 (ACE2) by SARS-CoV and HCoV-NL63, dipeptidyl peptidase 4 (DPP4) by\n MERS-CoV and 9-O-acetylated sialic acid by HCoV-OC43 and HCoV-HKU1</strong>.</p>\n \n <p>Apart from the conventional endosomal route of entry, some CoVs may also gain entry into\n the cell via the non-endosomal pathway, or a combination of both. The low pH in the cellular\n environment and endosomal cysteine protease cathepsins may help to facilitate membrane fusion and\n endosomal CoV cell entry . Recent evidence has supported the role of cathepsin L in SARS-CoV and\n MERS-CoV entry. Other host proteases, such as transmembrane protease serine 2 (TMPRSS2)\n and airway trypsin-like protease TMPRSS11D, could also perform S1/S2 cleavage to activate the S\n protein for non-endosomal virus entry at the cell plasma membrane during HCoV-229E and SARS-CoV\n infection. In addition, MERS-CoV is also activated by furin, a serine endopeptidase that has\n been implicated in the cell entry of other RNA viruses and S1/S2 cleavage during viral egress.</p>\n</blockquote>\n\n<p>It's worth reading some of the more <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/16339146\" rel=\"nofollow noreferrer\">in-depth papers</a> on how NL63 entry differs from SARS (despite both using ACE2):</p>\n\n<blockquote>\n <p>Here we show that SARS-CoV, but not HCoV-NL63, utilizes the enzymatic activity of the cysteine protease cathepsin L to infect ACE2-expressing cells. Inhibitors of cathepsin L blocked infection by SARS-CoV and by a retrovirus pseudotyped with the SARS-CoV spike (S) protein but not infection by HCoV-NL63 or a retrovirus pseudotyped with the HCoV-NL63 S protein. Expression of exogenous cathepsin L substantially enhanced infection mediated by the SARS-CoV S protein and by filovirus GP proteins but not by the HCoV-NL63 S protein or the vesicular stomatitis virus G protein. Finally, an inhibitor of endosomal acidification had substantially less effect on infection mediated by the HCoV-NL63 S protein than on that mediated by the SARS-CoV S protein. Our data indicate that two coronaviruses that utilize a common receptor nonetheless enter cells through distinct mechanisms.</p>\n</blockquote>\n\n<p><a href=\"https://jvi.asm.org/content/82/17/8887\" rel=\"nofollow noreferrer\">https://jvi.asm.org/content/82/17/8887</a>: </p>\n\n<blockquote>\n <p>The S protein in the SARS-CoV spike apparently exposes a protease-accessible loop between the S1 and S2 subunits that can be targeted by different enzymes, such as cathepsin L, trypsin, and, under physiological conditions, local enzymes such as elastase. Consistent with the presence of such a loop, the syncytium-inducing capacity of expressed SARS-CoV S protein was dramatically enhanced after the introduction of a functional furin cleavage site in the S1/S2 junction region (8, 14). No such loop has been detected yet in spikes of HCoV-NL63 or of most other subgroup 1 coronaviruses. The resistance of the HCoV-NL63 spike ectodomain to cleavage by cathepsin L and trypsin that we observed here is in agreement with our inability to inhibit infection with HCoV-NL63 or an NL63 spike protein-pseudotyped retrovirus by using a broad spectrum of protease inhibitors (10). It is conceivable that during its low-pH-independent cell entry, HCoV-NL63 uses an alternative, possibly nonproteolytic way to activate the fusion function.</p>\n</blockquote>\n\n<p>So yeah, it looks easier to block SARS than even the NL63 common cold using the same receptor...</p>\n\n<p>A more recent <a href=\"https://www.sciencedirect.com/science/article/pii/S0092867420302622\" rel=\"nofollow noreferrer\">paper</a>, taking into account SARS-CoV-2 (Covid-19) has proposed that the more general distinction between the common colds and the more deadly coronaviruses is that:</p>\n\n<blockquote>\n <p>S glycoprotein trimers found in highly pathogenic human coronaviruses appear to exist in partially opened states, while they remain largely closed in human coronaviruses associated with common colds. [...] most pathogenic coronaviruses will exhibit S glycoprotein trimers spontaneously sampling closed and open conformations, as is the case for SARS-CoV-2, SARS-CoV and MERS-CoV.</p>\n</blockquote>\n\n<p>Also of note is that 229E and NL63 despite using different receptors are fairly related to each other, prompting the title of <a href=\"https://www.sciencedirect.com/science/article/pii/S0929664609600668\" rel=\"nofollow noreferrer\">one paper</a> \"close yet still so far [apart]\". (Those two viruses have 65% sequence identity, in retrospect less than SARS and SARS-CoV-2 similarity of around 80%.) But also</p>\n\n<blockquote>\n <p>ACE2 belongs to the same protease family as CD13 [(also known as aminopeptidase N)]</p>\n</blockquote>\n\n<p>Also of some interest, <a href=\"https://www.nature.com/articles/s41598-018-37747-5/figures/4\" rel=\"nofollow noreferrer\">in some immunoassay</a> SARS scored as a mix of 229E and NL63 response (plus some specific response). And an <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309958/\" rel=\"nofollow noreferrer\">article</a> on the putative common origin of 229E and NL63 in African bats.</p>\n", "score": 4 } ]

[ "infectious-diseases", "virus" ]

[ { "answer_id": 23518, "body": "<h2>Non-steroidal anti-inflammatory drugs and the kidneys</h2>\n\n<p>You’re right that non-steroidal anti-inflammatory drugs (NSAIDs) have an effect on the glomerular arterioles by inhibiting prostaglandin production. This is why they can be renotoxic; if the affereny arteriole constricts, the filtration pressure drops and this can lead to renal failure in susceptible individuals or those on interacting drugs (like angiotensin converting enzyme (ACE) inhibitors, which dilate the efferent arteriole).</p>\n\n<h2>Nephrolithiasis (kidney stones)</h2>\n\n<p>However, these arterioles are blood vessels. Kidney stones (renal calculi) form in the nephron or further down the drainage system in the ureters by the precipitation and crystallisation of calcium or oxalate salts.</p>\n\n<p>NSAIDs do reduce excretion of calcium, so it was thought they might reduce the formation of calculi. However, they also reduce secretion of other protective factors (such as glucosaminoglycans, or GAG), so there is no significant overall benefit, other than analgesia.</p>\n\n<p>I found this old paper from the <em>International Journal of Clinical Pharmacology, Therapy and Toxicology</em> that looked at the effects of the NSAID diclofenac in people with hypercalciuria (higher than normal calcium levels in the urine).</p>\n\n<blockquote>\n <p>Non-steroidal anti-inflammatory drugs decrease urinary calcium excretion in male\n Sprague-Dawley rats. Indomethacin decreases significantly the urinary\n calcium excretion in hypercalciuric patients. These observations\n encouraged the use of NSAID in the treatment of nephrolithiasis with\n encouraging initial results. However, NSAID (indomethacin and\n naproxen) retard both glycosaminoglycans (GAGs) synthesis and\n degradation thereby causing a significant reduction in the urinary\n excretion of GAGs, known to be potent inhibitors of calcium oxalate\n crystallization. Therefore, the effect of another NSAID, diclofenac-Na\n (50 mg t.i.d. for 4 weeks) was studied on 31 recurrent calcium oxalate\n nephrolithiasis patients who were not hypercalciuric or\n hyperuricosuric. The 24-h urinary excretion of creatinine, calcium and\n uric acid remained unchanged at 2 weeks and 4 weeks of therapy.\n However, after treatment of 2 weeks and 4 weeks, there was a\n significant decrease in the 24-h urinary excretion of GAGs (from 17.04\n +/- 7.39 mumol to 11.54 +/- 7.02 and 12.7 +/- 6.2 mumol, respectively), and urinary concentration of GAGs (from 10.77 +/- 7.09\n mumol/l to 6.03 +/- 5.00 mumol/l and 7.35 +/- 4.81 mumol/l,\n respectively). Thus diclofenac-Na (50 mg t.i.d.) did not reduce\n urinary excretion of calcium but significantly lowered the urinary\n excretion and concentration of GAGs in normocalciuric nephrolithiasis\n patients, an observation which cautions against the use of\n diclofenac-Na in prevention of nephrolithiasis in this group of\n patients.</p>\n</blockquote>\n\n<h2>Summary</h2>\n\n<p>Thus, the reason NSAIDs are used is for analgesia. They do not have an overall effect to reduce e stone formation and there is no mechanism by which they facilitate the passage of the stone. This is in keeping with <a href=\"https://www.qxmd.com/r/27032222\" rel=\"nofollow noreferrer\">current practice</a> on the management of neprolithiasis.</p>\n\n<p>To help facilitate the passage of a stone, <em><a href=\"https://europepmc.org/article/med/27032222\" rel=\"nofollow noreferrer\">alpha adrenoceptor antagonists</a></em> (like doxazosin) can be used. They relax the smooth muscle surrounding the ureters and urethra, allowing any calculi to pass more easily.</p>\n\n<hr>\n\n<h2>References</h2>\n\n<p>A K Hemal, H Sidhu, S K Thind, R Nath, S Vaidyanathan. Effect of diclofenac-Na on 24-hour urinary excretion of creatinine, calcium, uric acid and glycosaminoglycans in adult patients with recurrent calcium oxalate nephrolithiasis. <em>International Journal of Clinical Pharmacology, Therapy, and Toxicology</em>. 1989 Jan; 27 (1) : 44-6.</p>\n\n<p>Conor P Moran, Aisling E Courtney. Managing acute and chronic renal stone disease. <em>Practitioner</em>. 2016 Feb; 260 (1790) : 17-20, 2-3.</p>\n\n<p>Renee R. Koski, PharmD, CACP, FMPA and William H. Zufall, PharmD. Efficacy and Safety of Alpha-Blockers for Kidney Stones in Adults. <em>Journal of Pharmacy Technology</em>, 2018 Apr; 34(2): 54–61. DOI: 10.1177/8755122517750398</p>\n", "score": 3 } ]

[ "nsaids-pain-meds", "kidney-stones" ]

[ { "answer_id": 23576, "body": "<p>From <a href=\"https://clinicaltrials.gov/ct2/about-studies/learn#WhatIs\" rel=\"nofollow noreferrer\">https://clinicaltrials.gov/ct2/about-studies/learn#WhatIs</a>:</p>\n\n<blockquote>\n <p>A clinical study involves research using human volunteers (also called participants) that is intended to add to medical knowledge. There are two main types of clinical studies: clinical trials (also called interventional studies) and observational studies. </p>\n</blockquote>\n\n<p>Note that unlike what the quote says, participants/subjects don't have to be human, e.g. see veterinary clinical trials.</p>\n", "score": 2 }, { "answer_id": 24938, "body": "<p>I think the term &quot;clinical study&quot; is broader in meaning than the term 'clinical trial'.</p>\n<p>I think a 'clinical trial' is a clinical study to obtain approval for an investigational drug or medical device, and the notion of the 'clinical study' includes studies that are not aimed at obtaining approval.</p>\n<p>So, 'the study to find the effect of &quot;Azadirachta indica&quot;' is a clinical study, but I think it is somewhat incongruous to call this a clinical trial. However, if the active ingredient is purified and then sought for approval as a drug, I think it would regarded as a clinical trial.</p>\n<p>The <a href=\"https://www.clinicaltrials.gov/ct2/about-studies/learn\" rel=\"nofollow noreferrer\">website</a> of ClinicalTrials.gov has following descriptions;</p>\n<blockquote>\n<p>There are two main types of clinical studies: clinical trials (also called interventional studies) and observational studies. ClinicalTrials.gov includes both interventional and observational studies.</p>\n</blockquote>\n<p>According to the description above, if it is an interventional study, it might be called a clinical trial.</p>\n", "score": 0 } ]

[ "clinical-study" ]

[ { "answer_id": 23930, "body": "<p>Unilateral carotid compression (Carotid Compression Test) is an important procedure before performing vascular surgery for either of the carotid arteries, because during the surgery, they need to be compressed upstream for obvious reasons.</p>\n<p>Numbers vary, but in 6%¹ to 26%² of patients, the compensation through the circle of willis was insufficient:</p>\n<blockquote>\n<p>Forty five patients showed no changes during the carotid compression. Two cases showed both weakness of the contralateral side and altered consciousness within 10 seconds of compression. A third patient developed profound altered consciousness with no discernable lateralizing signs. In all 3 cases, these findings were completely reversed within 5 seconds of release of digital compression.</p>\n</blockquote>\n<hr />\n<p>¹: <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866623/\" rel=\"noreferrer\">Naraynsingh V, Harnarayan P, Maharaj R, Dan D, Hariharan S. Preoperative digital carotid compression as a predictor of the need for shunting during carotid endarterectomy. Open Cardiovasc Med J. 2013;7:110-112. Published 2013 Nov 15. doi:10.2174/1874192401307010110</a></p>\n<p>²: <a href=\"http://Hetzel%20A,%20von%20Reutern%20G,%20Wernz%20MG,%20Droste%20DW,%20Schumacher%20M.%20The%20carotid%20compression%20test%20for%20therapeutic%20occlusion%20of%20the%20internal%20carotid%20artery.%20Comparison%20of%20angiography%20with%20transcranial%20Doppler%20sonography.%20Cerebrovasc%20Dis.%202000;10(3):194-199.%20doi:10.1159/000016056\" rel=\"noreferrer\">Hetzel A, von Reutern G, Wernz MG, Droste DW, Schumacher M. The carotid compression test for therapeutic occlusion of the internal carotid artery. Comparison of angiography with transcranial Doppler sonography. Cerebrovasc Dis. 2000;10(3):194-199. doi:10.1159/000016056</a></p>\n", "score": 5 } ]

[ "neurology", "stroke" ]

[ { "answer_id": 24105, "body": "<p>Its primary action is as NaSSA (a noradrenergic and specific serotonergic antidepressant), not as 5-HT3 inhibitor. If you have a look at e. g. the Wikipedia page (<a href=\"https://en.wikipedia.org/wiki/Mirtazapine#Pharmacodynamics\" rel=\"nofollow noreferrer\">https://en.wikipedia.org/wiki/Mirtazapine#Pharmacodynamics</a>), you will see that nausea is listed as side effect under &quot;discontinuation syndrome&quot;, i. e. sudden withdrawal from continuous 5-HT3 blocking.\nAs a side note, it also has H1-blocking effects, which are antiemetic as well.</p>\n<p>There are more withdrawal symptoms listed here: <a href=\"https://www.nami.org/About-Mental-Illness/Treatments/Mental-Health-Medications/Types-of-Medication/Mirtazapine-(Remeron)\" rel=\"nofollow noreferrer\">https://www.nami.org/About-Mental-Illness/Treatments/Mental-Health-Medications/Types-of-Medication/Mirtazapine-(Remeron)</a></p>\n", "score": 2 }, { "answer_id": 24129, "body": "<p>I was mistaken, the 5HT3 inhibitor of Vortioxetine is not responsible for the nausea, see <a href=\"https://www.google.com/search?client=firefox-b-d&amp;q=vortioxetine+nausea\" rel=\"nofollow noreferrer\">here</a></p>\n<blockquote>\n<p>Its additional antagonism of 5-HT3 receptors may partly counteract gastrointestinal adverse effects but nausea has an important role on drug discontinuation.</p>\n</blockquote>\n<p>His 5HTI agonist property contributes to Nausea.</p>\n<p>Its additional antagonism of 5-HT3 receptors may partly counteract gastrointestinal adverse effects but nausea has an important role on drug discontinuation.</p>\n", "score": 1 } ]

[ "antidepressants", "nausea", "ssri-selective-serotonin" ]

[ { "answer_id": 24157, "body": "<p>It's really simple, your misunderstanding just comes from mixing macro- and microanatomy.<br> Macroscopically, all of bone marrow is located <em>inside the bone</em>, in the medullar cavity.<br>\nMicroscopically, bone marrow tissue consists of different cells, some of which are endothelial cells that comprise sinuses, and <em>alongside</em> them (or <em>outside</em> of them, if you will; <em>in the bone marrow's stroma</em>) you find all other cell types.<br><br>\nI'll attach <em><a href=\"https://en.wikipedia.org/wiki/Bone_marrow\" rel=\"nofollow noreferrer\">this wiki page</a></em> as reference just in case, your textbook is a much better option though I suppose, this was just a clarification question.</p>\n", "score": 2 }, { "answer_id": 24160, "body": "<p><a href=\"https://i.stack.imgur.com/EiZHI.jpg.\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/EiZHI.jpg.\" alt=\"enter image description here\" /></a></p>\n<p>Image source: <a href=\"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/bone-marrow\" rel=\"nofollow noreferrer\">cancer .gov</a>.</p>\n<p>Bone marrow is a semi-solid tissue found within the spongy or cancellous (denoting bone tissue with a meshlike structure containing many pores, typical of the interior of mature bones) portions of bones. As you can see in the image above the hematopoiesis occur at the ends of long bones where red bone marrow is present. In red bone marrow the ratio of stem cells to fat cells are more in comparison to yellow bone marrow which is present in shaft of long bones of adults.</p>\n<p><strong>Look at the image below:</strong>.</p>\n<p><a href=\"https://i.stack.imgur.com/jjh1v.jpg.\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/jjh1v.jpg.\" alt=\"bone marrow sinuses\" /></a></p>\n<p>Image source: <a href=\"http://flipper.diff.org/app/items/info/550\" rel=\"nofollow noreferrer\">flipper.diff.org</a></p>\n<p>This is a microstructure of bone marrow sinuses with the hematopoietic stem cells near by. These hematopoietic stems cells <a href=\"https://journals.sagepub.com/doi/full/10.1080/01926230600939856#:%7E:text=The%20bone%20marrow%20is%20found,a%20meshwork%20of%20trabecular%20bone.\" rel=\"nofollow noreferrer\">traverse the walls of sinuses</a> once they are differentiated and mature and then comes into circulation. These sinuses are just lined by endothelial cells, they ultimately forms connection between arterioles and venules. For megakaryocyte, it extends cytoplasmic process inside the sinus which ultimately breaks down to form platelets.</p>\n<p><a href=\"https://i.stack.imgur.com/lNflx.jpg.\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/lNflx.jpg.\" alt=\"the HSC in bone marrow\" /></a></p>\n<p>Image source:<a href=\"https://www.frontiersin.org/articles/10.3389/fimmu.2016.00184/full\" rel=\"nofollow noreferrer\">frontiersin.org</a></p>\n<p>Here is another image showing how HSC clinging to endosteum differentiate and matures as it moves toward the sinuses which then ultimately traverse through the sinus wall.</p>\n", "score": 2 } ]

[ "blood", "bones", "bone-marrow" ]

[ { "answer_id": 24188, "body": "<p>It is impossible to make a definite diagnosis based solely on the given data. But there are some likely options which should all be checked. Here are the possibilities and test which should be done to check them:</p>\n<ol>\n<li>Bilirubin is a product of erythrocyte breakdown. That's why predominantly unconjugated hyperbilirubinemia could be a symptom of hemolysis or dyserythropoiesis which are simple to check. The patient should check their reticulocyte level (which should be high as the bone marrow tries to compensate for the breakdown of erythrocytes), lactate dehydrogenase level (which should be high because it's a product of erythrocyte breakdown, especially if hemolysis in intravascular), haptoglobin level (which should be low because of an increase of free hemoglobin which binds to haptoglobin). The patient should also check their hemoglobin level which should be elevated in case of intravascular hemolysis, but will be normal if hemolysis is extravascular. If any of the mentioned substances aren't within normal range, peripheral blood smear test should be further made to check for abnormalities of red blood cells. (<a href=\"https://www.aafp.org/afp/2018/0915/p354.html\" rel=\"nofollow noreferrer\">Hemolytic Anemia: Evaluation and Differential Diagnosis</a>)</li>\n<li>Any type of viral hepatitis could be the reason for elevated bilirubin. Viral markers should be checked. (<a href=\"https://en.wikipedia.org/wiki/Bilirubin#Hyperbilirubinemia\" rel=\"nofollow noreferrer\">Wikipedia - Hyperbilirubinemia</a>)</li>\n<li>Any biliary stricture can cause a moderate rise in bilirubin level. This includes gallstones, benign and malignant tumors (pancreatic adenocarcinoma or cholangiocarcinoma). Portosystemic shunt could also cause elevated indirect bilirubin because some amount of blood with indirect bilirubin would bypass the liver and the process of conjugation. (<a href=\"https://en.wikipedia.org/wiki/Bilirubin#Hyperbilirubinemia\" rel=\"nofollow noreferrer\">Wikipedia - Hyperbilirubinemia</a>) Both of these conditions can be seen with ultrasonography. However, these conditions are not likely because biliary strictures predominantly cause conjugated hyperbilirubinemia. (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324869/\" rel=\"nofollow noreferrer\">Biliary strictures: diagnostic considerations and approach</a>) Still, they should be checked because these conditions are very serious.</li>\n<li>The patient should be asked about their history of drug use. Some medications, such as gemfibrozil, irinotecan and the protease inhibitors, atazanavir, and indinavir, can elevate the level of unconjugated bilirubin because they reduce the hepatic uptake of it. (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424929/\" rel=\"nofollow noreferrer\">Evaluating Elevated Bilirubin Levels in Asymptomatic Adults</a>) The patient should also be asked whether they have had any surgeries or suffered any traumas lately which could cause hematoma which is connected to erythrocyte breakdown and consequently a rise in unconjugated bilirubin.</li>\n<li>If all of previous conditions don't exist then we can suppose that the patient has either Gilbert's or syndrome or Crigler-Najjar syndrome. If indirect bilirubin continues to rise and rises above 85 micromole/litre we can suppose that the patient has Crigler-Najjar syndrome and if the value is lower than 85 micromole/litre we can suppose that the patient has Gilbert's syndrome. Both of the syndromes are mostly harmless in adults. Potential jaundice can be treated with phenobarbital. Both syndromes can be definitely proven with genetic tests. (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424929/\" rel=\"nofollow noreferrer\">Evaluating Elevated Bilirubin Levels in Asymptomatic Adults</a>)</li>\n</ol>\n<p>If there are some other possible causes which I missed, please write another answer or let me know in the comments.</p>\n", "score": 3 } ]

[ "blood-tests", "liver", "bilirubin" ]

[ { "answer_id": 24190, "body": "<p>Offhand it would appear that surgical masks of the type you have cited would be regulated by the US government <strong>if they were to be used in a medical setting</strong>. Check out this FDA page, you will see that masks to be used in medical setting must conform to 21 CFR 878.4040. It is entirely possible that there is no physical difference between the medical and non-medical surgical (loose fitting) masks, however if the manufacturer labels it as a medical device or apparel they may have to have an FDA approval. See <a href=\"https://www.fda.gov/medical-devices/personal-protective-equipment-infection-control/n95-respirators-surgical-masks-and-face-masks#s2\" rel=\"nofollow noreferrer\">FDA web site on surgical masks</a></p>\n<p>Update: a wealth of information about the 'grades' and conformance/performance of so-called surgical masks can be found here <a href=\"https://www.astm.org/standardization-news/?q=features/standards-medical-face-masks-and-protective-clothing-.html&amp;fbclid=IwAR23HZ-VrE9d-oEFdC050ZUqvIojmjn78ADWjui5Owk-Hr8Xv5HIhu1NK6M\" rel=\"nofollow noreferrer\">ASTM </a></p>\n", "score": 1 } ]

[ "covid-19", "face-mask-respirator" ]

[ { "answer_id": 24292, "body": "<p>In normal patients fever can reduce our efficiency or <a href=\"https://pubmed.ncbi.nlm.nih.gov/21357332/\" rel=\"nofollow noreferrer\">comfort</a> for doing work. For mild infections one may wait for the fever to get over and let our immune response do their job.</p>\n<p>For <strong>early and effective</strong> treatment we prefer antibiotics with antipyretics as antibiotics can do their job alone and fever might not be necessary here. It will give early response than giving antipyretic alone or letting fever be alone.<br />\nThe other point is that, we prefer antibiotics with antipyretics because the organism inflicting it may cause more damage to our body before getting killed by immune system and thus increasing morbidity and mortality.</p>\n<p>Fever is not the only mechanism to fight infection, some people take antipyretics alone which reduces fever and provides comfort but our immune system alone is effective enough to curb some mild infections, so people who take antipyretics alone are not in too much danger but it may <a href=\"https://clinicaltrials.gov/ct2/show/NCT01891084\" rel=\"nofollow noreferrer\">prolong the illness</a> in some cases. It is not the general prescribed method and antipyretics <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145646/#:%7E:text=Antipyretics%20should%20be%20used%20with,or%20not%20is%20still%20controversial\" rel=\"nofollow noreferrer\">should be used with indications like other drugs and not for fever per se</a> (though this reference is for the pediatric population but in general practice, antipyretics are generally not given alone for infections and the same argument can be applied)</p>\n<p>For some common viral fevers only conservative treatment is required. Antipyretics are given if temperature is too high because in that case its benifit can outweigh the effects of having fever, otherwise we must let fever to happen recognising the fact that <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145646/#:%7E:text=Antipyretics%20should%20be%20used%20with,or%20not%20is%20still%20controversial\" rel=\"nofollow noreferrer\">fever is beneficial or not is still controversial</a> (considering the fact that fever in this case can be benificial.)</p>\n<p>Finally, there can be many other indications for the use of antipyretic to reduce fever, not just considering a simple argument that it can enhance the immune response eg. paracetamol is given in dengue fever or antipyretics are given to prevent febrile seizures. So I recommend taking antipyretics under the prescription of the concerned medical professional only.</p>\n", "score": 4 }, { "answer_id": 24279, "body": "<p>As you have already described, the hypothalamus regulate the set point at which the body temperature is maintained. This set point is elevated in fever, reflecting an infection, or resulting from tissue damage, inflammation, etc. These conditions all enhance formation of cytokines such as IL-1beta, IL-6, TNF-alfa, and interferons, which act as endogenous pyrogens; this first phase is mediated by ceramide release in neurons of the preoptic area in the anterior hypothalamus. The second phase is mediated by coordinate induction of COX-2 and formation of PGE2 which (by a cascade of reactions) will trigger the hypothalamus to elevate body temperature by promoting an increase in heat generation and decrease in heat loss.</p>\n<p>NSAID's (Nonsteroidal Anti-Inflammatory Drug) supress this response by inhibiting COX-2 and thus as well as the synthesis of PGE2. This is the fundamental therapeutic effect of this class of drugs - inhibit prostaglandin (PG).</p>\n<p>Now regarding your question specifically, NSAID's reduce fever in most situations, but not the circadian variation in temperature or the rise in response to exercise or increased ambient temperature. Normal body temperature in healthy humans is not affected by NSAID's because there are no PG's triggering the hypothalamus in normal conditions.</p>\n<p>There is a danger however... and that is due to toxicological effects specially with paracetamol (acetaminophen) which may cause liver injury with unintentional overdose; and if the drug has too much affinity for COX-2 enzymes (some companies were very well sued for that)</p>\n<p><strong>References</strong></p>\n<p>Rang &amp; Dale's Pharmacology</p>\n<p>Sorry, I misread your whole question.. the question was if it is good or not to have fever, you can remove the upvote if you like.</p>\n<p>I've found this <a href=\"https://pubmed.ncbi.nlm.nih.gov/26436473/\" rel=\"nofollow noreferrer\">article</a> which concludes that</p>\n<blockquote>\n<p>Early administration of acetaminophen to treat fever due to probable infection did not affect the number of ICU-free days</p>\n</blockquote>\n<p>That is a true dilemma, in one hand it is relatively safe to not take any antipyretic medication for minor illnesses, and let the system defend itself, on the other as some studies reveal it does not affect or worsen the outcomes.</p>\n", "score": 2 } ]

[ "fever" ]

[ { "answer_id": 24311, "body": "<p>Till now probably there is no evidence of whether we should use aspirin alone in Covid 19 patients to prevent blood clot unless he is suffering from some cardiovascular\ndisorder . This may be probably due to no <a href=\"https://www.sciencedirect.com/science/article/pii/S0306987720312408?via%3Dihub\" rel=\"nofollow noreferrer\">well conducted RCT</a> taking aspirin into consideration. Although there are suggestion it can be useful. Earlier there were claims that use of NSAIDS were associated with adverse respiratory effects but as concluded by WHO currently there are <a href=\"https://www.who.int/news-room/commentaries/detail/the-use-of-non-steroidal-anti-inflammatory-drugs-(nsaids)-in-patients-with-covid-19\" rel=\"nofollow noreferrer\">no such evidence</a>.</p>\n<p>There are many antiplatelet drugs which are superior to aspirin thus making them a relatively better choice. Regarding antithrombotic therapy, in presentations consistent with ACS due to plaque rupture (i.e., type 1 MI), <a href=\"https://www.onlinejacc.org/content/75/23/2950\" rel=\"nofollow noreferrer\">dual antiplatelet therapy and full-dose anticoagulation</a> as per the American College of Cardiology (ACC)/American Heart Association (AHA) and ESC guidelines should be administered, unless there are contraindications. If there is high prevalence of bleeding less potent antiplatelet like clopidogrel should be used. This point signifies that antiplatelet drugs has been used for prophylaxis together with LMWH and since there are better drug than aspirin they are preferred. (Remember, by prophylaxis, I mean that when patient is admitted to hospital, at the same time treatment is given because inflammatory conditions and coagulation cascade take time to occur. But if one is late for admission antiplatelet drug can be benificial if already taken.)</p>\n<p>Currently, the standard therapy for <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298694/#!po=1.19048\" rel=\"nofollow noreferrer\">thromboprophylaxis</a> in thromboembolism associated with COVID-19 is LMWH.</p>\n<p><em>This paragraph is a little extra, may not be specific to the question, non interested users may skip.</em> The microvascular clots and microvascular pulmonary thrombosis is associated with the inflammatory condition. One of the <a href=\"https://www.ncbi.nlm.nih.gov/books/NBK554776/\" rel=\"nofollow noreferrer\">main protagonist of this inflammatory condition is IL-6</a>, there were trials of <a href=\"https://emedicine.medscape.com/article/2500114-treatment#d14\" rel=\"nofollow noreferrer\">tocilizumab</a>, a monoclonal antibody against IL-6, but the trial did not meet its primary endpoint of improved clinical status in patients with COVID-19–associated pneumonia or the secondary endpoint of reduced patient mortality. The trial did show a positive trend in time to hospital discharge among patients who received it(Tocilizumab was in use in areas I know before the result came). It was <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229910/\" rel=\"nofollow noreferrer\">hypothesised</a> to be useful in preventing hypercoagulation.</p>\n<p><strong>Now, coming up to your point :-Can aspirin be used as a prophylactic measure?</strong></p>\n<p>Well, antiplatelet drugs can be used for prophylaxis of thrombotic condition especially of arterial etiology ( like atherosclerotic plaque) as I mentioned above but there are many superior drugs for use than aspirin amongst the antiplatelet drugs to use. In this <a href=\"https://www.sciencedirect.com/science/article/pii/S0306987720312408?via%3Dihub#bb0070\" rel=\"nofollow noreferrer\">article</a> it is mentioned that COVID-19 patients taking low dose aspirin for secondary prevention of cardiovascular disease should continue their treatment.<br />\nAspirin has some other <a href=\"https://www.sciencedirect.com/science/article/pii/S0306987720312408?via%3Dihub#bb0070\" rel=\"nofollow noreferrer\">limitations</a> too, which might have been taken into consideration for initiation in non cardiac patients instead of anticoagulants like LMWH:-</p>\n<ol>\n<li><p>The drug irreversibly inhibits platelet cyclooxygenase, and its effect persists for the circulating life of platelets making its use controversial in COVID-19 patients.</p>\n</li>\n<li><p>Aspirin is not indicated for the treatment of DIC, or other venous thromboembolic complication that might be associated with severe COVID-19, and may increase the bleeding risk in severely thrombocytopenic patient.</p>\n</li>\n</ol>\n<p>Lastly, if one talk about taking aspirin even before having any symptoms of Covid 19 the person need to be concerned about risk ( risk like increase G.I bleeding related to aspirin inhibiting substances that protect stomach lining , allergic reaction) of daily intake of aspirin . Normal person if hospitalised, is recommended with use of LMWH, which itself becomes a prophylactic measure and will be enough to reduce thromboembolic condition ( Covid patients were at <a href=\"https://www.ncbi.nlm.nih.gov/books/NBK554776/\" rel=\"nofollow noreferrer\">higher risk of venous thromboembolism</a> that prompted us to use LMWH instead of antiplatelet drug) related mortality in a normal person. Although, in person with coronary artery disease and already taking aspirin, together with LMWH in hospitals can help to reduce mortality.</p>\n", "score": 2 } ]

[ "covid-19", "blood", "blood-clotting" ]

[ { "answer_id": 24431, "body": "<p>In three recent past outbreaks involving a new virus (or an old virus spreading)—the Ebola outbreaks in West Africa and the Congo, the Zika outbreak in South America, and the 2009 H1N1 (swine flu) influenza pandemic-- the WHO or its subsidiaries (PAHO) have played a prominent role in tracking the outbreak and making regular reports about disease spread available to the public. These have included (variously) cumulative case counts, counts per population, deaths, deaths per population by country.\nHere is information from the WHO/PAHO about their tracking and communication efforts for these three outbreaks.</p>\n<p>Ebola\n<a href=\"https://www.who.int/csr/disease/ebola/situation-reports/archive/en/\" rel=\"nofollow noreferrer\">https://www.who.int/csr/disease/ebola/situation-reports/archive/en/</a></p>\n<p>Zika\n<a href=\"https://www.paho.org/data/index.php/en/?option=com_content&amp;view=article&amp;id=524:zika-weekly-en&amp;Itemid=352\" rel=\"nofollow noreferrer\">https://www.paho.org/data/index.php/en/?option=com_content&amp;view=article&amp;id=524:zika-weekly-en&amp;Itemid=352</a></p>\n<p>2009 H1N1 (swine flu)\n<a href=\"https://www.who.int/csr/disease/swineflu/updates/en/\" rel=\"nofollow noreferrer\">https://www.who.int/csr/disease/swineflu/updates/en/</a></p>\n<p>The existence of daily reports for SARS-CoV-2 and the accessibility of information to the public seem unique. The graphical presentation of information about SARS-CoV-2 seems more sophisticated than for the past outbreaks.</p>\n", "score": 1 } ]

[ "covid-19", "statistics", "public-health", "history" ]

[ { "answer_id": 24448, "body": "<p>This approach is not meant to yield a vaccine that will prevent infection with SARS-CoV-2. It is meant to be an antibody treatment for COVID-19.</p>\n<p><strong>BACKGROUND</strong></p>\n<p>Antibodies are infection-fighting proteins made by the immune system that can bind to the surface of viruses and prevent them from infecting cells. When a person is infected with a virus, the person makes his/her own antibodies. If all goes well, these antibodies prevent the person from being re-infected with the virus. However, it is not known with certainty that whether the antibodies produced in a person who has been infected with the SARS-CoV-2 virus will prevent re-infection and how long this protection might last.</p>\n<p>Vaccines seek to mimic the antibody response that comes from “natural” infection with the SARS-CoV-2 virus without causing serious disease or perhaps any disease. Other yet (August 2020) unproven approaches to prevention and treatment of SARS-CoV-2 and COVID-19 involve other ways of manipulating antibodies and the immune response.</p>\n<p><strong>HUMAN CONVALESCENT PLASMA</strong></p>\n<p>It is possible to identify and remove anti-SARS-CoV-2 virus antibodies from the blood of a person who has been infected with the virus. These antibodies can be re-infused into another person, where they would (if all goes well) modify the course of illness (make the illness less severe). The efficacy t of this kind of antibody treatment (convalescent plasma) has been evaluated in a small clinical trial in China that is described here.\n<a href=\"https://jamanetwork.com/journals/jama/fullarticle/2766940\" rel=\"nofollow noreferrer\">https://jamanetwork.com/journals/jama/fullarticle/2766940</a></p>\n<p><strong>BIO-ENGINEERED MONOCLONAL ANTIBODIES/ANTIBODY “COCKTAILS”</strong></p>\n<p>It is also possible to “engineer” monoclonal (one specific protein) antibodies that might prevent infection with the SARS-CoV-2 virus or make the disease less severe in people who are infected and develop COVID. A number of pharmaceutical companies are trying to do this in order to make a commercially available product to prevent infection and/or treat people who develop COVID-19. This is a pre-print that describes early results of animal studies of use a monoclonal antibody “cocktail” (two different monoclonal antibodies) to modify the course of SARS-CoV-2 infection.\n<a href=\"https://www.biorxiv.org/content/10.1101/2020.08.02.233320v1\" rel=\"nofollow noreferrer\">https://www.biorxiv.org/content/10.1101/2020.08.02.233320v1</a></p>\n<p><strong>EQUINE HYPERIMMUNE (ANTI)-SERUM</strong></p>\n<p>The paper cited describes a plan to use antibodies to treat COVID-19 that involves antibodies made in horses. As the authors point out, treatments based on equine antibodies have been used for decades in the management of snake, scorpion and spider envenomation and digoxin poisoning.</p>\n<p><a href=\"https://link.springer.com/referenceworkentry/10.1007%2F978-3-319-20790-2_176-1\" rel=\"nofollow noreferrer\">https://link.springer.com/referenceworkentry/10.1007%2F978-3-319-20790-2_176-1</a></p>\n<p>The authors describe immunization of horses with the receptor-binding domain of the viral spike glycoprotein of SARS-CoV-2. Plasma was collected from two horses and then digested, yielding F(ab´)2 fragments from the immunoglobulin molecules. The fragments were further purified, anofiltered (20 nm), and sterilized. The hyperimmune anti-serum will be evaluated as a therapy in patients with moderate to severe COVID-19.</p>\n<p>This approach has been advocated as an alternative to convalescent plasma to treat COVID-19 for low and middle income countries by Stuart Ainsworth , Stefanie Menzies, Richard J. Pleass writing in June 2020.</p>\n<p>“We therefore advocate immunization of larger animals, e.g. horses and sheep, such as is already the standard to generate antivenoms, anti-toxins, and anti-rabies therapeutics for human use. “ Page 2</p>\n<p><a href=\"https://doi.org/10.12688/wellcomeopenres.15990.1\" rel=\"nofollow noreferrer\">https://doi.org/10.12688/wellcomeopenres.15990.1</a></p>\n<p>Ainsworth, Menzies and Pleass go on to point out that:</p>\n<p>“The polyclonal nature of antisera raised in animals makes it particularly suited to neutralizing multiple antigens, toxins and enzymes that in humans bitten by snakes cause coagulopathies that are also observed in COVID-19 patients.” Page 2</p>\n<p>In the past, use of equine antibodies in humans carried a high risk of serum sickness. The use of antibody fragments has decreased this risk. There is concern about a possible adverse effect of antibody treatments, including treatments using human antibodies, on lung function in patients with COVID-19.</p>\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478436/\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478436/</a></p>\n", "score": 2 } ]

[ "covid-19", "immune-system", "vaccination", "coronavirus", "antibodies" ]

[ { "answer_id": 24473, "body": "<p>The entire point of having a placebo control from a statistics perspective is that <em>the only thing different between the groups is the treatment</em>. You cannot say this is true if you also tell people which group they are in: if you do this, there are now two differences between groups, 1) Treatment vs placebo, 2) Knowing they are in the placebo group vs. knowing they are in the treatment group.</p>\n<p>Your logic does not make sense: It doesn't matter if an &quot;open placebo&quot; also has some treatment effect in some situation. You would instead need to verify that there is no difference of effect between knowingly getting a placebo and knowingly getting an ultimately ineffective treatment.</p>\n<p>Furthermore, you would need to show this for <em>every single condition</em> you might want to investigate, not just one, and not just no <em>statistically significant</em> difference, you would actually need <em>exactly the same effect</em>, which you cannot ever demonstrate (and which will reasonably never be true, anyways). Otherwise, you will have unknown bias in your study that could cause you to falsely think a treatment is better than it actually is.</p>\n<p>There are other good reasons to have a placebo control, besides statistics: doctors and other study staff might be hoping to find a positive result, so they may (intentionally or unintentionally) bias their approach to the placebo and treatment groups. Ideal placebo controls blind the researchers and staff, too, not just the patient (of course with some things like a surgical intervention this is not entirely possible, but you still try to do it to the extent possible).</p>\n<p>Patients may also report things differently if they know what group they are in. If they are concerned about side effects, maybe they report more side effects on the treatment than they would have on the placebo. If they are hopeful for the treatment, they might mask side effects if they know they are in the treatment group.</p>\n<p>Placebo controls aren't possible in all circumstances, and there is lots of clinical research that does not use a placebo, especially exploratory research. There are also some studies where it's not really possible to completely hide that someone is in a certain group. But the randomized controlled trial is the gold standard for important statistical and methodological reasons, and a double-blind placebo control is the gold standard comparison when comparing to no treatment.</p>\n", "score": 3 } ]

[ "medications", "research", "clinical-study", "placebo" ]

[ { "answer_id": 24894, "body": "<p>It appears that there is indeed an association between pharmacokinetics and development of addiction to psychostimulant drugs.</p>\n<p>First, as a general note, it should be noted that pharmacokinetics govern a drug's plasma level, while pharmacodynamics govern the body's response to the drug (i.e. to the drug's plasma level), and in this case, addiction may be thought of as a pharmaco<strong>dynamic</strong> concept, since it is the result of activation and modulation of certain receptors in the central nervous system (more specifically, in the mesolimbic system). These two concepts - pharmacokinetics and pharmacodynamics, or PK-PD for short - when combined together, give the full picture of the relationship between the body and the drug as effect over time, from first contact to biological response.</p>\n<p><a href=\"https://i.stack.imgur.com/HaxQi.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/HaxQi.png\" alt=\"PK-PD relationship\" /></a></p>\n<p>Another general note is that PK-PD relationship is not always simple to evaluate and explain and is not always 'linear', in the sense that the body's response does not always directly reflect the plasma level of the drug, and vice versa. Therefore, we must not simplify the discussion by saying that the steeper the slope (i.e. the faster the absorption of the drug), the more addictive the drug is, or in other words, the rate of absorption is not the only, and may not even be the primary, factor in determining addictiveness of a drug. Addiction is a multi-factorial condition, based on genetic predisposition, social factors, etc. as well as pharmacokinetics (<a href=\"https://ajp.psychiatryonline.org/doi/pdfplus/10.1176/appi.ajp.160.1.1\" rel=\"nofollow noreferrer\">source</a>).</p>\n<p>Now, to be more particular, the slope of the curve in the absorption phase is dependent on the route of administration (and the formulation) of the drug, since different routes of administration provide different rates of absorption depending on the path the drug has to take to reach the general circulation, where we measure its plasma levels.<br> <a href=\"https://i.stack.imgur.com/M7B13.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/M7B13.png\" alt=\"Route of administration curves\" /></a> <br>Thus, common non-oral routes of administration such as IV infusion, intranasal administration (snorting) and smoking all allow the drug to reach the general circulation quickly through small blood vessels in the nose and lungs, or directly, as in the case of an IV infusion. Once a drug reaches the general circulation it quickly reaches the brain (provided its molecules are able to penetrate the blood-brain barrier), <strong>and it has indeed been found that rapid routes of delivery increase the risk for developing an addiction</strong>. To quote from <a href=\"https://www.sciencedirect.com/science/article/abs/pii/S0149763415001669?via%3Dihub\" rel=\"nofollow noreferrer\">a very comprehensive review</a>, which deals with that subject precisely:</p>\n<blockquote>\n<p>Addiction is more likely and more severe in individuals who\ntake drugs via rapid routes of drug delivery. For instance,\naddiction to cocaine, amphetamine, methamphetamine, nicotine\nor heroin is more probable in people who consume these drugs\nvia smoking or i.v. injection than in individuals who use slower\nroutes of drug administration (e.g., the intranasal or transdermal\nroutes; Barrio et al., 2001, Budney et al., 1993, Carpenter et al.,\n1998, Ferri and Gossop, 1999, Gossop et al., 1992, Gossop et\nal., 1994, Hatsukami and Fischman, 1996, Hughes, 1989,\nRawson et al., 2007, Van Dyke and Byck, 1982, Volkow and\nSwanson, 2003 and Winger et al., 1992). Compared to\nintranasal drug users, individuals who smoke or inject drugs\ni.v. also use drugs more frequently, for a longer time, spend\nmore money on drugs, report a greater loss of control over drug\ntaking and are more likely to overdose (Barrio et al., 2001,\nCarpenter et al., 1998, Ferri and Gossop, 1999, Gossop et al.,\n1992, Gossop et al., 1994, Hatsukami and Fischman, 1996,\nHughes, 1989, Rawson et al., 2007, Van Dyke and Byck, 1982,\nVolkow and Swanson, 2003 and Winger et al., 1992).</p>\n</blockquote>\n<p>That review and the sources cited in it (especially those mentioned in the cited paragraph above) will probably provide enough evidence for this association.</p>\n", "score": 3 } ]

[ "medications", "addiction" ]

[ { "answer_id": 30997, "body": "<p>The reason for that association is not known. Neither etiology of these two diseases is undiscussed. Arguably, neighbouring veins exerting pressure on the trigeminal nerve cause trigeminal neuralgia. Conversely, it is still unclear if auto-immunity and antibodies cause multiple sclerosis. Accordingly, my internet search brought up no theory to explain the coincidence of both diseases.</p>\n<p>Thus, substantially, your question must be answered to &quot;we do not know&quot;.</p>\n<p>See, however Wikipedia on the cause of <a href=\"https://en.wikipedia.org/wiki/Trigeminal_neuralgia\" rel=\"nofollow noreferrer\">Trigeminal neuralgia</a>:&quot;The exact cause is unknown, but believed to involve loss of the myelin of the trigeminal nerve.[...] This might occur due to compression from a blood vessel as the nerve exits the brain stem, multiple sclerosis, stroke, or trauma.[...] Less common causes include a tumor or arteriovenous malformation.&quot;</p>\n<p>Thus, a more speculative if formal answer might read: &quot;<em>In spite</em> of common classification of trigeminal nerve as not part of the cns, de-myelination, which is known cause for <a href=\"https://en.wikipedia.org/wiki/Multiple_sclerosis\" rel=\"nofollow noreferrer\">multiple sclerosis</a>, might also affect this nerve.</p>\n<p>On a more formal level your question, in the light of its explanatory text, indeed, seems to focus on the difference between cranial nerves I, II and the trigeminal nerve, termed no. V.</p>\n<p>Thus, it should be correct paraphrasing your question to &quot;how can it be&quot; that symptoms from trigeminus nerve are considered symptoms of multiple sclerosis when the latter is a disease of the central nervous system and trigeminus neuralgia a disease of the peripheral nervous system.</p>\n<p>First, it should be mentioned that counterintuitively not only the nerves of the central nervous system, cns, but those of the peripheral nervous system, pns, as well do feature a myelin sheath (which the question implies as for nerves I, II, and was implicitely stated above). Thus, it is not the lack of myelin that - anatomically - precludes association of trigeminus neuralgia and multiple sclerosis.</p>\n<p>Second, it is in good agreement with accepted formal criteria to consider not only - as you mentioned - nerves I, II as being part of the CNS, but, at least in the context of common causes for multiple sclerosis and neuralgia, the trigeminus nerve as well.</p>\n<p>What is the reason for and why <a href=\"https://treehozz.com/is-the-optic-nerve-part-of-the-central-nervous-system\" rel=\"nofollow noreferrer\">Is the optic nerve part of the central nervous system?</a> &quot;<em>because</em> it is derived from an out-pouching of the diencephalon (optic stalks) during embryonic development&quot;. Then, &quot;...in fact, II is myelinated by oligodendrocytes rather than Schwann cells. Therefore, cranial nerves I and II are part of the CNS, and the rest are considered part of the PNS.&quot;</p>\n<p>However, see <a href=\"https://en.wikipedia.org/wiki/Cranial_nerves#:%7E:text=The%20cranial%20nerves%20are%20considered%20components%20of%20the,which%20emerge%20from%20segments%20of%20the%20spinal%20cord.?msclkid=222fa385b83e11ec8435919753348fa6\" rel=\"nofollow noreferrer\">Wikipedia</a>on that point, that seems crucial in respect of your question: &quot;...The cranial nerves are considered components of the peripheral nervous system (PNS),[...] although on a structural level the olfactory (I), optic (II), <em><strong>and trigeminal (V) nerves</strong></em> <em><strong>are more accurately considered part of the central nervous system</strong></em> (CNS).[...]&quot;</p>\n<p>Most scientific papers do not seem to differentiate in any formal categorizing way (which might have been reason to ask), cp. e.g. <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652082/\" rel=\"nofollow noreferrer\">Yaday et al.</a> &quot;...neurovascular conflict is the most accepted theory. Artery or vein[...] is usually compressing the TR N near the pons injuring myelin sheath and causing erratic hyperactive functioning of the nerve.&quot;</p>\n", "score": 1 } ]

[ "neurology", "autoimmune-disease", "multiple-sclerosis", "myelin-sheath" ]

[ { "answer_id": 25291, "body": "<p>TLDR summary of what I found:</p>\n<ul>\n<li>diet-wise brassica vegetables, in particular broccoli seems to have this effect (but other vegetables that share P450 inhibitors in common with citrus fruits have the opposite effect)</li>\n<li>medication-wise, the OTC &quot;heartburn&quot; drug Omeprazole has been fairly consistently reported to have this effect (but many, many more drugs of various classes have the opposite effect)</li>\n<li>out of the cigarette smoke components, it's the carcinogenic aromatic hydrocarbons and not the nicotine that's responsible for this interaction with caffeine.</li>\n</ul>\n<hr />\n<p>There is a more extensive list of caffeine-drug interactions in <a href=\"https://pharmrev.aspetjournals.org/content/70/2/384/tab-figures-data\" rel=\"noreferrer\">Pharma. Rev.</a>, but few drugs shorten the half-life of caffeine, mainly some (but not all) proton pump inhibitors (&quot;heartburn&quot; drugs) like Omeprazole (−41%) and Cimetidine (−31%). (I think PPIs like Omeprazole are generally available without prescription.)</p>\n<p>I would caution on using the claims that source without double-checking with the primary studies because they listed Fluvoxamine (an antidepressant) as −80% &quot;decreases caffeine half-life by sixfold&quot;. Most other drugs in this class have the opposite effect on caffeine half-life. And it seems they misinterpreted that <a href=\"https://pubmed.ncbi.nlm.nih.gov/8807660/\" rel=\"noreferrer\">study</a> as Fluvoxamine is one of the more potent inhibitors of P450 pathway involved, actually having the opposite effect on caffeine half-life:</p>\n<blockquote>\n<p>The selective serotonin reuptake inhibitor fluvoxamine is a very potent inhibitor of the liver enzyme CYP1A2, which is the major P450 catalysing the biotransformation of caffeine. [...] During fluvoxamine, the median of the total clearance of caffeine decreased from 107 ml min-1 to 21 ml min-1 and the half-life increased from 5 to 31 h</p>\n</blockquote>\n<p>31 / 5 = 6.2 so they almost used this study as a ref, but misinterpreted the direction of the effect.</p>\n<p>But their listing of PPIs effect on caffeine metabolism is probably correct; a quick search found a <a href=\"https://pubmed.ncbi.nlm.nih.gov/8162667/\" rel=\"noreferrer\">paper</a> tiled &quot;Accelerated caffeine metabolism after omeprazole treatment [...]&quot;</p>\n<blockquote>\n<p>Omeprazole has previously been shown to induce hepatic cytochrome P4501A2 activity, as evidenced by an accelerated N-3-demethylation in the 13C-[N-3-methyl]-caffeine breath test [...]</p>\n</blockquote>\n<p>A <a href=\"https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2036.2000.00788.x\" rel=\"noreferrer\">review of PPIs</a> (see table 3) confirms this with additional studies, i.e. there is indeed <strong>increased/faster caffeine clearance on Omeprazole</strong>.</p>\n<p>The Pharma Rev source alas also claims that some anti-psoriasis / anti-eczema drugs decrease caffeine half-life, listing Methoxsalen (−70%) and 5-Methoxypsoralen (−31%)... but again that seem to be an error because a <a href=\"https://pubmed.ncbi.nlm.nih.gov/3690940/\" rel=\"noreferrer\">primary study</a> I found says:</p>\n<blockquote>\n<p>During the period of maximum inhibition the mean elimination half-life of caffeine increased from 5.6 hours at baseline to 57 hours after administration of methoxsalen</p>\n</blockquote>\n<p>And likewise <a href=\"https://pubmed.ncbi.nlm.nih.gov/8735685/\" rel=\"noreferrer\">for 5-methoxypsoralen</a>.</p>\n<p>There is a much longer list of drugs that increase the half-life of caffeine though (presumably mostly by competing on the P450 pathway). I would not be surprised if some foods do the same (given the known interactions between e.g. <a href=\"https://en.wikipedia.org/wiki/Grapefruit%E2%80%93drug_interactions\" rel=\"noreferrer\">grapefruit and some drugs</a>), but I couldn't find any data specific to foods and caffeine, except for grapefruit, which does increase caffeine half-life too.</p>\n<hr />\n<p>From an older <a href=\"https://link.springer.com/article/10.2165/00003088-200039020-00004\" rel=\"noreferrer\">(2000) review</a> on the same caffeine-drug interaction issue, it seems indeed that Omeprazole is the only drug with such a significant effect (well included in the review):</p>\n<p><a href=\"https://i.stack.imgur.com/Nq7oX.png\" rel=\"noreferrer\"><img src=\"https://i.stack.imgur.com/Nq7oX.png\" alt=\"enter image description here\" /></a></p>\n<p>In fact that 2000 review lists Cimetidine in the opposite direction than Pharma Rev, which actually <a href=\"https://pubmed.ncbi.nlm.nih.gov/7306430/\" rel=\"noreferrer\">seems</a> to be the correct one.</p>\n<hr />\n<p>There's also an interesting <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243019/\" rel=\"noreferrer\">2011 study</a> on what exact components of cigarette smoke accelerate the clearance of caffeine. It seems that these components of cigarette smoke are the polycyclic aromatic hydrocarbons.</p>\n<blockquote>\n<p>Cigarette smoking accelerates the metabolism of certain drugs, particularly those primarily metabolized by cytochrome P450 1A2 (CYP1A2) and, to a lesser extent, CYP2E1 and some UDP-glucuronosyltransferases [1, 2]. The induction of CYP1A2 is mediated by binding of polycyclic aromatic hydrocarbons of the tobacco smoke to the aryl hydrocarbon receptor (AHR) with consequent transcriptional activation of the CYP1A2 gene. Furthermore, CYP1A1 and CYP1B1 enzymes are induced by tobacco smoking via AHR in various human tissues such as lung and placenta.</p>\n</blockquote>\n<p><a href=\"https://en.wikipedia.org/wiki/Polycyclic_aromatic_hydrocarbon#Human_health\" rel=\"noreferrer\">PAHs are carcinogenic</a> and don't seem to have any uses as drugs.</p>\n<p>The 2011 study itself looked at whether nicotine itself contributes to this effect on caffeine clearance, but the contribution from nicotine seems to be nonexistent (or at least undetectable after 8 days of dosing with nicotine.)</p>\n<blockquote>\n<p>There was no significant influence of nicotine administration on the pharmacokinetic parameters of caffeine or the formation pharmacokinetics of paraxanthine, theophylline and theobromine. Since caffeine metabolism to paraxanthine is a specific probe reaction for CYP1A2 [13], it can be concluded that CYP1A2 activity is not affected by 8 days of nicotine dosing. Although previous studies in experimental animals have provided evidence for the role of nicotine in the induction of CYP1A1 and CYP1A2 enzymes [4–10], our study disproves the hypothesis that nicotine induces CYP1A2 activity in humans in vivo. The discrepancy between human and animal data may be explained by tissue and species specific expression patterns. The human caffeine phenotyping probes the hepatic CYP1A2 activity, whereas the animal studies are mainly on extrahepatic CYP1A1 induction or based on methods not capable of differentiating between CYP1A1 and CYP1A2 enzymes.</p>\n</blockquote>\n<p>Now on the ARH angle, it seems that Omeprazole also works this way with regard to caffeine (being listed in a <a href=\"https://pubmed.ncbi.nlm.nih.gov/12540743/\" rel=\"noreferrer\">review</a> on the receptor), but the evidence is pretty muddy (or at least was in the year 2003 when that review was written):</p>\n<blockquote>\n<p>Interestingly, some chemicals have\nbeen identified that can induce AhR-dependent gene expression, yet they reportedly\nfail to competitively bind to the AhR (Table 1 [first entry there is Omeprazole]). It has been proposed that\nthese chemicals are not AhR ligands themselves, but that they can activate AhR-dependent\ngene expression indirectly, either via metabolic conversion into a ligand\nor by their ability to affect some cellular pathway that results in AhR activation.\nThese conclusions are difficult to reconcile, especially given what is known about\nthe AhR-dependent mechanism of gene activation. Although these weak inducers\nhave not been observed to competitively bind to the AhR, they may still be AhR\nligands, albeit ligands that bind with relatively low affinity. Demonstration of the\nability of weak ligands (Kd in the uM range) to competitively bind to the AhR in\nstandard binding assays is technically challenging, especially given the extremely\nhigh AhR binding affinity of TCDD [Kd in the pM range (143)]. Recent modifications\nof the AhR ligand binding assay that favor competitive binding by weak\nAhR ligands (i.e., reduction of [3H]TCDD and increased competitor concentration)\nhave been used to demonstrate that carbaryl, previously reported to not bind to\nthe AhR (144, 145), is actually a weak AhR ligand (146). The 300,000-fold lower\npotency of carbaryl, as compared to TCDD (146), likely explains its inability to\ncompetitively displace [3H]TCDD from the AhR ligand binding domain using the\nligand binding assay conditions described by those investigators. In addition, <strong>the\ncompetitive binding of Trp metabolites (namely tryptamine and indole acetic\nacid) and several benzimidazoles (omeprazole, thiabendazole, albendazole, and fenbendazole) has also been observed (87, 147), even though these chemicals were\npreviously reported to induce AhR-dependent gene expression in a ligand independent\nmanner</strong> (148–151). Not only are these binding results consistent with what is\nknown about other CYP1A1 inducers and AhR activators, but it is likely that many\n(if not all) of the other chemicals that reportedly induce in an AhR-independent\nmanner (Table 1) are actually weak AhR ligands. The absolute requirement for\nthe AhR in the chemical-inducible response, combined with the demonstration\nthat some “ligand independent” inducers actually bind to the AhR, raises questions\nas to the existence of these proposed alternative induction pathways. Unlike\nother ligand-dependent receptors (i.e., steroid hormone receptors) that can be\nactivated in a ligand-independent manner by processes such as phosphorylation\n(152, 153), ligand-independent activation for the AhR remains to be confirmed.</p>\n</blockquote>\n<p>And on other sources of ArH ligands, particularly dietary, it notes that:</p>\n<blockquote>\n<p>The formation\nof relatively potent AhR ligands from precursors that have little or no AhR\nagonist activity is significant, especially considering that most dietary ligands are\nthemselves relatively weak AhR ligands/agonists. Flavonoids, including flavones,\nflavanols, flavanones, and isoflavones, represent the largest group of naturally\noccurring dietary AhR ligands. Although the majority of these natural plant products\nare AhR antagonists (43–47), numerous agonists, such as quercetin (48),\ndiosmin (49), tangeritin (50), and tamarixetin (43), have also been identified. In\naddition to interacting with the AhR, many of these flavonoids are also substrates\nfor CYP1A1 (51). These chemicals are widely distributed in dietary vegetables,\nfruits, and teas (52–55), and flavonoid levels in human blood have been reported\nto be in the low uM-range (56–58), concentrations sufficient to inhibit/activate the\nAhR. Thus, it is not surprising that crude extracts of a large number of different\nvegetables, teas, fruits, and natural herbal products have AhR agonist and/or antagonist\nactivity (59, 60). Thus, plant-derived materials appear to commonly contain\nAhR ligands or products that can readily be converted into AhR ligands, and as\nsuch, they are perhaps the largest class of natural AhR ligands to which humans\nand animals are exposed.</p>\n</blockquote>\n<p>So it seems somewhat plausible that some dietary sources of such ligands might have a similar effect to PAHs on caffeine clearance, but insofar I haven't found some specific studies on the interaction in the direction of increased clearance. Actually, there's <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082882\" rel=\"noreferrer\">one study</a> in the opposite direction that we might have hoped for:</p>\n<blockquote>\n<p>Quercetin significantly inhibits the caffeine metabolism</p>\n</blockquote>\n<p>There is actually one <a href=\"https://academic.oup.com/carcin/article/21/6/1157/2896318\" rel=\"noreferrer\">year 2000 study</a> on diets and CYP1A2 activity, as\nmeasured by excreted caffeine metabolites. It found that adding <strong><a href=\"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/brassica-vegetable\" rel=\"noreferrer\">brassica\nvegetables</a> (specifically, they added broccoli, cabbage, radish sprouts, and cauliflower)</strong> to a diet increased caffeine\nmetabolism (by some 18-37%), while apiaceous vegetables (carrots, parsnips,\ncelery, dill and parsley) had the opposite effect by 13-25%. (Exact measure\ndepends on the metabolite.)</p>\n<p>It also notes that furanocoumarins are probably responsible for the latter\neffect, in common with that observed with citrus fruits and caffeine, while for the increased caffeine clearance on brassica vegetables, they suggest glucosinolates are responsible. (There's an <a href=\"https://pubmed.ncbi.nlm.nih.gov/8625493/\" rel=\"noreferrer\">older study</a> adding just broccoli, which found the same effect. The broccoli-only study was also <a href=\"https://pubmed.ncbi.nlm.nih.gov/17266520/\" rel=\"noreferrer\">replicated</a>.)</p>\n", "score": 6 } ]

[ "caffeine", "metabolism" ]

[ { "answer_id": 25272, "body": "<p>Consider this a very tentative answer, employing analogy rather than any hard data on the Pfizer vaccine.</p>\n<p>In general it can be <a href=\"https://www.aaaai.org/ask-the-expert/Vaccine-allergy-testing#:%7E:text=A%3A,live%20zoster%20vaccine%20(1)\" rel=\"nofollow noreferrer\">fairly difficult</a> to know exactly what component in a vaccine caused the allergic reaction. So, an option is indeed to test with the actual vaccine. An AAAAI Q&amp;A on the matter points to <a href=\"https://pubmed.ncbi.nlm.nih.gov/17276555/\" rel=\"nofollow noreferrer\">this study</a> that experimented with the influenza and measles vaccines:</p>\n<blockquote>\n<p>the results of the skin prick test (undiluted vaccine) and the intradermal skin test (1:10 diluted vaccine) indicated that the latter was more useful in both cases of measles (54 patients) and influenza vaccine (69 patients) Overall, the skin test using 1:10 diluted vaccine was the more suitable for predicting an immediate-type reaction to measles and influenza vaccinations. Patients having negative 1:10 skin tests can be expected to show no adverse reactions to the remaining injections and even the positive subjects will complete the course of vaccine doses by the stepwise method.</p>\n</blockquote>\n<p>Frankly, I find the abstract (and the rest of the paper) fairly confusing in their terminology. I think they use &quot;skin test&quot; interchangeably with intradermal [skin] test, and in opposition to [skin] prick test, i.e. I think they ultimately recommend an intradermal 1:10 v/v diluted solution as the best method in terms of balancing risk of a severe reaction with actually detecting one at all.</p>\n<p>Actually, they have this protocol illustrated in the paper, which does a prick test first, followed by an intradermal only if the prick test was negative.</p>\n<p><a href=\"https://i.stack.imgur.com/RCmiQ.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/RCmiQ.png\" alt=\"enter image description here\" /></a></p>\n<p>But the conclusions of the paper are just about as confusing as the abstract. It's not terribly clear to me if they recommend following this more elaborate protocol, or just doing the intradermal test.</p>\n", "score": 3 } ]

[ "covid-19", "immune-system", "side-effects", "vaccination", "allergy" ]

[ { "answer_id": 25362, "body": "<p>There are no other mRNA vaccines with an allowance for use yet. There have been promising tests before COVID-19 though. See this review article:</p>\n<p>Pardi, N., Hogan, M., Porter, F. et al. mRNA vaccines — a new era in vaccinology. Nat Rev Drug Discov 17, 261–279 (2018). <a href=\"https://doi.org/10.1038/nrd.2017.243\" rel=\"nofollow noreferrer\">https://doi.org/10.1038/nrd.2017.243</a></p>\n<p>Available <a href=\"https://www.nature.com/articles/nrd.2017.243\" rel=\"nofollow noreferrer\">here</a> (Last accessed December 2020)</p>\n", "score": 4 } ]

[ "covid-19", "vaccination" ]

[ { "answer_id": 25391, "body": "<p>We don't know, and may never know or won't know for a long time.</p>\n<p>The reason we think the recently approved mRNA vaccines are effective is due to randomized controlled trials. You take a population of people who haven't previously gotten COVID-19, give half the vaccine and half the placebo, and determine efficacy based on the ratio of subsequent infections in both groups.</p>\n<p>To answer your question, whether there is a benefit to vaccination after having COVID-19, you'd have to repeat the same trial in people who were already infected. That's...probably not going to happen. For one, any protection that prior infection provides is going to mean the &quot;control&quot; group in such a trial has a lower infection rate. This means that the overall <em>power</em> of the study will be lower for the same vaccine protection, so they trial may need to be <em>much much larger</em> to show an effect. Trials are expensive, and there's little reason to do this trial so little chance anyone will want to fund it. Companies manufacturing the vaccine want to show it works in the uninfected population, because most people still remain uninfected. Secondly, to answer conclusively that the vaccine has <strong>no</strong> benefit in people previously infected is even more difficult; it's actually statistically impossible to demonstrate this so it's necessary to set a threshold&gt;0 to compare to. It's very unusual to design trials like this for anything but safety.</p>\n<p>Overall, it's likely that people who have had COVID-19 before will still be recommended to get vaccinated. We won't have sufficient data to recommend against it, and can't be certain those people won't benefit from the vaccine. Prior knowledge of other coronaviruses causing &quot;common cold&quot; illnesses suggests that coronavirus immunity is not long-lasting; the worry is that people with generally cold-like symptoms will only get cold-like immunity to the virus, and hope that the vaccines will elicit a stronger immune response. We still don't know exactly how long vaccine protection will last (because the vaccines are still so new), but it's far more likely for us to understand the extent of vaccine protection than to understand the effect of natural infection since the former is possible in a controlled study setting.</p>\n", "score": 8 }, { "answer_id": 25417, "body": "<p>As I understand the matter:</p>\n<ul>\n<li>there are case of C19 where the same person is <a href=\"https://www.cdc.gov/coronavirus/2019-ncov/your-health/reinfection.html\" rel=\"nofollow noreferrer\">re-infected after recovery</a></li>\n<li>Moderna / Pfizer vaccines tout <a href=\"https://lmgtfy.app/?q=covid%2019%20vaccine%20efficacy%20rate\" rel=\"nofollow noreferrer\">90%+ efficacy</a>.</li>\n</ul>\n<p>If this is the case and 90%+ efficacy holds for recovered patients, then it follows that yes, it is reasonable to expect a benefit of a COVID-19 vaccination if one had COVID-19.</p>\n", "score": 1 }, { "answer_id": 25719, "body": "<p>There's now more data supporting a <strong>yes</strong> answer: Moderna just published results of a phase 2 trial that found that vaccinated individuals had higher antibody responses than people who had symptomatic COVID-19. See Figure 3 of <a href=\"https://www.sciencedirect.com/science/article/pii/S0264410X21001535\" rel=\"nofollow noreferrer\">Chu 2021</a>. While antibody levels aren't a direct measure of protection from disease, those two things generally correlate very well.</p>\n", "score": 1 } ]

[ "covid-19", "vaccination" ]

[ { "answer_id": 25457, "body": "<p><strong>Tetanus</strong> infections do not produce immunity. Vaccination with the tetanus toxoid does. (<a href=\"https://www.cdc.gov/tetanus/clinicians.html\" rel=\"nofollow noreferrer\">ref</a>)</p>\n<p>Moderna recently published results from a Phase II study for <strong>SARS-CoV-2</strong> that showed that people who were vaccinated had higher spike-binding and neutralizing antibody responses than serum from people who had symptomatic COVID-19 (see Figure 3 of <a href=\"https://www.sciencedirect.com/science/article/pii/S0264410X21001535\" rel=\"nofollow noreferrer\">Chu 2021</a>). Note that this is just looking at antibody responses, not protection from disease.</p>\n<p><strong>Dengue virus</strong> famously exhibits &quot;<a href=\"https://en.wikipedia.org/wiki/Antibody-dependent_enhancement\" rel=\"nofollow noreferrer\">antibody-dependent enhancement</a>&quot; of disease, meaning that it's typically worse each time you get the disease. There's no vaccine for dengue, but if there were, it would necessarily be more protective than infection.</p>\n", "score": 2 } ]

[ "vaccination" ]

[ { "answer_id": 25600, "body": "<p>I found a different upper bound. From <a href=\"https://marginalrevolution.com/marginalrevolution/2021/01/the-new-strain-and-the-need-for-speed.html\" rel=\"nofollow noreferrer\">https://marginalrevolution.com/marginalrevolution/2021/01/the-new-strain-and-the-need-for-speed.html</a> (emphasis mine):</p>\n<blockquote>\n<p>One of the big virtues of mRNA vaccines is that much like switching a bottling plant from Sprite to 7-Up we could tweak the formula and produce a new vaccine using exactly the same manufacturing plants. Moreover, Marks and Hahn at the FDA have said that the FDA would not require new clinical trials for safety and efficacy just smaller, shorter trials for immune response (similarly we don’t do new large-scale clinical trials for every iteration of the flu vaccine.) Thus, if we needed it, <strong>we could modify mRNA vaccines (not other types) for a new variant in say 8-12 weeks</strong>. As Zeynep notes, however, the vaccines are very likely to work well for the new variant. It’s nice to know, however, that we do have some flexibility.</p>\n</blockquote>\n<p>And <a href=\"https://www.axios.com/biontech-vaccine-covid-variant-2388f93a-190a-45f4-ba97-ac50f33fabe6.html\" rel=\"nofollow noreferrer\">this reference</a> says that the BioNTech CEO said it would be 2-6 weeks plus testing.</p>\n", "score": 2 } ]

[ "covid-19", "vaccination" ]

[ { "answer_id": 25769, "body": "<p>First, we should focus on &quot;ivermectin plus covid19 or a virus that mimics covid19.\nFor now, the <a href=\"https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy\" rel=\"nofollow noreferrer\">FDA</a> recognizes ivermectin as an antiviral drug. Therefore, the comparison should be &quot;antiviral drug + covid19 or covid19-mimicking virus&quot;.</p>\n<p>The <a href=\"https://covid19criticalcare.com/\" rel=\"nofollow noreferrer\">FLCCC</a> may have a bit of a bias because they are enthusiastic proponents of ivermectin, but their <a href=\"https://covid19criticalcare.com/wp-content/uploads/2020/11/FLCCC-Ivermectin-in-the-prophylaxis-and-treatment-of-COVID-19.pdf\" rel=\"nofollow noreferrer\">report</a> has the following description;</p>\n<blockquote>\n<p>Arevalo et al investigated in a murine model infected with a type 2 family RNA coronavirus\nsimilar to SARS-CoV-2, (mouse hepatitis virus), the response to 500 mcg/kg of ivermectin vs.\nplacebo (Arevalo et al., 2020). The study included 40 infected mice, with 20 treated with ivermectin,\n20 with phosphate buffered saline, and then 16 uninfected control mice that were also given phosphate\nbuffered saline. At day 5, all the mice were euthanized to obtain tissues for examination and viral load\nassessment. The 20 non-ivermectin treated infected mice all showed severe hepatocellular necrosis\nsurrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic\nviral load (52,158 AU), while in the ivermectin treated mice a much lower viral load was measured\n(23,192 AU; p&lt;0.05), with only few livers in the ivermectin treated mice showing histopathological\ndamage such that the differences between the livers from the uninfected control mice were not\nstatistically significant. <br><br>\nDias De Melo and colleagues recently posted the results of a study they did with golden\nhamsters that were intranasally inoculated with SARS-CoV-2 virus, and at the time of the infection,\nthe animals also received a single subcutaneous injection of ivermectin at a dose of 0.4mg/kg on day 1\n(de Melo et al., 2020). Control animals received only the physiologic solution. They found the\nfollowing among the ivermectin treated hamsters; a dramatic reduction in anosmia (33.3% vs 83.3%,\np=.03) which was also sex-dependent in that the male hamsters exhibited a reduction in clinical score\nwhile the treated female hamsters failed to show any sign of anosmia. They also found significant\nreductions in cytokine concentrations in the nasal turbinate’s and lungs of the treated animals despite\nthe lack of apparent differences in viral titers</p>\n</blockquote>\n<p>Based on this statement, the following two papers seem to fit our purpose. However, it should be noted that these are preprints.</p>\n<ul>\n<li><a href=\"https://www.biorxiv.org/content/10.1101/2020.11.02.363242v1\" rel=\"nofollow noreferrer\">Arevalo et al</a></li>\n<li><a href=\"https://www.biorxiv.org/content/10.1101/2020.11.21.392639v1\" rel=\"nofollow noreferrer\">de Melo et al</a></li>\n</ul>\n<p>Arevalo et al has following description;</p>\n<blockquote>\n<p>However, experimental conditions with SARS-CoV2 are not easily available in research laboratories due to biosecurity reasons, thus having in vivo preclinical data is not always easy.</p>\n</blockquote>\n<p><strong>Isn't this description the answer to your question?</strong> If it is clinical research, there is no need to contain infected animals in a laboratory. It must be quite difficult to control a virus that is considered more dangerous than the flu. Also, in the case of influenza, the pharmaceutical companies are probably planning and conducting trials over a long period of time. In contrast, MSD does not seem to be active in the coronary indication of ivermectin.</p>\n", "score": 3 } ]

[ "reference-request", "antivirals", "animal-model" ]

[ { "answer_id": 25723, "body": "<p>On the same CDC website, there is a section titled:</p>\n<blockquote>\n<p><a href=\"https://www.cdc.gov/nchs/covid19/mortality-overview.htm\" rel=\"nofollow noreferrer\">COVID-19 Mortality Overview</a></p>\n</blockquote>\n<p>A link on this page (last but one) leads to a detailed analysis of comorbidalities:</p>\n<blockquote>\n<p><a href=\"https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm#Comorbidities\" rel=\"nofollow noreferrer\">Most Frequently Listed Comorbidities with COVID-19 Deaths</a></p>\n</blockquote>\n<p>and also adds that as of 2nd Feb 2021, deaths involving:</p>\n<ul>\n<li>Influenza/Pneumonia (44%)</li>\n<li>Hypertension (20%)</li>\n<li>Diabetes (16%)</li>\n<li>Dementias (15%)</li>\n<li>Sepsis (9%)</li>\n</ul>\n<p>i.e. the patients already had these illnesses <strong>before</strong> catching COVID-19, and later died.</p>\n", "score": 1 } ]

[ "covid-19", "statistics", "death", "covid-19-datasets", "pneumonia" ]

[ { "answer_id": 25928, "body": "<p><a href=\"https://www.chop.edu/news/long-term-side-effects-covid-19-vaccine\" rel=\"noreferrer\">This general-audience article</a> from Children's Hospital of Philadelphia gives a good overview of reasons to believe that long-term side effects are unlikely. To summarize its two main points:</p>\n<ul>\n<li>Previous vaccine research and development has found that most side effects occur within about two months. The FDA approval process for COVID vaccines required the trial to follow participants for eight weeks before submitting the vaccine for approval.</li>\n<li>Although the Pfizer and Moderna vaccines are the first mRNA vaccines in wide use, previous mRNA vaccines were developed and tested for Zika, influenza, and other diseases. Thus although the technology is &quot;new&quot; it is not as if this is the first time anyone has been injected with mRNA.</li>\n</ul>\n<p>In assessing long-term side effects, one problem is you have to wait a long time, but another problem is that the longer you wait, the more difficult it becomes to track the results and determine which events can be attributed to the vaccine. Answers to <a href=\"https://medicalsciences.stackexchange.com/questions/23094/was-there-ever-a-vaccine-candidate-that-showed-negative-side-effects-many-months\">this question</a> discuss such issues with the oral polio vaccine.</p>\n<p>There is no way to completely rule out the possibility of totally unexpected side effects that don't show up until much later. You can't really know what will happen in ten years until ten years have passed. However, all that is known from previous vaccines suggests it is unlikely that some catastrophic side effect will suddenly arise years later.</p>\n<p>Your last question is also relevant: any decision about the use of the vaccine has to take into account the risks of <em>not</em> using it. Given the massive public health crisis and other societal damage caused by COVID-19, there would probably need to be significant justification for waiting, say, an extra year &quot;just to be sure&quot; that no side effects emerged in that time. Also, preliminary data on &quot;long COVID&quot; mean that it is also possible there will be long-term &quot;side effects&quot; of COVID-19 itself, meaning that delaying the vaccine to avoid its possible side effects could just result in people suffering different long-term effects from the disease. So even if a catastrophic vaccine side effect <em>did</em> arise years later, that could still be better than not getting the vaccine. (Of course, we won't know the long-term effects of COVID until time passes, just as we won't know the long-term effects of the vaccine.)</p>\n<p>Another thing to remember is that people's subjective feelings about risk levels are often only vaguely connected to reality. I'm sure there are people out there who worry about the risk of the COVID vaccine but smoke a pack of cigarettes a day; three guesses which one of those is likely to pose a greater health risk. Some people worry about the risk of dying in a crash when they get on a commercial airline flight in the US, despite the fact that annual total deaths from such events rarely exceed zero. (<a href=\"https://scholarsbank.uoregon.edu/xmlui/bitstream/handle/1794/22549/Slovic_089.pdf\" rel=\"noreferrer\">Here</a> is one classic paper on risk perception.) Fear of long-term side effects is as likely to be due to the human tendency to exaggerate unfamiliar risks as it is to be due to any actual risk from the vaccine. In other words, even apart from the scientific evidence for the safety of this vaccine, there is a fair amount of scientific evidence that how safe you think something is may not be a good predictor of how safe it actually is.</p>\n", "score": 8 }, { "answer_id": 26213, "body": "<p>Since there are a number of vaccine technologies being used for Covid vaccines, a complete answer is complex.</p>\n<p>Perhaps the simplest situation is that of the mRNA vaccines (e.g. Pfizer and Moderna). With these, a short piece of mRNA (the genetic &quot;working instructions&quot; that direct the production of one or more proteins) is injected into a person, enters some of their cells, and directs them to make a slightly modified version of the Covid &quot;spike&quot; protein. Only the mRNA and some fatty molecules that coat the mRNA and protect it until it gets into the cell are injected.</p>\n<p>The fatty molecules are small and simple and quite safe. Although a very few people may have an allergic reaction to them, that shows up very quickly and is the reason for the post-shot 15-30 minute waiting period. We are confident that there will be no long-term effects from the tiny amount of fatty molecules.</p>\n<p>The mRNA is essentially a small snippet of the virus's mRNA. The spike protein it codes for is used by a full-blown intact virus to attach to a cell and &quot;inject&quot; a full virus mRNA into that cell as the first stage of infection. However, the vaccine mRNA snippet contains no instructions for the other viral proteins, so no infection results and no working viruses are produced. The spike protein that is made appears on the cell's surface, both whole and in pieces, and the body's immune system recognizes these as foreign molecules appearing on the body's own cells, triggering an immune response. What happens over the next few weeks is that out of the body's many antibody-producing cells (B cells), each recognizing a single semi-random shape, those that match the shape of part of the spike protein get activated, divide over and over, and produce lots of antibodies matching that shape. At the same time, T cells, also each recognizing a single semi-random shape, get activated and divide if they match the shape of part of the spike protein. Some of these T cells directly kill cells showing part of the spike protein on their surface (presumably, infected cells). Some of the T cells activate B cells matching the spike protein so they produce more antibodies, which circulate in the blood.</p>\n<p>Over a time span of months, the antibody levels slowly drop if no further spike protein is present, but a small number of the B cells and T cells continue to circulate for months or years. If they are again activated by the presence of spike protein, they quickly jump-start the reaction process to produce more B cells, antibodies and T cells in only a day or two instead of the few-week process from a first exposure. The 2nd shot of 2-dose vaccines triggers this second phase, which helps the &quot;memory&quot; effect last even longer and be more potent at the next exposure (i.e. when actually exposed to the real virus).</p>\n<p>The whole process triggered by the vaccine mRNA is a subset of that in the real viral infection -- the actual viral infection also involves more viral genes and additional attacks on immune system and other cells. Thus, any reaction that is due to the vaccine should also happen in an actual viral infection, so in theory there is nothing to be gained and much to lose by forgoing an mRNA vaccine and instead waiting to get an actual Covid virus infection.</p>\n<p>There is an additional danger in waiting to get vaccinated: the live Covid virus is mutating, and selection seems to be favoring &quot;variants&quot; that infect people much more easily and/or make people sicker once they are infected. Thus, the longer one waits to get a vaccine, the greater the chance of being infected by Covid once exposed, and the greater the chance of more serious illness once infected.</p>\n<p>The above analysis does not apply for other types of vaccines, such as those that use modified or crippled helper viruses to introduce parts of the Covid virus genetic material into cells, as the additional material introduced into cells is substantially more complex than just some fatty molecules.</p>\n<p>PS - In general, a vaccine just gives the body's immune response a &quot;preview&quot; of a likely future infectious agent, so that system is able to respond within hours or days instead of weeks once that agent infects the body, and clear it with little or no obvious illness symptoms. We are constantly exposed to infectious agents, triggering the specific immune system at some level probably daily. This immune response is so important to continued life that the system has been maintained and extended by evolution over hundreds of millions of years in vertebrate animals. That would likely not have been the case if it were easy to induce negative long-term consequences by triggering it (e.g. from vaccines). Thus, you can think of &quot;vaccines&quot; as essentially having a many-hundred-million year good safety record.</p>\n", "score": 1 } ]

[ "covid-19", "virus" ]

[ { "answer_id": 25953, "body": "<p>Well, it turns out I was wrong: The Pfizer-BioNTech vaccine's <strong>Phase 3 trials have not been completed</strong>: <a href=\"https://clinicaltrials.gov/ct2/show/NCT04368728\" rel=\"nofollow noreferrer\">US Government listing of the trials</a>. They will not be over before 2023...</p>\n<p>The FDA approval requirements/process is summarized as follows:</p>\n<ol>\n<li>An Investigational New Drug application</li>\n<li>Pre-licensure vaccine clinical trials</li>\n<li>A Biologics License Application (BLA)</li>\n<li>Inspection of the manufacturing facility</li>\n<li>Presentation of findings to FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC)</li>\n<li>Usability testing of product labeling</li>\n</ol>\n<p>it seems the vaccine is (as of March 2021) in step 2 of the above. Although it theoretically may have already cleared steps (3.), (4.) and (6.) independently. Perhaps others can shed light on this point.</p>\n", "score": 2 } ]

[ "covid-19", "clinical-study", "regulatory-agencies" ]

[ { "answer_id": 26033, "body": "<p>Viruses of the herpes family tend to be capable of causing long-term issues due to their particular habit of latent infections. <a href=\"https://en.wikipedia.org/wiki/Shingles\" rel=\"noreferrer\">Shingles</a> is a specific well-known consequence, caused by reactivation of the same virus that causes chickenpox (most often in children). <a href=\"https://en.wikipedia.org/wiki/Epstein%E2%80%93Barr_virus\" rel=\"noreferrer\">Epstein-Barr virus</a> is another herpesvirus that has been associated with long-term symptoms. Both of these are also associated with illness during the acute phase, but these symptoms are quite different from the long-term symptoms and the acute illness can be quite mild.</p>\n<p><a href=\"https://en.wikipedia.org/wiki/Human_papillomavirus_infection\" rel=\"noreferrer\">HPV</a> are a family of viruses most associated with genital warts, but also cervical and other cancers. In particular, the strains most associated with cancer may produce no notable skin infection at all and the first symptoms of the infection are those related to cancer.</p>\n<p>Of course, coronaviruses are not particularly similar to either of these virus families, and worries about long-term effects in youth are <strong>mostly being motivated by the long-term symptoms seen with COVID-19 itself</strong>, including in young people, not only by hypothetical comparisons to other unrelated viruses. As far as I know so far these are mostly case studies or small single-center studies and not all have been peer-reviewed, like <a href=\"https://www.medrxiv.org/content/10.1101/2021.01.23.21250375v1.full\" rel=\"noreferrer\">this one</a> and <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753397/\" rel=\"noreferrer\">this one</a>, and further study is needed, but some things simply can't be known at this time because the pandemic is only just over a year old.</p>\n", "score": 5 } ]

[ "virus" ]

[ { "answer_id": 26286, "body": "<p>I'm not a biologist, and it's difficult to find a straightforward explanation, but it sounds like the cells present the spike protein on their surface, and are then recognized as infected and killed by T-cells.</p>\n<blockquote>\n<p>Some of the spike proteins form spikes that migrate to the surface of the cell and stick out their tips. The vaccinated cells also break up some of the proteins into fragments, which they present on their surface. These protruding spikes and spike protein fragments can then be recognized by the immune system<br />\n…<br />\nThe antigen-presenting cells can also activate another type of immune cell called a killer T cell to seek out and destroy any coronavirus-infected cells that display the spike protein fragments on their surfaces.</p>\n</blockquote>\n<p><a href=\"https://www.nytimes.com/interactive/2020/health/moderna-covid-19-vaccine.html\" rel=\"nofollow noreferrer\">https://www.nytimes.com/interactive/2020/health/moderna-covid-19-vaccine.html</a></p>\n<p>In an article about N protein vaccines:</p>\n<blockquote>\n<p>Tiny fragments of N protein are then displayed on the surface of infected cells. T cells recognise these fragments, identify cells as infected, then kill the cell and consequently any virus.</p>\n</blockquote>\n<p><a href=\"https://theconversation.com/covid-vaccines-focus-on-the-spike-protein-but-heres-another-target-150315\" rel=\"nofollow noreferrer\">https://theconversation.com/covid-vaccines-focus-on-the-spike-protein-but-heres-another-target-150315</a></p>\n<p>Presumably vaccinated cells present the spike protein on the surface the same way as infected cells, and are killed in the same way, but neither of these articles explicitly say so, and I can't find any that do.</p>\n<p><a href=\"https://www.youtube.com/watch?v=rDEduT62Awc\" rel=\"nofollow noreferrer\">https://www.youtube.com/watch?v=rDEduT62Awc</a></p>\n", "score": 1 } ]

[ "vaccination", "mrna" ]

[ { "answer_id": 26293, "body": "<p>Assuming no underlying health problems and similar muscle stores, the obese person would survive significantly longer.</p>\n<p>When eating normally, the body gets most of its energy from free glucose and glycogen stores. After a day or two of no food intake, the body will switch to get most of its energy from the breakdown of fat tissue. Some cell types can't utilize energy from fat, so those cells will get energy from the breakdown of muscle protein which can be converted to glucose (<a href=\"https://www.ncbi.nlm.nih.gov/books/NBK22414/\" rel=\"noreferrer\">Biochemistry Textbook - 30.3.1</a>).</p>\n<p>Death from starvation can occur due to running out of fat tissue, or running out of muscle tissue that can be safely broken down. A person of average body weight would generally run out of fat tissue first, whereas an obese person would run out of muscle tissue first (<a href=\"https://watermark.silverchair.com/12.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAApYwggKSBgkqhkiG9w0BBwagggKDMIICfwIBADCCAngGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM7kXz8ihHKFkF-nGBAgEQgIICSRUCL3Zaqv4xt1DDaWoEP8PSFEFoyxsEhoYtpWDTS6XTn1d4R_TCafoYl9K-LuUtZmQ1btjnF5ld1DSatPQsaR2V2-KoAblzVq1CbymPtIYplz9C5elGh1DsLI1cp4cThIaVWdnYcWAmuj7-ZQ6EHUSy18PSMUjL1yVwDHjdZFhOmNolv_EIZCJGZAbuiHbYEveT00ElX7I60onRhTKWGKhkcCdqL-rEN7UKYv9jn3Go3ONI4eHHr7-H3tPVjgMPGREnj2amF-fzOIlWpnYp9yNn1OayfKQnc-WxU2ascwiAXeNdNm7PNL-QgSbav07uVfyWNE06UMBQx4Cno7uLDr5fxVPhaGf1Dbzp6yrMx5_Aif0uSMTvYBhwFFn53mO9DzICvlKuKMjuSDFAFUn0ZxQ22wIy33IIXtP0PTWMJxOAaZ1TAaCRwh9LjMBGjDNWIFLN94BF9-iWxCUooe8Vnk08scUS9RziNJO6Kx4UZ7VwjoapWg0aEcXARkJNyNqSZROcKmBL3e_t9fKvF_i03dqdcTV4UFt6ALbiXPA2ZYnumypDLxZNDyCaPzRVpmr3zQrx2y5XroU-L3iOH6RMqgqRiE-eX1KJDIymJGO2O-BGwUcRyDVk9xarN9daTIb1Y12_MpFZPmB7b7Mt2N4yWZe1OSFdcgYmSNdOnkfj8QKgm22kRDbIj6zWGrDu8SjUCkVd03YMFUYSyY2ghufwqA9dxig3uV0ZTYF_CKzIs5jcFJWwlozH4wkAGzsqYY3uT5UOI3B_c25YAw\" rel=\"noreferrer\">Review Article - see pg. 15</a>). Assuming they started with the same amount of muscle tissue, that means the obese person would survive longer.</p>\n<p>A caveat: The immune system is significantly weakened in starvation due to metabolic changes, making deadly infections common (<a href=\"https://www.who.int/emergencies/humanitarian-emergencies/famine/en/\" rel=\"noreferrer\">WHO</a>). An obese person would not have advantage against those infections.</p>\n<p>To answer your second framing:</p>\n<p>The average person can survive a long time without eating - about 1 to 3 months (<a href=\"https://www.ncbi.nlm.nih.gov/books/NBK22414/\" rel=\"noreferrer\">Biochemistry Textbook - 30.3.1</a>) (<b>NOTE: This does NOT mean a person can safely fast for more than a day or so at a time. After a few days there will be significant, often permanent damage to many organs</b>). That said, vitamin deficiencies take even longer to develop in most cases (<a href=\"https://www.betterhealth.vic.gov.au/health/healthyliving/vitamins-common-misconceptions#deficiencies-and-illness\" rel=\"noreferrer\">Victoria Dept. of Health</a>), so taking a multivitamin wouldn't help much.</p>\n", "score": 7 }, { "answer_id": 26292, "body": "<p>Yes ... unless the fit person uses their advantage to kill and eat the other.</p>\n<p>This is probably the evolutionary cause of obesity: if you have an irregular food supply, it is sensible to build up a stock, either externally stored food or internally stored fat. This gave us physiology, and preferences, that work less well in rich countries, where you are surrounded 24/7 by a buffet.</p>\n", "score": 3 } ]

[ "body-fat" ]

[ { "answer_id": 27581, "body": "<p>Several folks working together (Chris Rogers, agoodnurse, Carey Gregory) come to a consensus about this certificate as follows.</p>\n<p>CVA is virtually certain to be &quot;Cerebrovascular Accident,&quot; which is an (acute) stroke.</p>\n<p>The term “ASDH” is likely a transposition of the last two letters of “ASHD,” and thus means &quot;Atherosclerotic Heart Disease”.</p>\n<p>Bad handwriting makes &quot;generalized&quot; look like &quot;serialized,&quot; which can be seen by blowing up the image and inspecting with a magnifier. A photo of the blown up image (courtesy of Carey Gregory) is here.\n<a href=\"https://drive.google.com/file/d/1YfmV3Q5_l_6AWEv1fO7OB9oI-ysDjKXE/view\" rel=\"nofollow noreferrer\">enter link description here</a></p>\n<p>AS is a recognized as abbreviation for &quot;Atherosclerosis.&quot;</p>\n<p>Thus, the whole phrase on the second line of the “Other Significant Conditions” box would be “Atherosclerotic Heart Disease with generalized Atherosclerosis.”</p>\n<p>The entire sequence of events appears to be “Acute Congestive Heart Failure” for a few hours and pneumonia for one day, with an acute stroke (CVA or cerebrovascular accident) leading up to the pneumonia and congestive heart failure. These events occurred in a person who had, for years, Parkinson’s Disease, atherosclerotic heart disease with generalized atherosclerosis, and chronic brain disease.</p>\n", "score": 3 }, { "answer_id": 27389, "body": "<p>(I am a molecular biologist, not a doctor)</p>\n<p>(earlier text deleted as wrong)</p>\n<p>My naive reading is that a stroke (CVA) happened, and after a few weeks indirectly caused orthostatic pneumonia (apparently &quot;an older term that refers to pneumonia that develops because the patient is on prolonged bedrest&quot;), which rapidly led to congestive heart failure.</p>\n<p>PS - I think Ankylosing Spondilitis is more of an autoimmune arthritis of the bones of the spine</p>\n", "score": 0 } ]

[ "brain", "neurology", "death", "parkinson" ]

[ { "answer_id": 28923, "body": "<p>This may not be exactly the controls you want, but here is <a href=\"https://www.voanews.com/covid-19-pandemic/vaccines-reduce-risk-long-covid-symptoms-study-finds\" rel=\"nofollow noreferrer\">news</a> about one study that compared &quot;long Covid&quot; symptoms in vaccinated (breakthrough infection) vs unvaccinated:</p>\n<blockquote>\n<p>In a study published Wednesday in the Lancet Infectious Diseases journal, scientists at King’s College London surveyed more than one million fully vaccinated volunteers who used a mobile app to log their symptoms, tests and vaccination status, and compared them to a control group of unvaccinated volunteers.</p>\n<p>The study says that only a fraction of the vaccinated volunteers reported so-called “breakthrough infections,” and that those who did were 73% less likely to be hospitalized. It also said <strong>the chances the vaccinated respondents would continue to suffer from so-called “long COVID” symptoms is reduced by nearly half</strong>.</p>\n</blockquote>\n<p>Slightly more commentary in the <a href=\"https://www.kcl.ac.uk/news/double-vaccination-halves-risk-of-long-covid\" rel=\"nofollow noreferrer\">press release</a>:</p>\n<blockquote>\n<p>Professor Tim Spector from King’s College London and Lead investigator of ZOE COVID Study comments: “Vaccinations are massively reducing the chances of people getting Long COVID in two ways. Firstly, by reducing the risk of any symptoms by 8 to 10 fold and then by halving the chances of any infection turning into Long COVID, if it does happen.”</p>\n</blockquote>\n<p>In the methods section of the <a href=\"https://doi.org/10.1016/S1473-3099(21)00460-6\" rel=\"nofollow noreferrer\">actual paper</a> the (vaccinated) controls are detailed as follows:</p>\n<blockquote>\n<p>For the risk factor analysis, cases had received a first or second dose of a COVID-19 vaccine between Dec 8, 2020, and July 4, 2021; had either a positive COVID-19 test at least 14 days after their first vaccination (but before their second; cases 1) or a positive test at least 7 days after their second vaccination (cases 2); and had no positive test before vaccination. Two control groups were selected (who also had not tested positive for SARS-CoV-2 before vaccination): users reporting a negative test at least 14 days after their first vaccination but before their second (controls 1) and users reporting a negative test at least 7 days after their second vaccination (controls 2). Controls 1 and controls 2 were matched (1:1) with cases 1 and cases 2, respectively, by the date of the post-vaccination test, health-care worker status, and sex. In the disease profile analysis, we sub-selected participants from cases 1 and cases 2 who had used the app for at least 14 consecutive days after testing positive for SARS-CoV-2 (cases 3 and cases 4, respectively). Controls 3 and controls 4 were unvaccinated participants reporting a positive SARS-CoV-2 test who had used the app for at least 14 consecutive days after the test, and were matched (1:1) with cases 3 and 4, respectively, by the date of the positive test, health-care worker status, sex, body-mass index (BMI), and age. We used univariate logistic regression models (adjusted for age, BMI, and sex) to analyse the associations between risk factors and post-vaccination infection, and the associations of individual symptoms, overall disease duration, and disease severity with vaccination status.</p>\n</blockquote>\n", "score": 1 } ]

[ "covid-19", "statistics" ]

[ { "answer_id": 27629, "body": "<p>The short answer is maybe, but rarely, and the whole Covid virus has never been seen to integrate into the cell's DNA intact. Any integration requires &quot;helper&quot; molecules not found in the Covid virus, and only very rarely found in a normal cell.</p>\n<p>It's been known for many decades that RNA in a cell can be converted into DNA and integrated into the cell's genomic DNA. This is extremely rare except under certain conditions. For example, a class of viruses (including HIV) called &quot;retroviruses&quot; carries an enzyme called reverse transcriptase or RT that the viruses use to convert their RNA genome into DNA and &quot;hide&quot; by splicing that into the cell's own DNA. Covid does NOT have such an enzyme.</p>\n<p>However, during evolution, our cells have picked up many small DNA elements (&quot;jumping genes&quot; or transposons), many of which &quot;hop&quot; by reverse-transcribing their transcript and inserting that new DNA somewhere in the cell's DNA. They continue to &quot;hop&quot; to this day, rarely. Occasionally, they make an error and convert some of the other mRNA in the cell into DNA and insert it into the genome. LINE1 elements in particular make up almost 20% of our cellular DNA, so the paper's authors tried to see if any LINE1 elements were able to (rarely) incorporate Covid fragments into a cell's DNA.</p>\n<p>Greatly simplified, the authors tried to answer the following questions:</p>\n<ol>\n<li><p>Can laboratory cells which have been engineered to make lots of the LINE1 transposase, then infected with Covid, end up with fragments of Covid virus in their DNA?</p>\n</li>\n<li><p>Can &quot;normal&quot;, non-engineered laboratory cells infected with Covid, end up with fragments of Covid virus in their DNA?</p>\n</li>\n<li><p>Do any patient samples from Covid-infected patients show any fragments of Covid virus in their cellular DNA?</p>\n</li>\n</ol>\n<p>The method the authors used to check this was to massively sequence mRNAs from cells, and look for any that had normal cellular gene sequences spliced onto Covid sequences. Their reasoning was that such chimeric transcripts must represent genes with reverse-transcribed Covid DNA spliced into the genomic DNA of the gene, and so appearing in the gene's RNA transcript. It turned out there was a big technical problem with this (hence the wishy washy conclusions of the paper) - the sequencing sample preparation process will also rarely splice two mRNA sequences together even if they were not spliced in the cell. However, that artificial process tends to almost always only splice two &quot;antisense&quot; strands, while the LINE1 process should have no preference between sense and antisense. Thus, the authors reasoned that if they were finding only antisense/antisense that could be an artifact, while significant amounts of antisense/sense splices would indicate real splices from the genomic DNA.</p>\n<p>The answers they inferred were roughly:</p>\n<ol>\n<li>Yes, artifcially expressing lots of LINE1 tranposase resulted in detectable integration of partial Covid virus sequences in the cellular DNA.</li>\n<li>With more normal laboratory cells, they found many fewer integrated Covid virus fragments, but still found some.</li>\n<li>With patient samples, there were many additional technical problems; they think they found some Covid fragments integrated in cells from 1 patient, but are not nearly as confident with that result as for (1) and (2).</li>\n</ol>\n<p>In any case, the integrated Covid sequences they found seem to be only fragments of the virus (although their techniques could not be fully sure on this); they never found a whole virus integrated into any cell.</p>\n<p>As a practical matter, the &quot;consensus&quot; is correct, but given billions of people and quadrillions of Covid viruses, there might be a few outliers.</p>\n<p>Paper ref:\nReverse-transcribed SARS-CoV-2 RNA can integrate into the genome of cultured human cells and can be expressed in patient-derived tissues\nPNAS May 25, 2021 118 (21) e2105968118; <a href=\"https://doi.org/10.1073/pnas.2105968118\" rel=\"nofollow noreferrer\">https://doi.org/10.1073/pnas.2105968118</a></p>\n<p>LINE1 review: &quot;LINE-1 Elements in Structural Variation and Disease&quot;\nAnnu Rev Genomics Hum Genet. 2011; 12: 187–215.\ndoi: 10.1146/annurev-genom-082509-141802\nAuthor's manuscript freely downloadable from <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124830/pdf/nihms606127.pdf\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124830/pdf/nihms606127.pdf</a></p>\n<p><a href=\"https://biology.stackexchange.com/questions/107418/is-this-pfizer-related-paper-reliable\">Related Question explaining why another paper is NOT reliable</a>:\n&quot; Intracellular Reverse Transcription of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 In Vitro in Human Liver Cell Line by Alden et al. ( Curr. Issues Mol. Biol. 2022, 44(3), 1115-1126; &quot;</p>\n<p><strong>Update Apr 2022</strong>: Here are two additional papers comments that are highly relevant:</p>\n<p><a href=\"https://journals.asm.org/doi/10.1128/JVI.00294-21\" rel=\"nofollow noreferrer\">journals.asm.org/doi/10.1128/JVI.00294-21</a>&quot;Host-Virus Chimeric Events in SARS-CoV-2-Infected Cells Are Infrequent and Artifactual&quot;</p>\n<p><a href=\"https://doi.org/10.1073/pnas.2109066118\" rel=\"nofollow noreferrer\">https://doi.org/10.1073/pnas.2109066118</a>&quot;No evidence of SARS-CoV-2 reverse transcription and integration as the origin of chimeric transcripts in patient tissues&quot;</p>\n", "score": 14 }, { "answer_id": 30960, "body": "<p>Answering on</p>\n<p>&quot;If my understanding is true, why is there a consensus saying that mRNA cannot go into the DNA ?&quot;</p>\n<p>I highlighted several quotes from the paper's references that may answer your question:</p>\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038843/\" rel=\"nofollow noreferrer\">Akira Shimizu, Characterisation of cytoplasmic DNA complementary to non-retroviral RNA viruses in human cells</a>, 2014:\n&quot;...Thus, the genetic information of the <em>non-retroviral RNA virus genome <strong>can flow into the DNA</strong></em> of mammalian cells expressing LINE-1-like elements.&quot; That study was on &quot;infection of various human cell lines and primary fibroblasts with the vesicular stomatitis virus (VSV)&quot;.</p>\n<p><a href=\"https://pubmed.ncbi.nlm.nih.gov/19150848/\" rel=\"nofollow noreferrer\">Geuking et al., Recombination of Retrotransposon and Exogenous RNA Virus Results in Nonretroviral cDNA Integration, 2009</a>:\n&quot;We found that <em><strong>illegitimate</strong></em> recombination between an exogenous <em>nonretroviral</em> RNA virus, lymphocytic choriomeningitis virus, and the endogenous intracisternal A-type particle (IAP) retrotransposon occurred and led to reverse transcription of exogenous viral RNA.&quot;</p>\n<p><a href=\"https://www.nature.com/articles/36740\" rel=\"nofollow noreferrer\">Weiss/Kellam, <em><strong>Illicit</strong></em> viral DNA</a>,, Nature volume 390, pages235–236 (1997):</p>\n<p>&quot;More than 20 years ago, the late Victor Zhdanov (...) claiming that complementary DNA copies of RNA viruses such as measles and polio occurred in retrovirus-infected cells. The observations raised eyebrows at the time, because promiscuous cDNA synthesis seemed to run counter to everything known about viral replication. But the data were neither confirmed nor refuted, and were soon forgotten.&quot;</p>\n<p>These quotes show that Crick's dogma - from DNA to RNA, with the exception of retro-viruses - still holds. The fact that the study you refer to was severely scrutinized and its validity questioned by peer review seems to lay proof that the dogma you speak of is valid even today.</p>\n<p>To sum up: Crick's dogma still holds (and will), and the study in question contradicts that rule in its results.</p>\n<p>Note:\nSee Geuking et al. in the context of the quote about distinguishing between retro-transcription and integration into the genome. These authors speak of, in particular, &quot;recombination&quot; between non-retro-virus and retro-transcriptional elements termed endogenous virus (virus-viral recombination). Crick's rule, in a restricted sense, may not cover integration of DNA into the genome, and, conversely, it may play down the role of non-genome DNA, external or episomal.</p>\n", "score": 0 } ]

[ "covid-19", "sars-cov-2", "dna", "mrna" ]

[ { "answer_id": 29463, "body": "<p>I will try to summarize what I have gathered till now from reading on my own and insights from other people.</p>\n<p>In the <a href=\"https://www.frontiersin.org/articles/10.3389/fimmu.2019.03054/full\" rel=\"nofollow noreferrer\">study 1</a> that I have cited, they have found that on mice, a dose of 100 micrograms of TLR7, 3 times a week, for 8 weeks not only leads to development of lupus-like disease, but is also lethal. But human beings are larger than mice. If we assume a rough <a href=\"https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1539-6924.1988.tb01158.x\" rel=\"nofollow noreferrer\">scaling factor for toxicity</a> as (body weight)^0.67, and assume that human beings are 3000 times heavier than mice, we find a scaling factor of 3000^0.67 which is approximately 200. That is, a similar test done on human beings, but with a dose of 20 milligram instead, will give similar results.</p>\n<p>So, we observe the following 2 points.</p>\n<ol>\n<li><p>A single dose of Covaxin contains 15 microgram of TLR 7/8 agonist.\nThat is, one dose of Covaxin gives about 1 part in 1400 of the dose\nthat was given to the mice.</p>\n</li>\n<li><p>Also, it should be noted that human beings are exposed to a total of\n2 doses of Covaxin, 4-6 weeks apart, in contrast with the 24 doses\nthat the mice received in 8 weeks.</p>\n</li>\n</ol>\n<p>I do not know what to conclude from these two points. But these points gives us some frame of reference to judge the situation.</p>\n<p>Now, it should be noted that the people who developed Covaxin did do a maximum tolerated dose study <a href=\"https://www.biorxiv.org/content/10.1101/2020.09.09.285445v2\" rel=\"nofollow noreferrer\">(study 2)</a> on mice. They found that the mice tolerated a single dose of 20 microgram of TLR7/8 agonist, and</p>\n<blockquote>\n<p>demonstrated lack of erythema, edema or any other macroscopic lesions\nat the site of injection. (...) Histopathology examination of the injection\nsite showed active inflammation, as demonstrated by mononuclear cell\ninfiltration, which is likely a physiological local inflammatory\nreaction caused by aluminium salt in the vaccine adjuvant preparation.\nIn any of the studies conducted, there were no mortality or no changes\nobserved in clinical signs, body weight gain, body temperature, or\nfeed consumption in the treated animals. (...) All animals were necropsied and examined macroscopically.</p>\n</blockquote>\n<p>Now, a single dose of 20 microgram is equivalent to about a 4 milligram dose in human beings, if you account for the scaling factor of 200. That is, they exposed the mice to about 300 times of what a human being would be exposed in a single dose of Covaxin (15 microgram), and found no red flags.</p>\n<p>One potential issue could be that unlike in the <a href=\"https://www.frontiersin.org/articles/10.3389/fimmu.2019.03054/full\" rel=\"nofollow noreferrer\">study 1</a>, the <a href=\"https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1539-6924.1988.tb01158.x\" rel=\"nofollow noreferrer\">study 2</a> perhaps did not actively look for the link between TLR7 agonism and development of lupus-like disease. For example, the study 1 found that TLR7 Stimulation Accelerates\nGlomerulonephritis in NZM2410 Mice and also leads to Splenomegaly (enlargement of spleen). Perhaps the <a href=\"https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1539-6924.1988.tb01158.x\" rel=\"nofollow noreferrer\">study 2</a> did not look for nephritis. As for Splenomegaly, they may have examined the spleen and did not found any enlargement in the spleen, which is a good sign. They did not actively mention this observation.</p>\n<p>My point is, in <a href=\"https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1539-6924.1988.tb01158.x\" rel=\"nofollow noreferrer\">study 2</a>, they have not mentioned issues like autoimmunity or lupus like disease anywhere in the paper. I think they should made a reference to why this is something not to be worried about.</p>\n", "score": 2 } ]

[ "covid-19", "vaccination", "risks", "autoimmune-disease" ]

[ { "answer_id": 28937, "body": "<ul>\n<li><a href=\"https://pubmed.ncbi.nlm.nih.gov/\" rel=\"nofollow noreferrer\"><strong>PubMed</strong></a> comprises more than 32 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full text content from PubMed Central and publisher web sites.</li>\n</ul>\n<p>After you search using the search box on the main web site, select in the left column this filter:\n<code>text availability: free full text</code>.</p>\n<ul>\n<li><a href=\"https://www.ncbi.nlm.nih.gov/pmc/\" rel=\"nofollow noreferrer\"><strong>PubMed Central</strong></a> (PMC) is a free <strong>full-text</strong> archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health's National Library of Medicine (NIH/NLM).</li>\n</ul>\n", "score": 2 }, { "answer_id": 28915, "body": "<p>There are several open access journals and collections that you can search.</p>\n<ul>\n<li>The <a href=\"https://jamanetwork.com/journals/jamanetworkopen\" rel=\"nofollow noreferrer\">Journal of the American Medical Association (JAMA) Open Access network</a>.</li>\n<li>The <a href=\"https://www.nejm.org/about-nejm/access-levels\" rel=\"nofollow noreferrer\">New England Journal of Medicine allows open access to certain articles</a>.</li>\n<li><a href=\"https://www.thelancet.com/open-access\" rel=\"nofollow noreferrer\">Several journals in the Lancet family are open access</a>.</li>\n<li>The British Medical Journal has an open access counterpart, <a href=\"https://bmjopen.bmj.com/\" rel=\"nofollow noreferrer\">BMJ Open</a>.</li>\n</ul>\n<p>Also, for many articles, the authors will happily share a copy with you if you email them and ask politely. Since they're busy, it might take a while for them to reply, but at least with academics, many are happy to share their work.</p>\n", "score": 1 }, { "answer_id": 28917, "body": "<p>It's often useful to search on a big database (like <a href=\"https://pubmed.ncbi.nlm.nih.gov/\" rel=\"nofollow noreferrer\">PubMed</a>) to find articles you're interested in, then next try to figure out how to access them.</p>\n", "score": 1 }, { "answer_id": 28948, "body": "<ul>\n<li><a href=\"http://scholar.google.com/\" rel=\"nofollow noreferrer\">Google Scholar</a> is another good place to try to find a freely available PDF for a given article.</li>\n<li><a href=\"https://www.medrxiv.org/\" rel=\"nofollow noreferrer\">https://www.medrxiv.org/</a>: preprints of medical papers</li>\n<li><a href=\"https://www.biorxiv.org/\" rel=\"nofollow noreferrer\">https://www.biorxiv.org/</a>: preprints of biology papers</li>\n<li><a href=\"https://connect.medrxiv.org/relate/content/181\" rel=\"nofollow noreferrer\">https://connect.medrxiv.org/relate/content/181</a>: COVID-specific articles.</li>\n</ul>\n", "score": 0 } ]

[ "covid-19", "research" ]

[ { "answer_id": 29057, "body": "<p>Carpiano et al (2019) found that lower parent education is associated with higher odds of being concerned about measles, mumps, and rubella (MMR) vaccination. Kumar et al (2016) discuss the link between vaccine hesitancy and the level of parental education.</p>\n<blockquote>\n<p>SES [socioeconomic status] [(parent education, household income)] differences in KAB [knowledge, attitudes, and beliefs ... about vaccinations] mostly center on vaccine-specific side effect and safety concerns, with lower education and income levels associated with higher odds of being concerned.</p>\n</blockquote>\n<p><em>Carpiano RM, Polonijo AN, Gilbert N, Cantin L, Dubé E. Socioeconomic status differences in parental immunization attitudes and child immunization in Canada: Findings from the 2013 Childhood National Immunization Coverage Survey (CNICS). Prev Med. 2019 Jun;123:278-287. doi: 10.1016/j.ypmed.2019.03.033. Epub 2019 Mar 20. PMID: 30904601. <a href=\"https://pubmed.ncbi.nlm.nih.gov/30904601/\" rel=\"nofollow noreferrer\">abstract</a></em></p>\n<blockquote>\n<p><strong>Host/parental specific factors</strong><br />\nRace, education and income: These individual characteristics may have a direct impact on the person’s concept of the risks and benefits of vaccination along with the risks and sequelae of a VPD. Some studies demonstrate that African-Americans have lower immunization coverage levels compared to other race groups in America. This supports the fact that ethnicity/race is associated with differential levels and types of immunization concerns. However recent data after adjusting for poverty status have not shown significant difference in coverage levels by racial groups [53]. One of the factors implicated in vaccine hesitancy is the level of parental education and studies in the past have demonstrated greater distrust for medical professionals amongst communities with less formal education. Due to the lower education level, their information about vaccines and their effect is less as compared to more educated parents and the parents seek out alternative sources such as family members and other parents in the community or the media for reliable information.</p>\n</blockquote>\n<p><em>Kumar, D., Chandra, R., Mathur, M. et al. Vaccine hesitancy: understanding better to address better. Isr J Health Policy Res 5, 2 (2016). <a href=\"https://doi.org/10.1186/s13584-016-0062-y\" rel=\"nofollow noreferrer\">https://doi.org/10.1186/s13584-016-0062-y</a>: <a href=\"https://link.springer.com/article/10.1186/s13584-016-0062-y\" rel=\"nofollow noreferrer\">full text</a></em></p>\n", "score": 3 }, { "answer_id": 29061, "body": "<p>There is a <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078590/\" rel=\"nofollow noreferrer\">2016 study (Larson et al.)</a> on 67 countries (Africa is underrepresented, but the rest of the continents have decent coverage). Regarding education it found that</p>\n<blockquote>\n<p>Any level of education elevates pro-vaccine views for importance, efficacy, and religious compatibility but not for vaccine safety.</p>\n<p><a href=\"https://i.stack.imgur.com/eoDmq.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/eoDmq.png\" alt=\"enter image description here\" /></a></p>\n</blockquote>\n<p>(I've cropped the table to the relevant part. It has odds ratios and their 95% CIs in a logistic regression model. The paper claims to have followed <a href=\"https://en.wikipedia.org/wiki/Strategic_Advisory_Group_of_Experts\" rel=\"nofollow noreferrer\">SAGE</a>-suggested questions in selecting those factors.)</p>\n<p>It also says that</p>\n<blockquote>\n<p>Further systematic reviews have highlighted the variability of correlations found between education and vaccine confidence, with no clear pattern except to show that education does not always imply confidence (Brown et al., 2010, Larson et al., 2014a, Larson et al., 2014b).</p>\n</blockquote>\n<p>(They are self-citations to an extent as Larson is also lead author for this 2016 survey)</p>\n<p>Of those &quot;Understanding vaccine hesitancy around vaccines and vaccination\nfrom a global perspective: A systematic review of published literature,\n2007–2012&quot; says (I'm quoting two paras because SES was linked with education):</p>\n<blockquote>\n<p>Level of income/Socioeconomic Status (SES) was identified\nas a significant factor affecting vaccine acceptance in eight stud-\nies. In two studies in the USA, both high and low\nincome/SES were indicated as barriers to vaccination. In Nigeria,\nlow income/SES was identified as both a barrier and promoter, and in Burkina Faso, two studies identified high income/SES as\na promoter. In India, higher income was noted as a promoter\nwhile in Bangladesh, both high and low income/SES were\nfound to promote vaccination. Middle income was non-significant. The reasons why these factors were influential are not always\nexplained, and when they are, other influencing factors are usually\ncited. For example, lower income in the USA was linked to issues\nof trust in the health provider and in Nigeria it was a barrier because it related to both low education as well as to access\nissues.</p>\n<p>Level of education presents an equally mixed set of results. Six\nstudies about India consistently found caregivers’ higher education\nto be a promoter. Studies about China, Lebanon, Israel, Bangladesh and USA all identified higher\neducation as a potential barrier, whereas studies about Greece,\nThe Netherlands, Nigeria and Pakistan identified\nit as a promoter of vaccination. Low education was identified as a\nbarrier in studies about Nigeria, India, China, Kyrgyzstan, and as both a promoter and barrier in the USA. In the DR Congo, both high and low educations were represented as barriers. Additionally, low education was reported as having different effects; in India, illiteracy indicates more of\nan issue with knowledge, whereas in Nigeria and Kyrgyzstan, low\neducation was associated with higher levels of anti-vaccination\nattitudes. The evidence from this review suggests that individual\nfactors cannot be considered in isolation as multiple influences are\nat play.</p>\n</blockquote>\n<p>There are about three dozen papers cited in those two paras, so I'm not going to list them here.</p>\n", "score": 3 } ]

[ "vaccination", "reference-request", "correlation", "social" ]

[ { "answer_id": 29171, "body": "<p>TLDR: in the actual paper/preprint, neither for the raw antibody values nor for the ratio relative to day 1 is there a statistically significant difference between Moderna-after-Moderna and Pfzier-after-Moderna.</p>\n<hr />\n<p>Well, if the <a href=\"https://www.medrxiv.org/content/10.1101/2021.10.10.21264827v1.full.pdf\" rel=\"nofollow noreferrer\">first pdf</a> you linked to is the study all sources talk about, in that one 3x Moderna elicited higher antibodies than anything else... at day 15 post booster; but do note the 95% confidence interval of that figure overlaps the one for\nPfizer-boosting-Moderna (immediately to the right of it), and to a lesser extent also overlaps Moderna-boosting-Pfizer. So you cannot really draw a conclusion from this which of these three combos is better, but Moderna as an initial vaccine seems to have a consistent trend of outperforming the others. Pfizer-boosting-Pfizer (rightmost figure) is outside the confidence interval of Moderna-boosting-Moderna though.</p>\n<p><a href=\"https://i.stack.imgur.com/GoBZF.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/GoBZF.png\" alt=\"enter image description here\" /></a></p>\n<p>There are a two more caveats to this:</p>\n<ul>\n<li><p>They only have data against the alpha variant spike in that pdf. They say on p.15 that data for beta and delta is not yet available (except for Moderna).</p>\n</li>\n<li><p>The Moderna booster dose used in this study is the same as in the original vax (100 mcg), but the FDA panel <a href=\"https://www.biopharminternational.com/view/fda-advisory-council-unanimously-supports-moderna-covid-19-booster-eua\" rel=\"nofollow noreferrer\">gave approval</a> to the 50mcg booster, based on different studies.</p>\n</li>\n</ul>\n<p>The table from &quot;drswanda.com&quot; (that you've also posted) is rather confusing: it chose to transform those raw figures into multipliers. In this transformation vaccines that had lower initial antibodies (J&amp;J, Pfizer) show higher multipliers when boosted, but that doesn't mean they are better. Dr. Swanda chose do this calculation using day-1 as baseline, e.g. for moderna-moderna vs moderna-pfizer:</p>\n<p><a href=\"https://i.stack.imgur.com/xmdgT.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/xmdgT.png\" alt=\"enter image description here\" /></a></p>\n<p>However, those day-1 values are rather questionable baselines. Look at column 2 vs column 8 for day-1 in the original paper; there is a statistically significant difference (non overlapping CIs) in the day 1 values for moderna vs moderna after two does?? That makes the multipliers using that baseline rather meaningless.</p>\n<p>The main paper doesn't make this terribly clear, but in the <a href=\"https://www.medrxiv.org/content/10.1101/2021.10.10.21264827v2.supplementary-material\" rel=\"nofollow noreferrer\">supplementary tables</a>, the &quot;day 1&quot; measure is pre-boost throughout. So that means they indeed started with two moderna-vaxed groups that had statistically different baselines and ended up with with an overlapping measure post boost (either moderna of pfizer). Unfortunately this doesn't let you make any real inference, except as a trend, maybe.</p>\n<p>By the way, this is discussed to some extent in the paper:</p>\n<blockquote>\n<p>Our study has limitations. It was not designed to directly compare responses between different booster regimens. The sample size is insufficient for inter-group comparison [...] Volunteers were not randomized into groups, nor stratified with respect to population characteristics or interval from last vaccination.</p>\n</blockquote>\n<p>The last bit might actually explain the significant differences in starting antibody titers between sub-groups that were vaccinated with the same initial vaccine (e.g. Moderna x2).</p>\n<p>So really the press and the twitterati are trying to push this study to conclusions that can't be safely inferred, and which the authors are probably not going to try and (statistically) test... although there is this bit in the preprint mostly singling out the J&amp;J as inferior to the mRNA boosters:</p>\n<blockquote>\n<p>Persons who received an mRNA-based booster vaccination had a four-fold increase in their neutralization response more frequently than those who were boosted with Ad26.COV.S.</p>\n</blockquote>\n<p>That is largely supported by 2nd half of that table 2, but for a strict statistical test, you'd have to pool the data for each booster... because one of those cells (Ad26.COV.S after Pfizer) does overlap some mRNA booster cells in the confidence interval--most ironically perhaps with Moderna after Moderna. I suspect there's some kind of ceiling effect (or diminishing returns) with that one.</p>\n<p><a href=\"https://i.stack.imgur.com/AkxV5.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/AkxV5.png\" alt=\"enter image description here\" /></a></p>\n<p>Also, I don't really see a discussion/explanation why the 4-fold increase in anti-bodies is a clinically relevant threshold.</p>\n<p>More to the point of your question, this 2nd half of the table does have the ratios that were published by Dr. Swanda and they even have confidence intervals here, but there's overlap between Moderna x3 and Pfizer-after-Moderna: the &quot;7.9&quot; has a 6.2-10.1 CI, and the &quot;9.7&quot; has 8.0-11.8. So it's not very sensible to say statistically significant difference exists between those ratios, based on this study.</p>\n", "score": 2 } ]

[ "covid-19", "statistics", "covid-19-datasets", "data", "vaccine" ]

[ { "answer_id": 29225, "body": "<p>You're asking for two (or three) slightly different (but closely related) <a href=\"https://wiki.ecdc.europa.eu/fem/Pages/Incubation%20period,%20Latent%20period%20and%20Generation%20time..aspx\" rel=\"noreferrer\">things</a></p>\n<blockquote>\n<p>The period between exposure and infection is called 'latent period', since the pathogen is present in a 'latent' stage, without clinical symptoms or signs of infection in the host.</p>\n<p>The period between exposure and onset of clinical symptoms is called 'incubation period'.</p>\n<p>The host may become infectious (i.e. able to transmit the pathogen to other hosts) at any moment of the infection. This moment will vary per pathogen.</p>\n</blockquote>\n<p>For Delta, based on the Guangzhou outbreak this summer, the latent period (to PCR detection) <a href=\"https://www.medrxiv.org/content/10.1101/2021.07.07.21260122v2\" rel=\"noreferrer\">has been</a> estimated at 3-5 days interquartile range, fairly centered at 3.7 days average. (Mainstream press coverage <a href=\"https://www.abc.net.au/news/2021-09-29/covid-delta-variant-what-the-science-says/100497804\" rel=\"noreferrer\">here</a>; that press article also says the incubation period is 4-6 days, but there's no clear source of data cited for that. It might come from China CDC, which has been <a href=\"https://www.globaltimes.cn/page/202107/1227847.shtml\" rel=\"noreferrer\">quoted</a> in the Chinese press as saying that the average incubation time was 4.4 days for the Guangdong outbreak.)</p>\n<p>Public health England <a href=\"https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/993879/Variants_of_Concern_VOC_Technical_Briefing_15.pdf\" rel=\"noreferrer\">has put</a> the Delta incubation period (exposure to onset of symptoms) to 2-6 days (interquartile range) with a median of four days for household exposure and to 3-6 days IQR (also with median of 4 days) for non-household exposure.</p>\n<p>Whether someone whose infection is detectable by PCR (at low levels) also capable of transmitting the virus to other is slightly more contentious (and harder to test), but it's probably reasonable to assume the the capability to infect tracks closely the thresholds mentioned above.</p>\n<p>Aside: a <a href=\"https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00648-4/fulltext\" rel=\"noreferrer\">recent study</a> from the UK has highlighted that protection against mere infection (with Delta) from a known &quot;close and prolonged&quot; exposure inside the household to a previously confirmed index case is less than what people might have hoped for (34% to 52% vaccine effectiveness, for a mixture of vaccines; most of those that had such breakthroughs had been vaccinated with the AZ one, but that's probably just a reflection of the UK's vaccine rollout structure.)</p>\n", "score": 8 } ]

[ "covid-19" ]

[ { "answer_id": 29366, "body": "<p>A <a href=\"https://en.wikipedia.org/wiki/Mutation\" rel=\"noreferrer\">mutation</a> is just a genetic change. Mutations include point changes that are simply changes of one base to another (e.g., an &quot;A&quot; to a C, G, or T/U), insertions or deletions of single bases, or larger changes like insertion or duplication of a whole chunk of DNA/RNA.</p>\n<p>Variants for viruses are a bit like a &quot;subspecies&quot; or perhaps even species for other organisms. Species definitions more generally are <a href=\"https://biology.stackexchange.com/questions/100579/defining-species-are-species-an-emergent-property-or-an-ensemble-of-quantitat\">somewhat</a> <a href=\"https://biology.stackexchange.com/questions/39664/how-could-humans-have-interbred-with-neanderthals-if-were-a-different-species\">arbitrary</a> - they are <em>useful categories</em>, and one can define criteria to identify species, but no one criterion is &quot;more correct&quot; than another, and every set of criteria we have come up with so far is dissatisfying in some fashion, such that it isn't typically followed strictly.</p>\n<p>The important consistent thing about species names across all biology, though, is that they are labels for a <em>lineage</em>, a group of entities related by descent.</p>\n<p>I've written an answer about virus variants on <a href=\"https://biology.stackexchange.com/a/101760/27148\">Biology.SE</a>. Quoting from my own answer there:</p>\n<blockquote>\n<p>A virus &quot;species&quot; is just a label to a lineage at one point in time. When we discover separate lineages of a virus, historically they have gotten a new label. It's then possible follow the lineages from there into strains/substrains, etc.</p>\n</blockquote>\n<p>It would be possible to give a new lineage name to each and every virus particle that has a mutation that makes it different from the parent virus it was copied from, but this wouldn't be very practical. Most of these mutations or combinations of mutations aren't practically relevant, so even if these are all <em>technically</em> variants it's not necessary to give each a name (instead you'd refer to the location and substance of the mutation(s)). If they either don't become prominent in the population of viruses of a given type, or if they behave exactly like their parent viruses, there isn't much use in giving a new name. However, when a mutation or group of mutations (and, practically, it's usually going to be a group, even if many of those mutations are not influential) cause part of a virus lineage to stand out in some way (different infection behavior, higher transmission/prevalence) it becomes useful to give it a name, and that's what the named &quot;variants&quot; are that you hear about in the news: names given to lineages that have diverged from the parent virus.</p>\n<p>There are <a href=\"https://talk.ictvonline.org/\" rel=\"noreferrer\">study groups that sit around and talk about these things to decide when we should give a new name</a> and they have some <a href=\"https://en.wikipedia.org/wiki/International_Committee_on_Taxonomy_of_Viruses#Rules_for_taxa\" rel=\"noreferrer\">criteria they use for guidance</a>, but ultimately the purpose of these names is entirely practical. See also <a href=\"https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/\" rel=\"noreferrer\">https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/</a></p>\n<p>In the popular press, you'll probably find that people use terminology a lot more loosely than they do in scientific venues. A variant is a virus lineage that shows one or more impactful mutations from an ancestral version of that virus, so you might hear someone call it a &quot;mutant strain/line/etc&quot;.</p>\n", "score": 11 } ]

[ "covid-19", "genetics" ]

[ { "answer_id": 29376, "body": "<p>The VAERS guideline has this:</p>\n<blockquote>\n<p><strong>What are healthcare providers required to report to VAERS?</strong></p>\n<p>Healthcare providers are required by law to report to VAERS:</p>\n<ul>\n<li>Any adverse event listed in the <a href=\"https://vaers.hhs.gov/docs/VAERS_Table_of_Reportable_Events_Following_Vaccination.pdf\" rel=\"nofollow noreferrer\">VAERS Table of Reportable Events Following Vaccination</a> that occurs within the specified time period\nafter vaccination</li>\n<li>An adverse event listed by the vaccine manufacturer as a contraindication to further doses of the vaccine</li>\n</ul>\n<p>Healthcare providers are strongly encouraged to report:</p>\n<ul>\n<li>Any adverse event that occurs after the administration of a vaccine licensed in the United States, whether or not it is clear that a\nvaccine caused the adverse event</li>\n<li>Vaccine administration errors</li>\n</ul>\n<p>Vaccine manufacturers are required to report to VAERS all adverse\nevents that come to their attention.</p>\n</blockquote>\n<p>The link to that table is:</p>\n<p><a href=\"https://vaers.hhs.gov/docs/VAERS_Table_of_Reportable_Events_Following_Vaccination.pdf\" rel=\"nofollow noreferrer\">https://vaers.hhs.gov/docs/VAERS_Table_of_Reportable_Events_Following_Vaccination.pdf</a></p>\n<p>...and in that table, the days required are listed individually by vaccine. The default is seven (7) days, and in no case does the table indicate a reporting time greater than forty-two (42) days. Because the COVID vaccines are not expressly listed, one would assume that the legal reporting requirement was seven days, the default as listed for the final entry in the table.</p>\n<div class=\"s-table-container\">\n<table class=\"s-table\">\n<thead>\n<tr>\n<th>Vaccine/Toxoid</th>\n<th>Event and interval** from vaccination</th>\n</tr>\n</thead>\n<tbody>\n<tr>\n<td>Any new vaccine recommended by the Centers for Disease Control and Prevention for routine administration to children</td>\n<td>A. Shoulder Injury Related to Vaccine Administration (7 days)<br>B. Vasovagal syncope (7 days) <br>C. Any acute complication or sequelae (including death) of above events (interval - not applicable)<br>D. Events described in manufacturer’s package insert</td>\n</tr>\n</tbody>\n</table>\n</div>\n<p>NOTE: VAERS reporting for the COVID-19 vaccine is NOT required in certain circumstances, as quoted below.</p>\n<blockquote>\n<p>VAERS reporting is not required for the following situations:</p>\n<ul>\n<li>If a mixed series is given intentionally (e.g., due to hypersensitivity to a vaccine ingredient)</li>\n<li>Mixing and matching of booster doses (as of October 21, 2021, mixing and matching of booster doses is allowed)</li>\n</ul>\n</blockquote>\n<p>Full details <a href=\"https://vaers.hhs.gov/faq.html\" rel=\"nofollow noreferrer\">HERE.</a></p>\n<hr />\n<p>More information regarding the vaccine guidelines can be found via the information packaged with it. This may be difficult to find online, but the following site seems to have some of it.</p>\n<p><a href=\"https://vaxopedia.org/2020/12/09/where-are-the-covid-19-package-inserts/\" rel=\"nofollow noreferrer\">https://vaxopedia.org/2020/12/09/where-are-the-covid-19-package-inserts/</a></p>\n<p>More information, on a per-vaccine/vaccine maker basis, can be found via the FDA information, such as the following:</p>\n<p><strong>Moderna</strong>\n<a href=\"https://www.fda.gov/media/144637/download\" rel=\"nofollow noreferrer\">https://www.fda.gov/media/144637/download</a></p>\n<p><strong>Janssen</strong>\n<a href=\"https://www.fda.gov/media/146304/download\" rel=\"nofollow noreferrer\">https://www.fda.gov/media/146304/download</a></p>\n<p><strong>Comirnaty and Pfizer-BioNTech (US formulation)</strong>\n<a href=\"https://www.fda.gov/media/153713/download\" rel=\"nofollow noreferrer\">https://www.fda.gov/media/153713/download</a></p>\n<p><strong>Comirnaty and Pfizer-BioNTech (alternative, non-US formulation)</strong>\n<a href=\"https://www.fda.gov/media/153715/download\" rel=\"nofollow noreferrer\">https://www.fda.gov/media/153715/download</a></p>\n", "score": 1 } ]

[ "covid-19", "vaccination", "legal", "adverse-events" ]

[ { "answer_id": 30659, "body": "<h1>Issues with the 2015 study</h1>\n<h3>Demographics</h3>\n<p>First of all, any conclusions in the paper about the connection between creatine use and TGCC apply almost entirely to Caucasian males, not <em>all</em> males, as you can see from Table 1 that 95% of the cases in the study, and 89% of the control group, involved Caucasians:</p>\n<div class=\"s-table-container\">\n<table class=\"s-table\">\n<thead>\n<tr>\n<th>Race</th>\n<th>Cases</th>\n<th>Controls</th>\n</tr>\n</thead>\n<tbody>\n<tr>\n<td>White</td>\n<td>338</td>\n<td>459</td>\n</tr>\n<tr>\n<td>Other</td>\n<td>18</td>\n<td>54</td>\n</tr>\n</tbody>\n</table>\n</div>\n<p>Combining this with the fact that fewer than 19% of the case subjects and fewer than 13% of the control group ever used MBS (this amounts to only about 3 non-Caucasian TGCC patients in the study having ever used MBS, and only about 6 non-Caucasian control group members having ever used MBS, making no conclusions about non-Caucasians to be convincing here).</p>\n<h3>The study was <em>not</em> about creatine</h3>\n<p>The paper's claim is that there's a correlation between MBSs and TGCC, but creatine was just one of the 30 different types of MBSs included in the survey in which participants essentially said &quot;yes&quot; or &quot;no&quot; to questions about whether or not they had used MBSs, and for how long. <strong>The effect <em>specifically</em> from creatine was never isolated in the study.</strong> So the <em><strong>correlation</strong></em> between MBSs and TGCC was not necessarily <em><strong>caused</strong></em> by creatine, it could have (for example) have been caused by any one of the other 29 ingredients grouped together under the MBS umbrella for the purposes of the study.</p>\n<p>Creatine was mentioned in the following quote (which turned out to also be <em>part of</em> the longer quote you included in your question):</p>\n<blockquote>\n<p>&quot;The interview included an assessment of 30 different types\nof MBS powders or pills. The major ingredients, including creatine, protein, and androstenedione or its booster, were abstracted according to the product ingredients.&quot;</p>\n</blockquote>\n<p>After that, they never mentioned creatine again, except in the following quote (which it turns out, you also found):</p>\n<blockquote>\n<p>&quot;We further conducted exploratory stratified\nanalyses examining associations with TGCC for the major types\nof MBS use reported by the study population and found that the\nuse of MBS containing ingredients of both creatine and proteins\nincreased the risk of TGCC significantly (OR = 2.55, 95% CI:\n1.05–6.15).&quot;</p>\n</blockquote>\n<p>But the number &quot;2.55&quot; does not show up anywhere in the paper, as what is being mentioned here is supplementary to the main results reported in the paper. Usually the data behind a number like this, which is <em>mentioned</em> in the paper but without details about where it originated, would be described in the paper's &quot;Supplemental Material&quot;, but this paper unfortunately did not have any. Again, this study was not about creatine, it was about MBSs, of which creatine was only 1 of 30, so it was not the goal of the authors to make any convincing conclusions about the impact of creatine (so those Reddit users were perhaps flawed in singling out creatine here). </p>\n<h3>Some other, more minor issues</h3>\n<p>The paper says:</p>\n<blockquote>\n<p>&quot;The prevalence of cryptorchidism and injury to the testes or groin was higher in cases than that in controls&quot;</p>\n</blockquote>\n<p><em><strong>Each of these</strong></em> were about 10% higher, according to Table 1. Also, the paper didn't mention that the same table also shows in the row labeled &quot;Family history of TGCC&quot;, that it was 2x higher in cases than controls. While the latter amounts to a minor issue on its own, combined with the 10% difference we see for cryptorchidism <em><strong>and</strong></em> for previous testes injury, there's a fair amount of other factors (specifically: prior cryptorchidism, testes injury, and family history of TGCC) that are <em><strong>significantly higher in the TGCC patients than in the control group.</strong></em></p>\n<p>Table 2 shows that the use of MBS was higher in the cases than in the controls, by less than 6%, which is smaller than the percentage of TGCC patients who had the other three pre-existing factors more than the control group. Combined with everything else said so far, this suggests that the 2015 paper may have been a good start to studying the connection between MBSs and TGCC, but a larger study would have to be done to answer <em>your</em> question.</p>\n<h1>Further reading</h1>\n<p>Since your question is about creatine, but the paper discussed throughout your entire question's body was about MBSs, for which creatine was only one of 30 and was never studied in isolation or at least with its own emphasis, I'll first recommend some work specifically about creatine, then some about TGCC, and then some about MBSs in general (some of these were done by the same group as the 2015 paper you described).</p>\n<h3>Specifically about creatine</h3>\n<ul>\n<li><a href=\"https://www.nature.com/articles/bjc2015294\" rel=\"nofollow noreferrer\">&quot;Is it the creatine or the anabolic androgenic steroids? Need for assessing the steroids role in testicular cancer&quot; (Journal article)</a></li>\n<li><a href=\"https://www.taylorfrancis.com/chapters/edit/10.4324/9780429465567-7/creatine-supplementation-sport-exercise-health-eric-rawson-eimear-dolan-bryan-saunders-meghan-williams-bruno-gualano\" rel=\"nofollow noreferrer\">&quot;Creatine supplementation in sport, exercise and health&quot; (Book Chapter)</a></li>\n<li><a href=\"https://physoc.onlinelibrary.wiley.com/doi/pdfdirect/10.1113/JP270861\" rel=\"nofollow noreferrer\">&quot;Can creatine supplementation form carcinogenic\nheterocyclic amines in humans?&quot; (Journal article, PDF)</a></li>\n</ul>\n<h3>Specifically about TGCC</h3>\n<ul>\n<li><a href=\"https://www.sciencedirect.com/science/article/pii/S2352340921002985\" rel=\"nofollow noreferrer\">&quot;Dataset of testicular germ cell tumors (TGCT) risk associated with serum polychlorinated biphenyl (PCB) by age at diagnosis and histologic types (Journal article)&quot;</a></li>\n<li><a href=\"https://www.sciencedirect.com/science/article/pii/S0269749121000361?casa_token=Kb1iaGpjBAkAAAAA:aVQYosreVozT3SiA0KO2ZnnhJdYo_LIwOBywjH_SWU6mOx_pqcJxcmXpEfDF1tbjiDFLSTVhAEM\" rel=\"nofollow noreferrer\">&quot;Serum polychlorinated biphenyl (PCB) levels and risk of testicular germ cell tumors: A population-based case-control study in Connecticut and Massachusetts&quot; (Journal article)</a></li>\n</ul>\n<h3>About the effects of MBSs in general</h3>\n<ul>\n<li><a href=\"https://journals.humankinetics.com/view/journals/ijsnem/28/2/article-p104.xml?tab=pdf\" rel=\"nofollow noreferrer\">&quot;IOC Consensus Statement: Dietary Supplements and the High-Performance Athlete&quot; (Article)</a></li>\n<li><a href=\"https://journals.humankinetics.com/view/journals/ijsnem/28/2/article-p212.xml\" rel=\"nofollow noreferrer\">&quot;Making Decisions About Supplement Use&quot; (Article)</a></li>\n<li><a href=\"https://www.sciencedirect.com/science/article/pii/S1054139X19301636?casa_token=RslctBHVPLgAAAAA:NPViYMEhQ9bOFXdManOh_vPQ5VTK6Aih_K-ZaLBf18kB6M-fmCKO_WJTVLmXZY5JBac9tDcH3Mo\" rel=\"nofollow noreferrer\">&quot;Taking Stock of Dietary Supplements' Harmful Effects on Children, Adolescents, and Young Adults&quot;</a></li>\n<li><a href=\"https://pativey.com/wp-content/uploads/2020/06/Adulterated-dietary-supplements-threaten-the-health-and-sporting-career-of-up-and-coming-young-athletes.pdf\" rel=\"nofollow noreferrer\">Adulterated dietary supplements threaten the\nhealth and sporting career of up-and-coming\nyoung athletes (Journal article, PDF)</a></li>\n<li><a href=\"https://www.proquest.com/openview/17b3005b06df2604cd0ece3941ffa357/1?pq-origsite=gscholar&amp;cbl=18750\" rel=\"nofollow noreferrer\">&quot;PREVALENCE AND PREDICTORS OF HIGH-RISK SUPPLEMENT USE AMONG\nCOLLEGIATE ATHLETES&quot; (Masters Thesis)</a></li>\n<li><a href=\"https://books.google.ca/books?hl=en&amp;lr=&amp;id=IAWcDwAAQBAJ&amp;oi=fnd&amp;pg=PT13&amp;ots=hyKijLuz24&amp;sig=BkrUNU6VBjrKq7VFq_uhHmFbnmo&amp;redir_esc=y#v=onepage&amp;q&amp;f=false\" rel=\"nofollow noreferrer\">&quot;Dietary Supplementation in Sport and Exercise: Evidence, Safety and&quot; (Book)</a></li>\n</ul>\n", "score": 4 } ]

[ "cancer", "steroids", "creatine" ]

[ { "answer_id": 30714, "body": "<p>Antibody tests can identify prior infection for at least several months after acute infection, but more than that is unknown.</p>\n<p>Vaccination produces antibodies against the S protein; testing for antibodies against the N protein (the nucleocapsid) can distinguish between infection and vaccination.</p>\n<p>See:</p>\n<ul>\n<li><p><a href=\"https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests-guidelines.html\" rel=\"nofollow noreferrer\">Interim Guidelines for COVID-19 Antibody Testing</a></p>\n</li>\n<li><p><a href=\"https://www.cdc.gov/coronavirus/2019-ncov/testing/serology-overview.html\" rel=\"nofollow noreferrer\">Test for Past Infection</a></p>\n</li>\n</ul>\n", "score": 2 } ]

[ "covid-19", "test", "test-results", "length-of-time" ]