Ingo Langner

Cohort Mortality Study of German Cockpit Crew, 1960 -1997

Background. Cockpit crew in civil aviation are exposed to several potential health hazards, among them cosmic ionizing radiation. To assess the influence of occupational and other factors on mortality we conducted a cohort study among cockpit crew. Methods. All pilots and other cockpit personnel of two German airlines were traced through registries and other sources for the period 1960–1997. Standardized mortality ratios, with German population rates as the reference, were calculated. We estimated the individual radiation dose based on individual job histories and assessed dose-response trends in stratified and regression analyses. Results. We compiled a cohort of 6061 male cockpit personnel, yielding 105,037 person-years of observation. The maximum estimated individual radiation dose was 80.5 mSv. Among 255 deaths overall (standardized mortality ratio [SMR] = 0.48; 95% confidence interval [CI] = 0.42–0.54) there were 76 cancer deaths (SMR = 0.56; CI = 0.43 – 0.74). Most cancer and cardiovascular SMRs were reduced. A slight increase was seen for brain cancer (SMR = 1.68; CI = 0.66–3.62). Employment duration was associated with the all-cancer mortality in Poisson regression analyses. No other dose-response relation was found. Conclusions. German cockpit crew have a low overall and cancer mortality. The role of occupational causes, and particularly cosmic radiation, appears limited.

Age-Specific Prevalence, Incidence of New Diagnoses, and Drug Treatment of Attention-Deficit/Hyperactivity Disorder in Germany

OBJECTIVE The purpose of this study was to estimate the prevalence and incidence of new diagnoses of attention-deficit/hyperactivity disorder (ADHD) and assess drug treatment of ADHD in the 3-17 year age group in Germany. METHOD We analysed data from the German Pharmacoepidemiological Research Database (GePaRD) for the years 2004-2006. The GePaRD includes claim records of 14,000,000 members of four statutory health insurances, representing 17% of the German population. The assessment of ADHD diagnoses was based on International Classification of Diseases version 10 (ICD-10) codes in outpatient and hospital data. RESULTS In 2005, the age-standardized prevalence and incidence of new diagnoses were 2.5% and 9/1000 person-years, respectively. Both measures were 3-4 times higher for males than for females. Incidence of new ADHD diagnoses increased linearly up to the age of 8 years for boys and 9 years for girls and decreased abruptly thereafter. In the calendar quarter of the initial ADHD diagnosis, 9.4% (95% confidence interval [CI] 8.9-9.8%) received methylphenidate or atomoxetine and 36.8% (95% CI 36.1-37.6%) received at least one prescription of either drug within the first year. Initiation of drug treatment and choice of drug were similar for both sexes. CONCLUSIONS ADHD is a common condition among children and youth in Germany. There are substantial differences by sex in the prevalence and incidence of new ADHD diagnoses, but only a small difference in drug treatment among those diagnosed with ADHD. A relatively low percentage of children receives drug treatment in the first year after the initial diagnosis of ADHD.

Drug treatment patterns of attention-deficit/hyperactivity disorder in children and adolescents in Germany: results from a large population-based cohort study.

OBJECTIVE Despite a substantial increase in total methylphenidate (MPH) prescriptions in Germany over the last 20 years, and the introduction of modified release MPH (MR MPH) and atomoxetine (ATX), remarkably little is known about treatment patterns of attention- deficit/hyperactivity disorder (ADHD) in individual patients. METHODS Usage patterns of ADHD drugs in children and adolescents in Germany were analyzed using data from one large German health insurance including >7,200,000 members. Of those, 6210 ADHD patients newly diagnosed in 2005 were followed for a maximum of 4 years. Kaplan-Meier estimates were calculated for onset and discontinuation of ADHD drug treatment. Predictors of time until drug treatment initiation were assessed by Cox regression. RESULTS During follow-up, 52.0% of ADHD subjects (53.4% of boys, 47.5% of girls) received ADHD drug treatment. The majority of them (91.6%) were started on MPH, with immediate release MPH (IR MPH) being the initial treatment choice in 75.3%. In these subjects, change to drug treatment with MR MPH in the first year occurred in 48% by switch or addition. Significant predictors of drug treatment were behavioral and emotional disorders (HR=1.13; 95% CI 1.03-1.24) and a diagnosis of ADHD with conduct disorder (HR=1.21, 95% CI 1.12-1.32), whereas young age showed a protective effect. After 6, 12, and 24 months of treatment initiation, 22.4%, 43.4%, and 66.3% of treated girls, and 17.8%, 36.1%, and 54.1% of treated boys had discontinued ADHD treatment. CONCLUSION Drug treatment of ADHD was relatively common in Germany and more frequent in boys than in girls. IR MPH was the predominant treatment choice at treatment initiation. Approximately 20% of treated subjects discontinued drug treatment within the first 6 months, with girls stopping drug treatment earlier than boys. The reasons for early drug discontinuation need to be further explored.

Comorbidities in ADHD children treated with methylphenidate: a database study

BackgroundMethylphenidate (MPH) is the most common drug treatment of attention deficit / hyperactivity disorder (ADHD) in children. Treatment with MPH is contraindicated in the presence of certain psychiatric, cerebro- and cardiovascular conditions. We assessed MPH treatment prevalence and incidence and the frequency of comorbid conditions related to these contraindications in new MPH users compared to a control group without ADHD and ADHD medication.MethodsWe used health care data for the years 2004 to 2006 from the German Pharmacoepidemiological Research Database (GePaRD) which includes about 18% of the German population. MPH treatment prevalence and incidence was assessed based on at least one MPH prescription in the given year. In MPH users, the prevalence of psychiatric and other comorbidities was assessed in the quarter of the first MPH prescription and the three preceding quarters, whereas in controls it was assessed in the earliest four quarters of continuous insurance time starting at 01.01.2004 or the start of insurance if this was later. Differences in the presence of comorbid diagnoses between MPH users and controls were tested by logistic regression.ResultsIn 2005, 1.5% of all children and adolescents aged 3 to 17 years (2.3% of males and 0.6% of females) received MPH in Germany. The proportion of children with a record of a psychiatric comorbidity in any of the nine ICD categories of diagnoses was substantially higher in new MPH users (83%) compared to controls (20%). Cerebro- and cardiovascular comorbidities were rare in general. Still, among new MPH users, 2% of males and females had a diagnosis of a pre-existing cardiovascular disorder but only 1.2% of controls.ConclusionsBesides MPH treatment prevalence we first publish age-specific incidence rates for Germany. A high proportion of children who were started on MPH had a record of a psychiatric comorbidity preceding the first prescription. Cerebro- and cardiovascular conditions were rare in the studied age range, but still higher among children who received MPH than in the control group. Results show that in a substantial subgroup of patients, comorbidities require a thorough weighting of possible risks of MPH medication against the risks of untreated ADHD.

Injury prevention by medication among children with attention-deficit/hyperactivity disorder: a case-only study.

IMPORTANCE Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) have an increased risk of injuries. Attention-deficit/hyperactivity disorder is often treated with medication, but the evidence regarding prevention of injuries is inconclusive. OBJECTIVE To determine via a case-only design whether the use of methylphenidate hydrochloride or atomoxetine hydrochloride reduces the risk of injuries among children and adolescents with ADHD. DESIGN, SETTING, AND PARTICIPANTS We used the German Pharmacoepidemiological Research Database, which includes records from about 17 million insurees (approximately 20% of the population) from 4 statutory health insurance providers in Germany to identify children aged 3 to 17 years with new diagnoses of ADHD in 2005 and 2006. We identified 37,650 children with ADHD based on inpatient and outpatientdiagnostic codes (F90.0, F90.1, and F90.9) from the German modification of the International Statistical Classification of Diseases and Related Health Problems, 10th Revision. Among them, we identified those with an inpatient injury diagnosis during follow-up until 2009. A total of 2128 children with any injury diagnosis at hospitalization, 821 of whom had a brain injury diagnosis, were included in the analysis. We applied the self-controlled case series design to control for time-invariant characteristics of the patients and time trends in the exposure. EXPOSURES Treatment with methylphenidate or atomoxetine based on prescription data. MAIN OUTCOMES AND MEASURES Hospitalization because of any injury or brain injury according to the injury mortality diagnosis matrix. RESULTS Incidence rate ratios for the periods with medication compared with nonmedicated periods were 0.87 (95% CI, 0.74-1.02) for hospitalization with any injuries and 0.66 (95% CI, 0.48-0.91) for brain injuries only in the full sample. These estimates remained stable in sensitivity analyses restricting the sample to a narrower age range or to patients with a single hospitalization. There was no indication that medication prescriptions are increased after hospitalizations. CONCLUSIONS AND RELEVANCE No significant risk reduction for hospitalizations with injury diagnoses was observed during periods of ADHD medication, but there was a preventive effect on the risk of brain injuries (34% risk reduction). The effects were controlled for time-invariant characteristics of the patients by the study design.

Treatment of paediatric epilepsy in Germany: Antiepileptic drug utilisation in children and adolescents with a focus on new antiepileptic drugs

BACKGROUND Treatment of paediatric epilepsy has advanced with the development of new antiepileptic drugs (AEDs). There are few data for Germany to which extent new AEDs are used in the treatment of childhood epilepsy. AIMS To characterise utilisation of antiepileptics in children and adolescents with a specific emphasis on new AEDs. METHODS Data were obtained from the German Pharmacoepidemiological Research Database for the period 2004-2006. Descriptive analyses were performed to assess prevalence and incidence of AED use stratified by age and sex. Mono- and combination therapy were considered as well as diagnoses and physician speciality. RESULTS We identified 13,197 children with AED use who received a total of 226,856 AED prescriptions. The majority of children treated with an AED were diagnosed with epilepsy (11,872; 89.96%). Of all AED prescriptions, 140,992 (62.15%) were for conventional and 85,864 (37.85%) were for new AEDs. One-year prescribing prevalence ranged between 4.10 and 4.11 per 1000 children. Incidence of AED use was 0.91 (95% CI: 0.87-0.95) per 1000 person-years in 2005 and 0.84 (95% CI: 0.81-0.89) per 1000 person-years in 2006. Monotherapy (9821; 74.42%) was more prevalent than combination therapy. Most AEDs were prescribed by paediatricians (147,150; 64.86%). CONCLUSIONS The introduction of the new AEDs had less impact on prescribing of AEDs in children than has been reported for adults. AED prescribing overall was in line with published guidelines.

Estimating the prevalence of Parkinson's disease (PD) and proportions of patients with associated dementia and depression among the older adults based on secondary claims data

While the epidemiology of Parkinsons disease (PD) has been extensively studied, data on the prevalence of PD among the older adults in Germany are scarce, based on small samples, and limited to primary data designs. This study estimated the PD prevalence among the older adults in Germany in 2006 using secondary data.

Regional variation in caesarean deliveries in Germany and its causes

BackgroundDeterminants of regional variation in caesarean sections can contribute explanations for the observed overall increasing trend of caesarean sections. We assessed which mechanism explains the higher rate of caesarean sections in the former West than East Germany: a more liberal use of caesarean sections in the case of relative indications or more common caesarean sections without indications.MethodsWe used a health insurance database from all regions of Germany with approximately 14 million insured individuals (about 17% of the total population in Germany). We selected women who gave birth in the years 2004 to 2006 and identified indications for caesarean section on the basis of hospital diagnoses in 30 days around birth. We classified pregnancies into three groups: those with strong indications for caesarean section (based on classification of absolute indications recommended by the Unmet Obstetrics Need network), those with moderate indications (other indications increasing the probability of caesarean section) and those with no indications. We investigated the percentage of caesarean sections among all births, presence of strong or moderate indications in all pregnancies, the probability of caesarean sections in the presence of indications and the fraction of caesarean sections attributable to strong, moderate and no indications.ResultsIn total, 294,841 births from 2004–2006 were included in the analysis. In the former West Germany, 30% births occurred by caesarean section, while in the former East Germany the caesarean section rate was 22%. Proportions of pregnancies with strong and moderate indications for caesarean section were similar in both regions. For strong indications the probability of caesarean section was similar in East and West Germany, but the probability of caesarean section among women with moderate indications was substantially higher in the former West Germany. Caesarean sections were also more common among women with no indications in the former West (8%) than in the former East (4-5%). The higher probability of caesarean section in the case of strong or moderate indications in the former West than in the East explained 87% of the difference between section rates in these two regions, while caesarean sections without indications contributed to only 13% of the difference observed.ConclusionsThe observed difference between caesarean section rates in the former East and West Germany was most likely due to different medical practice in handling relative indications.

Exposure to metal-working fluids in the automobile industry and the risk of male germ cell tumours.

Introduction In a previous analysis of a case–control study of testicular cancer nested in a cohort of automobile workers, we observed an increased risk for testicular cancer among workers who had ever been involved in occupational metal-cutting tasks. We investigated whether this risk increase was due to exposure to metal-working fluids (MWF). Methods Occupational exposure to MWF was assessed in detail using a job-specific questionnaire for metal-cutting work. We calculated ORs and associated 95% CIs individually matched for age (±2 years) and adjusted for a history of cryptorchidism by conditional logistic regression. Results The prevalence of exposure to MWF was 39.8% among cases and 40.1% among controls. For total germ cell tumours and seminomas we did not observe risk increases for metal-cutting tasks or occupational exposure to MWF (OR 0.95; 95% CI 0.69 to 1.32 and OR 0.88; 95% CI 0.58 to 1.35, respectively). However, dermal exposure to oil-based MWF was associated with an increased risk for non-seminomatous testicular cancer. Dermal exposure to oil-based MWF for more than 5000 h showed particularly high risk estimates (OR 4.72; 95% CI 1.48 to 15.09). Discussion Long-term dermal exposure to oil-based MWF was a risk factor for the development of non-seminomatous testicular germ cell cancer. Possible measures to reduce exposure include the introduction of engineering control measures such as venting or enclosing of machines, and enforcing the use of personal protective equipment during metal cutting.

Development and evaluation of a tool for retrospective exposure assessment of selected endocrine disrupting chemicals and EMF in the car manufacturing industry.

OBJECTIVES A system for retrospective occupational exposure assessment combining the efficiency of a job exposure matrix (JEM) and the precision of a subsequent individual expert exposure assessment (IEEA) was developed. All steps of the exposure assessment were performed by an interdisciplinary expert panel in the context of a case-control study on male germ cell cancer nested in the car manufacturing industries. METHODS An industry-specific JEM was developed and automatic exposure estimation was performed based on this JEM. A subsample of exposure ratings was done by IEEA to identify determinants of disagreement between the JEM and the individual review. Possible determinants were analyzed by calculating odds ratios (ORs) of disagreement between ratings with regard to different dimensions (e.g. high versus low intensity of exposure). Disagreement in ≥20% of the sampled exposure ratings with a statistically significant OR was chosen as a threshold for inclusion of the exposure ratings into a final IEEA. RESULTS The most important determinants of disagreement between JEM and individual review were working outside of the production line (disagreement 80%), low probability of exposure (disagreement 25%), and exposure depending on specific activities like usage of specific lacquers (disagreement 32%) for jobs within the production line. These determinants were the selection criteria of exposure ratings for the subsequent final IEEA. CONCLUSIONS Combining a JEM and a subsequent final IEEA for a selected subset of exposure ratings is a feasible and labor-saving approach for exposure assessment in large occupational epidemiological studies.