Impact of pre-existing mental health diagnoses on development of post-COVID and related symptoms: a claims data-based cohort study.

This study aimed to examine the association of prior mental health diagnoses with the onset of Post-COVID-19 condition (PCC). We conducted a retrospective comparative cohort study and secondary analysis of routinely collected claims data from participants in statutory health insurance in Bavaria, Germany, from January 2015 to June 2022. Study participants were 619,560 patients with confirmed COVID-19, 42,969 with other respiratory tract infection (ORI), and 438,023 controls. Using diagnoses coded according to the German modification of the ICD-10, the associations between prior mental health diagnoses and a PCC diagnosis (primary outcome) or associated symptoms (secondary outcomes) were estimated using multiple Cox proportional hazards regression models. Mental disorders (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.30-1.42), anxiety (HR 1.14, 95% CI 1.07-1.20), depression (HR 1.25, 95% CI 1.19-1.30) and somatoform disorders (HR 1.30, 95% CI 1.24-1.36) were associated with higher risks for PCC. Mental disorders were associated with the same or even greater risk for a diagnosis of malaise and fatigue in the control cohort (HR 1.71, 95% CI 1.52-1.93) and ORI cohort (HR 1.43, 95% CI 1.20-1.72), than in the COVID-19 cohort (HR 1.43, 95% CI 1.35-1.51). In summary, prior mental comorbidity was associated with an increased risk of PCC and its associated symptoms in all cohorts, not specifically in COVID-19 patients.

Time-Varying Use of Proton Pump Inhibitors and Cognitive Impairment and Dementia: A Real-World Analysis from Germany.

BACKGROUND: Cumulative evidence of dementia risk in patients taking proton pump inhibitors (PPIs) is still inconclusive, probably due to a variety of study designs. OBJECTIVE: This study aimed to compare how the association between dementia risk and use of PPIs differs by different outcome and exposure definitions. METHODS: We conceptualized a target trial using claims data with 7,696,127 individuals aged 40 years or older without previous dementia or mild cognitive impairment (MCI) from the Association of Statutory Health Insurance Physicians in Bavaria. Dementia was defined as either including or excluding MCI to compare how the results alter by different outcome definitions. We used weighted Cox models to estimate the PPI initiation effect on dementia risk and weighted pooled logistic regression to assess the effect of time-varying use versus non-use during 9 years of study period, including 1 year of wash-out period (2009-2018). The median follow-up time of PPI initiators and non-initiators was 5.4 and 5.8 years, respectively. We also evaluated the association between each PPI agent (omeprazole, pantoprazole, lansoprazole, esomeprazole, and combined use) and dementia risk. RESULTS: A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk. A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk. CONCLUSION: Our large study supports existing evidence that PPI use is related to an increased risk of dementia.

Do proton pump inhibitors increase the risk of dementia? A systematic review, meta-analysis and bias analysis.

AIM: Previous studies on the association between proton pump inhibitor (PPI) intake and the increased risk of dementia has shown discrepancies in their conclusions. We aimed to provide updated evidence based on extensive bias assessments and quantitative sensitivity analyses. METHODS: We searched the databases PubMed, EMBASE, SCOPUS, CENTRAL and clinicaltrials.gov for prospective studies that examined an association between PPI use and dementia, up to February 2022. Each study was assessed using the Cochrane risk of bias assessment tools for non-randomized studies of interventions (ROBINS-I) or randomized trials (RoB2). Pooled risk ratios (RRs) and 95% prediction intervals were computed using random-effects models. Sensitivity analyses were adjusted for small-study bias. RESULTS: We included nine observational studies with 204 108 dementia cases in the primary analysis on the association between PPI use vs. non-use and dementia, and the RR was 1.16 (95% CI = 1.00; 1.35). After adjusting for small-study bias by Copas selection model and Rücker's shrinkage procedure, the RR was 1.16 (1.02; 1.32) and 1.15 (1.13; 1.17), respectively. A subgroup analysis of PPI use vs. non-use regarding Alzheimer's disease risk yielded an RR of 1.15 (0.89; 1.50). The secondary analysis on the risk of dementia by use of PPI vs. histamine-2 receptor antagonist showed an RR of 1.03 (0.66; 1.62). CONCLUSION: This meta-analysis provided no clear evidence for an association between PPI intake and the risk of dementia. Due to discrepancies in sensitivity analyses, however, some risk of dementia by PPI use cannot be ruled out. Since an unequivocal conclusion is still pending, further research is warranted.

HPV vaccination leads to decrease of anogenital warts and precancerous lesions of the cervix uteri in young women with low vaccination rates: a retrospective cohort analysis.

BACKGROUND: Although the human papillomavirus (HPV) vaccine has been recommended in Germany for girls since 2007, no organised vaccination programme was introduced and HPV vaccine coverage remains low. We investigated the HPV vaccination rates from 2008 to 2018 and the effects of HPV vaccination on anogenital warts and precancerous lesions in young women in Bavaria, Germany, a state with low vaccination rates. METHODS: Retrospective analyses of claims data from the Bavarian Association of Statutory Health Insurance Physicians (KVB) on females born between 1990 and 2009 (9 to 28 years old in 2018) were conducted to calculate vaccination rates by birth cohort, proportion of vaccine types administered and incidence of anogenital warts and precancerous lesions of the cervix uteri. 942 841 Bavarian females 9 to 28 years old with available information on HPV vaccination were included to calculate vaccination rates. For the outcome analyses, data from 433 346 females 19 to 28 years old were analysed. Hazard ratios (HR) were computed from univariable and multivariable Cox regression models comparing vaccinated and unvaccinated women, considering type of vaccine used and contraceptive prescription. RESULTS: 40·9% of 18-year-olds and only 13·3% of 12-year-olds were fully vaccinated in 2018 in Bavaria. Gardasil® and Gardasil9® were most commonly administered. Vaccinated compared to unvaccinated women had a lower incidence of anogenital warts and cervical lesions, however only small differences were detected between fully and partially vaccinated women. Fully vaccinated women had a 63% (HR 0·37 (95% confidence interval (CI) 0·34 to 0·40) and 23% (HR 0·77, 95%CI 0·71 to 0·84) lower risk of anogenital warts and cervical lesions, respectively. Women who were prescribed contraceptives prior to vaccination had a 49% higher risk of developing anogenital warts (HR 1·49, 95%CI 1·25 to 1·79) or cervical lesions (HR 1·49, 95%CI 1·27 to 1·75) compared to vaccinated women without contraceptive prescription. CONCLUSIONS: The evaluation of the effects of HPV vaccination in Bavaria showed a promising decline of anogenital warts and precancerous lesions in vaccinated young women. However, an increase in vaccination rates is necessary to achieve a greater population impact in preventing HPV-related diseases.

[How robust are studies of currently permanently included digital health applications (DiGA)? Methodological quality of studies demonstrating positive health care effects of DiGA]. / Wie belastbar sind Studien der aktuell dauerhaft aufgenommenen digitalen Gesundheitsanwendungen (DiGA)? Methodische Qualität der Studien zum Nachweis positiver Versorgungseffekte von DiGA.

INTRODUCTION: Since September 2020 digital health applications (DiGA) can be prescribed by physicians and psychotherapists and are reimbursed within the German Statutory Health Insurance (SHI) system for the first time worldwide. For full reimbursement, the manufacturers have to provide evidence based on scientific studies that the DiGA can provide 'positive health care effects'. This study aims to analyze and evaluate the methodological quality of efficacy studies of DiGA in the categories 'Nervensystem' and 'Psyche' of the DiGA register that are permanently accepted. METHODS: The methodological quality was assessed using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The risk of bias was assessed for the primary endpoint of each study according to an intention-to-treat analysis. RESULTS: Six DiGA were assessed for their methodological quality. Randomized controlled trials were conducted for all 6 DiGA that showed a high risk of bias, which was, in particular, due to a lack of blinding of the studies. In addition, drop-outs were significantly higher in the intervention group than in the control group in most studies. For most of the DiGA no published study protocol was available in advance so an analysis of a potential selective choice of the evaluation methodology was not possible. DISCUSSION: For reasons of transparency, verifiability, and comprehensibility of the study results, registration in a study registry and, more importantly, the publication of study protocols should be mandatory before the start of the studies. In addition, studies should be blinded by comparing the DiGA with a 'sham application' to reduce the high risk of bias. Differences in the drop-out rates of the investigated studies could indicate a lack of efficacy of the treatment in the intervention group, (technical) problems in the application of the DiGA, or a lack of motivation of the participants. CONCLUSION: The interim results 18 months after the introduction of DiGA in the German SHI system show that the studies on the evidence of the benefits of DiGA have a high potential for bias in certain areas. However, it should be positively emphasized that the manufacturers submitted randomized controlled trials to prove the medical benefit of the DiGAs investigated.

Proton pump inhibitors and the risk of cardiovascular events and cardiovascular mortality: A systematic review and meta-analysis of observational studies.

BACKGROUND AND AIMS: Observational research has indicated that proton pump inhibitors (PPIs) might increase the long-term risk of cardiovascular events. This study evaluated the evidence from observational studies for an effect of PPI monotherapy on the risk of incident cardiovascular events and cardiovascular mortality. METHODS: The databases MEDLINE, EMBASE, and Scopus were systematically searched up to September 2021. The primary outcome was first cardiovascular event, i.e. first myocardial infarction or first ischaemic stroke. The secondary outcome was cardiovascular mortality. Studies were included following a detailed risk of bias assessment with the ROBINS-I tool. Sensitivity and bias analyses adjusted for potential publication bias, immortal time bias, and unmeasured confounding. RESULTS: We included ten studies with 75,371 first cardiovascular events, as well as seven studies on cardiovascular mortality with 50,329 cardiovascular deaths in total. The pooled hazard ratios (HRs) for PPI use and cardiovascular events were 1.05 with a 95% confidence interval of (0.96; 1.15) before and 0.99 (0.93; 1.04) after adjusting for observational study design bias. The pooled HRs for PPI use and cardiovascular mortality were 1.27 (1.11; 1.44) before and 1.06 (0.96; 1.16) after adjusting for publication bias and observational study design bias. CONCLUSION: It is questionable, whether PPI monotherapy constitutes a cardiovascular risk factor.

Incidence of post-COVID syndrome and associated symptoms in outpatient care in Bavaria, Germany: a retrospective cohort study using routinely collected claims data.

OBJECTIVES: To estimate the treatment incidence of post-COVID syndrome (postinfectious sequelae present at least 12 weeks following infection) in the context of ambulatory care in Bavaria, Germany, and to establish whether related diagnoses occur more frequently than in patients with no known history of COVID-19. DESIGN: Retrospective cohort analysis of routinely collected claims data. SETTING: Ambulatory care in Bavaria, Germany, observed from January 2020 to March 2022 (data accessed May 2022). PARTICIPANTS: 391 990 patients with confirmed COVID-19 diagnosis, 62 659 patients with other respiratory infection and a control group of 659 579 patients with no confirmed or suspected diagnosis of COVID-19. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome is diagnosis of post-COVID syndrome documented in ambulatory care. Secondary outcomes are: chronic fatigue syndrome, psychological disorder, fatigue, mild cognitive impairment, disturbances of taste and smell, dyspnoea, pulmonary embolism and myalgia. RESULTS: Among all patients with confirmed COVID-19, 14.2% (95% CI 14.0% to 14.5%) received a diagnosis of a post-COVID syndrome, and 6.7% (95% CI 6.5% to 6.9%) received the diagnosis in at least two quarterly periods during a 2-year follow-up. Compared with patients with other respiratory infections and with controls, patients with COVID-19 more frequently received a variety of diagnoses including chronic fatigue syndrome (1.6% vs 0.6% and 0.3%, respectively), fatigue (13.3% vs 9.2% and 6.0%), dyspnoea (9.9% vs 5.1% and 3.2%) and disturbances of taste and smell (3.2% vs 1.2% and 0.5%). The treatment incidence of post-COVID syndrome was highest among adults aged 40-59 (19.0%) and lowest among children aged below 12 years (2.6%). CONCLUSIONS: Our results demonstrate a moderately high incidence of post-COVID syndrome 2 years after COVID-19 diagnosis. There is an urgent need to find efficient and effective solutions to help patients with dyspnoea, fatigue, cognitive impairment and loss of smell. Guidelines and treatment algorithms, including referral criteria, and occupational and physical therapy, require prompt and coherent implementation.

Emulating a target trial of proton pump inhibitors and dementia risk using claims data.

BACKGROUND AND PURPOSE: Understanding the adverse effects of proton pump inhibitors (PPIs) is important due to their widespread use, but the available evidence for an increased dementia risk amongst patients taking PPIs is inconclusive. The present study aimed to estimate the causal effect of PPIs on the risk of dementia by target trial emulation and time-varying exposure modeling. METHODS: Using claims data of 2,698,176 insured people of a large German statutory health insurer, a target trial was conceptualized in which individuals aged 40 years and older were classified as PPI initiators or non-initiators between 2008 and 2018, and were followed until diagnosis of dementia, death, loss to follow-up or end of study. Incidence of dementia (International Classification of Diseases 10 codes F00, F01, F03, F05.1, G30, G31.0, G31.1, G31.9 and F02.8+G31.82) was defined applying a 1-year lag window. Weighted Cox models were used to estimate the effect of PPI initiation versus non-initiation on dementia risk and weighted pooled logistic regression was used to estimate the effect of time-varying use versus non-use. RESULTS: In all, 29,746 PPI initiators (4.4%) and 26,830 non-initiators (1.3%) were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio for dementia was 1.54 (95% confidence interval 1.51-1.58). The hazard ratio for time-dependent PPI use versus non-use was 1.56 (95% confidence interval 1.50-1.63). Differentiated subtypes, including unspecified dementia, Alzheimer's disease and vascular dementia, showed increased risk by PPI initiation and time-varying PPI use. CONCLUSIONS: This study suggests that PPI initiation and time-varying PPI use may increase overall dementia risk.

[The Development of General Practices in Ambulatory Care in the Last Decades - An Analysis of the Physicians' Registry of Bavaria]. / Entwicklung der hausärztlichen Versorgung innerhalb der letzten Jahrzehnte ­ eine Analyse des Basisdatensatzes der Kassenärztlichen Vereinigung Bayerns.

AIM OF THE STUDY: There is an increasing shortage of general practitioners (GPs) in Germany. An in-depth understanding of the variation regarding the characteristics of the GPs in the last decades might help to optimize primary health care. The aim of the analysis of the characteristic features of GPs as preserved by the registry of the Bavarian Association of Statutory Health Insurance of Physicians (KVB) was to delineate the time interval between passing the medical state examination and establishment of one's own private practice, the development of group practices and employments, and the number of additional qualifications. METHODS: The physicians' registry of the KVB was used to analyse the time intervals, additional qualifications, and development of group practices and employments. Data were analysed descriptively. RESULTS: The time interval from passing the medical state examination and establishing one's own private practice increased remarkably since the 70s from 5 years to 12 years on average. There was an increasing trend towards group practices. The number of newly established practices remained constant around 200 practices per year. Beyond that, there was an increasing trend towards employment in practices. The number of additional qualifications decreased over time, which was in particular true of complementary medicine and sports medicine. CONCLUSIONS: The period of vocational traineeship should be organised efficiently to decrease the length of training. Young GPs should be motivated and receive incentives to establish their own private practice. However, it is also necessary to facilitate employment in the practices.

Who gets prescriptions for proton pump inhibitors and why? A drug-utilization study with claims data in Bavaria, Germany, 2010-2018.

PURPOSE: The German annual drug prescription-report has indicated overuse of proton pump inhibitors (PPIs) for many years; however, little was known about the characteristics of people using PPIs. This study aimed to provide comprehensive utilization data and describe frequencies of potential on- and off-label PPI-indications in Bavaria, Germany. METHODS: Claims data of statutorily insured people from 2010 to 2018 were used. Defined daily doses (DDDs) of PPIs by type of drug, prevalence of PPI-use and DDDs prescribed per 1000 insured people/day were analyzed. For 2018, proportions of users and DDDs per 1000 insured people were calculated by age and sex. To elucidate changes in prescribing practices due to a suspected drug-drug interaction, we examined co-prescribing of clopidogrel and PPIs between 2010 and 2018. For PPI new users, sums of DDDs and frequencies of potential indications were examined. RESULTS: PPI prescribing increased linearly from 2010 to 2016 and gradually decreased from 2016 to 2018. In 2018, 14.7% of women and 12.2% of men received at least one prescription, and 64.8 DDDs (WHO-def.) per 1000 insured people/day were prescribed. Overall, omeprazole use decreased over the observation period and was steadily replaced by pantoprazole, especially when co-prescibed with clopidogrel. An on-label PPI-indication was not reported at first intake in 52.0% of new users. CONCLUSIONS: The utilization of prescribed PPIs has decreased since 2016. However, a large proportion of new PPI-users had no documentation of a potential indication, and the sums of DDDs prescribed often seemed not to comply with guidelines.

The long-term risk for myocardial infarction or stroke after proton pump inhibitor therapy (2008-2018).

BACKGROUND: Proton pump inhibitors (PPIs) are well tolerated in the short term but have recently been associated with increased long-term cardiovascular risk in observational studies. AIMS: To evaluate long-term risks of myocardial infarction (MI) and ischaemic stroke (IS) associated with PPI vs H2 -receptor antagonist (H2 RA) therapy in adults without pre-existing cardiovascular or cerebrovascular disease METHODS: Using administrative claims data (2008-2018), we emulated a target trial comparing MI and IS risks in new users of PPIs vs H2 RAs. Treatment was identified using dispensed prescriptions. MI and IS were defined using hospital discharge codes. Inverse probability weighting was used to adjust for confounding, and Cox models to estimate hazard ratios (HRs). Survival curves were estimated using weighted Kaplan-Meier estimators. RESULTS: We identified 1 143 948 new users of PPIs and 36 229 new users of H2 RAs who were free of prevalent cardiovascular or cerebrovascular disease. The mean follow-up time was 6.2 years for PPI initiators and 5.3 years for H2 RA initiators. After 10 years, the HRs for MI and IS were 0.96 (95% confidence interval (CI): 0.80-1.16) and 0.98 (95% CI: 0.89-1.08), respectively. CONCLUSIONS: This analysis of claims data of a large German health insurer did not provide evidence that PPI therapy increased the risk of MI or IS in the first decade after treatment initiation.

Ambulatory specialist costs and morbidity of coordinated and uncoordinated patients before and after abolition of copayment: A cohort analysis.

To strengthen the coordinating function of general practitioners (GPs) in the German healthcare system, a copayment of €10 was introduced in 2004. Due to a perceived lack of efficacy and a high administrative burden, it was abolished in 2012. The present cohort study investigates characteristics and differences of GP-coordinated and uncoordinated patients in Bavaria, Germany, concerning morbidity and ambulatory specialist costs and whether these differences have changed after the abolition of the copayment. We performed a retrospective routine data analysis, using claims data of the Bavarian Association of the Statutory Health Insurance Physicians during the period 2011-2012 (with copayment) and 2013-2016 (without copayment), covering 24 quarters. Coordinated care was defined as specialist contact only with referral. Multinomial regression modelling, including inverse probability of treatment weighting, was used for the cohort analysis of 500 000 randomly selected patients. Longitudinal regression models were calculated for cost estimation. Coordination of care decreased substantially after the abolition of the copayment, accompanied by increasing proportions of patients with chronic and mental diseases in the uncoordinated group, and a corresponding decrease in the coordinated group. In the presence of the copayment, uncoordinated patients had €21.78 higher specialist costs than coordinated patients, increasing to €24.94 after its abolition. The results indicate that patients incur higher healthcare costs for specialist ambulatory care when their care is uncoordinated. This effect slightly increased after abolition of the copayment. Beyond that, the abolition of the copayment led to a substantial reduction in primary care coordination, particularly affecting vulnerable patients. Therefore, coordination of care in the ambulatory setting should be strengthened.

Mental Health Surveillance at federal state level - Reporting on psychiatry in Bavaria.

In Germany, mental health reporting is organised at the federal, federal state and municipal level. At federal level, a number of concepts and approaches are implemented. In 2020 and 2021, in accordance with Article 4 of the Mental Health Assistance Act the first Bavarian Psychiatry Report was prepared. Important data bases include the billing and care data of Bavaria's Association of Statutory Health Insurance Physicians and the administrative data of the Bavarian districts. The aim is to enhance coordination between these federal state projects and Mental Health Surveillance at national level, in particular regarding the use of health care data.

Prescribers' compliance with summary of product characteristics of dabigatran, rivaroxaban and apixaban-A European comparative drug utilization study.

Despite a tremendous increase of direct oral anticoagulants (DOACs) prescriptions in recent years, only few data is available analysing prescribers' adherence to Summary of Product Characteristics (SmPC). We aimed to assess adherence to registered indications, contraindications, special warnings/precautions, and potential drug-drug interactions for three DOAC compounds (dabigatran, rivaroxaban, and apixaban) in six databases of five European countries (The Netherlands, United Kingdom, Spain, Denmark, and Germany). We included adult patients (≥18 years) initiating DOACs between 2008 and 2015. For several SmPC items, broad definitions were used due to ambiguous SmPC terms or lacking data in some databases. Within the study period, a DOAC was initiated in 407 576 patients (rivaroxaban: 240 985 (59.1%), dabigatran: 95 303 (23.4%), and apixaban: 71 288 (17.5%)). In 2015, non-valvular atrial fibrillation was the most common indication (>60% in most databases). For the whole study period, a substantial variation between the databases was found regarding the proportion of patients with at least one contraindication (inter-database range [IDR]: 8.2%-55.7%), with at least one special warning/precaution (IDR: 35.8%-75.2%) and with at least one potential drug-drug interaction (IDR: 22.4%-54.1%). In 2015, the most frequent contraindication was "malignant neoplasm" (IDR: 0.7%-21.3%) whereas the most frequent special warning/precaution was "prescribing to the elderly" (≥75 years; IDR: 25.0%-66.4%). The most common single compound class interaction was "concomitant use of non-steroidal anti-inflammatory drugs" (IDR: 3.0%-25.3%). Contraindications, special warnings/precautions, and potential drug-drug interactions were present in a relevant number of new DOAC users. Due to broad definitions used for some SmPC terms, overall proportions for contraindications are prone to overestimation. However, for unambiguous SmPC terms documented in the databases sufficiently, the respective estimates can be considered valid. Differences between databases might be related to "true" differences in prescription behaviour, but could also be partially due to differences in database characteristics.

Impact of the abolition of copayments on the GP-centred coordination of care in Bavaria, Germany: analysis of routinely collected claims data.

OBJECTIVES: In 2012, Germany abolished copayment for consultations in ambulatory care. This study investigated the effect of the abolition on general practitioner (GP)-centred coordination of care. We assessed how the proportion of patients with coordinated specialist care changed over time when copayment to all specialist services were removed. Furthermore, we studied how the number of ambulatory emergency cases and apparent 'doctor shopping' changed after the abolition. DESIGN: A retrospective routine data analysis of the Bavarian Association of Statutory Health Insurance Physicians, comparing the years 2011 and 2012 (with copayment), with the period from 2013 to 2016 (without copayment). Therefore, time series analyses covering 24 quarters were performed. SETTING: Primary care in Bavaria, Germany. PARTICIPANTS: All statutorily insured patients in Bavaria, aged ≥18 years, with at least one ambulatory specialist contact between 2011 and 2016. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the percentage of patients with GP-coordinated care (every regular specialist consultation within a quarter was preceded by a GP referral). Secondary outcomes were the number of ambulatory emergency cases and apparent 'doctor shopping'. RESULTS: After the abolition, the proportion of coordinated patients decreased from 49.6% (2011) to 15.5% (2016). Overall, younger patients and those living in areas with lower levels of deprivation showed the lowest proportions of coordination, which further decreased after abolition. Additionally, there were concomitant increases in the number of ambulatory emergency contacts and to a lesser extent in the number of patients with apparent 'doctor shopping'. CONCLUSIONS: The abolition of copayment in Germany was associated with a substantial decrease in GP coordination of specialist care. This suggests that the copayment was a partly effective tool to support coordinated care. Future studies are required to investigate how the gatekeeping function of GPs in Germany can best be strengthened while minimising the associated administrative overhead.

Differences in treatment and monitoring of chronic myeloid leukemia with regard to age, but not sex: Results from a population-based study.

There are established guidelines for treatment and monitoring of chronic myeloid leukemia (CML) but little is known about routine care. Data on ICD-10 codes as well as prescribed medications were available for 10.5 million patients in the statutory health insurance system in Bavaria for the years 2010 to 2016. Also, data on the molecular and cytogenetic monitoring were integrated. A total of 1714 adult patients with CML were observed. Only 50.8% received more than 67.5 daily doses per quarter year (target: 91.5) while 18.2% did not receive any tyrosine kinase inhibitor (TKI). The median number of daily doses was at least 80 doses per quarter year for all age groups in men, but decreased to 62 doses in elderly women. With this exception, no differences between men and women were observed. The percentage of patients without any TKI increased with age. The median number of molecular examinations was 3.54 independent of age and sex. Even in a highly developed country, still a considerable number of patients with CML seem to not receive adequate treatment, whereas molecular monitoring can be considered satisfactory.

"What they see is what you get": Prescribing antibiotics for respiratory tract infections in primary care: Do high prescribers diagnose differently? An analysis of German routine data.

BACKGROUND: Characteristics of high and low prescribers of antibiotics in German primary care were analysed using population data. We aimed to evaluate differences in prescribing rates and factors being associated with high prescribing, and whether high prescribers made the diagnosis of perceived bacterial infections more often. METHODS: Routine data were provided by the Bavarian Association of Statutory Health Insurance Physicians. Routine data are delivered by primary care practices on a quarterly basis. We analysed data from 2011 and 2012. Patients older than 15 years with respiratory tract infections consulting a primary care physician were selected (6.647 primary care practices). Patient and physician characteristics associated with high prescribing were identified using stepwise logistic regression. RESULTS: Mean prescribing rate of antibiotics was 24.9%. Prescribing rate for high prescribers was 43.5% compared to 8.5% for low prescribers. High prescribers made the diagnosis of perceived bacterial infections more often (Mhigh = 64.5%, Mlow = 45.2%). In the adjusted regression model, perceived bacterial infections were strongly associated with high prescribing (OR = 13.9, 95% CI [10.2, 18.8]). Treating patients with comorbidities was associated with lower prescribing of antibiotics (OR = 0.6, 95% CI [0.4, 0.8]). High prescribers had a higher practice volume, a higher degree of prescribing dominance, and were situated more often in deprived areas and in rural settings. INTERPRETATION: Compared to findings of studies in other European countries, prescribing rates were low. There was a considerable difference between prescribing rates of high and low prescribers. Diagnostic labelling was the best predictor for high prescribing. Current guidelines recommend considering antibiotic treatment for patients with co-morbidities. In our study, treating a large number of high-risk patients was not associated with high prescribing.

Impact of regional socioeconomic variation on coordination and cost of ambulatory care: investigation of claims data from Bavaria, Germany.

OBJECTIVES: A considerable proportion of regional variation in healthcare use and health expenditures is to date still unexplained. The aim was to investigate regional differences in the gatekeeping role of general practitioners and to identify relevant explanatory variables at patient and district level in Bavaria, Germany. DESIGN: Retrospective routine data analysis using claims data held by the Bavarian Association of Statutory Health Insurance Physicians. PARTICIPANTS: All patients who consulted a specialist in ambulatory practice within the first quarter of 2011 (n=3 616 510). OUTCOMES MEASURES: Of primary interest is the effect of district-level measures of rurality, physician density and multiple deprivation on (1) the proportion of patients with general practitioner (GP) coordination of specialist care and (2) the mean amount in Euros claimed by specialist physicians. RESULTS: The proportion of patients whose use of specialist services was coordinated by a GP was significantly higher in rural areas and in highly deprived regions, as compared with urban and less deprived regions. The hierarchical models revealed that increasing age and the presence of chronic diseases are the strongest predictive factors for coordination by a GP. In contrast, the presence of mental illness, an increasing number of medical condition categories and living in a city are predictors for specialist use without GP coordination. The amount claimed per patient was €10 to €20 higher in urban districts and in regions with lower deprivation. Hierarchical models indicate that this amount is on average higher for patients living in towns and lower for patients in regions with high deprivation. CONCLUSION: The present study shows that regional deprivation is closely associated with the way in which patients access primary and specialist care. This has clear consequences, both with respect to the role of the general practitioner and the financial costs of care.