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Background There have been no studies of the patterns of post-marketing withdrawals of medicinal products to which adverse reactions have been attributed. We identified medicinal products that were withdrawn because of adverse drug reactions, examined the evidence to support such withdrawals, and explored the pattern of withdrawals across countries. Methods We searched PubMed, Google Scholar, the WHO’s database of drugs, the websites of drug regulatory authorities, and textbooks. We included medicinal products withdrawn between 1950 and 2014 and assessed the levels of evidence used in making withdrawal decisions using the criteria of the Oxford Centre for Evidence Based Medicine. Results We identified 462 medicinal products that were withdrawn from the market between 1953 and 2013, the most common reason being hepatotoxicity. The supporting evidence in 72 % of cases consisted of anecdotal reports. Only 43 (9.34 %) drugs were withdrawn worldwide and 179 (39 %) were withdrawn in one country only. Withdrawal was significantly less likely in Africa than in other continents (Europe, the Americas, Asia, and Australasia and Oceania). The median interval between the first reported adverse reaction and the year of first withdrawal was 6 years (IQR, 1–15) and the interval did not consistently shorten over time. Conclusion There are discrepancies in the patterns of withdrawal of medicinal products from the market when adverse reactions are suspected, and withdrawals are inconsistent across countries. Greater co-ordination among drug regulatory authorities and increased transparency in reporting suspected adverse drug reactions would help improve current decision-making processes.

Randomization, allocation concealment, and blind outcome assessment have been shown to reduce bias in human studies. Authors from the Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies (CAMARADES) collaboration recently found that these features protect against bias in animal stroke studies. We extended the scope the work from CAMARADES to include investigations of treatments for any condition. We conducted an overview of systematic reviews. We searched Medline and Embase for systematic reviews of animal studies testing any intervention (against any control) and we included any disease area and outcome. We included reviews comparing randomized versus not randomized (but otherwise controlled), concealed versus unconcealed treatment allocation, or blinded versus unblinded outcome assessment. Thirty-one systematic reviews met our inclusion criteria: 20 investigated treatments for experimental stroke, 4 reviews investigated treatments for spinal cord diseases, while 1 review each investigated treatments for bone cancer, intracerebral hemorrhage, glioma, multiple sclerosis, Parkinson's disease, and treatments used in emergency medicine. In our sample 29% of studies reported randomization, 15% of studies reported allocation concealment, and 35% of studies reported blinded outcome assessment. We pooled the results in a meta-analysis, and in our primary analysis found that failure to randomize significantly increased effect sizes, whereas allocation concealment and blinding did not. In our secondary analyses we found that randomization, allocation concealment, and blinding reduced effect sizes, especially where outcomes were subjective. Our study demonstrates the need for randomization, allocation concealment, and blind outcome assessment in animal research across a wide range of outcomes and disease areas. Since human studies are often justified based on results from animal studies, our results suggest that unduly biased animal studies should not be allowed to constitute part of the rationale for human trials.

Background We identified anti-obesity medications withdrawn since 1950 because of adverse drug reactions after regulatory approval, and examined the evidence used to support such withdrawals, investigated the mechanisms of the adverse reactions, and explored the trends over time. Methods We conducted searches in PubMed, the World Health Organization database of drugs, the websites of drug regulatory authorities, and selected full texts, and we hand searched references in retrieved documents. We included anti-obesity medications that were withdrawn between 1950 and December 2015 and assessed the levels of evidence used for making withdrawal decisions using the Oxford Centre for Evidence-Based Medicine criteria. Results We identified 25 anti-obesity medications withdrawn between 1964 and 2009; 23 of these were centrally acting, via monoamine neurotransmitters. Case reports were cited as evidence for withdrawal in 80% of instances. Psychiatric disturbances, cardiotoxicity (mainly attributable to re-uptake inhibitors), and drug abuse or dependence (mainly attributable to neurotransmitter releasing agents) together accounted for 83% of withdrawals. Deaths were reportedly associated with seven products (28%). In almost half of the cases, the withdrawals occurred within 2 years of the first report of an adverse reaction. Conclusions Most of the drugs that affect monoamine neurotransmitters licensed for the treatment of obesity over the past 65 years have been withdrawn because of adverse reactions. The reasons for withdrawal raise concerns about the wisdom of using pharmacological agents that target monoamine neurotransmitters in managing obesity. Greater transparency in the assessment of harms from anti-obesity medications is therefore warranted.

Surgical innovation is an important part of surgical practice. Its assessment is complex because of idiosyncrasies related to surgical practice, but necessary so that introduction and adoption of surgical innovations can derive from evidence-based principles rather than trial and error. A regulatory framework is also desirable to protect patients against the potential harms of any novel procedure. In this first of three Series papers on surgical innovation and evaluation, we propose a five-stage paradigm to describe the development of innovative surgical procedures.

The cacoethes scribendi, the itch to write¸ has also prompted them, and I have suggested that the source of that itch is a desire, whether conscious or unconscious, to find out for themselves what they think.2 Although academics will undoubtedly have welcomed any money that accrued from such activities, typically in royalties earned from the publication of textbooks and monographs, the amounts earned have on the whole been small, the lion’s share of the profits having gone to their publishers, and publication of research papers and reviews has been unpaid. If it be true that, for the time being at least, the quality of American sociological writing is in inverse ratio to its quantity, the reason is to be sought, among other things, in the fact, first, that the system of promotion used in our universities amounts to the warning, ‘Publish or perish!’ In the second place, publication in general is more easy than formerly ; and in the third place, there is an insistent demand for sociological text-books on the part of the great publishing houses, many of whom are busily creating what they call ‘Social Science Series,’ in which they and their respective corps of authors are industriously duplicating one another’s output.” 5 Then, in 1942, the man who is sometimes credited, wrongly, as we can see, with having introduced the term, Logan Wilson, in a book called The Academic Man,6 commented that “The reactions of the instructors also mention other sources of tension—the ‘lip service to teaching,’ departmental policies resting on ‘caprice rather than considered judgment . . . and a balanced view,’ the issue of judgment on intrinsic merits or cultivation of special fields, emphasis on ‘quantity rather than quality’ in publication, the ‘publish or perish’ legend.” Numerous media exist to furnish outlets for the printed results of research and to give recognition to achievements of scholars and scientists (not to mention the disseminative functions of scientific meetings), so that any new formulation or discovery may be added almost immediately to the total sum of knowledge.”

Use of these drugs is premature and potentially harmful

A deficiency in the availability of a pharmaceutical product is usually known as a shortage. However, the term “stock-out” has also been used to describe a deficiency that occurs locally. It is sometimes hard to determine when a stock-out becomes a shortage, and that may be why stock-outs have been less well studied than shortages. In addition, because they are local, stock-outs may be thought by some to be less important than shortages. However, the causes of stock-outs may be different from the causes of shortages and they are as important to those who are affected as shortages are, even though there are fewer of them.

The original definition of the word “bias,” when it entered the English language in the 16th century, was a diagonal line, and specifically one that cut across the warp or weft of a woven fabric. It later came to mean the tendency of a bowl, the asymmetrically shaped ball-like object used in the game of bowls, to take a curving course when rolled across a lawn, and eventually, among other things, something that produces distortion of a statistical result. Based on a study of its etymology, usages, previous definitions, and sources, I propose the following definition of a bias in research:bias, n. /ˈbʌɪəs/ A systematic distortion, due to a design problem, an interfering factor, or a judgment, that can affect the conception, design, or conduct of a study, or the collection, analysis, interpretation, presentation, or discussion of outcome data, causing erroneous overestimation or underestimation of the probable size of an effect or association [ancient Greek ἐπικάρσιος, crosswise, esp. at right angles, via French biais]This defines the count noun, a bias. The non-count noun, bias, could be defined as a tendency to produce biases.

Hospes in Latin means both a host and a guest. It’s a Janus word that reflects a reciprocal arrangement between not so much opposites as counterparts. Hospes gives us the word hospitality, which is what a guest would expect from a host. It also gives us the words hospice and hospital. Although the word “hospitalist” had been used occasionally to mean someone who ran a hospice or a hospital, it had been long obsolete when it was reintroduced in the USA in the late 20th century to describe a general in-house doctor in a hospital responsible for providing complete care for patients with general medical problems, no matter what organ or system was affected. Early reports of the outcomes of instituting hospitalist programmes were generally positive. The Re:State think tank, in a recent report on the UK hospital of the future, has suggested introducing hospitalists here, in order to reduce the problems of internal and external bottlenecks that restrict the flow of patients through and out of the hospital. We therefore have the opportunity to institute a pilot scheme whereby the benefit to harm balance of introducing hospitalists into UK hospitals would be studied, with a view to introducing them widely if the scheme proved to be successful.

A Janus word or phrase has two meanings, each the opposite of the other. Janus words are named after the two-faced Roman god of archways and doors, Janus. There are many such words in English, the classical example being “cleave,” which means to divide or to unite, coming as it does from two different Old English words, cleofan and clifian. However, there are relatively few medical Janus words, which may be just as well, since ambiguity should be avoided whenever possible.