Validating epilepsy diagnoses in routinely collected data

Purpose: Anonymised, routinely-collected healthcare data is increasingly being used for epilepsy research. We validated algorithms using general practitioner (GP) primary healthcare records to identify people with epilepsy from anonymised healthcare data within the Secure Anonymised Information Linkage (SAIL) databank in Wales, UK. Method: A reference population of 150 people with definite epilepsy and 150 people without epilepsy was ascertained from hospital records and linked to records contained within SAIL (containing GP records for 2.4 million people). We used three different algorithms, using combinations of GP epilepsy diagnosis and anti-epileptic drug (AED) prescription codes, to identify the reference population. Results: Combining diagnosis and AED prescription codes had a sensitivity of 84% (95% ci 77–90) and specificity of 98% (95–100) in identifying people with epilepsy; diagnosis codes alone had a sensitivity of 86% (80–91) and a specificity of 97% (92–99); and AED prescription codes alone achieved a sensitivity of 92% (70–83) and a specificity of 73% (65–80). Using AED codes only was more accurate in children achieving a sensitivity of 88% (75–95) and specificity of 98% (88–100). Conclusion: GP epilepsy diagnosis and AED prescription codes can be confidently used to identify people with epilepsy using anonymised healthcare records in Wales, U

Adverse paediatric outcomes of antibiotic treatment in pregnancy

Although most antibiotics are considered safe, evidence from a mega-trial suggests that antibiotic use during pregnancy may increase the risk of adverse paediatric neurological outcomes. Understanding the results and potential implications of this mega-trial is important. However, evidence which could corroborate or refute the mega-trial is unlikely to be obtained from new trials. I considered two potential explanations for the unanticipated results of the mega-trial. First, I conducted a systematic review and meta-analysis to determine whether antibiotic treatment in pregnancy could prolong survival of neurologically damaged fetuses. I hypothesised that prolonged fetal survival in the mega-trial could have resulted in a spurious association between prenatal antibiotic treatment and adverse neurological outcome in surviving children. I found no evidence to support or contradict this explanation. Second, I conducted a cohort study using primary-care data to understand whether antibiotic treatment may have had a direct adverse effect on fetuses in the mega-trial. Whilst I found no evidence to suggest that prenatal antibiotic prescribing in general was associated with an adverse childhood outcome of cerebral palsy and/or epilepsy (adjusted hazard ratio [HR] 1.04; 95% confidence interval [CI] 0.9-1.19), I found that macrolide versus penicillin prescribing in pregnancy was associated with an increased risk of cerebral palsy and/or epilepsy. This risk remained after controlling for potential confounders including maternal infection (adj.HR 1.78; 95% CI 1.18-2.69). Of the two hypotheses I considered, the former is unlikely to account for the unanticipated findings of the mega-trial, while the latter is both unsupported (in general) and supported (for specific antibiotics). Regardless, the finding of harm associated with macrolide prescribing in pregnancy cannot be ignored, particularly given the growing body of evidence of harm with macrolide antibiotics in pregnant and non-pregnant populations. Further research on the effect of macrolide antibiotics on the fetus is warranted

COPD treatment pathways in France: a retrospective analysis of electronic medical record data from general practitioners

Wilhelmine Meeraus,1 Robert Wood,2 Rafal Jakubanis,2 Tim Holbrook,2 Geoffray Bizouard,3 Johanna Despres,3 Camille Correia Da Silva,4 Gaelle Nachbaur,4 Sarah H Landis,1 Yogesh Punekar,5 Bernard Aguilaniu,6 Afisi S Ismaila7,8 1GlaxoSmithKline, Stockley Park West, Uxbridge, UK; 2Adelphi Real World, Bollington, Cheshire, UK; 3IQVIA, Paris, France; 4GlaxoSmithKline, Rueil-Malmaison, France; 5ViiV Healthcare, Brentford, Middlesex, UK; 6Faculty of Medicine, University Grenoble-Alpes, Grenoble, France; 7GlaxoSmithKline, Collegeville, PA, USA; 8Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada Background: Increasing availability of therapeutic options for COPD may drive new treatment pathways. This study describes COPD treatment in France, focusing on identifying initial treatment modifications in patients with COPD who either initiated long-acting bronchodilator (LABD)-based therapy or escalated to triple therapy (long-acting muscarinic antagonist [LAMA] + long-acting β2-agonist [LABA] + inhaled corticosteroid [ICS]). Methods: This retrospective analysis of patients with COPD in a large general practitioner database (IQVIA Longitudinal Patient Database) in France included two cohorts: Cohort 1 – new initiators of LABD-based therapy (LAMA, LABA, LAMA + LABA, LAMA + ICS, LABA + ICS or LAMA + LABA + ICS); Cohort 2 – patients escalating to triple therapy from mono- or dual-bronchodilator-based maintenance treatment. Both cohorts were indexed on the date of initiation/escalation (January 2008–December 2013), and the first treatment modification (at class level) within the 18-month post-index observational period was described. Five mutually exclusive outcomes were defined: continuous use (no modification), discontinuation (permanent [≥91 days with no restart] or temporary [≥91 days with subsequent restart]), switch, and augmentation (Cohort 1 only). Exploratory analysis of Cohort 1 explored potential drivers of treatment initiation. Results: Overall, 5,065 patients initiated LABD-based therapy (Cohort 1), and 501 escalated to triple therapy (Cohort 2). In Cohort 1, 7.0% of patients were continuous users, 46.5% discontinued permanently, 28.5% discontinued temporarily, 2.8% augmented (added LAMA and/or LABA and/or ICS), and 15.2% switched therapy. In Cohort 2, 18.2% of patients were continuous users, 7.2% discontinued permanently, 27.9% discontinued temporarily, and 46.7% switched therapy. Exploratory analyses showed that time since COPD diagnosis was first recorded, pre-index exacerbation events, and concomitant medical conditions were potential drivers of initial maintenance treatment choices. Conclusion: Discontinuation among new initiators of LABD-based therapy was high in France, whereas few switched or augmented treatment. In comparison, permanent discontinuation within 18 months was low in patients escalating to triple therapy. Keywords: triple therapy, France, treatment pathways, treatment modification, maintenance therap