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INTRODUCTION: Since being designated as medicines by World Health Organization (WHO), blood components are subject to pharmacovigilance reporting. Using VigiBase, the WHO global database of individual case safety reports (ICSRs), we characterized reports of adverse reactions for all blood products. STUDY DESIGN AND METHODS: ICSRs involving blood products as the suspected medicine in VigiBase between 1968 and 2021 were extracted. MedDRA preferred terms and the International Society of Blood Transfusion haemovigilance definitions were used to stratify adverse reactions. Descriptive statistics were used to characterize ICSR demographics. RESULTS: A total of 111,033 ICSRs containing 577,577 suspected adverse reactions with 6152 MedDRA preferred terms were reported for 34 blood products. There were 12,153 (10.9%) reports for blood components, 98,135 (88.4%) reports for plasma-derived medicines, and 745 (0.7%) reports for recombinant products. The majority of reports (21.0% and 19.7%, respectively) were from patients aged 45-64 and over 65 years. The Americas contributed the most ICSRs (49.7%). Top reported suspected adverse reactions were for the following MedDRA preferred terms: headache (3.5%), pyrexia (2.8%), chills (2.8%), dyspnoea (1.8%), and nausea (1.8%). CONCLUSION: VigiBase already has a large number of reports on blood products. When compared to other existing haemovigilance databases, our study found reports from a broader range of countries and reporters. This may provide us with new perspectives, but for VigiBase to reach its full potential in haemovigilance some alterations in what is captured in reports are required.

Background: People with multiple sclerosis (pwMS) have an increased risk of infections; risk factors include underlying disease, physical impairment and use of some disease-modifying treatments. Objective: To quantify changes in population-level infection rates among pwMS and compare these to the general population and people with rheumatoid arthritis (pwRA), and identify patient characteristics predictive of infections after MS diagnosis. Methods: We conducted a multi-database study using data on 23,226 people with MS diagnosis from the UK Clinical Practice Research Datalink Aurum and GOLD (January 2000–December 2020). PwMS were matched to MS-free controls and pwRA. We calculated infection rates, and estimated incidence rate ratios (IRR) and 95% confidence intervals (CI) of predictors for infections ⩽ 5 years after MS diagnosis using Poisson regression. Results: Among pwMS, overall infection rates remained stable – 1.51-fold (1.49–1.52) that in MS-free controls and 0.87-fold (0.86–0.88) that in pwRA – although urinary tract infection rate per 1000 person-years increased from 98.7 (96.1–101) (2000–2010) to 136 (134–138) (2011–2020). Recent infection before MS diagnosis was most predictive of infections (1 infection: IRR 1.92 (1.86–1.97); ⩾2 infections: IRR 3.00 (2.89–3.10)). Conclusion: The population-level elevated risk of infection among pwMS has remained stable despite the introduction of disease-modifying treatments.

Pharmacogenomic testing is a method to prevent adverse drug reactions. Pharmacogenomics could be relevant to optimize statin treatment, by identifying patients at high risk for adverse drug reactions. We aim to investigate the clinical validity and utility of pre-emptive pharmacogenomics screening in primary care, with SLCO1B1 c.521T>C as a risk factor for statin-induced adverse drug reactions. The focus was on changes in therapy as a proxy for adverse drug reactions observed in statin-users in a population-based Dutch cohort. In total, 1136 statin users were retrospectively genotyped for the SLCO1B1 c.521T>C polymorphism (rs4149056) and information on their statin dispensing was evaluated as cross-sectional research. Approximately half of the included participants discontinued or switched their statin treatment within three years. In our analyses, we could not confirm an association between the SLCO1B1 c.521T>C genotype and any change in statin therapy or arriving at a stable dose sooner in primary care. To be able to evaluate the predictive values of SLCO1B1 c.521T>C genotype on adverse drug reactions from statins, prospective data collection of actual adverse drug reactions and reasons to change statin treatment should be facilitated.

Aims Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are antidiabetic agents that can have direct cardiac effects by impacting on cardiac ion transport mechanisms that control cardiac electrophysiology. We studied the association between SGLT-2i use and all-cause mortality and the risk of sudden cardiac arrest (SCA) in patients with type 2 diabetes. Methods Using data from the UK Clinical Practice Research Datalink, a cohort study among patients initiating a new antidiabetic drug class on or after January 2013 through September 2020 was conducted. A Cox regression with time-dependent covariates was performed to estimate the hazard ratios (HRs) of SCA and all-cause mortality comparing SGLT-2is with other second- to third-line antidiabetic drugs. Stratified analyses were performed according to sex, diabetes duration ( Results A total of 152 591 patients were included. Use of SGLT-2i was associated with a reduced HR of SCA when compared with other second- to third-line antidiabetic drugs after adjustment for common SCA risk factors, although this association marginally failed to reach statistical significance [HR: 0.62, 95% confidence interval (95% CI): 0.38–1.01]. The HR of all-cause mortality associated with SGLT-2i use when compared with other second- to third-line antidiabetics was 0.43 (95% CI: 0.39–0.48) and did not vary by sex, diabetes duration, or the presence of cardiovascular disease. SGLT-2i use remained associated with lower all-cause mortality in patients without concomitant insulin use (HR: 0.56, 95% CI: 0.50–0.63). Conclusion SGLT-2i use was associated with reduced all-cause mortality in patients with type 2 diabetes. The association between use of SGLT-2i and reduced risk of SCA was not statistically significant.

ObjectiveTo evaluate the association between regulatory drug safety advisories and changes in drug utilisation.DesignWe conducted controlled, interrupted times series analyses with administrative prescription claims data to estimate changes in drug utilisation following advisories. We used random-effects meta-analysis with inverse-variance weighting to estimate the average postadvisory change in drug utilisation across advisories.Study populationWe included advisories issued in Canada, Denmark, the UK and the USA during 2009–2015, mainly concerning drugs in common use in primary care. We excluded advisories related to over-the-counter drugs, drug-drug interactions, vaccines, drugs used primarily in hospital and advisories with co-interventions within ±6 months.Main outcome measuresChange in drug utilisation, defined as actual versus predicted percentage change in the number of prescriptions (for advisories without dose-related advice), or in the number of defined daily doses (for dose-related advisories), per 100 000 population.ResultsAmong advisories without dose-related advice (n=20), the average change in drug utilisation was −5.83% (95% CI −10.93 to –0.73; p=0.03). Advisories with dose-related advice (n=4) were not associated with a statistically significant change in drug utilisation (−1.93%; 95% CI −17.10 to 13.23; p=0.80). In a post hoc subgroup analysis of advisories without dose-related advice, we observed no statistically significant difference between the change in drug utilisation following advisories with explicit prescribing advice, such as a recommendation to consider the risk of a drug when prescribing, and the change in drug utilisation following advisories without such advice.ConclusionsAmong safety advisories issued on a wide range of drugs during 2009–2015 in 4 countries (Canada, Denmark, the UK and the USA), the association of advisories with changes in drug utilisation was variable, and the average association was modest.

Aim Activated blood platelet products facilitate myocardial intracellular Ca2+ overload, thereby provoking afterdepolarizations and increasing susceptibility of ischemic myocardium to ventricular fibrillation (VF). These effects are counteracted in vitro by acetylsalicylic acid (ASA), but no prior study investigated whether ASA is associated with decreased out-of-hospital cardiac arrest (OHCA) risk on a population level. Therefore, we studied whether ASA and other antiplatelet drugs (carbasalate calcium, clopidogrel) are associated with decreased risk of OHCA. Methods We conducted a population-based case-control study among individuals (772 OHCA-cases with documented VT/VF, 2444 non-OHCA-controls) who had used antiplatelet drugs in the year before index-date (OHCA-date), and studied the association between current antiplatelet drug use and OHCA-risk with multivariable logistic regression analysis. Results ASA use was associated with reduced OHCA-risk (adjusted odds ratio (ORadj) 0.6 [0.5–0.8]), and more so in women (ORadj 0.3 [0.2–0.6]) than in men (ORadj 0.7 [0.5–0.95], Pinteraction 0.021). Carbasalate calcium was associated with decreased OHCA-risk in women (ORadj 0.5 [0.3–0.9]), but not in men (ORadj 1.3 [0.96–1.7], Pinteraction 0.005). Clopidogrel was not associated with reduction in OHCA-risk. Risk reduction associated with ASA in patients with OHCA was similar in the presence of acute myocardial infarction (AMI) (ORadj 0.6 [0.4–0.9]) and in the absence of AMI (ORadj 0.7 [0.4–1.2]). Conclusion ASA use was associated with reduced OHCA-risk in both sexes, and more so in women, while carbasalate calcium only protected women. Clopidogrel was not associated with reduced OHCA-risk.

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), commonly used antihypertensive drugs, may have a protective effect against depression in older individuals, but evidence in humans is limited. Aims: We evaluated the risk of depression, among older individuals with hypertension, comparing ACE or ARB initiators to thiazide(-like) diuretic initiators. Thiazide(-like) diuretics were used as control because these drugs are not associated with mood disorders. Methods: We used a propensity score-matched new user cohort design with routinely collected data from general practices in England from the Clinical Practice Research Datalink database. We matched 12,938 pairs of new users of ACEIs/ARBs and thiazide(-like) diuretics with hypertension (mean age 67.6 years; 54.7% women). Follow-up time started on the date of drug initiation and ended on the date of treatment discontinuation plus 30 days, or switch to a comparator, occurrence of a study event, death, date of patient’s transfer out of practice, or end of the study period. The primary outcome was a composite endpoint of treated depression and nonfatal and fatal self-harm. Results/outcomes: Compared to the thiazide(-like) diuretic group, ACEIs/ARBs use was not associated with a lower risk of the primary outcome (hazard ratio 0.96 (95% confidence interval: 0.79; 1.15)). Results did not differ according to lipophilicity, duration of use, and average daily dose, or class (ACEIs or ARBs). Conclusions/Interpretation: New use of ACEIs or ARBs is not associated with a lower risk of depression among individuals with hypertension.

Supplemental material, sj-docx-1-jop-10.1177_02698811221082470 for Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and risk of depression among older people with hypertension by Thomas T van Sloten, Patrick C Souverein, Coen DA Stehouwer and Johanna HM Driessen in Journal of Psychopharmacology

Supplemental material, sj-docx-1-msj-10.1177_13524585221094218 for Mapping the risk of infections in patients with multiple sclerosis: A multi-database study in the United Kingdom Clinical Practice Research Datalink GOLD and Aurum by Melissa WY Leung, Marloes T Bazelier, Patrick C Souverein, Bernard MJ Uitdehaag, Olaf H Klungel, Hubert GM Leufkens and Romin Pajouheshnia in Multiple Sclerosis Journal

Supplemental material, sj-docx-2-msj-10.1177_13524585221094218 for Mapping the risk of infections in patients with multiple sclerosis: A multi-database study in the United Kingdom Clinical Practice Research Datalink GOLD and Aurum by Melissa WY Leung, Marloes T Bazelier, Patrick C Souverein, Bernard MJ Uitdehaag, Olaf H Klungel, Hubert GM Leufkens and Romin Pajouheshnia in Multiple Sclerosis Journal