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.

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.

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.

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.

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.

Trends and regional distribution of outpatient claims for asthma, 2009-2016, Germany.

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.

Mental and somatic comorbidity of depression: a comprehensive cross-sectional analysis of 202 diagnosis groups using German nationwide ambulatory claims data.

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.

Are patients willing to accept longer travel times to decrease their risk associated with surgical procedures? A systematic review.

BACKGROUND: Distance to a hospital is an influencing factor for patients´ decision making when choosing a hospital for surgery. It is unclear whether patients prefer to travel further to regional instead of local hospitals if the risk associated with elective surgery is lower in the farther hospital. The aim of our systematic review was to investigate patient preferences for the location of care, taking into consideration surgical outcomes and hospital distance. METHODS: MEDLINE (PubMed), EconLit, PsycInfo and EMBASE were searched until November 2019. We included experimental choice studies in which participants were asked to make a hypothetical decision where to go for elective surgery when surgical risk and/or distance to the hospitals vary. There was no restriction on the type of intervention or study. Reviewers independently extracted data using a standardized form. The number and proportion of participants willing to accept additional risk to obtain surgery in the local hospital was recorded. We also extracted factors associated with the decision. RESULTS: Five studies exploring participants´ preferences for local care were included. In all studies, there were participants who, independently of a decreased mortality risk or a higher survival benefit in the regional hospital, adhered to the local hospital. The majority of the patients were willing to travel longer to lower their surgical risk. Older age and fewer years of formal education were associated with a higher risk tolerance in the local hospital. CONCLUSIONS: Whether patients were willing to travel for a lower surgery-associated risk could not be answered in a straightforward manner. The studies we identified showed that decision making also relies on factors other than on rational information on risk or distance to hospital. TRIAL REGISTRATION: International prospective register of ongoing systematic reviews (PROSPERO): CRD42016033655. Registered 1 January 2016.

Marked reductions in outpatient antibiotic prescriptions for children and adolescents - a population-based study covering 83% of the paediatric population, Germany, 2010 to 2018.

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.

[Retrospective cross-sectional study based on nationwide data of drug prescriptions and contractional data of outpatient offices regarding Morbus Wilson's disease]. / Retrospektive Querschnittsstudie von bundesweiten Arzneiverordnungsdaten und vertragsärztlichen Abrechnungsdaten von Morbus Wilson.

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.

Patterns of the initiation of disease-modifying antirheumatic drugs in incident rheumatoid arthritis: a German perspective based on nationwide ambulatory drug prescription data.

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.

Trends in paediatric macrolide use in five European countries-a population-based study.

PURPOSE: The study aims to analyse overall as well as subgroup-specific outpatient paediatric macrolide use in five European countries, including time trends of macrolide prescription rates, and to provide potential targets for future interventions aiming to promote judicious macrolide use. METHODS: Macrolide prescription rates per 1000 person years to paediatric outpatients (≤18 years) were calculated using healthcare databases from Denmark, Germany, Italy, The Netherlands and the UK. Poisson regression analysis was used to estimate the influence of increasing calendar year on total macrolide and subgroup-specific prescription rates based on monthly data, adjusted for seasonal variations. Time periods for which data were available varied between 4 (Italy 2007-10, Germany 2005-8) and 10 years (UK 2000-9). RESULTS: Paediatric macrolide use in 2008 varied between 199 (Italy) and 47 (Netherlands) prescriptions per 1000 person years. Prescription rates of short-acting macrolides declined significantly in all countries but the UK. The use of intermediate-acting macrolides significantly rose with increasing calendar year in Denmark (rate ratio (RR) = 1.12) and the UK (RR = 1.06), but decreased in Germany (RR = 0.84) and The Netherlands (RR = 0.97). Prescription rates of long-acting agents increased in Denmark (RR = 1.05), The Netherlands (RR = 1.05) and the UK (RR = 1.11) (all trends p < 0.05). The greatest seasonal variations of macrolide use between summer and winter months were observed in Italy and Germany. CONCLUSIONS: The observed trend toward increased prescribing of intermediate- and/or long-acting agents might further increase resistance pressure on bacterial pathogens due to their prolonged plasma half-life and broader antibacterial activity. Marked seasonality of prescription rates in the high-utilising countries, Italy and Germany, suggests frequent prescription of macrolides to treat respiratory infections which may be of viral origin.

Systemic antibiotic prescribing to paediatric outpatients in 5 European countries: a population-based cohort study.

BACKGROUND: To describe the utilisation of antibiotics in children and adolescents across 5 European countries based on the same drug utilisation measures and age groups. Special attention was given to age-group-specific distributions of antibiotic subgroups, since comparison in this regard between countries is lacking so far. METHODS: Outpatient paediatric prescriptions of systemic antibiotics during the years 2005-2008 were analysed using health care databases from the UK, the Netherlands, Denmark, Italy and Germany. Annual antibiotic prescription rates per 1,000 person years were estimated for each database and stratified by age (≤4, 5-9, 10-14, 15-18 years). Age-group-specific distributions of antibiotic subgroups were calculated for 2008. RESULTS: With 957 prescriptions per 1000 person years, the highest annual prescription rate in the year 2008 was found in the Italian region Emilia Romagna followed by Germany (561), the UK (555), Denmark (481) and the Netherlands (294). Seasonal peaks during winter months were most pronounced in countries with high utilisation. Age-group-specific use varied substantially between countries with regard to total prescribing and distributions of antibiotic subgroups. However, prescription rates were highest among children in the age group ≤4 years in all countries, predominantly due to high use of broad spectrum penicillins. CONCLUSIONS: Strong increases of antibiotic prescriptions in winter months in high utilising countries most likely result from frequent antibiotic treatment of mostly viral infections. This and strong variations of overall and age-group-specific distributions of antibiotic subgroups across countries, suggests that antibiotics are inappropriately used to a large extent.

Eight-year nationwide study of the bidirectional association between type 2 diabetes and depression in nearly 8 million German outpatients.

INTRODUCTION: Research linking type 2 diabetes and depression mostly relied on hospital-based diagnoses or prescription data, overlooking many outpatient diagnoses. We aimed to quantify the risks of depression in individuals newly diagnosed with type 2 diabetes, and type 2 diabetes in those newly diagnosed with depression, while exploring potential risk differences depending on age, sex, and follow-up time. RESEARCH DESIGN AND METHODS: We conducted a matched cohort study using German nationwide outpatient claims data from 2012 to 2022. Participants were individuals newly diagnosed with type 2 diabetes (N=294 642) or depression (N=1 271 537) in 2015, matched in a 1:4 ratio to controls without these conditions by age, sex, and region. The bidirectional risk was evaluated over an 8-year period using mixed-effects Cox proportional hazards models, adjusting for the Charlson Comorbidity Index, urbanicity, and area-level deprivation. RESULTS: New type 2 diabetes diagnosis was associated with higher depression risk over 8 years (N=54 561 with depression, HR=1.23, 99% CI=1.21 to 1.24). Similarly, depression diagnosis was linked to an increased type 2 diabetes risk (N=71 848 with type 2 diabetes, HR=1.15, 99% CI=1.14 to 1.17). The association between depression and type 2 diabetes was stronger in younger age groups, especially under 34 years. Findings held across sex-stratified analyses. Time stratification showed a more pronounced association between type 2 diabetes and depression risk during the earlier follow-up quarters, whereas the risk of developing type 2 diabetes after depression diagnosis remained constant throughout the follow-up period. CONCLUSIONS: Our findings confirm a bidirectional link between type 2 diabetes and depression, particularly in younger individuals. As type 2 diabetes and depression are frequent, future research needs to study whether preventive approaches can reduce the risk of developing this comorbidity.

Systemic antibiotic use among children and adolescents in Germany: a population-based study.

UNLABELLED: The aim of the study was to comprehensively describe antibiotic use among children and young adolescents in Germany. Outpatient prescriptions of systemic antibiotics to children (<15 years) were analysed using data from four German statutory health insurances for the years 2004 to 2006. Annual prevalence of antibiotic prescriptions was determined using the average number of insured children during the respective year as reference population. Annual antibiotic prescription rates were calculated per 1,000 person years. Both figures were stratified by age (0-4, 5-9 and 10-14 years) and sex. Frequent indications for prescribing were analysed. Annual prevalence of antibiotic prescriptions rose from 35.68 % [95 % confidence intervals (CI), 35.62-35.75] in 2004 to 37.79 % [95 % CI, 37.72-37.86] in 2006. Prescription rates slightly increased by 6.01 % from 668.54 [95 % CI, 667.34-669.72] antibiotic prescriptions per 1,000 person years in 2004 to 708.71 [95 % CI, 707.47-709.95] in 2006. In 2006, prescriptions of broad-spectrum penicillins (25.09 %), second-generation cephalosporins (18.11 %) and narrow-spectrum penicillins (16.45 %) were most frequent. The most common indication for antibiotic prescribing was tonsillitis followed by bronchitis, otitis media, acute upper respiratory infections and scarlet fever. CONCLUSION: In contrast to other northern European countries, paediatric prescription rates are high in Germany. This and the frequent prescribing of broad spectrum agents for the treatment of mostly viral self-limiting conditions indicate limited adherence to evidence-based practice guidelines in antibiotic prescribing in the German outpatient setting.

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.

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.

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.

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.

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.