Comparative effectiveness of factor Xa non-vitamin K antagonist oral anticoagulants versus phenprocoumon in patients with non-valvular atrial fibrillation.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) have largely supplanted vitamin K antagonists (VKAs) for oral anticoagulation in non-valvular atrial fibrillation (NVAF). However, data on the real-world effectiveness of NOACs vs. phenprocoumon, a VKA widely used in Germany, are limited. The RELOADED study aimed to compare effectiveness of factor Xa NOACs and phenprocoumon in NVAF in clinical practice. METHODS: Patients who started on a factor Xa NOAC or phenprocoumon for NVAF during the study period were enrolled from the Institute for Applied Healthcare Research Berlin. Patients were followed from first prescription until the end of exposure or available data. Primary outcomes were analyzed by Cox proportional hazard regression models and included ischemic stroke and systemic embolism for effectiveness, and intracranial hemorrhage (ICH) for safety. Subgroups of interest were patients with diabetes and patients with renal impairment. RESULTS: The total study population was 64,920; 36.3% of patients initiated phenprocoumon, 34.4% initiated rivaroxaban, 25.0% apixaban, and 4.4% edoxaban. Treatment with phenprocoumon is associated with a similar risk of ischemic stroke/systemic embolism as treatment with rivaroxaban or apixaban; while rivaroxaban (adjusted hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.43-0.75) and apixaban (adjusted HR 0.43, 95% CI 0.31-0.6) were associated with a lower risk of ICH compared to phenprocoumon in NVAF patients. The use of rivaroxaban and apixaban was associated with a lower risk of developing kidney failure in patients with diabetes or renal impairment in comparison to those treated with phenprocoumon. CONCLUSION: The factor Xa NOACs rivaroxaban and apixaban demonstrated similar effectiveness and lower rates of ICH compared with phenprocoumon in this study.

Sick leave before, during, and after short-term outpatient psychotherapy: a cohort study on sick leave days and health care costs between behavioral and psychodynamic psychotherapies on anonymized claims data.

BACKGROUND: Sick leave due to mental disorders poses a relevant societal and economic burden. Research on sick leave over a patient journey of individuals who received one of two treatment approaches - either behavioral (BT) or psychodynamic (PDT) psychotherapy - is scarce. METHODS: We conducted a cohort study on anonymized German claims data for propensity-score matched patients who received short-term outpatient BT or PDT. We analyzed sick leave days and direct health care costs one year before, during, and one year after psychotherapy. RESULTS: We analyzed data of patients who received BT and PDT, with N = 14 530 patients per group after matching. Patients showed sick leave days per person year of 33.66 and 35.05 days before, 35.99 and 39.74 days during, and 20.03 and 20.95 days after BT and PDT, respectively. Sick leave rates were overall higher in patients who received PDT. Both patient groups showed reductions of roughly 14 sick leave days per year, or 40%, from before to after therapy without a difference between BT and PDT (difference-in-difference [DiD] = -0.48, 95%-confidence interval [CI] -1.61 to 0.68). Same applies to direct health care costs which reduced in both groups by roughly 1800 EUR (DiD = 0, 95%-CI -158 to 157). CONCLUSIONS: Results suggest similar reductions in sick leave days and direct health care costs from before to after BT and PDT. As sick leave is discussed to serve as an indicator of overall health and functioning in mental disorders, both treatments may have a similar positive impact on mental health.

Effectiveness and Safety of Direct Oral Anticoagulants Among Octogenarians with Venous Thromboembolism: An International Multidatabase Cohort Study.

BACKGROUND: The effects of direct oral anticoagulants (DOACs) among octogenarian patients with venous thromboembolism remains poorly understood. To address this knowledge gap, our study aimed to assess the effectiveness and safety of DOACs compared to vitamin K antagonists (VKAs) among octogenarians with venous thromboembolism. METHODS: We conducted an international cohort study using administrative health care databases from Québec, Canada, and Germany. We assembled 2 population-based cohorts of octogenarians with incident venous thromboembolism initiating treatment with DOACs or VKAs. The study period spanned from January 2012 to the most recent date of data availability (Québec: December 2016; Germany: December 2019). Using an as-treated exposure definition, we compared use of DOACs to use of VKAs, applying inverse probability of treatment weighting based on high-dimensional propensity scores to balance exposure groups. Cox proportional hazards models estimated site-specific hazard ratios (HRs) and 95% confidence intervals (CIs) of recurrent venous thromboembolism, major bleeding, and all-cause mortality. The results were meta-analyzed using random-effects models. RESULTS: Overall, our study included 6737 octogenarians with venous thromboembolism (Québec: n = 2556; Germany: n = 4181) who initiated use of DOACs (n = 3778) or VKAs (n = 2959). When compared to VKAs, DOACs were associated with similar risks of recurrent venous thromboembolism (weighted HR, 0.80; 95% CI, 0.43-1.46; I2 = 0.00), major bleeding (weighted HR, 0.96; 95% CI, 0.57-1.63; I2 = 0.59), and all-cause mortality (weighted HR, 1.04; 95% CI, 0.81-1.34; I2 = 0.00). CONCLUSIONS: Among octogenarians with venous thromboembolism, DOACs showed a comparable effectiveness and safety compared to VKAs. Our results support the use of DOACs in this high-risk group.

Increased Risk of Stroke Due to Non-adherence and Non-persistence with Direct Oral Anticoagulants (DOACs): Real-World Analyses Using a Nested Case-Control Study from The Netherlands, Italy and Germany.

BACKGROUND: A high degree of adherence to direct oral anticoagulants is essential for reducing the risk of ischaemic stroke and systemic embolism in patients with atrial fibrillation, owing to the rapid decline in anticoagulation activity when doses are omitted (i.e. rebound effect). OBJECTIVE: We aimed to assess the relationship between non-adherence and non-persistence with direct oral anticoagulants and the incidence of ischaemic stroke in patients with atrial fibrillation. METHODS: A nested case-control study was conducted in the Netherlands, Italy and Germany among patients with atrial fibrillation starting direct oral anticoagulants between the drug approval date and the end of database availability. Patients with an ischaemic stroke during the follow-up were selected as cases and compared with matched controls (matched on age ± 5 years, sex, year of cohort entry date and CHA2DS2-VASc-score at cohort entry date). The cohort entry date was the first dispensing date. Study patients were those aged ≥ 45 years, with ≥ 1 year database history, ≥ 1 year follow-up and at least two direct oral anticoagulant dispensings after the cohort entry date. Adherence and persistence to direct oral anticoagulant treatment were defined as the proportion of days covered ≥ 80% or direct oral anticoagulant continuous use between the cohort entry date and the index date (i.e. date of ischaemic stroke), respectively. RESULTS: In The Netherlands, Italy and Germany, 105 cases and 395 controls, 1580 cases and 6248 controls, and 900 cases and 3570 controls were included, respectively. Odds ratios (ORs) for stroke among current users who were non-adherent compared to adherent users were 0.43 (95% confidence interval [CI] 0.09-1.96) in The Netherlands, 1.11 (95% CI 0.98-1.26) in Italy and 1.21 (95% CI 1.01-1.45) in Germany. The risk of stroke was significantly higher among non-persistent users compared with persistent users in all three databases [OR 1.56 (95% CI 1.00-2.44), OR 1.48 (1.32-1.65) and OR 1.91 (95% CI 1.64-2.22), respectively]. In The Netherlands and Germany, the risk of stroke was higher the longer a patient had stopped using direct oral anticoagulants. CONCLUSIONS: Both non-adherence (in Germany) and non-persistence increased the risk of stroke, either using a once-daily or twice-daily regime.

Treatment Patterns and Healthcare Resource Utilization Among Patients with Atopic Dermatitis: A Retrospective Cohort Study Using German Health Claims Data.

INTRODUCTION: Atopic dermatitis (AD) is a common inflammatory skin disease. Many patients are initiating a systemic therapy, if the disease is not adequately controlled with topical treatment only. Currently, there is little real-world evidence on the AD-related medical care situation in Germany. This study analyzed patient characteristics, treatment patterns, healthcare resource utilization and costs associated with systemically treated AD for the German healthcare system. METHODS: In this descriptive, retrospective cohort study, aggregated anonymized German health claims data from the InGef research database were used. Within a representative sample of four million insured individuals, patients with AD and systemic drug therapy initiation (SDTI) in the index year 2017 were identified and included into the study cohort. Systemic drug therapy included dupilumab, systemic corticosteroids (SCS) and systemic immunosuppressants (SIS). Patients were observed for one year starting from the date of SDTI in 2017. RESULTS: 9975 patients were included (57.8% female, mean age 39.6 years [SD 25.5]). In the one-year observation period, the most common systemic drug therapy was SCS (> 99.0%). Administrations of dupilumab (0.3%) or dispensations of SIS were rare (cyclosporine: 0.5%, azathioprine: 0.6%, methotrexate: 0.1%). Median treatment duration of SCS, cyclosporine and azathioprine was 27 days, 102 days, and 109 days, respectively. 2.8% of the patients received phototherapy; 41.6% used topical corticosteroids and/or topical calcineurin inhibitor. Average annual costs for medications amounted to € 1237 per patient. Outpatient services were used by 99.6% with associated mean annual costs of € 943; 25.4% had at least one hospitalization (mean annual costs: € 5836). 5.3% of adult patients received sickness benefits with associated mean annual costs of € 5026. CONCLUSIONS: Despite unfavorable risk-benefit profile, this study demonstrated a common treatment with SCS, whereas other systemic drug therapy options were rarely used. Furthermore, the results suggest a substantial economic burden for patients with AD and SDTI.

Deep learning for prediction of population health costs.

BACKGROUND: Accurate prediction of healthcare costs is important for optimally managing health costs. However, methods leveraging the medical richness from data such as health insurance claims or electronic health records are missing. METHODS: Here, we developed a deep neural network to predict future cost from health insurance claims records. We applied the deep network and a ridge regression model to a sample of 1.4 million German insurants to predict total one-year health care costs. Both methods were compared to existing models with various performance measures and were also used to predict patients with a change in costs and to identify relevant codes for this prediction. RESULTS: We showed that the neural network outperformed the ridge regression as well as all considered models for cost prediction. Further, the neural network was superior to ridge regression in predicting patients with cost change and identified more specific codes. CONCLUSION: In summary, we showed that our deep neural network can leverage the full complexity of the patient records and outperforms standard approaches. We suggest that the better performance is due to the ability to incorporate complex interactions in the model and that the model might also be used for predicting other health phenotypes.

Effectiveness and safety of direct oral anticoagulants with antiplatelet agents in patients with venous thromboembolism: A multi-database cohort study.

BACKGROUND: Patients with venous thromboembolism (VTE) often have comorbidities that require use of antiplatelets. However, evidence on the effects of concomitant use of direct oral anticoagulants (DOACs) and antiplatelets in this high-risk population is scarce. Our international, multi-database cohort study assessed the real-world effectiveness and safety of concomitant use of DOACs and antiplatelets among patients with VTE. METHODS: We assembled two population-based cohorts using administrative health care databases from Québec and Germany. We included patients with incident VTE who initiated treatment with a DOAC or a vitamin K antagonist (VKA), while being exposed to antiplatelets (acetylsalicylic acid, clopidogrel, ticagrelor, prasugrel, dipyridamole). The study period spanned from 2012 to 2016 (Québec) or 2019 (Germany). Concomitant use of DOACs and antiplatelets was compared with concomitant use of VKAs and antiplatelets, using inverse probability of treatment weighting to balance exposure groups. Cox proportional hazards models estimated site-specific hazard ratios (HRs) and 95% confidence intervals (CIs) of major bleeding, all-cause mortality (primary outcomes), and recurrent VTE (secondary outcome). Site-specific estimates were meta-analyzed using random-effects models. RESULTS: Overall, 4971 patients with VTE initiated concomitant use of a DOAC (n = 2289) or a VKA (n = 2682) and antiplatelets. Compared with concomitant use of VKAs and antiplatelets, concomitant use of DOACs and antiplatelets was associated with similar risks of major bleeding (HR, 0.81; 95% CI, 0.46-1.45), all-cause mortality (HR, 1.25; 95% CI, 0.87-1.79), and recurrent VTE (HR, 0.96; 95% CI, 0.40-2.27). CONCLUSIONS: Among patients with VTE using antiplatelets, there were no major differences in effectiveness and safety between DOACs and VKAs.

Sodium-Glucose Co-Transporter 2 Inhibitors and the Risk of Venous Thromboembolism in Patients with Type 2 Diabetes: A Cohort Study.

PURPOSE: We assessed whether sodium-glucose co-transporter type 2 (SGLT2) inhibitors are associated with a higher incidence rate of venous thromboembolism in patients with type 2 diabetes. METHODS: We conducted a population-based cohort study using the InGef database including patients with type 2 diabetes newly treated with noninsulin antidiabetic drugs between 2012 and 2018. Cases of venous thromboembolism identified during follow-up were matched to 40 controls on age, sex, cohort entry date, and duration of follow-up. Using a nested case-control approach, conditional logistic regression estimated incidence rate ratios (RRs) with 95% confidence intervals (CIs) of venous thromboembolism adjusted for sociodemographic and clinical variables, comparing current use of SGLT2 inhibitors with current use of dipeptidyl peptidase-4 (DPP-4) inhibitors. RESULTS: In a cohort of 219,538 patients, we identified 2152 cases of venous thromboembolism and matched them to 85,104 controls. Compared with DPP-4 inhibitors, current use of SGLT2 inhibitors was associated with a lower rate of venous thromboembolism (RR, 0.75; 95% CI, 0.59-0.94). Effect estimates were similar for dapagliflozin (RR, 0.77; 95% CI, 0.57-1.03) and empagliflozin (RR, 0.71; 95% CI, 0.52-0.98). CONCLUSIONS: Compared with DPP-4 inhibitors, SGLT2 inhibitors were not associated with a higher rate of venous thromboembolism, providing reassurance regarding their thromboembolic safety.

Comparison of Approaches to Select a Propensity Score Matched Control Group in the Absence of an Obvious Start of Follow Up for this Group: An Example Study on the Economic Impact of the DMP Bronchial Asthma.

BACKGROUND: Claims data are a valuable data source to investigate the economic impact of new health care services. While the date of enrollment into the new service is an obvious start of follow-up for participants, the strategy to select potential controls is not straightforward due to a missing start of follow-up to ascertain possible confounders. The aim of this study was to compare different approaches to select controls via Propensity Score Matching (PSM) using the disease management program (DMP) bronchial asthma (BA) as an example. METHODS: We conducted a retrospective cohort study of BA patients between 2013 and 2016 to examine total one-year health care costs and all-cause mortality. We implemented different scenarios regarding the selection of potential controls: I) allotment of a random index date with subsequent PSM, II) calendar year-based PSM (landmark analysis) and III) calendar quarter-based PSM. In scenario I, we applied 2 approaches to assign a random index date: a) assign random index date among all quarters with a BA diagnosis and b) assign random index date and thereafter examine if a BA diagnosis was documented in that quarter. RESULTS: No significant differences in total one-year health care costs between DMP BA participants and non-participants were observed in any of the scenarios. This could to some extent be explained by the higher mortality in the control groups in all scenarios. CONCLUSION: If the loss of potential controls can be compensated, scenario Ib is a pragmatic option to select a control group. If that is not the case, scenario III is the more sophisticated approach, with the limitation that baseline characteristics prior PSM cannot be depicted and computational time or memory size needed to conduct the analysis need to be sufficient.

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.

Robust versus consistent variance estimators in marginal structural Cox models.

In survival analyses, inverse-probability-of-treatment (IPT) and inverse-probability-of-censoring (IPC) weighted estimators of parameters in marginal structural Cox models are often used to estimate treatment effects in the presence of time-dependent confounding and censoring. In most applications, a robust variance estimator of the IPT and IPC weighted estimator is calculated leading to conservative confidence intervals. This estimator assumes that the weights are known rather than estimated from the data. Although a consistent estimator of the asymptotic variance of the IPT and IPC weighted estimator is generally available, applications and thus information on the performance of the consistent estimator are lacking. Reasons might be a cumbersome implementation in statistical software, which is further complicated by missing details on the variance formula. In this paper, we therefore provide a detailed derivation of the variance of the asymptotic distribution of the IPT and IPC weighted estimator and explicitly state the necessary terms to calculate a consistent estimator of this variance. We compare the performance of the robust and consistent variance estimators in an application based on routine health care data and in a simulation study. The simulation reveals no substantial differences between the 2 estimators in medium and large data sets with no unmeasured confounding, but the consistent variance estimator performs poorly in small samples or under unmeasured confounding, if the number of confounders is large. We thus conclude that the robust estimator is more appropriate for all practical purposes.

Use and Characteristics of Antipsychotic/Methylphenidate Combination Therapy in Children and Adolescents with a Diagnosis of Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) frequently have comorbidities that are potential indications for antipsychotics (APs). Some studies have suggested that the combined use of methylphenidate (MPH) and APs is increasing in this population group. Longitudinal analyses and in-depth investigations on the substance level are lacking. This study aimed to estimate the cumulative proportion of concomitant AP/MPH use in children and adolescents with ADHD over a follow-up of up to 9 years and to describe patient characteristics stratified by specific AP drug. METHODS: Based on claims data, concomitant AP/MPH use was identified among 67,595 children and adolescents with ADHD starting MPH treatment between 2005 and 2013. Characteristics and diagnoses-including those indicating appropriateness of AP use according to approved indications and/or guidelines-were examined at the time of first AP/MPH combination therapy. In addition, subsequent use of AP/MPH combination therapy was evaluated. RESULTS: The cumulative proportion of individuals with any AP/MPH combination therapy rose to over 6% within 9 years after initiating MPH. The most frequent APs first used in combination with MPH were risperidone (72%), pipamperone (15%), and tiapride (8%). Percentages of psychiatric hospitalization in the year preceding the first combination therapy with MPH were 33%, 43%, and 19%, respectively. The proportion of individuals with potentially appropriate use was high (>72%) in risperidone/MPH and tiapride/MPH and low (15%) in pipamperone/MPH combination users. Conduct disorders and tic disorders were frequent in users who were prescribed MPH with risperidone and tiapride, respectively. One-quarter of patients with AP/MPH combination therapy were one-time-only combination users. CONCLUSION: Our study suggests that a considerable proportion of children and adolescents with ADHD receive MPH in combination with APs and that this is a factor not only during the first years of MPH treatment. ADHD guidelines should specify algorithms concerning the use of AP medication.

The Potential of High-Dimensional Propensity Scores in Health Services Research: An Exemplary Study on the Quality of Care for Elective Percutaneous Coronary Interventions.

OBJECTIVE: Evaluating the potential of the high-dimensional propensity score (HDPS) to control for residual confounding in studies analyzing quality of care based on administrative health insurance data. DATA SOURCE: Secondary data from 2004 to 2009 from three German statutory health insurance providers. STUDY DESIGN: We conducted a retrospective cohort study in patients with elective percutaneous coronary interventions (PCIs) and compared the mortality risk between the in- and outpatient setting using Cox regression. Adjustment for predefined confounders was performed using conventional propensity score (PS) techniques. Further, an HDPS was calculated based on predefined and empirically selected confounders from the database. PRINCIPAL FINDINGS: Conventional PS methods showed a decreased mortality risk for outpatient compared to inpatient PCIs, while trimming of patients with nonoverlap in the HDPS distribution and weighting resulted in a comparable risk. Most comorbidities were less prevalent in the HDPS-trimmed population compared to the original one. CONCLUSION: The HDPS methodology may reduce residual confounding by rendering the studied cohort more comparable through restriction. However, results cannot be generalized for the entire study population. To provide unbiased results, full assessment of all unmeasured confounders from proxy information in the database would be necessary.

Incidence of herpes zoster amongst adults varies by severity of immunosuppression.

OBJECTIVES: We examined the incidence of herpes zoster in immunocompromised adults (≥18 years) with different severities of immunosuppression and assessed the prevalence of complications and of various kinds of healthcare resource utilisation. METHODS: German claims data from more than ten million adults were used to calculate annual incidence rates of herpes zoster for the years 2006-2012 and to analyse the prevalence of complications, physician visits, hospitalisations, and antiviral and analgesic treatments using a cohort design. The analyses were stratified by age, sex, and severity of immunosuppression, defined by immunocompromising conditions and drug therapies. RESULTS: The incidence rate per 1000 person-years of herpes zoster was almost twice as high in immunocompromised patients (11.5 (95% confidence interval (CI): 11.4-11.6)) compared to immunocompetent subjects (5.9 (95% CI: 5.8-5.9)). The incidence rate was higher in highly immunocompromised patients (13.4 (95% CI: 13.2-13.6)) than in patients with a low severity of immunosuppression (10.0 (95% CI: 9.8-10.1)). These differences were observed for both sexes and in all age groups. Complications, outpatient physician visits, hospitalisations, and analgesic treatments occurred more frequently in immunocompromised patients as well. CONCLUSIONS: Our results show that immunocompromised individuals are affected by the disease in particular and that the burden of herpes zoster is highest in severely immunocompromised patients.

Prevalence, Duration and Severity of Parkinson's Disease in Germany: A Combined Meta-Analysis from Literature Data and Outpatient Samples.

BACKGROUND: Epidemiological data on the prevalence of Parkinson's disease (PD) in Germany are limited. The aims of this study were to estimate the age- and gender-specific prevalence of PD in Germany as well as the severity and illness duration. SUMMARY: A systematic literature search was performed in 5 different databases. European studies were included if they reported age- and gender-specific numbers of prevalence rates of PD. Meta-analytic approaches were applied to derive age- and gender-specific pooled prevalence estimates. Data of 4 German outpatient samples were incorporated to calculate the proportion of patients with PD in Germany grouped by Hoehn and Yahr (HY) stages and disease duration. In the German population, 178,169 cases of PD were estimated (prevalence: 217.22/100,000). The estimated relative illness duration was 40% with less than 5 years, 31% with 5-9 years, and 29% with more than 9 years. The proportions for different HY stages were estimated at 13% (I), 30% (II), 35% (III), 17% (IV), and 4% (V), respectively. Key Message: We provide an up-to-date estimation of age- and gender-specific as well as severity-based prevalence figures for PD in Germany. Further community studies are needed to estimate population-based severity distributions and distributions of non-motor symptoms in PD.

Initiation and duration of dual antiplatelet therapy after inpatient percutaneous coronary intervention with stent implantation in Germany: An electronic healthcare database cohort study.

BACKGROUND: Studies assessing the routine outpatient dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in Germany are scarce. The aim of this study was (i) to investigate the initiation and duration of DAPT after inpatient PCI with stent implantation in Germany, and (ii) to identify factors associated with DAPT discontinuation during the recommended treatment period. METHODS: This retrospective cohort study was based on data from a large German electronic healthcare database of the years 2004 to 2009. The study population comprised four groups of patients with acute coronary syndrome (ACS) or stable angina pectoris undergoing inpatient PCI with either bare metal stent (BMS) or drug eluting stent (DES) implantation between 2005 and 2008. Initiation of outpatient DAPT within a period from 100 days before the PCI to 60 days after the PCI was ascertained. Time until end of treatment was analysed using the Kaplan-Meier method. Factors potentially associated with DAPT discontinuation, like sex, age, cardiovascular comorbidity, contraindications, and other antithrombotic drugs were analysed in a Cox proportional hazard model. RESULTS: The cohort comprised 37,001 patients. Depending on the type of stent and the indication for the PCI, DAPT was initiated in 85 % (ACS/BMS) and 95 % (AP/DES) of all patients. Of those, 12 % (AP/DES) and 64 % (ACS/BMS) discontinued DAPT during the recommended treatment duration. An age of over 80 years (OR 1.2-1.5 compared to patients aged 0-49 years) and the use of phenprocoumon (OR 2.7-5.0 compared to no phenprocoumon) were associated with an increased risk of DAPT discontinuation. CONCLUSIONS: A high proportion of patients with coronary artery disease undergoing inpatient PCI with stent implantation received DAPT. However, DAPT discontinuation during the recommended time span was frequent, particularly in patients suffering from ACS. On the other hand, especially patients with AP and DES were often treated longer than recommended.

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.

Comparative risk for cardiovascular diseases of dipeptidyl peptidase-4 inhibitors vs. sulfonylureas in combination with metformin: Results of a two-phase study.

AIMS: The aim was to assess whether the use of additional data from the Disease Management Program (DMP) diabetes mellitus type 2 to minimize the potential for residual confounding will alter the estimated risk of either myocardial infarction, ischemic stroke or heart failure in patients with type 2 diabetes using sulfonylureas compared to dipeptidyl peptidase-4 (DPP-4) inhibitors in addition to metformin based on routine health care data. METHODS: We conducted a nested two-phase case-control study using claims data of one German health insurance from 2004 to 2013 (phase 1) and data of the DMP from 2010 to 2013 (phase 2). Adjusted odds ratios (ORs) for the combined cardiovascular event myocardial infarction, ischemic stroke or heart failure were calculated using a two-phase logistic regression. RESULTS: Phase 1 comprised 3179 patients (289 cases; 2890 controls) and phase 2 comprised 1968 patients (168 cases; 1800 controls). We observed an adjusted OR of 0.83 for the combined cardiovascular event (95% CI: 0.61-1.13). CONCLUSIONS: We observed a non-significantly reduced risk for cardiovascular diseases in patients using DPP-4 inhibitors compared to sulfonylureas in addition to metformin. This finding was not altered by the inclusion of additional information of the DMP in the analysis. However, due to the low power of this study, further studies are needed to reproduce our findings.

[Percutaneous coronary interventions : Use between 2004 and 2012 in Germany]. / Perkutane koronare Interventionen : Einsatz zwischen 2004 und 2012 in Deutschland.

BACKGROUND AND OBJECTIVE: Percutaneous coronary interventions (PCIs) are increasingly being performed in the treatment of coronary artery disease. The aim of this study is to describe the frequency of PCIs by age, sex, type, and setting of the intervention in Germany. METHODS: Based on routine data of more than eight million insurants from three statutory health insurance funds, quarterly sex- and age-specific intervention rates were calculated between 2004 and 2012. Moreover, inpatient PCIs were subdivided into PCIs with conventional bare metal stents (BMS) and PCIs with drug-eluting stents (DES). Rates were age- and sex-standardized according to the age and sex distribution of the particular years in Germany. RESULTS: Standardized rates increased from 277.3 to 382.2 per 100,000 person-years between 2004 and 2012. The intervention rate was three times higher in men than in women. The relative increase in the overall rate and in the rate of PCI with DES during the study period were 38 and 548 % respectively, whereas the rate of PCI with BMS declined by 48 %. Of all PCIs, 7-11 % were outpatient PCIs during the study period. CONCLUSIONS: PCIs are increasingly being performed in Germany, particularly PCI with DES. The frequency of PCI with BMS implantation is decreasing. Sex-specific differences in the frequency of PCI go beyond differences that would have been expected because of a differing morbidity profile. Our analyses indicate that comparatively few outpatient PCIs are performed.

Duration of sick leave after shoulder arthroscopy in Germany: analysis of health care data.

INTRODUCTION: The expected duration of incapacity after arthroscopic shoulder surgery is an important factor for therapy planning. The aim of this study was to analyze the duration of sick leave after arthroscopic shoulder surgery in Germany and to identify factors associated with a longer duration of sick leave. We hypothesized that certain patient-related factors may be associated with a longer duration of sick leave. METHODS: Routine health care data of all patients insured by one German health insurance company who underwent inpatient arthroscopic shoulder surgery between 2010 and 2012 were included in the analysis of the duration of sick leave in this retrospective cohort study (level III evidence). Comparisons were performed for different arthroscopic surgical procedures using the log-rank test. Possible factors that might be associated with a longer duration of incapacity were analyzed. RESULTS: Sick leave was reported in 303 of 660 cases. The median duration of sick leave was 82 days after subacromial decompression and 157 days after rotator cuff repair (p = 0.004). The duration of sick leave was longer in patients older than 50 years (p = 0.044) and in patients with sick leave that started prior to surgery (p < 0.001). Patients not receiving physiotherapy had a longer period of sick leave (p = 0.058). The median period of prescribed physiotherapy (64 days) was shorter than the period of incapacity. The duration of disability was not notably longer in female patients, patients taking opioid or antidepressant medication or diabetics. CONCLUSIONS: The duration of sick leave after arthroscopic shoulder surgery in Germany does not exceed sick leave duration in other countries. More complex procedures, advanced age and sick leave beginning prior to surgery resulted in longer durations of sick leave. Preoperative prognosis of the necessary duration of postoperative sick leave may not always be realistic. An extended period of sick leave can be expected after more complex procedures and in patients older than 50 years of age. Future studies should investigate whether a longer period of physiotherapy may help to shorten the period of postoperative sick leave.