<h4>Background</h4>Problems arising from medicines usage are recognised as a key patient safety issue. Children are a particular concern, given that they are more likely than adults to experience medication-related harm. While previous reviews have provided an estimate of prevalence in this population, these predate recent developments in the delivery of paediatric care. Hence, there is a need for an updated, focussed and critical review of the prevalence and nature of drug-related problems in hospitalised children in the UK, in order to support the development and targeting of interventions to improve medication safety.<h4>Methods</h4>Nine electronic databases (Medline, Embase, CINAHL, PsychInfo, IPA, Scopus, HMIC, BNI, The Cochrane library and clinical trial databases) were searched from January 1999 to April 2019. Studies were included if they were based in the UK, reported on the frequency of adverse drug reactions (ADRs), adverse drug events (ADEs) or medication errors (MEs) affecting hospitalised children. Quality appraisal of the studies was also conducted.<h4>Results</h4>In all, 26 studies were included. There were no studies which specifically reported prevalence of adverse drug events. Two adverse drug reaction studies reported a median prevalence of 25.6% of patients (IQR 21.8-29.9); 79.2% of reactions warranted withdrawal of medication. Sixteen studies reported on prescribing errors (median prevalence 6.5%; IQR 4.7-13.3); of which, the median rate of dose prescribing errors was 11.1% (IQR 2.9-13). Ten studies reported on administration errors with a median prevalence of 16.3% (IQR 6.4-23). Administration technique errors represented 53% (IQR 52.7-67.4) of these errors. Errors detected during medicines reconciliation at hospital admission affected 43% of patients, 23% (Range 20.1-46) of prescribed medication; 70.3% (Range 50-78) were classified as potentially harmful. Medication errors detected during reconciliation on discharge from hospital affected 33% of patients and 19.7% of medicines, with 22% considered potentially harmful. No studies examined the prevalence of monitoring or dispensing errors.<h4>Conclusions</h4>Children are commonly affected by drug-related problems throughout their hospital journey. Given the high prevalence and risk of patient harm,, there is a need for a deeper theoretical understanding of paediatric medication systems to enable more effective interventions to be developed to improve patient safety.

Abstract Background Despite previous efforts, medication safety in paediatrics remains a major concern. To inform improvement strategies and further research especially in outpatient care, we systematically reviewed the literature on the frequency and nature of drug-related hospital admissions in children. Methods Searches covered Embase, Medline, Web of Science, grey literature sources and relevant article citations. Studies reporting epidemiological data on paediatric drug-related hospital admissions published between 01/2000 and 01/2024 were eligible. Study identification, data extraction, and critical appraisal were conducted independently in duplicate using templates based on the ’Joanna Briggs Institute’ recommendations. Results The review included data from 45 studies reporting > 24,000 hospitalisations for adverse drug events (ADEs) or adverse drug reactions (ADRs). Due to different reference groups, a total of 52 relative frequency values were provided. We stratified these results by study characteristics. As a percentage of inpatients, the highest frequency of drug-related hospitalisation was found with ‘intensive ADE monitoring’, ranging from 3.1% to 5.8% (5 values), whereas with ‘routine ADE monitoring’, it ranged from 0.2% to 1.0% (3 values). The relative frequencies of ‘ADR-related hospitalisations’ ranged from 0.2% to 6.9% for ‘intensive monitoring’ (23 values) and from 0.04% to 3.8% for ‘routine monitoring’ (8 values). Per emergency department visits, five rel

Pharmacoepidemiology in pre-approval clinical trial safety monitoring. Applications of pharmacoepidemiology to the pre-approval safety monitoring of investigational drugs are examined and compared with the post-approval applications. Pre-approval epidemiologic assessments of drug safety can complement clinical assessments of rare, serious adverse events occurring in open label uncontrolled clinical trials. Applications include retrospective identification of patient risk factors for adverse drug events and incidence comparisons based on historical controls. While similar in concept to applications of pharmacoepidemiology in the analyses of uncontrolled open label post-marketing surveillance studies, answers are often needed in days rather than weeks and the emphasis is on whether human studies can continue. Advance planning of historical data sources is essential as is an effective clinical trial data management system. Implications for methodologic research and for drug development are discussed. Published in Journal of clinical epidemiology (1991)

Priorities in the benefit-risk assessment of new drugs. With the present emphasis on animal safety data, human benefit and risk may be inadequately quantified at the clinical trial stage and the assessment of risk from adverse reaction reporting is also based on methods that lack epidemiological precision. Under these conditions there must be serious doubts about the accuracy of assessment of some of the new drugs that come under suspicion. Suggestions have been made for improving the situation. A closer scrutiny of human data at the clinical trial stage, while involving some increase in the requirements for clinical trial data, would be advantageous for the pharmaceutical industry as well as for other interested parties if it were part of a deliberate change of emphasis from animal to human evidence of safety and from absolute to relative efficacy data in the assessment of product licenses. Published in Adverse drug reactions and acute poisoning reviews (1984)

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been widely recommended for glucose control and cardiovascular risk reduction in patients with type 2 diabetes, and more recently, for weight loss. However, the associations of GLP-1 RAs with gallbladder or biliary diseases are controversial. To evaluate the association of GLP-1 RA treatment with gallbladder and biliary diseases and to explore risk factors for these associations. MEDLINE/PubMed, EMBASE, Web of Science, and Cochrane Library (inception to June 30, 2021), websites of clinical trial registries (July 10, 2021), and reference lists. There were no language restrictions. Randomized clinical trials (RCTs) comparing the use of GLP-1 RA drugs with placebo or with non-GLP-1 RA drugs in adults. Two reviewers independently extracted data according to the PRISMA recommendations and assessed the quality of each study with the Cochrane Collaboration risk-of-bias tool. Pooled relative risks (RRs) were calculated using random or fixed-effects models, as appropriate. The quality of evidence for each outcome was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. The primary outcome was the composite of gallbladder or biliary diseases. Secondary outcomes were biliary diseases, biliary cancer, cholecystectomy, cholecystitis, and cholelithiasis. Data analyses were performed from August 5, 2021, to September 3, 2021. A total of 76 RCTs involving 103 371 patients (mean [SD] age, 57.8 (6.2) years; 41 868 [40.5%] women) were included. Among all included trials, randomization to GLP-1 RA treatment was associated with increased risks of gallbladder or biliary diseases (RR, 1.37; 95% CI, 1.23-1.52); specifically, cholelithiasis (RR, 1.27; 95% CI, 1.10-1.47), cholecystitis (RR, 1.36; 95% CI, 1.14-1.62), and biliary disease (RR, 1.55; 95% CI, 1.08-2.22). Use of GLP-1 RAs was also associated with increased risk of gallbladder or biliary diseases in trials for weight loss (n = 13; RR, 2.29; 95% CI, 1.64-3.18) and for type 2 diabetes or other diseases (n = 63; RR, 1.27; 95% CI, 1.14-1.43; P <.001 for interaction). Among all included trials, GLP-1 RA use was associated with higher risks of gallbladder or biliary diseases at higher doses (RR, 1.56; 95% CI, 1.36-1.78) compared with lower doses (RR, 0.99; 95% CI, 0.73-1.33; P = .006 for interaction) and with longer duration of use (RR, 1.40; 95% CI, 1.26-1.56) compared with shorter duration (RR, 0.79; 95% CI, 0.48-1.31; P = .03 for interaction). This systematic review and meta-analysis of RCTs found that use of GLP-1 RAs was associated with increased risk of gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss. PROSPERO Identifier: CRD42021271599.

Management of hypertension: risk-benefit ratio. The justification for drug treatment of mild hypertension rests upon epidemiological data demonstrating an increased risk of heart attack and stroke and a very small number of controlled clinical trials. These data provide a slender basis for mass treatment and leave many vital questions unanswered. The incidence of stroke (and heart attack in some countries) appears to be falling irrespective of antihypertensive therapy. Are historic epidemiological findings still relevant? The level of diastolic blood pressure where risk begins to increase appears to be about 95 mmHg. Ought this also to be the target value for blood pressure reduction? Do thiazide diuretics have added risks and beta-adrenergic blocking drugs added benefits over and above their effect upon blood pressure? If the MRC Hypertension trial turns out to be the last of the big placebo controlled trials in hypertension how shall we assess the effects of new types of drugs upon outcome? Published in Journal of hypertension. Supplement : official journal of the International Society of Hypertension (1984)

Ethical issues relating to the use of the injectable contraceptive in developed and developing countries alike involve public policy decisions concerning both criteria for testing a new drug and individual choices about using a specific form of contraception approved for national distribution. Drug testing consists of an important but still evolving set of procedures. Depo-Provera is not qualitatively different from any other drug and some unpredictable risks are inevitable, even after extensive animal experiments and clinical trials. In assessing the risks and benefits of Depo-Provera use, epidemiological data from large scale human use is now beginning to become more important than data from animal experiments and clinical trials. The consumer's best interest is central to any ethically responsible system of drug distribution. Systems of informed choice are needed, even in societies where illiteracy remains common and medical services are weak. In the case of a contraceptive, risks of nonuse leading to unintended pregnancy, which can result in high mortality, are relevant as well as are the side effects of the method.

experiments; provide part of the community-level data needed to design more informative pragmatic clinical trials; and inform clinical practice." In In fields such as epidemiology, social sciences, psychology and statistics, an observational study draws conclusions without controlling the independent variable due to ethical or practical limitations. One common example studies the effect of a treatment, where the researcher does not assign subjects to treatment or control group. This is in contrast with experiments, such as randomized controll provide information on 'real world' use and practice; detect signals about the benefits and risks of...[the] use [of practices] in the general population; help formulate hypotheses to be tested in subsequent experiments; provide part of the community-level data needed to design more informative pragmatic clinical trials; and inform clinical practice."