Feasibility of implementing a web-based tool built from pharmacy claims data (e-MEDRESP) to monitor adherence to respiratory medications in primary care.

OBJECTIVE: e-MEDRESP is a novel web-based tool that provides easily interpretable information on patient adherence to asthma/chronic obstructive pulmonary disease (COPD) medications, using pharmacy claims data. This study investigated the feasibility of implementing e-MEDRESP in primary care. MATERIAL AND METHODS: In this 16-month prospective cohort study, e-MEDRESP was integrated into electronic medical records. Nineteen family physicians and 346 of their patients were enrolled. Counters embedded in the tool tracked physician use during the follow-up. Patient/physician satisfaction with e-MEDRESP was evaluated though telephone interviews and online questionnaires. The capacity of e-MEDRESP to improve adherence was explored using a pre-post analysis. RESULTS: Overall, 245 patients had at least one medical visit during follow-up. e-MEDRESP was consulted by 15 (79%) physicians for 85 (35%) patients during clinic visits. Seventy-three patients participated in telephone interviews; 84% reported discussing their medication use with their physician; 33% viewed their e-MEDRESP report and indicated that it was easy to interpret. The physicians reported that the tool facilitated their evaluation of their patients' medication adherence (mean ± standard deviation rating: 4.8 ± 0.7, on a 5-point Likert scale). Although the pre-post analysis did not reveal improved adherence in the overall cohort, adherence improved significantly in patients whose adherence level was <80% and who were prescribed inhaled corticosteroids (26.9% [95% CI 14.3-39.3%]) or long-acting muscarinic agents (26.4% [95% CI 12.4-40.2%]). CONCLUSIONS: e-MEDRESP was successfully integrated in clinical practice. It could serve as a useful tool to help physicians monitor their patients' medication adherence.

Electrocatalytic reduction of CO2 in water by a C-functionalized Ni-cyclam complex grafted onto carbon.

We present here a novel strategy based on the covalent grafting of a C-functionalized Ni-cyclam complex onto glassy carbon to achieve heterogeneous electrocatalytic CO2 reduction in neutral water at low overpotential (-500 mV vs. NHE), with moderate turnover number (TON = 454), high selectivity (85% CO produced) and good faradaic efficiency (56% CO). Direct comparison with the N-functionalized Ni-cyclam analogue highlights the benefits of this approach in terms of CO2 electroreduction.

Identifying asthma patients at high risk of exacerbation in a routine visit: A machine learning model.

BACKGROUND: Tools capable of predicting the risk of asthma exacerbations can facilitate asthma management in clinical practice. However, existing tools require additional data from patients beyond electronic medical records. OBJECTIVE: To predict asthma exacerbation in an upcoming year using electronically accessible data conditional on past adherence to asthma medications. METHODS: This retrospective cohort study included patients with ≥1 hospitalization or ≥2 medical claims for asthma within 2 consecutive years between 2002 and 2015 in Quebec administrative databases. Cohort entry (CE) was defined as the date of the first asthma-related ambulatory visit on or after meeting the operational definition of asthma. Adherence to each controller medication and use of each rescue medication was measured in the year prior to CE. Elastic-net regularized logistic regression was applied. RESULTS: Among 98,823 patients, the mean age was 55.9 years and 36.2% were men. The area under the curve for prediction was 0.708. In the model, the use of long-acting anticholinergic or long-acting ß2-agonists in the year prior to CE increased the odds of exacerbation by 24% and 21%, respectively. Among patients who received rescue medication, low and high adherence to controller medications increased the odds by 2%-5% compared with patients with medium adherence. Patients with a predicted risk of ≥0.20 were more likely to develop future exacerbation. CONCLUSION: This risk prediction indicated that asthma-related medication use increased the risk of asthma exacerbation. A potential U-shaped relationship between adherence to controller medications and the risk of exacerbation was identified among users of rescue medications.

Association Between Asthma Control Trajectories in Preschoolers and Long-Term Asthma Control.

BACKGROUND: The potential influence of asthma control in early life on long-term outcomes in childhood remains largely unknown. OBJECTIVE: To examine whether asthma control trajectories in the 2 years after diagnosis in preschoolers are associated with long-term unsatisfactory asthma control. METHODS: We conducted a multicenter population-based retrospective cohort study, including four Canadian provincial birth cohorts derived from administrative databases. We included preschoolers (aged <5 years) with a diagnosis of asthma, defined as having one hospitalization or two physician visits for asthma within 2 years. Asthma control trajectories, ascertained over four 6-month periods after diagnosis using a validated index, were classified as controlled throughout, improving control, fluctuating control, worsening control, and out of control throughout. Long-term unsatisfactory control was defined as four or more short-acting ß2-agonist average doses per week or an exacerbation, measured within 6 months before index ages 6, 8, 10, 12, 14, and 16 years. Average risk ratios for long-term unsatisfactory control across all index ages were estimated using a robust Poisson model by province and meta-analyzed with a random effects model. RESULTS: In 50,188 preschoolers with asthma, the pooled average risk of having unsatisfactory control at any index age was 42% (95% confidence interval, 34.6-49.4). Compared with children who were controlled throughout, incrementally higher average risk ratios (95% confidence interval) of long-term unsatisfactory control were observed in each trajectory: improving control, 1.38 (1.28-1.49); fluctuating control, 1.54 (1.40-1.68); worsening control, 1.70 (1.55-1.86) and out of control throughout, 2.00 (1.80-2.21). CONCLUSIONS: Suboptimal asthma control trajectories shortly after a preschool diagnosis were associated with long-term unsatisfactory asthma control. Early control trajectories appear to be promising for predicting the risk for long-term adverse outcomes.

Development of an operational definition of treatment escalation in adults with asthma adapted to healthcare administrative databases: A Delphi study.

BACKGROUND: In recent years, there has been growing interest in studying asthma treatment escalation patterns in the real-world setting, particularly with the advent of expensive biologic therapies. Healthcare administrative claims databases can be used to study treatment escalation patterns at a population-level; however, the reported definitions for claims-based asthma treatment escalation are highly variable in the literature. OBJECTIVE: The aim of this study was to develop an operational definition of treatment escalation in adults with asthma that can be applied to healthcare administrative data. METHODS: A mixed-methods research design incorporating the Delphi process was used to establish an expert consensus for this definition. A multi-disciplinary expert panel participated in three iterative rounds of online questionnaires covering treatment escalation criteria inspired by a systematic review, which was conducted as part of this study. The final definition was constructed using criteria for which a 75% level of agreement was achieved among the experts. RESULTS: We developed a claims-based treatment escalation definition that was adapted from the Global Initiative for Asthma (GINA) strategy. The definition comprised seven treatment steps, as well as escalation options for treatments that are not typically included in clinical guidelines. The definition also incorporated methods to identify treatments in severe asthma, such as oral corticosteroid maintenance therapy and chronic azithromycin use. CONCLUSIONS: The operational definition of treatment escalation developed in this study bridges the gap between clinical guidelines and real-world clinical practice and lays the groundwork for future observational studies on treatment escalation patterns among patients with asthma.

Predictors of Asthma Control and Exacerbations: A Real-World Study.

BACKGROUND: Achieving optimal asthma control and minimizing the risk of exacerbation are the main goals of asthma treatment. OBJECTIVE: This study aimed to assess the predictors of poor asthma control and asthma exacerbations within a population of moderate to severe asthmatic patients treated in a tertiary-care center. METHODS: We conducted a cohort study assessing 738 patients enrolled in the Quebec registry in respiratory health (RESP) with a diagnosis of asthma confirmed by a respirologist and treated in a tertiary care center from April 2010 to March 2016. Sociodemographic and clinical data, including Asthma Control Questionnaire score, were collected at enrollment in the registry (ie, cohort entry) and patients were followed for a 2-year period thereafter. The information regarding exacerbations that occurred during follow-up was collected in administrative databases (Régie d l'assurance médicale du Québec [RAMQ], Maintenance et exploitation des données pour l'étude de la clientèle hospitalière [MED-ECHO], and medication data registry [reMed]). RESULTS: We assessed 738 subjects (64% women). Psychological distress (odds ratio [OR] 1.91; 95% confidence interval [95% CI] 1.21-3.02), smoking (OR 3.72; 95% CI 1.72-8.05]), and poor lung function, forced expiratory volume in 1 second less than 50% (OR 4.1; 95% CI 1.48-11.34]) appeared as significant factors associated with uncontrolled asthma. Occurrence of previous asthma exacerbations (hazard ratio [HR] 6.25; 95% CI 4.01-9.75]), poor asthma control (HR 1.60; 95% CI 1.07-2.38]), forced expiratory volume in 1 second between 50% and 80% (HR 2.25; 95% CI 1.58-3.34]), and older age (HR 2.26; 95% CI 1.37-3.74]) were associated with asthma exacerbations. Adherence to asthma treatment was very low in patients with (44.4% ± 34.4%) and without asthma exacerbations (37.5% ± 33.0%). CONCLUSIONS: Psychological distress and current smoking are modifiable factors that need to be addressed in tailored behavioral interventions to improve asthma control. Asthma exacerbations are mostly associated with the intrinsic severity of the disease.

Association between the timing of asthma diagnosis and medication use during pregnancy.

STUDY OBJECTIVE: To assess whether asthma medication use during pregnancy differs in women newly diagnosed with asthma early in pregnancy (first 19 weeks of pregnancy) compared to those newly diagnosed up to 2 years pre-pregnancy. DESIGN: A retrospective population-based cohort study. DATA SOURCE: To conduct this study, we used the Quebec Asthma and Pregnancy Database (QAPD) constructed by linking two administrative health databases from the province of Quebec (Canada): the Régie de l'Assurance Maladie du Québec and Maintenance et Exploitation des Données pour l'Étude de la Clientèle Hospitalière databases. PATIENTS: A cohort comprising pregnant women newly diagnosed with asthma at any time in the 2 years prior to pregnancy or during the first 19 weeks of pregnancy was selected from the QAPD. MEASUREMENTS AND MAIN RESULTS: We assessed the number of filled prescriptions of inhaled corticosteroids (ICS), ICS/long-acting ß2 agonists (LABA), and short-acting ß2 agonists (SABA), as well as the number of days' supply of oral corticosteroid (OCS) from the 20th week of pregnancy until delivery. Poisson regression was used to compare the rates of asthma medication use in women diagnosed pre-pregnancy versus early in pregnancy. The cohort included 1731 women newly diagnosed with asthma pre-pregnancy and 359 women newly diagnosed with asthma early in pregnancy. Women diagnosed early in pregnancy were more likely to use ICS (adjusted rate ratio: 1.9, 95% confidence interval (CI): 1.6-2.3) and SABA (adjusted rate ratio: 2.0, 95% CI: 1.7-2.4) from the 20th week of pregnancy until delivery than those newly diagnosed pre-pregnancy. No significant differences were observed in the use of ICS/LABA [adjusted rate ratio: 0.9, 95% CI: 0.7-1.3] and OCS [adjusted rate ratio: 0.8, 95% CI: 0.6-1.2]. CONCLUSION: The higher use of ICS and SABA observed in women newly diagnosed with asthma early in pregnancy may suggest a more persistent asthma phenotype caused by pregnancy-triggered hormonal changes.

Association between asthma control trajectories in preschoolers and disease remission.

INTRODUCTION: Early disease morbidity has been associated with asthma persistence in wheezing preschoolers; however, whether asthma control trajectories shortly after diagnosis could influence remission is unknown. We examined the association between asthma control trajectories 2 years post-diagnosis in preschoolers and subsequent disease remission. METHODS: We conducted a multicentre population-based retrospective cohort study consisting of 48 687 children with asthma diagnosed before 5 years old and born between 1990 and 2013 in four Canadian provinces who had prolonged disease activity post-diagnosis. Prolonged disease activity was defined as one or more medical visits or medications for asthma every 6-month period for at least four of the six periods post-diagnosis. Follow-up began at 3 years post-diagnosis (at cohort entry). Remission was defined as 2 consecutive years without drug claims or medical visits for asthma or asthma-like conditions following cohort entry. Asthma control trajectories, ascertained over four 6-month periods following diagnosis using a validated index, were classified as: "controlled throughout", "improving control", "worsening control", "out of control throughout" and "fluctuating control". Adjusted Cox models estimated associations between asthma control trajectories and time to remission. A random effects meta-analysis summarised province-specific hazard ratios (HRs). RESULTS: The pooled remission rate was 8.91 (95% CI 8.80-9.02) per 100 person-years. Compared with children controlled throughout, poorer asthma control was associated with incrementally lower hazard ratios of remission in four other trajectories: improving control (HR 0.89, 95% CI 0.82-0.96), fluctuating control (HR 0.78, 95% CI 0.71-0.85), worsening control (HR 0.68, 95% CI 0.62-0.75) and out of control throughout (HR 0.52, 95% CI 0.45-0.59). CONCLUSIONS: Asthma control trajectories 2 years following a diagnosis in preschoolers were associated with remission, highlighting the clinical relevance of documenting control trajectories in early life.

Impact of discretization of the timeline for longitudinal causal inference methods.

In longitudinal settings, causal inference methods usually rely on a discretization of the patient timeline that may not reflect the underlying data generation process. This article investigates the estimation of causal parameters under discretized data. It presents the implicit assumptions practitioners make but do not acknowledge when discretizing data to assess longitudinal causal parameters. We illustrate that differences in point estimates under different discretizations are due to the data coarsening resulting in both a modified definition of the parameter of interest and loss of information about time-dependent confounders. We further investigate several tools to advise analysts in selecting a timeline discretization for use with pooled longitudinal targeted maximum likelihood estimation for the estimation of the parameters of a marginal structural model. We use a simulation study to empirically evaluate bias at different discretizations and assess the use of the cross-validated variance as a measure of data support to select a discretization under a chosen data coarsening mechanism. We then apply our approach to a study on the relative effect of alternative asthma treatments during pregnancy on pregnancy duration. The results of the simulation study illustrate how coarsening changes the target parameter of interest as well as how it may create bias due to a lack of appropriate control for time-dependent confounders. We also observe evidence that the cross-validated variance acts well as a measure of support in the data, by being minimized at finer discretizations as the sample size increases.

Development of a Web-Based Tool Built From Pharmacy Claims Data to Assess Adherence to Respiratory Medications in Primary Care.

BACKGROUND: Medication adherence in asthma and COPD is notoriously low. To intervene effectively, family physicians need to assess adherence accurately, which is a challenging endeavor. In collaboration family physicians and individuals with asthma or COPD, we aimed to explore the barriers and facilitators of assessing medication adherence in clinical practice (exploratory phase), and to develop a novel web-based tool (e-MEDRESP) that will allow physicians to monitor adherence using pharmacy claims data (development phase). METHODS: We used qualitative research methods and a framework inspired by user-centered design principles. Five focus groups were held: 2 with subjects (n = 15) and 3 with physicians (n = 20), and 10 individual interviews were conducted with physicians. In the exploratory phase, data were analyzed using thematic networks. In the development phase, we identified components to be included in an e-MEDRESP prototype through an iterative approach. The web-based e-MEDRESP tool was constructed by applying algorithms to pharmacy claims data that reflected end-users' recommendations through an informatics approach designed for electronic medical records. RESULTS: The main barriers to assessing medication adherence included a lack of objective information regarding medication use and short duration of medical visits. Physicians emphasized that identifying patients at risk for nonadherence requires a team effort from pharmacists, respiratory therapists, and nurses. Subjects also agreed that the use of easily interpretable pharmacy claims data could be an important facilitator and contributed to the development of the e-MEDRESP prototype, which contains graphical representations of the adherence to respiratory controller medications and dispensing of rescue medications. CONCLUSIONS: The e-MEDRESP tool has the potential to allow physicians to measure adherence objectively and to facilitate patient-physician communication concerning medication use. Future studies are needed to evaluate the feasibility of implementing e-MEDRESP in clinical practice. It would be relevant to develop strategies that could facilitate the sharing of information presented in e-MEDRESP among primary care health professionals.

Timing of Maternal Asthma Diagnosis in Relation to Adverse Perinatal Outcomes.

BACKGROUND: It is unclear if asthma diagnosed during pregnancy puts the fetus at a higher risk of poor perinatal outcomes than pre-existing asthma. OBJECTIVE: To assess if the risks of prematurity, major malformations, and small-for-gestational age (SGA) are higher in women with asthma diagnosed during versus pre-pregnancy. METHODS: We retrospectively analyzed a cohort of pregnant women aged ≥15 years with and without incident asthma, constructed from health administrative databases. Follow-up began 24 months before pregnancy onset (cohort entry) and ended at delivery. Incident asthma was defined as a first diagnosis among those without asthma in the 8 years before cohort entry. Time was classified into pre-pregnancy and each trimester until delivery. We fit inverse probability weighted Poisson models to estimate marginal relative risks (RRs) for prematurity (delivery <37th week), major malformations, and SGA (birth weight <10th percentile) comparing women with and without asthma, assessing the asthma timing of diagnosis interaction term via a Wald test. RESULTS: In a cohort of 122,880 deliveries, the increased risk of prematurity, but not SGA, due to incident asthma was higher in those diagnosed during the second (RR, 1.34; 95% confidence interval [CI], 1.08-1.65; Wald P = .05) and third (RR, 1.93; 95% CI, 1.62-2.29; Wald P < .01) trimesters relative to pre-pregnancy (RR, 1.06; 95% CI, 0.98-1.15). A trend toward an increased risk of major malformations was observed in those diagnosed during the first trimester (RR, 1.18; 95% CI, 0.94-1.49; Wald P = .15) than pre-pregnancy (RR, 0.99; 95% CI, 0.92-1.07). CONCLUSIONS: Asthma diagnosed during, versus before, pregnancy was associated with a greater prematurity risk, suggesting an important role of preconception and prenatal screening.

Understanding and diagnosing the potential for bias when using machine learning methods with doubly robust causal estimators.

Data-adaptive methods have been proposed to estimate nuisance parameters when using doubly robust semiparametric methods for estimating marginal causal effects. However, in the presence of near practical positivity violations, these methods can produce a separation of the two exposure groups in terms of propensity score densities which can lead to biased estimates of the treatment effect. To motivate the problem, we evaluated the Targeted Minimum Loss-based Estimation procedure using a simulation scenario to estimate the average treatment effect. We highlight the divergence in estimates obtained when using parametric and data-adaptive methods to estimate the propensity score. We then adapted an existing diagnostic tool based on a bootstrap resampling of the subjects and simulation of the outcome data in order to show that the estimation using data-adaptive methods for the propensity score in this study may lead to large bias and poor coverage. The adapted bootstrap procedure is able to identify this instability and can be used as a diagnostic tool.

Development of a graphical tool to measure medication adherence in asthma patients: A mixed-methods pilot study.

OBJECTIVES: ( 1 ) To develop Med-Resp, a graphical tool based on prescription refills to measure adherence and use of asthma medications; ( 2 ) To test the feasibility of implementing Med-Resp in a hospital outpatient asthma clinic; ( 3 ) To explore the effectiveness of Med-Resp to improve medication adherence to asthma controller medications. METHODS: A sequential exploratory design was used: ( 1 ) Prototype design in collaboration with respiratory physicians and patients via focus groups; ( 2 ) Med-Resp creation based on algorithms developed and applied to prescription refills data recorded in the drug claims database reMed; ( 3 ) Feasibility assessment of the implementation of Med-Resp in the outpatient asthma clinic; and ( 4 ) Exploration of the effectiveness of Med-Resp through a pre-post design. RESULTS: A total of 29 patients and six respiratory physicians participated in this pilot study. The tool was highly appreciated by the participants, while the majority believed that Med-Resp has the potential to enhance physician-patient communication and aid in treatment decisions. The feasibility of implementing Med-Resp in clinical practice was demonstrated. However, we did not observe an increase in medication adherence in the six months following its implementation. CONCLUSION: In the clinical setting, the use of prescription refills data may constitute a non-invasive and objective measure of medication adherence. This study highlights the importance of providing clinicians with objective and easily interpretable measures of medication adherence and use in routine clinical practice. Med-Resp has the potential to become implemented on a larger scale if integrated in electronic medical records.

Risk of Postpartum Depression Among Women with Asthma.

BACKGROUND: Several epidemiological studies have suggested that the risk of depression is increased in patients with asthma, but the impact of asthma during pregnancy on postpartum depression remains unknown. OBJECTIVE: To assess the association between maternal asthma and postpartum depression in a population-based cohort study retrieved from administrative databases. METHODS: A cohort of 35,520 pregnancies in women with asthma during pregnancy and 197,057 pregnancies in women without asthma who delivered between 1998 and 2009 was extracted from the Quebec Asthma and Pregnancy Database. They were followed from the day of delivery up to 1 year postpartum. A generalized estimating equation model was used to estimate the adjusted odds ratios of postpartum depression with 95% CIs in women with asthma during pregnancy versus women without asthma. RESULTS: Postpartum depression within 1 year after delivery occurred in 6.1% of women with asthma versus 2.9% of women without asthma. After adjusting for several potential confounders, including depression/postpartum depression up to 10 years before pregnancy, we found that women with asthma were 58% more likely to experience postpartum depression within 1 year after delivery than women without asthma during pregnancy (adjusted odds ratio, 1.58; 95% CI, 1.50-1.67). CONCLUSIONS: Our findings suggest that women with asthma are more likely to suffer from postpartum depression. A close monitoring of signs of depression for pregnant women with asthma is indicated, allowing prompt and efficient interventions if needed.

Long-Acting ß2-Agonists and Risk of Hypertensive Disorders of Pregnancy: A Cohort Study.

BACKGROUND: Maternal asthma has been found to be associated with an increased risk of hypertensive disorders of pregnancy (HDP), that is, gestational hypertension, preeclampsia, and eclampsia. There is limited data, however, regarding the relationship between the use of long-acting beta-agonists (LABAs) during pregnancy and these outcomes. OBJECTIVE: To investigate whether exposure to a LABA in addition to an inhaled corticosteroid increases the risk of HDP or preeclampsia/eclampsia, as compared with nonexposure to LABAs, in pregnant women with asthma. METHODS: A cohort of 8,936 pregnancies in women with asthma who delivered between 1998 and 2010 was reconstructed using Quebec (Canada) health administrative databases. Cox proportional hazard regression models, adjusted for potential confounders, were used for statistical analyses. The primary exposure was LABA use (yes/no) measured on the first day of the 20th week of pregnancy. HDP were identified on the basis of recorded diagnoses and on prescriptions of antihypertensive drugs filled on or after the first day of week 20 of gestation. RESULTS: There were 567 (6.3%) cases of HDP and 256 (2.9%) cases of preeclampsia/eclampsia in the cohort, and the rates of both disorders were similar in women exposed or not exposed to LABAs. LABA use was not associated with increased risks of HDP (adjusted hazard ratio, 0.96; 95% CI, 0.69-1.33) or preeclampsia/eclampsia (adjusted hazard ratio, 0.89; 95% CI, 0.53-1.50). CONCLUSIONS: The results of this study provide evidence suggesting the safety of LABAs for the treatment of asthma in pregnancy, in terms of the risks of HDP and preeclampsia/eclampsia.

Adherence and Persistence to Long-Acting Anticholinergics Treatment Episodes in Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: No studies have examined adherence or persistence to long-acting anticholinergics (LAAC) treatment episodes in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To estimate 1-year adherence and 5-year persistence to LAAC during treatment episodes, and the likelihood of initiating a subsequent treatment episode. METHODS: A retrospective cohort of LAAC-treated COPD patients was reconstructed from Quebec databases. A treatment episode was initiated at cohort entry, defined as the first LAAC prescription date on/after the first COPD diagnosis date recorded between October 1, 2003, and March 31, 2014. We identified a subsequent treatment episode up to 5 years after the end of the episode initiated at cohort entry. We measured adherence as the proportion of days covered over 1 year. Persistence was defined as prescription renewal within 90 days of the previous prescription and was plotted using Kaplan-Meier curves over 5 years. The 5-year hazard and cumulative incidence of initiating a subsequent episode were estimated with survival analyses. We compared adherence and persistence between the treatment episodes using t and log-rank tests. RESULTS: The cohort included 113 435 COPD patients. Adherence and persistence to LAAC were significantly lower in the subsequent treatment episode (55% vs 63%; P < 0.0001). The likelihood of initiating a subsequent episode was greatest immediately after the cessation of the initial episode, with 59% of patients starting a subsequent episode within 1 year. CONCLUSION: Adherence and persistence to LAAC were lower in the subsequent treatment episode. Interventions should be offered quickly after LAAC cessation.

The Impact of Different Case Ascertainment Definitions on the Prevalence of Major Congenital Malformations and their Association with Asthma During Pregnancy.

Objectives To compare the prevalence of major malformations using different case ascertainment definitions and to evaluate their impact on maternal asthma-major malformations association. Methods A cohort of pregnancies with and without asthma between 1990 and 2010 was formed. We used two classification methods: the Two step Congenital Malformation Classification (TCMC) and the Canadian Congenital Anomalies Surveillance System (CCASS). Within each method, three case definitions were compared: (1) ≥1 diagnosis in the hospital database; (2) ≥1 diagnosis in the hospital database or ≥2 in the medical claims; and (3) ≥1 diagnosis in the hospital database or ≥1 in the medical claims. We calculated the prevalence of major malformations and adjusted odds ratios (aORs) for maternal asthma association. Results Of 467,946 pregnancies, 12.3 % were with active asthma. The prevalence estimates were: TCMC 5.10-7.08 % and CCASS 7.03-10.57 %. Asthma-major malformations association was weaker with the CCASS (aOR 1.14-1.20) versus TCMC (aOR 1.22-1.26). Discussion The case ascertainment definitions with ≥1 hospitalization are likely to be the most reliable in similar administrative databases. The case ascertainment definition had a considerable impact on the prevalence of major malformations, but hardly influenced the aORs. Future studies should formally assess the validity of the case ascertainment definitions and allow generalizability to other maternal exposures.

Assessing adherence to inhaled corticosteroids in asthma patients using an integrated measure based on primary and secondary adherence.

PURPOSE: There are very few studies on primary adherence (i.e., first filling of a prescription) to inhaled corticosteroids (ICS) in asthma patients; two have involved children. Moreover, adherence can be overestimated when considering only secondary adherence (i.e., following the medication recommendations for a defined period) and ignoring primary adherence. We aimed thus to evaluate the real-world primary and secondary adherence to ICS and to develop an integrated primary and secondary adherence (IPSA) measure. METHODS: From two clinical databases of pediatric and adult asthma patients, we included 198 children and 206 adults with one ICS prescription recorded in their medical chart between 2010 and 2012 and follow-up data for ≥12 months. Adherence was estimated from written prescriptions and prescription claims data. Primary adherence was defined as filling the ICS prescription at a pharmacy within 12 months. Secondary adherence was defined as the proportion of days covered (PDC) in subjects who filled their prescription at least once. The IPSA was based on the PDC with a correction factor for primary adherence. RESULTS: Primary adherence to ICS at 12 months was 89.4 % in children and 69.4 % in adults. Secondary adherence at 12 months in children was 33.9 %, and the IPSA was 30.3 %. These values were 52.8 and 36.6 %, respectively, in adults. CONCLUSIONS: Primary adherence to ICS is low in adults and secondary adherence is poor in children and adults. Using the PDC as a unique measure of adherence led to significant overestimation in adults; IPSA leads to more valid estimates of adherence to ICS.