Utilisation de médicaments pour le traitement de l’asthme durant la grossesse et impact sur les issues périnatales

L’asthme est l’une des pathologies chroniques les plus fréquemment rencontrées durant la grossesse, affectant environ 8% des femmes enceintes. Les lignes directrices pour le traitement de l’asthme affirment que le risque d’un développement non optimal du fœtus dû à un asthme mal maîtrisé est supérieur au risque associé à la prise de médicaments pour le traitement de l’asthme durant la grossesse. Des questions persistent par contre sur l’innocuité des hautes doses de corticostéroïdes inhalés (CSI) et très peu de données sont publiées pour les bêta2-agonistes à longue action (BALA). Un programme de recherche en deux volets a été développé afin de répondre à certaines de ces questions. Dans un premier volet, une cohorte de femmes asthmatiques accouchant au Québec de 1998 à 2008 a été assemblée à partir des bases de données de la Régie de l’assurance maladie du Québec et de MED-ÉCHO afin d’évaluer l’impact de la prise de CSI ou de BALA sur la prévalence de faible poids à la naissance (FPN), de prématurité et de bébé petit pour l’âge gestationnel (PAG). La cohorte était composée de 7376 grossesses dont 56,9% étaient exposées aux CSI et 8,8% aux BALA. Dans cette cohorte, l’utilisation de BALA n’était pas associée à des prévalences plus élevées de FPN (OR=0,81, IC95%:0,58–1,12), prématurité (OR=0,84, IC95%:0,61–1,15) ou PAG (OR=0,92, IC95%:0,70–1,20). Lors de la comparaison des BALA (salmétérol comparé au formotérol comme référence) la différence la plus importante était pour le PAG (OR=1,16, IC95%:0,67–2,02). Pour les CSI, une tendance à une augmentation de FPN, prématurité et PAG a été observée avec l’augmentation des doses. Le OR le plus élevé était pour une dose > 500 ug/jour (équivalent fluticasone) pour le FPN: (OR=1,57, IC95%:0,86–2,87). La comparaison des CSI les plus utilisés (fluticasone comparé au budésonide comme référence) montre des différences non statistiquement significatives avec la différence maximale observée pour le PAG (OR=1,10, IC95%:0,85–1,44). Dans un second volet, une sous-cohorte de femmes asthmatiques avec visites médicales pour exacerbation d’asthme au Centre hospitalier universitaire de Sherbrooke (CHUS) a été constituée pour comparer le traitement des exacerbations durant et hors grossesse. Les résultats montrent que le traitement par CS était moins fréquent et différé pour les femmes enceintes comparées aux femmes non-enceintes. Le traitement de maîtrise de l’asthme (CSI et/ou BALA) dans l’année précédant l’exacerbation était sous-optimal. Les résultats présentés dans cette thèse démontrent l’innocuité des BALA et des doses faibles à modérées de CSI pendant la grossesse pour les issues de FPN, prématurité et PAG alors que des études supplémentaires sont nécessaires afin d’évaluer l’innocuité des hautes doses de CSI. Une innocuité comparable entre les CSI (budésonide, fluticasone) et les BALA étudiés (formotérol, salmétérol) a également été démontrée. Les résultats montrent également un recours moindre aux CS pour le traitement des exacerbations d’asthme durant la grossesse comparativement à hors grossesse. Ces résultats sont un ajout important aux évidences permettant aux cliniciens et aux femmes enceintes asthmatiques de faire les meilleurs choix pour optimiser le traitement pharmacologique durant la grossesse.Asthma is one of the most common chronic medical conditions encountered during pregnancy, affecting approximately 8% of pregnant women. Current asthma treatment guidelines emphasize the importance and safety of the use of asthma medications during pregnancy compared to the risk of poorly controlled asthma for the fetus. In the evaluation of the safety of asthma medications during pregnancy, the literature review shows that questions persist, amongst others, on the safety of high inhaled corticosteroids (ICSs) doses and that there is a paucity of data on the safety of long-acting beta2-agonists (LABAs). A two components research program was developed to answers some of these questions. In the first component, a cohort of asthmatic women giving birth from 1998 to 2008 was constructed from the Régie de l’assurance maladie du Québec (RAMQ) et de MED-ÉCHO databases to assess the impact of the use of long-acting β2-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). The cohort included 7,376 pregnancies: 8.8% exposed to LABAs and 56.9% exposed to ICSs. LABA use was not found to be associated with increased prevalence of LBW (OR=0.81; 95%CI: 0.58–1.12), PB (OR=0.84; 95%CI: 0.61–1.15), or SGA (OR=0.92; 95%CI: 0.70–1.20). In the LABAs comparison (salmeterol compared to formoterol as reference), the most important difference was observed for PAG (OR=1.16, 95%CI: 0.67–2.02). For the ICSs, increasing doses were associated with a trend of increased LBW, PB, and SGA. The maximal observed OR was for a dose > 500 ug/day (fluticasone-equivalent) for LBW: (OR=1.57, 95%CI: 0.86–2.87). The comparison of the most frequently used ICSs (fluticasone compared to budesonide as reference) revealed non-statistically significant differences with a maximal difference observed for SGA (OR=1.10, 95%CI: 0.85–1.44). In the second component, a sub-cohort of asthmatic women with medical visits for asthma exacerbations was constructed to compare the treatment of exacerbations during and outside of pregnancy. The results show a reduced and delayed use of systemic corticosteroids for the treatment of asthma exacerbations in women when pregnant than when non-pregnant. The preventive treatment of asthma (ICSs and/or BALAs) could also be optimized. The results presented in this thesis support the safety of the use during pregnancy of LABAs and low to moderate doses of ICSs for the outcomes of LBW, PB and SGA and point to the need for additional data on the safety of high ICS doses. A comparable safety between studied ICSs (budesonide and fluticasone) and BALAs (formoterol and salmeterol) was also demonstrated. We also observed a reduced and delayed use of systemic corticosteroids for the treatment of asthma exacerbations in women when pregnant than when non-pregnant

Association between anticholinergic drug use and health-related quality of life in community-dwelling older adults.

Background The use of drugs with anticholinergic properties (AC drugs) has been associated with decreased functioning and impaired cognition in older adults. Studies assessing the association between AC-drug use and healthrelated quality of life (HRQoL) show conflicting results. Objective The aim was to evaluate the association between AC-drug use and HRQoL in community-dwelling older adults. Methods The NuAge cohort study enrolled 1793 men and women aged 68–82 years. The participants were free of disabilities in activities of daily living, not cognitively impaired at recruitment and followed annually for 3 years (December 2003–May 2005). AC-drug exposure was assessed using the Anticholinergic Cognitive Burden Scale (ACBS). HRQoL was assessed using the physical (PCS) and mental (MCS) component summaries of the 36-item Short Form Survey (SF-36) questionnaire. The association between AC drug and HRQoL was determined by a mixed model analysis using four annual time points. Results At recruitment the mean age was 74.4 ± 4.2 years, 52% were female and 33% of participants were prescribed at least one AC drug. The mean PCS and MCS (/100) scores were 49.0 ± 8.2 and 54.9 ± 8.1, respectively. In the mixed model analysis, an increase of 1 on the ACBS was associated with a decrease of -0.50 (95% CI -0.68 to -0.31) in the PCS and an increase of 0.19 (95% CI 0.01–0.37) in the MCS. Conclusions In a cohort of generally healthy communitydwelling older adults, AC-drug exposure was associated with a statistically significant decrease in the PCS and increase in the MCS throughout the entire follow-up period. However, the effects on the PCS and MCS were small and likely not clinically relevant

Mortality attributable to nosocomial Clostridium difficile–associated disease during an epidemic caused by a hypervirulent strain in Quebec

BACKGROUND: Since 2002 an epidemic of Clostridium difficile–associated disease (CDAD) caused by a hypervirulent toxinotype III ribotype 027 strain has spread to many hospitals in Quebec. The strain has also been found in the United States, the United Kingdom and the Netherlands. The effects of this epidemic on mortality and duration of hospital stay remain unknown. We measured these effects among patients admitted to a hospital in Quebec during 2003 and 2004. METHODS: We compared mortality and total length of hospital stay among inpatients in whom nosocomial CDAD developed and among control subjects without CDAD matched for sex, age, Charlson Comorbidity Index score and length of hospital stay up to the diagnosis of CDAD in the corresponding case. RESULTS: Thirty days after diagnosis 23.0% (37/161) of the patients with CDAD had died, compared with 7.0% (46/656) of the matched control subjects (p < 0.001). Twelve months after diagnosis, mortality was 37.3% (60/161) among patients with CDAD and 20.6% (135/656) among the control subjects (p < 0.001), for a cumulative attributable mortality of 16.7% (95% confidence interval 8.6%–25.2%). Each case of nosocomial CDAD led, on average, to 10.7 additional days in hospital. INTERPRETATION: This study documented a high attributable mortality among elderly patients with CDAD mostly caused by a hypervirulent strain, which represents a dramatic change in the severity of this infection

Impact of a reduction in the use of high-risk antibiotics on the course of an epidemic of Clostridium difficile-associated disease caused by the hypervirulent napi/027 strain. Clinical Infectious Diseases, 45(Supplement 2):Si12-Si21

A series of measures were implemented, in a secondary/tertiary-care hospital in Quebec, to control an epidemic of nosocomial Clostridium difficile-associated disease (n-CDAD) caused by a virulent strain; these measures included the development of a nonrestrictive antimicrobial stewardship program. Interrupted time-series analysis was used to evaluate the impact of these measures on n-CDAD incidence. ), but implementation of the antimicrobial stewardship program was followed by P p .63 a marked reduction in incidence ( ). This suggests that nonrestrictive measures to optimize antibiotic P p .007 usage can yield exceptional results when physicians are motivated and that such measures should be a mandatory component of n-CDAD control. The inefficacy of infection control measures targeting transmission through hospital personnel might be a result of their implementation late in the epidemic, when the environment was heavily contaminated with spores

Inferring depth-dependent plasma motions from surface observations using the DeepVel neural network

Coverage of plasma motions is limited to the line-of-sight component at the Sun’s surface. Multiple tracking and inversion methods were developed to infer the transverse motions from observational data. Recently, the DeepVel neural network was trained with computations performed by numerical simulations of the solar photosphere to recover the missing transverse component at the surface and at two additional optical depths simultaneously from the surface white light intensity in the Quiet Sun. We argue that deep learning could provide additional spatial coverage to existing observations in the form of depth-dependent synthetic observations, i.e. estimates generated through the emulation of numerical simulations. We trained different versions of DeepVel using slices from numerical simulations of both the Quiet Sun and Active Region at various optical and geometrical depths in the solar atmosphere, photosphere and upper convection zone to establish the upper and lower limits at which the neural network can generate reliable synthetic observations of plasma motions from surface intensitygrams. Flow fields inferred in the photosphere and low chromosphere τ ∈ [0.1, 1) are comparable to inversions performed at the surface (τ ≈ 1) and are deemed to be suitable for use as synthetic estimates in data assimilation processes and data-driven simulations. This upper limit extends closer to the transition region (τ ≈ 0.01) in the Quiet Sun, but not for Active Regions. Subsurface flows inferred from surface intensitygrams fail to capture the small-scale features of turbulent convective motions as depth crosses a few hundred kilometers. We suggest that these reconstructions could be used as first estimates of a model’s velocity vector in data assimilation processes to nowcast and forecast short term solar activity and space weather

Antimicrobial stewardship in acute care centres: A survey of 68 hospitals in Quebec

BACKGROUND: Antimicrobial stewardship programs (ASPs) and quantitative monitoring of antimicrobial use are required to ensure that antimicrobials are used appropriately in the acute care setting, and have the potential to reduce costs and limit the spread of antimicrobial-resistant organisms and Clostridium difficile. Currently, it is not known what proportion of Quebec hospitals have an ASP and/or monitor antimicrobial use

Problems in Coordinating and Accessing Primary Care for Attached and Unattached Patients Exacerbated During the COVID-19 Pandemic Year (the PUPPY Study): Protocol for a Longitudinal Mixed Methods Study

BackgroundThe COVID-19 pandemic has significantly disrupted primary care in Canada, with many walk-in clinics and family practices initially closing or being perceived as inaccessible; pharmacies remaining open with restrictions on patient interactions; rapid uptake of virtual care; and reduced referrals for lab tests, diagnostics, and specialist care. ObjectiveThe PUPPY Study (Problems in Coordinating and Accessing Primary Care for Attached and Unattached Patients Exacerbated During the COVID-19 Pandemic Year) seeks to understand the impact of the COVID-19 pandemic across the quadruple aims of primary care, with particular focus on the effects on patients without attachment to a regular provider and those with chronic health conditions. MethodsThe PUPPY study builds on an existing research program exploring patients’ access and attachment to a primary care practice, pivoted to adapt to the emerging COVID-19 context. We intend to undertake a longitudinal mixed methods study to understand critical gaps in primary care access and coordination, as well as compare prepandemic and postpandemic data across 3 Canadian provinces (Quebec, Ontario, and Nova Scotia). Multiple data sources will be used such as a policy review; qualitative interviews with primary care policymakers, providers (ie, family physicians, nurse practitioners, and pharmacists), and patients (N=120); and medication prescriptions and health care billing data. ResultsThis study has received funding by the Canadian Institutes of Health Research COVID-19 Rapid Funding Opportunity Grant. Ethical approval to conduct this study was granted in Ontario (Queens Health Sciences & Affiliated Teaching Hospitals Research Ethics Board, file 6028052; Western University Health Sciences Research Ethics Board, project 116591; University of Toronto Health Sciences Research Ethics Board, protocol 40335) in November 2020, Québec (Centre intégré universitaire de santé et de services sociaux de l'Estrie, project 2020-3446) in December 2020, and Nova Scotia (Nova Scotia Health Research Ethics Board, file 1024979) in August 2020. ConclusionsTo our knowledge, this is the first study of its kind to explore the effects of the COVID-19 pandemic on primary care systems, with particular focus on the issues of patient’s attachment and access to primary care. Through a multistakeholder, cross-jurisdictional approach, the findings of the PUPPY study will inform the strengthening of primary care during and beyond the COVID-19 pandemic, as well as have implications for future policy and practice. International Registered Report Identifier (IRRID)DERR1-10.2196/2998

Communication between hospitals, Family Medicine Groups and community pharmacists during transitions of care interventions

International audienceBackground: Pharmacist-led transitions of care (TOC) interventions have been associated with improved health outcomes. Community pharmacists' (CP) TOC communications have been described whereas limited evidence is available for hospital pharmacists (HP) and none for non-dispensing pharmacists, integrated into Family Medicine Groups (FMG).Objective: To assess information needs and perceptions about TOC communications of HP, FMG pharmacists (FMG-P) and CP and to identify optimal TOC practices and their barriers.Methods: In a cross-sectional design, a survey was distributed via email to the 70 pharmacists who participated in a multicenter, single group, longitudinal TOC intervention study for older adults at risk of medication-related harm. All pharmacists were surveyed on their TOC practices before the TOC study, as part of usual care. Pharmacists who followed TOC study patients were also surveyed on their TOC practices during the TOC study.Results: Survey responses were received from 35 pharmacists (50%), including 8 HP, 6 FMG-P and 21 CP. The frequency of communication between pharmacists of different settings increased significantly during the TOC study, with more than 80% of pharmacists reporting satisfaction with the quality of the information provided. At hospital discharge, in optimal TOC, the FMG-P and CP reported that the most important information to transfer was the reasons of hospitalization, patient weight and height, and the therapeutic intent of the medications. The main barriers to TOC implementation were the lack of clinical information about patients for FMG-P and CP and understaffing for HP. FMG-P and CP reported a similar high degree of interest in assuming responsibility for the new extended scope of practice activities of medication adjustments according to therapeutic targets or laboratory results and the implementation of a plan for gradual dose increases or drug tapering.Conclusions: The surveyed pharmacists reported an increased frequency of communication and satisfaction with the information exchanged between the pharmacists of different settings during the TOC study compared to usual care, before the study. The pharmacists extended scope of practice offers new opportunities to optimize TOC interventions

Pharmacist-led transitions of care for older adults at risk of drug-related problems : a feasibility study

Background: Transitions of care (TOC) is one of three key action areas identified in the World Health Organization (WHO)’s third Global Patient Safety Challenge, Medication Without Harm, released in 2017. Systematic reviews have shown that TOC interventions can improve health outcomes, although few studies have evaluated the role of the community pharmacist. Objective: To evaluate the feasibility of a pharmacist-led TOC intervention for older adults at risk of drug-related problems. Methods: Pragmatic feasibility study conducted in hospital and community pharmacies in a health region of Quebec, Canada. The interventions consisted of a pharmaceutical care plan developed by the hospital pharmacist and transferred at hospital discharge to the patients’ community pharmacist, who completed patient consultations in the week following discharge and monthly for six months thereafter. Feasibility evaluations included recruitment, retention, time required, types of interventions, and modified classes of medications, based on clinical data entered in an electronic health record accessible to clinicians in all settings. Results: Of the 90 recruited patients, 76 were discharged with a pharmaceutical care plan. The mean age of these 76 subjects was 79.5 years, and 52.6% were female. The most frequent inclusion criteria were 15 or more medications (57.9%), two or more emergency department visits (past three months), or one or more hospitalization (past twelve months) (42.1%). The hospital pharmacist interventions took a mean time of 222 min. The community pharmacist interventions took a mean time of 52 min and 32 min for the first and subsequent visits, respectively. Therapeutic goals were documented for 60.5% of patients. Conclusions: This study shows the feasibility of implementing a pharmacist-led TOC intervention in the Canadian context. Development of the TOC model in three health regions is currently being pursued along with the inclusion of primary care clinics who recently added pharmacists to their interdisciplinary teams