Identifying rare diseases using electronic medical records: the example of allergic bronchopulmonary aspergillosis.

PURPOSE: The purpose of the study is to evaluate whether primary care electronic medical records (EMRs) from patients with severe asthma can be used to identify allergic bronchopulmonary aspergillosis (ABPA) cases. METHODS: This cross-sectional feasibility study was conducted in adults with active and severe asthma registered with the Clinical Practice Research Datalink. A set of keywords flagged terms potentially indicative of ABPA in free-text comments of patients' EMRs to produce a grid on the basis of keywords' hit or miss. The grid was examined for occurrence and concurrence of keywords to discern patterns of concurrence potentially indicative of an underlying diagnosis of ABPA. RESULTS: The analyses included 3 653 169 free-text items from 21 054 patients. In total, 52 patients (0.25%) had at least one mention of 'ABPA' in their medical record; 67% of these patients also had a mention of 'aspergillus/aspergillosis', 54% of 'bronchiectasis', 42% of 'itraconazole' and 62% of 'IgE'. The term 'aspergillus/aspergillosis' occurred with a proportion of 1.84% (N = 387); 9% of these patients also had a mention of 'ABPA', and the remaining 91% were potential additional cases of ABPA. From the observed concurrence of keywords, we were able to devise a potential algorithm to identify cases with varying degrees of specificity. CONCLUSIONS: This study suggests that analysis of free text within asthmatic patients' EMRs may be used to identify potential cases of ABPA. This could be an efficient approach to identify rare conditions and to quantify their potential burden. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

Importance of feasibility assessments before implementing non-interventional pharmacoepidemiologic studies of vaccines: lessons learned and recommendations for future studies.

PURPOSE: Investigational and marketed vaccines are increasingly evaluated, and manufacturers are required to put in place mechanisms to monitor long-term benefit-risk profiles. However, generating such evidence in real-world settings remains challenging, especially when rare adverse events are assessed. Planning of an appropriate study design is key to conducting a valid study. The aim of this paper is to illustrate how feasibility assessments support the generation of robust pharmacoepidemiological data. METHODS: Following an initiative launched by the International Society for Pharmacoepidemiology in May 2014, a working group including members of the private and public sectors, was formed to assess the value of conducting feasibility assessments as a necessary step before embarking on larger-scale post-licensure studies. Based on five real-life examples of feasibility assessments, lessons learned and recommendations were issued by the working group to support scientific reasoning and decision making when designing pharmacoepidemiologic vaccine studies. RESULTS: The working group developed a toolbox to provide a pragmatic approach to conducting feasibility assessments. The toolbox contains two main components: the scientific feasibility and the operational feasibility. Both components comprise a series of specific questions aimed at overcoming methodological and operational challenges. CONCLUSIONS: A feasibility assessment should be formalized as a necessary step prior to the actual start of any pharmacoepidemiologic study. It should remain a technical evaluation and not a hypothesis testing. The feasibility assessment report may facilitate communication with regulatory agencies toward improving the quality of study protocols and supporting the endorsement of study objectives and methods addressing regulatory commitments. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.

Risk of solid organ transplant rejection following vaccination with seasonal trivalent inactivated influenza vaccines in England: A self-controlled case-series.

BACKGROUND: Annual seasonal influenza vaccination is recommended for transplant recipients. No formal pharmacoepidemiology study has been published on the association between solid organ transplant (SOT) rejection and vaccination with seasonal trivalent inactivated influenza vaccines (TIIVs). METHODS: The risk of SOT (liver, kidney, lung, heart or pancreas) rejection after TIIV vaccination was assessed using a self-controlled case-series method (NCT01715792). SOT recipients in England with transplant rejection were selected from the Clinical Practice Research Datalink and linked Hospital Episode Statistics inpatient data. The study period (September 2006 to August 2009) encompassed three consecutive influenza seasons. We calculated the relative incidence (RI) of SOT rejection between the 30- and 60-day post-vaccination risk periods and the control periods (any follow-up period excluding risk periods), using a Poisson regression model. RESULTS: In seasons 2006/07, 2007/08, 2008/09 and pooled seasons, 132, 136, 168 and 375 subjects, respectively, experienced at least one transplant rejection; approximately half (45%-51%) of these subjects had received a TIIV. For season 2006/07, the RI of rejection of any organ, adjusted for time since transplantation, was 0.74 (95% CI: 0.24-2.28) and 0.58 (95% CI: 0.24-1.38) during the 30-day and 60-day risk periods, respectively. Corresponding RIs for season 2007/08 were 1.21 (95% CI: 0.55-2.64) and 1.31 (95% CI: 0.69-2.48); for season 2008/09, 0.99 (95% CI: 0.43-2.28) and 0.64 (95% CI: 0.31-1.33); and for pooled seasons 1.01 (95% CI: 0.58-1.76) and 0.88 (95% CI: 0.56-1.38). The results of a separate analysis of kidney rejections and analyses that took into account additional potential confounders were consistent with those of the main analyses, with 95% CIs including 1 and upper limits below 3. CONCLUSION: This study provides reassuring evidence of the safety profile of TIIVs in SOT recipients, thus supporting current recommendations to vaccinate this risk group annually.

Profile of adverse events in patients receiving treatment for malaria in urban Ghana: a cohort-event monitoring study.

BACKGROUND: Antimalarial treatment strategies have changed much in the last 15 years, resulting in an increased variety of medicines available. Active pharmacovigilance methods are important for continued safety surveillance of these medicines, particularly in environments in which there is variability in treatments prescribed and limited confirmatory diagnostic capacity as well as limited ability of spontaneous reporting pharmacovigilance systems to generate much needed safety information quickly and efficiently. OBJECTIVE: Our objective was to use the cohort-event monitoring (CEM) technique to gather drug utilization and adverse event data for patients prescribed antimalarial medicines in an outpatient setting. METHODS: The characteristics of a large urban African cohort of outpatients (n = 2,831) receiving antimalarial medications are described. The cohort was actively surveyed over the subsequent week to record adverse events, using follow-up phone calls, paper reports, and/or voluntary return clinic visits. Adverse events reported in the cohort were analysed overall and by clinically relevant age and medication groupings. RESULTS: At least one event was reported in 29.4 % of patients. Adverse events were more likely to be reported in subjects older than 12 years of age, and by patients prescribed an artesunate-amodiaquine combination. A range of adverse events were reported, the most frequent higher level terms being asthenic conditions (10.1 % of total cohort), neurological signs and symptoms (4.5 %), headaches (3.1 %), appetite disorders (2.1 %), and disturbances in consciousness (1.6 %). There were three reports of possible extrapyramidal events (two cases of tremor "hand and back shaking all over" and one case of tongue protrusion), which may appear to be related to combinations including amodiaquine and an artemisinin. CONCLUSION: The CEM methodology is a useful tool for monitoring the safety of widely available and utilized medicines, particularly in an urban environment where spontaneous reporting yields poor results and where the availability of various regimens and high levels of medicine usage can give valuable 'real-life' safety data. The types and frequencies of events reported reflected the types of events expected in patients prescribed antimalarials and nearly all events reported are listed in the summary of product characteristics of the medicines involved.

Epidemiological trends of dengue disease in Brazil (2000-2010): a systematic literature search and analysis.

UNLABELLED: A literature survey and analysis was conducted to describe the epidemiology of dengue disease in Brazil reported between 2000 and 2010. The protocol was registered on PROSPERO (CRD42011001826: http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42011001826). Between 31 July and 4 August 2011, the published literature was searched for epidemiological studies of dengue disease, using specific search strategies for each electronic database. A total of 714 relevant citations were identified, 51 of which fulfilled the inclusion criteria. The epidemiology of dengue disease in Brazil, in this period, was characterized by increases in the geographical spread and incidence of reported cases. The overall increase in dengue disease was accompanied by a rise in the proportion of severe cases. The epidemiological pattern of dengue disease in Brazil is complex and the changes observed during this review period are likely to have been influenced by multiple factors. Several gaps in epidemiological knowledge regarding dengue disease in Brazil were identified that provide avenues for future research, in particular, studies of regional differences, genotype evolution, and age-stratified seroprevalence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42011001826.