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To improve understanding of real-world asthma treatment and inform physician education, we evaluated regional variation in asthma prevalence and oral corticosteroid (OCS) use across Germany. We developed a machine learning gradient boosted tree model with IMS® Disease Analyzer electronic medical records, which cover 3% of German patients. This model had a 91% accuracy in predicting the presence of asthma and chronic obstructive pulmonary disease. We applied the model to the IMS® Longitudinal Prescription database, with 82% national coverage, to classify patients receiving treatment for airflow obstruction from October 2017–September 2018 in 63 regions in Germany. Of 2.4 million individuals under statutory health insurance with predicted high OCS use for asthma (defined as 1 tablet per day for the duration of therapy), 13.7%, 18.7%, 36.5%, 29.4%, and 1.7% were categorised as receiving Global Initiative for Asthma (GINA) Steps 1, 2, 3, 4, and 5 treatment, respectively. Approximately 7–15% of those receiving GINA Steps 1–4 treatment, and 35% of those receiving Step 5 treatment received ≥1 acute OCS prescription (duration

In Australia, the regional prevalence of difficult-to-treat asthma is unknown. We aimed to describe regional variation in difficult-to-treat asthma prevalence and oral corticosteroid (OCS) use. In this retrospective, observational, longitudinal study using data from March 2018–February 2019 in the NostraData longitudinal database, prescriptions dispensed for obstructive airway disease were processed through a high-level algorithm to identify patients with asthma. Difficult-to-treat asthma was defined by ≥2 high-dosage inhaled corticosteroids plus long-acting beta-agonist prescriptions over 6 months. Patients who additionally received OCS prescriptions sufficient to treat ≥2 exacerbations over 6 months were classified as having uncontrolled difficult-to-treat asthma. Patient-level data were analyzed across 340 geographic areas in Australia to determine regional prevalence of difficult-to-treat asthma, uncontrolled difficult-to-treat asthma, and OCS use. Of 1 851 129 people defined as having asthma, 440 800 (24%) were classified as having difficult-to-treat disease. Of those difficult-to-treat asthma patients, 96 338 (22%) were considered to have uncontrolled disease. Between 29% and 48% of patients had difficult-to-treat asthma in 49 geographic areas, most frequently located in Western Australia. Between 26% and 67% of patients had uncontrolled difficult-to-treat asthma in 29 geographic areas (mostly in Eastern Australia). Overall, a wide variability of asthma severity and control was observed among regions. Despite global and national guidelines, regional differences in the prevalence of difficult-to-treat asthma and uncontrolled difficult-to-treat asthma and OCS use exist in Australia. Understanding these regional variations should inform policy and target management in the areas with the greatest unmet need.

Introduction Patients with asthma typically increase short-acting β2-agonists (SABA) use with worsening symptoms. Excessive SABA use may lead to a higher risk of adverse outcomes. We evaluated, in a large population cohort, an association between SABA inhaler use and asthma exacerbations and healthcare utilization. Methods As part of the SABINA (SABA use IN Asthma) global program, we conducted a retrospective longitudinal observational study (SABINA I) using UK primary care electronic healthcare records (Clinical Practice Research Datalink; 2007–2017) from asthma patients aged ≥ 12 years. SABA inhaler use was classified as ‘high use ’ 3 canisters/year versus ‘low use’, 0–2 canisters/year. Taking into consideration all their asthma prescriptions, patients were categorized into a treatment step according to 2016 British Thoracic Society (BTS) asthma management guidelines. Multivariable regression assessed the association of SABA inhaler use by BTS treatment steps (grouped as BTS steps 1/2 and 3–5), separately, and with outcomes of exacerbations or asthma-related healthcare utilization (primary care and hospital outpatient consultations); only patients with linked hospital data were included in this analysis. Results Of the 574,913 patients included, 218,365 (38%) had high SABA inhaler use. Overall, 336,412 patients had linked hospital data. High SABA inhaler use was significantly associated with an increased risk of exacerbations [adjusted hazard ratio, 95% confidence interval (CI): BTS steps 1/2 = 1.20, 1.16–1.24; BTS steps 3–5 = 1.24, 1.20–1.28], asthma-related primary care consultations [adjusted incidence rate ratio (IRR), 95% CI: BTS steps 1/2 = 1.24, 1.23–1.26; BTS steps 3–5 = 1.13, 1.11–1.15), and asthma-related hospital outpatient consultations (adjusted IRR, 95% CI: BTS steps 1/2 = 1.19, 1.12–1.27; BTS steps 3–5 = 1.19, 1.13–1.26). Conclusion High SABA inhaler use was frequent across BTS steps and was associated with a significant increase in exacerbations and asthma-related healthcare utilization.

Patients with asthma typically increase short-acting βAs part of the SABINA (SABA use IN Asthma) global program, we conducted a retrospective longitudinal observational study (SABINA I) using UK primary care electronic healthcare records (Clinical Practice Research Datalink; 2007-2017) from asthma patients aged ≥ 12 years. SABA inhaler use was classified as 'high use', ≥ 3 canisters/year versus 'low use', 0-2 canisters/year. Taking into consideration all their asthma prescriptions, patients were categorized into a treatment step according to 2016 British Thoracic Society (BTS) asthma management guidelines. Multivariable regression assessed the association of SABA inhaler use by BTS treatment steps (grouped as BTS steps 1/2 and 3-5), separately, and with outcomes of exacerbations or asthma-related healthcare utilization (primary care and hospital outpatient consultations); only patients with linked hospital data were included in this analysis.Of the 574,913 patients included, 218,365 (38%) had high SABA inhaler use. Overall, 336,412 patients had linked hospital data. High SABA inhaler use was significantly associated with an increased risk of exacerbations [adjusted hazard ratio, 95% confidence interval (CI): BTS steps 1/2 = 1.20, 1.16-1.24; BTS steps 3-5 = 1.24, 1.20-1.28], asthma-related primary care consultations [adjusted incidence rate ratio (IRR), 95% CI: BTS steps 1/2 = 1.24, 1.23-1.26; BTS steps 3-5 = 1.13, 1.11-1.15], and asthma-related hospital outpatient consultations (adjusted IRR, 95% CI: BTS steps 1/2 = 1.19, 1.12-1.27; BTS steps 3-5 = 1.19, 1.13-1.26).High SABA inhaler use was frequent across BTS steps and was associated with a significant increase in exacerbations and asthma-related healthcare utilization.

Introduction Globally, individuals with asthma tend to overrely on short-acting β2-agonists (SABAs) and underuse inhaled corticosteroids, thereby undertreating the underlying inflammation. Such relief-seeking behavior has been reinforced by long-standing treatment guidelines, which until recently recommended SABA-only use for immediate symptom relief. We aimed to describe the current burden of SABA use among European individuals with asthma within the SABA use IN Asthma (SABINA) program. Methods Prescription and/or dispensing data during 2006–2017 from electronic medical records and/or national patient registries in the United Kingdom (UK), Germany, Italy, Spain, and Sweden were analyzed. Individuals aged at least 12 years old with a current asthma diagnosis and no other chronic respiratory conditions were included. Asthma treatment step and severity were based on treatment guidelines in use in each individual country. The proportion of individuals prescribed SABA was measured during a 12-month period. SABA overuse was defined as at least three SABA canisters per year. Results More than one million individuals with asthma were included across five European countries. Overall, the majority of individuals were over 45 years of age, except in Sweden (mean age 27.6 years) where individuals aged over 45 years were excluded to avoid a potential chronic obstructive pulmonary disease co-diagnosis. The study population was predominantly female (55–64%), except in the UK (46%). The prevalence of SABA overuse was 9% in Italy, 16% in Germany, 29% in Spain, 30% in Sweden, and 38% in the UK. In the UK, SABA overuse was greater in individuals with moderate-to-severe asthma versus individuals with mild asthma (58% versus 27%, respectively), while SABA overuse was similar in individuals with both mild (9–32%) and moderate-to-severe (8–31%) asthma in the other European countries. Conclusions The findings of this study from the SABINA program show that SABA overuse (at least three canisters per year) is common across Europe, despite the different healthcare and reimbursement policies of each country.

Oral corticosteroids (OCS) are used to manage asthma exacerbations and severe, uncontrolled asthma, but OCS use is associated with adverse effects. We aimed to describe the patterns of OCS use in the real-world management of patients with asthma in western Europe. We used electronic medical records from databases in France, Germany, Italy and the United Kingdom from July 2011 through February 2018. Patients aged ≥12 years with an asthma diagnosis, at least one non-OCS asthma medication within ±6 months of diagnosis, and available data ≥6 months prior to and ≥90 days after cohort entry were included. High OCS use was defined as OCS ≥450 mg prescribed in a 90-day window during follow-up. Baseline characteristics and OCS use during follow-up were described overall and by OCS use status. Of 702 685 patients with asthma, 14–44% were OCS users and 6–9% were high OCS users at some point during follow-up. Annual prevalence of high OCS use across all countries was ∼3%. High OCS users had a mean of between one and three annual OCS prescriptions, with an average daily OCS dosage of 1.3–2.2 mg. For patients who continued to meet the high-use definition, daily OCS exposure was generally stable at 5.5–7.5 mg for ≥2 years, increasing the risk of adverse effects. Our study demonstrates that OCS use is relatively common across the four studied European countries. Data from this study may provide decisive clinical insights to inform primary care physicians and specialists involved in the management of severe, uncontrolled asthma., This study gives a real-world snapshot of oral corticosteroid (OCS) use in western Europe, by highlighting an opportunity to shift towards corticosteroid-sparing therapies or safer alternatives that mitigate the risk of OCS-associated adverse effects http://bit.ly/3cB8kk8

Introduction and objectives A better understanding of differences in asthma prevalence between regions will inform disease management and treatment. To examine regional variations in prevalence of severe asthma and severe, uncontrolled asthma, we analyzed pharmacy records from the United Kingdom. Methods Data for 4,356,990 patients who received treatment for fixed airflow obstruction during 2018 were extracted from IQVIA’s longitudinal database of UK pharmacy records, which included data for 61% of all UK patients from 46% of pharmacies. Indications for prescriptions were not available. Therefore, patients aged Results We identified >3 million patients with asthma. Severe asthma prevalence was approximately 25% overall and was greatest in the southwest and east of England and in parts of Wales (figure). Prevalence of severe asthma was comparatively less for greater London and other metropolitan areas. Prevalence of severe, uncontrolled asthma was greatest for Northern Ireland. Pharmacy migration, nonadherence to medication, and inability to link patients across pharmacies may have resulted in the underestimation of prescriptions, particularly in urban areas where populations are more likely to be transient. However, a sensitivity analysis that included only patients with 100% ICS coverage (adherent and nontransient) did not reveal any large differences in relative prevalences from the primary analysis. Conclusions Regional patterns of severe asthma and severe, uncontrolled asthma were notably different. For some regions, relatively high prevalence might be explained by small patient numbers. Patients may have received high ICS dosages rather than biologic therapies, based on local access restrictions. Despite data limitations, this first heat map analysis of unmet needs for UK patients with severe asthma provides important tools for the discussion on improving severe asthma care.

Background Safety signal detection in spontaneous reporting system databases and electronic healthcare records is key to detection of previously unknown adverse events following immunization. Various statistical methods for signal detection in these different datasources have been developed, however none are geared to the pediatric population and none specifically to vaccines. A reference set comprising pediatric vaccine-adverse event pairs is required for reliable performance testing of statistical methods within and across data sources. Methods The study was conducted within the context of the Global Research in Paediatrics (GRiP) project, as part of the seventh framework programme (FP7) of the European Commission. Criteria for the selection of vaccines considered in the reference set were routine and global use in the pediatric population. Adverse events were primarily selected based on importance. Outcome based systematic literature searches were performed for all identified vaccine-adverse event pairs and complemented by expert committee reports, evidence based decision support systems (e.g. Micromedex), and summaries of product characteristics. Classification into positive (PC) and negative control (NC) pairs was performed by two independent reviewers according to a pre-defined algorithm and discussed for consensus in case of disagreement. Results We selected 13 vaccines and 14 adverse events to be included in the reference set. From a total of 182 vaccine-adverse event pairs, we classified 18 as PC, 113 as NC and 51 as unclassifiable. Most classifications (91) were based on literature review, 45 were based on expert committee reports, and for 46 vaccine-adverse event pairs, an underlying pathomechanism was not plausible classifying the association as NC. Conclusion A reference set of vaccine-adverse event pairs was developed. We propose its use for comparing signal detection methods and systems in the pediatric population.

Background: Oral corticosteroids (OCS) are often prescribed for treatment of asthma exacerbations, or as part of daily maintenance therapy for patients with severe asthma, although they are associated with adverse effects Aims and Objectives: To describe the patterns of OCS use and characteristics of patients with asthma by OCS use status in Italy. Methods: Electronic medical records from the Longitudinal Patient Database for general practice in Italy from 1/7/11–31/12/17 were used. Included patients were ≥12 years old with ≥1 asthma diagnosis and had data available for ≥183 days before and ≥90 days after cohort entry. Long-term (LT) use was defined as ≥450 mg OCS prescribed in a 90-day period during follow up. Patients were classified by their OCS use: non-user or OCS user (including non-LT and LT). Baseline characteristics and OCS prescription patterns during follow up were described overall and by OCS use. Results: Among the 97,187 study patients, 42.6% were OCS users and 8.7% were LT OCS users at some point during follow up. One-year prevalence of LT OCS use from cohort entry was 3.7%. OCS users, especially LT OCS users, were older, were more likely to be female, be obese, have severe asthma, and have more comorbidities, and were less likely to be active smokers than non-OCS users. The mean annual number of OCS prescriptions was 1.7 for LT users and 0.6 for non-LT users. Mean daily OCS dosage was 1.4 mg for LT users and 0.3 mg for non-LT users. Conclusion: OCS use is relatively common in asthma treatment in Italy, suggesting suboptimal asthma management. OCS therapy should be considered carefully to avoid associated adverse effects.

Background: Characterization of regional variation in asthma treatment across Germany will improve understanding of real-world therapy and inform physician education. Aims and Objectives: We aimed to describe regional variation in asthma prevalence and oral corticosteroid (OCS) use in Germany. Methods: We developed a machine learning gradient boosted tree model, with 91% accuracy in predicting the presence of asthma and COPD, using IMS® Disease Analyzer electronic medical records, which cover 3% of German patients. This model was applied to the IMS Longitudinal Prescription database, with 75% national coverage, to classify patients receiving airflow obstruction treatment from Oct 2017–Sept 2018 in 63 regions. Results: Of 2.4 million patients predicted to have asthma, 13.7%, 18.7%, 36.5%, 29.4%, and 1.7% were categorized as GINA stages 1, 2, 3, 4, and 5, respectively. At least one short-term OCS prescription was received by 7–15% of patients in GINA stages 1–4 and 35% of patients in stage 5. At least one maintenance OCS prescription was received by 1–3% of patients in GINA stages 1–4 and 86% in stage 5. Cumulative OCS dosage and percentage of OCS-treated patients differed substantially across regions (figure). Regions with less maintenance OCS use had greater biologic use. Conclusions: Maintenance and short-term OCS use varied across Germany and were greater than recommended by guidelines across the spectrum of asthma severity.

As SABA overuse is associated with exacerbations and mortality, GINA no longer recommends SABA only as a preferred reliever in asthma. A consistent pattern of high SABA use from the SABINA programme would indicate a global public health issue.http://bit.ly/33XDrlb

Background Some observational studies and randomized controlled trials (RCTs) have suggested an association between abacavir (ABC) use and myocardial infarction (MI), whereas others have not. Methods This pooled analysis of 66 phase II–IV RCTs estimates exposure-adjusted incidence rates (IRs) and relative rates (RRs) of MI and cardiovascular events (CVEs) in participants receiving ABC- and non-ABC-containing combination antiretroviral therapy (cART). The primary analysis of MI included ABC-randomized trials with ≥48-week follow-up. Sensitivity analyses of MI and CVEs included non-ABC-randomized and Results In 66 clinical trials, 13 119 adults (75% male, aged 18–85 years) were on ABC-containing cART and 7350 were not. Exposure-adjusted IR for MI was 1.5 per 1000 person-years (PY; 95% confidence interval [CI], 0.67–3.34) in the ABC-exposed group and 2.18 per 1000 PY (95% CI, 1.09–4.40) in the unexposed group. The IR for CVEs was 2.9 per 1000 PY (95% CI, 2.09–4.02) in the exposed group and 4.69 per 1000 PY (95% CI, 3.40–6.47) in the unexposed group with studies of ≥48 weeks of follow-up, with an RR of 0.62 (95% CI, 0.39–0.98). The inclusion of nonrandomized and shorter-duration trials did not significantly change the RR for MI or coronary artery disease. Conclusions This pooled analysis found comparable IRs for MI and CVEs among ABC-exposed and -unexposed participants, suggesting no increased risk for MI or CVEs following ABC exposure in a clinical trial population. Modifiable risk factors for MI and CVEs should be addressed when prescribing ART.

BACKGROUND: Low birth weight and low 5-min Apgar scores have been associated with developmental delay, while older maternal age is a protective factor. Little is known about trajectories and predictors of developmental skills in infant twins, who are generally born with lower birth weights, lower Apgar scores and to older mothers. METHODS: Developmental skills were assessed at 3, 6, 9, 12, 18 and 24 months using the Ages and Stages Questionnaires in 152 twins from the Birmingham Registry for Twin and Heritability Studies. Multilevel spline and linear regression models (adjusted for gestational age, gender, maternal age) were used to estimate developmental trajectories and the associations between birth weight, maternal age and Apgar scores on developmental skills. RESULTS: Twins performed worse than singletons on communication, gross motor, fine motor, problem solving and personal-social skills (p

Group B Streptococcus (GBS) is a leading cause of meningitis and sepsis in infancy, but burden of disease data are scarce for Asia. We performed two hospital-based, prospective, descriptive, observational studies using similar protocols in the Philippines and Thailand to evaluate neonatal GBS disease epidemiology. Infants aged90 days with a GBS-positive culture from normally sterile sites using routine microbiological standards were eligible for inclusion. Awareness of GBS symptoms was raised by informing all women at delivery and follow-up for 90 days post-delivery. Infections were classified as early onset disease (EOD) if they occurred within 6 days of birth and late Onset disease (LOD) if they occurred 7-89 days after birth. Due to ethical requirements in Thailand, consent for study participation, including periodic post-discharge telephone calls, was obtained at delivery. Parents in the Philippines gave consent for study participation at case identification. The clinical outcomes of GBS infections were recorded. During the 6-month study period, two cases (one fatal) of EOD were identified among 8,409 live births at the study hospitals in Thailand and three cases (two fatal) of EOD were identified among 11,768 live births reported at the study hospitals in the Philippines. Incidence rates per 1,000 live births were 0.2 (95% CI: 0.0-0.8) and 0.3 (95% CI: 0.1-0.8) in Thailand and the Philippines, respectively. There were no cases of reported LOD. The low number of cases precluded analysis of serotype distribution and case fatality rates. Large epidemiological studies are needed to better understand the factors influencing GBS infection incidence in Asia.

Background Several observational studies and randomized controlled trials (RCTs) have suggested an association between abacavir (ABC) use and myocardial infarction (MI) but others, including meta-analyses of clinical trial data, have not. Methods This updated meta-analysis estimates exposure-adjusted incidence rate (IR) and relative rate (RR) of MI and coronary artery disease (CAD) in subjects receiving ABC and non ABC-containing combination antiretroviral therapy (cART). Summary data from 52 Phase II-IV RCTs from a previous meta-analysis were combined with aggregate data from 14 new RCTs. Subjects were either randomized to ABC cART vs. other cARTs, or ABC was prescribed as a background medication. Primary analyses included ABC-randomized trials with a follow-up of ≥48 weeks and focused on MI. Secondary analyses included shorter duration trials and non-ABC-randomized trials and estimated IR and RR for both MI and CAD. Results In 66 clinical trials (75% male, aged 18–85 years), 13,119 adults were on ABC-containing cART and 7,350 were not. Exposure-adjusted IR for MI was 1.5 per 1,000 person-years (PY) [95% Confidence Interval (CI) 0.67–3.34] in the ABC-exposed group, and 2.18 per 1,000 PY (95% CI 1.09–4.40) in the unexposed group with a RR of 0.69 (95% CI 0.24–1.98). RR for MI was 0.69 (95% CI 0.24–1.99) with inclusion of shorter duration studies, and 0.83 (95% CI 0.44–1.60) with inclusion of ABC non-randomized studies. The IR for CAD was 2.9 per 1,000 PY (95% CI 2.09–4.02) in the ABC-exposed group and 4.69 per 1,000 PY (95% CI 3.4–6.47) in the unexposed group with studies of ≥48 weeks of follow-up, with a RR of 0.62 (95% CI 0.39–0.98). With inclusion of studies of

Background: A global federation of available healthcare databases on infants, children, and adolescents could provide currently missing power and data comparability to improve knowledge on disease burden, and drug/ vaccine use and safety. Objectives: To identify and describe globally automated healthcare databases as a first step to create a collaborative network. Methods: In frame of the Global Research in Paediatric (GRiP) network (http://www.grip-network.org), we performed a web-based survey among all databases that were identified through manual revision of the pharmacoepidemiology/pharmacovigilance conference abstracts, the Bridge.to.Data database or by direct knowledge of the GRiP network members. The survey solicited information on the database contact, available population, exposure and outcome, as well as access, governance and sharing possibilities. Results: A total of 125 databases were identified globally (Europe, North- and South-America, Asian/Pacific area, and Africa) and were invited to participate to a survey. To date, 61 answers were received (49%), with 52% of respondents (N = 32) agreeing to collaborate with the GRiP network in future pharmacoepidemiology studies. Collaborating databases are located in 8 different European countries (N = 21), in 4 Asian/Pacific area countries (N = 5), in Canada (N = 4) and in the US (N = 2); one is available in more than one country. The data sources comprise a total of 40 million children (

Increased body mass index (BMI) is a worldwide health issue. Individual differences in the susceptibility to increased BMI could be related to genes or environment. We performed a systematic review of genetic studies on BMI in pre-adolescence, young adulthood and late adulthood. We searched PubMed and EMBASE with heritability, body mass index, BMI, weight, height, anthropometry and twins as search terms. Studies reporting intra-pair correlations of healthy twin pairs that were raised together were included. This resulted in the inclusion of 8,179 monozygotic (MZ) and 9,977 dizygotic (DZ) twin pairs from twelve published studies in addition to individual participant data for 629 MZ and 594 DZ pairs from four twin registries. Structural equation modelling with intra-pair twin correlations showed that the heritability of BMI remained high over all age categories ranging from 61 % (95 % CI 54-64 %) to 80 % (95 % CI 76-81 %) for male and female subjects combined, while unique environmental influences increased from 14 % (95 % CI 13-15 %) to 40 % (95 % CI 37-43 %) with increasing age. Heritability of BMI remains consistently high over different age categories. Environmental changes over time do not seem to have as big a relative impact on an individual's weight as previously reported, suggesting a mainly genetic influence on variation in BMI over the years. © Springer-Verlag 2012.