Comparative analysis of outpatient antibiotic prescribing in early life: A population-based study across birth cohorts in Denmark and Germany

INTRODUCTION: Comparing antibiotic prescribing between countries can provide important insights into potential needs of improving antibiotic stewardship programs. We aimed to compare outpatient antibiotic prescribing in early life between children born in Denmark and Germany. METHODS: Using the Danish nationwide healthcare registries and a German claims database (GePaRD, ~ 20% population coverage), we included children born between 2004 and 2016, and followed them regarding outpatient antibiotic prescriptions until end of enrollment or the end of 2018. We then determined the median time to first antibiotic prescription. Based on all prescriptions in the first 2 years of life, we calculated the rate of antibiotic treatment episodes and for the children’s first prescriptions in this period, we determined established quality indicators. All analyses were stratified by birth year and country. RESULTS: In the 2016 birth cohorts, the median time to first antibiotic prescription was ~ 21 months in Denmark and ~ 28 in Germany; the rate of antibiotic treatment episodes per 1000 person-years was 537 in Denmark and 433 in Germany; the percentage of prescribed antibiotics with higher concerns regarding side effects and/or resistance potential was 6.2% in Denmark and 44.2% in Germany. In the 2016 birth cohorts, the age at first antibiotic prescription was 50–59% higher compared to the 2004 birth cohorts; the rate of antibiotic treatment episodes was 43–44% lower. CONCLUSIONS: Infants in Denmark received antibiotics markedly earlier and more frequently than in Germany, while quality indicators of antibiotic prescribing were more favorable in Denmark. Although both countries experienced positive changes towards more rational antibiotic prescribing in early life, our findings suggest potential for further improvement. This particularly applies to prescribing antibiotics with a lower potential for side effects and/or resistance in Germany

Stability of the frequent COPD exacerbator in the general population:A Danish nationwide register-based study

Exacerbation frequency is central in treatment strategies for chronic obstructive pulmonary disease. However, whether chronic obstructive pulmonary disease patients from the general population with frequent exacerbations continue to have frequent exacerbations over an extended period of time is currently unknown. In this study, we aimed to investigate the stability of the frequent exacerbator in a population-based setting. To this end, we conducted a nationwide register-based descriptive study with a 10-year follow-up period of chronic obstructive pulmonary disease patients with at least one medically treated exacerbation in 2003. Each subsequent year, we divided the population into frequent, infrequent and non-exacerbators and quantified the flow between categories. Further, we estimated the percentage of frequent exacerbators at baseline who stayed in this category each year during a 5-year follow-up. We identified 19,752 patients with chronic obstructive pulmonary disease and an exacerbation in 2003. Thirty percent were frequent exacerbators. Overall, the majority of exacerbators in 2003 were non-exacerbators in the following years (60% in 2004 increasing to 68% in 2012). Approximately half of frequent exacerbators in one year experienced a decrease in exacerbation frequency and had either zero or one exacerbation in the subsequent year. This pattern was stable throughout follow-up. During a 5-year follow-up period, a substantial proportion (42%) of frequent exacerbators in 2003 had no additional years as frequent exacerbators, while the minority (6%) remained in this category each year. In conclusion, the rate of exacerbations shows considerable variation over time among chronic obstructive pulmonary disease patients in the general population. This might hold implications for chronic obstructive pulmonary disease treatment guidelines and their practical application.CHRONIC OBSTRUCTIVE LUNG DISEASE: VARIATIONS IN DISEASE PROGRESSION: Patients with chronic obstructive pulmonary disease (COPD) who suffer from frequent exacerbations do not necessarily persist with such severity over time. Exacerbations in COPD are defined by worsening respiratory symptoms that result in changes to treatment, hospitalization and, at worst, death. However, clarity is needed on whether frequent exacerbations is a stable feature of some patients' disease. Mette Reilev at the University of Southern Denmark and co-workers followed, over 10 years, 19,752 COPD patients living in Denmark who suffered at least one exacerbation in 2003. By 2004, 60% of patients were classed as infrequent or non-exacerbators, rising to 68% by 2012. Very few patients remained "frequent exacerbators", suggesting the rate of exacerbations changes considerably over time. This could hold implications for COPD treatment and challenge assumptions made about disease progression

Methodology of the brodalumab assessment of hazards: a multicentre observational safety (BRAHMS) study

INTRODUCTION: Safe and effective pharmacological treatment is of paramount importance for treating severe psoriasis. Brodalumab, a monoclonal antibody against interleukin (IL) 17 receptor A, was granted marketing authorisation in the EU in 2017. The European Medicines Agency requested a postauthorisation safety study of brodalumab to address potential safety issues raised during drug development regarding major adverse cardiovascular events, suicidal conduct, cancer and serious infections. METHODS AND ANALYSIS: BRodalumab Assessment of Hazards: A Multinational Safety is a multicentre observational safety study of brodalumab running from 2017 to 2029 using population-based healthcare databases from Denmark, Sweden, Norway, Netherlands, Germany and three different centres in Italy. A distributed database network approach is used, such that only aggregate data are exchanged between sites.Two types of designs are used: a case-time-control design to study acute effects of transient treatment and a variation of the new user active comparator design to study the effects of transient or chronic treatment. As comparators, inhibitors of TNF-α, inhibitors of IL-12 and IL-23, and other inhibitors of cytokine IL-17A are included.In the self-controlled case-time-control design, the risk of developing the outcome of interest during periods of brodalumab use is compared within individuals to the risk in periods without use.In the active comparator cohort design, new users of brodalumab are identified and matched to new users of active comparators. Potential baseline confounders are adjusted for by using propensity score modelling. For outcomes that potentially require large cumulative exposure, an adapted active comparator design has been developed. ETHICS AND DISSEMINATION: The study is approved by relevant authorities in Denmark, Norway, Sweden, the Netherlands, Germany and Italy in line with the relevant legislation at each site. Data confidentiality is secured by the distributed network approach. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EUPAS30280