Association between asthma control trajectories in preschoolers and disease remission.

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

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

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

Development of a 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.

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.

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.

Co-transcriptional recruitment of Puf6 by She2 couples translational repression to mRNA localization.

Messenger RNA (mRNA) localization is coupled to the translational repression of transcripts during their transport. It is still unknown if this coupling depends on physical interactions between translational control and mRNA localization machineries, and how these interactions are established at the molecular level. In yeast, localization of transcripts like ASH1 to the bud depends on the RNA-binding protein She2. During its transport, ASH1 mRNA translation is repressed by Puf6. Herein, we report that She2 recruits Puf6 on ASH1 co-transcriptionally. The recruitment of Puf6 depends on prior co-transcriptional loading of Loc1, an exclusively nuclear protein. These proteins form a ternary complex, in which Loc1 bridges Puf6 to She2, that binds the ASH1 3'UTR. Using a genome-wide ChIP-chip approach, we identified over 40 novel targets of Puf6, including several bud-localized mRNAs. Interestingly, the co-transcriptional recruitment of Puf6 on genes coding for these bud-localized mRNAs is also She2- and Loc1-dependent. Our results suggest a coordinated assembly of localization and translational control machineries on localized mRNAs during transcription, and underline the importance of co-transcriptional events in establishing the cytoplasmic fate of mRNAs.

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.

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.

Efficient chemisorption of organophosphorous redox probes on indium tin oxide surfaces under mild conditions.

We report a mild and straightforward one-step chemical surface functionalization of indium tin oxide (ITO) electrodes by redox-active molecules bearing an organophosphoryl anchoring group (i.e., alkyl phosphate or alkyl phosphonate group). The method takes advantage of simple passive adsorption in an aqueous solution at room temperature. We show that organophosphorus compounds can adsorb much more strongly and stably on an ITO surface than analogous redox-active molecules bearing a carboxylate or a boronate moiety. We provide evidence, through quantitative electrochemical characterization (i.e., by cyclic voltammetry) of the adsorbed organophosphoryl redox-active molecules, of the occurrence of three different adsorbate fractions on ITO, exhibiting different stabilities on the surface. Among these three fractions, one is observed to be strongly chemisorbed, exhibiting high stability and resistance to desorption/hydrolysis in a free-redox probe aqueous buffer. We attribute this remarkable stability to the formation of chemical bonds between the organophosphorus anchoring group and the metal oxide surface, likely occurring through a heterocondensation reaction in water. From XPS analysis, we also demonstrate that the surface coverage of the chemisorbed molecules is highly affected by the degree of surface hydroxylation, a parameter that can be tuned by simply preconditioning the freshly cleaned ITO surfaces in water. The lower the relative surface hydroxide density on ITO, the higher was the surface coverage of the chemisorbed species. This behavior is in line with a chemisorption mechanism involving coordination of a deprotonated phosphoryl oxygen atom to the non-hydroxylated acidic metal sites of ITO.

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.

Relative perinatal safety of salmeterol vs formoterol and fluticasone vs budesonide use during pregnancy.

BACKGROUND: Recent asthma guidelines endorse the safety of long-acting ß2-agonists (LABAs) and of mild and moderate doses of inhaled corticosteroids (ICSs) when required to control asthma during pregnancy, yet do not state a preferred medication within each class. OBJECTIVE: To estimate the relative perinatal safety with the use of salmeterol and formoterol (LABAs) and that of fluticasone and budesonide (ICSs) during pregnancy. METHODS: A subcohort of pregnancies from asthmatic women was selected from health care administrative databases of Quebec, Canada. Low birth weight (LBW) was defined as weight less than 2,500 g, preterm birth (PB) as delivery before 37 weeks of gestation, and small for gestational age (SGA) as a birth weight below the 10th percentile. The effect of treatment with salmeterol vs formoterol and fluticasone vs budesonide on the outcomes was determined with generalized estimating equation models. RESULTS: The LABA and ICS subcohorts were composed of 547 (385 salmeterol and 162 formoterol users) and 3,798 (3,190 fluticasone and 608 budesonide users) pregnancies, respectively. No statistically significant differences were observed for LBW (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.44-1.88), PB (OR, 1.11; 95% CI, 0.56-2.23), and SGA (OR, 1.16; 95% CI, 0.67-2.02) newborns between women exposed to salmeterol vs formoterol or between women exposed to fluticasone vs budesonide (LBW: OR, 1.08; 95% CI, 0.76-1.52; PB: OR, 1.07; 95% CI, 0.78-1.49; and SGA, OR: 1.10; 95% CI, 0.85-1.44). CONCLUSION: This study does not provide evidence of greater perinatal safety for one LABA or one ICS over the other.

Synthesis and reactivity of tripodal complexes containing pendant bases.

The synthesis of a new tripodal ligand family that contains tertiary amine groups in the second-coordination sphere is reported. The ligands are tris(amido)amine derivatives, with the pendant amines attached via a peptide coupling strategy. They were designed to function as new molecular catalysts for the oxygen reduction reaction (ORR), in which the pendant acid/base group could improve the catalyst performance. Two members of the ligand family were each metalated with cobalt(II) and zinc(II) to afford trigonal-monopyramidal complexes. The reaction of the cobalt complexes [Co(L)](-) with dioxygen reversibly generates a small amount of a cobalt(III) superoxo species, which was characterized by electron paramagnetic resonance (EPR) spectroscopy. Protonation of the zinc complex Zn[N{CH2CH2NC(O)CH2N(CH2Ph)2}3)](-) ([Zn(TN(Bn))](-)) with 1 equiv of acid occurs at a primary-coordination-sphere amide moiety rather than at a pendant basic site. The addition of excess acid to any of the complexes [M(L)](-) results in complete proteolysis and formation of the ligands H3L. These undesired reactions limit the use of these complexes as catalysts for the ORR. An alternative ligand with two pyridyl arms was also prepared but could not be metalated. These studies highlight the importance of the stability of the primary-coordination sphere of ORR electrocatalysts to both oxidative and acidic conditions.

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.

Work-exacerbated asthma and occupational asthma: do they really differ?

BACKGROUND: Although work-exacerbated asthma (WEA) is a prevalent condition likely to have an important societal burden, there are limited data on this condition. OBJECTIVES: The aims of this study were (1) to compare the clinical, functional, and inflammatory characteristics of workers with WEA and occupational asthma (OA) and (2) compare health care use and related costs between workers with WEA and OA, as well as between workers with work-related asthma (WRA; ie, WEA plus OA) and those with non-work-related asthma (NWRA) in a prospective study. METHODS: We performed a prospective observational study of workers with and without WRA with a 2-year follow-up. The diagnosis of OA and WEA was based on the positivity and negativity of results on specific inhalation challenges, respectively. RESULTS: One hundred fifty-four subjects were enrolled: 53 with WEA, 68 with OA, and 33 control asthmatic subjects (NWRA). WEA was associated with more frequent prescriptions of inhaled corticosteroids (odds ratio [OR], 4.4; 95% CI, 1.4-13.6; P = .009), a noneosinophilic phenotype (OR, 0.3; 95% CI, 0.1-0.9; P = .04), a trend toward a lower FEV1 (OR, 0.9; 95% CI, 0.9-1.0; P = .06), and a higher proportion of smokers (OR, 2.5; 95% CI, 0.96-9.7; P = .06) than the diagnosis of OA. The health care use of WRA and related costs were 10-fold higher than those of NWRA. CONCLUSION: Workers with WEA appeared to have features of greater asthma severity than workers with OA. In contrast with OA, WEA was associated with a noneosinophilic phenotype. Both OA and WEA were associated with greater health care use and 10-fold higher direct costs than NWRA.

Impact of maternal use of asthma-controller therapy on perinatal outcomes.

BACKGROUND: Asthma during pregnancy usually requires treatment with controller medications about which more safety information is needed. The objectives are to assess the impact of the use of long-acting ß2-agonists (LABAs) and the dose of inhaled corticosteroids (ICSs) during pregnancy on the prevalence of low birth weight (LBW), preterm birth (PB) and small for gestational age (SGA). METHODS: A cohort of women with asthma giving birth from 1998 to 2008 was constructed from Québec (Canada) administrative databases. LBW was defined as weight <2500 g, PB as delivery before 37 weeks' gestation and SGA as a birth weight below the 10th percentile. The impact of the use of LABAs and the dose of ICSs during pregnancy on the outcomes was determined with generalised-estimating-equation models. RESULTS: The cohort included 7376 pregnancies: 8.8% exposed to LABAs and 56.9% exposed to ICSs. All LABA users also received ICSs. The prevalence of LBW, PB and SGA was 7.7%, 9.5% and 13.5%, respectively. LABA use was not found to be associated with increased prevalence of LBW (OR 0.81; 95% CI 0.58 to 1.12), PB (OR 0.84; 95% CI 0.61 to 1.15) or SGA (OR 0.92; 95% CI 0.70 to 1.20). Mean ICSs doses >125 µg/day (fluticasone-equivalent) were associated with a non-significant trend of increased LBW, PB and SGA. CONCLUSIONS: Despite the possibility of residual confounding due to uncontrolled or more severe asthma or smoking status, the use of LABA and low to moderate doses of ICSs were not associated with increased prevalence of perinatal outcomes. Additional research on higher ICSs doses is required to better evaluate their safety during pregnancy.

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.

Does hospitalization influence patients' medication adherence and community pharmacists' interventions?

BACKGROUND: Medication adherence reduces disease morbidity. Data regarding changes in a patient's adherence before and after hospitalization and how this hospitalization influences a pharmacist's interventions are scarce. OBJECTIVE: To assess changes in adherence to cardiovascular and respiratory medications in the year preceding and following a hospitalization; explore patients' perceptions about medication adherence and the pharmacist's role; and describe pharmacists' interventions regarding medication adherence. METHODS: This cohort study included patients hospitalized for acute coronary syndrome, acute worsening of heart failure, or acute COPD exacerbations. Adherence to cardiovascular and respiratory medications was measured by calculating the proportion of days covered (PDC) from prescription refills. Patient interviews were completed to explore their perceptions about medication adherence and the role of the pharmacist. Community pharmacists were invited to complete an online survey and to participate in focus groups to discuss interventions to improve medication adherence. RESULTS: Medication adherence was assessed for 61 patients; the mean PDC was 69.8% 12 months before hospitalization and 72.4% 12 months following hospitalization. Patients reported that they felt the need to take their medications to prevent worsening of their disease. They were satisfied with current pharmaceutical services. A total of 136 questionnaires completed by pharmacists were analyzed and 9 participants attended the focus groups. Most pharmacists reported monitoring prescription renewals to assess adherence, with no significant influence from the hospitalization itself. The patient's interest was reported to be an important facilitator, whereas a lack of time and face-to-face interaction with patients who had their medication delivered to their home was reported a main barrier to interventions. This study was limited by a small sample size. CONCLUSIONS: Patient medication adherence did not significantly change following hospitalization. Hospitalization does not appear to significantly influence patient and pharmacist behavior towards medication adherence.

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.

Impact of maternal asthma on perinatal outcomes: a two-stage sampling cohort study.

There are conflicting results concerning the impact of maternal asthma during pregnancy on perinatal outcomes. The present study investigated the associations between maternal asthma during pregnancy and the risk of a small-for-gestational-age (SGA) infant, a low-birth-weight (LBW) infant, and preterm birth. A population-based cohort of 40,788 pregnancies from asthmatic and non-asthmatic women was reconstructed through the linking of three Quebec (Canada) administrative databases between 1990 and 2002. A two-stage sampling cohort design was used to collect additional information by way of a mailed questionnaire. The generalized estimation equation models were used to obtain adjusted odds ratios of SGA, LBW and preterm birth comparing asthmatic and non-asthmatic women. The cohort included 13,007 pregnancies from asthmatic and 27,781 pregnancies from non-asthmatic women. Final estimates showed that the odds of SGA (odds ratio: 1.27, 95% confidence interval: 1.14, 1.41), LBW (1.41: 1.22, 1.63) and preterm delivery (1.64: 1.46, 1.83) were significantly higher among asthmatic than non-asthmatic women. Mothers with asthma during pregnancy are more likely to have SGA, LBW, or preterm birth infants than non-asthmatic women. These results can be more easily generalized to women with lower socio-economic status since the cohort under represents women with high socio-economic status.