Die ambulante Antibiotikatherapie : Methoden der Anwendungsforschung und Strategien der Förderung rationaler Verordnungsmuster

The rise of antibiotic resistance is widely acknowledged to be an increasing threat to global public health. Promoting rational antibiotic prescribing patterns is one important approach to counter this development. Comprehensive analysis of patterns of antibiotic utilization and its quality in routine care is a perquisite to the design of effective tailored interventions to promote rational and judicious antibiotic prescribing. Automated health care databases facilitate the analysis of antibiotic utilization in outpatient care in large populations and can be used for international comparison of prescribing habits. In the German health care setting administrative databases of statutory health insurance companies (SHIs) capture all outpatient dispensations of prescription drugs and allow for the population-based and detailed analysis of antibiotic use in primary care. This doctoral thesis is based onone study on paediatric antibiotic use in German primary care and two studies comparing outpatient prescribing of systemic antibiotics to children and adolescents in the age group 0-18 years between Denmark, Italy, Germany, the Netherlands and the UK. These publications are complemented by a systematic review on the effectiveness of computer-aided clinical decision support systems in strengthening rational outpatient antibiotic prescribing. Here the aim is to (1) to further explore the significance of the published results in the light of the current state of research and (2) to amplify the discussion of important methodological issues and limitations. This comprises a critical review of the strengths and weaknesses of administrative data of German SHIs and comparable European databases as a basis for population-based studies of outpatient antibiotic utilization and cross-national comparison between European countries. In addition, an overview of the current state of knowledge regarding interventions to foster rational and judicious outpatient antibiotic prescribing is given and specific methodological challenges of the synthesis of evidence in this field are discussed. By allowing detailed cross-national comparisons of age- and gender-specific measures of antibiotic use, administrative data from German SHIs and similar European health care databases close an important gap in the surveillance of outpatient patterns of antibiotic use and the assessment of prescribing quality. Additional research is warranted to assess the validity of disease-specific measures of use based on German SHIs data. In recent years outpatient antibiotic use decreased in Germany, most remarkably in the paediatric setting. Nevertheless, further room for improvement exists. In particular, this concerns relatively high prescribing of broad spectrum agents as first line treatment of seasonal respiratory infections. Notably higher prescribing in contrast to other European countries such as the Netherlands, Denmark, Sweden or the UK can be seen for chinolones, cephalosporines (2nd and 3rd generation) and new macrolides. So far, a large number of international studies has been published aiming to improve quality of outpatient antibiotic prescription, mostly showing marginal to moderate intervention effects. Nevertheless, a selection of recently published studies consistently shows favourable effectiveness for some types of intervention, including the use of specific point-of-care tests

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

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 s

Outpatient antibiotic therapy

The rise of antibiotic resistance is widely acknowledged to be an increasing threat to global public health. Promoting rational antibiotic prescribing patterns is one important approach to counter this development. Comprehensive analysis of patterns of antibiotic utilization and its quality in routine care is a perquisite to the design of effective tailored interventions to promote rational and judicious antibiotic prescribing. Automated health care databases facilitate the analysis of antibiotic utilization in outpatient care in large populations and can be used for international comparison of prescribing habits. In the German health care setting administrative databases of statutory health insurance companies (SHIs) capture all outpatient dispensations of prescription drugs and allow for the population-based and detailed analysis of antibiotic use in primary care. This doctoral thesis is based onone study on paediatric antibiotic use in German primary care and two studies comparing outpatient prescribing of systemic antibiotics to children and adolescents in the age group 0-18 years between Denmark, Italy, Germany, the Netherlands and the UK. These publications are complemented by a systematic review on the effectiveness of computer-aided clinical decision support systems in strengthening rational outpatient antibiotic prescribing. Here the aim is to (1) to further explore the significance of the published results in the light of the current state of research and (2) to amplify the discussion of important methodological issues and limitations. This comprises a critical review of the strengths and weaknesses of administrative data of German SHIs and comparable European databases as a basis for population-based studies of outpatient antibiotic utilization and cross-national comparison between European countries. In addition, an overview of the current state of knowledge regarding interventions to foster rational and judicious outpatient antibiotic prescribing is given and specific methodological challenges of the synthesis of evidence in this field are discussed. By allowing detailed cross-national comparisons of age- and gender-specific measures of antibiotic use, administrative data from German SHIs and similar European health care databases close an important gap in the surveillance of outpatient patterns of antibiotic use and the assessment of prescribing quality. Additional research is warranted to assess the validity of disease-specific measures of use based on German SHIs data. In recent years outpatient antibiotic use decreased in Germany, most remarkably in the paediatric setting. Nevertheless, further room for improvement exists. In particular, this concerns relatively high prescribing of broad spectrum agents as first line treatment of seasonal respiratory infections. Notably higher prescribing in contrast to other European countries such as the Netherlands, Denmark, Sweden or the UK can be seen for chinolones, cephalosporines (2nd and 3rd generation) and new macrolides. So far, a large number of international studies has been published aiming to improve quality of outpatient antibiotic prescription, mostly showing marginal to moderate intervention effects. Nevertheless, a selection of recently published studies consistently shows favourable effectiveness for some types of intervention, including the use of specific point-of-care tests

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.Peer Reviewe

Diabetes mellitus and comorbidities – A cross-sectional study with control group based on nationwide ambulatory claims data

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

Quality ratings of reviews in overviews: a comparison of reviews with and without dual (co-)authorship

Abstract Background Previous research shows that many authors of Cochrane overviews were also involved in some of the included systematic reviews (SRs). This type of dual (co-)authorship (DCA) may be a conflict of interest and a potential source of bias. Our objectives were to (1) additionally investigate DCA in non-Cochrane overviews; (2) investigate whether there is an association between DCA and quality assessments of SRs in Cochrane and non-Cochrane overviews. Methods We selected a sample of Cochrane (n = 20) and non-Cochrane (n = 78) overviews for analysis. We extracted data on the number of reviews affected by DCA and whether quality assessment of included reviews was conducted independently. Differences in mean quality scores between SRs with and without DCA were calculated in each overview. These differences were standardized (using the standardized mean difference (SMD)) and meta-analyzed using a random effects model. Results Forty out of 78 non-Cochrane overviews (51%) and 18 out of 20 Cochrane overviews (90%) had included at least one SR with DCA. For Cochrane overviews, a median of 5 [interquartile range (IQR) 2.5 to 7] SRs were affected by DCA (median of included reviews 10). For non-Cochrane overviews a median of 1 [IQR 0 to 2] of the included SRs were affected (median of included reviews 14). The meta-analysis showed a SMD of 0.58 (95% confidence interval (CI) 0.27 to 0.90) indicating higher quality scores in reviews with overlapping authors. The test for subgroup differences shows no evidence of a difference between Cochrane (SMD 0.44; 95% CI 0.07 to 0.81) and non-Cochrane overviews (SMD 0.62; 95% CI 0.06 to 1.17). Conclusions Many authors of overviews also often have an authorship on one or more of the underlying reviews. Our analysis shows that, on average, authors of overviews give higher quality ratings to SRs in which they were involved themselves than to other SRs. Conflict of interest is one explanation, but there are several others such as reviewer expertise. Independent and blinded reassessments of the reviews would provide more robust evidence on potential bias arising from DCA

Diabetes mellitus und Komorbiditäten – Querschnittsstudie mit Kontrollgruppe anhand vertragsärztlicher Abrechnungsdaten

Diabetes mellitus ist mit Risikofaktoren und Krankheiten wie Adipositas assoziiert. Gleichzeitig sind insbesondere kardiovaskuläre Erkrankungen häufige Folge eines Diabetes. Bislang fehlen Bundesweite Ergebnisse Mit Daten Gesetzlich Krankenversicherter, Die Gleichzeitig Die Prävalenz Des Diabetes Und Der Mit Ihm Häufig Zusammen Auftretenden Krankheiten Darstellen. Die Vorliegende Studie Berechnet Auf Basis Aller Ambulanten Vertragsärztlichen Abrechnungsdaten Die Dokumentierte Prävalenz Bezüglich Diabetes In 2019. Zusätzlich Wird Die Prävalenz Von Adipositas, Bluthochdruck, Koronarer Herzkrankheit, Herzinsuffizienz, Schlaganfall Und Depression Bei Personen Mit Und Ohne Diabetes Berechnet Und Das Prävalenz-Ratio (PR) Als Quotient Ermittelt. Hierfür Wurde Ein Fall-Kontroll-Design Gewählt, Welches jedem Diabetesfall eine hinsichtlich Alter, Region und Geschlecht vergleichbare Person ohne Diabetes als Kontrolle zuordnet. Alle untersuchten Krankheiten zeigen bei Personen mit Diabetes in allen Altersgruppen eine PR von größer 1 und damit eine höhere Prävalenz im Vergleich zu Personen ohne Diabetes. Die höchste PR über alle Altersgruppen findet sich bei Frauen (3,8) und Männern (3,7) für Adipositas. Im zeitlichen Vergleich stagniert die bundesweite Abrechnungsprävalenz des Diabetes. Mit Ausnahme der Depression stimmen die dokumentierten Prävalenzen der Begleiterkrankungen gut mit den Prävalenzen aus bevölkerungsweiten Untersuchungssurveys überein

Comorbidity profile of patients with concurrent diagnoses of asthma and COPD in Germany

Abstract 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

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