Drugs for rare disorders.

Estimates of the frequencies of rare disorders vary from country to country; the global average defined prevalence is 40 per 100 000 (0.04%). Some occur in only one or a few patients.

CARE guidelines for case reports: explanation and elaboration document.

Background: Well-written and transparent case reports (1) reveal early signals of potential benefits, harms, and information on the use of resources; (2) provide information for clinical research and clinical practice guidelines, and (3) inform medical education. High-quality case reports are more likely when authors follow reporting guidelines. During 2011-2012, a group of clinicians, researchers, and journal editors developed recommendations for the accurate reporting of information in case reports that resulted in the CARE (CAse REport) Statement and Checklist.

Post-marketing drug withdrawals: Pharmacovigilance success, regulatory problems.

Modern pharmacovigilance began in the 1960s, since when the subject has grown markedly, interest having particularly increased since 2010. One index of its success is the increasing speed with which serious adverse drug reactions are discovered after marketing of a medicinal product. However, the speed with which products have subsequently been withdrawn as a result of the discovery of serious adverse reactions has not consistently changed.

Biomarkers-A General Review.

A biomarker is a biological observation that substitutes for and ideally predicts a clinically relevant endpoint or intermediate outcome that is more difficult to observe. The use of clinical biomarkers is easier and less expensive than direct measurement of the final clinical endpoint, and biomarkers are usually measured over a shorter time span. They can be used in disease screening, diagnosis, characterization, and monitoring; as prognostic indicators; for developing individualized therapeutic interventions; for predicting and treating adverse drug reactions; for identifying cell types; and for pharmacodynamic and dose-response studies.

Post-Marketing Regulation of Medicines Withdrawn from the Market Because of Drug-Attributed Deaths: An Analysis of Justification.

Introduction: Several medicinal products have been withdrawn from the market because of drug-attributed deaths. However, there has been no investigation of whether such withdrawals were justified, and the extent to which confirmatory studies are used to investigate drug-adverse event relationships when deaths are reported is uncertain. We documented medicinal products withdrawn from the market because of drug-attributed deaths, identified confirmatory studies investigating the drug-adverse event relationships, examined whether withdrawals of medicinal products because of drug-attributed deaths after marketing were justified based on a mechanistic analysis, and examined the trends over time.

Poor medication adherence in clinical trials: consequences and solutions.

Poor adherence to medicines in clinical trials can undermine the value of the trials; for example, by compromising estimates of the benefits and risks of a medicine. In this article, we highlight such consequences and also discuss approaches to tackle this problem.

Nominal ISOMERs (Incorrect Spellings Of Medicines Eluding Researchers)-variants in the spellings of drug names in PubMed: a database review.

Objective:  To examine how misspellings of drug names could impede searches for published literature.

Design:  Database review.

Data Source:  PubMed.

Post-marketing withdrawal of anti-obesity medicinal products because of adverse drug reactions: a systematic review.

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.

Inhibiting the proton pump: mechanisms, benefits, harms, and questions.

Inhibition of the H/K-adenosine triphosphatase (the proton pump) is the final common mechanistic pathway in reducing gastric acid secretion pharmacologically. Proton pump inhibitors are widely used in upper gastrointestinal diseases, including gastric and duodenal ulcers, eradication of Helicobacter pylori in combination with antibiotics, gastroesophageal reflux disease, Zollinger-Ellison syndrome, eosinophilic esophagitis, and prevention of non-steroidal anti-inflammatory drug-induced peptic ulceration. Reviewing their benefits and harms in BMC Medicine, Scarpignato et al.

Methods for meta-analysis of pharmacodynamic dose-response data with application to multi-arm studies of alogliptin.

Standard methods for meta-analysis of dose-response data in epidemiology assume a model with a single scalar parameter, such as log-linear relationships between exposure and outcome; such models are implicitly unbounded. In contrast, in pharmacology, multi-parameter models, such as the widely used E model, are used to describe relationships that are bounded above and below. We propose methods for estimating the parameters of a dose-response model by meta-analysis of summary data from the results of randomized controlled trials of a drug, in which each trial uses multiple doses of the drug of interest (possibly including dose 0 or placebo).

Defining 'nutraceuticals': neither nutritious nor pharmaceutical.

There are widespread inconsistencies and contradictions in the many published definitions of 'nutraceuticals' and 'functional foods', demonstrating wholesale uncertainty about what they actually are. Furthermore, in a 2014 lecture, the inventor of the term 'nutraceutical', confessing that nutraceuticals do not work, said that 'the quest to demonstrate whether … long-term supplementation [with nutraceuticals] can prevent serious diseases … has come to an end'. Definitions of 'nutraceuticals' and related terms, still widely used, should therefore be explored systematically.

Worldwide withdrawal of medicinal products because of adverse drug reactions: a systematic review and analysis.

We have systematically identified medicinal products withdrawn worldwide because of adverse drug reactions, assessed the level of evidence used for making the withdrawal decisions, and explored the patterns of withdrawals over time. We searched PubMed, the WHO database of withdrawn products, and selected texts. We included products that were withdrawn after launch from 1950 onwards, excluding non-human and over-the-counter medicines.

Evidence of Misclassification of Drug-Event Associations Classified as Gold Standard 'Negative Controls' by the Observational Medical Outcomes Partnership (OMOP).

Introduction: Pharmacovigilance includes analysis of large databases of information on drugs and events using algorithms that detect disproportional frequencies of associations. In order to test such algorithms, attempts have been made to provide canonical reference lists of so-called 'positive controls' and 'negative controls'. Reference sets with even modest levels of misclassification may result in under- or overstatement of the performance of algorithms.

Post-marketing withdrawal of 462 medicinal products because of adverse drug reactions: a systematic review of the world literature.

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.

Patient Safety in Medication Nomenclature: Orthographic and Semantic Properties of International Nonproprietary Names.

Background: Confusion between look-alike and sound-alike (LASA) medication names (such as mercaptamine and mercaptopurine) accounts for up to one in four medication errors, threatening patient safety. Error reduction strategies include computerized physician order entry interventions, and 'Tall Man' lettering. The purpose of this study is to explore the medication name designation process, to elucidate properties that may prime the risk of confusion.

Medication errors detected in non-traditional databases: types of errors in methotrexate dosing as listed in four different Danish registers.

Aims: We have looked for medication errors involving the use of low-dose methotrexate, by extracting information from Danish sources other than traditional pharmacovigilance databases. We used the data to establish the relative frequencies of different types of errors.

Methods: We searched four databases for cases involving low-dose methotrexate between 1999 and 2011: the Danish Patient Safety Databases (DPSD), controlled by the Danish National Agency for Patients' Rights and Complaints, the Patient Compensation Association (PCA), the Danish Poison and Information Centre (DPIC), and the online database of the Department for Patient Complaints (DPC).

Cato Guldberg and Peter Waage, the history of the Law of Mass Action, and its relevance to clinical pharmacology.

We have traced the historical link between the Law of Mass Action and clinical pharmacology. The Law evolved from the work of the French chemist Claude Louis Berthollet, was first formulated by Cato Guldberg and Peter Waage in 1864 and later clarified by the Dutch chemist Jacobus van 't Hoff in 1877. It has profoundly influenced our qualitative and quantitative understanding of a number of physiological and pharmacological phenomena.

The law of mass action and the pharmacological concentration-effect curve: resolving the paradox of apparently non-dose-related adverse drug reactions.

Background: Adverse drug reactions are sometimes described as being 'non-dose-related' because no relationship has been found between increasing doses and either the intensity of the response or the proportion of individuals in whom the response occurs; furthermore, hypersensitivity reactions are often regarded as being non-dose-related, even if different doses have not been studied. However, the law of mass action implies that all pharmacological effects are concentration related and should increase in intensity with increasing dose. We set out to explain this paradox.

Toward standardized reporting of drug interactions: the READI checklist for anecdotal reports.

Anecdotal reports contribute 30% of the literature on adverse drug reactions and interactions. However, the quality of such reports has not been uniformly high. Standardized reporting of clinical studies is of increasing interest, including the CARE guidelines on reporting anecdotal cases in general.

Delays in the post-marketing withdrawal of drugs to which deaths have been attributed: a systematic investigation and analysis.

Background: Post-marketing withdrawal of medicinal products because of deaths can be occasioned by evidence obtained from case reports, observational studies, randomized trials, or systematic reviews. There have been no studies of the pattern of withdrawals of medicinal products to which deaths have been specifically attributed and the evidence that affects such decisions. Our objectives were to identify medicinal products that were withdrawn after marketing in association with deaths, to search for the evidence on which withdrawal decisions were based, and to analyse the delays involved and the worldwide patterns of withdrawal.

Quantifying the effects of diuretics and β-adrenoceptor blockers on glycaemic control in diabetes mellitus - a systematic review and meta-analysis.

Aims: Although there are reports that β-adrenoceptor antagonists (beta-blockers) and diuretics can affect glycaemic control in people with diabetes mellitus, there is no clear information on how blood glucose concentrations may change and by how much. We report results from a systematic review to quantify the effects of these antihypertensive drugs on glycaemic control in adults with established diabetes.

Methods: We systematically reviewed the literature to identify randomized controlled trials in which glycaemic control was studied in adults with diabetes taking either beta-blockers or diuretics.

Pycnodysostosis and the making of an artist.

Henri de Toulouse-Lautrec, a 19th century artist celebrated for his depictions of the Moulin Rouge and Parisian nightlife, suffered from an unknown disorder. His symptoms were not only rare, but also difficult to determine. Both during his lifetime and following his death potential diagnoses have proved controversial, including the most popularly supported suggestion of pycnodysostosis.