Competing Benefits and Competing Hazards: The Benefit to Harm Balance in Individual Patients in Rational Therapeutics.

For any therapeutic intervention in an individual, there is a balance between the potential benefits and the possible harms. The extent to which the benefits are desirable in a given condition depends on the efficacy of the intervention, the chance of obtaining it and the seriousness and intensity of the condition. The extent to which the harms are undesirable depends on the nature of the hazard that can lead to harm, the chance that the harm will occur and its seriousness and intensity.

Preventable deaths involving opioids in England and Wales, 2013-2022: a systematic case series of coroners' reports.

Background: Opioid deaths have increased in England and Wales. Coroners' Prevention of Future Deaths reports (PFDs) provide important insights that may enable safer use and avert harms, yet reports implicating opioids have not been synthesized. We aimed to identify opioid-related PFDs and explore coroners' concerns to prevent future deaths.

Effectiveness of biosimilar adoption within a UK tertiary hospital: 6-year follow-up.

Health systems encourage switching from originators to biosimilars as biosimilars are more cost-effective. The speed and completeness of biosimilar adoption is a measure of efficiency. We describe the approach to biosimilar adoption at a single hospital Trust and compare its efficiency against the English average.

Drug shortages. Part 2: Trends, causes and solutions.

Drug shortages make it difficult or impossible to meet the therapeutic needs of individual patients or populations. In the first part of this review we proposed an operational definition that incorporates the processes by which products are manufactured, the causes of shortages and stock-outs (local shortages), and the contributory factors. Here we discuss causes and possible solutions.

Drug shortages. Part 1. Definitions and harms.

Drug shortages are repeatedly in the news. The earliest drug shortages were reported during the First World War, but the numbers of shortages have increased in recent years. In the first part of this two-part review, we discuss definitions of drug shortages and so-called stockouts, which are localized shortages, and the harms that they can cause.

Recognition of Coroners' Concerns to Prevent Future Deaths from Medicines: A Systematic Review.

Background: Coroners, who hold inquests to determine the causes of unnatural deaths in England and Wales, having recognised factors that could cause other deaths, are legally obliged to signal concerns by sending 'Reports to Prevent Future Deaths' (PFDs) to interested persons. We aimed to establish whether Coroners' concerns about medications are widely recognised.

Methods: We searched MEDLINE, Embase and Web of Science up to 30 November, 2022 for publications linking PFDs and medications using a combination of search terms "coroner*", "inquest*", "medicine*", "medication*" and "prevent*".

How to assess pharmacogenomic tests for implementation in the NHS in England.

Aims: Pharmacogenomic testing has the potential to target medicines more effectively towards those who will benefit and avoid use in individuals at risk of harm. Health economies are actively considering how pharmacogenomic tests can be integrated into health care systems to improve use of medicines. However, one of the barriers to effective implementation is evaluation of the evidence including clinical usefulness, cost-effectiveness, and operational requirements.

Treatment of insulin poisoning: A 100-year review.

Background: Insulin poisoning, as opposed to hypoglycaemia induced by therapeutic doses of insulin, is rare, and guidelines on management differ. We have reviewed the evidence on treatment of insulin poisoning.

Methods: We searched PubMed, EMBASE and J-Stage with no restrictions of date or language for controlled studies on treatment of insulin poisoning, collected published cases of insulin poisoning from 1923, and used data from the UK National Poisons Information Service.

Preventable Deaths Involving Medicines: A Systematic Case Series of Coroners' Reports 2013-22.

Introduction: Medicines cause over 1700 preventable deaths annually in England. Coroners' Prevention of Future Death reports (PFDs) are produced in response to preventable deaths to facilitate change. The information in PFDs may help reduce medicine-related preventable deaths.

Medicines legislation and regulation in the United Kingdom 1500-2020.

The initial purposes of regulation of medicines in England, and latterly in the United Kingdom, were principally to raise government revenue, to discourage murder by poisoning and to regulate the activities of pharmacists. It was only much later that regulators sought to ensure that medicines were of good quality, reasonably safe, and at least somewhat effective, and to curtail misuse of drugs. Here we survey the history of the regulation of medicines and poisons in England from the perspective of clinicians with an interest in therapeutics.

Prescribing direct-acting oral anticoagulants - Mind the evidence gap.

Direct-acting oral anticoagulants (DOACs) are licensed for the prevention of thromboembolism in non-valvular atrial fibrillation, amongst other indications. Prescribers use information derived from the summary of product characteristics which is based on the key trials supporting the DOAC's market authorisation. However, prescribers may not be aware of the limitations within these trials regarding underrepresentation of patient populations commonly encountered in clinical practice and how this may adversely impact them.

Phenytoin and damage to the cerebellum - a systematic review of published cases.

Introduction: The antiseizure medication phenytoin has been associated with changes in the cerebellum, cerebellar signs, and permanent cerebellar damage. We have systematically reviewed the clinical and radiological features, and their correlation.

Areas Covered: We identified sixty case reports and case series of the effects of phenytoin on the cerebellum by searching Medline and Embase and relevant reference lists.

Spontaneous Reporting to Regulatory Authorities of Suspected Adverse Drug Reactions to COVID-19 Vaccines Over Time: The Effect of Publicity.

Introduction: The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published frequent summaries of spontaneous reports of suspected adverse drug reactions (ADRs) (Yellow Cards) to vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The EudraVigilance database has provided similar data for the European Economic Area.

Objective: Our objective was to characterize the evolution over time of spontaneous reports of suspected ADRs to coronavirus disease 2019 (COVID-19) vaccines and to observe the effect of a publicized reaction (cerebral venous and sinus thrombosis [CVST]) on reporting rates.

Coping with COVID: Preparing prescribers during the pandemic.

In response to the COVID-19 pandemic, Health Education England (HEE) and the University of Birmingham provided National Health Service (NHS) staff free access to SCRIPT, a national eLearning programme for safer prescribing and therapeutics. The eLearning was particularly for those returning to work or being redeployed. In the year March 2020-21, 3412 users registered to access portfolios and opened an aggregate of 17 198 modules.

Free-of-charge medicine schemes in the NHS: A local and regional drug and therapeutic committee's experience.

Introduction: Free-of-charge (FoC) medicine schemes are increasingly available and allow access to investigational treatments outside clinical trials or in advance of licensing or NHS commissioning.

Methods: We retrospectively reviewed FoC medicine schemes evaluated between 2013 and 2019 by a single NHS trust and a regional drug and therapeutics committee (DTC). The details of each locally reviewed FoC scheme, and any nationally available Medicines and Healthcare products Regulatory Agency Early Access to Medicines Scheme (MHRA EAMS) in the same period, were recorded and categorised.

Establishing a service to tackle problematic polypharmacy.

Introduction: Polypharmacy is increasingly common and can increase the risk of adverse drug reactions (ADRs), accounting for a significant proportion of hospital admissions. It may also impair functional status and quality of life. Current efforts to improve polypharmacy take place largely in primary care, but there may be a role for increased support from medicines specialists in the secondary care setting.

Analysis of reports of unintended pregnancies associated with the combined use of non-enzyme-inducing antibiotics and hormonal contraceptives.

Background: Enzyme-inducing antibacterial drugs can impair the efficacy of hormonal contraceptives. Suspicion that other antibiotics might do likewise led to advice that extra contraceptive precautions should be taken during a course of antibiotics. However, current advice is that the purported interaction does not occur, based on small studies observing few pregnancies, assuming that all women are susceptible, and without measuring unbound hormone concentrations.