Search

Manas K Akmatov,* Jakob Holstiege,* Lotte Dammertz, Joachim Heuer, Claudia Kohring, Jörg Bätzing Department of Epidemiology and Health Care Atlas, Central Research Institute of Ambulatory Health Care, Berlin, Germany*These authors contributed equally to this workCorrespondence: Manas K Akmatov; Jakob Holstiege, Tel +49 3040052414 ; +49 3040052467, Fax +49 304005272414 ; +49304005272467, Email makmatov@zi.de; jholstiege@zi.dePurpose: We aimed to examine possible variations in diagnostic prevalence of hay fever between urban and rural regions as well as in age-specific temporal developments.Patients and Methods: We used nationwide outpatient claims data from the years 2010 to 2019. The data contain information for all individuals with statutory health insurance (SHI) in Germany who were treated at least once in respective years (n = 71,410,121 in 2019). Individuals with a confirmed diagnosis of hay fever were defined as prevalent cases. We examined the association between the degree of urbanization and age- and sex-standardized prevalence of hay fever. We used the age- and sex-structure of SHI insurees in the year 2010 as a reference population for direct standardization.Results: The standardized prevalence of hay fever increased from 6.2% in 2010 to 7.2% in 2019, corresponding to a relative increase of 16%. However, we observed a clear decrease in prevalence among children, with the strongest relative reduction in young children (0– 2 years: − 53%). The standardized prevalence in the total population in 2019 was lowest in rural areas with a low population density (6.6%) and highest in big urban municipalities (7.8%). In stark contrast, prevalence in 0– 14-year-olds was lowest in big urban municipalities (4.3%).Conclusion: We observed a decrease in the prevalence of hay fever in children and increase in the older age groups. A clear urban–rural association observed over years may be explained by environmental factors. Deviations from this general regional pattern in children of the age group 0– 14 years may be explained by differing age-specific risk factors of hay fever.Keywords: diagnostic prevalence, hay fever, urban–rural differences, statutory health insurance, temporal trends, Germany

Objective: We aimed to identify spatial clusters of high HIV prevalence in Germany. Methods: Using nationwide outpatient claims data comprising information of about 88% of the total German population (N = 72 041 683), we examined spatial variations and spatial clusters of high HIV prevalence at the district level (N = 401). People with HIV were identified using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD‐10 codes) B20, B22, and B24 (HIV disease) documented as 'confirmed'. Results: Among 72 041 683 people with statutory health insurance in Germany in 2021, 72 636 had diagnosed HIV, which corresponds to a prevalence of 101 per 100 000 individuals (0.10%). Of these, 56 895 were males (78%). At a district level, the HIV prevalence varied by a factor of 32 between 13 in a rural district in Bavaria and 417 per 100 000 individuals in the German capital, Berlin. The spatial autocorrelation coefficient was 0.24 (p < 0.0001, Global Moran's I). Several high‐prevalence spatial clusters of different sizes were identified, mostly located in western Germany. The largest cluster comprised eight districts in the southern part of Hesse, including the city of Frankfurt and the city of Mainz in Rhineland‐Palatinate. The second cluster consisted of four districts in North Rhine‐Westphalia, including the cities of Cologne and Düsseldorf. Two districts in southern Germany (Mannheim and Ludwigshafen) formed the third cluster. Only urban districts were observed in spatial clusters of high HIV prevalence. Conclusions: The current study identified for the first time spatial clusters with high HIV prevalence in Germany. This understanding is of particular importance when planning the general and specialized medical care of patients with HIV and to support preventive measures. [ABSTRACT FROM AUTHOR]

Copyright of Die Dermatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Antibiotic consumption is considered an important risk factor for Clostridioides difficile infection (CDI). This ecological analysis investigates the influence of outpatient antibiotic prescriptions in statutory health insurance (SHI) on the admission prevalence of CDI in German hospitals participating in voluntary CDI surveillance through the hospital infection surveillance system (Krankenhaus-Infektions-Surveillance-System; KISS)., Methods: The annual CDI admission prevalence of a hospital at the federal state level was associated with the outpatient antibiotic consumption of the corresponding federal state. The quantification of outpatient antibiotic prescriptions was determined as the average DDD per 1000 insured persons per day. The risk factors for CDI on hospital admission included the annual consumption of the eight substance groups aminopenicillin combinations/staphylococcal penicillins, basic penicillins, cephalosporins, quinolones, lincosamides/macrolides, nitrofurantoin/fosfomycin/nitroxoline, sulphonamides/trimethoprim and tetracyclines, the type of care provided by the hospital, and the calendar year, and were examined using multivariable regression analyses (generalized estimating equations models)., Results: Between 2011 and 2019, the number of outpatient antibiotic prescriptions decreased from 13.9 to 10.4 DDD per 1000 insured persons per day (-25%), and the CDI admission prevalence decreased from 0.22 to 0.12 per 100 patients (-45%). Basic penicillins and cephalosporins were identified as risk factors for increased CDI admission prevalence, while nitrofurantoin/fosfomycin/nitroxoline and sulphonamides/trimethoprim were associated with decreased CDI admission prevalence., Conclusions: A decrease in outpatient antibiotic prescriptions with known risk of developing CDI was associated with a decrease in hospital CDI admission prevalence. Our ecological analysis indicates that rational and restrained antibiotic use in the outpatient setting may reduce the incidence of CDI in the population requiring inpatient treatment., (© The Author(s) 2025. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Importance: A growing body of literature suggests the presence of a prodromal period with nonspecific signs and symptoms before onset of multiple sclerosis (MS)., Objective: To systematically assess diseases and symptoms diagnosed in the 5 years before a first MS- or central nervous system (CNS) demyelinating disease-related diagnostic code in pediatric patients compared with controls without MS and controls with another immune-mediated disorder, juvenile idiopathic arthritis (JIA)., Design, Setting, and Participants: This population-based, matched case-control study included children and adolescents (aged <18 years) in Germany with statutory health insurance from January 2010 to December 2020. The study population consisted of 3 groups: case individuals with MS, control individuals without MS, and control individuals with JIA. Data were analyzed from November 2023 to April 2024., Exposures: Diagnoses coded according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, German Modification (ICD-10-GM)., Main Outcome and Measures: The main outcome was incident cases of MS, defined as the first confirmed diagnosis of MS (ICD-10-GM code G35) in 1 quarter between 2013 and 2020 and at least 1 additional diagnosis in the following quarters. In total, 163 ICD-10-GM codes before a first MS diagnosis were assessed using univariable and multivariable logistic regression analyses., Results: The study population consisted of 1091 children and adolescents with MS, 10 910 without MS, and 1068 with JIA. Of the children and adolescents with MS, 788 (72.2%) were female. Mean (SD) age at disease diagnosis was 15.7 (1.7) years. Nine ICD-10-GM codes were present more frequently among children and adolescents with MS in the 5 years before their first MS diagnosis than among controls without MS: obesity (adjusted odds ratio [AOR], 1.70; 95% CI, 1.42-2.02), disorders of eye refraction and accommodation (AOR, 1.26; 95% CI, 1.09-1.47), visual disturbances (AOR, 1.31; 95% CI, 1.10-1.55), gastritis and duodenitis (AOR, 1.35; 95% CI, 1.08-1.70), patella disorders (AOR, 1.47; 95% CI, 1.13-1.90), heartbeat abnormalities (AOR, 1.94; 95% CI, 1.27-2.96), flatulence (AOR, 1.43; 95% CI, 1.01-2.01), skin sensation disturbances (AOR, 12.93; 95% CI, 8.98-18.62), as well as dizziness and giddiness (AOR, 1.52; 95% CI, 1.22-1.89). Four of these ICD-10-GM codes were significantly more prevalent in children and adolescents with MS than in controls with JIA: obesity (AOR, 3.19; 95% CI, 2.03-5.02), refraction and accommodation disorders (AOR, 3.08; 95% CI, 2.33-4.08), visual disturbances (AOR, 1.62; 95% CI, 1.13-2.33), and skin sensation disturbances (AOR, 27.70; 95% CI, 6.52-117.64)., Conclusions and Relevance: In this population-based, matched case-control study, children and adolescents with MS had diverse metabolic, ocular, musculoskeletal, gastrointestinal, and cardiovascular symptoms, signs, or diagnoses within 5 years before their first MS diagnosis. Better characterization of early symptoms and/or risk factors, comorbid disorders, and possible prodromal features of MS may have considerable implications for early recognition and subsequent progression of the disease.

Background and Purpose: Idiopathic Parkinson's disease (IPD) is a progressive neurodegenerative disorder that is strongly associated with age. The aim of the present study was to describe current sex- and age-specific trends and regional differences in the incidence of IPD diagnosed in older people in Germany., Methods: This study was based on nationwide outpatient claims and drug prescription data from the German Statutory Health Insurance, covering approximately 87% of the general population. We conducted a cohort study in patients aged 50 years or older with observation time of at least 4 years. To assess the robustness of nationwide annual IPD incidence trends from 2013 to 2019, three case definitions with varying levels of stringency regarding coded outpatient diagnoses and drug prescriptions were applied., Results: In 2019, the population at risk comprised 30,575,726 persons. Using the primary and most specific case definition, annual age- and sex-standardized cumulative IPD incidence decreased stepwise from 137 (2013) to 106 (2019) new cases per 100,000 persons. The decline in incidence was seen in both sexes, in all age groups and in the majority of German regions. The relative decrease (2013-2019) in the annual age- and sex-standardized IPD incidence varied from 23% to 28% among case definitions., Conclusion: Our findings indicate a nationwide decline in the age- and sex-standardized incidence of IPD from 2013 to 2019 in Germany. This trend was consistent using different case definitions. Further research is needed to elucidate the factors underlying this trend., (© 2023 European Academy of Neurology.)

Background: This claims-based study aimed to assess recent nationwide trends in pediatric incidence of atopic diseases in Germany., Methods: Incidence of atopic dermatitis, asthma, and hay fever was assessed from 2013 to 2021 in annual cohorts of 0- to 17-year-old children and adolescents with statutory health insurance (N = 11,828,525 in 2021)., Results: Incidence of atopic dermatitis remained largely unchanged (15.2 cases per 1000 children in 2021) while hay fever incidence exhibited a fluctuating trend over the study period and amounted to 8.8 cases per 1000 in 2021. Asthma incidence decreased gradually between 2013 (12.4/1000) and 2019 (8.9/1000). This downward trend was followed by a further disproportionate reduction from 2019 to 2020 (6.3/1000) and a re-increase in 2021 (7.2/1000)., Conclusion: The findings complement nationwide prevalence surveys of atopic diseases in children and adolescents in Germany. Knowledge about temporal variations in risk of atopic diseases are crucial for future investigations of explanatory factors to enhance the development of preventive measures. While asthma incidence followed a declining trend throughout the study period, an unprecedentedly strong reduction in pediatric asthma risk was observed in 2020, the first year of the COVID-19-pandemic., Competing Interests: The authors reported no financial interests or potential conflicts of interest related to this study., (© 2023 The Author(s).)

Background: Venous thromboembolism (VTE) and arterial thromboembolism (ATE) are considered as two separate disease-entities. In recent years, studies have reported clear associations between VTE and atherosclerosis. We aimed to evaluate the long-term risk of ATE in VTE patients in comparison to controls without VTE., Methods: Nationwide outpatient claims data of all inhabitants with statutory health insurance in Germany were used for secondary data analysis between the years 2011 and 2020. Patients treated in 2013 were stratified by VTE event, and groups were 1:2-matched by age and sex. The hazard for an ATE event in a 5-year follow-up period between patients with and without VTE was calculated with multivariable Cox regression adjusted for age, sex, cardiovascular risk factors, and comorbidities., Results: Of 69,699,277 individuals treated in the year 2013 by German physicians in outpatient care, in total 686,382 individuals (age 59.8 ± 17.5 years, 65.4 % females) were included comprising 228,794 patients with VTE and 457,588 controls without VTE. VTE patients more often had cardiovascular risk factors (81.6 % vs. 62.2 %) and traditional VTE risk factors. The occurrence of ATE events during follow-up was 1.8 %-points higher in VTE patients in comparison to the controls (9.7 % vs. 7.9 %). VTE events were independently associated with increased occurrence of ATE events within follow-up (HR adjusted 1.19 [99%CI 1.16-1.23], p < 0.0001)., Conclusions: Patients with a VTE event have an increased long-term risk for subsequent arterial cardiovascular events. Large prospective cohorts are needed to identify patient subgroups with a very high ATE risk after VTE., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Karsten Keller reports no conflict of interests. Claudia Kohring reports no conflict of interests. Ioannis T. Farmakis reports no conflict of interests. Luca Valerio reports no conflict of interests. Stefano Barco received lecture/consultant fees from Bayer HealthCare, Concept Medical, BTG Pharmaceuticals, INARI, Boston Scientific, and LeoPharma; institutional grants from Boston Scientific, Bentley, Bayer HealthCare, INARI, Medtronic, Concept Medical, Bard, and Sanofi; and economical support for travel/congress costs from Daiichi Sankyo, BTG Pharmaceuticals, and Bayer HealthCare, outside the submitted work. Jörg Bätzing reports no conflict of interests. Manas K. Akmatov reports no conflict of interests. Stavros Konstantinides reports institutional grants and personal lecture/advisory fees from Bayer AG, Daiichi Sankyo, and Boston Scientific; institutional grants from Inari Medical; and personal lecture/advisory fees from MSD and Bristol Myers Squibb/Pfizer. Thomas Münzel reports no conflict of interests. TM is PI of the DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Mainz, Germany. Lukas Hobohm received lecture/consultant fees from MSD and Actelion, outside the submitted work. Jakob Holstiege reports no conflict of interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Importance: The prodromal phase of Parkinson disease (PD) may last for more than 10 years. Recognition of the spectrum and occurrence of risk factors, comorbidities, and prodromal features of PD can increase understanding of the causes and development of the disease and help identify individuals at risk., Objective: To identify the association of a subsequent diagnosis of PD with a range of risk factors and prodromal features, including lifestyle factors, comorbidities, and potential extracerebral manifestations of PD., Design, Setting, and Participants: This was a case-control study using insurance claims of outpatient consultations of patients with German statutory health insurance between January 1, 2011, and December 31, 2020. Included were patients with incident diagnosis of PD without a previous diagnosis of parkinsonism or dementia and controls matched 1:2 for age, sex, region, and earliest year of outpatient encounter., Exposures: Exposures were selected based on previous systematic reviews, case-control and cohort studies reporting on risk factors, comorbidities, and prodromal features of PD., Main Outcomes and Measures: Previously postulated risk factors and prodromal features of PD, using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) coding., Results: A total of 138 345 patients with incident PD (mean [SD] age, 75.1 [9.8] years; 73 720 male [53.3%]) and 276 690 matched controls (mean [SD] age, 75.1 (9.8) years; 147 440 male [53.3%]) were identified. Study participants were followed up for a mean (SD) of 6.0 (2.0) years. Consistent with previous reports, risk factors and prodromal features associated with PD included traumatic brain injury, odds ratio (OR), 1.62; 95% CI, 1.36-1.92; alcohol misuse, OR, 1.32; 95% CI, 1.21-1.44; hypertension, OR, 1.29; 95% CI, 1.26-1.31; anosmia, OR, 2.16; 95% CI, 1.59-2.93; and parasomnias (including RBD), OR, 1.62; 95% CI, 1.42-1.84. In addition, there were associations with restless legs syndrome (OR, 4.19; 95% CI, 3.91-4.50), sleep apnea (OR, 1.45; 95% CI, 1.37-1.54), epilepsy (OR, 2.26; 95% CI, 2.07-2.46), migraine (OR, 1.21; 95% CI, 1.12-1.29), bipolar disorder (OR, 3.81; 95% CI, 3.11-4.67), and schizophrenia (OR, 4.48; 95% CI, 3.82-5.25). The following diagnoses were also found to be associated with PD: sensory impairments beyond anosmia, such as hearing loss (OR, 1.14; 95% CI, 1.09-1.20) and changes of skin sensation (OR, 1.31; 95% CI, 1.21-1.43). There were also positive associations with skin disorders (eg, seborrheic dermatitis, OR, 1.30; 95% CI, 1.15-1.46; psoriasis, OR, 1.13; 95% CI, 1.05-1.21), gastrointestinal disorders (eg, gastroesophageal reflux, OR, 1.29; 95% CI, 1.25-1.33; gastritis, OR, 1.28; 95% CI, 1.24-1.33), conditions with a potential inflammatory component (eg, seronegative osteoarthritis, OR, 1.21; 95% CI, 1.03-1.43), and diabetes types 1 (OR, 1.32; 95% CI, 1.21-1.43) and 2 (OR, 1.24; 95% CI, 1.20-1.27). Associations even 5 to 10 years before diagnosis included tremor (odds ratio [OR], 4.49; 95% CI, 3.98-5.06), restless legs syndrome (OR, 3.73; 95% CI, 3.39-4.09), bipolar disorder (OR, 3.80; 95% CI, 2.82-5.14), and schizophrenia (OR, 4.00; 95% CI, 3.31-4.85)., Conclusions and Relevance: Results of this case-control study suggest that the associations found between PD and certain risk factors, comorbidities, and prodromal symptoms in a representative population may reflect possible early extrastriatal and extracerebral pathology of PD. This may be due to shared genetic risk with PD, medication exposure, or direct causation, or represent pathophysiologically relevant factors contributing to the pathogenesis of PD.

The aim of the study was to examine whether the COVID-19 pandemic had any effect on antibiotic prescription rates in children in Germany. Using the nationwide outpatient prescription data from the Statutory Health Insurance from 2010 to 2021, changes in the monthly prescriptions of systemic antibiotics dispensed to children aged 0-14 years were examined ( n = 9,688,483 in 2021). Interrupted time series analysis was used to assess the effect of mitigation measures against SARS-COV-2, introduced in March and November 2020, on antibiotic prescription rates. In the pre-pandemic period, the antibiotic prescription rates displayed a linear decrease from 2010 to 2019 (mean annual decrease, -6%). In 2020, an immediate effect of mitigation measures on prescription rates was observed; in particular, the rate decreased steeply in April (RR 0.24, 95% CI: 0.14-0.41) and November 2020 (0.44, 0.27-0.73). The decrease was observed in all ages and for all antibiotic subgroups. However, this effect was temporary. Regionally, prescription rates were highly correlated between 2019 and 2020/2021. Substantial reductions in antibiotic prescription rates following the mitigation measures may indicate limited access to medical care, changes in care-seeking behavior and/or a decrease of respiratory infections. Despite an all-time low of antibiotic use, regional variations remained high and strongly correlated with pre-pandemic levels., Competing Interests: The authors declare no conflicts of interest.

IntroductionEvidence of nationwide and regional morbidity of Lyme borreliosis (LB) in Germany is lacking.AimsWe calculated the total number of incident LB cases in Germany in 2019, compared regional variations, investigated the extent of possible under-reporting in notification data and examined the association between high incidence areas and land cover composition.MethodsWe used outpatient claims data comprising information for people with statutory health insurance who visited a physician at least once between 2010 and 2019 in Germany (n = 71,411,504). The ICD-10 code A69.2 was used to identify incident LB patients. Spatial variations of LB were assessed by means of Global and Local Moran's Index at district level. Notification data were obtained for nine federal states with mandatory notification from the Robert Koch Institute (RKI).ResultsOf all insured, 128,177 were diagnosed with LB in 2019, corresponding to an incidence of 179 per 100,000 insured. The incidence varied across districts by a factor of 16 (range: 40-646 per 100,000). We identified four spatial clusters with high incidences. These clusters were associated with a significantly larger proportion of forests and agricultural areas than low incidence clusters. In 2019, 12,264 LB cases were reported to the RKI from nine federal states, while 69,623 patients with LB were found in claims data for those states. This difference varied considerably across districts.ConclusionsThese findings serve as a solid basis for regionally tailored population-based intervention programmes and can support modelling studies assessing the development of LB epidemiology under various climate change scenarios.

Background: This study aimed to describe recent developments of multiple sclerosis (MS) prevalence in Germany and to assess utilization patterns of disease-modifying drugs (DMDs)., Methods: We used nationwide outpatient claims data of the statutory health insurance (SHI) from the years 2012 to 2019, covering 87% of the total German population. In annual cross-sectional analyses, MS prevalence was measured as the percentage of the SHI population affected by MS. Annual agent-specific prescription prevalence of DMDs was calculated by the number of patients receiving the DMD per 1.000 MS patients., Results: From 2012 to 2019, the prevalence of MS increased gradually from 0.27% to 0.34%. The overall DMD prescription prevalence in MS patients rose from 436 per 1,000 MS patients (2012) to 483 (2019). From 2012 to 2019 the prescription prevalence of interferon-beta 1a and interferon-beta 1b decreased sharply from 180.2 to 70.8 (-61%) and 80.2 to 34.1 (-57%), respectively. In contrast, the prescription prevalence of teriflunomide (2012: 8.5; 2019: 54.5) and fingolimod (2012: 28.5; 2019: 63.8) exhibited a pronounced increase by factors of 5.4 and 2.2, respectively., Conclusion: MS prevalence in Germany steadily increased in recent years. MS treatment patterns changed markedly indicating a shifting predominance of DMD injectable drugs to oral medications., (Copyright © 2022. Published by Elsevier B.V.)

Background: The manifestation of multiple sclerosis (MS) in childhood and adolescence occurs in 3%-5% of all MS cases. However, the immunomodulatory and symptomatic treatment options in this population group are still limited., Objective: We aimed to elucidate the prescription frequency of medications used in pediatric patients with multiple sclerosis (PwMS) compared with the general population, considering the entire spectrum of medications prescribed., Methods: Based on nationwide outpatient drug prescription data and statutory health insurance (SHI) physicians' claims data from 2018, we conducted a population-based cross-sectional study in Germany. Children and adolescents aged ⩽17 years ( n  = 11,381,939) diagnosed with MS ( n  = 613), and a matched (age, sex, and health insurance sector) control group ( n  = 6130) were included. The prescription prevalence was measured as the proportion of MS patients with ⩾1 prescription., Results: Of the 613 pediatric PwMS with a median age of 16 years, 403 (65.7%) were female. For 15 out of the 18 different active agents analyzed, PwMS had a significantly higher prescription prevalence than the control group (Fisher's exact test: p  ⩽ 0.037). The most frequently prescribed drugs in PwMS were ibuprofen (28.4%; anti-inflammatory drug), cholecalciferol (23.0%; vitamin D3), and interferon beta-1a (21.5%; disease-modifying drug, DMD). The proportions of DMD prescriptions and antibiotic prescriptions were higher among PwMS aged 15-17 years than among those ⩽14 years (DMD: 43.4% vs 34.2%, p  = 0.05; antibiotic: 34.1% vs 24.8%, p  = 0.031). In contrast, younger PwMS were more likely to receive a prescription for anti-inflammatory/anti-rheumatic drugs (36.6% vs 26.5%, p  = 0.02)., Conclusion: Our study analyzing real-world medication data showed that interferon beta, anti-inflammatory drugs, and vitamins play an essential role in the treatment of pediatric PwMS. Future research should evaluate longitudinal treatment patterns of pediatric PwMS, paying particular attention to the time of diagnosis, time of first DMD initiation, and therapy switches., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.B., Ja.Ho., Ju.Ha., and M.K.A. declare no competing interests. D.E., M.P. had no personal financial interests to disclose other than being employees of the German MS Registry funded by many public and corporate sponsors. N.F. is an employee of the MSFP. Moreover, NF is an employee of the University Medical Center Rostock and received travel funds for research meetings from Novartis. None resulted in a conflict of interest. P.S.R. has received speaking fees, honoraria from advisory boards, and financial support for research activities from AbbVie, Alexion, Almirall, Amicus, Biogen, Celgene, Daiichi-Sankyo, Merck Serono, Novartis, Roche, Sandoz, Sanofi Genzyme, and Teva. None resulted in a conflict of interest. AS has no personal financial interests to disclose, other than being the leader of the German MS Registry, which receives funding from a range of public and corporate sponsors, recently including The German Innovation Fund (G-BA), The German MS Trust, German MS Society, Biogen, Celgene (Bristol Myers Squibb), Merck, Novartis, Roche, and Sanofi. None resulted in a conflict of interest. U.K.Z. has received speaking fees, travel support, and financial support for research activities from Alexion, Almirall, Bayer, Biogen, Janssen, Merck Serono, Novartis, Octapharm, Roche, Sanofi Genzyme, Teva, as well as EU, BMBF, BMWi, and DFG. None resulted in a conflict of interest., (© The Author(s), 2021.)

Background: Research has shown that the risk for a severe course of COVID-19 is increased in the elderly population and among patients with chronic conditions. The aim of this study was to provide estimates of the size of vulnerable populations at high risk for a severe COVID-19 course in Germany based on the currently available risk factor data., Methods: We used nationwide outpatient claims data from the years 2010 to 2019 collected according to § 295 of the Code of Social Law V, covering data for all statutory health insurees (SHI) which is nearly 87% of the entire German population. We considered 15 chronic disorders based on the current state of knowledge about clinically relevant risk factors. Three risk groups for a severe COVID-19 course were defined: 1. individuals in the age group 15 to 59 years with at least two comorbid disorders; 2. individuals aged 60 to 79 years with at least one disorder and 3. all individuals 80 years and older irrespective of the presence of chronic conditions. Regional analysis was conducted at the level of administrative districts (n = 401)., Results: Overall, 26% of individuals over 15 years were at high risk for a severe COVID-19 course in 2019 amounting to a total number of nearly 18.5 million individuals in Germany. This included 3.8 million individuals in risk group 1, 9.2 million in risk group 2, and 5.4 million in risk group 3, corresponding to 8, 50 and 100% of German inhabitants in the respective age groups. On the level of the 17 administrative regions formed by the Association of SHI Physicians (ASHIP regions), the proportion of individuals at high risk ranged between 21% in Hamburg and 35% in Saxony-Anhalt. Small-area estimates varied between 18% in Freiburg (Baden-Württemberg) and 39% in the district Elbe-Elster (Brandenburg)., Conclusions: The present study provides small-area estimates of populations at high risk for a severe COVID-19 course. These data are of particular importance for planning of preventive measures such as vaccination., Trial Registration: not applicable., (© 2021. The Author(s).)

Background and Purpose: Prevalence data are needed to reveal trends regarding the pediatric multiple sclerosis (MS) situation worldwide. The aim was to identify changes in MS diagnosis prevalence in pediatric patients over a 10-year period in Germany., Methods: This analysis is based on nationwide outpatient claims data of children aged <18 years covered by the German statutory health insurance (n = 11,381,939 in 2018). People with MS (PwMS) had ≥1 documented MS diagnosis (International Classification of Diseases, 10th Revision, German modification code G35.x). The annual pediatric MS diagnosis prevalence was analyzed regarding age, sex, and place of residence during 2009-2018., Results: The prevalence of pediatric MS developed from 5.3 (2009) to 5.4 (2018)/100,000 insured population aged <18 years. The MS prevalence in patients aged 15-17 years showed a moderate increase over 10 years (19.6-22.7/100,000), whereas patients ≤14 years old showed a slight decrease (1.9-1.7/100,000). The sex ratio (female:male) in 2018 was relatively balanced in PwMS aged ≤14 years (1.32) but female-dominated in those aged 15-17 years (2.47). The formerly different prevalence of pediatric MS between East and West Germany has converged since 2012., Conclusions: So far, this is the largest study of pediatric MS prevalence in terms of source population size (87% of German children <18 years of age, n = 11,381,939 in 2018) and study period (2009-2018) worldwide. The analyses revealed an increase in MS prevalence and a female-dominated sex ratio in "older" adolescents compared to younger patients., (© 2021 European Academy of Neurology.)

Background: The study aim was to examine the secular trends and regional variations in pharmacotherapy of children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in Germany., Methods: We used nationwide drug prescription data of outpatient care (2009 to 2016). The study population comprised patients aged between 5 and 14 years with the diagnoses "hyperkinetic disorders" (ICD-10 code F90) (e.g. n = 262,766 in 2016). The examined drugs were methylphenidate, amphetamines, atomoxetine and guanfacine., Results: Overall, the proportion of patients received any prescription showed a decreasing trend over years (2010, 51%; 2016, 44%). The proportion of methylphenidate prescription was higher in Western than Eastern federal states. However, atomoxetine was more often prescribed in Eastern than Western federal states. The proportion of methylphenidate prescriptions issued by pediatric psychiatrists increased from 28% (2009) to 41% (2016)., Conclusion: A decreasing trend in use of pharmacotherapy may be explained by prescription restrictions issued by the Federal Joint Committee in recent years., (© 2021. The Author(s).)

As a condition, diabetes mellitus is associated with risk factors and diseases such as obesity. At the same time, cardiovascular diseases are a frequent consequence of diabetes. There have yet to be any findings on the Germany-wide prevalence of diabetes and diabetes comorbidities based on statutory health insurance data. This study estimates the documented prevalence of diabetes in 2019 on the basis of all ambulatory physicians' claims data of German statutory health insurance. In addition, the prevalence of obesity, high blood pressure, coronary heart disease, heart failure, stroke and depression is calculated for diabetes and non-diabetes patients, and the prevalence ratio (PR) is determined as a quotient. The approach used was a case-control design, which assigns a control person without diabetes to each diabetes patient who is similar in terms of age, region and sex. In diabetes patients, a PR greater than 1 was observed for all examined diseases across all age groups, thus demonstrating a higher prevalence compared to persons without diabetes. The highest PR across all age groups for women (3.8) and men (3.7) was found for obesity. In a comparison over time, documented prevalence figures of diabetes in Germany stagnate. With the exception of depression, the documented prevalences of comorbidities correspond well with the prevalences found in population-wide examination surveys., Competing Interests: Conflicts of interest The authors declared no conflicts of interest., (© Robert Koch Institute. All rights reserved unless explicitly granted.)

Objective: This study examined the full spectrum of comorbid disorders in all statutory-health-insured children aged 5 to 14 years with ADHD in 2017 by using nationwide claims data in Germany. Method: Children with ADHD ( n = 258,662) were compared for the presence of 864 comorbid diseases with a control group matched by gender, age, and region of residence ( n = 2,327,958). Results: Among others, metabolic disorders (odds ratio [OR] = 9.18; 95% confidence interval [CI] = [8.43, 9.99]), viral pneumonia (OR = 4.95; 95% CI = [2.37, 10.33]), disorders of white blood cells (OR = 4.55; 95% CI = [3.83, 5.40]), kidney failure (OR = 3.33; 95% CI = [2.65, 4.18]), hypertension (OR = 3.26; 95% CI = [3.00, 3.55]), obesity (OR = 2.85; 95% CI = [2.80, 2.91]), type 2 diabetes (OR = 2.61; 95% CI = [2.11, 3.23]), migraine (OR = 2.49; 95% CI = [2.37, 2.61]), asthma (OR = 2.19; 95% CI = [2.16, 2.22]), atopic dermatitis (OR = 2.10; 95% CI = [2.16, 2.23]), juvenile arthritis (OR = 1.56; 95% CI = [1.39, 1.76]), glaucoma (OR = 1.51; 95% CI = [1.30, 1.75]), and type 1 diabetes (OR = 1.30; 95% CI = [1.20, 1.40]) were more likely to be diagnosed in ADHD children. Conclusion: Along with psychiatric diseases, various somatic diseases were more common in ADHD children. The results have direct implications for patient care, including fine-grained diagnostics and personalized therapy.

Background: Individuals with chronic diseases have a higher risk of serious complications or even death in case of influenza infection. The European Union (EU) set a goal to reach a vaccination coverage of 75% in seniors and chronically ill individuals. The aim of this study was to assess influenza vaccination uptake among individuals with a wide spectrum of chronic diseases and examine its regional variations and temporal trends over a period of the last ten years., Methods: We used nationwide SHI-physician outpatient claims data from the years 2009 to 2018 covering 87% of the total German population to assess influenza vaccination uptake among individuals over 1 year of age with at least one of the following chronic diseases: pulmonary, cardiovascular, liver, kidney, metabolic, neurological and musculoskeletal diseases, as well as immune deficiency disorders, including HIV infection., Results: Influenza vaccination coverage varied across patient populations between 19% (multiple sclerosis) and 44% (chronic kidney disease) in the influenza season 2017/18. Vaccination coverage was slightly higher among females than males, except for HIV/AIDS patients. Among HIV-patients vaccination coverage was higher by 7 percent points among males (43%) than females (37%). The coverage was higher nearly for all patient groups in the eastern than western federal states. Over the observation period vaccination uptake showed decreasing trends in most of the target groups. Among patients with HIV/AIDS and immune deficiency disorders a stagnating trend was observed., Conclusions: Vaccination uptake among chronically ill individuals is suboptimal and far from the EU-defined target of 75%. There were substantial variations in coverage by disease groups, individual factors and regions. The disease-specific evaluation of the current study allows identification of populations at higher risk with considerable vaccination gaps. Further efforts are needed to improve vaccination uptake in these vulnerable population groups., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction:  In this article, the prevalence of the Morbus Wilson disease in Germany is determined. This is based on nationwide data of drug prescriptions and contractional data of outpatient offices. The prevalence is set in ratio to the found prevalence of prescriptions in Germany., Method:  The descriptive evaluation is based on the database of the Central Research Institute of Ambulatory Health Care (Zi) in Germany. Additionally, data of the Federal Office of Statistics regarding inpatient treatment are available., Results:  It can be seen that there is a notable difference between the prevalence of patients undergoing therapy and the patients with verified diagnoses. In total, prevalence is increasing. The incidence on hand and the given dynamic of the patient population could indicate that, possibly, there is an increased rate of misdiagnosis in the first year of diagnosis. According to data, the hepatic form is the more often diagnosed form. The human genetic diagnostic increases, on average, are most distinct., Attributes:  Wilson Disease, Prevalence, Incidence, Trientine, Trientintetrahydrochlorid, D-Penicillamin, Zinc acetat, Zinc., Competing Interests: KHW ist in beratender oder sprechender Tätigkeit für Alexion, Univar BV, GMP-orphan, Vivet therapeutics, Ultragenyx, Eisai, Chiesi, Novartis, Bayer tätig., (Thieme. All rights reserved.)

The aim of this study was to estimate the prevalence of concurrent diagnoses of asthma/COPD and examine its full spectrum of comorbid disorders in Germany. We used nationwide outpatient claims data comprising diagnoses of all statutory health insurees (40+ years) in 2017 (N = 40,477,745). The ICD-10 codes J44 (COPD) and J45 (asthma) were used to identify patients. The odds of 1,060 comorbid disorders were examined in a case-control study design. Of all insurees, 4,632,295 (11%) were diagnosed with either asthma or COPD. Of them, 43% had asthma only, 44% COPD only and 13% both diseases. The prevalence of concurrent asthma/COPD was 1.5% with a slightly higher estimate among females than males (1.6% vs. 1.4%) and constant increase by age in both sexes. Comorbid disorders were very common among these patients. 31 disorders were associated with a strong effect size (odds ratio > 10), including other respiratory diseases, but also bacterial (e.g., mycobacteria, including tuberculosis) and fungal infections (e.g., sporotrichosis and aspergillosis). Patients with concurrent asthma/COPD suffer from comorbid disorders involving various body systems, which points to the need of a multidisciplinary care approach. Regular screening for common comorbid disorders may result in better clinical course and prognosis as well as improvement of patients' quality of life.

Background: A central component of the German antibiotic resistance strategy is to monitor the outpatient prescribing of systemic antibiotics nationwide, across all of the statutory health-insurance providers, in order to provide a basis for targeted quality-assurance measures., Methods: All outpatient drug prescription data from patients covered by the statutory health-insurance carriers in Germany in the age groups 0-14, 15-64, and ≥ 65 years were assessed. The chosen primary outcome measure under study was the prescription rate (number of antibiotic prescriptions per 1000 insurees per year) for the years 2010 to 2018., Results: Over the period of the study, a 21% decline was seen in the use of systemic antibiotics in outpatients, from 562 to 446 prescriptions per 1000 insurees per year in 2010 and 2018, respectively. The most marked reduction in the prescription rate-by 41%-was seen among child and adolescent insurees (in other age groups: -17% among those aged 15-64, -12% among those aged 65 and older). A downward trend was seen in all regions of Germany, and for most of the active substance groups for which data were obtained. In 2018, the prescription rate varied by a factor of 1.8 among regions, with the highest rate in the Saarland (572 per 1000 insurees per year) and the lowest in Brandenburg (318 per 1000 insurees per year)., Conclusion: The observed nationwide decline in the prescription of antibiotics to outpatients in all age groups may be a result of the numerous initiatives that have been put into action to reinforce the appropriate use of antibiotics in Germany. A change in pediatric prescribing practices is demonstrated by the marked reduction in this age group. The remaining major differences across German regions underscore the importance of regionally tailored programs for the promotion of rational antibiotic use.

Background: Estimating the number of persons tested for HIV in Germany is challenging. HIV testing can be reimbursed by statutory health insurance (SHI) under certain circumstances. This study aimed to use SHI physician claims data to determine the number of persons tested in the outpatient sector., Methods: The Central Research Institute for Ambulatory Health Care in Germany (Zi) aggregated a dataset of persons tested for HIV among all SHI insurees. Descriptive analysis differentiated between screening and confirmatory HIV tests. Time trends were explored using linear regression. Insurees with confirmatory tests were compared to newly diagnosed HIV (ndHIV) cases., Results: Between 2010 and 2015, 1.7% of insurees were annually screened by SHI physicians. Screening tests increased significantly between 2010 and 2015. Among persons screened, 82.5% were women and of those 81.2% had a screening test during pregnancy. Confirmatory tests were performed on 16,034 insurees (0.3% with screening test; 51.2% men). A total of 18,446 (82.8% men) ndHIV cases were notified between 2010 and 2015., Conclusions: For the first time, the number of persons with HIV tests in the SHI sector was estimated. The high number of screened women is due to tests during pregnancy. The higher number of ndHIV cases indicates an unknown number of persons tested at other testing sites.

BackgroundPrescribing of systemic antibiotics in general and of cephalosporins in particular in German paediatric outpatients has previously been reported to be higher than in other European countries.AimOur objective was to assess recent trends in antibiotic prescribing in German children.MethodsThis study was conducted as consecutive annual cross-sectional analyses and included all children aged 0-14 years (n = 9,389,183 in 2018) covered by statutory health insurance in Germany. Annual antibiotic prescription rates from 2010 to 2018 were calculated for the age groups 0-1, 2-5, 6-9 and 10-14 years. Poisson regression was used to estimate trends of prescription rates by age group and antibiotic subgroup.ResultsOverall, the age-standardised antibiotic prescription rate decreased significantly by 43% from 746 prescriptions per 1,000 persons in 2010 to 428 per 1,000 in 2018 (p < 0.001). Reductions were most pronounced in the age groups 0-1 year (-50%) and 2-5 years (-44%). The age group 2-5 years exhibited the highest prescription rate with 683 per 1,000 in 2018 (0-1 year: 320/1,000; 6-9 years: 417/1,000; 10-14 years: 273/1,000). Cephalosporins (second and third generation) accounted for 32% of prescribed antibiotics.ConclusionsMarked reductions in antibiotic prescribing during the last decade indicate a change towards more judicious paediatric prescribing habits. Compared with other European countries, however, prescribing of second- and third-generation cephalosporins remains high in Germany, suggesting frequent first-line use of these substances for common respiratory infections. Considerable regional variations underline the need for regionally targeted interventions.

Background: Studies based on health insurance funds unanimously indicate a rise in administrative prevalence of depression, while population surveys with standardized diagnostic procedures do not. We describe recent trends in the prevalence of depressive disorders as diagnosed in routine care from 2009-2017 in Germany., Methods: We used nationwide ambulatory claims data from all residents with statutory health insurance, covering 87% of the total population. Cases were defined as persons with at least one documented diagnosis of depression (ICD-10-GM codes: F32, F33 or F34.1). The administrative prevalence was computed for each year according to age, sex, degree of urbanization and severity of depression diagnosis., Results: The prevalence increased from 12.5% in 2009 to 15.7% in 2017 (+26%). Overall, women were twice as likely as men to receive a diagnosis, although the prevalence increased more strongly in men compared to women (+40% vs. +20%). Age- and sex-stratified analyses revealed the highest prevalence increase in adolescents and young men at the ages of 15-19 years (+95%) and 20-25 years (+72%). Rural areas with a low population density showed the highest rise in administrative prevalence (+34%), while big urban municipalities showed the lowest (+25%)., Limitations: Administrative claims data rely on diagnoses coded for billing purposes and thus depend on coding practice as well as patients' help seeking behavior., Conclusions: Depressive disorders are of increasing importance in ambulatory health care in Germany. Parts of the increase may be attributed to changing cultural constructions of mental health along with the expansion of mental health care supply., Competing Interests: Declaration of Competing Interests The authors declare that they have no competing interests., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Depression is frequently accompanied by other mental disorders and various somatic diseases; however, previous comorbidity studies often relied on self-reported data and have not simultaneously assessed the entire spectrum of mental and somatic diagnoses. The aim is to provide a complete picture of mental and somatic comorbidity of depression in routine outpatient care in a high income country with a relatively well equipped health care system., Methods: Using ambulatory claims data covering 87% of the German population (age 15+), we designed a cross-sectional study by identifying persons diagnosed with mild, moderate and severe depression in 2017 (N = 6.3 million) and a control group matched 4:1 on sex, 5-year age group and region of residence (N = 25.2 million). Stratified by severity, we calculated the prevalence of 202 diagnosis groups included in the ICD-10 in persons with depression as compared to matched controls using prevalence ratios (PR)., Results: Nearly all mental disorders were at least twice as prevalent in persons with depression relative to controls, showing a dose-response relationship with depression severity. Irrespective of severity, the three most prevalent somatic comorbid diagnosis groups were 'other dorsopathies' (M50-M54), 'hypertensive diseases' (I10-I15) and 'metabolic disorders' (E70-E90), exhibiting PRs in moderate depression of 1.56, 1.23 and 1.33, respectively. Strong associations were revealed with diseases of the central nervous system (i.e. multiple sclerosis) and several neurological diseases, among them sleep disorders, migraine and epilepsy, most of them exhibiting at least 2- to 3-fold higher prevalences in depression relative to controls. Utilization of health care was higher among depression cases compared to controls., Conclusions: The present study based on data from nearly the complete adolescent and adult population in Germany comprehensively illustrates the comorbidity status of persons diagnosed with depression as coded in routine health care. Our study should contribute to increasing the awareness of the strong interconnection of depression with all other mental and the vast majority of somatic diseases. Our findings underscore clinical and health-economic relevance and the necessity of systematically addressing the high comorbidity of depression and somatic as well as other mental diseases through prevention, early identification and adequate management of depressive symptoms.

Objective: To investigate asthma morbidity in Germany by calculating current prevalence, examining its temporal and spatial trends and estimating the total number of asthmatics in Germany and calculating age-, sex- and residence-specific risk., Methods: We used claims data reported by physicians during 2009-2016, including outpatient diagnoses of all statutory health insured individuals, comprising 85.3% (70 416 019/82 521 653) of the total population in Germany in 2016. We performed a spatial analysis of asthma prevalence according to administrative district by calculating Global and Local Moran's  I . We assessed the risk of asthma by sex, age, type of residence (rural versus urban) and federal state (East versus West) using a multilevel parametric survival regression., Findings: We estimated that 4.7 million individuals were affected by asthma in 2016, including 0.8 million children and 3.9 million adults. We observed a slightly higher prevalence (with an increasing trend) among adults (5.85%; 3 408 622/58 246 299) compared to children (5.13%; 624 899/12 169 720), and calculated an age-standardized prevalence of 5.76% (95% confidence interval, CI: 5.76-5.77). We found evidence of a strong spatial autocorrelation (Global Moran's  I : 0.50, P  < 0.0001), and identified local spatial clusters with higher levels of prevalence. Living in the western (versus eastern) federal states and living in densely populated large urban municipalities (versus rural area) were independently associated with an increased risk of asthma, with hazard ratios of 1.33 (95% CI: 1.32-1.34) and 1.32 (95% CI: 1.31-1.32), respectively., Conclusion: Our insights into the spatial distribution of asthma morbidity may inform public health interventions, including region-specific prevention programmes and control., ((c) 2020 The authors; licensee World Health Organization.)

Background: So far the extent of regional variation of heart failure (HF) prevalence in Germany is unknown., Methods: Using a full sample of nationwide claims data covering ambulatory care of approximately 87% of the German population, this study aimed to (i) examine regional differences of HF prevalence on the level of 402 German administrative districts and (ii) investigate factors associated with HF prevalence. This study included all statutory health-insured patients aged ≥ 40 years in 2017, comprising about 40 million individuals. Age- and sex-standardized HF prevalence was estimated on the district level. Two-level logistic regression analysis was employed to study the influence of the district-related factors degree of urbanisation and regional socio-economic status on HF diagnosis, adjusted for the individual's age and sex., Results: HF prevalence in 2017 was 6.0%. Standardized prevalence on the district level varied by a factor of 4.3 (range 2.8-11.9%). Regional socio-economic status and degree of urbanisation were independently associated with HF prevalence. The prevalence increased with decreasing degree of urbanisation. The adjusted risk of suffering from HF was 40% higher in 'rural areas with a low population density' as compared to 'big urban municipalities' (odds ratio 1.40, 99% CI 1.24-1.59)., Conclusion: Strong regional variations in HF prevalence may inform future public health policies regarding targeted resource planning and prevention strategies. High prevalence in areas with low population density adds to the challenge of ensuring universal access to health services in rural German regions.

This study aimed at providing a current and nearly complete picture of the patterns of the initiation of disease-modifying antirheumatic drugs (DMARDs) in patients with newly diagnosed RA. Based on ambulatory drug prescription data and physician billing claims data covering 87% of the German population, we assembled a cohort of incident RA patients aged 15-79 years (n = 54,896) and assessed the prescription frequency of total DMARDs, conventional synthetic (csDMARDs) and biologic DMARDs (bDMARDs) within the first year of disease. Using multiple logistic regression, we estimated the chance of early DMARD receipt based on age, sex, serotype and specialty of prescribing physician while controlling for region of residence. In total, 44% of incident RA patients received a DMARD prescription within the first year of disease. In multiple regression, younger patients (< 35 years) had 1.7-fold higher chances of receiving a csDMARD than patients aged ≥ 65 years [odds ratio (OR): 1.65 with 95% confidence interval (CI) 1.51-1.80] and almost tenfold higher chances to receive a bDMARD [OR (95% CI) 9.5 (8.0-11.3)]. Seropositivity and a visit to a rheumatologist were positively associated with DMARD initiation [OR (95% CI) 2.8 (2.6-2.9) and 5.9 (5.6-6.2) for csDMARDs, respectively]. Based on data covering 87% of the German population, the present study revealed that less than half of incident RA patients receive DMARDs within the first year of disease and that marked differences exist according to age. The study highlights the importance of involving a rheumatologist early in the management of RA.