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.

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*".

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.

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.

Medical Devices: Definition, Classification, and Regulatory Implications.

We propose the following definition of a medical device: "A contrivance designed and manufactured for use in healthcare, and not solely medicinal or nutritional." Current regulatory classifications of medical devices are complex and designed primarily for regulators. We propose a simpler classification, based on (1) the site of application of the device, (2) the time scale of its use, and (3) whether it has an external power source.

Medical Devices: Classification and Analysis of Faults Leading to Harms.

Introduction: Harms from medical devices are important, but have been much less well studied than adverse drug reactions. Information provided to device users is of variable quality.

Objective: Our aim was to define "medical device fault" and "adverse effect of a medical device"; to establish whether medical device faults arise in design, manufacture, or use; and to consider ways of mitigating the adverse effects of medical devices.

Efficacy and toxicity of antihypertensive pharmacotherapy relative to effective dose 50.

Antihypertensive drugs have usually been approved at doses near the top of their respective dose-response curves. Efficacy plateaus but adverse drug reactions (ADRs), such as falls, cerebral or renal ischaemia, increase as dose is increased, especially in older patients with comorbidities. ADRs reduce adherence and may be difficult to ascertain reliably.

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.

Antithrombotic dose: Some observations from published clinical trials.

The clinical doses of antithrombotics-antiplatelet and anticoagulant agents-need to balance efficacy and safety. It is not clear from the published literature how the doses currently used in clinical practice have been derived from preclinical and clinical data. There are few large randomised controlled trials (RCTs) that compare outcomes with different doses vs placebo.

The relationship between antemortem and postmortem morphine concentrations.

An important forensic problem is whether the presence of a drug such as morphine caused or contributed to a death or was merely incidental. The reliance that can be based on postmortem drug concentrations remains controversial. To investigate this further we obtained antemortem and postmortem samples of individuals admitted to hospital who were receiving morphine and who died in hospital.

Preventing Future Deaths from Medicines: Responses to Coroners' Concerns in England and Wales.

Introduction: Coroners inquire into sudden, unexpected, or unnatural deaths. We have previously established 99 cases (100 deaths) in England and Wales in which medicines or part of the medication process or both were mentioned in coroners' 'Regulation 28 Reports to Prevent Future Deaths' (coroners' reports).

Objective: We wished to see what responses were made by National Health Service (NHS) organizations and others to these 99 coroners' reports.

Deaths from Medicines: A Systematic Analysis of Coroners' Reports to Prevent Future Deaths.

Introduction: Since legislation in 2009, coroners in England and Wales must make reports in cases where they believe it is possible to prevent future deaths. We categorised the reports and examined whether they could reveal preventable medication errors or novel adverse drug reactions.

Methods: We examined 500 coroners' reports by pre-defined criteria to identify those in which medicines played a part, and to collect information on coroners' concerns.

Unlicensed and off-label uses of medicines: definitions and clarification of terminology.

The terms 'licensed', 'unlicensed', and 'off-label', often used in relation to marketing and prescribing medicinal products, may confuse UK prescribers. To market a medicinal product in the UK requires a Marketing Authorization ('product licence') for specified indications under specified conditions, regulated by the Medicines and Healthcare products Regulatory Agency (MHRA). The Marketing Authorization includes the product's agreed terms of use (the 'label'), described in the Summary of Product Characteristics (SmPC).

The toxicological significance of post-mortem drug concentrations in bile.

Context: Some authors have proposed that post-mortem drug concentrations in bile are useful in estimating concentrations in blood. Both The International Association of Forensic Toxicologists (TIAFT) and the US Federal Aviation Administration recommend that samples of bile should be obtained in some circumstances. Furthermore, standard toxicological texts compare blood and bile concentrations, implying that concentrations in bile are of forensic value.