Tania Schink

Incidence of anogenital warts in Germany: a population-based cohort study

BackgroundHuman papilloma virus (HPV) types 6 and 11 account for 90 percent of anogenital warts (AGW). Assessment of a potential reduction of the incidence of AGW following introduction of HPV vaccines requires population-based incidence rates. The aim of this study was to estimate incidence rates of AGW in Germany, stratified by age, sex, and region. Additionally, the medical practitioner (gynaecologist, dermatologist, urologist etc.) who made the initial diagnosis of AGW was assessed.MethodsRetrospective cohort study in a population aged 10 to 79 years in a population-based healthcare insurance database. The database included more than 14 million insurance members from all over Germany during the years 2004-2006. A case of AGW was considered incident if a disease-free period of twelve months preceded the diagnosis. To assess regional variation, analyses were performed by federal state.ResultsThe estimated incidence rate was 169.5/100,000 person-years for the German population aged 10 to 79 years. Most cases occurred in the 15 to 40 years age group. The incidence rate was higher and showed a peak at younger ages in females than in males. The highest incidence rates for both sexes were observed in the city-states Berlin, Hamburg and Bremen. In females, initial diagnosis of AGW was most frequently made by a gynaecologist (71.7%), whereas in males, AGW were most frequently diagnosed by a dermatologist (44.8%) or urologist (25.1%).ConclusionsIncidence of AGW in Germany is comparable with findings for other countries. As expected, most cases occurred in the younger age groups. The frequency of diagnoses of AGW differs between sexes and women and men receive treatment by doctors of different specialties.

Risk of febrile convulsions after MMRV vaccination in comparison to MMR or MMR+V vaccination

BACKGROUND In July 2006, Priorix-Tetra™, a combined measles-mumps-rubella-varicella (MMRV) vaccine, was licensed in Germany. Since a postlicensure study had shown a more than twofold elevated risk of febrile convulsions (FC) after first dose vaccination with the combined MMRV vaccine ProQuad(®) compared to separately administered MMR and V vaccines (MMR+V), the Paul-Ehrlich-Institute, the German regulatory agency for vaccine licensing and safety, requested a study investigating the risk of FC for Priorix-Tetra™. METHODS We performed a matched cohort study based on claims data of more than 17 million insurees in the German Pharmacoepidemiological Research Database. All children born between 01.01.2004 and 31.12.2008 who received a 1st dose of MMRV vaccine were matched to children vaccinated with MMR, MMR+V and MMR or MMR+V (combined group), respectively, by sex, age, month of vaccination and statutory health insurance. The primary outcome was defined as hospitalization with a diagnosis of FC without any alternative plausible cause of FC, e.g. an infection or neurological condition, coded as main discharge diagnosis. The secondary outcome excluded only neurological conditions to provide a more comparable outcome definition to the one used in the ProQuad(®) study. Numbers needed to harm (NNH), risk ratios and confounder adjusted odds ratios (ORs) with 95% CIs were estimated to compare the exposure groups. RESULTS In the main risk period 5-12 days after immunization, the adjusted ORs of the primary endpoint for immunization with MMRV vaccine relative to the comparator vaccine indicated in brackets were 4.1 [95% CI 1.3-12.7; MMR], 3.5 [0.7-19.0; MMR+V], and 4.1 [1.5-11.1; MMR and MMR+V]. The corresponding ORs for the secondary outcome were 2.3 [1.4-3.9; MMR], 1.5 [0.8-2.9; MMR+V] and 2.4 [1.5-3.9; MMR and MMR+V]. CONCLUSIONS This study in children younger than 5 years, 90% of them between 11 and 23 months, shows a risk of FC similar in magnitude for Priorix-Tetra™ as has previously been reported for ProQuad(®) suggesting a class effect for these quadrivalent vaccines.

Systemic antibiotic prescribing to paediatric outpatients in 5 European countries: a population-based cohort study

BackgroundTo describe the utilisation of antibiotics in children and adolescents across 5 European countries based on the same drug utilisation measures and age groups. Special attention was given to age-group-specific distributions of antibiotic subgroups, since comparison in this regard between countries is lacking so far.MethodsOutpatient paediatric prescriptions of systemic antibiotics during the years 2005-2008 were analysed using health care databases from the UK, the Netherlands, Denmark, Italy and Germany. Annual antibiotic prescription rates per 1,000 person years were estimated for each database and stratified by age (≤4, 5-9, 10-14, 15-18 years). Age-group-specific distributions of antibiotic subgroups were calculated for 2008.ResultsWith 957 prescriptions per 1000 person years, the highest annual prescription rate in the year 2008 was found in the Italian region Emilia Romagna followed by Germany (561), the UK (555), Denmark (481) and the Netherlands (294). Seasonal peaks during winter months were most pronounced in countries with high utilisation. Age-group-specific use varied substantially between countries with regard to total prescribing and distributions of antibiotic subgroups. However, prescription rates were highest among children in the age group ≤4 years in all countries, predominantly due to high use of broad spectrum penicillins.ConclusionsStrong increases of antibiotic prescriptions in winter months in high utilising countries most likely result from frequent antibiotic treatment of mostly viral infections. This and strong variations of overall and age-group-specific distributions of antibiotic subgroups across countries, suggests that antibiotics are inappropriately used to a large extent.

Incidence of herpes zoster and its complications in Germany, 2005-2009.

OBJECTIVES After introduction of a herpes zoster (HZ) vaccine in Germany in 2013, a potential recommendation by the German Standing Vaccination Committee is still pending. This study estimated data on the disease burden of HZ in Germany to extend the data basis for the decision process. METHODS A retrospective cohort study on data from 7 million statutory health insurance members from 2005 to 2009 was conducted. HZ cases were identified using ICD-10-codes. IRs of HZ and complications were estimated overall, by age, sex and immune status. The proportion of postherpetic neuralgia (PHN), hospitalizations, the diagnosing physician specialty and systemic antiviral therapy were assessed. RESULTS Annual standardized IRs ranged between 5.3 and 5.5 per 1000 person-years (PY) between 2006 and 2009 with higher IRs in females. In 2009, 72.4% of HZ patients were without complications, while 15.5% suffered from nervous system involvement. The age-related increase was higher for HZ complications than for uncomplicated HZ. Immunocompromised patients suffered slightly more complications than immunocompetent patients. The PHN proportion increased to 15% in 2009 with a steady age-related increase. About 3% of HZ cases were hospitalized. CONCLUSIONS Age-related increases of HZ complications and PHN suggest that particularly older patients might benefit from HZ vaccination.

Incidence and relative risk of hearing disorders in professional musicians.

Background Hearing disorders have been associated with occupational exposure to music. Musicians may benefit from non-amplified and low-intensity music, but may also have high risks of music-induced hearing loss. Aims To compare the incidence of hearing loss (HL) and its subentities in professional musicians with that in the general population. Methods We performed a historical cohort study among insurants between 19 and 66 years who were employed subject to social insurance contributions. The study was conducted with data from three German statutory health insurance providers covering the years 2004–2008 with about 7 million insurants. Incidence rates with 95% CIs of HL and the subentities noise-induced hearing loss (NIHL), conductive HL, sensorineural HL, conductive and sensorineural HL, as well as tinnitus were estimated stratified by age, sex and federal state. A Cox regression analysis was conducted to estimate adjusted HRs and two-sided 95% CIs for HL and its subentities. Results More than 3 million insurants were eligible, of whom 2227 were identified as professional musicians (0.07%). During the 4-year observation period, 283 697cases of HL were seen, 238 of them among professional musicians (0.08%), leading to an unadjusted incidence rate ratio of 1.27. The adjusted hazard ratio of musicians was 1.45 (95% CI 1.28 to 1.65) for HL and 3.61 (95% CI 1.81 to 7.20) for NIHL. Conclusions Professional musicians have a high risk of contracting hearing disorders. Use of already available prevention measures should reduce the incidence of HL in professional musicians.

Comparative risk of death in older adults treated with antipsychotics: A population-based cohort study

Although the use of antipsychotics has been associated with an increased risk of death, data on the safety of individual substances is scarce. We thus aimed to compare the risk of death in new users of individual antipsychotics aged =>65 years and conducted a cohort study in the German Pharmacoepidemiological Research Database between 2005 and 2011. Patients were followed from initiation of treatment until death, 90 days after cohort entry, end of insurance or the end of the study period. Multivariable cox regression was used to estimate confounder adjusted hazard ratios (aHR) of death for 14 individual antipsychotics compared to risperidone. In sensitivity analyses, we also applied high-dimensional propensity score (HDPS) methods to explore possible unmeasured confounding. In a cohort of 137,713 new users of antipsychotics, a higher risk of death was found for haloperidol (aHR: 1.45; 95% confidence interval: 1.35-1.55), levomepromazine (aHR: 1.34; 1.16-1.54), zuclopenthixol (aHR: 1.32; 1.02-1.72) and to a lesser extent for melperone (aHR: 1.13; 1.07-1.19) compared to risperidone. Lower risks were observed for quetiapine, prothipendyl, olanzapine, tiapride, clozapine, perazine and flupentixol. In subgroup analyses, levomepromazine and chlorprothixene were only associated with a higher risk of death in patients aged =>80 years and with dementia. The application of HDPS methods did not substantially change the results. In conclusion, our study suggests that initiation of haloperidol, levomepromazine, zuclopenthixol and chlorprothixene treatment is associated with an increased risk of death compared to risperidone and should be avoided in older patients except in palliative care when treatment alternatives are available.

Use of azithromycin and risk of ventricular arrhythmia

BACKGROUND: There are conflicting findings from observational studies of the arrhythrogenic potential of azithromycin. Our aim was to quantify the association between azithromycin use and the risk of ventricular arrhythmia. METHODS: We conducted a nested case–control study within a cohort of new antibiotic users identified from a network of 7 population-based health care databases in Denmark, Germany, Italy, the Netherlands and the United Kingdom for the period 1997–2010. Up to 100 controls per case were selected and matched by age, sex and database. Recency of antibiotic use and type of drug (azithromycin was the exposure of interest) at the index date (occurrence of ventricular arrhythmia) were identified. We estimated the odds of ventricular arrhythmia associated with current azithromycin use relative to current amoxicillin use or nonuse of antibiotics (≥ 365 d without antibiotic exposure) using conditional logistic regression, adjusting for confounders. RESULTS: We identified 14 040 688 new antibiotic users who met the inclusion criteria. Ventricular arrhythmia developed in 12 874, of whom 30 were current azithromycin users. The mean age of the cases and controls was 63 years, and two-thirds were male. In the pooled data analyses across databases, azithromycin use was associated with an increased risk of ventricular arrhythmia relative to nonuse of antibiotics (adjusted odds ratio [OR] 1.97, 95% confidence interval [CI] 1.35–2.86). This increased risk disappeared when current amoxicillin use was the comparator (adjusted OR 0.90, 95% CI 0.48–1.71). Database-specific estimates and meta-analysis confirmed results from the pooled data analysis. INTERPRETATION: Current azithromycin use was associated with an increased risk of ventricular arrhythmia when compared with nonuse of antibiotics, but not when compared with current amoxicillin use. The decreased risk with an active comparator suggests significant confounding by indication.

Treatment patterns and characteristics of older antipsychotic users in Germany.

The aim of this study was to investigate the characteristics and treatment patterns of older antipsychotic (AP) users in Germany. We carried out a cohort study in the German Pharmacoepidemiological Research Database and identified new AP users aged at least 65 years between 2005 and 2011. Possible indications, comedication, and information on persistence and adherence, concurrent multiple use, and switch of APs were assessed. Overall, 298 847 individuals were included in the cohort. Almost 70% entered the cohort with a typical antipsychotic (TAP). Melperone (23.4%) was used most frequently, followed by promethazine (18.3%), sulpiride (11.0%), and risperidone (10.3%). AP users had a low prevalence of schizophrenia and bipolar disorders in contrast to dementia. Initiators of atypical antipsychotics had more treatment episodes compared with TAPs (median 3 vs. 2), but lower median persistence (14 vs. 22 days). Persistence was also lower in patients with, rather than without, dementia. The overall percentage of concurrent multiple use and switch to other APs was low with 5.6%, but higher in patients with, rather than without, dementia. In conclusion, APs were used for a broad range of indications, mostly other than schizophrenia and bipolar disorders. Low persistence and a high number of treatment episodes suggest frequent ‘as-needed’ treatment, especially in dementia patients.

Risk of Stroke after Herpes Zoster – Evidence from a German Self-Controlled Case-Series Study

Background Herpes zoster (HZ) is caused by reactivation of the latent varicella-zoster virus (VZV). A severe complication of HZ is VZV vasculopathy which can result in ischemic or hemorrhagic stroke. The aims of our study were to assess the risk of stroke after the onset of HZ and to investigate the roles of stroke subtype, HZ location and the time interval between HZ onset and stroke. Methods A self-controlled case-series study was performed on a cohort of patients with incident stroke recorded in the German Pharmacoepidemiological Research Database (GePaRD), which covers about 20 million persons throughout Germany. We estimated adjusted incidence rate ratios (IRR) by comparing the rate of stroke in risk periods (i.e., periods following HZ) with the rate of stroke in control periods (i.e., periods without HZ) in the same individuals, controlling for both time-invariant and major potentially time-variant confounders. Results The cohort included 124,462 stroke patients, of whom 6,035 (5%) had at least one HZ diagnosis identified in GePaRD either as main hospital discharge diagnosis or as HZ treated with antivirals. The risk of stroke was about 1.3 times higher in the risk periods 3 months after HZ onset, than in the control periods (IRR: 1.29; 95% confidence interval: 1.16–1.44). An elevated risk of similar magnitude was observed for ischemic and unspecified stroke, but a 1.5-fold higher risk was observed for hemorrhagic stroke. A slightly stronger effect on the risk of stroke was also observed during the 3 months after HZ ophthalmicus (HZO) onset (1.59; 1.10–2.32). The risk was highest 3 and 4 weeks after HZ onset and decreased thereafter. Conclusions Our study corroborates an increased risk of stroke after HZ, which is highest 3 to 4 weeks after HZ onset. The results suggest that the risk is more pronounced after HZO and is numerically higher for hemorrhagic than for ischemic stroke.

Prescribing pattern of antipsychotic drugs during the years 1996-2010: a population-based database study in Europe with a focus on torsadogenic drugs.

INTRODUCTION Antipsychotic drugs (APDs) are used to treat several mental illnesses. Some APDs have long been known to be associated with QT prolongation, potentially leading to torsades de pointes (TdP) and sudden cardiac death (SCD). In 2005, thioridazine was withdrawn because of the risk of SCD, bringing further attention to the arrhythmogenic potential of APDs. AIM The aim of the current study was to evaluate the use of APDs in five European countries during the years 1996-2010. METHODS A cohort study was conducted using prescription/dispensing data from seven healthcare databases [the AARHUS University Hospital Database (Denmark), the German Pharmacoepidemiological Research Database (GePaRD) (Germany), Health Search Database/Thales (HSD) and Emilia Romagna Regional Database (ERD) (Italy), PHARMO Database Network and Integrated Primary Care Information (IPCI) (the Netherlands) and The Health Improvement Network (THIN) (the UK), covering a population of 27 million individuals. The annual prescription rate of APDs was measured overall and for individual medications. APDs were classified as torsadogenic according to the Arizona-CERT list. All analyses were stratified by age, gender and calendar year. RESULTS A total of 559 276 person-years (PYs) of exposure to APDs was captured. The crude annual prescription rate of APD use ranged from 3.0/1000 PYs in ERD to 7.7/1000 PYs in AARHUS. Among APDs with established torsadogenic potential, thioridazine was the most frequently used medication in the UK. Haloperidol was commonly prescribed in Italy and the Netherlands. The use of APDs with torsadogenic potential was much higher in elderly patients. CONCLUSIONS Substantial use of APDs with torsadogenic potential has been reported in Europe in recent years, in spite of increasing concerns about their arrhythmogenic potential. This use was even greater in elderly patients, who are at higher risk of SCD.