Spironolactone and risk of upper gastrointestinal events: population based case-control study

OBJECTIVE: To confirm and quantify any association between spironolactone and upper gastrointestinal bleeding and ulcers. DESIGN: Population based case-control study. SETTING: A primary care information database in the Netherlands. PARTICIPANTS: All people on the database who were aged 18 or more between 1 January 1996 and 30 September 2003. Patients with a history of alcoholism or gastrointestinal cancer were excluded. Ten controls were matched to each case of gastroduodenal ulcer or upper gastrointestinal bleeding by age (year of birth), sex, and index date. MAIN OUTCOME MEASURES: The occurrence of an upper gastrointestinal event (bleeding or ulcers), adjusted for potential confounders with conditional logistic regression analysis. RESULTS: Within the source population of 306 645 patients, 523 cases of gastric or duodenal ulcer or upper gastrointestinal

Unlicensed and off-label prescription of respiratory drugs to children

Many respiratory drugs are not available in formulations suitable for infants and toddlers. Efficacy and safety research is mostly restricted to older children. However, respiratory drugs are frequently used in children for common diseases like asthma, upper and lower respiratory tract infections, rhinitis and sinusitis. The unlicensed and off-label use of respiratory drugs in children were studied. A population-based cohor

Application of a systems pharmacology-based placebo population model to analyze long-term data of postmenopausal osteoporosis

Osteoporosis is a progressive bone disease characterized by decreased bone mass resulting in increased fracture risk. The objective of this investigation was to test whether a recently developed disease systems analysis model for osteoporosis could describe disease progression in a placebo-treated population from the Early Postmenopausal Intervention Cohort (EPIC) study. First, we qualified the model using a subset from the placebo arm of the EPIC study of 222 women who had similar demographic characteristics as the 149 women from the placebo arm of the original population. Second, we applied the model to all 470 women. Bone mineral density (BMD) dynamics were changed to an indirect response model to describe lumbar spine and total hip BMD in this second population. This updated disease systems analys

Isotretinoin exposure during pregnancy: A population-based study in the Netherlands

Objective: To estimate isotretinoin exposure in Dutch pregnant women despite the implemented pregnancy prevention programme (PPP) and second, to analyse the occurrence of adverse fetal or neonatal outcomes in these isotretinoin exposed pregnancies.Design: Population-based study.Setting: The Netherlands.Participants: A cohort of 203 962

Leading the green insurance revolution

Anthropogenic climate change is a significant and growing challenge. Insurance has thus far not taken a leadership role in its response to the challenge, partly because of modeling uncertainties and partly because of unclear customer expectations. It is, however, too large a sector to wait on the sidelines and a more proactive approach is required. The demand for a program we developed for insurance companies in 2021 sends a positive signal for this development. Insurers have started incorporating ESG criteria in their product and service development and have taken steps to control their environmental footprint. Both are challenging, as they involved deep collaboration across the organization and along the value chain. Investment management and risk management have also been evolving to meet the challenge, with the latter especially well-positioned to deliver also market-facing services to insurance customers. Claims handling, however, is not typically considered in an insurer’s footprint and has lagged behind. This is unfortunate, as the potential for a broader societal impact through claims is significant. There are several best practices for transforming organizations to deliver more value along corporate responsibility criteria, and insurance companies need to make treasure of this experience. Further, they need to start developing their purpose beyond purely financial dimensions to align important stakeholders and deliver the promise of insurance as a social good in the 21st Century

Antibiotic-Induced Liver Injury in Paediatric Outpatients: A Case-Control Study in Primary Care Databases

Introduction: Antibiotics are the most commonly prescribed drug class in children. Real-world data mining on the paediatric population showed potential associations between antibiotic use and acute liver injury. Objective: We assessed risk estimates of liver injury associated with antibiotic use in children and adolescent outpatients. Methods: A large, multi-database, population-based, case-control study was performed in people <18 years of age from two European countries (Italy and The Netherlands) during the period 2000–2008. All potential cases of liver injury were automatically extracted from three databases and then manually validated based on Council for International Organizations of Medical Sciences (CIOMS) criteria and by exclusion of all competing causes for liver injury. Up to 100 control participants were sampled for each case and were matched on index date of the event, age, sex and database. Based on prescription data, antibiotic exposure was categorized as current, recent or past use by calculating the time period between the end of prescription and the index date. Multivariate conditional logistic regression analyses were applied to calculate odds ratios (ORs) as a measure of the association (with 95% confidence interval [CI]). Results: We identified 938 cases of liver injury and matched to 93,665 controls. Current use of overall antibiotics is associated with a threefold increased risk of liver injury compared with past use (adjusted OR [ORadj] 3.22, 95% CI 2.57–4.03). With regard to individual antibiotics, the risk is significantly increased for current use of each antibiotic (p < 0.005), except for azithromycin. Risk estimates vary from the lowest ORadj of 1.86 (95% CI 1.08–3.21) for amoxicillin to the highest ORadj of 24.16 (95% CI 11.78–49.54) for cotrimoxazole (i.e. sulphamethoxa

Prolonged QTc Interval and Risk of Sudden Cardiac Death in a Population of Older Adults

ObjectivesThis study sought to investigate whether prolongation of the heart rate-corrected QT (QTc) interval is a risk factor for sudden cardiac death in the general population.BackgroundIn developed countries, sudden cardiac death is a major cause of cardiovascular mortality. Prolongation of the QTc interval has been associated with ventricular arrhythmias, but in most population-based studies no consistent association was found between QTc prolongation and total or cardiovascular mortality. Only very few of these studies specifically addressed sudden cardiac death.MethodsThis study was conducted as part of the Rotterdam Study, a prospective population-based cohort study that comprises 3,105 men and 4,878 women aged 55 years and older. The QTc interval on the electrocardiogram was determined during the baseline visit (1990 to 1993) and the first follow-up examination (1993 to 1995). The association between a prolonged QTc interval and sudden cardiac death was estimated using Cox proportional hazards analysis.ResultsDuring an average follow-up period of 6.7 years (standard deviation, 2.3 years) 125 patients died of sudden cardiac death. An abnormally prolonged QTc interval (>450 ms in men, >470 ms in women) was associated with a three-fold increased risk of sudden cardiac death (hazard ratio, 2.5; 95% confidence interval, 1.3 to 4.7), after adjustment for age, gender, body mass index, hypertension, cholesterol/high-density lipoprotein ratio, diabetes mellitus, myocardial infarction, heart failure, and heart rate. In patients with an age below the median of 68 years, the corresponding relative risk was 8.0 (95% confidence interval 2.1 to 31.3).ConclusionsAbnormal QTc prolongation on the electrocardiogram should be viewed as an independent risk factor for sudden cardiac death