Bie, S. de

Prescription of nonselective NSAIDs, coxibs and gastroprotective agents in the era of rofecoxib withdrawal - A 617 400-patient study (Article)

2012-10-01T00:00:00Z

Background Gastroprotective strategies are recommended for nonsteroidal anti-inflammatory drug (NSAID) users at risk of upper gastrointestinal (UGI) complications. Aim To compare the use of gastroprotective strategies in NSAID users in three countries, and the subsequent impact of rofecoxib withdrawal. Methods We conducted a population-based cohort study in three general practice (GP) databases: (i) United Kingdom's (UK) GP Research Database (1998-2008); (ii) Italy's (IT) Health Search/CSD Longitudinal Patient Database (2000-2007); and (iii) the Dutch (NL) Integrated Primary Care Information database (1996-2006). Study cohorts comprised incident NSAID users ≥50 years. Preventive strategies included: (i) co-prescription of gastroprotective agents; or (ii) cyclooxygenase-2-selective inhibitor use. Under-use was defined as no gastroprotection in patients with ≥1 UGI risk factor (history of UGI event, age ≥65 years, concomitant use of anticoagulants, antiplatelets or glucocorticoids). Interrupted time-series analysis was performed to assess the impact of rofecoxib withdrawal on preventive strategies. Results The study populations consisted of 384 649 UK, 177 747 IT and 55 004 NL NSAID users. In UK, under-use of preventive strategies fell from 91% to 71% [linear trend (lt) P = 0.001], in NL from 92% to 58% (lt P < 0.001) and in IT from 90% to 76% (lt P = 0.38) in high-risk NSAID users. In 2000 and 2006, under-use was significantly lower in NL compared with UK and IT (P < 0.001) in high-risk users. After rofecoxib's withdrawal, under-use increased significantly in UK and NL. Conclusions The prescription of gastropreventive strategies followed a similar pattern across countries. Despite a temporary negative effect of rofecoxib withdrawal on under-use, improvement of gastroprotection with nonsteroidal anti-inflammatory drugs was observed.

Safety of pandemic H1N1 vaccines in children and adolescents (Article)

2011-10-06T00:00:00Z

During the 2009 influenza A (H1N1) pandemic several pandemic H1N1 vaccines were licensed using fast track procedures, with relatively limited data on the safety in children and adolescents. Different extensive safety monitoring efforts were put in place to ensure timely detection of adverse events following immunization. These combined efforts have generated large amounts of data on the safety of the different pandemic H1N1 vaccines, also in children and adolescents. In this overview we shortly summarize the safety experience with seasonal influenza vaccines as a background and focus on the clinical and post marketing safety data of the pandemic H1N1 vaccines in children. We identified 25 different clinical studies including 10,505 children and adolescents, both healthy and with underlying medical conditions, between the ages of 6 months and 23 years. In addition, large monitoring efforts have resulted in large amounts of data, with almost 13,000 individual case reports in children and adolescents to the WHO. However, the diversity in methods and data presentation in clinical study publications and publications of spontaneous reports hampered the analysis of safety of the different vaccines. As a result, relatively little has been learned on the comparative safety of these pandemic H1N1 vaccines - particularly in children. It should be a collective effort to give added value to the enormous work going into the individual studies by adhering to available guidelines for the collection, analysis, and presentation of vaccine safety data in clinical studies and to guidance for the clinical investigation of medicinal products in the pediatric population. Importantly the pandemic has brought us the beginning of an infrastructure for collaborative vaccine safety studies in the EU, USA and globally.

Changes during exercise of ECG intervals related to increased risk for ventricular arrhythmia in repaired tetralogy of Fallot and their relationship to right ventricular size and function (Article)

2008-03-14T00:00:00Z

Purpose: Our study aimed to assess pro-arrhythmogenic electrocardiographic changes during maximal physical exercise in patients operated for Tetralogy of Fallot (TOF). Methods: TOF patients prospectively underwent: 1) bicycle ergometry, 2) cardiac MRI, and 3) 24-hour Holter. ECG data was analyzed at rest, at 60% of peak exercise and at peak exercise. R-R duration, QRS-, QT- and JT-duration and dispersions were assessed. Changes of ECG parameters during exercise were calculated and correlated to RV volume, RVEF, RV wall-mass, PR-percentage and VO2max. Exercise ECG data from healthy controls were used as reference. Results: Thirty-one patients (mean age at repair (SD) 0.8 (0.5) years, age at study 16 (5) years) and 25 controls (age 12 (2) years) were included. With exercise mean QTc and JTc dispersions increased in patients (p < 0.001), but not in controls. At peak exercise JTc dispersion was larger in patients (p < 0.01). QTc did not change with exercise in patients (p = 0.14) and decreased in controls (p < 0.05). At all levels of exercise mean QTc, QRS and QRS dispersion were larger in patients (all p < 0.001). Significant associations were found for; 1) a larger increase of JTc dispersion with a higher PR-percentage, a larger RV volume, a larger RV wall-mass, 2) a larger QTc increase with a larger RV volume and worse RVEF. Conclusion: During physical exercise inhomogeneity of repolarisation, known to predispose for re-entry ventricular arrhythmia, increases in repaired TOF. Larger inhomogeneity is found with more severe PR.