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.

Asthma exacerbations during the first trimester of pregnancy and congenital malformations: revisiting the association in a large representative cohort.

BACKGROUND: We previously reported an increased prevalence of any congenital malformation among women experiencing moderate-to-severe asthma exacerbations during the first trimester of pregnancy, based on a study in which 90.1% of the cohort of women were social welfare recipients. This study re-examined the association between asthma exacerbations and congenital malformations in a new large representative cohort of asthmatic pregnant women. METHODS: A cohort of 36 587 pregnancies in asthmatic women was reconstructed from Québec Province administrative databases (1998-2009). Occurrences of asthma exacerbations during the first trimester of pregnancy were assessed and categorised into severe, moderate and no such exacerbations. For comparison, we also considered moderate and severe asthma exacerbations combined. Congenital malformations were identified using diagnoses recorded in the hospitalisation database. Generalised estimation equations were used to estimate adjusted ORs of congenital malformations. RESULTS: The prevalence of any congenital malformation was 19.1%, 11.7% and 12.0% among women with severe, moderate and no such exacerbations during the first trimester, respectively. The adjusted OR for all malformations was 1.64 (95% CI 1.02 to 2.64) when women with severe exacerbations were compared with those in the reference group, while no association was seen for moderate exacerbations. Also, no association was observed between cases of moderate and severe asthma exacerbations combined and any congenital malformation. CONCLUSIONS: Only severe asthma exacerbations were found to significantly increase the risk of congenital malformations in this representative study. Previous studies possibly overestimated the risk because they were based mainly on women at a lower socioeconomic status.

Is drug insurance status an effect modifier in epidemiologic database studies? The case of maternal asthma and major congenital malformations.

BACKGROUND: Our previous work on the association between maternal asthma and congenital malformations was based on cohorts formed by women with public drug insurance, i.e., over-represented by women with lower socioeconomic status, questioning the generalizability of our findings. This study aimed to evaluate whether or not drug insurance status, as a proxy of socioeconomic status, is an effect modifier for the association between maternal asthma and major congenital malformations. METHODS: A cohort of 36,587 pregnancies from asthmatic women and 198,935 pregnancies from nonasthmatic women selected independently of their drug insurance status was reconstructed with Québec administrative databases (1998-2009). Asthmatic women were identified using a validated case definition of asthma. Cases of major congenital malformations were identified using diagnostic codes recorded in the hospitalization database. Drug insurance status at the beginning of pregnancy was classified into three groups: publicly insured with social welfare, publicly insured without social welfare, and privately insured. Adjusted odds ratios were estimated with generalized estimation equations, including an interaction term between maternal asthma and drug insurance status. RESULTS: The prevalence of congenital malformations was 6.8% among asthmatic women and 5.8% among nonasthmatics. The impact of asthma on the prevalence of congenital malformations was significantly greater in women publicly insured with social welfare (odds ratio = 1.42; 95% confidence interval, 1.25-1.61) than in the other two groups ([odds ratio = 1.10; 1.00-1.21] in the publicly insured without social welfare and [odds ratio = 1.13; 1.07-1.20] in the privately insured group). CONCLUSION: The increased risk of major congenital malformation associated with asthma was significantly higher among pregnant women publicly insured with social welfare than among those privately insured. As a result of this effect modification by drug insurance status, findings from Québec observational studies using databases mainly formed of patients publicly insured with social welfare may not be generalized to the entire population.

Associations of maternal asthma severity and control with pregnancy complications.

OBJECTIVES: To assess the associations of maternal asthma severity and control with pregnancy-induced hypertension (PIH), gestational diabetes and cesarean delivery. METHODS: A cohort of 41 660 pregnancies from women with and without asthma who delivered between 1990 and 2002 was constructed by linking Québec's administrative databases. Maternal asthma was defined by at least one asthma diagnosis and one dispensed prescription for an asthma medication in the 2 years before or during pregnancy. Asthma severity and control were assessed using validated indexes during the entire pregnancy to study cesarean delivery and 1-year prior to week 20 of gestation to study PIH and gestational diabetes. Generalized Estimation Equation models were used to obtain odds ratios (OR) for PIH, gestational diabetes and cesarean in association with maternal asthma severity and control. RESULTS: Almost one-third of the women had uncontrolled asthma and up to 5% had severe asthma. Severe asthma increased the risk of cesarean delivery (OR = 1.35; 95% CI: 1.11-1.63) compared with mild asthma, but no association was found between asthma severity and the other outcomes. The level of asthma control was not associated with any of the outcomes, except for a near-significant increased risk of PIH among uncontrolled women (OR = 1.18; 95% CI: 0.97-1.42). CONCLUSIONS: The risk of gestational diabetes was not associated with asthma severity or control, and the risk of PIH was not associated with asthma severity. However, further studies are needed to clarify the association between asthma control and PIH. The increased risk of cesarean among women with severe asthma may be explained by the physician's and patient's concerns over the safety of normal delivery.

Relationship between maternal asthma, its severity and control and abortion.

STUDY QUESTION: Are women with asthma, and more specifically those with severe or uncontrolled asthma, at higher risk of spontaneous and induced abortions? SUMMARY ANSWER: Pregnant women with asthma, notably when uncontrolled, are at higher risk of spontaneous abortion. WHAT IS KNOWN ALREADY: Only one study has examined the association between asthma and spontaneous and induced abortions and revealed a modest increase in the risk of spontaneous abortions, particularly in women with more severe asthma and those with previous exacerbations, and a marginal decrease in the risk of induced abortions. STUDY DESIGN, SIZE, DURATION: A cohort of pregnancies from asthmatic (n = 15,107) and non-asthmatic (n = 34,331) women was reconstructed by linking three administrative databases from Quebec (Canada), between 1992 and 2002. The cohort included 7870 spontaneous abortions, 14,596 induced abortions and 26,972 live births. PARTICIPANTS/MATERIALS, SETTING, METHODS: Pregnant women with and without asthma were analyzed. Asthma was defined by at least one asthma diagnosis and one dispensed prescription for an asthma medication in the 2 years prior to or during pregnancy. Asthma severity and control were assessed using validated indexes in the year before the 20th week of pregnancy or the termination of the pregnancy. Logistic polytomous regression models were used to estimate the relationship between asthma and asthma severity and control on the risk of abortion, while adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of spontaneous and induced abortions was 15.9 and 29.5%, respectively. Maternal asthma was associated with an increased risk of a spontaneous abortion [odds ratio (OR) = 1.41; 95% confidence interval (CI): 1.33-1.49] and a decreased risk of induced abortions (OR = 0.92; 0.88-0.97). No association was observed between asthma severity and abortion, while uncontrolled asthma increased the risk of a spontaneous abortion by 26% (95% CI: 14-41%) and the risk of induced abortions by 11% (95% CI: 1-21%). LIMITATIONS, REASONS FOR CAUTION: It is possible that the study results were confounded by imbalances between groups in variables that are not recorded in the databases, but that are known to be associated with spontaneous abortions, such as alcohol consumption, obesity or maternal smoking. However, we performed sensitivity analyses which revealed that these factors are unlikely to explain the observed increased risk for a spontaneous abortion. It is also possible that women with asthma are more likely to have abortions recorded in the databases, because subjects with a chronic disease tend to visit a physician more often than those without asthma. Therefore, our odds estimates for these outcomes may be overestimated when asthmatic women were compared with non-asthmatic women. A further limitation of the study is that it would have been more appropriate to measure the severity and control of asthma only during the pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: Our cohort is less representative of women in the upper socio-economic level. This is not a threat to internal validity, but it could limit the external validity if the impact of asthma on the risk of abortion differed according to the socio-economic status of the mother. Despite the absence of supporting data, this possibility cannot be completely excluded. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Canadian Institutes of Health Research and Genentech. L.B. received research grants from Astra-Zeneca, Pfizer, sanofi-aventis, Novartis and Merck for research projects and co-chairs the Astra-Zeneca Endowment Pharmaceutical Chair in Respiratory Health. F.Z.K and A.F. have no competing interests to declare.

Validity of congenital malformation diagnostic codes recorded in Québec's administrative databases.

PURPOSE: To assess the validity of the diagnostic codes of congenital malformations (CMs) recorded in two of Québec's administrative databases. METHODS: A cohort of pregnancies and infants born to asthmatic and non-asthmatic women in 1990-2002 was reconstructed using Québec's administrative databases. From this cohort, we selected 269 infants with a CM and 144 without CM born to asthmatic women, together with 284 and 138 infants, respectively, born to non-asthmatic women. The diagnoses of CMs recorded in the databases were compared with the diagnoses written by the physicians in the infants' medical charts. The positive predictive values (PPV) and negative predictive values (NPV) for all, major, and several specific CMs were estimated. RESULTS: The PPVs for all CMs and major CMs were 82.2% (95% confidence interval (CI): 78.5%-85.9%) and 78.1% (74.1%-82.1%), respectively, in the asthmatic group and were 79.2% (75.4%-83.1%) and 69.0% (64.6%-73.4%), respectively, in the non-asthmatic group. PPVs >80% were found for several specific CMs, including cardiac, cleft, and limb CMs in both groups. The NPV for any CM was 88.2% (95% CI: 85.1%-91.3%) in the asthmatic group and 94.2% (92.2%-96.2%) in the non-asthmatic group. CONCLUSIONS: Québec's administrative databases are valid tools for epidemiological research of CMs. The results were similar between infants born to women with and without asthma.

New measure of adherence adjusted for prescription patterns: the case of adults with asthma treated with inhaled corticosteroid monotherapy.

BACKGROUND: Common measures of adherence to prescribed medications derived from administrative databases reflect both patients' and physicians' behavior, even if the measures are often interpreted as reflecting only the patient's adherence. Adherence to inhaled corticosteroids (ICSs) has been shown to be low among patients with asthma. OBJECTIVE: To develop a new measure of patients' adherence adjusted for prescription patterns and to evaluate the extent to which the low use of ICSs in asthma is due to patients' nonadherence or suboptimal prescribing practices. METHODS: The new measure of adherence, called the proportion of prescribed days covered (PPDC), is defined as the ratio of the total days' supply dispensed to the total days' supply prescribed during the study period. The PPDC is a modification of an existing adherence measure, the proportion of days covered (PDC). The PPDC and PDC for ICSs, therapy that should be prescribed for chronic daily use to patients with persistent asthma, were compared within a cohort of 4190 ICS-naïve patients with asthma aged 18-45 years derived from the administrative health databases of Quebec, Canada. We estimated the mean and the 95% confidence interval of the PPDC and PDC for ICSs over 1 year, and we calculated the part of nonadherence attributed to patients when measured with the PDC that can be attributed to nonoptimal prescribing of ICSs for chronic daily use with the following formula: [(1-PDC)-(1-PPDC)]/(1-PDC). RESULTS: The mean PPDC and PDC during the 1-year study were 52.6% (95% CI 51.6 to 53.6) and 19.1% (95% CI 18.6 to 19.6), respectively. Forty-one percent of nonadherence attributed to patients when measured with the PDC could be, in fact, attributed to nonprescribing of ICSs for chronic daily use. CONCLUSIONS: Our new adherence measure, the PPDC, may be considered as another way to assess patient adherence, taking into account differing prescribing patterns.

Effect of maternal asthma on the risk of specific congenital malformations: A population-based cohort study.

BACKGROUND: There is a lack of consensus in the literature about the effect of maternal asthma on the development of congenital malformations. OBJECTIVE: To further examine the association between maternal asthma and the risk of congenital malformations. METHODS: A cohort of 41,637 pregnancies from women with and without asthma who delivered between 1990 and 2002 was reconstructed by linking three Quebec (Canada) administrative databases. All cases of malformations were identified using either the medical services or the hospital databases. The main exposure was maternal asthma, defined by the presence of at least one asthma diagnosis and at least one prescription for an asthma medication at any time in the two years before or during pregnancy. Generalized Estimation Equation models were performed to estimate the adjusted odds ratio (OR) of congenital malformations as a function of maternal asthma. RESULTS: The crude prevalences of any congenital malformation were 9.5% and 7.5% for women with and without asthma, respectively. Maternal asthma was significantly associated with an increased risk of any malformation (OR=1.30; 95% CI: 1.20-1.40) and three specific groups (at the 0.0028 level): nervous system (excluding spina bifida: OR=1.83; 1.37-2.83); respiratory system (OR=1.75; 1.21-2.53); and digestive system (OR=1.48; 1.19-1.85). CONCLUSIONS: Maternal asthma increases the risk of specific groups of congenital malformations. The disease itself, through fetal oxygen impairment, is likely to play a role in this increased risk, but more research is needed to disentangle the relative effect of asthma and medications used to treat this disease.

Impact of a better adherence to antihypertensive agents on cerebrovascular disease for primary prevention.

BACKGROUND AND PURPOSE: The benefits of antihypertensive (AH) drugs on the risks of major cardiovascular outcomes have been demonstrated in clinical trials. However, approximately half of hypertensive patients do not adhere well to their prescribed AH therapy in actual practice. The purpose of this study was to assess the impact of adherence to AH agents on the incidence of cerebrovascular disease (CD) in real-world practice. METHODS: A cohort of 83 267 hypertensive patients was reconstructed from the Régie de l'assurance maladie du Québec databases. Subjects included were between 45 and 85 years old, initially free of cardiovascular disease, and newly treated for hypertension with AH agents between 1999 and 2004. A nested case-control design was conducted to study CD occurrence. Every case was matched for age and duration of follow-up with up to 15 randomly selected control subjects. The adherence to AH drugs was measured by calculating the medication possession ratio. Conditional logistic regression models were performed to assess the association between adherence to AH agents and CD adjusting for various potential confounders. RESULTS: At cohort entry, the mean patient age was 65 years, 37.3% were male, 8.6% had diabetes, and 19.5% had dyslipidemia. High adherence (>/=80%) to AH drugs significantly decreased the risk of CD by 22% (rate ratio, 0.78; 95% CI, 0.70 to 0.87) compared with lower adherence. Male gender, occurrence of cardiovascular disease during follow-up, and dyslipidemia were risk factors for CD. CONCLUSIONS: High adherence to AH therapy is associated with a reduced risk of CD outside the context of clinical trials in primary prevention.

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.

Impact of Patient Reimbursement Timing and Patient Out-of-Pocket Expenses on Medication Adherence in Patients Covered by Private Drug Insurance Plans.

BACKGROUND: Adherence to prescribed medications used in the treatment of chronic diseases is suboptimal, and drug insurance plans can have an impact on adherence. There is little evidence on the impact of patient reimbursement timing on medication adherence. OBJECTIVE: To compare adherence to prescribed medications in privately insured patients from Quebec, Canada, with different patient reimbursement timing and levels of patient out-of-pocket expenses. METHODS: A retrospective cohort was constructed by selecting privately insured patients aged 18-64 years from the reMed database (2008-2012) who filled at least 1 prescription for a medication belonging to 1 of the 10 most prescribed drug classes for chronic diseases. Patient reimbursement timing was classified as immediate (immediate patient reimbursement at the point of service of the portion of the medication cost covered by the insurer) or deferred (patient reimbursement at a later time). Patient outof-pocket expenses related to the medication under study at cohort entry (available only for the immediate patient reimbursement group), which included the deductible and the coinsurance, were categorized into 5 levels (null category and quartiles): $0, $0.01-$3.59, $3.60-$8.11, $8.12-$14.40, and $14.41-$89.99. Adherence was measured with the proportion of days covered (PDC) over 1 year among new users of the medication under study. Linear regression models were used to estimate the adjusted mean difference of PDC between groups. RESULTS: There was no difference in medication adherence between the immediate (n = 1,345) and deferred patient reimbursement (n = 437; difference, 0.0%; 95% CI, -3.0 to 3.0). Patients with the highest patient out-of-pocket expenses were less adherent than those with the lowest patient out-of-pocket expenses (difference, -19.0%; 95% CI, -24.0 to -13.0); however, patients with no patient out-of-pocket expenses were less adherent than those with low patient out-of-pocket expenses (difference, -9.0%; 95% CI, -15.0 to -2.0). CONCLUSIONS: Medication adherence appeared to be unaffected by patient reimbursement timing but was affected by the level of patient out-of-pocket expenses. The absence of a correlation between medication adherence and timing of patient reimbursement might be explained by the relatively rapid reimbursement of expenses by insurance companies in Canada. Subjects with no patient out-of-pocket expenses at the point of service might be less adherent because they place less value on their medications than do patients who must pay even a small amount. DISCLOSURES: This study was funded by Pfizer Canada, Montréal, Québec, Canada. Blais received research grants or honorarium from AstraZeneca, Pfizer Canada, Sanofi, Novartis, Almirall, GlaxoSmithKline, and Merck for research projects and co-chairs the AstraZeneca Endowment Pharmaceutical Chair in Respiratory Health. Després, Kettani, and Forget have no competing interests to declare. All authors contributed to the concept and design of the study. Data were collected by Blais and Forget. Data analysis was conducted by Després. The manuscript was written by Després and revised by all authors.

Beta2-agonists use during pregnancy and perinatal outcomes: a systematic review.

BACKGROUND: Short and long-acting beta2-agonists (SABA and LABA) have a crucial role in asthma management during pregnancy, as stated in the current guidelines. OBJECTIVE: To systematically review the evidence on beta2-agonists use during pregnancy and adverse perinatal outcomes. DATA SOURCES AND STUDY SELECTION: Six databases were searched before January 1, 2013 for beta2-agonists use during pregnancy and congenital malformations, small for gestational age, mean and low birth weight, gestational age and preterm delivery. Original English language articles were included with no cut-off date. Quality assessment and post-hoc power calculations were performed. RESULTS: Twenty-one original studies were identified. Four studies reported a significant increased risk of congenital malformations with SABA, while one study reported a significant decreased risk with high doses of SABA. One study reported a significant increased risk of congenital malformations with LABA and four studies reported a significant increased risk of congenital malformations with beta2-agonists (SABA and/or LABA). One study reported a decrease in birth weight centiles among LABA users. LIMITATIONS: All studies reporting significant results, except two, used non-asthmatic women as reference group, making it difficult to differentiate between the effect of the disease from the one of the beta2-agonists. Non-significant results should be interpreted with caution due to the low statistical power of several studies. CONCLUSION: Methodological limitations and lack of power of several studies prevent us to conclude on the perinatal safety of beta2-agonists. Until further evidence is available, physicians should continue prescribing them as recommended in the guidelines whenever needed to attain asthma control.

Impact of drug plans on adherence to and the cost of antihypertensive medications among patients covered by a universal drug insurance program.

BACKGROUND: This study aimed to assess the impact of the type of drug plan on adherence to antihypertensive medication treatment as well as the cost of these medications within universal drug insurance programs. METHODS: To compare adherence to antihypertensive medication treatment and the cost of antihypertensive medications between adults with public and private drug insurance in the province of Québec, Canada, we reconstructed a matched retrospective cohort by linking data recorded in 3 administrative databases between March 2008 and May 2010. The cohort included 186 privately and 1747 publicly insured patients aged 18-64 years who were treated with 1 or 2 antihypertensive medications. Adherence measured with the proportion of days covered (PDC) over 1 year and the cost of antihypertensive medications were evaluated for new and prevalent users separately. RESULTS: More than 70% of patients were 50-64 years old and 90% of the publicly and 72% of the privately insured patients were using only 1 antihypertensive medication. The mean PDC among new users of 1 antihypertensive medication was 58.8% for privately insured patients and 65.0% for publicly insured patients, but the difference was not statistically significant. However, privately insured patients treated with 2 antihypertensive medications were more likely to be adherent (PDC-P, 15.0%; 95% confidence interval, 7.0-24.0). Privately insured patients (CAD$41.52) had to pay significantly more for their antihypertensive medications than did publicly insured patients (CAD$32.21). CONCLUSIONS: The cost of antihypertensive medications was higher for patients with private drug insurance, although adherence was similar in both groups. The results may reflect regulation of dispensing fees for publicly insured patients.

Accuracy of the days' supply and the number of refills allowed recorded in Québec prescription claims databases for inhaled corticosteroids.

OBJECTIVES AND HYPOTHESES: Adherence to inhaled corticosteroids (ICS) is a major issue in asthma. This study aimed to estimate the accuracy of the days' supply and number of refills allowed, variables recorded in Québec claims databases and used to estimate adherence, and to develop correction factors, if required. We hypothesised that the accuracy of the days' supply for ICS would be low whereas the accuracy of the number of refills allowed would be high. SETTING: 40 community pharmacies in Québec (Canada) and a medication registry. PARTICIPANTS: We collected data for 1108 ICS original prescriptions stored in the 40 pharmacies (sample 1), and we obtained a second sample of 2676 ICS prescriptions selected from reMed, a medication registry (sample 2). PRIMARY AND SECONDARY OUTCOMES: We estimated the concordance of the days' supply and number of refills between Québec claims databases and the original prescription from sample 1. We developed a correction factor for the days' supply in sample 1 and validated it in sample 2. Analyses were stratified by age: 0-11 and 12-64 years. RESULTS: In sample 1, the concordance for the days' supply was 39.6% (95% CI 37.6% to 41.6%) in those aged 0-11 years and 56% (54.9% to 57.2%) in those aged 12-64 years. The concordance increased to 59.4% (58.2% to 60.5%) in those aged 0-11 years and 74.2% (73.5% to 74.9%) in those aged 12-64 years after applying the correction factors in sample 2. The concordance for the refills allowed was 92.1% (91% to 93.1%) in those aged 0-11 years and 93.1% (92.5% to 93.7%) in those aged 12-64 years in sample 1. CONCLUSIONS: The accuracy of the days' supply was moderate among those aged 0-11 years and substantial among those aged 12-64 years after applying the correction factors. The accuracy of the number of refills was almost perfect in both groups.

The impact of the type of insurance plan on adherence and persistence with antidepressants: a matched cohort study.

OBJECTIVE: To compare adherence to, and persistence with, antidepressants (AD) in Quebec patients who are covered by private and public drug insurance. METHOD: A matched cohort study was conducted using prescription claims databases: reMed, a medication data registry for Quebec residents covered by private drug insurance, and Régie de l'assurance maladie du Québec database for Quebec residents with public drug insurance. Patients were aged 18 to 64 years and filled at least 1 prescription for an AD in monotherapy between December 2007 and September 2009 (194 privately and 2055 publicly insured patients). Adherence over 1 year was estimated using the proportion of prescribed days covered (PPDC). The difference in mean PPDC between patients with private and public drug insurance was estimated with linear regression. Persistence was compared between the groups with a Cox regression model. RESULTS: The PPDC was 86.4% (95% CI 83.3% to 89.5%) in privately insured and 82.2% (95% CI 78.5% to 85.9%) in publicly insured patients and the adjusted mean difference was 5.1% (95% CI 1.6% to 8.6%). Persistence was 51.0% in the private group and 19.7% in the public group at 1 year (P < 0.001); the adjusted hazard ratio was 0.49 (95% CI 0.30 to 0.79). CONCLUSION: Better adherence and persistence were observed in privately insured patients. Adherence difference may be due to lower copayment among privately insured patients.

Impact of obesity on perinatal outcomes among asthmatic women.

BACKGROUND: Only one study has investigated the combined effect of maternal asthma and obesity on perinatal outcomes; however, it did not consider small-for-gestational age and large-for-gestational age infants. OBJECTIVES: To examine the impact of obesity on perinatal outcomes among asthmatic women. METHODS: A cohort of 1386 pregnancies from asthmatic women was reconstructed using three of Quebec's administrative databases and a questionnaire. Women were categorized using their prepregnancy body mass index. Underweight, overweight and obese women were compared with normal weight women. The primary outcome was the birth of a small-for-gestational-age infant, defined as a birth weight below the 10th percentile for gestational age and sex. Secondary outcomes were large-for-gestational-age infants (birth weight >90th percentile for gestational age) and preterm birth (<37 weeks' gestation). Logistic regression models were used to obtain the ORs of having small-for-gestational-age infants, large-for-gestational-age infants and preterm birth as a function of body mass index. RESULTS: The proportions of underweight, normal weight, overweight and obese women were 10.8%, 53.3%, 19.7% and 16.2%, respectively. Obese asthmatic women were not found to be significantly more at risk for giving birth to small-for-gestational-age infants (OR 0.6 [95% CI 0.4 to 1.1]), large-for-gestational-age infants (OR 1.2 [95% CI 0.7 to 2.2]) or having a preterm delivery (OR 0.7 [95% CI 0.4 to 1.3]) than normal-weight asthmatic women. CONCLUSIONS: No significant negative interaction between maternal asthma and obesity on adverse perinatal outcomes was observed.

Relationship between changes in inhaled corticosteroid use and markers of uncontrolled asthma during pregnancy.

STUDY OBJECTIVE: To describe changes in inhaled corticosteroid use during pregnancy and markers of uncontrolled asthma, and to evaluate the association between them. DESIGN: Population-based, cross-sectional study. DATA SOURCE: Three administrative claims databases in Québec, Canada. PATIENTS: A cohort of 4434 asthmatic women (4920 pregnancies) who delivered their infants between 1990 and 2002 and who used inhaled corticosteroids before their pregnancy. MEASUREMENTS AND MAIN RESULTS: The average daily doses of inhaled corticosteroids during pregnancy and during the 9 months before conception were compared; the change in use was categorized as discontinuation (reduction of ≥75%), reduction (26-75% reduction), no change (±25% change), or increase (increase of ≥25%). The markers of uncontrolled asthma included at least one asthma exacerbation and the use of three or more doses/week of a short-acting ß(2) -agonist during pregnancy. Generalized estimating equation models were used for statistical analyses. In nearly 50% of the pregnancies (2388 [48.5%] of 4920), the women either stopped or reduced their doses of corticosteroid during pregnancy, and these doses were already quite low before pregnancy. The proportion of women who had an asthma exacerbation during pregnancy was 8.2% among women who discontinued corticosteroids and greater than 20% in all of the other groups. All of the groups used frequent doses of short-acting ß(2) -agonists. Discontinuing inhaled corticosteroid use during pregnancy was associated with a lower risk of exacerbations (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.33-0.54), whereas increasing inhaled corticosteroid use was associated with a higher risk (OR 1.42, 95% CI 1.17-1.72), compared with no change in use. CONCLUSION: Because of residual confounding by asthma severity, our study was not able to show that women who stopped inhaled corticosteroids during pregnancy were at increased risk of having an asthma exacerbation. However, women who stopped corticosteroids tended to have a milder form of asthma, which is reassuring and suggests that women can recognize, to a certain extent, the need to continue taking their controller agents if necessary.

Inhaled corticosteroids vs. leukotriene-receptor antagonists and asthma exacerbations in children.

BACKGROUND: Compared to inhaled corticosteroids (ICS), better use of leukotriene-receptor antagonists (LTRA) may lead to a greater reduction in exacerbations among asthmatic children in real-life settings. METHODS: To test this hypothesis, we used the Quebec administrative databases and identified a cohort of 27,355 asthmatic children aged 5-15 years in whom ICS or LTRA monotherapy was initiated in 1998-2005. The primary outcome was the rate of moderate-or-severe asthma exacerbations (emergency department visit or hospitalization for asthma or a dispensed prescription of oral corticosteroids) over the subsequent year. The adjusted rate ratios (RR) of asthma exacerbations were estimated with Poisson regression models. To minimize confounding by indication, all analyses were stratified by the presence or not of an asthma exacerbation in the year before treatment initiation. We also measured the proportion of days with supply prescribed and patient's adherence with the Proportion of Prescribed Days Covered (PPDC). RESULTS: The risk of exacerbations was significantly higher in the ICS than the LTRA group among children with no previous exacerbation (RR = 2.3; 95% CI:1.3-4.0), but not in those with ≥1 exacerbations (RR = 1.6; 0.8-3.1). The PPDC was similar between the groups (66%) but the proportion of days with supply prescribed was significantly higher in the LTRA than the ICS group (52% vs. 34%), resulting in higher use. CONCLUSIONS: While confounding by indication cannot be firmly ruled out, ICS appears to be more frequently prescribed as an intermittent than a daily controller therapy resulting in less use, which may contribute to the apparent lower effectiveness compared to LTRA.