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

Interdependenz zwischen der Schulstruktur und der Sozialstruktur von Stadtbezirken am Beispiel Bielefelds und Essens und ihre Einflüsse auf die Bildungschancen

Holstiege F. Interdependenz zwischen der Schulstruktur und der Sozialstruktur von Stadtbezirken am Beispiel Bielefelds und Essens und ihre Einflüsse auf die Bildungschancen. Bielefeld: Universität Bielefeld; 2012.Die systematische Benachteiligung von Kindern unterer sozialer Schichten wurde nicht zuletzt durch die PISA-Studien als ein Hauptproblem des deutschen Schulsystems aufgezeigt. In der Bildungsforschung sieht man die Verteilung der Kinder nach der Grundschule auf unterschiedliche Sekundar- und Förderschulen als eine der Hauptursachen für diese Problematik. Geklärt werden soll im Rahmen dieser Arbeit, ob zwischen der Verteilung vor allem der Sekundar- und Förderschulen und der sozialräumlichen Strukturierung der Städte Interdependenzen bestehen und inwieweit diese Bildungschancen von Kindern beeinflussen. Verwendet wurden Daten der Statistik- und Schulämter, über die Verteilung von Einkommen und Arbeitslosigkeit in Essen und Bielefeld sowie die Verteilung der Schulen und der Übergangsquoten von den Grundschulen auf die weiterführenden Schulen. Diese wurden wechselseitig miteinander verglichen, um zu klären, ob sich die Verteilung des Schulangebots und der Grundschulübergangsquoten nach der Sozialstruktur richtet und ob es Zusammenhänge zwischen den Übergangsquoten und der räumlichen Anordnung der Sekundarschulen gibt. Insbesondere für Essen konnte gezeigt werden, dass die Verteilung der Sekundar- und Förderschulen mit der Verteilung von Wohlstand über die Stadt übereinzustimmen scheint, dementsprechend Gymnasien häufiger in den reicheren Bezirken zu finden sind und Gesamt- und Hauptschulen vermehrt in den ärmeren Bezirken. Des weiteren scheinen die Grundschulübergangsquoten räumlich mit der Verteilung der Sekundarschulen zusammen zuhängen, wobei hier die Zusammenhänge zwischen den unterschiedlichen Sekundarschulformen in ihrer Stärke zu variieren scheinen. Da höhere soziale Schichten bezüglich der Schulwahl im Gegensatz zu unteren sozialen Schichten eine größere räumliche Mobilität an den Tag zu legen scheinen, wirkt sich bei letzteren die räumliche Nähe zu z.B. einer Hauptschule stärker aus. Es kann geschlussfolgert werden, dass die Verteilung der Sekundar- und Förderschulen teilweise mit der sozialräumlichen Strukturierung der Städte korrespondiert und somit die Bildungschancen der Kinder innerhalb der beiden Städte räumlich variieren

Using Prescription Patterns in Primary Care to Derive New Quality Indicators for Childhood Community Antibiotic Prescribing.

BACKGROUND: To describe patterns of antibiotic outpatient use in three European countries, including two new pediatric-specific quality indicators (QIs). METHODS: A cohort study was conducted, 2001-2010, using electronic primary care records of 2,196,312 children up to 14 (Pedianet, Italy) or 18 years (THIN, UK; IPCI, the Netherlands) contributing 12,079,620 person-years. Prevalence rates of antibiotic prescribing per year were calculated and antibiotics accounting (drug utilization) for 90% of all antibiotic prescriptions were identified (DU90% method). The ratio between users of broad to narrow-spectrum penicillins, cephalosporins and macrolides (B/N ratio) and two pediatric-specific quality indicators (QIs): the proportion of amoxicillin users (amoxicillin index, AI) and the ratio between users of amoxicillin to broad-spectrum penicillins, cephalosporins and macrolides (A/B ratio) were determined. RESULTS: The overall annual prevalence of antibiotic prescriptions was 18.0% in the Netherlands, 36.2% in the UK and 52.0% in Italy. Use was maximal in the first years of life. The number of antibiotics accounting for the DU90% was comparable. The B/N ratio varied widely from 0.3 to 74.7. The AI was highest in the Netherlands and the UK (50-60%), lowest in Italy (30%) and worsened over time in the UK and Italy. The A/B ratio in 2010 was 0.3 in Italy, 1.7 in the Netherlands and 5.4 in the UK. CONCLUSIONS: The patterns of antibiotic prescribing varied highly with age and country. The pediatric-specific QIs combined with the total prevalence rate of use provide a clear picture of the trends of community childhood antibiotic prescribing, allowing monitoring of the impact of policy interventions

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

Comparing outpatient oral antibiotic use in Germany and the Netherlands from 2012 to 2016

PURPOSE: Overuse of antibiotics is of concern, but may differ between European countries. This study compares outpatient use of oral antibiotics between Germany (DE) and the Netherlands (NL). METHODS For DE, we used the DAPI database with information on dispensings at the expense of the Statutory Health Insurance Funds from > 80% of community pharmacies. For NL, data were obtained from the Dutch Foundation for Pharmaceutical Statistics. Use of oral antibiotics was estimated as defined daily doses per 1000 inhabitants per day (DID), except for age comparisons as packages per 1000 inhabitants annually. National time trends were assessed with linear regression, stratified for the major antibiotic classes, and individual substances. RESULTS: From 2012 to 2016, outpatient antibiotic use was lower in NL than in DE (9.64 vs 14.14 DID in 2016) and non‐significantly decreased slightly over time in both countries. In DE, dispensings of oral antibiotics to children were higher compared with NL for the age groups 2 to 5 (2.0‐fold in 2016) and 6 to 14 years (2.7‐fold in 2016). Use of cephalosporins was very low in NL (0.02 DID in 2016), but the second most frequently dispensed class in DE (2.95 DID in 2016). CONCLUSION: From 2012 to 2016, outpatient use of oral antibiotics was lower in NL than in DE. Differences were primarily observed in the age groups 2 to 5 and 6 to 14 years, although the recommendations of evidence‐based guidelines in both countries were in agreement

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

'Use of antipsychotics in children and adolescents: a picture from the ARITMO population-based European cohort study'

Aims. Prevalence of the use of antipsychotics (APs) in the paediatric population is globally increasing. The aim of this study was to describe multinational trends and patterns in AP use in children and adolescents in Europe. Methods. This was a dynamic retrospective cohort study comprising all children and adolescents (⩽18 years of age). Data were extracted from five population-based electronic healthcare databases in Europe (Denmark, Germany, Italy, the Netherlands and United Kingdom) from 2000 to 2010. Yearly prevalence and incidence of AP use was expressed per 1000 person-years (PYs). Results. Prevalence increased from 1.44 to 3.41/1000 PYs (2008) in Denmark and from 2.07 to 4.35/1000 PYs in the NL (2009), moderately increased from 2.8 to 3.24/1000 in UK (2009) and from 1.53 to 1.74/1000 PYs in Germany (2008) and remained low from 0.61 to 0.34/1000 PYs in Italy (2010). Similarly, incidence rates increased from 0.69 to 1.52/1000 PYs in Denmark and from 0.86 to 1.49/1000 PYs in the NL, stabilised from 2.29 to 2.37/1000 PYs in the UK and from 0.79 to 0.80/1000 PYs in Germany and remained low from 0.32 to 0.2/1000 PYs in Italy. AP use was highest in 15–18 year olds and in boys compared to girls. Yet, the use observed in the 5–9 year olds was found to be comparatively high in the NL. Prescriptions of second generation APs, especially risperidone, were privileged but the first generation APs were still prescribed in the youngest. Conclusions. A steady increase in AP use in children and adolescents was observed essentially in the NL and Denmark. The use in Germany and Italy was lowest among countries. The use of APs under 9 years of age underlines their off-label use and should be carefully monitored as the risk/benefit ratio of these medications remains unclear in young children. AP use was altogether lower in Europe as compared to that reported in North America

A systematic review of clinical decision support systems for antimicrobial management: are we failing to investigate these interventions appropriately?

Objectives Clinical decision support systems (CDSS) for antimicrobial management can support clinicians to optimize antimicrobial therapy. We reviewed all original literature (qualitative and quantitative) to understand the current scope of CDSS for antimicrobial management and analyse existing methods used to evaluate and report such systems. Method PRISMA guidelines were followed. Medline, EMBASE, HMIC Health and Management and Global Health databases were searched from 1 January 1980 to 31 October 2015. All primary research studies describing CDSS for antimicrobial management in adults in primary or secondary care were included. For qualitative studies, thematic synthesis was performed. Quality was assessed using Integrated quality Criteria for the Review Of Multiple Study designs (ICROMS) criteria. CDSS reporting was assessed against a reporting framework for behaviour change intervention implementation. Results Fifty-eight original articles were included describing 38 independent CDSS. The majority of systems target antimicrobial prescribing (29/38;76%), are platforms integrated with electronic medical records (28/38;74%), and have a rules-based infrastructure providing decision support (29/38;76%). On evaluation against the intervention reporting framework, CDSS studies fail to report consideration of the non-expert, end-user workflow. They have narrow focus, such as antimicrobial selection, and use proxy outcome measures. Engagement with CDSS by clinicians was poor. Conclusion Greater consideration of the factors that drive non-expert decision making must be considered when designing CDSS interventions. Future work must aim to expand CDSS beyond simply selecting appropriate antimicrobials with clear and systematic reporting frameworks for CDSS interventions developed to address current gaps identified in the reporting of evidence