Updated Multiple Sclerosis Incidence, 2015-2022.

This cohort study uses population-based claims data to provide an update of multiple sclerosis incidence in Germany.

The Incidence of Endometriosis, 2014­2022. An Analysis of Nationwide Claims Data From Physicians in Private Practice.

BACKGROUND: The epidemiological characterization of endometriosis, particularly with regard to its incidence, has been inadequate to date both in Germany and other countries. The goal of this study was to determine trends in the incidence of diagnosed endometriosis and changes in age structure at the time of first diagnosis over the period 2014-2022. METHODS: Nationwide claims data from physicians in private practice, obtained according to relevant German law (§ 295 SGB V), were used to identify the population at risk for a first assured diagnosis of endometriosis (ICD-10-GM: N80) during each year of the study period, consisting of women and girls aged 10-52 who were insured by the statutory health insurance system and for whom at least two years of prior observation were possible. Patients were defined as incident if they were documented as having received a first confirmed diagnosis of endometriosis, according to the case definition, during the study year. The case definition comprised multiple options for validating the diagnosis. RESULTS: The incidence of diagnosed endometriosis rose over the period of the study from 2.8 per 1000 persons at risk in 2014 to 4.1 per 1000 in 2022, corresponding to a 44% relative increase. There was also a marked shift in age-specific incidence toward higher values at younger ages: the median age at diagnosis fell from 37 years (2014) to 34 (2022). CONCLUSION: This is the first study providing nationwide population-based data on the incidence of endometriosis in Germany. The observed rise in newly diagnosed cases is presumably mainly due to an increased awareness of endometriosis and to the growing recognition of the disease.

Trends and projections of age-appropriate vaccination coverage in 41 low- and middle- income countries in Asia and Sub-Saharan Africa, 2000-2030.

Introduction: Routine immunization programs have focused on increasing vaccination coverage, which is equally important for decreasing vaccine-preventable diseases (VPDs), particularly in low- and lower-middle-income countries (LMICs). We estimated the trends and projections of age-appropriate vaccination coverage at the regional and national levels, as well as place of residence and wealth index in LMICs. Methods: In total, 174 nationally representative household surveys from 2000 to 2020 from 41 LMICs were included in this study. Bayesian hierarchical regression models were used to estimate trends and projections of age-appropriate vaccination. Results: The trend in coverage of age-appropriate Bacillus Calmette-Guérin (BCG), third dose of diphtheria, tetanus, and pertussis (DTP3), third dose of polio (polio3), and measles-containing vaccine (MCV) increased rapidly from 2000 to 2020 in LMICs. Findings indicate substantial increases at the regional and national levels, and by area of residence and socioeconomic status between 2000 and 2030. The largest rise was observed in East Africa, followed by South and Southeast Asia. However, out of the 41 countries, only 10 countries are estimated to achieve 90% coverage of the BCG vaccine by 2030, five of DTP3, three of polio3, and none of MCV. Additionally, by 2030, wider pro-urban and -rich inequalities are expected in several African countries. Conclusion: Significant progress in age-appropriate vaccination coverage has been made in LMICs from 2000 to 2020. Despite this, projections show many countries will not meet the 2030 coverage goals, with persistent urban-rural and socioeconomic disparities. Therefore, LMICs must prioritize underperforming areas and reduce inequalities through stronger health systems and increased community engagement to ensure high coverage and equitable vaccine access.

Elevated phospholipids and acylcarnitines C4 and C5 in cerebrospinal fluid distinguish viral CNS infections from autoimmune neuroinflammation.

BACKGROUND: Viral and autoimmune encephalitis may present with similar symptoms, but require different treatments. Thus, there is a need for biomarkers to improve diagnosis and understanding of pathogenesis. We hypothesized that virus-host cell interactions lead to different changes in central nervous system (CNS) metabolism than autoimmune processes and searched for metabolite biomarkers in cerebrospinal fluid (CSF) to distinguish between the two conditions. METHODS: We applied a targeted metabolomic/lipidomic analysis to CSF samples from patients with viral CNS infections (n = 34; due to herpes simplex virus [n = 9], varicella zoster virus [n = 15], enteroviruses [n = 10]), autoimmune neuroinflammation (n = 25; autoimmune anti-NMDA-receptor encephalitis [n = 8], multiple sclerosis [n = 17), and non-inflamed controls (n = 31; Gilles de la Tourette syndrome [n = 20], Bell's palsy with normal CSF cell count [n = 11]). 85 metabolites passed quality screening and were evaluated as biomarkers. Standard diagnostic CSF parameters were assessed for comparison. RESULTS: Of the standard CSF parameters, the best biomarkers were: CSF cell count for viral infections vs. controls (area under the ROC curve, AUC = 0.93), Q-albumin for viral infections vs. autoimmune neuroinflammation (AUC = 0.86), and IgG index for autoimmune neuroinflammation vs. controls (AUC = 0.90). Concentrations of 2 metabolites differed significantly (p < 0.05) between autoimmune neuroinflammation and controls, with proline being the best biomarker (AUC = 0.77). In contrast, concentrations of 67 metabolites were significantly higher in viral infections than controls, with SM.C16.0 being the best biomarker (AUC = 0.94). Concentrations of 68 metabolites were significantly higher in viral infections than in autoimmune neuroinflammation, and the 10 most accurate metabolite biomarkers (AUC = 0.89-0.93) were substantially better than Q-albumin (AUC = 0.86). These biomarkers comprised six phosphatidylcholines (AUC = 0.89-0.92), two sphingomyelins (AUC = 0.89, 0.91), and acylcarnitines isobutyrylcarnitine (C4, AUC = 0.92) and isovalerylcarnitine (C5, AUC = 0.93). Elevated C4 and C5 concentrations suggested dysfunctional mitochondrial ß-oxidation and correlated only moderately with CSF cell count (Spearman ρ = 0.41 and 0.44), indicating that their increase is not primarily driven by inflammation. CONCLUSIONS: Changes in CNS metabolism differ substantially between viral CNS infections and autoimmune neuroinflammation and reveal CSF metabolites as pathophysiologically relevant diagnostic biomarkers for the differentiation between the two conditions. In viral CNS infections, the observed higher concentrations of free phospholipids are consistent with disruption of host cell membranes, whereas the elevated short-chain acylcarnitines likely reflect compromised mitochondrial homeostasis and energy generation.

The Changing Epidemiology of Viral Hepatitis in a Post-Soviet Country-The Case of Kyrgyzstan.

Historically, viral hepatitis has been a considerable public health problem in Central Asian countries, which may have worsened after the dissolution of the Soviet Union. However, up-to-date seroepidemiological studies are lacking. The aim of the present study was, therefore, to provide current estimates of the seroprevalence of viral hepatitis in Kyrgyzstan, one of the economically least developed countries in the region. We conducted a population-based cross-sectional study in 2018 in the capital of Kyrgyzstan, Bishkek (n = 1075). Participants, children and adults, were recruited from an outpatient clinic. The data were collected during face-to-face interviews. A blood sample (6 mL) was collected from each participant and tested with ELISA for the presence of serological markers for five viral hepatitides (A, B, C, D, and E). Post-stratification weighing was performed to obtain nationally representative findings. The overwhelming majority of the study participants were positive for anti-HAV (estimated seroprevalence, 75.3%; 95% confidence interval, 72.5-77.9%). The weighted seroprevalence estimates of HBsAg, anti-HCV, and anti-HDV were 2.2% (1.5-3.3%), 3.8% (2.8-5.1%), and 0.40% (0.15-1.01%), respectively. Anti-HEV seropositivity was 3.3% (2.4-4.5%). Of the 33 HBsAg-positive participants, five (15%) were anti-HDV-positive. Our study confirms that Kyrgyzstan remains a highly endemic country for hepatitis virus A and C infections. However, seroprevalences of HBV and HDV were lower than previously reported, and based on these data, the country could potentially be reclassified from high to (lower) intermediate endemicity. The observed anti-HEV seroprevalence resembles the low endemicity pattern characteristic of high-income countries.

Falling incidence of Parkinson's disease in Germany.

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.

Trends in incidence of atopic disorders in children and adolescents - Analysis of German claims data.

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.

Impact of venous thromboembolism on incidence of arterial thromboembolism - An analysis of German outpatient claims data.

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 (HRadjusted 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.

Widening the Spectrum of Risk Factors, Comorbidities, and Prodromal Features of Parkinson Disease.

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.

Distinct immunological and molecular signatures underpinning influenza vaccine responsiveness in the elderly.

Seasonal influenza outbreaks, especially in high-risk groups such as the elderly, represent an important public health problem. Prevailing inadequate efficacy of seasonal vaccines is a crucial bottleneck. Understanding the immunological and molecular mechanisms underpinning differential influenza vaccine responsiveness is essential to improve vaccination strategies. Here we show comprehensive characterization of the immune response of randomly selected elderly participants (≥ 65 years), immunized with the adjuvanted influenza vaccine Fluad. In-depth analyses by serology, multi-parametric flow cytometry, multiplex and transcriptome analysis, coupled to bioinformatics and mathematical modelling, reveal distinguishing immunological and molecular features between responders and non-responders defined by vaccine-induced seroconversion. Non-responders are specifically characterized by multiple suppressive immune mechanisms. The generated comprehensive high dimensional dataset enables the identification of putative mechanisms and nodes responsible for vaccine non-responsiveness independently of confounding age-related effects, with the potential to facilitate development of tailored vaccination strategies for the elderly.

The Effect of the COVID-19 Pandemic on Outpatient Antibiotic Prescription Rates in Children and Adolescents-A Claims-Based Study in Germany.

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.

Secular Trends and Rural-Urban Differences in Diagnostic Prevalence of Hay Fever: A Claims-Based Study in Germany.

Purpose: 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.

Epidemiology of Lyme borreliosis based on outpatient claims data of all people with statutory health insurance, Germany, 2019.

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.

Trends in administrative prevalence of multiple sclerosis and utilization patterns of disease modifying drugs in Germany.

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.

Treatment patterns in pediatric patients with multiple sclerosis in Germany-a nationwide claim-based analysis.

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.

Patients at high risk for a severe clinical course of COVID-19 - small-area data in support of vaccination and other population-based interventions in Germany.

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.

Secular trends and regional variations in pharmacotherapy of attention-deficit/hyperactivity disorder (ADHD) among children and adolescents in Germany.

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.

Prevalence of pediatric multiple sclerosis in Germany: A nationwide population-based analysis.

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.

Utilization of influenza vaccination among chronically ill individuals in Germany: A nationwide claims-based analysis.

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.

Reduced Exhaled Breath Condensate pH and Severity of Allergic Sensitization Predict School Age Asthma.

BACKGROUND: We previously reported that deaerated breath condensate pH (dEBC pH) can identify preschool children with recurrent wheezing at high asthma risk. OBJECTIVE: To assess the ability of preschool dEBC pH to predict asthma risk at school age. METHODS: Children of the baseline cohort were recontacted for follow-up. Asthma diagnosis at school age was evaluated according to Global Initiative for Asthma recommendations in 135 children who at baseline had been classified into the following groups: (asymptomatic) atopic wheezers (n = 30), (asymptomatic) nonatopic wheezers (n = 57), allergic rhinitis only (n = 14), and healthy controls (n = 34). RESULTS: All (100%) former atopic wheezers, 12 (21%) of nonatopic wheezers, 2 (14%) of allergic rhinitis group, and 1 (3%) of healthy controls had developed asthma at follow-up. Among all children with baseline wheezing, baseline dEBC pH predicted asthma at follow-up with an area under the receiver operating characteristic curve (AUC) of 0.72 (sensitivity, 0.67; specificity, 0.76; at pH 7.83). Combining pH and Capacity class (CAP) led to substantial gain in sensitivity (0.96) and negative predictive value (NPV, 0.94). Additional clinical information (Asthma Predictive Index, family atopy, family asthma, and inhaled corticosteroids) further increased the potential to predict asthma (AUC, 0.94) and raised sensitivity (0.98) and NPV (0.97) to nearly perfect values. CONCLUSION: Our findings suggest (1) that dEBC pH combined with CAP class may serve as highly sensitive, noninvasive marker for the early detection of young asymptomatic preschool children with increased asthma risk, and (2) the need for additional biomarkers with high specificity to optimize early risk stratification in this clinically challenging scenario.