[Show abstract][Hide abstract] ABSTRACT: 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.
40 community pharmacies in Québec (Canada) and a medication registry.
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).
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.
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.
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.
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BMJ Open 11/2014; 4(11):e005903. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract 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 caesarean 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.
[Show abstract][Hide abstract] ABSTRACT: Short and long-acting beta2-agonists (SABA and LABA) have a crucial role in asthma management during pregnancy, as stated in the current guidelines.
To systematically review the evidence on beta2-agonists use during pregnancy and adverse perinatal outcomes.
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.
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.
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.
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.
Respiratory medicine 12/2013; · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Canadian journal of psychiatry. Revue canadienne de psychiatrie 04/2013; 58(4):233-9. · 2.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Background
To assess the impact of the type of drug plan on adherence to and the cost of antihypertensive medications within universal drug insurance programs.
To compare adherence to and the cost of antihypertensive medications between adults with public and private drug insurance in the province of Quebec, Canada, we reconstructed a matched retrospective cohort by linking data recorded in three administrative databases between March 2008 and May 2010. The cohort included 186 privately and 1,747 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.
Over 70% of patients were 50–64 years old and 90% of the publicly and 72% of the privately insured patients had 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 wasn’t statistically significant. However, privately insured patients treated with 2 antihypertensive medications were more likely to be adherent (PDC-P: 15.0%, 95% confidence interval [CI]: 7.0, 24.0). Privately insured patients (CAN$41.52) had to pay significantly more for their antihypertensive medications than publicly insured patients (CAN$32.21).
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.
The Canadian journal of cardiology 01/2013; · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To describe changes in inhaled corticosteroid use during pregnancy and markers of uncontrolled asthma, and to evaluate the association between them.
Population-based, cross-sectional study.
Three administrative claims databases in Québec, Canada.
A cohort of 4434 asthmatic women (4920 pregnancies) who delivered their infants between 1990 and 2002 and who used inhaled corticosteroids before their pregnancy.
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 β(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 β(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.
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.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
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.
Our new adherence measure, the PPDC, may be considered as another way to assess patient adherence, taking into account differing prescribing patterns.
Annals of Pharmacotherapy 03/2011; 45(3):335-41. · 2.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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).
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.
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.
Respiratory medicine 12/2010; 105(6):846-55. · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is a lack of consensus in the literature about the effect of maternal asthma on the development of congenital malformations.
To further examine the association between maternal asthma and the risk of congenital malformations.
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.
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).
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.
Birth Defects Research Part A Clinical and Molecular Teratology 04/2010; 88(4):216-22. · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
High adherence to AH therapy is associated with a reduced risk of CD outside the context of clinical trials in primary prevention.