Validation of myocarditis diagnoses in the Swedish patient register for analyses of potential adverse reactions to COVID-19 vaccines.

Background: Coronavirus disease 2019 (COVID-19) mRNA vaccines are associated with an increased risk of myocarditis using hospital discharge diagnoses as an outcome. The validity of these register-based diagnoses is uncertain.

Methods: Patient records for subjects < 40 years of age and a diagnosis of myocarditis in the Swedish National Patient Register were manually reviewed.

Utility of registries for post-marketing evaluation of medicines. A survey of Swedish health care quality registries from a regulatory perspective.

Aim: The aim of this study was to describe content and procedures in some selected Swedish health care quality registries (QRs) of relevance to regulatory decision-making.

Methods: A workshop was organized with participation of seven Swedish QRs which subsequently answered a questionnaire regarding registry content on drug treatments and outcomes. Patient populations, coverage, data handling and quality control, as well as legal and ethical aspects are presented.

Increased availability of paracetamol in Sweden and incidence of paracetamol poisoning: using laboratory data to increase validity of a population-based registry study.

Purpose: To estimate the incidence trend and outcome of paracetamol poisoning, in relation to increased availability of paracetamol from non-pharmacy outlets in 2009.

Method: Patients' serum paracetamol results over 14 years (2000-2013) from 20 (out of 21) regions in Sweden were linked to national registers of hospital care, cause of death, and prescriptions. Paracetamol poisonings were defined by serum paracetamol levels, hospital diagnoses, or cause of death.

Influence of age, sex and seriousness on reporting of adverse drug reactions in Sweden.

Purpose: To investigate how reporting of adverse drug reactions (ADRs) among adults in Sweden is associated to age and sex, in addition to seriousness of the reaction and drug utilisation.

Methods: Individual case safety reports (ICSRs) reported by healthcare professionals to the national pharmacovigilance database 2008-2011 were related to defined daily dose (DDD) in the Swedish Prescribed Drug Register (SPDR) for individual's ≥20 years. Data were stratified into five age groups.

Adverse Drug Reactions in a Tertiary Care Emergency Medicine Ward - Prevalence, Preventability and Reporting.

Purpose: To identify the prevalence and preventability of adverse drug reactions (ADRs) in an emergency ward setting in a tertiary hospital in Sweden and to what extent the detected ADRs were reported to the Medical Product Agency (MPA).

Methods: In this prospective cross sectional observational study, 706 patients admitted to one of the Emergency Wards, at the Karolinska University Hospital in Solna, Stockholm during September 2008 -September 2009, were included. The electronic patient records were reviewed for patients' demographic parameters, prevalence of possible ADRs and assessment of their preventability.

Sex differences in spontaneous reports on adverse bleeding events of antithrombotic treatment.

Purpose: To explore if sex differences are found in spontaneously reported adverse events for clopidogrel, low-dose aspirin and warfarin treatment in routine care.

Methods: A cross-sectional analysis combining data on bleeding events from the Swedish Spontaneous Adverse Drug Event Reporting System (SWEDIS) with data from the National Prescribed Drug register. Bleeding event reports from 1999 to 2010 and 2005 to 2010 were adjusted to the number of prescriptions and the number of exposed patients respectively among women and men.

A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose.

We report the first genome-wide association study (GWAS) whose sample size (1,053 Swedish subjects) is sufficiently powered to detect genome-wide significance (p<1.5 x 10(-7)) for polymorphisms that modestly alter therapeutic warfarin dose. The anticoagulant drug warfarin is widely prescribed for reducing the risk of stroke, thrombosis, pulmonary embolism, and coronary malfunction.

Influence of CYP2C9 genotype on warfarin dose requirements--a systematic review and meta-analysis.

Purpose: To quantify the influence of common cytochrome P450 2C9 (CYP2C9) polymorphisms on warfarin dose requirements.

Methods: A systematic review and a meta-analysis, calculating the warfarin dose reduction associated with the five most common variant CYP2C9 genotypes.

Results: Thirty-nine studies (7,907 patients) were included in the meta-analysis.

The largest prospective warfarin-treated cohort supports genetic forecasting.

Genetic variants of cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) are known to influence warfarin dose, but the effect of other genes has not been fully elucidated. We genotyped 183 polymorphisms in 29 candidate genes in 1496 Swedish patients starting warfarin treatment, and tested for association with response. CYP2C9*2 and *3 explained 12% (P = 6.

Incidence and predictors of severe bleeding during warfarin treatment.

Background: Optimal warfarin prescription requires correct, individualized assessment of the warfarin-related bleeding risk, which randomised controlled trials may underestimate . Observational studies have reported a range of bleeding risks that differ 40-fold. This variation may be caused by time trends, variation in bleeding definition and study subject selection.

Several-fold increase in risk of overanticoagulation by CYP2C9 mutations.

Objective: Our objective was to prospectively study the impact of CYP2C9 polymorphism (*2 and *3) on the risk of overanticoagulation during the induction phase of warfarin therapy.

Methods: Blood samples for genotyping were collected from 219 patients requiring warfarin therapy, and clinical data were prospectively collected during the first 3 weeks of medication. Patients were divided into 3 groups according to CYP2C9 genotype, as follows: *1 (homozygous), *2 (*1/*2 and *2/*2), and *3 (any genotype containing the *3 allele).