The validity of diagnostic algorithms to identify asthma patients in healthcare administrative databases: a systematic literature review.

Objectives To review the available evidence supporting the validity of algorithms to identify asthma patients in healthcare administrative databases.Methods A systematic literature search was conducted on multiple databases from inception to March 2020 to identify studies that reported the validity of case-finding asthma algorithms applied to healthcare administrative data. Following an initial screening of abstracts, two investigators independently assessed the full text of studies which met the pre-determined eligibility criteria. Data on study population and algorithm characteristics were extracted. A revised version of the Quality Assessment of Diagnostic Accuracy Studies tool was used to evaluate the risk of bias and generalizability of studies.Results: A total of 20 studies met the eligibility criteria. Algorithms which incorporated ≥1 diagnostic code for asthma over a 1-year period appeared to be valid in both adult and pediatric populations (sensitivity ≥ 85%; specificity ≥ 89%; PPV ≥ 70%). The validity was enhanced when: (1) the time frame to capture asthma cases was increased to two years; (2) ≥2 asthma diagnostic codes were considered; and (3) when diagnoses were recorded by a pulmonologist. Algorithms which integrated pharmacy claims data appeared to correctly identify asthma patients; however, the extent to which asthma medications can improve the validity remains unclear. The quality of several studies was high, although disease progression bias and biases related to self-reported data was observed in some studies.ConclusionsHealthcare administrative databases are adequate sources to identify asthma patients. More restrictive definitions based on both asthma diagnoses and asthma medications may enhance validity, although further research is required to confirm this hypothesis.

Physician's perspective regarding asthma guided self-management: directives or guidance?

INTRODUCTION: Asthma guided self-management enhances patients' control of their condition under the guidance of the treating physician. The aim of the present study was to understand how physicians perceive, endorse, uptake, and support asthma guided self-management. METHODS: We conducted a secondary supplementary analysis of data originally collected as part of a multicenter collective case study in which physicians treating patients with asthma were interviewed. Using reflective thematic analysis, we aimed to explore physicians' understanding of guided asthma self-management as related to four ideas, namely: (a) understanding of the disease management and treatment goals; (b) defining medical frame and guidance; (c) describing the importance of patient-physician relationship; and (d) implementing asthma guided self-management. RESULTS: Evidence indicates that physicians perceived optimal guided self-management as related to patients' adherence to physician's instructions and recommendations, supported by the adjustment of prescribed pharmaceutical therapy contingent upon patient's symptoms. Some physicians also perceived behavior change and environmental control along with the medical recommendations. While physicians' perception of asthma and its treatment were aligned with the recommended guidelines-i.e., patient-centered care approach based on guided self-management, the actual guidance offered to patients remained primarily directive and paternalistic. Non-pharmacological approaches, such as exercise, smoking cessation, patient self-monitoring, and self-management supported by education and written self-management plans, were given little consideration in the context of the recommended treatment plan.

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.

Chronic pain patients' willingness to share personal identifiers on the web for the linkage of medico-administrative claims and patient-reported data: The chronic pain treatment cohort.

PURPOSE: The linkage between patient-reported data and medico-administrative claims is of great interest for epidemiologic research. The goal of this study was to assess the willingness of people living with chronic pain to share personal identifiers on the web for the linkage of medico-administrative and patient-reported data. METHODS: This methodological investigation was achieved in the context of the implementation of the chronic pain treatment (COPE) cohort. A web-based recruitment initiative targeting adults living with chronic pain was conducted in the province of Quebec (Canada). RESULTS: A total of 1935 participants completed the questionnaire (mean age: 49.86 ± 13.27; females: 83.69%), 921 (47.60%) of which agreed to data linkage and shared their personal identifiers (name, date of birth, health insurance number online). The most common reasons for refusal were: (1) concerns regarding data security/privacy (25.71%) and (2) the belief that the requested data were too personal/intrusive (13.52%). Some participants did not understand the relevance of data linkage (11.81%). Participants from the COPE cohort and those from the subsample who agreed to data linkage were comparable to other random samples of chronic pain individuals in terms of age and pain characteristics. CONCLUSIONS: Although approximately half of the participants refused data linkage, our approach allowed for the implementation of a data platform that contains a diverse and substantial sample. This investigation has also led to the formulation of recommendations for web-based data linkage, including placing items designed to assess willingness to share personal identifiers at the end of the questionnaire, adding explanatory videos, and using a mixed-mode questionnaire.

Pregnancy outcomes in the omalizumab pregnancy registry and a disease-matched comparator cohort.

BACKGROUND: The Observational Study of the Use and Safety of Xolair (omalizumab) during Pregnancy (EXPECT) pregnancy registry was a prospective observational study established in 2006 to evaluate perinatal outcomes in pregnant women exposed to omalizumab and their infants. OBJECTIVE: This analysis compares EXPECT outcomes with those from a disease-matched population of pregnant women not treated with omalizumab. Data from a substudy of platelet counts among newborns are also presented. METHODS: The EXPECT study enrolled 250 women with asthma exposed to omalizumab during pregnancy. The disease-matched external comparator cohort of women with moderate-to-severe asthma (n = 1153), termed the Quebec External Comparator Cohort (QECC), was created by using data from health care databases in Quebec, Canada. Outcome estimates were age adjusted based on the maternal age distribution of the EXPECT study. RESULTS: Among singleton infants in the EXPECT study, the prevalence of major congenital anomalies was 8.1%, which was similar to the 8.9% seen in the QECC. In the EXPECT study 99.1% of pregnancies resulted in live births, which was similar to 99.3% in the QECC. Premature birth was identified in 15.0% of EXPECT infants and 11.3% in the QECC. Small for gestational age was identified in 9.7% of EXPECT infants and 15.8% in the QECC. CONCLUSION: There was no evidence of an increased risk of major congenital anomalies among pregnant women exposed to omalizumab compared with a disease-matched unexposed cohort. Given the observational nature of this registry, however, an absence of increased risk with omalizumab cannot be definitively established.

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.

Validity of Algorithms for Identification of Individuals Suffering from Chronic Noncancer Pain in Administrative Databases: A Systematic Review.

BACKGROUND: Secondary analysis of health administrative databases is indispensable to enriching our understanding of health trajectories, health care utilization, and real-world risks and benefits of drugs among large populations. OBJECTIVES: This systematic review aimed at assessing evidence about the validity of algorithms for the identification of individuals suffering from nonarthritic chronic noncancer pain (CNCP) in administrative databases. METHODS: Studies reporting measures of diagnostic accuracy of such algorithms and published in English or French were searched in the Medline, Embase, CINAHL, AgeLine, PsycINFO, and Abstracts in Social Gerontology electronic databases without any dates of coverage restrictions up to March 1, 2018. Reference lists of included studies were also screened for additional publications. RESULTS: Only six studies focused on commonly studied CNCP conditions and were included in the review. Some algorithms showed a ≥60% combination of sensitivity and specificity values (back pain disorders in general, fibromyalgia, low back pain, migraine, neck/back problems studied together). Only algorithms designed to identify fibromyalgia cases reached a ≥80% combination (without replication of findings in other studies/databases). CONCLUSIONS: In summary, the present investigation informs us about the limited amount of literature available to guide and support the use of administrative databases as valid sources of data for research on CNCP. Considering the added value of such data sources, the important research gaps identified in this innovative review provide important directions for future research. The review protocol was registered with PROSPERO (CRD42018086402).

Monitoring and managing medication adherence in community pharmacies in Quebec, Canada.

BACKGROUND: Community pharmacists have direct access to prescription refill information and regularly interact with their patients. Therefore, they are in a unique position to promote optimal medication use. OBJECTIVES: To describe how community pharmacists in Quebec, Canada, identify nonadherent patients, monitor medication use and promote optimal medication adherence. METHODS: An invitation to complete a web-based survey was published online through different platforms, including a Facebook pharmacists' group, an electronic newsletter, a pharmacy network forum and e-mail. The survey included questions on participant characteristics, methods used by pharmacists to identify nonadherent patients and monitor medication use and interventions they used to promote medication adherence. RESULTS: In total, 342 community pharmacists completed the survey. The participants were mainly women (71.6%), staff pharmacists (56.7%) and aged 30 to 39 years (34.2%). The most common method to identify nonadherent patients was to check gaps between prescription refills (98.8%). The most common intervention to promote adherence was patient counselling (82.5%). The most common barriers to identifying nonadherent patients were lack of time (73.1%) and lack of prescription information (65.8%), whereas the most common barriers to intervening were anticipation of a negative reaction from their patients (91.2%) and lack of time (64%). CONCLUSION: Lack of time and lack of prescription information are frequent challenges encountered by community pharmacists regarding effective monitoring and management of patients with poor medication adherence. Pharmacists could benefit from electronic tools based on prescription refills that would provide quick and easily interpretable information on their patients' medication adherence. Can Pharm J (Ott) 2020;153:xx-xx.

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.

Using a Mixture-of-Bivariate-Regressions Model to Explore Heterogeneity of Effects of the Use of Inhaled Corticosteroids on Gestational Age and Birth Weight Among Pregnant Women With Asthma.

Asthma is a heterogeneous disease, and responses to asthma medications vary noticeably among patients. A substantively oriented objective of this study was to explore the potentially heterogeneous effects of exposure to maternal inhaled corticosteroids (ICS) on gestational age (GA) at delivery and birth weight (BW) using a cohort of 6,197 pregnancies among women with asthma (Quebec, Canada, 1998-2008). A methodologically oriented objective was to comprehensively describe the application of a Bayesian 2-component mixture-of-bivariate-regressions model to address this issue and estimate the effects of ICS on GA and BW jointly. Based on the proposed model, no association between ICS and GA/BW was found for a large proportion of asthmatic pregnancies. However, a positive association between ICS exposure and GA/BW was revealed in a small subset of pregnancies comprising mainly preterm and low-birth-weight infants. A novel application of this model was also subsequently performed using BW z score instead of BW as the outcome variable. In conclusion, the studied mixture-of-bivariate-regressions model was useful for detecting heterogeneity in the effect of ICS on GA and BW in our population of women with asthma. These analyses pave the way for analogous uses of this model for general assessment of exposure effect heterogeneity for these perinatal outcomes.

A Bayesian finite mixture of bivariate regression model for causal mediation analyses.

Building on the work of Schwartz et al, Joint Bayesian analysis of birthweight and censored gestational age using finite mixture models in Statistics in Medicine, we propose a Bayesian finite mixture of bivariate regression model for causal mediation analyses. Using an identifiability condition within each component of the mixture, we express the natural direct and indirect effects of the exposure on the outcome as functions of the component-specific regression coefficients. On the basis of simulated data, we examine the behavior of the model for estimating these effects in situations where the associations between exposure, mediator, and outcome are confounded or not. Additionally, we demonstrate that this mixture model can be used to account for heterogeneity arising through unmeasured binary or categorical mediator-outcome confounders. Considering gestational age as a potential mediator, we then illustrate our mediation mixture model to estimate the natural direct and indirect effects of exposure to inhaled corticosteroids during pregnancy on birthweight using a cohort of asthmatic women from the province of Quebec (Canada).

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.

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.

Predictors of Direct Oral Anticoagulants Utilization for Thromboembolism Prevention in Atrial Fibrillation.

PURPOSE: Several factors have been associated with the prescription of direct oral anticoagulants (DOAC) over warfarin such as younger age, fewer concomitant medications, and lower CHADS2 or bleeding scores. The primary objective of this study was to identify predictors of DOAC choice compared with warfarin for patients who are starting a new oral anticoagulant (OAC) for atrial fibrillation (AF). The secondary objective was to describe the proportion of DOAC prescriptions in new users of OAC for AF. METHODS: A retrospective cross-sectional study was conducted in a teaching hospital in Canada. Medical records of adult patients hospitalized in any medical units between October 1st, 2011 and October 1st, 2014, who were newly prescribed an OAC for non valvular AF were systematically reviewed. Baseline characteristics of warfarin and DOAC users were compared and a multivariate logistic regression analysis was completed to identify predictors of DOAC use. Variables included in the multiple regression analysis were: age, hypertension, diabetes, history of stroke or transient ischemic attack, coronary artery disease, peripheral arterial disease, CHADS2 score of 2 or more, creatinine clearance 30mL/min or more, polypharmacy, concomitant use of ASA or clopidogrel, and prescription by a neurologist. RESULTS: Among OAC users (144 patients on DOAC and 295 patients on warfarin), older age (odds ratio [OR] 0.97; 95%CI 0.95-0.98), peripheral arterial disease (OR: O.41;95%CI: 0.21-0.82), polypharmacy (OR: 0.30;95%CI:0.10-0.89), and concomitant use of clopidogrel (OR: 0.19;95%CI:0.07-0.56) decreased the probability of DOAC use. Prescription by a neurologist (OR: 2.77;95%CI:1.34-5.76) and an estimated creatinine clearance of at least 30mL/min (OR: 3.53;95%CI:1.18-10.57) increased the likelihood of DOAC prescription. CONCLUSION: To the best of our knowledge, this is the first observational study finding that concomitant use of clopidogrel reduced the likelihood of DOAC utilization while prescription by a neurologist increased the probability of receiving a DOAC over warfarin in patients with AF.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

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.

Characterization of Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome: A Qualitative Analysis.

Approximately 15-20% of patients with chronic obstructive pulmonary disease (COPD) also display characteristics of asthma. In May 2014, the asthma-COPD overlap syndrome (ACOS) was briefly addressed in the Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy documents. We evaluated how pulmonologists diagnose and treat ACOS and how they assess its control. Pulmonologists from two university healthcare centers, having ≥ 1 year experience, treating patients with asthma, COPD, or ACOS, were invited to participate in focus groups. Two focus groups (1 hour duration) were convened with seven and five participants, respectively. According to pulmonologists from both institutions, ACOS is a new name for an existing syndrome rather than a new disease. It is characterized by incomplete reversible airflow limitations and changes in forced expiratory volume in one second over time. The pulmonologists noted that its diagnosis must be based on clinical characteristics, pulmonary function test results, and clinical intuition. To diagnose ACOS, pulmonologists must rely on their clinical judgment. They also agreed that the treatment of patients with ACOS should target the features of both asthma and COPD. Pulmonologists from both institutions used asthma control criteria to assess ACOS control. A deeper understanding would enable clinicians to establish specific criteria for the diagnosis, treatment, and follow-up of subjects with ACOS.

[Initiating an antipsychotic drug treatment for schizophrenia: the situation in Quebec, Canada, from 1998 to 2006]. / Amorcer un traitement antipsychotique en schizophrénie : la situation au Québec de 1998 à 2006.

Objectives To describe factors associated with the following characteristics of the first prescription of an antipsychotic drug treatment (ADT): 1) prescribing physician type (psychiatrist vs. general practitioner); 2) second-generation vs. first-generation antipsychotic drug; 3) in conjunction with at least one additional antipsychotic drug (multitherapy); 4) never renewed by the patient.Methods This is a pharmacoepidemiologic study using administrative data from the Régie de l'assurance maladie du Québec (RAMQ), the public healthcare insurer in Quebec, Canada. Available data sample was exhaustive for adults with a diagnosis of schizophrenia who received an ADT under RAMQ drug coverage from 1998 to 2006. We report multiple logistic regression results.Results Among 16,225 patients who met inclusion criteria 46.2% were women and 70% were beneficiaries of governmental financial assistance. Patients who had their ADT prescribed by psychiatrists tended to be younger and were more burdened by their mental illness. Multitherapy was associated with hospitalization with a psychotic disorder as main diagnosis, lower socioeconomic status, and age between 35 and 64. Second-generation antipsychotic use became progressively more prominent during the period under study. Antipsychotic non renewal was correlated with substance use disorders and was less likely to happen following hospitalization with a psychiatric main diagnosis. Conclusions Although this study is subject to the intrinsic limitations of secondary analysis of administrative data, the database available for study was exhaustive within the Quebec healthcare system and included data from both general practice and specialized care, which allowed us to draw a relevant picture of how ADT were initiated for schizophrenia in Quebec, Canada, from 1998 to 2006. This timeframe is especially relevant since the 1990s were marked by the introduction of second-generation antipsychotics in Canada.

Systematic procedure for the classification of proven and potential teratogens for use in research.

BACKGROUND: Although there is strong evidence that some medications are teratogenic, the current lists of teratogens to be used in research are outdated. The objective of this study was to develop an updatable and systematic procedure to the classification of medications proven and potentially teratogenic in the first trimester of pregnancy, for use in research. METHODS: We developed a two-step procedure for teratogen classification. Step 1 includes classifying the medications from Drugs in Pregnancy and Lactation: a Reference Guide to Fetal and Neonatal Risk (9th ed.) into two provisional lists: (1) teratogenic medications, and (2) potentially teratogenic medications. We also searched other references to add other medications. In Step 2, the Teratology Information System (TERIS) database was searched, and the medication was classified as teratogenic or potentially teratogenic according to a newly developed scheme. Expert consensus was used if a medication was not recorded in TERIS. RESULTS: A total of 114 medications were identified in Drugs in Pregnancy and Lactation: a Reference Guide to Fetal and Neonatal Risk, with 57 medications in each provisional list. Seventy-eight medications were identified in other sources. A total of 135 medications were included in Step 2; the TERIS scheme classified 23 medications, and 112 medications required expert opinion. The two experts agreed on 78.6% of the medications (kappa = 0.63). We identified 91 teratogenic and 81 potentially teratogenic medications. CONCLUSION: Using reliable references, we established a systematic procedure to the classification of medications with evidence of or potential teratogenic risk. These exhaustive lists will be useful in teratology research and related fields.

Ventricular tachyarrhythmia and sudden cardiac death with domperidone use in Parkinson's disease.

AIM: Domperidone is preferentially used over other antiemetic agents to treat digestive symptoms in Parkinson's disease (PD). Concerns have been raised regarding an increased risk of ventricular tachyarrhythmia and sudden cardiac death (VT/SCD) associated with domperidone in the general population. However, the risk in PD is unknown. METHODS: We conducted a multicentre retrospective cohort study using administrative databases from seven Canadian provinces and the UK Clinical Practice Research Datalink. Using a nested case-control analysis, we estimated the rate ratios (RRs) of VT/SCD associated with domperidone use compared to no use in patients newly-diagnosed with PD. VT/SCD events were identified using administrative medical records and vital statistics with a manual review of all potential cases. Meta-analytic methods were used to estimate overall effects across sites. RESULTS: Among 214 962 patients with PD, 2907 cases of VT/SCD were identified during 886 581 person-years of follow-up (incidence rate 3.28 per 1000 persons per year). Current use of domperidone was associated with a non-statistically significant 22% increased risk of VT/SCD (RR 1.22; 95% CI 0.99-1.50) compared with no use. The risk was significantly elevated in those with a history of cardiovascular disease (RR 1.38; 95% CI 1.07-1.78), but not in those without (RR 1.21; 95% CI 0.81-1.81). Dose and duration of use did not affect the magnitude of the risk. CONCLUSION: Domperidone use may increase the risk of VT/SCD in patients with PD, particularly those with a history of cardiovascular disease. This risk may be underestimated because of imprecision in identifying VT/SCD events.

Risk of congenital malformations for asthmatic pregnant women using a long-acting ß2-agonist and inhaled corticosteroid combination versus higher-dose inhaled corticosteroid monotherapy.

BACKGROUND: Current recommendations for managing persistent asthma during pregnancy when low-dose inhaled corticosteroids (ICSs) are insufficient include adding a long-acting ß2-agonist (LABA) or increasing the ICS dose. However, there are no data to help clinicians evaluate the safest regimen during pregnancy. OBJECTIVE: We sought to compare the risk of major congenital malformations in asthmatic women exposed to a LABA plus ICS combination and those exposed to ICS monotherapy at higher doses during the first trimester. METHODS: A cohort of asthmatic pregnant women exposed to ICSs during the first trimester who delivered between January 1990 and March 2009 was established. The primary outcome was major malformation recorded at birth or during the first year of life. Two subcohorts were established as follows: (1) users of a LABA plus low-dose ICS combination or users of a medium-dose ICS and (2) users of a LABA plus medium-dose ICS combination or users of a high-dose ICS. Generalized estimating equations were used to compare the risk of major malformations between the groups. RESULTS: In one subcohort there were 643 women who used a LABA plus low-dose ICS and 305 who used a medium-dose ICS; the other subcohort included 198 users of a LABA plus medium-dose ICS and 156 users of a high-dose ICS. The prevalence of major malformations was 6.9% and 7.2%, respectively. The adjusted odds ratio for major malformations was 1.1 (95% CI, 0.6-1.9) when a LABA plus low-dose ICS was used compared with a medium-dose ICS and 1.2 (95% CI, 0.5-2.7) when a LABA plus medium-dose ICS was used compared with a high-dose ICS. CONCLUSION: The risk of major malformations was similar with a LABA plus ICS combination and ICS monotherapy at higher doses, suggesting that both therapeutic options can be considered during pregnancy.