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.

Trends in Prescription Chronic Pain Medication Use before and during the First Wave of the COVID-19 Pandemic in Québec, Canada: An Interrupted Time Series Analysis.

BACKGROUND: In Canada, a state of health emergency was declared in May 2020 as a result of the COVID-19 pandemic. This study aimed to assess trends in the use of prescription medication for pain management by people living with chronic pain before and during the first wave of the pandemic. METHODS: Participants (n = 177) were adults reporting chronic pain who had completed a web-based questionnaire in 2019 and for whom complete longitudinal private and public insurance prescription claims were available. The monthly prevalence of medication use for nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and prescribed cannabinoids was assessed. An interrupted time series analysis was then performed to evaluate if the COVID-19 pandemic had had an impact on trends in pain medication use. RESULTS: The beginning of the first wave of the pandemic was associated with the onset of a downward trend in opioid use (p < 0.05); no such association was found regarding NSAIDs. However, point prevalence of opioid use at the beginning (Nov. 2019) and at the end (Mai 2020) of the study period remained somewhat stable (17.0% vs. 16.4%). Regarding prescribed cannabinoids, a gradual increase in use was observed over the entire study period independently from the impact of the first wave of the pandemic (15.3% vs. 22.6%, p < 0.05). CONCLUSION: While the occurrence of the first wave did have an impact on opioid use among people living with chronic pain, access to and use of opioids appear to have returned to normal before the end of the first wave of COVID-19.

Risk factors for the long-term incidence and progression of knee osteoarthritis in older adults: role of nonsurgical injury.

Background: For one of the most chronic medical conditions, osteoarthritis, uncertainties remain on the impact of injury chronology, the role of repeat injury on the incidence/progression of this disease and the need for knee arthroplasty. Objectives: To explore, in an older adult population, how nonsurgical knee injuries relate to osteoarthritis incidence/progression and the weight of independent risk factors for arthroplasty. Design: A cohort study design evaluates the long-term impact of injuries on knee osteoarthritis outcomes. Methods: Knees with no prior injury (n = 6358) and with at least one injury (n = 819) ⩽20 years before study inclusion were from the Osteoarthritis Initiative cohort. Sociodemographic, clinical and structural [X-ray, magnetic resonance imaging (MRI)] data at study inclusion and changes within 96 months were analysed. Statistics included a mixed model for repeated measurements, generalized estimating equations and multivariable Cox regression with covariates. Results: At inclusion, knees with prior injury demonstrated greater incidence and severity of osteoarthritis (p ⩽ 0.001). At 96 months, there was a greater increase in symptoms [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, p = 0.002], joint space width (JSW, p = 0.039) loss, medial cartilage volume loss (CVL, p ⩽ 0.001) and bone marrow lesion size (BML, p ⩽ 0.049). Knees with/without injury at inclusion but with new ones over time had a pronounced increase in symptoms (all WOMAC scores, p ⩽ 0.001), JSW loss, lateral (without) and medial CVL, lateral (without) and medial meniscal extrusion and medial BML (without; all p ⩽ 0.030). Levels of lateral and medial meniscal extrusion (without) and symptoms (with/without; all WOMAC scores, p ⩽ 0.001) were all accentuated with a repeated new injury. Risk factors associated with the highest knee arthroplasty occurrence are new meniscal extrusion and new injury (p ⩽ 0.001). Conclusion: This study highlights the importance of nonsurgical knee injury in older adults as an independent risk factor for knee osteoarthritis and arthroplasty. These data will be beneficial in clinical practice as they will help identify individuals at greater risk of significant disease progression and worst disease outcomes for a customized therapeutic approach.

Increased Imminent Fracture Risk in Liver Transplant Recipients Despite Bisphosphonate Therapy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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.

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.

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.

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%.

Risk factors associated with the occurrence of total knee arthroplasty in patients with knee osteoarthritis: a nested case-control study.

Objectives: The aim of this study was to investigate changes over time in osteoarthritis risk factors most closely associated with the occurrence of total knee arthroplasty (TKA). We hypothesize that the robustness of a longitudinal case-control study will provide new information on the association between changes in various clinical and structural parameters in different time frames before TKA. Methods: Cases (195; TKA after cohort entry) and controls (468) matched for age, gender, income, WOMAC pain, Kellgren-Lawrence grade and follow-up duration were from the Osteoarthritis Initiative cohort. Associations between changes in sociodemographic, clinical, imaging and osteoarthritis therapies with the occurrence of TKA were performed using conditional logistic regression analyses. Results: Worsening of WOMAC scores (cOR 1.02-1.20, p ⩽ 0.012), KOOS (1.02-1.04, p ⩽ 0.014), knee injuries sustained in the previous 30-40 years (women 2.70, p = 0.034) and valgus alignment (1.10, p = 0.052) were associated with the occurrence of TKA. Also associated with TKA was cartilage volume loss in the lateral (overall 1.76, p = 0.025; women 1.93, p = 0.047) and medial compartments (⩾10%, overall 1.54, p = 0.027; men 2.34, p = 0.008), occurrence of medial meniscal extrusion (overall 1.77, p = 0.046; men 2.86, p = 0.028), and increase in bone marrow lesions (BMLs) for women (1.09, p = 0.048). The association of risk factors with TKA was reinforced when both an increase in WOMAC pain and cartilage volume loss (1.85, p = 0.001) were combined. Pain medication usage, mainly narcotics and intra-articular steroid injections (IASI), was also associated with TKA, with no impact on changes in cartilage loss or structure. Conclusion: This study provides new information about gender differences in risk factors associated with the occurrence of TKA. Worsening of valgus alignment, cartilage volume loss in the lateral compartment, BMLs and older injuries are important risk factors in women, while medial compartment cartilage loss and meniscal extrusion are in men. The use of pain medication and IASI although associated was found not causal with TKA.

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.

Characteristics of Persons Seeking Care for Moderate to Severe Pain Due to Chronic Low Back Pain and Osteoarthritis: A Cross-Sectional Study.

Purpose: To assess the associations between pain severity or physical (pQoL) and mental (mQoL) health-related quality of life and disability status or health-care utilization among persons living with moderate/severe pain due to chronic low back pain (CLBP) or osteoarthritis (OA), who received treatments in Quebec's tertiary care pain centers. Materials and Methods: This retrospective study was carried out using the Quebec Pain Registry (Canada) from 2008 to 2014 and contains data on persons referred to tertiary pain management clinics. Participants were selected if they were diagnosed with CLBP (N = 2663) or OA (N = 139) of more than 3 months duration and of pain intensity ≥5 on the Numeric Rating Scale (0-10) and completed baseline questionnaires. Results: Less than 5% of persons were hospitalized in the 6 months before their first visit at the pain clinic, and 11.9% and 18.9% of persons with OA and CLBP, respectively, had a pain-related emergency room (ER) visit. Less than 1/5 and more than 1/4 of persons with OA and CLBP were receiving disability benefits, respectively. Persons with CLBP who had visited the ER, those on disability and those receiving disability benefits, reported higher levels of pain severity, interference, and lower levels of mQoL (and pQoL for those on disability or receiving benefits) compared to those who did not consult the ER, those not on disability or not receiving disability benefits, respectively (all p < 0.05). For OA, disability status was the only variable associated with pain interference and QoL (all p < 0.05). Conclusion: Pain severity, pain interference and mQoL were associated with health-care utilization and disability status in persons with CLBP. These results were globally not found among persons with OA, which might be due to smaller sample size or unique characteristics of this population.

Are primary care and continuity of care associated with asthma-related acute outcomes amongst children? A retrospective population-based study.

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.

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.

Epilepsy in children with cerebral palsy: a data linkage study.

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.

Acute kidney injury in the pediatric intensive care unit: outpatient follow-up.

BACKGROUND: Few studies have characterized follow-up after pediatric acute kidney injury (AKI). Our aim was to describe outpatient AKI follow-up after pediatric intensive care unit (PICU) admission. METHODS: Two-center retrospective cohort study (0-18 years; PICU survivors (2003-2005); noncardiac surgery; and no baseline kidney disease). Provincial administrative databases were used to determine outcomes. EXPOSURE: AKI (KDIGO (Kidney Disease: Improving Global Outcomes) definitions). OUTCOMES: post-discharge nephrology, family physician, pediatrician, and non-nephrology specialist visits. Regression was used to evaluate factors associated with the presence of nephrology follow-up (Cox) and the number of nephrology and family physician or pediatrician visits (Poisson), among AKI survivors. RESULTS: Of n = 2041, 355 (17%) had any AKI; 64/355 (18%) had nephrology; 198 (56%) had family physician or pediatrician; and 338 (95%) had family physician, pediatrician, or non-nephrology specialist follow-up by 1 year post discharge. Only 44/142 (31%) stage 2-3 AKI patients had nephrology follow-up by 1 year. Inpatient nephrology consult (adjusted hazard ratio (aHR) 7.76 [95% confidence interval (CI) 4.89-12.30]), kidney admission diagnosis (aHR 4.26 [2.21-8.18]), and AKI non-recovery by discharge (aHR 2.65 [1.55-4.55]) were associated with 1-year nephrology follow-up among any AKI survivors. CONCLUSIONS: Nephrology follow-up after AKI was uncommon, but nearly all AKI survivors had follow-up with non-nephrologist physicians. This suggests that AKI follow-up knowledge translation strategies for non-nephrology providers should be a priority. IMPACT: Pediatric AKI survivors have high long-term rates of chronic kidney disease (CKD) and hypertension, justifying regular kidney health surveillance after AKI. However, there is limited pediatric data on follow-up after AKI, including the factors associated with nephrology referral and extent of non-nephrology follow-up. We found that only one-fifth of all AKI survivors and one-third of severe AKI (stage 2-3) survivors have nephrology follow-up within 1 year post discharge. However, 95% are seen by a family physician, pediatrician, or non-nephrology specialist within 1 year post discharge. This suggests that knowledge translation strategies for AKI follow-up should be targeted at non-nephrology healthcare providers.

Outpatient Nephrotoxic Medication Prescription after Pediatric Intensive Care Acute Kidney Injury.

BACKGROUND: Nephrotoxic medication (NTM) avoidance may prevent further kidney damage in children with acute kidney injury (AKI). We compared outpatient NTM prescriptions in children with or without AKI during pediatric intensive care (PICU) hospitalization. We hypothesize that children with AKI are prescribed NTMs at the same rate as those without it. METHODS: This was a retrospective administrative data study of children <18 years, admitted to two PICUs in Montreal, Canada, from 2003 to 2005, with ≥30 days of provincial drug coverage. We evaluated the presence of ≥3 outpatient NTM prescriptions during the first year and 5 years after PICU discharge. RESULTS: Of 970 children, 23% had PICU AKI. In the 1st-5th years after discharge, 18% AKI vs. 10% non-AKI and 13% AKI vs. 4% non-AKI patients received ≥3 NTM prescriptions, respectively. There was no association between PICU AKI and prescription of ≥3 NTMs during the first year (adjusted RR 1.02 [95% CI 0.95-1.10]) nor in the first 5 years post-discharge (adjusted RR 1.04 [95%CI 0.96-1.12]). CONCLUSIONS: By offering a better understanding of the current state of outpatient NTM prescription to children with AKI, our study is a step toward considering strategies such as knowledge translation interventions for decreasing NTM exposure and improving outcomes in children with AKI.