Mark C.H. De Groot

Exposure to benzodiazepines (anxiolytics, hypnotics and related drugs) in seven European electronic healthcare databases: a cross-national descriptive study from the PROTECT-EU Project

Studies on drug utilization usually do not allow direct cross‐national comparisons because of differences in the respective applied methods. This study aimed to compare time trends in BZDs prescribing by applying a common protocol and analyses plan in seven European electronic healthcare databases.

The High Impact of Penicillin Allergy Registration in Hospitalized Patients.

BACKGROUND Suspected penicillin allergy (Pen-A) is often not verified or excluded by diagnostic testing. OBJECTIVE To assess the prevalence and impact of Pen-A registration in a Dutch University Medical Center. METHODS In a prospective matched cohort study, all admitted patients (July 2013-July 2014) who underwent a pharmacotherapeutic interview were selected. Patients with a registered Pen-A were matched on age, sex, and department of admission with up to 3 patients without a registered Pen-A. Relative risks (RRs) of receiving a reserve antibiotic, death during hospitalization, and rehospitalization were compared in the 2 cohorts. The number and type of antibiotics prescribed during admission and duration of hospitalization were compared. RESULTS Of 17,959 patients, 1010 (5.6%) patients (66.7% women; median age, 55 years) had a Pen-A registration. These patients had a higher risk of receiving reserve antibiotics (RR, 1.38; 95% CI, 1.22-1.56) and of being rehospitalized within 12 weeks (RR, 1.28; 95% CI, 1.10-1.49). A significantly larger proportion of Pen-A registered patients received reserve antibiotics such as tetracyclines (1.8% vs 0.8%), macrolides/lincosamides/streptogramins (12.5% vs 4.9%), and quinolones (7.9% vs 4.3%) or received 2 or more types of antibiotics during hospitalization (21.7% vs 16.9%). CONCLUSIONS Prevalence of Pen-A registration in hospitalized patients is high, has high impact on antibiotic prescribing, and is associated with a higher risk of readmission. Verification of the Pen-A in hospitalized patients might restrict the use of reserve antibiotics and improve patient outcome.

Antiepileptic drug use in seven electronic health record databases in Europe : a methodologic comparison

The annual prevalence of antiepileptic drug (AED) prescribing reported in the literature differs considerably among European countries due to use of different type of data sources, time periods, population distribution, and methodologic differences. This study aimed to measure prevalence of AED prescribing across seven European routine health care databases in Spain, Denmark, The Netherlands, the United Kingdom, and Germany using a standardized methodology and to investigate sources of variation.

Prevalence of antibiotic use : a comparison across various European health care data sources

There is widespread concern about increases in antibiotic use, but comparative data from different European countries on rates of use are lacking. This study was designed to measure and understand the variation in antibiotic utilization across five European countries.

Hip/femur fractures associated with the use of benzodiazepines (anxiolytics, hypnotics and related drugs) : a methodological approach to assess consistencies across databases from the PROTECT-EU project

Results from observational studies may be inconsistent because of variations in methodological and clinical factors that may be intrinsically related to the database (DB) where the study is performed.

Understanding inconsistency in the results from observational pharmacoepidemiological studies : the case of antidepressant use and risk of hip/femur fractures

Results from observational studies on the same exposure–outcome association may be inconsistent because of variations in methodological factors, clinical factors or health care systems. We evaluated the consistency of results assessing the association between antidepressant use and the risk of hip/femur fractures in three European primary care databases using two different study designs.

Calcium channel blockers and cancer : A risk analysis using the UK Clinical Practice Research Datalink (CPRD)

Objective The evidence of an association between calcium channel blockers (CCBs) and cancer is conflicting. The objective of the present study was to evaluate the risk of cancer (all, breast, prostate and colon cancers) in association with exposure to CCB. Methods This is a population-based cohort study in patients exposed to CCBs from across the UK, using two comparison cohorts: (1) patients with no exposure to CCB (non-CCB) matched on age and gender and (2) unmatched patients unexposed to CCB and at least one other antihypertensive (AHT) prescription. Cancer incidence rates computed in the exposed and the two unexposed groups were compared using HRs and 95% CIs obtained from multivariate Cox regression analyses. Results Overall, 150 750, 557 931 and 156 966 patients were included, respectively, in the CCB, non-CCB and AHT cohorts. Crude cancer incidence rates per 1000 person-years were 16.51, 15.75 and 10.62 for the three cohorts, respectively. Adjusted HRs (CI) for all cancers comparing CCB, non-CCB and AHT cohorts were 0.88 (0.86 to 0.89) and 1.01 (0.98 to 1.04), respectively. Compared to the AHT cohort, adjusted HRs (CI) for breast, prostate and colon cancer for the CCB cohort were 0.95 (0.87 to 1.04), 1.07 (0.98 to 1.16) and 0.89 (0.81 to 0.98), respectively. Analyses by duration of exposure to CCB did not show excess risk. Conclusions This large population-based study provides strong evidence that CCB use is not associated with an increased risk of cancer. The analyses yielded robust results across all types of cancer and different durations of exposure to CCBs.

Risk of acute liver injury associated with use of antibiotics. Comparative cohort and nested case–control studies using two primary care databases in Europe

To assess the impact of varying study designs, exposure and outcome definitions on the risk of acute liver injury (ALI) associated with antibiotic use.

Multi-centre, multi-database studies with common protocols: Lessons learnt from the IMI PROTECT project

To assess the impact of a variety of methodological parameters on the association between six drug classes and five key adverse events in multiple databases.

The IMI PROTECT project : purpose, organizational structure, and procedures

The Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium (PROTECT) initiative was a collaborative European project that sought to address limitations of current methods in the field of pharmacoepidemiology and pharmacovigilance. Initiated in 2009 and ending in 2015, PROTECT was part of the Innovative Medicines Initiative, a joint undertaking by the European Union and pharmaceutical industry. Thirty‐five partners including academics, regulators, small and medium enterprises, and European Federation of Pharmaceuticals Industries and Associations companies contributed to PROTECT. Two work packages within PROTECT implemented research examining the extent to which differences in the study design, methodology, and choice of data source can contribute to producing discrepant results from observational studies on drug safety. To evaluate the effect of these differences, the project applied different designs and analytic methodology for six drug–adverse event pairs across several electronic healthcare databases and registries. This papers introduces the organizational structure and procedures of PROTECT, including how drug–adverse event and data sources were selected, study design and analyses documents were developed, and results managed centrally. Copyright