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Background: Wait time information and compliance with national guidelines are limited to a few adult conditions in the province of Quebec. We aimed to assess compliance with Paediatric Canadian Access Targets for Surgery (P-CATS) guidelines and determine the burden incurred due to waiting for 3 common elective surgical conditions (inguinal hernia, cryptorchidism and hypospadias) in a pediatric population.Methods: We carried out a population-based retrospective cohort study of randomly selected children residing in Quebec without complex chronic medical conditions, using administrative databases belonging to the Régie de l'assurance maladie du Québec for the period 2010-2013. Disability-adjusted life years (DALYs) were calculated to measure the burden due to waiting. Multivariate forward regression identified risk factors for compliance with national guidelines.Results: Surgical wait time information was assessed for 1515 patients, and specialist referral wait time was assessed for 1389 patients. Compliance with P-CATS benchmarks was 76.6% for seeing a specialist and 60.7% for receiving surgery. Regression analysis identified older age (p < 0.0001) and referring physician specialty (p = 0.001) as risk factors affecting specialist referral wait time target compliance, whereas older age (p = 0.040), referring physician specialty (p = 0.043) and surgeon specialty (p = 0.002) were significant determinants in surgical wait time compliance. The total burden accrued due to waiting beyond benchmarks was 35 DALYs.Conclusion: Our results show that provincial compliance rates with wait time benchmarks are still inadequate and need improvement. Patient age and physician specialty were both found to have significant effects on wait time target compliance. [ABSTRACT FROM AUTHOR]

Background In kidney transplant recipients, episodes of bacteriuria are often treated regardless of the presence of symptoms because of the lack of clear treatment guidelines suggesting otherwise. This practice may lead to the development of antimicrobial resistance. Our aim was to determine the incidence, determinants, and impact of antimicrobial resistance in kidney transplant recipients with gram-negative bacteriuria. Method We conducted a single-center, retrospective cohort study in patients who underwent kidney transplantation between January 2008 and June 2013. To identify risk factors for the development of resistance, we used a logistic regression model with generalized estimating equations to account for within-subject correlation. Results Among the 318 patients who underwent kidney transplantation during the study period, 147 patients developed 555 gram-negative episodes of bacteriuria. Resistance to trimethoprim-sulfamethoxazole and quinolones, and production of extended-spectrum β-lactamase ( ESBL) occurred in 52%, 21%, and 5% of isolated microorganisms, respectively. An increased risk of resistance to quinolones and production of ESBL were associated with concomitant diabetes (odds ratio [ OR]: 2.29, 95% confidence interval [ CI]: 1.11-4.74), the first year post transplantation ( OR: 2.88, 95% CI: 1.36-6.09), and antibiotic treatment in the previous 6 months ( OR: 3.36, 95% CI: 1.66-6.81). This resistance profile was also associated with the presence of symptoms, a longer duration of antibiotic treatment, and a higher rate of hospitalization. Conclusion Antimicrobial resistance to quinolones and production of ESBL were commonly seen, and were shown to demonstrate an adverse impact on outcomes in kidney transplant recipients with gram-negative bacteriuria. The decision on treatment for asymptomatic bacteriuria should be made with caution, given the potential for the selection of resistant strains. [ABSTRACT FROM AUTHOR]

The link between cardiovascular (CV) risk factors or diseases and dementia is documented. There is conflicting evidence whether age moderates the association. We need to study this gap so that research and clinical initiatives target appropriate age groups. A cohort of 320,630 adult patients without dementia was built using Quebec healthcare databases (1998–2010). The CV risk factors were hypertension, diabetes and dyslipidemia, while diseases included stroke, myocardial infarction (MI), chronic heart failure (HF), and atrial fibrillation (AF). Dementia risk and CV risk factors or diseases were assessed using incidence rate ratios and Cox regression across age groups. The cohort presented by mainly female sex (67.7%) and mean age of 74.1 years. Incident rate of dementia increased with age, ranging from 4.1 to 93.5 per 1000 person-years. Diabetes, stroke, HF and AF were significantly associated with dementia risk, hazard ratios ranged from 1.08 to 3.54. The strength of association decreased in advanced age for diabetes, stroke and HF. The results suggest that prevention of diabetes, stroke, HF and AF are crucial to mitigate dementia risk. The pathophysiology of dementia in younger and older populations seems to differ, with less impact of CV risk factors in advanced age. [ABSTRACT FROM AUTHOR]

The link between cardiovascular (CV) risk factors or diseases and dementia is documented. There is conflicting evidence whether age moderates the association. We need to study this gap so that research and clinical initiatives target appropriate age groups. A cohort of 320,630 adult patients without dementia was built using Quebec healthcare databases (1998–2010). The CV risk factors were hypertension, diabetes and dyslipidemia, while diseases included stroke, myocardial infarction (MI), chronic heart failure (HF), and atrial fibrillation (AF). Dementia risk and CV risk factors or diseases were assessed using incidence rate ratios and Cox regression across age groups. The cohort presented by mainly female sex (67.7%) and mean age of 74.1 years. Incident rate of dementia increased with age, ranging from 4.1 to 93.5 per 1000 person-years. Diabetes, stroke, HF and AF were significantly associated with dementia risk, hazard ratios ranged from 1.08 to 3.54. The strength of association decreased in advanced age for diabetes, stroke and HF. The results suggest that prevention of diabetes, stroke, HF and AF are crucial to mitigate dementia risk. The pathophysiology of dementia in younger and older populations seems to differ, with less impact of CV risk factors in advanced age. [ABSTRACT FROM AUTHOR]

The risk stratification of conservatively managed patients presenting with non–ST elevation (NSTE) acute coronary syndromes (ACS) is frequently accomplished by the use of myocardial perfusion scintigraphy (MPS) in clinical practice. However, whether one can predict the extent of coronary artery disease (CAD) on angiography by MPS in this setting is unknown. In this study, the correspondence of findings on MPS to those on coronary angiography was retrospectively analyzed in 55 patients presenting with NSTE ACS. Patients'' mean age was 64 years, 55% were men, and 87% had positive troponins. Of these patients, 42% of patients with perfusion defects involving the anterior wall presented with significant extensive CAD on coronary angiography, consisting of left main disease, 3-vessel disease, or 2-vessel disease involving the left anterior descending coronary artery. In patients with perfusion defects limited to 1 territory, 50% also had extensive CAD. A “negative” result on MPS was associated with extensive CAD in 37% of patients and the absence of significant lesions in only 8%. In conclusion, these findings suggest that MPS alone may be of limited clinical utility in distinguishing troponin-positive NSTE ACS patients with extensive CAD from those with more limited disease and should prompt further investigation of the use of MPS for this indication. [Copyright &y& Elsevier]

Background. Leukotriene receptor antagonists (LTRAs) and inhaled corticosteroids (ICSs) must be taken continuously to control persistent asthma. We compared the use of LTRAs and ICSs in patients with similar level of asthma control at treatment initiation with particular attention to treatment persistence. Methods. Two cohorts of 15 to 45 year old patients with asthma were selected from the Quebec Health Insurance Plan Database between January 1, 1998, and December 31, 2000. We first identified new users of LTRAs and from the remaining patients, we selected new users of ICSs. The ICS patients were then one-to-one matched to LTRA patients on the use of short-acting ß 2 -agonists and oral corticosteroids in the year prior to the date of the first LTRA or ICS dispensation (index date). We compared compliance to initial therapies using Cox proportional hazards models. Results. Each of the LTRA and ICS cohorts included 2200 patients. Multivariate model showed that compliance was significantly better for LTRAs than for ICSs [adjusted rate ratio of treatment discontinuation (aRR), 0.46; 95% confidence interval (CI), 0.42–0.49]. If in both groups all medications filled were taken at the prescribed dose, the annual percent of days on therapy for LTRA users would have been twice that for ICS users (38% vs. 19%; p [ABSTRACT FROM AUTHOR]

AbstractBackground: There is strong evidence to support the treatment of abnormal blood lipid levels among people with cardiovascular disease. Primary prevention is problematic because many individuals with lipid abnormalities may never actually develop cardiovascular disease. We evaluated the 1998 Canadian lipid guidelines to determine whether they accurately identify high-risk adults for primary prevention.Methods: Using data from the Lipid Research Clinics and receiver operating characteristic (ROC) curves, we compared the diagnostic performance of the 1998 lipid guidelines when risk factors for coronary artery disease (CAD) were counted versus calculating risk using Framingham risk equations. We also compared the diagnostic accuracy of the 1998 guidelines with guidelines previously published by the National Cholesterol Education Program in the United States and the 1988 Canadian Consensus Conference on Cholesterol and then used Canadian Heart Health Survey data to forecast lipid screening and treatment rates for the Canadian population.Results: The Framingham risk equations were more accurate than counting risk factors for predicting CAD risk (areas under the ROC curves, 0.83 [standard deviation (SD) 0.02] v. 0.77 [SD 0.03], p < 0.05). Risk counting was a particularly poor method for predicting risk for women. The 1998 Canadian guidelines identified high-risk individuals more accurately than the earlier guidelines, but the increased accuracy was largely due to a lower false-positive rate or a higher true-negative rate (i.e., increased test specificity). Using the 1998 lipid guidelines we estimate that 5.9 million Canadians currently free of cardiovascular disease would be eligible for lipid screening and 322 705 (5.5%) would require therapy.Interpretation: Calculating risk using risk equations is a more accurate method to identify people at high risk for CAD than counting the number of risk factors present, especially for women, and the 1998 Canadian lipi... [ABSTRACT FROM AUTHOR]

Presents a study to compare the prevalence of modifiable risk factors for cardiovascular disease among hypertensive and nonhypertensive adults and to estimate the effect of treating hyperlipidemia of hypertension to reduce the risk of death from coronary artery disease. Methods; Results; Interpretation.

Cox models with time‐dependent coefficients and covariates are widely used in survival analysis. In high‐dimensional settings, sparse regularization techniques are employed for variable selection, but existing methods for time‐dependent Cox models lack flexibility in enforcing specific sparsity patterns (ie, covariate structures). We propose a flexible framework for variable selection in time‐dependent Cox models, accommodating complex selection rules. Our method can adapt to arbitrary grouping structures, including interaction selection, temporal, spatial, tree, and directed acyclic graph structures. It achieves accurate estimation with low false alarm rates. We develop the sox package, implementing a network flow algorithm for efficiently solving models with complex covariate structures. sox offers a user‐friendly interface for specifying grouping structures and delivers fast computation. Through examples, including a case study on identifying predictors of time to all‐cause death in atrial fibrillation patients, we demonstrate the practical application of our method with specific selection rules. [ABSTRACT FROM AUTHOR]

Background: Acute kidney Injury (AKI) in children undergoing cardiac surgery (CS) is strongly associated with hospital morbidity. Post-discharge CS AKI outcomes are less clear. We evaluated associations between AKI and post-discharge (a) healthcare utilization, (b) chronic kidney disease (CKD) or hypertension and (c) mortality. Methods: This is a retrospective two-centre cohort study of children surviving to hospital discharge after CS. Primary exposures were post-operative ≥Stage 1 AKI and ≥Stage 2 AKI defined by Kidney Disease Impoving Global Outcomes. Association of AKI with time to outcomes was determined using multivariable Cox-Proportional Hazards analysis. Results: Of 350 participants included (age 3.1 (4.5) years), 180 [51.4%] developed AKI and 60 [17.1%] developed ≥Stage 2 AKI. Twenty-eight (9%) participants developed CKD or hypertension (composite outcome), and 17 (5%) died within 5 years of discharge. Post-operative ≥Stage 1 and ≥Stage 2 AKI were not associated with post-discharge hospitalizations, emergency room (ER) visits, physician visits or CKD or hypertension in adjusted analyses. A trend was observed between ≥Stage 2 AKI and mortality but was not statistically significant. In unadjusted stratified analyses, AKI was associated with post-discharge hospitalizations in children with RACHS-1 score ≥3, complex chronic disease classification and children living in urban areas. Conclusions: Post-CS AKI is not associated with post-discharge healthcare utilization, death and CKD or hypertension, though it may be associated with healthcare utilization in more complex paediatric CS children. Studies should aim to better understand post-CS healthcare utilization patterns and non-AKI risk factors for CKD, hypertension and mortality, to reduce adverse long-term outcomes after CS. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to investigate whether diacerein has comparable efficacy with celecoxib in pain reduction for treatment in symptomatic knee OA patients. Methods This randomized double-blind multicentre non-inferiority trial evaluated diacerein vs celecoxib treatment in patients with Kellgren–Lawrence grade 2–3 and pain scoring ≥4 (10-cm VAS). Patients were randomized to 6 months of treatment with diacerein 50 mg (n  = 187) once daily for 1 month and twice daily thereafter, or celecoxib 200 mg (n  = 193) once daily. The primary outcome was the change in WOMAC pain score (0–50 cm) at 6 months, and the secondary outcomes were WOMAC sub-scores, VAS pain score, and the OMERACT–OARSI responder rate. Results In the per protocol population, the adjusted mean change from baseline in the WOMAC pain score was –11.1 ( 0.9) with diacerein (n  = 140) and –11.8 (0.9) with celecoxib (n  = 148). The intergroup difference was 0.7 (95% CI: −1.8, 3.2; P = 0.597), meeting the non-inferiority margin. Supportive analysis of the intention-to-treat population gave similar results. Other outcomes showed no significant difference between treatment groups. The incidence of treatment-related adverse events was low and balanced between groups, but a greater incidence of diarrhoea occurred with diacerein (10.2% vs 3.7%). Diarrhoea was considered mild-to-moderate in all but one case with complete resolution. Conclusions Diacerein was non-inferior to celecoxib in reducing knee OA pain and improving physical function. Diacerein also demonstrated a good safety profile. Trial registration A multicentre study on the effect of DIacerein on Structure and Symptoms vs Celecoxib in Osteoarthritis is a National Institutes of Health (NCT02688400) and European Clinical Trial Database (2015–002933-23) registered phase III (Canada) or IV (Europe) study. [ABSTRACT FROM AUTHOR]

This study aims to investigate the effect of antipsychotic agents on cardiovascular and cerebrovascular diseases (CVD/CEV) and mortality risks in the older population living in a community. A cohort of 42,650 new users of antipsychotic agents was built using Quebec healthcare databases (1998–2011). The outcomes were CVD/CEV and mortality incidence in 5 years of follow-up in the total cohort, sub-cohort of patients with no schizophrenia/dementia, sub-cohort with schizophrenia, and sub-cohort with dementia. Comparisons were made between the new users who continued the treatment (adherent level ≥ 60%) vs. those ceasing treatment (adherence level < 60%) using inverse probability of treatment weighting and Cox models. Comparing high adherence vs. low levels, CVD/CEV risk was increased by 36% in the sub-cohort with schizophrenia for atypical antipsychotic users and by 25% in the sub-cohort with dementia for typical antipsychotic users. An increasing mortality risk of 2- to 3-fold was linked with the typical antipsychotic use in all cohorts except the sub-cohort with schizophrenia; in addition, mortality risk is linked with the use of high vs. low doses. Antipsychotics were not linked with CVD/CEV risk, except for atypical antipsychotics in patients with schizophrenia and typical antipsychotics in patients with dementia. The mortality risk was linked with the use of typical antipsychotics and the dose used. [ABSTRACT FROM AUTHOR]

A number of cross-sectional studies report extensive use of psychiatric services and high healthcare costs in autistic youths. However, little is known about how the use of these services evolves from the time of diagnosis, as children grow up. Our objectives were to investigate the use, costs, and predictors of psychiatric services following autism spectrum diagnosis. We built a cohort of 1227 newly diagnosed autism spectrum individuals identified in the Quebec (Canada) Régie de l'assurance maladie du Québec administrative database (January 1998 to December 2010). Mean number and cost per individual of psychiatric healthcare use (hospitalizations, medical visits, psychoactive drug use) were calculated yearly for 5 years following autism spectrum diagnosis. Mean number of psychiatric visits decreased over time by more than threefold (7.5 vs 2.1 visits) from year 1 to year 5, whereas psychoactive drug use increased from 16.0 to 25.2 claims. Psychiatric hospitalizations decreased during follow-up, but still represented the greatest costs per individual (CAD9820 for year 1; CAD4628 for year 5). Antipsychotics represented over 50% of drug costs. Mixed-effect model with repeated measures showed that previous psychoactive drug use was the strongest predictor of greater psychiatric healthcare cost during follow-up (odds ratio: 9.96; 95% confidence interval: 7.58–13.10). These trends contrast with guidelines advocating cautious prescribing of antipsychotics with periodical re-assessment of their benefit. [ABSTRACT FROM AUTHOR]

BACKGROUND: Current clinical decision tools for assessing bleeding risk in individuals with atrial fibrillation (AF) have limited performance and were developed for individuals treated with warfarin. This study develops and validates a clinical risk score to personalize estimates of bleeding risk for individuals with atrial fibrillation taking direct-acting oral anticoagulants (DOACs). METHODS: Among individuals taking dabigatran 150 mg twice per day from 44 countries and 951 centers in this secondary analysis of the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy), a risk score was developed to determine the comparative risk for bleeding on the basis of covariates derived in a Cox proportional hazards model. The risk prediction model was internally validated with bootstrapping. The model was then further developed in the GARFIELDAF registry (Global Anticoagulant Registry in the Field-Atrial Fibrillation), with individuals taking dabigatran, edoxaban, rivaroxaban, and apixaban. To determine generalizability in external cohorts and among individuals on different DOACs, the risk prediction model was validated in the COMBINE-AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) pooled clinical trial cohort and the Quebec Régie de l'Assurance Maladie du Québec and Med-Echo Administrative Databases (RAMQ) administrative database. The primary outcome was major bleeding. The risk score, termed the DOAC Score, was compared with the HAS-BLED score. RESULTS: Of the 5684 patients in RE-LY, 386 (6.8%) experienced a major bleeding event, within a median follow-up of 1.74 years. The prediction model had an optimism-corrected C statistic of 0.73 after internal validation with bootstrapping and was wellcalibrated based on visual inspection of calibration plots (goodness-of-fit P=0.57). The DOAC Score assigned points for age, creatinine clearance/glomerular filtration rate, underweight status, stroke/transient ischemic attack/embolism history, diabetes, hypertension, antiplatelet use, nonsteroidal anti-inflammatory use, liver disease, and bleeding history, with each additional point scored associated with a 48.7% (95% CI, 38.9%-59.3%; P<0.001) increase in major bleeding in RE-LY. The score had superior performance to the HAS-BLED score in RE-LY (C statistic, 0.73 versus 0.60; P for difference <0.001) and among 12 296 individuals in GARFIELD-AF (C statistic, 0.71 versus 0.66; P for difference = 0.025). The DOAC Score had stronger predictive performance than the HAS-BLED score in both validation cohorts, including 25 586 individuals in COMBINE-AF (C statistic, 0.67 versus 0.63; P for difference <0.001) and 11 945 individuals in RAMQ (C statistic, 0.65 versus 0.58; P for difference <0.001). CONCLUSIONS: In individuals with atrial fibrillation potentially eligible for DOAC therapy, the DOAC Score can help stratify patients on the basis of expected bleeding risk. [ABSTRACT FROM AUTHOR]

Background: Baseline serum creatinine (bSCr) is required for diagnosing acute kidney injury (AKI). In children, bSCr is commonly defined as the lowest measurement within 3 months of admission. Measured values are often missing and estimating bSCr using height-based glomerular filtration rate (GFR) equations is problematic when height is unavailable. Methods: This is a retrospective cohort study including 538 children admitted to the intensive care unit (ICU) between 2003 and 2005 at two centers in Canada, with measured bSCr, height, and ICU-SCr values. We evaluated the bias, accuracy, and precision of back-calculating bSCr from height-dependent and height-independent GFR equations. Agreement of AKI defined using measured and estimated bSCr was calculated. Multivariate analyses were performed to assess the impact of bSCr estimation methods on the association between AKI and ICU mortality, length of stay, and duration of mechanical ventilation. Results: Both methods underestimated bSCr by 1-3%, showed good accuracy (∼30% of patients with estimated bSCr within 10% of measured bSCr), but poor precision (wide 95% limits of agreement). The agreement between AKI defined by estimated versus measured bSCr was >80% (κ >0.5). The height-independent method performed best in children >13 years old; however, overall, both methods performed similarly across age subgroups. AKI was associated with longer stay, prolonged mechanical ventilation, and ICU mortality using measured and estimated bSCr. Conclusions: Height-dependent and height-independent bSCr estimation methods were comparable. This may have significant implications for performing pediatric AKI research using large databases, and in clinical care to define AKI when height is unknown. [ABSTRACT FROM AUTHOR]

Background: Cerebral palsy is the most common cause of childhood physical disability, with multiple associated comorbidities. Administrative claims data provide population-level prevalence estimates for cerebral palsy surveillance; however, their diagnostic accuracy has never been validated in Quebec. This study aimed to assess the accuracy of administrative claims data for the diagnosis of cerebral palsy. Methods: We conducted a retrospective cohort study of children with cerebral palsy born between 1999 and 2002 within 6 health administrative regions of Quebec. Provincial cerebral palsy registry data (reference standard) and administrative physician claims were linked. We explored differences between true-positive and false-negative cases using subgroup sensitivity analysis. Results: A total of 301 children were identified with confirmed cerebral palsy from the provincial registry, for an estimated prevalence of 1.8 (95% confidence interval [CI] 1.6-2.1) per 1000 children 5 years of age. The sensitivity and specificity of administrative claims data for cerebral palsy were 65.5% (95% CI 59.8%-70.8%) and 99.9% (95% CI 99.9%-99.9%), respectively, yielding a prevalence of 2.0 (95% CI 1.9-2.3) per 1000 children 5 years of age. The positive and negative predictive values were 58.8% (95% CI 53.3%-64.1%) and 99.9% (95% CI 99.9%-99.9%), respectively. The κ value was 0.62 (95% CI 0.57-0.67). Administrative claims data were more sensitive for children from rural regions, born preterm, with spastic quadriparesis and with higher levels of motor impairment. Interpretation: Administrative claims data do not capture the full spectrum of children with cerebral palsy. This suggests the need for a more sensitive case definition and caution when using such data without validation. [ABSTRACT FROM AUTHOR]

• Despite bisphosphonate therapy after an orthotopic liver transplant, the cumulative incidence of fragility fracture was high (17.5%) during the 36-month follow-up. • The median time to first fracture was 10 months, and most fractures occurred within the first 2 years after transplant. • Age 60 years or older and female sex increase the risk of fracture in liver recipients. • Post-transplant diabetes mellitus and cholestatic disease were associated with fragility fractures. Bone loss is significant after orthotopic liver transplant (OLT) and is associated with increased fracture risk and decreased quality of life. In post-transplant fracture prevention, the cornerstone of therapeutic management is bisphosphonates. We conducted a retrospective study in a cohort of 155 OLT recipients who received a bisphosphonate prescription at hospital discharge between 2012 and 2016 to investigate post-OLT fragility fracture incidence and predictive risk factors. Before OLT, 14 patients presented a T score < −2.5 SD, and 23 patients (14.8%) had a history of fracture. During follow-up, the cumulative incidence of fractures on bisphosphonates (99.4% risedronate/alendronate) was 9.7% at 12 months and 13.1% at 24 months. The median time to first fragility fracture was 10 months (IQR, 3-22 months) and thus within the first 2 years of follow-up. Predictive factors of fragility fractures in multivariate Cox regression analyses included age 60 years or older (hazard ratio [HR], 2.61; 95% CI, 1.14-6.01; P =.02), post-transplant diabetes mellitus (HR, 3.82; 95% CI, 1.55-9.44; P =.004), and cholestatic disease (HR, 5.93; 95% CI, 2.30-15.26; P =.0002). Additionally, the female sex was associated with a strong trend toward increased fracture risk in univariate analysis (HR, 2.27; 95% CI, 1.00-5.15; P =.05), as well as a post-transplant absolute decrease in bone mineral density at the femoral neck and total hip (P =.08). This real-world study reports a high incidence of fractures post-OLT despite bisphosphonate therapy. Age 60 years or older, post-transplant diabetes mellitus, cholestatic disease, female sex, and femoral neck and/or total hip bone mineral density loss contribute to increased imminent fracture risk in liver transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Low-dose direct oral anticoagulant (DOAC) use is quite prevalent in clinical practice, but evidence of its effectiveness and safety compared with high-dose DOAC in patients with atrial fibrillation (AF) remains limited. We aimed to assess the effectiveness and safety of low-dose and high-dose DOACs in patients with AF with similar baseline characteristics. Methods: We used a cohort of hospitalized patients with a primary or secondary diagnosis of AF after discharge to the community, whose data were stored in the Quebec administrative databases, from 2011 to 2017. Older adults with AF newly prescribed with rivaroxaban (15 or 20 mg) or apixaban (2.5 mg or 5 mg) were classified as under treatment (UT) and intent to treat (ITT). We used an inverse probability treatment weighting study of new users of rivaroxaban and apixaban to address confounding by indication. The primary effectiveness outcome was ischemic stroke/systemic embolism (SE), while the primary safety outcome was major bleeding (MB). We used Cox proportional models to estimate the marginal hazard ratios (HRs). Findings: A total of 1,722 and 4,639 patients used low-dose and standard-dose rivaroxaban, respectively, while 3,833 and 6,773 patients used low-dose and standard-dose apixaban, respectively. No significant difference was observed in the incidence of comparative stroke/SE and MB between low-dose and standard-dose rivaroxaban, except for the risk of acute myocardial infarction (AMI), which was increased with the low dose in the UT analysis. For apixaban, no difference was found in the bleeding rates, but the risk of stroke/SE (HR: 1.95; 95% confidence interval (CI): 1.38–2.76) and death (HR: 1.99; 95% CI: 1.46–2.70) were greater in the low-dose group than in the standard-dose group in the UT analysis. Similar results were observed for the ITT analysis. Conclusion: No significant differences were observed in the effectiveness or safety outcome between low-dose and standard-dose rivaroxaban, except for AMI. However, low-dose apixaban was associated with a greater risk of stroke/SE and death without a reduction in the bleeding rates. [ABSTRACT FROM AUTHOR]

The aim was to identify sex‐specific factors linked with oral anticoagulant initiation in a cohort of patients with atrial fibrillation using administrative data from Quebec (Canada) between 2014 and 2017. Cohort entry defined as new users, that is, no claims in last 12 months, a cohort of 32 050 patients was stratified in two groups, that is, women and men. Multivariable regression models were used to identify factors of initiations for low‐ and standard‐dose direct oral anticoagulants (DOACs) versus warfarin, and low‐ versus standard‐dose DOACs. In both sexes, warfarin initiation decreased and DOAC initiation increased, with year of initiation as major factors of DOACs use. In 2017, the increase was of 2‐ to 4‐fold and 3‐ to 8‐fold for low‐ and standard‐dose DOACs (vs. warfarin), respectively. The proportion of patients starting on a low‐dose DOAC was higher in women than men. Older age for both sexes and CHADS2 score ≥2 (only women) were major factors of low‐dose dabigatran and rivaroxaban versus warfarin use. The only significant factor of standard‐dose DOAC versus warfarin use was age of 65–79 for women or men treated with apixaban by 1.8‐ and 1.4‐fold, respectively. Factors that made women and men less likely to receive a standard‐dose DOAC versus warfarin were higher CHADS2 (for dabigatran and rivaroxaban), HAS‐BLED and frailty scores, prior coronary disease, major bleeding, and chronic kidney disease (CKD) status. The choice of a low‐ versus standard‐dose DOAC was mainly driven by age and CKD, and higher CHADS2 score (for dabigatran and apixaban) for both sexes. [ABSTRACT FROM AUTHOR]

Objective. Limited studies have explored the association between adipokines and knee OA structural progression using quantitative MRI (qMRI), and very few have included total knee replacement (TKR) as a disease outcome. The objective of this study was to compare serum levels of five adipokines to cartilage volume loss (CVL) and investigate their predictive value for TKR. Methods. The according-to-protocol population (n = 138) of a knee OA trial was used. Serum levels of adipsin (complement factor D), leptin, adiponectin, resistin and serpin E1, and cartilage volume were determined at baseline and 24 months with specific ELISAs and qMRI, respectively. Study knee TKR incidence up to 4 years post-trial was also assessed. Results. Greater baseline values of adipsin and leptin correlated with increased CVL in the global knee and medial femur (P ≤ 0.032) and of adipsin in the lateral compartment and femur (P ≤ 0.028). Adiponectin showed an inverse correlation in the medial compartment and femur (P ≤ 0.027). Resistin and serpin E1 were not associated with CVL. Multivariate analyses revealed that patients in the highest tertile at baseline of adipsin presented a greater odds ratio of CVL in the lateral compartment and femur (≥2.87; P ≤ 0.011), and those in the highest tertile of leptin in the medial compartment (2.78; P = 0.038). Most clinically relevant, patients in the highest tertile of adipsin or leptin at baseline had significantly greater incidence of TKR (P = 0.027). Conclusion. Data demonstrate that both adipsin and leptin predict greater CVL over time in the lateral and medial compartment, respectively. Importantly, this study also demonstrates that higher baseline levels of adipsin or leptin are associated with higher incidence of TKR. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is associated with morbidity, rehospitalization and polypharmacy. The incidence rate of mortality in HF patients with polypharmacy is poorly studied. We examine the association of polypharmacy with mortality risk in incident hospitalized HF patients with a primary diagnosis after discharge from the hospital using Quebec administrative databases, Canada from 1999 to 2015. Polypharmacy, cardiovascular (CV) polypharmacy and non-CV polypharmacy were respectively defined as exposure to ≥ 10 drugs, ≥ 5 CV drugs and ≥ 5 non-CV drugs within three months prior to the case or the control selection date. We conducted a nested case–control study to estimate rate ratios (RR) of all-cause mortality using a multivariate conditional logistic regression during one-year of follow-up. We identified 12,242 HF patients with a mean age of 81.6 years. Neither CV polypharmacy (RR 0.97, 95%CI 0.82–1.15) nor non-CV polypharmacy (RR 0.93, 95%CI 0.77–1.12) were associated with lower mortality risk. However, all polypharmacy (RR 1.31, 95%CI 1.07–1.61) showed an association with mortality risk. Myocardial infarction, valvular disease, peripheral artery disease, diabetes, major bleeding, chronic kidney disease, high comorbidity score, high Frailty score, hydralazine and spironolactone users were associated with increasing mortality risk, ranging from 15 to 61%, while use of angiotensin II inhibitors, beta-blockers, statins, anticoagulant, and antiplatelets were associated with lower risk, ranging from 23 to 32%. [ABSTRACT FROM AUTHOR]

The article is a response to a letter regarding the development and validation of the DOAC Score, a bleeding risk prediction tool for patients with atrial fibrillation on direct-acting oral anticoagulants (DOACs). The DOAC Score was developed and refined using data from various sources, including clinical trials, registries, and administrative databases. The score demonstrated moderate discrimination and outperformed the HAS-BLED Score in terms of predicting bleeding risk. The authors emphasize that the DOAC Score should be used as a risk stratification tool tailored to the specific population it is applied to. The article also includes acknowledgments and disclosures of potential conflicts of interest. [Extracted from the article]

Uncontrolled hypertension is associated with an increased risk of end-stage renal disease (ESRD). Intensified blood pressure control may slow progression of chronic kidney disease; however, the impact of antihypertensive agent adherence on the prevention of ESRD has never been evaluated. Here we assessed the impact of antihypertensive agent adherence on the risk of ESRD in 185,476 patients in the RAMQ databases age 45 to 85 and newly diagnosed/treated for hypertension between 1999 and 2007. A case cohort study design was used to assess the risk of and multivariate Cox proportional models were used to estimate the adjusted hazard ratio of ESRD. Adherence level was reported as a medication possession ratio. Mean patient age was 63 years, 42.2% male, 14.0% diabetic, 30.3% dyslipidemic, and mean follow-up was 5.1 years. A high adherence level of 80% or more to antihypertensive agent(s) compared to a lower one was related to a risk reduction of ESRD (hazard ratio 0.67; 95% confidence intervals 0.54-0.83). Sensitivity analysis revealed that the effect is mainly in those without chronic kidney disease. Risk factors for ESRD were male, diabetes, peripheral artery disease, chronic heart failure, gout, previous chronic kidney disease, and use of more than one agent. Thus, our study suggests that a better adherence to antihypertensive agents is related to a risk reduction of ESRD and this adherence needs to be improved to optimize benefits. [ABSTRACT FROM AUTHOR]

Aim: To compare the prevalence of epilepsy in children with cerebral palsy (CP) to peer controls and their differences in healthcare utilization. Method: The Quebec CP registry was linked to the provincial administrative health database. Two CP cohorts were identified from the registry (n=302, 168 males, 1y 2mo–14y) and administrative data (n=370, 221 males, 2y 2mo–14y). A control cohort (n=6040, 3340 males, 10–14y) was matched by age, sex, and region to the CP registry cohort. Administrative data algorithms were used to define epilepsy cases. Data on hospitalizations and emergency department presentations were obtained. Results: Using the most sensitive epilepsy definition, prevalence was 42.05% in the CP registry, 43.24% in the CP administrative data, and 1.39% in controls. Prevalence rose with increasing Gross Motor Function Classification System level. Children with CP and epilepsy had increased number and length of hospitalizations and emergency department presentations compared to children with CP or epilepsy alone. Epilepsy accounted for approximately 5% of emergency department presentations and 10% of hospitalizations in children with epilepsy, with and without CP. Interpretation: Children with CP have an increased risk of epilepsy compared to their peers. Children with CP and coexisting epilepsy represent a unique subset with complex developmental disability and increased healthcare service utilization. This original article is commented by Chin on page 148 of this issue. [ABSTRACT FROM AUTHOR]

Background: Social inequalities in complications associated with diabetes mellitus persist. As a primary care sensitive condition (PCSC), this association could be related to differential access to primary care. Our objectives are to establish a typology of care trajectories following a new diagnosis, and to explore social determinants of trajectories.Methods: We used the TorSaDe (The Care Trajectories-Enriched Data) cohort, which links Canadian Community Health Survey respondents to health administrative data. Care trajectories were mapped over a two-year period following a new diagnosis and analysed using state sequence and clustering methods. Associations between individual and geographic characteristics with trajectory types were assessed with multinomial logistic regression.Results: Three trajectories were identified: Regular Family Physician (FP) Predominant, Specialist Physician Predominant, and Few Services. With Regular FP as the reference, males had higher odds of experiencing the Few Services trajectory, higher education was associated with higher odds of both the Few Services and the Specialist trajectories, and immigrants had higher odds of the Specialist trajectory. Diagnoses in a physician's office, as opposed to in hospital, were associated with higher odds of the Regular FP trajectory.Conclusions: The Regular FP trajectory most closely aligns with the management principles of the PCSC approach. We did not find strong evidence of social status privileging access to this trajectory. However, the association with location of diagnosis suggests that efforts to ensure patients diagnosed in hospital are well linked to a regular family physician for follow up may help to reduce unnecessary specialist use and meet PCSC goals. [ABSTRACT FROM AUTHOR]

Background: Having a primary care provider and a continuous relationship may be important for asthma outcomes. In this study, we sought to determine the association between 1) having a usual provider of primary care (UPC) and asthma-related emergency department (ED) visits and hospitalization in Québec children with asthma and 2) UPC continuity of care and asthma outcomes. Methods: Population-based retrospective cohort study using Québec provincial health administrative data, including children 2-16 years old with asthma (N = 39, 341). Exposures and outcomes were measured from 2010-2011 and 2012-2013, respectively. Primary exposure was UPC stratified by the main primary care models in Quebec (team-based Family Medicine Groups, family physicians not in Family Medicine Groups, pediatricians, or no assigned UPC). For those with an assigned UPC the secondary exposure was continuity of care, measured by the UPC Index (high, medium, low). Four multivariate logistic regression models examined associations between exposures and outcomes (ED visits and hospitalizations). Results: Overall, 17.4% of children had no assigned UPC. Compared to no assigned UPC, having a UPC was associated with decreased asthma-related ED visits (pediatrician Odds Ratio (OR): 0.80, 95% Confidence Interval (CI) [0.73, 0.88]; Family Medicine Groups OR: 0.84, 95% CI [0.75,0.93]; non-Family Medicine Groups OR: 0.92, 95% CI [0.83, 1.02]) and hospital admissions (pediatrician OR: 0.66, 95% CI [0.58, 0.75]; Family Medicine Groups OR: 0.82, 95% CI [0.72, 0.93]; non-Family Medicine Groups OR: 0.76, 95% CI [0.67, 0.87]). Children followed by a pediatrician were more likely to have high continuity of care. Continuity of care was not significantly associated with asthma-related ED visits. Compared to low continuity, medium and high continuity of care decreased asthma-related hospital admissions, but none of these associations were significant. Conclusion: Having a UPC was associated with reduced asthma-related ED visits and hospital admissions. However, continuity of care was not significantly associated with outcomes. The current study provides ongoing evidence for the importance of primary care in children with asthma. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has had a disproportionate impact on vulnerable populations, including individuals with chronic pain. We examined associations between geographical variations in COVID-19 infection rates, stress and pain severity, and investigated factors associated with changes in pain status and psychological distress among individuals living with chronic pain during the pandemic. Methods: This investigation is part of a larger initiative, the Chronic Pain & COVID-19 Pan-Canadian Study, which adopted a cross-sectional observational design. A total of 3159 individuals living with chronic pain completed a quantitative survey between 16 April and 31 May 2020. Results: Two-thirds (68.1%) of participants were between 40 and 69 years old, and 83.5% were women. Two-thirds (68.9%) of individuals reported worsened pain since pandemic onset. Higher levels of perceived pandemic-related risks (adjusted odds ratio: 1.27; 95% confidence interval: 1.03-1.56) and stress (1.21; 1.05-1.41), changes in pharmacological (3.17; 2.49-4.05) and physical/psychological (2.04; 1.62-2.58) pain treatments and being employed at the beginning of the pandemic (1.42; 1.09-1.86) were associated with increased likelihood of reporting worsened pain. Job loss (34.9% of individuals were employed pre-pandemic) was associated with lower likelihood (0.67; 0.48-0.94) of reporting worsened pain. Almost half (43.2%) of individuals reported moderate/severe levels of psychological distress. Negative emotions toward the pandemic (2.14; 1.78-2.57) and overall stress (1.43; 1.36-1.50) were associated with moderate/severe psychological distress. Conclusion: Study results identified psychosocial factors to consider in addition to biomedical factors in monitoring patients' status and facilitating treatment access for chronic pain patients during a pandemic. [ABSTRACT FROM AUTHOR]

Study Objective: Observational studies assessing direct oral anticoagulant (DOACs) dosage in atrial fibrillation (AF) reported that a lower proportion of patients received high‐dose DOACs compared to those in randomized controlled trials (RCTs). Effectiveness and safety of high‐dose DOACs relative to apixaban in a real‐world AF population need to be addressed. The aim is to assess comparative effectiveness and safety of high‐dose rivaroxaban relative to apixaban. Design: We conducted a cohort study. Setting: We built a cohort of patients hospitalized and discharged in community with a primary or secondary AF diagnosis from 2011‐2017 using Quebec administrative databases (Med‐Echo and RAMQ). Patients: Cohort entry was defined as the first OAC claim in new users of high‐dose rivaroxaban and apixaban, with no OAC claims in the prior year. Intervention: To compare effectiveness and safety of high‐dose rivaroxaban to apixaban. Measurement: We ascertained patient demographics, comorbidities, CHA2DS2‐VASc and HASBLED scores and Charlson score within 3 years prior to cohort entry. Primary effectiveness and safety were a composite of ischemic stroke/systemic thrombosis, death, myocardial infarction, and of intracranial bleeding (ICH), extracranial major bleeding, in the first year following drug initiation. We conducted propensity score matching and estimated hazard ratios (HRs) for outcomes using Cox proportional hazard models. All the analyses were conducted to account for competing risks. Main results: The cohort consisted of 4,632 and 6,771 patients received high‐dose rivaroxaban and apixaban, respectively. High‐dose rivaroxaban users were younger with a mean age of 73.2 years, presented less associated comorbidities and had lower CHA2DS2‐VASc scores compared to apixaban. High‐dose rivaroxaban at the intention to treat was associated with a higher risk of stroke/SE/death (HR 1.21, 95% CI 1.04‐1.40) and worse composite effectiveness (HR 1.21: 1.05‐1.40); under treatment exposure, those values were at HR (1.66: 1.21‐2.29) and HR (1.58:1.19‐2.10), respectively. And, rivaroxaban presented a less favorable safety profile relative to apixaban. Conclusion: In this study, composite effectiveness and safety varied between rivaroxaban and apixaban. High‐dose apixaban was observed to have a better effectiveness and safety. [ABSTRACT FROM AUTHOR]

Aim: Real-world predictors of major bleeding (MB) have been well-studied among warfarin users, but not among all direct oral anticoagulant (DOAC) users diagnosed with atrial fibrillation (AF). Thus, our goal was to build a predictive model of MB for new users of all oral anticoagulants (OAC) with AF. Methods: We identified patients hospitalized for any cause and discharged alive in the community from 2011 to 2017 with a primary or secondary diagnosis of AF in Quebec's RAMQ and Med-Echo administrative databases. Cohort entry occurred at the first OAC claim. Patients were categorized according to OAC type. Outcomes were incident MB, gastrointestinal bleeding (GIB), non-GI extracranial bleeding (NGIB) and intracranial bleeding within 1 year of follow-up. Covariates included age, sex, co-morbidities (within 3 years before cohort entry) and medication use (within 2 weeks before cohort entry). We used logistic-LASSO and adaptive logistic-LASSO regressions to identify MB predictors among OAC users. Discrimination and calibration were assessed for each model and a global model was selected. Subgroup analyses were performed for MB subtypes and OAC types. Results: Our cohort consisted of 14,741 warfarin, 3,722 dabigatran, 6,722 rivaroxaban and 11,196 apixaban users aged 70–86 years old. The important MB predictors were age, prior MB and liver disease with ORs ranging from 1.37–1.64. The final model had a c-statistic of 0.63 (95% CI 0.60–0.65) with adequate calibration. The GIB and NGIB models had similar c-statistics of 0.65 (95% CI 0.63–0.66) and 0.67 (95% CI 0.64–0.70), respectively. Conclusions: MB and MB subtype predictors were similar among DOAC and warfarin users. The predictors selected by our models and their discriminative potential are concordant with published data. Thus, these models can be useful tools for future pharmacoepidemiologic studies involving older oral anticoagulant users with AF. [ABSTRACT FROM AUTHOR]

Background: To develop a pediatric-specific hypertension algorithm using administrative data and use it to evaluate the association between acute kidney injury (AKI) in the intensive care unit (ICU) and hypertension diagnosis 5 years post-discharge. Methods: Two-center retrospective cohort study of children (≤ 18 years old) admitted to the pediatric ICU in Montreal, Canada, between 2003 and 2005 and followed until 2010. Patients with a valid healthcare number and without end-stage renal disease were included. Patients who could not be merged with the provincial database, did not survive admission, underwent cardiac surgery, had pre-existing renal disease associated with hypertension or a prior diagnosis of hypertension were excluded. AKI defined using the Kidney Disease: Improving Global Outcomes (KDIGO) definition. Using diagnostic codes and medications from administrative data, novel pediatric-specific hypertension definitions were designed. Both the evaluation of the prevalence of hypertension diagnosis and the association between AKI and hypertension occurred. Results: Nineteen hundred and seventy eight patients were included (median age at admission [interquartile range] 4.3 years [1.1–11.8], 44% female, 325 (16.4%) developed AKI). Of these patients, 130 (7%) had a hypertension diagnosis 5 years after discharge. Patients with AKI had a higher prevalence of hypertension diagnosis [non-AKI: 84/1653 (5.1%) vs. AKI: 46/325 (14.2%), p <.001]. Children with AKI had a higher adjusted risk of hypertension diagnosis (hazard ratio [95% confidence interval] 2.19 [1.47–3.26]). Conclusions: Children admitted to the ICU have a high prevalence of hypertension post-discharge and children with AKI have over two times higher risk of hypertension compared to those with no AKI. [ABSTRACT FROM AUTHOR]

Background and Purpose: Data on oral anticoagulant (OAC) uptake and pattern of use are limited. Real‐life data in patients with atrial fibrillation (AF) are important for understanding patient exposure. A cohort study of new OAC users was built to assess trends of drug use from 2011 to 2017, persistence rate, switching rate, adherence level, and predictors of adherence. Methods: We built a cohort using the Régie d'Assurance Maladie du Québec (RAMQ) and Med‐Echo administrative databases of new adult OAC users within 1 year following hospitalization with a diagnosis of AF. New users of OAC were defined as having no OAC claims in the year before cohort entry. We assessed trends of OAC use; persistence rate, defined as a gap between refills of no longer than two times the duration of the previous prescriptions; and adherence level, defined as the proportion of days covered (PDC) over a 1‐year period following initiation. Predictors of nonadherence (PDC less than 80%) were analyzed using logistic regression models. Results: The cohort consisted of 33,311 incident OAC users. Of total OAC claims, the proportions of warfarin claims decreased from 77.9% in 2011 to 12.7% in 2017, with direct oral anticoagulants (DOACs) accounting for 87.3% of claims, of which apixaban and rivaroxaban accounted for 60.1% and 23.4%, respectively, by the end of 2017. One year after OAC initiation, persistence rates ranged from 53% with warfarin to 77% with a high dose of apixaban. Approximately 75% of incident OAC users were considered "adherent" (PDC 80% or more), with a mean PDC of 95.6–98.1%, compared with "nonadherent," with a mean PDC varying between 43.1% and 50.7%. Older age, female sex, higher CHA2DS2‐VASc score (to predict thromboembolic risk in AF), prior stroke, and treatment with chronic cardiovascular disease drugs were associated with high adherence levels. Conclusion: The clinical uptake of DOACs increased over time, accounting for 87.3% of prescriptions in 2017. In our study, 25% of new OAC users presented a low adherence level. Adherence to OACs remains a significant challenge in patients with AF. [ABSTRACT FROM AUTHOR]

Purpose: Some evidence suggests that spironolactone may have a deleterious effect on glucose homeostasis. The objective of this study was to assess whether spironolactone use is associated with a higher risk of developing diabetes in a large cohort of patients with heart failure (HF). Methods: Two Quebec government administrative databases were used to identify a cohort of hospitalized patients discharged between January 1995 and December 2009 with a primary discharge diagnosis of HF and without secondary discharge diagnosis of diabetes. Patients were categorized as new users of spironolactone and non-users. The primary outcome was defined as new-onset diabetes (NOD) during 5 years of follow-up and was ascertained using ICD codes for diabetes or use of hypoglycemic agents. Results: Among the 2974 patients that were included in the cohort analysis, 769 were given a new prescription of spironolactone. The incidence rate of NOD was similar among spironolactone users (5.0 per 100 person-years) and non-users (4.9 per 100 person-years). There was no significant association between the use of spironolactone and NOD in the crude, unadjusted model (hazard ratio (HR) 1.01; 95% confidence interval (CI) 0.80–1.28; p = 0.9217), and it remained unchanged in the adjusted Cox proportional hazard model (HR = 0.92; 95% CI = 0.72–1.18; p = 0.5227). The results were consistent with those observed in sensitivity analyses of a 1:3 propensity score-matched cohort (HR = 0.97; CI = 0.76–1.25; p = 0.8169). Conclusion: We found no evidence supporting the claim that use of spironolactone is associated with a higher risk of diabetes among patients hospitalized for HF. [ABSTRACT FROM AUTHOR]

Summary: What is known and objective: The literature has reported suboptimal real‐world use of oral anticoagulants in patients with atrial fibrillation (AF). Anticoagulation management services (AMSs) in community pharmacy have rarely been evaluated, and no formal process is available to enable pharmacists to evaluate and improve their clinical practices. Our objective was to assess the feasibility of implementing, through a practice‐based research network (PBRN), a quality improvement programme on AMSs by community pharmacists for AF patients and explore its impact on the quality of clinical practices and pharmacists' knowledge. Methods: An uncontrolled pre/post‐pilot study was conducted through a PBRN. Pharmacists identified 5‐20 AF patients on oral anticoagulants per pharmacy and completed questionnaires at baseline (T0) and after 6 months (T6). Clinical practices were evaluated using a set of quality indicators (QIs). QI scores ranged from 0% (no QI achieved) to 100% (all QIs achieved). The programme included an audit and feedback based on QIs and a personalized training programme (including online videos). Participation rates and satisfaction were documented. Mean changes (T6‐T0), with 95% confidence interval (CI), in QIs and knowledge scores were computed. Results and discussion: A total of 37 pharmacies (50 pharmacists) identified 222 patients who had received either vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs), or both. All pharmacies received their baseline quality report (audit), and facilitators contacted by phone 97% of pharmacies (feedback). Each of the six online videos was completed by at least 48% of pharmacists. Baseline mean global QI scores for VKAs and DOACs were 39.1% (95% CI: 35.7%‐42.4%) and 12.3% (7.8%‐16.8%), respectively. Over a 6‐month period, they increased by 12.5% points (7.5%‐17.5%) and 9.9% points (3.8%‐16.1%), respectively. Baseline mean global knowledge score was 68.7% (65.4%‐72.0%) and increased by 4.3% points (1.2%‐7.4%). What is new and conclusion: Implementing a quality improvement programme for AMS in community pharmacy is relevant and feasible and may improve pharmacists' practices and knowledge. Anticoagulation management services (AMSs) in community pharmacy have rarely been evaluated. This study assessed the feasibility of implementing, through a practice‐based research network, a quality improvement programme on AMSs for atrial fibrillation patients. Results show the programme is relevant and feasible and may improve pharmacists' practices and knowledge. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess the impact of follow-up in renal protection clinics on the prescription of and adherence to cardioprotective drugs in patients with chronic kidney disease (CKD). Methods: We studied stage 4 and 5 CKD patients who initiated follow-up in three renal protection clinics. The prescription pattern of antihypertensive agents (AHA) and lipid-lowering agents (LLAs) was measured as the percentage of patients who are prescribed the agents of interest at a given time. Adherence to drug therapy was defined as the percentage of days, during a pre-defined observation period, in which patients have an on-hand supply of their prescribed medications. Results: A total of 259 CKD patients were enrolled and followed for up to 1 year after referral to renal protection clinics. There was a significant increase in the prescription of angiotensin-converting enzyme inhibitors (34-39%), angiotensin II receptor blockers (11-14%), beta-blockers (40-51%), calcium channel blockers (62-74%), diuretics (66-78%) and LLAs (39-47%) during follow-up in the renal protection clinic compared with baseline (P-values<0.01 for all comparisons). The proportions of patients with good (≤80%) and poor (<80%) adherence to AHA (P=0.41) and LLAs (P=0.11) were similar in the year preceding and the year following the first visit to the renal protection clinics. Conclusion: Our results suggest that referral and follow-up in a renal protection clinic may increase the prescription of cardioprotective agents in CKD patients, but does not appear to improve adherence to these medications. [ABSTRACT FROM AUTHOR]

Aims: A population-based cohort study design was used to estimate persistence rate, re-initiation rate after discontinuation, and adherence level among incident users of oral antidiabetics (OADs), and to investigate predictors of non-persistence and non-adherence. Methods: Incident OAD users were identified using healthcare databases of residents covered by the public drug insurance plan of the Province of Quebec, Canada. Patients initiated OAD therapy between January 2000 and October 2009 and were aged 45-85 years at cohort entry. Persistence rate, re-initiation after discontinuation, and adherence level were assessed over 2 years. Predictors of non-persistence and non-adherence were analyzed using Cox and logistic regression models, respectively. Results: The cohort included 160,231 incident OAD users at entry. One year after OAD initiation, persistence rate was 51 % and adherence level 67 %. Among those deemed non-persistent, 80.6 % re-initiated OAD therapy within 12 months of discontinuation; a proportion increasing with primary persistence duration. The 1-year persistence rate varied according to OAD classes; being the highest for thiazolidinediones (62 %) and the lowest for alpha-glucosidase inhibitors (30 %). The likelihood for non-persistence was 39-54 % higher when drug copayments were required. Conversely, OAD discontinuation was least likely for patients with schizophrenia [hazard ratio 0.70 (95 % CI 0.67-0.73)], dyslipidemia [0.85 (0.84-0.87)], anticoagulation [0.86 (0.83-0.88)], hypertension [0.87 (0.85-0.88)], and ≥7 medications [0.90 (0.88-0.91)]. Predictors of non-adherence were similar. Conclusions: Non-persistence and non-adherence to OAD therapy were common, although re-initiation rate was high. OAD classes, drug copayments, comorbidities and co-medications may help identifying those who were more likely to benefit from counseling. [ABSTRACT FROM AUTHOR]

Background Many patients delay or interrupt dual antiplatelet therapy (DAT) after drug-eluting stent (DES) implantation, which increases the risk of stent thrombosis and death. Objective To test the hypothesis that simple telephone contact made by nurses would improve adherence to and persistence of DAT. Design Randomised controlled trial. Patients and intervention A total of 300 patients (mean±SD 64±10 years, 73% male) were recruited immediately after DES implantation performed between June 2009 and June 2010. The last patient recruited reached the 1-year follow-up time point in June 2011. Patients were randomised to one of two groups: intervention, with four telephone follow-ups, versus a control group. In the intervention group, phone calls were made within 7 days of the DES implantation and at 1, 6 and 9 months to support drug adherence. Control patients were followed as per usual clinical practice. Pharmacy data were collected to assess drug prescription filling and refill. Setting Tertiary care university cardiovascular centre and community. Main outcome measures The primary end point was the proportion of days covered with aspirin and clopidogrel over the year after discharge as assessed by pharmacy refill data. Secondary outcome measures included persistence of aspirin and clopidogrel treatment, defined as no gaps longer than 14 days during follow-up. Results Most patients (73%) underwent DES implantation in the context of an acute coronary syndrome. All patients had drug insurance cover, either from the public plan (59%) or through private plans (41%). Complete pharmacy follow-up data were available for 96% of the cohort. At 12 months, median scores (25th-75th centile) for adherence to aspirin and clopidogrel were 99.2% (97.5-100%) and 99.3% (97.5-100%), respectively, in the intervention group compared with 90.2% (84.2- 95.4%) and 91.5% (85.1-96.0%), respectively, in the control group (p<0.0001 for aspirin and clopidogrel). Patients in the intervention group were significantly more persistent in the aspirin and clopidogrel treatment than those in the control group. For clopidogrel, 87.2% of patients in the intervention group were still persistent at 12 months compared with only 43.1% in the control group (p<0.0001). Conclusions A simple approach of four telephone calls to patients after DES implantation significantly improved 1-year drug adherence to near-perfect scores. Persistence of DAT was also significantly improved by the intervention. [ABSTRACT FROM AUTHOR]

Background. Lifestyle changes are advocated as a first line of treatment for dyslipidemia. However, few studies have directly compared various combinations of diets and exercise.Methods. In a randomized controlled pilot study, we compared the standard lifestyle recommendations (NCEP step I diet with regular exercise) and more intense interventions including the NCEP step I diet with a supervised aerobic exercise program and the step II diet with and without a supervised aerobic exercise program. We measured risk factors, dietary intake, time on treadmill, and health-related quality of life at baseline and after 3 months.Results. Out of 198 eligible subjects, 47 (24%) were willing to participate and 41 completed the study. No significant change were observed with standard lifestyle recommendations. In contrast, participants in the more intense interventions lost weight (−1.7 to −3.7 kg) and reduced their total cholesterol (−4% to −6%), low-density lipoprotein cholesterol (−6%), and systolic blood pressure (−7.3 to −8.8 mmHg). Participants in the exercise program significantly increased their exercise capacity (1.6 to 1.9 METS). Overall, each 10% reduction in body weight was associated with a 7.6% reduction in low-density lipoprotein cholesterol.Conclusion. Standard lifestyle recommendations had little effect on blood lipid levels but more intense lifestyle interventions may be effective at improving blood lipids, other risk factors, and quality of life. [Copyright &y& Elsevier]