Structured learning in time-dependent Cox models.

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.

Antipsychotics and Risks of Cardiovascular and Cerebrovascular Diseases and Mortality in Dwelling Community Older Adults.

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.

Association between cardiovascular diseases and dementia among various age groups: a population-based cohort study in older adults.

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.

Development and Validation of the DOAC Score: A Novel Bleeding Risk Prediction Tool for Patients With Atrial Fibrillation on Direct-Acting Oral Anticoagulants.

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 GARFIELD-AF 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 well-calibrated 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.

Androgen Deprivation Therapy and Risk of Cardiovascular Disease in Patients With Prostate Cancer Based on Existence of Cardiovascular Risk.

BACKGROUND: Controversy exists regarding the risk of cardiovascular disease (CVD) associated with androgen deprivation therapy (ADT) in patients with prostate cancer. We sought to evaluate the association between gonadotropin-releasing hormone (GnRH) agonists versus GnRH antagonist and the risk of CVD in patients with prostate cancer with or without prior CVD. PATIENTS AND METHODS: Using administrative databases from Quebec, Canada, we identified first-time GnRH agonists and antagonist (degarelix) users between January 2012 and June 2016. Follow-up ended at the earliest of the following: first CVD event (myocardial infarction [MI], stroke, ischemic heart disease [IHD], arrhythmia, and heart failure [HF]); switch of GnRH group; death; or December 31, 2016. Inverse probability of treatment weighting (IPTW) based on the propensity score was used to control for potential confounding. IPTW-Cox proportional hazards model accounting for competing risks was used to evaluate the association of interest. RESULTS: Among 10,785 patients identified, 10,201 and 584 were on GnRH agonists and antagonist, respectively. Median age was 75 years (interquartile range, 69-81 years) for both groups. A total of 4,152 (40.7%) men in the GnRH agonists group and 281 (48.1%) men in the GnRH antagonist group had CVD in the 3-year period prior to ADT initiation. Risk of HF was decreased in the antagonist group compared with the GnRH agonist group among patients with prior CVD (hazard ratio [HR], 0.46; 95% CI, 0.26-0.79). Risk of IHD was decreased in the antagonist group in patients without prior CVD (HR, 0.26; 95% CI, 0.11-0.65). Use of antagonist was associated with an increased risk of arrhythmia among patients with no prior CVD (HR, 2.34; 95% CI, 1.63-3.36). CONCLUSIONS: Compared with GnRH agonists, the GnRH antagonist was found to be associated with a decreased risk of HF, specifically among patients with prior CVD. Among those with no prior CVD, the GnRH antagonist was associated with a decreased risk of IHD but an increased risk of arrhythmia.

Evolution of and Evidence-Practice Gaps in Antithrombotic Management of Atrial Fibrillation Patients After Percutaneous Coronary Intervention.

Background: The management of atrial fibrillation and flutter (AF) patients undergoing percutaneous coronary intervention (PCI) has evolved rapidly in the past decade. We determine whether the publication of the 2016 Canadian Cardiovascular Society AF guidelines were associated with a shift in practice patterns. Methods: Using Quebec provincial administrative database information for the period from 2010-2017, a retrospective cohort of patients with inpatient or outpatient coding for AF, who subsequently underwent PCI with placement of a coronary stent, was created and analyzed for the antithrombotic regimen received in the following year. Prescribing behavior was compared among 3 time periods (2010-2011, 2012-2015, 2016-2017), and use of antithrombotics was compared to guideline-predicted therapy using the χ2 test. Predictors of oral anticoagulation (OAC) prescription were identified using adjusted logistic regression. Results: A total of 3740 AF patients undergoing PCI were included. The proportion of OAC prescription increased over time (2010-2011 = 51.4%; 2012-2015 = 54.3%; 2016-2017 = 56.6%; P = 0.13), with a significant increase in direct OAC prescription (P < 0.01). A substantial treatment gap in OAC prescription persisted after publication of the 2016 guidelines (56.6% observed vs 89.7% predicted; P < 0.01). Previous stroke, CHADS2 score, Charlson Comorbidity Index ≥ 4, and prior use of direct OAC or warfarin were predictors of being exposed to OAC claims; previous major bleeding, and low-dose acetylsalicylic acid or P2Y12 inhibitor use were predictors of not being exposed to OACs. Conclusion: Expert guidance contributed to an increase in OAC prescription following PCI, but up to 2017, substantial further changes in practice patterns would have been required to achieve the recommended rates of OAC prescription.

Contexte: La prise en charge des patients qui sont atteints de fibrillation auriculaire (FA) ou de flutter auriculaire et qui subissent une intervention coronarienne percutanée (ICP) a évolué rapidement au cours de la dernière décennie. Nous avons voulu déterminer si la publication des lignes directrices sur la fibrillation auriculaire de la Société canadienne de cardiologie en 2016 s'était traduite par un changement de pratiques. Méthodologie: À partir de renseignements recueillis dans la base de données administratives du Québec en ciblant la période allant de 2010 à 2017, nous avons créé une cohorte rétrospective de patients qui, selon le code diagnostique, avaient été hospitalisés ou reçus en consultation externe pour cause de FA ou de flutter auriculaire et qui avaient par la suite subi une ICP avec mise en place d'une endoprothèse coronaire. La cohorte a été l'objet d'une analyse visant à caractériser le traitement antithrombotique administré au cours de l'année suivant l'opération, et le comportement des prescripteurs a été comparé sur trois périodes (2010-2011, 2012-2015, 2016-2017). En outre, le recours aux antithrombotiques a été comparé au traitement prévu suivant les lignes directrices au moyen du test χ2. Les facteurs prédictifs de prescription d'anticoagulants oraux (ACO) ont été cernés par régression logistique corrigée. Résultats: Au total, 3 740 patients atteints de FA ou de flutter auriculaire et ayant subi une ICP ont été inclus dans la cohorte. La proportion d'ordonnances d'ACO a augmenté au fil du temps (2010-2011 = 51,4 %, 2012-2015 = 54,3 %, 2016-2017 = 56,6 %; P = 0,13), et la prescription d'ACO directs a connu une augmentation significative (P < 0,01). Un écart important sur le plan thérapeutique en matière de prescription d'ACO a persisté après la publication des lignes directrices en 2016 (proportion observée de 56,6 % vs proportion prévue de 89,7 %; P < 0,01). Les antécédents d'AVC, le score CHADS2, un indice de comorbidité de Charlson ≥ 4 et les antécédents de traitement par des ACO directs ou la warfarine étaient des facteurs prédictifs d'exposition aux ACO; les antécédents de saignement majeur et la prise à faible dose d'acide acétylsalicylique ou d'un inhibiteur de P2Y12 étaient des facteurs prédictifs de non-exposition aux ACO. Conclusion: Les avis des spécialistes ont contribué à une augmentation de la prescription d'ACO après une ICP. Toutefois, jusqu'en 2017, d'autres changements de pratique substantiels auraient été nécessaires pour atteindre les taux recommandés d'utilisation des ACO.

Psychological distress, social support, and use of outpatient care among adult men and women with coronary artery disease or other non-cardiovascular chronic disease.

OBJECTIVES: Psychological distress, as defined by elevations in symptoms of depression, anxiety, and/or perceived stress, is frequent in patients with chronic diseases, such as coronary artery disease (CAD). While psychological distress is known to impact disease outcomes, less is known about its influence on health care utilization, or on the factors that may modify these relationships. This prospective study examined whether 1) psychological distress predicts greater use of outpatient care services over a period of up to eight years in middle-aged to older individuals with CAD or other non-cardiovascular chronic diseases; 2) this relationship differs according to sex, presence of CAD, and/or social support. METHODS: Men and women (N = 1236; aged 60.85 ± 6.95 years) with and without CAD completed validated questionnaires on symptoms of depression, anxiety, perceived stress, and social support. Number of medical outpatient visits was obtained from the Régie de l'assurance maladie du Québec. Analyses included bivariate correlations, hierarchical regressions, and moderation analyses, controlling for sociodemographic and lifestyle variables. RESULTS: Psychological distress, social support, and yearly outpatient visits were significantly correlated (ps < 0.05). In regression analyses, only depressive symptoms were associated with significantly greater use of outpatient care (b = 0.048, p = .004), particularly among CAD patients (b = 0.085, p < .001). Neither sex nor social support moderated this relation. CONCLUSION: Depression predicted greater outpatient visits in patients with chronic disease, especially CAD patients. More research is needed to determine whether psychosocial interventions may have an impact on health care utilization.

Effectiveness and safety of apixaban and rivaroxaban vs warfarin in patients with atrial fibrillation and chronic kidney disease.

BACKGROUND: Randomized controlled trials (RCTs) of direct oral anticoagulants (DOACs) included a low proportion of atrial fibrillation (AF) patients with chronic kidney disease (CKD), and suggested that DOACs are safe and effective in patients with mild-to-moderate CKD. In a metanalysis of RCTs and observational studies, DOACs were associated with better efficacy (vs warfarin) in early CKD and had similar efficacy and safety profiles in patients with stages IV-V CKD. But few studies have provided data on the safety and effectiveness of each DOAC vs warfarin in patients with stage III CKD. The effectiveness and safety of DOACs in those patients are still subject to debate. AIM: To assess and compare the effectiveness and safety of apixaban and rivaroxaban vs warfarin in this patient population. METHODS: A cohort of patients with an inpatient or outpatient code for AF and stage III CKD who were newly prescribed apixaban and rivaroxaban was created using the administrative databases from the Quebec province of Canada between 2013 and 2017. The primary effectiveness outcome was a composite of ischemic stroke, systemic embolism, and death, whereas the primary safety outcome was a composite of major bleeding within a year of DOAC vs warfarin initiation. Treatment groups were compared in an under-treatment analysis using inverse probability of treatment weighting and Cox proportional hazards. RESULTS: A total of 8899 included patients filled out a new oral anticoagulation therapy claim; 3335 for warfarin and 5564 for DOACs. Compared with warfarin, 15 mg and 20 mg rivaroxaban presented a similar effectiveness and safety composite risk. Apixaban 5.0 mg was associated with a lower effectiveness composite risk [Hazard ratio (HR) 0.76; 95% confidence interval (CI): 0.65-0.88] and a similar safety risk (HR 0.94; 95%CI: 0.66-1.35). Apixaban 2.5 mg was associated with a similar effectiveness composite (HR 1.00; 95%CI: 0.79-1.26) and a lower safety risk (HR 0.65; 95%CI: 0.43-0.99. Although, apixaban 5.0 mg was associated with a better effectiveness (HR 0.76; 95%CI: 0.65-0.88), but a similar safety risk profile (HR 0.94; 95%CI: 0.66-1.35). The observed improvement in the effectiveness composite for apixaban 5.0 mg was driven by a reduction in mortality (HR 0.61; 95%CI: 0.43-0.88). CONCLUSION: In comparison with warfarin, rivaroxaban and apixaban appear to be effective and safe in AF patients with stage III CKD.

Effectiveness and safety of low-dose versus standard-dose rivaroxaban and apixaban in patients with atrial fibrillation.

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.

Polypharmacy and risk of mortality among patients with heart failure following hospitalization: a nested case-control study.

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%.

Trends of use and factors that determine the choice of oral anticoagulants in women and men with atrial fibrillation.

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.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants vs Warfarin Among Obese Patients With Atrial Fibrillation.

Background: Obese patients are underrepresented in clinical trials assessing the comparative effectiveness and safety of use of direct oral anticoagulants vs use in atrial fibrillation (AF) patients. Methods: Using data from Quebec provincial administrative databases, for the years2010-2017, we created a retrospective cohort of patients with inpatient or outpatient coding for AF and obesity who were newly prescribed an oral anticoagulant. The primary safety outcome was a composite of intracranial, gastrointestinal, and major bleeding from other sites, and the primary effectiveness outcome was a composite of ischemic stroke, systemic embolism, acute myocardial infarction, and death in the first year after oral anticoagulant initiation. Treatment groups were compared using inverse-probability-of-treatment-weighting Cox proportional-hazards models. Results: A total of 2263 patients were included, of whom 1253, 403, and 539 filled a warfarin, standard-dose rivaroxaban, and standard-dose apixaban prescription, respectively. Standard-dose rivaroxaban was associated with a similar composite safety (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.44-1.91) and composite effectiveness risk (HR 1.42; 95% CI 0.99-2.04) compared to warfarin, whereas standard-dose apixaban was associated with a lower composite safety (HR 0.40; 95% CI 0.16-0.98) and similar composite effectiveness risk (HR 0.96; 95% CI 0.67-1.39). Conclusion: Use of direct oral anticoagulants in obese AF patients was associated with a similar effectiveness and safety profile to that of warfarin use.

Introduction: Les patients obèses sont sous-représentés dans les essais cliniques qui portent sur l'évaluation de l'efficacité comparative et l'innocuité de l'utilisation d'anticoagulants oraux directs vs leur utilisation chez les patients atteints de fibrillation auriculaire (FA). Méthodes: À l'aide des données de la base de données administratives provinciales du Québec, des années 2010-2017, nous avons créé une cohorte rétrospective de patients dont le codage des séjours hospitaliers et en ambulatoire étaient la FA et l'obésité qui avaient récemment reçu une ordonnance d'anticoagulants oraux. Le principal critère d'évaluation de l'innocuité était un critère composite qui associait les hémorragies intracrâniennes, gastro-intestinales et majeures d'autres sites, et le principal critère d'évaluation de l'efficacité était un critère composite d'accident vasculaire cérébral, d'embolie systémique, d'infarctus aigu du myocarde et de décès dans la première année après l'amorce des anticoagulants oraux. Nous avons comparé les groupes de traitement à l'aide des modèles à risques proportionnels de Cox basés sur la probabilité inverse de pondération de traitement. Résultats: Nous avons retenu un total de 2 263 patients, dont 1 253, 403 et 539 ont pris de façon respective les médicaments prescrits suivants : la warfarine, le rivaroxaban à la posologie standard et l'apixaban à la posologie standard. Le rivaroxaban à la posologie standard était associé à un risque de survenue d'un événement compris dans le critère composite de l'innocuité (ratio d'incidence approché [RIA] 0,91; intervalle de confiance [IC] à 95 % 0,44-1,91) et un risque de survenue d'un événement compris dans le critère composite de l'efficacité (RIA 1,42; IC à 95 % 0,99-2,04) similaires par rapport à la warfarine, tandis que l'apixaban à la posologie standard était associé à un risque de survenue d'un événement compris dans le critère composite de l'innocuité plus faible (RIA 0,40; IC à 95 % 0,16-0,98) et un risque de survenue d'un événement compris dans le critère composite de l'efficacité similaire (RIA 0,96; IC à 95 % 0,67-1,39). Conclusion: L'utilisation d'anticoagulants oraux directs chez les patients obèses atteints de FA était associée à un profil d'efficacité et d'innocuité similaire à celui de l'utilisation de la warfarine.

Association of Nonrecovery of Kidney Function After Pediatric Acute Kidney Injury With 5-Year Kidney and Nonkidney Outcomes.

Acute kidney injury is common in critically ill children, but the long-term outcomes are not well defined. OBJECTIVES: Evaluated whether nonrecovery of kidney function, following acute kidney injury, was associated with postdischarge mortality, healthcare utilization, and chronic kidney disease. DESIGN: Retrospective, two-center, observational study. SETTING: Two ICUs at tertiary children's hospitals in Montreal, QC. PARTICIPANTS: Pediatric patients (age ≤ 18 yr) with index admission to intensive care between January 1, 2003, and March 31, 2005. Children were excluded if they 1) died during admission, 2) did not have serum creatinine or urine output measured, 3) did not develop acute kidney injury, 4) could not be linked to administrative health data, and 5) (for chronic kidney disease outcome) had pre-existing renal disease by chart review, baseline estimated glomerular filtration rate measurement, or administrative health data codes. MAIN OUTCOMES AND MEASURES: Three-hundred seventy-eight patients' data were included for long-term mortality and healthcare utilization outcomes; 316 patients for long-term chronic kidney disease outcome. Outcomes were defined using provincial administrative healthcare data diagnosis, procedure, and billing codes. MAIN RESULTS: Nonrecovery of kidney function, defined as serum creatinine greater than or equal to 1.5× baseline at ICU discharge, occurred in 51 patients (13%). Nonrecovery of kidney function was not associated with long-term mortality (at 5-7 yr following hospital discharge), increased hospitalizations or emergency department visits (at 30-days, 1-year, and 5-yr follow-up), or increased physician visits (at 1- and 5-yr follow-up). Nonrecovery was associated with increased 30-day physician visits (adjusted relative risk, 1.40; 95% CI, 1.13-1.73) and chronic kidney disease diagnosis within 5 years of discharge (adjusted hazard ratio, 4.92, 95% CI, 1.77-13.70). CONCLUSIONS AND RELEVANCE: Nonrecovery of kidney function following an episode of acute kidney injury in critically ill children is associated with nearly five-fold increased risk for long-term chronic kidney disease. Acute kidney injury nonrecovery may be a useful marker to identify patients that are particularly important to follow-up post discharge for chronic kidney disease detection.

Trajectories of Follow-up Compliance in a Fracture Liaison Service and Their Predictors: A Longitudinal Group-Based Trajectory Analysis.

INTRODUCTION/OBJECTIVES: Identification of groups of patients following similar trajectories of time-varying patient characteristics are often of considerable clinical value. This study provides an example of how the identification of trajectory groups of patients can be useful. METHODS: Using clinical and administrative data of a prospective cohort study aiming to improve the secondary prevention of osteoporosis-related fractures with a Fracture Liaison Service (FLS), trajectory groups for visit compliance over time (2-year follow-up) were predicted using group-based trajectory modeling. Predictors of trajectory groups were identified using multinomial logistic regressions. RESULTS: Among 532 participants (86% women, mean age 63 years), three trajectories were identified and interpreted as high followers, intermediate followers, and low followers. The predicted probability for group-membership was: 48.4% high followers, 28.1% intermediate followers, 23.5% low followers. A lower femoral bone mineral density and polypharmacy were predictors of being in the high followers compared to the low followers group; predictors for being in the intermediate followers group were polypharmacy and referral to a bone specialist at baseline. CONCLUSIONS: Results provided information on visit compliance patterns and predictors for the patients undergoing the intervention. This information has important implications when implementing such health services and determining their effectiveness.

Association of pediatric cardiac surgery-associated acute kidney injury with post-discharge healthcare utilization, mortality and kidney outcomes.

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.

Predicting major bleeding among hospitalized patients using oral anticoagulants for atrial fibrillation after discharge.

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.

Comparative effectiveness and safety of high-dose rivaroxaban and apixaban for atrial fibrillation: A propensity score-matched cohort study.

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.

Patient Healthcare Trajectory and its Impact on the Cost-Effectiveness of Fracture Liaison Services.

This study aimed to assess the cost-utility of a Fracture Liaison Service (FLS) with a systematic follow-up according to patients' follow-up compliance trajectories. The Lucky Bone™ FLS is a prospective cohort study conducted on women and men (≥40 years) with fragility fractures. Dedicated personnel of the program identified fractures, investigated, treated, and followed patients systematically over 2 years. Groups of follow-up compliance trajectories were identified, and Markov decision models were used to assess the cost-utility of each follow-up trajectory group compared to usual care. A lifetime horizon from the perspective of the healthcare payer was modeled. Costs were converted to 2018 Canadian dollars and incremental cost-utility ratios (ICURs) were measured. Costs and benefits were discounted at 1.5%. A total of 532 participants were followed in the FLS (86% women, mean age of 63 years). Three trajectories were predicted and interpreted; the high followers (HFs, 48.4%), intermediate followers (IFs, 28.1%), and low followers (LFs, 23.5%). The costs of the interventions per patient varied between $300 and $446 for 2 years, according to the follow-up trajectory. The FLS had higher investigation, treatment, and persistence rates compared to usual care. Compared to usual care, the ICURs for the HF, IF, and LF trajectory groups were $4250, $21,900, and $72,800 per quality-adjusted life year (QALY) gained, respectively ($9000 per QALY gained for the overall FLS). Sensitivity analyses showed that the HF and IF trajectory groups, as well as the entire FLS, were cost-effective in >67% of simulations with respect to usual care. In summary, these results suggest that a high-intensity FLS with a systematic 2-year follow-up can be cost-effective, especially when patients attend follow-up visits. They also highlight the importance of understanding the behaviors and factors that surround follow-up compliance over time as secondary prevention means that they are at high risk of re-fracture. © 2020 American Society for Bone and Mineral Research (ASBMR).

Automated E-Counseling for Chronic Heart Failure: CHF-CePPORT Trial.

BACKGROUND: International task force statements advocate telehealth programs to promote health-related quality of life for patients with chronic heart failure (CHF). To that end, we evaluated the efficacy and usability of an automated e-counseling program. METHODS: This Canadian multi-site double-blind randomized trial assessed whether usual care plus either internet-based e-counseling (motivational and cognitive-behavioral tools for CHF self-care) or e-based conventional CHF self-care education (e-UC) improved 12-month Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS). Secondary outcomes included program engagement (total logon weeks, logons, and logon hours), total CHF self-care behaviors, diet (fruit and vegetable servings), 6-minute walk test, and 4-day step count. The association between program engagement and health-related quality of life was assessed using KCCQ-OS tertiles. RESULTS: We enrolled 231 patients, median age =59.5 years, 22% female, and elevated median KCCQ-OS=83.0 (interquartile range, 68-93). KCCQ-OS increase ≥5 points was not more prevalent for e-counseling, n=29 (29.6%) versus e-UC, n=32 (34.0%), P=0.51. E-Counseling versus e-UC increased total logon weeks (P=0.02), logon hours (P=0.001), and logons (P<0.001). Only e-counseling showed a positive association between 12-month KCCQ-OS tertile and logon weeks (P=0.04) and logon hours (P=0.004). E-Counseling increased CHF self-care behavior and diet but not 6-minute walk test or 4-day step count. CONCLUSIONS: The primary KCCQ-OS end point was negative for this trial. Only e-counseling showed a positive association between program engagement and 12-month KCCQ-OS tertile, and it improved CHF self-care behavior and diet. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01864369.