German mammography screening program: program sensitivity between 2010 and 2016 estimated based on German health claims data.

BACKGROUND: Program sensitivity is a key quality indicator for mammography screening programs (MSP). Estimating program sensitivity usually requires a linkage of screening and cancer registry data. For the German MSP, such data linkage-based estimates have only been reported for two out of 16 federal states. We aimed to explore the potential of estimating program sensitivity for the German MSP based on information available in health claims data. METHODS: We used data from the second-largest statutory health insurance fund in Germany, BARMER (~ 9 million members all over Germany). We included women aged 50 to 69 years with a non-initial screening mammography between 2010 and 2016 and followed them up for two years. We estimated the rate of screen-detected and interval cancers as well as program sensitivity. RESULTS: Per year, we included 212,400 to 303,667 women (mean age: 60-61 years). Overall, 1,992,287 non-initial MSP screening examinations conducted in these women between 2010 and 2016 were considered for the analyses. Age-standardized program sensitivity ranged between 69.9% [95% CI: 67.3-72.0%] and 71.7% [95% CI: 69.5-73.9%] during the study period. Per 1,000 non-initial screening examinations, the rate of screen-detected breast cancer ranged between 4.6 and 5.3, and the rate of interval breast cancer rates ranged between 0.6 and 0.8 for the first and between 1.3 and 1.4 for the second year after screening. CONCLUSIONS: Our results were plausible and consistent with quality indicators estimated for the German MSP based on data linkage and thus support the value of German health claims data in this regard. The quality indicators estimated in our study are in line with levels expected according to European Guidelines.

German mammography screening program: adherence, characteristics of (non-)participants and utilization of non-screening mammography-a longitudinal analysis.

BACKGROUND: In Germany, all women aged 50-69 have been invited to biennial mammography screening since 2009. We aimed to assess longitudinal adherence over ten years in women aged 50 in 2009 and characterize the different adherence groups. METHODS: Using the German Pharmacoepidemiological Research Database (GePaRD, ~ 20% of the German population), we included women aged 50 in 2009 (baseline) with continuous health insurance coverage and without breast cancer or in-situ-carcinoma. We followed them until age 59 and categorized them according to mammography screening participation into the following groups: never, 1-2, 3-4, 5-6 times. We characterized these groups, inter alia, regarding the use of other preventive measures, non-screening mammography (i.e., mammography outside the organized screening program) and menopausal hormone therapy. RESULTS: Overall, 82,666 women were included. Of these, 27.6% never participated in the screening program, 15.1% participated 1-2 times, 31.7% participated 3-4 times and 25.6% participated regularly (5-6 times). Among regular participants, 91% utilized other preventive measures (e.g., cervical cancer screening, general health checkup) before baseline as compared to 66% among non-participants. Menopausal hormone therapy was least common among non-participants (11% vs. 18% among regular participants). Among non-participants, the proportions using ≥ 1, ≥ 2, and ≥ 3 non-screening mammographies between age 50-59 were 25%, 18%, and 15%, respectively. CONCLUSIONS: Using a large cohort based on claims data, this study provides novel insights into longitudinal adherence to the mammography screening program and the use of mammography outside of the program in Germany. Between age 50-59, 57% of eligible women participated at least three times in the German mammography screening program and 28% (~ 3 in 10 women) never participated. Among non-participants, 15% had at least three non-screening mammographies during this period, indicating potential gray screening. Participants more often utilized other preventive measures as compared to non-participants.

Dementia in health claims data: The influence of different case definitions on incidence and prevalence estimates.

OBJECTIVES: The epidemiology of dementia subtypes including Alzheimer's disease (AD) and vascular dementia (VD) and their reliance on different case definitions ("algorithms") in health claims data are still understudied. METHODS: Based on health claims data, prevalence estimates (per 100 persons), incidence rates (IRs, per 100 person-years), and proportions of AD, VD, and other dementias (oD) were calculated. Five algorithms of increasing strictness considered inpatient/outpatient diagnoses (#1, #2), antidementia drugs (#3) or supportive diagnostics (#4, #5). RESULTS: Algorithm 1 detected 213,409 cases (#2: 197,400; #3: 48,688; #4: 3033; #5: 3105), a prevalence for any dementia of 3.44 and an IR of 1.39 (AD: 0.80/0.21, VD: 0.79/0.31). The prevalence decreased by algorithms for any dementia (#2: 3.19; #3: 0.75; #4: 0.04; #5: 0.05) as did IRs (#2: 1.13; #3: 0.18; #4: 0.05, #5: 0.05). Algorithms 1-2, and 4-5 revealed similar proportions of AD (23.3%-26.6%), VD (19.9%-23.2%), and oD (53.1%-53.8%), algorithm 3 estimated 45% (AD), 12.1% (VD), and 43.0% (oD). CONCLUSIONS: Health claims data show lower estimates of AD than previously reported, due to markedly lower prevalent/incident proportions of patients with corresponding codes. Using medication in defining dementia potentially improves estimating the proportion of AD while supportive diagnostics were of limited use.

Effectiveness of Mammography Screening on Breast Cancer Mortality - A Study Protocol for Emulation of Target Trials Using German Health Claims Data.

Background: The efficacy of mammography screening in reducing breast cancer mortality has been demonstrated in randomized trials. However, treatment options - and hence prognosis - for advanced tumor stages as well as mammography techniques have considerably improved since completion of these trials. Consequently, the effectiveness of mammography screening under current conditions is unclear and controversial. The German mammography screening program (MSP), an organized population-based screening program, was gradually introduced between 2005 and 2008 and achieved nation-wide coverage in 2009. Objective: We describe in detail a study protocol for investigating the effectiveness of the German MSP in reducing breast cancer mortality in women aged 50 to 69 years based on health claims data. Specifically, the proposed study aims at estimating per-protocol effects of several screening strategies on cumulative breast cancer mortality. The first analysis will be conducted once 10-year follow-up data are available. Methods and Analysis: We will use claims data from five statutory health insurance providers in Germany, covering approximately 37.6 million individuals. To estimate the effectiveness of the MSP, hypothetical target trials will be emulated across time, an approach that has been demonstrated to minimize design-related biases. Specifically, the primary contrast will be in terms of the cumulative breast cancer mortality comparing the screening strategies of "never screen" versus "regular screening as intended by the MSP". Ethics and Dissemination: In Germany, the utilization of data from health insurances for scientific research is regulated by the Code of Social Law. All involved health insurance providers as well as the responsible authorities approved the use of the health claims data for this study. The Ethics Committee of the University of Bremen determined that studies based on claims data are exempt from institutional review. The findings of the proposed study will be published in peer-reviewed journals.

Stability of individual dementia diagnoses in routine care: Implications for epidemiological studies.

PURPOSE: Epidemiological and health care research frequently rely on diagnoses from routine care, but the intra-individual stability of diagnoses of Alzheimer's disease (AD), vascular dementia (VD) or other forms of dementia (oD) in patients over time is understudied. More data on the diagnostic stability is needed to appraise epidemiological findings from such studies. METHODS: Using health claims data of the years 2004-2016 from the German Pharmacoepidemiological Research Database, 160 273 patients aged ≥50 with incident dementia were identified and followed for 4 years. According to the incident ICD-10 codes patients were assigned to the categories AD, VD or oD. Changes between categories during follow-up were calculated. RESULTS: Overall, 18.8% had incident AD (VD: 21.5%, oD: 59.7%). Fifteen thousand eight hundred forty-two patients had only one dementia diagnosis during 4 years (AD: 7.4%, VD: 12.4%, oD: 9.8%). Among those with more than one diagnosis, the incident diagnosis matched the last diagnosis in 65.1% (AD), 53.9% (VD) and 73.8% (oD) of patients. Changes in the diagnostic category were higher in patients with AD (mean: 5.1) than in patients with VD (3.6) or oD (3.3). Patients with stable AD diagnoses during the observation period were younger (median: 76 vs. 79 years) and had less inpatient treatment days (median: 14 days) than patients with changes from an AD diagnosis to another category or from another category to AD (27 days). CONCLUSIONS: While health claims data are feasible for estimating the incidence of dementia in general, the substantial number of changes in dementia diagnoses during the course of the disease warrant caution on the interpretation of epidemiological data on specific dementia types.

Prevalence of multimodal treatment in children and adolescents with ADHD in Germany: a nationwide study based on health insurance data.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) ranks top among neurodevelopmental disorders in children and adolescents. Due to a large number of unfavorable outcomes including psychiatric comorbidities, school problems, and lower socioeconomic status, early and effective treatment of ADHD is essential. Multimodal treatment has become the gold standard in ADHD management, comprising pharmacotherapy and psychosocial interventions, e.g., psychotherapy. Yet, little is known about the prevalence of multimodal treatment in routine care. METHODS: Based on German health claims data for the years 2009-2017, we identified children and adolescents aged 3-17 years diagnosed with ADHD and characterized them cross-sectionally (per calendar year) in terms of treatment status and psychiatric comorbidities. The detection of pharmacotherapy was based on dispensations of drugs to treat ADHD (e.g., methylphenidate); psychotherapeutic treatment was based on corresponding billing codes. Multimodal treatment was assumed if ADHD medication and psychotherapeutic treatment were coded within the same calendar year. Psychiatric comorbidities were based on outpatient and inpatient diagnoses. Prevalences of ADHD and proportions of different treatment options were calculated and standardized by age and sex. RESULTS: In 2017, 91,118 children met the study criteria for ADHD (prevalence: 42.8/1000). Of these, 25.2% had no psychiatric comorbidity, 28.8% had one, 21.6% had two, and 24.5% had three or more. Regarding overall treatment status, 36.2% were treated only pharmacologically, 6.5% received multimodal treatment, and 6.8% were treated with psychotherapy only (neither treatment: 50.2%). With increasing numbers of psychiatric comorbidities, the proportions of patients with multimodal treatment increased from 2.2% (no psychiatric comorbidities) to 11.1% (three or more psychiatric comorbidities) while the proportions of untreated (from 56.8% to 42.7%) or only pharmacologically treated patients (38.4% to 35.0%) decreased. From 2009 to 2017, prevalences were stable and the proportion of patients with only pharmacotherapy decreased from 48% to 36.5%. Concurrently, the proportion of patients with neither pharmacotherapy nor psychotherapy increased from 40.5% to 50.2%. The fraction of patients with multimodal treatment ranged between 6.5% (2017) and 7.4% (2013). CONCLUSIONS: Multimodal treatment, although recommended as the standard of treatment, is rather the exception than the rule. It is, however, increasingly common in ADHD patients with psychiatric comorbidities.

Vaccination and the Risk of Childhood Cancer-A Systematic Review and Meta-Analysis.

INTRODUCTION: Infections may play a role in the etiology of childhood cancer and immunizations may be protective because vaccinations stimulate the immune system. Observational studies reported inconsistent associations between vaccination and risk of childhood cancer. Since a synthesis of the evidence is lacking, we conducted a meta-analysis stratified by histological and site-specific cancer. METHODS: We performed a systematic review (CRD42020148579) following PRISMA guidelines and searched for literature in MEDLINE, Embase, and the Science Citation Index databases. We identified in three literature databases 7,594 different articles of which 35 met the inclusion criteria allowing for 27 analyses of 11 cancer outcomes after exposure to nine different types of vaccinations. We calculated summary odds ratios (ORs) and 95% confidence intervals (CIs) using random effects models. RESULTS: We observed four inverse associations between childhood leukemia and certain vaccines as well as the number of vaccinations: OR 0.49 (95% CI = 0.32 to 0.74) for leukemia death after bacillus Calmette-Guérin vaccination; OR 0.76 (95% CI = 0.65 to 0.90) for acute lymphoblastic leukemia after Haemophilus influenzae type b vaccination; OR 0.57 (95% CI = 0.36 to 0.88) for leukemia; and OR 0.62 (95% CI = 0.46 to 0.85) for acute lymphoblastic leukemia after three or more vaccinations of any type. All other conducted analyses did not show any associations. DISCUSSION: The results are consistent with the hypothesis that vaccinations reduce the risk of childhood leukemia. However, the robustness and validity of these results is limited due to the small number, substantial heterogeneity, and methodological limitations of available studies.

Linkage of Routine Data to Other Data Sources in Germany: A Practical Example Illustrating Challenges and Solutions.

Routine data have a high potential for epidemiological and health care research but lack information, for instance, on the cause of death. Often detailed information, such as on lifestyle factors is also missing. In Germany, obtaining the missing information by linkage to data sources is challenging, mainly due to strict data protection regulations. One key challenge arises from the fact that routine data users usually have no access to person identifiers which would be necessary for record linkage. A second key challenge is that sensitive information (i. e., the cause of death) should not be transferred to an institution that holds person identifiers. In this paper, we illustrate these key challenges and present corresponding solutions based on a practical example where claims data from statutory health insurance providers are linked to an epidemiological cancer registry to obtain cause of death information. We describe the approval procedures necessary for the record linkage, the dataflow between the involved institutions and explain the rationale of the dataflow in view of the key challenges. Finally, we generalize the questions that need to be addressed when a record linkage is planned and point to additional potential challenges. Overall, we illustrate that a linkage between routine data and other data sources in Germany is feasible, but specific restrictions and hurdles need to be taken into consideration.

Assessing and Explaining Geographic Variations in Mammography Screening Participation and Breast Cancer Incidence.

Investigating geographic variations in mammography screening participation and breast cancer incidence help improve prevention strategies to reduce the burden of breast cancer. This study examined the suitability of health insurance claims data for assessing and explaining geographic variations in mammography screening participation and breast cancer incidence at the district level. Based on screening unit data (1,181,212 mammography screening events), cancer registry data (13,241 incident breast cancer cases) and claims data (147,325 mammography screening events; 1,778 incident breast cancer cases), screening unit and claims-based standardized participation ratios (SPR) of mammography screening as well as cancer registry and claims-based standardized incidence ratios (SIR) of breast cancer between 2011 and 2014 were estimated for the 46 districts of the German federal state of Lower Saxony. Bland-Altman analyses were performed to benchmark claims-based SPR and SIR against screening unit and cancer registry data. Determinants of district-level variations were investigated at the individual and contextual level using claims-based multilevel logistic regression analysis. In claims and benchmark data, SPR showed considerable variations and SIR hardly any. Claims-based estimates were between 0.13 below and 0.14 above (SPR), and between 0.36 below and 0.36 above (SIR) the benchmark. Given the limited suitability of health insurance claims data for assessing geographic variations in breast cancer incidence, only mammography screening participation was investigated in the multilevel analysis. At the individual level, 10 of 31 Elixhauser comorbidities were negatively and 11 positively associated with mammography screening participation. Age and comorbidities did not contribute to the explanation of geographic variations. At the contextual level, unemployment rate was negatively and the proportion of employees with an academic degree positively associated with mammography screening participation. Unemployment, income, education, foreign population and type of district explained 58.5% of geographic variations. Future studies should combine health insurance claims data with individual data on socioeconomic characteristics, lifestyle factors, psychological factors, quality of life and health literacy as well as contextual data on socioeconomic characteristics and accessibility of mammography screening. This would allow a comprehensive investigation of geographic variations in mammography screening participation and help to further improve prevention strategies for reducing the burden of breast cancer.

Implementation of an algorithm for the identification of breast cancer deaths in German health insurance claims data: a validation study based on a record linkage with administrative mortality data.

OBJECTIVE: To adapt a Canadian algorithm for the identification of female cases of breast cancer (BC) deaths to German health insurance claims data and to test and validate the algorithm by comparing results with official cause of death (CoD) data on the individual and the population level. DESIGN: Validation study, secondary data, medical claims. SETTING: Claims data of two statutory health insurance providers (SHIs) for inpatient and outpatient care, CoD added via record linkage with epidemiological cancer registry (ECR).ParticipantsAll women insured with the two SHIs and who deceased in the period 2006-2013, were residents of North Rhine Westphalia (NRW) and were linked with ECR data: n=22 413. MAIN OUTCOME MEASURES: Based on inpatient and outpatient diagnoses in the year before death, six algorithms were derived and the accordance of the algorithm-based CoD with the official CoD was evaluated calculating specificity, sensitivity, negative and positive predictive values (NPV, PPV). Furthermore, algorithm-based age-specific BC mortality rates covering several calendar years were calculated for the entire insured female population and compared with official national rates. RESULTS: Our final algorithm, derived from the NRW subsample, comprised codes indicating the presence of BC, metastases, a terminal illness phase and the absence of codes for other tumours. Overall, specificity, sensitivity, NPV and PPV of this algorithm were 97.4%, 91.3%, 98.9% and 81.7%, respectively. In the age range 40-80 years, sensitivity and PPV slightly decreased with increasing age. Algorithm-based age-specific BC mortality rates agreed well with official rates except for the age group 85 years and older. CONCLUSIONS: The algorithm-based identification of BC deaths in German claims data is feasible and valid, except for higher ages. The algorithm to ascertain BC mortality rates in an epidemiological study seems applicable when information on the official CoD is not available in the original database.

Individual mortality information in the German Pharmacoepidemiological Research Database (GePaRD): a validation study using a record linkage with a large cancer registry.

OBJECTIVE: Claims data need to be validated to assess their use for epidemiological research. This study aimed to examine the validity of mortality information in the German Pharmacoepidemiological Research Database (GePaRD). DESIGN: Validation study, secondary data, medical claims. SETTING: Claims data of two German nationwide acting statutory health insurance providers (SHIs) contributing data for GePaRD; record linkage with epidemiological cancer registry providing individual official mortality information. PARTICIPANTS: All women insured with the two SHIs whose insurance coverage ended in the period 2006-2013 and who were residents of North Rhine Westphalia. MEASURES: Descriptive statistics were used to analyse the performance of the linkage procedure. Further, we calculated measures of agreement between the official and the GePaRD-based vital status and assessed differences between the official and the GePaRD-based date of death. RESULTS: Of the 256 111 women of the linkage sample, 25 528 were classified as 'deceased' in GePaRD and the others as 'alive'. Compared with the official data, the GePaRD-based vital status showed a sensitivity of 95.9% and a specificity of 99.4%. The negative predictive value was 99.6% and the positive predictive value 94.3%. The date of death agreed in 96.3% between both data sources. CONCLUSIONS: The vital status recorded in GePaRD was of high accuracy and discrepancies between dates of death in GePaRD and official dates were rare. This underlines the potential of the database for conducting large cohort studies with mortality as the endpoint.

Potential Explanations for Increasing Methylphenidate Use in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder in Germany From 2004 to 2013.

BACKGROUND: Despite a decreasing population of children and adolescents, the cumulative total amount of dispensed methylphenidate (MPH), the first-choice treatment of attention-deficit/hyperactivity disorder (ADHD) in this age group, has increased dramatically in Germany. We investigated potential reasons for this increase such as changes in the ADHD prevalence over time and other potential explanations including the cumulative amount of dispensed MPH per person. METHODS: Based on German claims data, we calculated standardized annual ADHD prevalence rates, proportions of ADHD cases treated with MPH and/or psychotherapy, and mean cumulative defined daily doses of ADHD drugs for 3- to 17-year-old children and adolescents from 2004 to 2013. RESULTS: The ADHD prevalence increased continuously from 2004 to 2011 and remained stable thereafter. In ADHD cases, there was little variation in the proportion of individuals treated with drugs and in the frequency of psychotherapeutic treatment during the whole study period. The annual cumulative mean amount of MPH defined daily doses increased by approximately 30% from 2004 to 2008. CONCLUSIONS: Our analyses suggest that the increase in MPH use in Germany was mainly influenced by an increasing ADHD prevalence and increasing amounts of dispensed MPH per person.

[Enrichment of Claims Data with Official Causes of Death Using a Record Linkage with the Epidemiological Cancer Registry of North Rhine-Westphalia: Feasibility Study and Comparison of Procedures]. / Anreicherung eines GKV-Datensatzes mit amtlichen Todesursachen über einen Abgleich mit dem Epidemiologischen Krebsregister Nordrhein-Westfalen: Machbarkeitsstudie und Methodenvergleich.

BACKGROUND: Claims data of the statutory health insurance (SHI) are an important data source for the evaluation of cancer prevention programs. However, this source does not contain relevant information on cause of death. This study examined whether individual claims data can be enriched with data on the required cause of death using record linkage procedures with suitable external data sources. METHODS: In the German pharmacoepidemiologic research database (GePaRD) we identified a sample of 25,528 deceased female residents of North Rhine Westphalia (NRW) who, according to GePaRD information, died between 2006 and 2013. Date and cause of all deaths among inhabitants of NRW since 2005 were available in the epidemiological cancer registry of NRW. In cooperation with 2 SHI companies, we tried to match each individual of the sample with a case of death in NRW and the corresponding cause of death using a probabilistic and, alternatively, a deterministic linkage procedure. RESULTS: Of the study sample, 94.72% were successfully matched by the probabilistic and 93.36% by the deterministic method. CONCLUSIONS: The probabilistic and the deterministic record linkage approach produced comparably high matching rates. Cases without matches are probably due to errors occurring at the stage of personal data entry. Given the lower technical efforts, the deterministic approach appears to be the method of choice for the enrichment of claims data with cause of death information from suitable external data sources in Germany.

[Evaluation of organized cancer screening programs: general aspects and current status in Germany]. / Evaluation von organisierten Programmen zur Krebsfrüherkennung: Allgemeine Aspekte und aktueller Stand in Deutschland.

In the past decades, it has been increasingly recognized that cancer screening is not always or not exclusively beneficial and, in the case of some measures, the negative effects may even outweigh the benefits. This has fundamentally changed the significance and emphasis placed on the evaluation of cancer screening programs. Generally, there is a distinction between an endpoint evaluation, which assesses the effectiveness or risk/benefit ratio, and a process evaluation, which aims to ensure optimum implementation of the program.Prior to the nationwide introduction of a screening measure, proof of effectiveness should ideally be provided by a randomized controlled trial (RCT), in which persons without a screening offer form the control group. From a scientific point of view, this study design is by far the best method to evaluate the endpoint, as it avoids biases that may distort the results in observational studies. RCT evidence on cancer screening measures currently offered by statutory health insurance providers in Germany - if available at all - originates exclusively from other countries.When mammography screening was introduced as the first organized screening program in Germany, comprehensive measures for process evaluation were taken. In April 2013, the legal basis for the transfer of colorectal and cervical cancer screening into organized programs was created. According to the legal provisions, both a process and an endpoint evaluation are planned for the new programs. It remains to be seen how the necessary data flows will be conceptualized and later implemented in practice.

A cohort study of mammography screening finds that comorbidity measures are insufficient for controlling selection bias.

OBJECTIVE: To examine the potential of claims-based comorbidity measures for controlling selection bias in observational studies of mammography screening. STUDY DESIGN AND SETTING: Based on claims data of a large German Statutory Health Insurance fund, the single comorbidities considered by the Charlson, Elixhauser, Multipurpose Australian Comorbidity Scoring System, and M3 comorbidity measures were identified for mammography screening participants and nonparticipants. Total death rates within 4 years after screening invitation were compared. Cox proportional hazards regressions were performed unadjusted and adjusted for age, federal state of residence, and comorbidity. RESULTS: Among 1,247,919 insured women aged 50-68 years (56.2% participants), 10,311 participants (death rate 375.8/100,000 person-years) and 18,113 nonparticipants (death rate 854.8/100,000 person-years) died from any cause during the follow-up. The unadjusted hazard ratio (HR) for death from any cause for participants vs. nonparticipants was 0.44 (99.9% confidence interval 0.42-0.46). Adjustments attenuated the HR to a maximum of 0.52 (0.50-0.54). CONCLUSION: The lower short-term all-cause mortality among participants cannot be explained by mammography screening effects and should be interpreted as selection bias. Adjusting for comorbidities only slightly attenuated this bias. Future studies should examine whether claims data include further information that is beneficial to adequately control selection bias in observational studies of mammography screening.

The Risk of Hospitalizations with Injury Diagnoses in a Matched Cohort of Children and Adolescents with and without Attention Deficit/Hyperactivity Disorder in Germany: A Database Study.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder in children and adolescents worldwide, and children with ADHD have elevated risk of injuries. Our aim was to assess the risk of hospitalizations with injury diagnoses and their various subtypes in children and adolescents with newly diagnosed ADHD compared to those without ADHD, as well as to study sex effects on this risk in the setting of the German health care system. METHODS: The German Pharmacoepidemiological Research Database, in which 20 million insured from four statutory health insurances in Germany are included, was used to set up a matched cohort study of 3- to 17-year-old children and adolescents with and without ADHD. We calculated age-specific incidence rates and used Cox regression to obtain hazard ratios (HRs) for hospitalizations with injury diagnoses. We used the injury mortality diagnosis matrix for classification of injuries. RESULTS: The matched cohort comprised a total of 75,300 children. The age-specific incidence rates for hospitalization with injury diagnosis for males with ADHD displayed a u-shaped form with highest incidences in the in the age groups 3-6 years [26.2 per 1,000 person-years; 95% confidence interval (CI) 20.5-33.0] and 18-21 years (28.6; 22.4-36.0). Girls with ADHD were less affected in younger age-groups, but the incidence rate for 18-21 year olds was similar to boys with ADHD (26.4; 17.4-38.4). The adjusted HR for children with ADHD was 1.40 (95% CI 1.30-1.49) compared to non-affected children. With respect to nature of injury, ADHD was associated with hospitalization with injury diagnoses of the internal organs, open wounds, and contusions but not with other injuries. With respect to body regions, children with ADHD were more prone to hospitalizations with injuries of the abdomen, traumatic brain injuries, other head injuries, and system-wide injuries such as poisoning and intoxication. No significant associations were seen for the other body regions. Differences between sexes were only seen for system-wide injuries. CONCLUSION: Children and adolescents with ADHD are at an increased risk for hospitalizations with diagnoses of injuries compared to non-affected children. Despite differences in health-care systems, the risk increase is at a similar level in Germany as in other countries.

Validating mortality in the German Pharmacoepidemiological Research Database (GePaRD) against a mortality registry.

PURPOSE: The study aimed at validating the status and date of death of a large electronic health insurance database against data of a mortality registry, using a probabilistic record linkage. METHODS: Data were obtained from one local health insurance company contributing to the German Pharmacoepidemiological Research Database (GePaRD). Furthermore, data of the Bremen Mortality Index (BreMI) containing all information from death certificates were used as reference information. Both data sources were probabilistically linked. The study sample consisted of insurants dying in 2005 or 2006. RESULTS: Of 3245 deaths in GePaRD, 83.7% were successfully linked to BreMI records. The linkage success did not differ between men and women, age groups or insurance status groups. Date of death was accurate in 97.1% of all linked deaths. CONCLUSIONS: The accuracy of the status of death in GePaRD is likely to be underestimated in this study because of factors related to the record linkage procedure leading to failure of the probabilistic record linkage approach and the limited completeness of BreMI. A previous validation study comparing aggregate mortality information in GePaRD with German national statistics did not indicate an overreporting of deaths in GePaRD. Thus, a higher accuracy of the status of death in GePaRD than estimated here can be assumed. Copyright © 2016 John Wiley & Sons, Ltd.

Mortality in the German Pharmacoepidemiological Research Database (GePaRD) compared to national data in Germany: results from a validation study.

BACKGROUND: Electronic healthcare databases are of increasing importance in health research and mortality is one of the most relevant outcomes. However, data in these databases need to be validated, since they are often generated for reimbursement purposes. The aims of this study were to compare mortality figures from the German Pharmacoepidemiological Research Database (GePaRD) on an aggregated level with external data from the Federal Statistical Office of Germany (FSOG) and to assess consistency of records of death from core data and hospital data within GePaRD. METHODS: The study population comprised insurants of four statutory health insurances providing data for GePaRD with either continuous insurance coverage from January 1(st) to December 31(st) 2006 or until death. The sex-specific mortality rate, stratified and standardized by age, and the percentage of hospital deaths among all deaths was compared with data from the FSOG. Furthermore, the agreement between the dates of death according to hospital data and core data was assessed within GePaRD. RESULTS: The study population comprised 12,033,622 insurants. Compared to FSOG data, the age-standardised mortality rate in GePaRD was 21% and 29% lower in women and men, respectively. Regional analyses also indicated lower mortality rates in all federal states except for Bremen, where the age-standardised mortality rate was similar to FSOG data for both sexes. The percentage of hospital deaths among all deaths corresponded well with external data. The proportion of inpatient deaths also recorded in the health insurance core data was 98.5%. Furthermore, 94% of dates of death documented in hospital agreed with the dates of death according to the health insurance core data. CONCLUSIONS: The lower mortality rates in almost all federal states might result from the higher socioeconomic status of the GePaRD study population compared to the overall population in Germany. In the federal state of Bremen, where socioeconomic representativeness is higher due to additional inclusion of two local health insurances, the mortality rates were in good accordance with external data. Agreement of the percentage of hospital deaths among all deaths between GePaRD and national statistics suggested completeness of outpatient mortality information.

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.

Twin and sibling studies using health insurance data: the example of attention deficit/hyperactivity disorder (ADHD).

BACKGROUND AND AIMS: Twin studies are used to assess the contribution of genetic factors to the aetiology of diseases. To show the feasibility of such research on the basis of health insurance data, we analysed twin and sibling data on the attention deficit/hyperactivity disorder (ADHD) in the German Pharmacoepidemiological Research Database (GePaRD). METHODS: The GePaRD consists of data from four statutory health insurances, including around 17% of the total population of Germany. Among those insured in 2005, we identified 286,653 non-twin sibling pairs and 12,486 twin pairs. Each pair consisted of an index child (6 to 12 years old) and a co-sibling of equal age or up to five years older. ADHD cases were identified by hospital or ambulatory ICD-10 diagnoses (F90.0 or F90.1) and prescriptions. We estimated tetrachoric correlations, percentage of concordant pairs, concordance rates, and heritability. Weighted estimates for the indirect assessment of mono- and dizygotic pairs were derived. RESULTS: TETRACHORIC CORRELATIONS WERE HIGHEST FOR TWIN PAIRS OF THE SAME SEX (MALES: 0.85, 95% CI 0.81-0.89; females: 0.81, 95% CI 0.73-0.88) and lowest for opposite-sex non-twin sibling pairs (0.43, 95% CI 0.41-0.45). Heritability estimates were 0.88 (95% CI: 0.79-0.97) for males and 0.77 (95% CI: 0.60-0.95) for females. CONCLUSIONS: The study clearly reproduced the well-known strong genetic component in the aetiology of ADHD. This approach could be used for further assessments of genetic components in other diseases.