Susceptibility to adverse drug reactions.

The pharmacological effects of a drug depend on its concentration at the site of action, and therefore on the concentration in blood and on the dose. The relationship between the concentration or dose and the corresponding effect can usually be represented mathematically as a rectangular hyperbola; when effect is plotted against log concentration or log dose, the curve is sigmoidal. Inevitably, the effect size and the doses causing benefit and harm will differ among individuals, since they are biological phenomena: some individuals are more likely than others to suffer harm at any given dose.

The British Pharmacological Society's WDM Paton Memorial Lecture 2019: How doctors were informed about pharmaceutical products through advertising in the British Medical Journal from 1955/6 to 1985/6.

We have reviewed pharmaceutical advertisements in every available issue of the British Medical Journal (BMJ) in 12-month periods during 1955/6, 1965/6, 1975/6, and 1985/6. We have determined the amount of advertising, the therapeutic areas covered, and whether adverts reflected the large number of New Chemical Entities (NCEs) launched during that time. For each product we recorded the therapeutic indications, the marketing company, and the number of adverts appearing.

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

The original article [1] contains a minor error whereby the dates for year of first launch and year of first report of adverse reaction for iophendylate in e-Appendix Table 1 are mistakenly presented as 1946 and 1975 respectively.

Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis.

Oral hormone pregnancy tests (HPTs), such as Primodos, containing ethinylestradiol and high doses of norethisterone, were given to over a million women from 1958 to 1978, when Primodos was withdrawn from the market because of concerns about possible teratogenicity. We aimed to study the association between maternal exposure to oral HPTs and congenital malformations. We have performed a systematic review and meta-analysis of case-control and cohort studies that included data from pregnant women and were exposed to oral HPTs within the estimated first three months of pregnancy, if compared with a relevant control group.

Impact of food allergy on food insecurity and health literacy in a tertiary care pediatric allergy population.

Background: Food insecurity (FI), limited availability of or access to nutritional foods, is linked to poor child/caregiver health. We examined FI in food-allergic and non-food-allergic children to determine whether dietary limitations associated with food allergy increases risk of FI.

Methods: Food-allergic and non-food-allergic children (1-17 years) were recruited from Arkansas Children's Hospital allergy/asthma clinics.

Adverse events in people taking macrolide antibiotics versus placebo for any indication.

Background: Macrolide antibiotics (macrolides) are among the most commonly prescribed antibiotics worldwide and are used for a wide range of infections. However, macrolides also expose people to the risk of adverse events. The current understanding of adverse events is mostly derived from observational studies, which are subject to bias because it is hard to distinguish events caused by antibiotics from events caused by the diseases being treated.

Deep Brain Stimulation for Memory Modulation: A New Frontier.

Background: In the coming years the number of patients with cognitive disorders, such as Alzheimer disease and traumatic brain injury, is expected to dramatically increase, leading to an ever-increasing societal cost. Unfortunately, few medical and pharmacologic treatments have shown tangible benefit in the treatment of these diseases. Deep brain stimulation (DBS) is an established surgical technique to address multiple conditions, including Parkinson disease and essential tremor.

Practice variation in the use of tests in UK primary care: a retrospective analysis of 16 million tests performed over 3.3 million patient years in 2015/16.

Background: The UK's National Health Service (NHS) is currently subject to unprecedented financial strain. The identification of unnecessary healthcare resource use has been suggested to reduce spending. However, there is little very research quantifying wasteful test use, despite the £3 billion annual expenditure.

Temporal trends in use of tests in UK primary care, 2000-15: retrospective analysis of 250 million tests.

Objectives: To assess the temporal change in test use in UK primary care and to identify tests with the greatest increase in use.

Design: Retrospective cohort study.

Setting: UK primary care.

Reduced Salt Intake for Heart Failure: A Systematic Review.

Importance: Recent estimates suggest that more than 26 million people worldwide have heart failure. The syndrome is associated with major symptoms, significantly increased mortality, and extensive use of health care. Evidence-based treatments influence all these outcomes in a proportion of patients with heart failure.

Cognitive tasks and human ambulatory electrocorticography using the RNS System.

Background: Electrocorticography studies are typically conducted in patients undergoing video EEG monitoring, but these studies are subject to confounds such as the effects of pain, recent anesthesia, analgesics, drug changes, antibiotics, and implant effects.

New Method: Techniques were developed to obtain electrocorticographic (ECoG) data from freely moving subjects performing navigational tasks using the RNS System (NeuroPace, Inc., Mountain View, CA), a brain-responsive neurostimulation medical device used to treat focal onset epilepsy, and to align data from the RNS System with cognitive task events with high precision.

Examining the 'psychopharmacology revolution' (1950-1980) through the advertising of psychoactive drugs in the British Medical Journal.

Background: Many modern pharmaceutical products were launched during 1950-1980, as reflected in advertisements in the British Medical Journal ( BMJ). One of the first therapeutic areas to benefit from novel effective medications was psychiatry.

Methods: We examined BMJ advertising material between 1950 and 1980, including every other issue over six-month periods (October-March) in 1950/1951, 1955/1956, 1957/1958, 1960/1961, 1962/1963, 1965/1966, 1967/1968, 1970/1971, 1972/1973, 1975/1976, 1980/1981.

Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer's mouse model.

Adult hippocampal neurogenesis (AHN) is impaired before the onset of Alzheimer's disease (AD) pathology. We found that exercise provided cognitive benefit to 5×FAD mice, a mouse model of AD, by inducing AHN and elevating levels of brain-derived neurotrophic factor (BDNF). Neither stimulation of AHN alone, nor exercise, in the absence of increased AHN, ameliorated cognition.

Diagnostic test guidelines based on high-quality evidence had greater rates of adherence: a meta-epidemiological study.

Objectives: To determine the association between the quality of guidelines for diagnostic tests (both the quality and reporting and the quality of the evidence underpinning recommendations) and nonadherence.

Study Design And Setting: We conducted a meta-epidemiological study. We previously published a systematic review that quantified the percentage of test use that was nonadherent with guidelines.

The use of mechanistic evidence in drug approval.

The role of mechanistic evidence tends to be under-appreciated in current evidence-based medicine (EBM), which focusses on clinical studies, tending to restrict attention to randomized controlled studies (RCTs) when they are available. The EBM+ programme seeks to redress this imbalance, by suggesting methods for evaluating mechanistic studies alongside clinical studies. Drug approval is a problematic case for the view that mechanistic evidence should be taken into account, because RCTs are almost always available.

Anatomical Correlates of Uncontrollable Laughter With Unilateral Subthalamic Deep Brain Stimulation in Parkinson's Disease.

Introduction: Subthalamic nucleus deep brain stimulation (STN-DBS) is a well-established treatment for the management of motor complications in Parkinson's disease. Uncontrollable laughter has been reported as a rare side effect of STN stimulation. The precise mechanism responsible for this unique phenomenon remains unclear.

Integration of leadership training for graduate and medical students engaged in translational biomedical research: Examining self-efficacy and self-insight.

Introduction: Formal training in team leadership is not taught in biomedical research graduate training programs or medical schools.

Methods: We piloted a Leadership Training Workshop for graduate biomedical and medical students enrolled in our Interprofessional Research Design Course.

Results: The Kane-Baltes self-efficacy survey demonstrated improved leadership skills (median scores pretraining and post-training were 71 and 76.