Introduction The use of weapons of mass destruction against civilian populations is of serious concern to public health authorities. Chemical weapons are of particular concern. A few studies have investigated medical responses in prehospital settings in the immediate aftermath of a chemical attack, and they were limited by the paucity of clinical data. This study aims to describe the acute management of patients exposed to a chemical attack from the incident site until their transfer to a medical facility. Methods and analysis This international multicentric observational study addresses the period from 1970 to 2036. An online electronic case report form was created to collect data; it will be hosted on the Biomedical Telematics Laboratory Platform of the Quebec Respiratory Health Research Network. Participating medical centres and their clinicians are being asked to provide contextual and clinical information, including the use of protective equipment and decontamination capabilities for the medical evacuation of the patient from the incident site of the chemical attack to the moment of admission at the medical facility. In brief, variables are categorised as follows: (1) chemical exposure (threat); (2) prehospital and hospital/medical facility capabilities (staffing, first aid, protection, decontamination, disaster plans and medical guidelines); (3) clinical interventions before hospital admission, including the use of protection and decontamination and (4) outcomes (survivability vs mortality rates). Judgement criteria focus on decontamination drills applied to any of the patient’s conditions. Ethics and dissemination The Sainte-Justine Research Centre Ethics Committee approved this multicentric study and is acting as the main evaluating centre. Study results will be disseminated through various means, including conferences, indexed publications in medical databases and social media. Trial registration number NCT05026645 .
The phenotype of the rare HIV-infected cells persisting during ART remains elusive. We developed a single-cell approach that combines the phenotypic analysis of HIV-infected cells with near full-length sequencing of their associated proviruses. Individual cells carrying clonally expanded identical proviruses displayed very diverse phenotypes, indicating that cellular proliferation contributes to the phenotypic diversification of the HIV reservoir. Unlike most viral genomes persisting on ART, inducible and translation-competent proviruses rarely presented large deletions but were enriched in defects in the Ψ locus. Interestingly, the few cells harboring genetically intact and inducible viral genomes expressed higher levels of the integrin VLA-4 compared to uninfected cells or cells with defective proviruses. Viral outgrowth assay confirmed that memory CD4+ T cells expressing high levels of VLA-4 were highly enriched in replication-competent HIV (27-fold enrichment). We conclude that although clonal expansions diversify the phenotype of HIV reservoir cells, CD4+ T cells harboring replication-competent HIV retain VLA-4 expression.
Elite athletes are at greater risk of joint injuries linked to the subsequent risk of developing osteoarthritis (OA). Genetic factors such as mitochondrial (mt) DNA haplogroups have been associated with the incidence/progression of OA and athletic performance. This review highlights an area not yet addressed: is there a common pattern in the mtDNA haplogroups for OA occurrence in individuals and elite athletes of populations of the same descent? Haplotypes J and T confer a decreased risk of OA in Caucasian/European descent, while H and U increase this risk. Both J and T haplogroups are under-represented in Caucasian/European individuals and endurance athletes with OA, but power athletes showed a greater percentage of the J haplogroup. Caucasian/European endurance athletes had a higher percentage of haplogroup H, which is associated with increased athletic performance. In a Chinese population, haplogroup G appears to increase OA susceptibility and is over-represented in Japanese endurance athletes. In contrast, in Koreans, haplogroup B had a higher frequency of individuals with OA but was under-represented in the endurance athlete population. For Caucasian endurance athletes, it would be interesting to evaluate if those carrying haplotype H would be at an increased risk of accelerated OA, as well as the haplogroup G in Chinese and Japanese endurance athletes. The reverse might be studied for the Korean descent for haplogroup B. Knowledge of such genetic data could be used as a preliminary diagnosis to identify individuals at high risk of OA, adding prognostic information and assisting in personalising the early management of both populations.
Background Knee osteoarthritis is the most prevalent chronic musculoskeletal debilitating disease. Current treatments are only symptomatic, and to improve this, we need a robust prediction model to stratify patients at an early stage according to the risk of joint structure disease progression. Some genetic factors, including single nucleotide polymorphism (SNP) genes and mitochondrial (mt)DNA haplogroups/clusters, have been linked to this disease. For the first time, we aim to determine, by using machine learning, whether some SNP genes and mtDNA haplogroups/clusters alone or combined could predict early knee osteoarthritis structural progressors. Methods Participants (901) were first classified for the probability of being structural progressors. Genotyping included SNP genes TP63, FTO, GNL3, DUS4L, GDF5, SUPT3H, MCF2L, and TGFA; mtDNA haplogroups H, J, T, Uk, and others; and clusters HV, TJ, KU, and C-others. They were considered for prediction with major risk factors of osteoarthritis, namely, age and body mass index (BMI). Seven supervised machine learning methodologies were evaluated. The support vector machine was used to generate gender-based models. The best input combination was assessed using sensitivity and synergy analyses. Validation was performed using tenfold cross-validation and an external cohort (TASOAC). Results From 277 models, two were defined. Both used age and BMI in addition for the first one of the SNP genes TP63, DUS4L, GDF5, and FTO with an accuracy of 85.0%; the second profits from the association of mtDNA haplogroups and SNP genes FTO and SUPT3H with 82.5% accuracy. The highest impact was associated with the haplogroup H, the presence of CT alleles for rs8044769 at FTO, and the absence of AA for rs10948172 at SUPT3H. Validation accuracy with the cross-validation (about 95%) and the external cohort (90.5%, 85.7%, respectively) was excellent for both models. Conclusions This study introduces a novel source of decision support in precision medicine in which, for the first time, two models were developed consisting of (i) age, BMI, TP63, DUS4L, GDF5, and FTO and (ii) the optimum one as it has one less variable: age, BMI, mtDNA haplogroup, FTO, and SUPT3H. Such a framework is translational and would benefit patients at risk of structural progressive knee osteoarthritis.
Objective: The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is a pragmatic study that includes 2 randomized trials and registries of treated or conservatively managed patients. The authors report the results of the surgical registry. Methods: TOBAS patients are managed according to an algorithm that combines clinical judgment and randomized allocation. For patients considered for curative treatment, clinicians selected from surgery, endovascular therapy, or radiation therapy as the primary curative method, and whether observation was a reasonable alternative. When surgery was selected and observation was deemed unreasonable, the patient was not included in the randomized controlled trial but placed in the surgical registry. The primary outcome of the trial was mRS score > 2 at 10 years (at last follow-up for the current report). Secondary outcomes include angiographic results, perioperative serious adverse events, and permanent treatment-related complications leading to mRS score > 2. Results: From June 2014 to May 2021, 1010 patients were recruited at 30 TOBAS centers. Surgery was selected for 229/512 patients (44%) considered for curative treatment; 77 (34%) were included in the surgery versus observation randomized trial and 152 (66%) were placed in the surgical registry. Surgical registry patients had 124/152 (82%) ruptured and 28/152 (18%) unruptured arteriovenous malformations (AVMs), with the majority categorized as low-grade Spetzler-Martin grade I-II AVM (118/152 [78%]). Thirteen patients were excluded, leaving 139 patients for analysis. Embolization was performed prior to surgery in 78/139 (56%) patients. Surgical angiographic cure was obtained in 123/139 all-grade (89%, 95% CI 82%-93%) and 105/110 low-grade (95%, 95% CI 90%-98%) AVM patients. At the mean follow-up of 18.1 months, 16 patients (12%, 95% CI 7%-18%) had reached the primary safety outcome of mRS score > 2, including 11/16 who had a baseline mRS score ≥ 3 due to previous AVM rupture. Serious adverse events occurred in 29 patients (21%, 95% CI 15%-28%). Permanent treatment-related complications leading to mRS score > 2 occurred in 6/139 patients (4%, 95% CI 2%-9%), 5 (83%) of whom had complications due to preoperative embolization. Conclusions: The surgical treatment of brain AVMs in the TOBAS registry was curative in 88% of patients. The participation of more patients, surgeons, and centers in randomized trials is needed to definitively establish the role of surgery in the treatment of unruptured brain AVMs. Clinical trial registration no.: NCT02098252 (ClinicalTrials.gov).
Introduction Despite the importance to address mental health issues as early as possible, youth experiencing homelessness (YEH) often lack prompt and easy access to health services. Recently, there has been a surge of studies focusing on leveraging technology to improve access to mental health services for YEH; however, limited efforts have been made to synthesise this literature, which can have important implications for the planning of mental health service delivery. Thus, this scoping review aims to map and synthesise research on the use of information and communication technologies (ICTs) to provide mental health services and interventions to YEH. Methods and analysis A scoping review of the literature will be conducted, following Arksey and O’Malley’s proposed methodology, the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews and recent guidelines from the Joanna Briggs Institute. All peer-reviewed papers using ICTs as a means of intervention will be considered, as well as grey literature. Only documents in English or French will be included in the analysis. First, 10 electronic databases will be consulted. Next, all data will be extracted into Covidence. Then, two reviewers will independently conduct the screening and data extraction process, in the case of discrepancies, a third reviewer will be included. Finally, data will be synthesised according to our objectives. Ethics and dissemination Ethics approval is not required, as data will be collected from published literature. Findings will be disseminated through conference presentations and peer-reviewed journals.
Objective: We assessed the association between fetal sex and the likelihood of marriage during pregnancy. Methods: We analyzed a cohort of 1,334,911 women who were unmarried at conception and had a live birth between 1990 and 2018 in Quebec, Canada. The exposure was fetal sex, determined by ultrasound. The outcome was marriage during pregnancy. We estimated hazard ratios and 95% confidence intervals (CI) for the association of child sex with the likelihood of marriage during pregnancy according to region of origin. Results: Among women who were unmarried at conception, 13.1% of foreign-born women got married during pregnancy compared with 2.6% of Canadian-born women. Women from the Middle East and North Africa who were pregnant with boys were 1.13 times more likely to marry during pregnancy compared with women who were pregnant with girls (95% CI 1.02–1.26). There was no association among Canadian-born women. Conclusion: Women from some cultural minorities who are pregnant with boys may be more likely to marry during pregnancy in Western settings. Gender inequality may manifest as a preference for sons that influences the likelihood of marriage.
Aim This scoping review aims to better understand the extent and nature of research activity on the topic of mental health problems in young people with childhood-onset physical disabilities. Specifically, we document what has been investigated in terms of the occurrence and experience of mental health problems among young people with childhood-onset physical disabilities, and their access to mental health services. Methods We searched four databases (Medline, PsycINFO, CINAHL, Embase) for articles published between 2007 and 2019. Studies were included if they addressed: (1) young people between the ages of 13 and 24 with a childhood-onset physical disability, and (2) mental health assessment, treatment, or service access and use. Results We identified 33 peer-reviewed studies that focused mainly on young people with cerebral palsy, juvenile arthritis, and spina bifida. The most common mental health problems investigated were depression and mood related difficulties (73%), anxiety (39%), and social/behavioural issues (33%) and the most common age range was 13 to 17. Ten studies explored access, use, and experiences of mental health services; stigma; caregiver mental health; and value for comprehensive care, using qualitative, quantitative, or mixed methods. Conclusions Findings suggest the importance of developing integrated models of service delivery to identify and address the mental health needs of this population, and consensus on best practices for assessment and reporting rates of subclinical symptoms and psychiatric conditions.
There is limited evidence regarding the exposure‐effect relationship between lung‐cancer risk and hexavalent chromium (Cr(VI)) or nickel. We estimated lung‐cancer risks in relation to quantitative indices of occupational exposure to Cr(VI) and nickel and their interaction with smoking habits. We pooled 14 case‐control studies from Europe and Canada, including 16,901 lung‐cancer cases and 20,965 control subjects. A measurement‐based job‐exposure‐matrix estimated job‐year‐region specific exposure levels to Cr(VI) and nickel, which were linked to the subjects’ occupational histories. Odds ratios (OR) and associated 95% confidence intervals (CI) were calculated by unconditional logistic regression, adjusting for study, age group, smoking habits, and exposure to other occupational lung carcinogens. Due to their high correlation, we refrained from mutually adjusting for Cr(VI) and nickel independently. In men, ORs for the highest quartile of cumulative exposure to CR(VI) were 1.32 (95% CI 1.19‐1.47) and 1.29 (95% CI 1.15‐1.45) in relation to nickel. Analogous results among women were: 1.04 (95% CI 0.48‐2.24) and 1.29 (95% CI 0.60‐2.86), respectively. In men, excess lung‐cancer risks due to occupational Cr(VI) and nickel exposure were also observed in each stratum of never, former and current smokers. Joint effects of Cr(VI) and nickel with smoking were in general greater than additive, but not differerent from multiplicative. In summary, relatively low cumulative levels of occupational exposure to Cr(VI) and nickel were associated with increased ORs for lung cancer, particularly in men. However, we cannot rule out a combined classical measurement and Berkson‐type of error structure, which may cause differential bias of risk estimates. This article is protected by copyright. All rights reserved.
Episodic memory ability relies on hippocampal-prefrontal connectivity. However, few studies have examined relationships between memory performance and white matter (WM) microstructure in hippocampal-prefrontal pathways in schizophrenia-spectrum disorder (SSDs). Here, we investigated these relationships in individuals with first-episode psychosis (FEP) and chronic schizophrenia-spectrum disorders (SSDs) using tractography analysis designed to interrogate the microstructure of WM tracts in the hippocampal-prefrontal pathway. Measures of WM microstructure (fractional anisotropy [FA], radial diffusivity [RD], and axial diffusivity [AD]) were obtained for 47 individuals with chronic SSDs, 28 FEP individuals, 52 older healthy controls, and 27 younger healthy controls. Tractography analysis was performed between the hippocampus and three targets involved in hippocampal–prefrontal connectivity (thalamus, amygdala, nucleus accumbens). Measures of WM microstructure were then examined in relation to episodic memory performance separately across each group. Both those with FEP and chronic SSDs demonstrated impaired episodic memory performance. However, abnormal WM microstructure was only observed in individuals with chronic SSDs. Abnormal WM microstructure in the hippocampal-thalamic pathway in the right hemisphere was associated with poorer memory performance in individuals with chronic SSDs. These findings suggest that disruptions in WM microstructure in the hippocampal–prefrontal pathway may contribute to memory impairments in individuals with chronic SSDs but not FEP.
Objective The primary objective of this study was to evaluate the feasibility and acceptability of the study design of a randomized controlled trial, and an experimental neonatal nursing intervention. Design and Setting A pilot parallel randomized controlled trial was conducted in a level-III NICU. Participants Dyads of mothers and very preterm infants 27–32 weeks of gestational age. Methods Twenty mother-preterm infant dyads were enrolled and randomized in a 1:1 ratio to the experimental group (n = 10) or standard care group (n = 10). The intervention encompassed weekly individual sessions where nurses guided mothers in interacting with sensitivity with their infant while providing care and positioning. Results Results show that the intervention was acceptable for mothers and feasible for intervention neonatal nurses, but some challenges related to recruitment and data collection were noted. Conclusion A second pilot study to test adapted recruitment and data collection procedures should be conducted before a large-scale study. Trial registration clinicaltrial.gov (NCT03677752). Registered on September 19, 2018.
The transcriptome of a cell constitutes an essential piece of cellular identity and contributes to the multifaceted complexity and heterogeneity of cell-types within the mammalian brain. Thus, while a wealth of studies have investigated transcriptomic alterations underlying the pathophysiology of diseases of the brain, their use of bulk-tissue homogenates makes it difficult to tease apart whether observed differences are explained by disease state or cellular composition. Cell-type-specific enrichment strategies are, therefore, crucial in the context of gene expression profiling. Laser capture microdissection (LCM) is one such strategy that allows for the capture of specific cell-types, or regions of interest, under microscopic visualization. In this review, we focus on using LCM for cell-type specific gene expression profiling in post-mortem human brain samples. We begin with a discussion of various LCM systems, followed by a walk-through of each step in the LCM to gene expression profiling workflow and a description of some of the limitations associated with LCM. Throughout the review, we highlight important considerations when using LCM with post-mortem human brain samples. Whenever applicable, commercially available kits that have proven successful in the context of LCM with post-mortem human brain samples are described.
Objectives To determine the long-term risk of mortality among children with inborn errors of metabolism. Study design We conducted a retrospective cohort study of 1,750 children with inborn errors of metabolism (excluding mitochondrial disorders) and 1,036,668 children without errors of metabolism who were born in Quebec, Canada, between 2006-2019. Main outcome measures included all-cause and cause-specific mortality between birth and 14 years of age. We used adjusted survival regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between inborn errors of metabolism and mortality over time. Results Mortality rates were higher for children with errors of metabolism than for unaffected children (69.1 vs. 3.2 deaths per 10,000 person-years). During 7,702,179 person-years of follow-up, inborn errors of metabolism were associated with 21.2 times the risk of mortality compared with no error of metabolism (95% CI 17.23-26.11). Disorders of mineral metabolism were associated with greater mortality the first 28 days of life (HR 60.62, 95% CI 10.04-365.98), and disorders of sphingolipid metabolism were associated with greater mortality by 1 year (HR 284.73, 95% CI 139.20-582.44) and 14 years (HR 1066.00, 95% CI 298.91-3801.63). Errors of metabolism were disproportionately associated with death from hepatic/digestive (HR 208.21, 95% CI 90.28-480.22), respiratory (HR 116.57, 95% CI 71.06-191.23), and infectious causes (HR 119.83, 95% CI 40.56-354.04). Conclusions Children with errors of metabolism have a considerably elevated risk of mortality before 14 years, including death from hepatic/digestive, respiratory, and infectious causes. Targeting these causes of death may help improve long-term survival.
Background Prenatal maternal stress is increasingly recognized as a risk factor for offspring mental health challenges. DNA methylation may be a mechanism, but few studies directly tested mediation. These few integrative studies are reviewed along with studies from three research areas: prenatal maternal stress and child mental health, prenatal maternal stress and child DNA methylation, and child mental health and DNA methylation. Methods We conducted a narrative review of articles in each research area and the few published integrative studies to evaluate the state of knowledge. Results Prenatal maternal stress was related to greater offspring internalizing and externalizing symptoms and to greater offspring peripheral DNA methylation of the NR3C1 gene. Youth mental health problems were also related to NR3C1 hypermethylation while epigenome-wide studies identified genes involved in nervous system development. Integrative studies focused on infant outcomes and did not detect significant mediation by DNA methylation though methodological considerations may partially explain these null results. Limitations Operationalization of prenatal maternal stress and child mental health varied greatly. The few published integrative studies did not report conclusive evidence of mediation by DNA methylation. Conclusions DNA methylation likely mediates the association between prenatal maternal stress and child mental health. This conclusion still needs to be tested in a larger number of integrative studies. Key empirical and statistical considerations for future research are discussed. Understanding the consequences of prenatal maternal stress and its pathways of influence will help prevention and intervention efforts and ultimately promote well-being for both mothers and children.
Background In 2015, the Global Task Force on Radiotherapy for Cancer Control (GTFRCC) called for 80% of National Cancer Control Plans (NCCP) to include radiotherapy by 2020. As part of the ongoing ESTRO Global Impact of Radiotherapy in Oncology (GIRO) project, we assessed whether inclusion of radiotherapy in NCCPs correlates with radiotherapy machine availability, national income, and geographic region. Methods A previously validated checklist was used to determine whether radiotherapy was included in each country’s NCCP. We applied the CCORE optimal radiotherapy utilisation model to the GLOBOCAN 2020 data to estimate the demand for radiotherapy and compared this to the International Atomic Energy Agency (IAEA) Directory of Radiotherapy Centres (DIRAC) supply data, stratifying by income level and world region. World regions were defined according to the IAEA. Findings Complete data (including GLOBOCAN 2020, DIRAC and NCCP) was available for 143 countries. Over half (55%, n=79) included a radiotherapy-specific checklist item within the plan. Countries which included radiotherapy services planning in their NCCP had a higher median number of machines (1.68 vs 0.75 machines/1000 patients needing radiotherapy, p<0.001). There was significant regional and income-level heterogeneity in the inclusion of radiotherapy-related items in NCCPs. Low-income and Asia-Pacific countries were least likely to include radiation oncology services planning in their NCCP (p=0.06 and p=0.003, respectively). Few countries in the Asia-Pacific (18.6%) had a plan to develop or maintain radiation services, compared to 57% of countries in Europe. Interpretation Only 55% of current NCCPs included any information regarding radiotherapy, below the GTFRCC’s target of 80%. Prioritisation of radiotherapy in NCCPs was correlated with radiotherapy machine availability. There was regional and income-level heterogeneity regarding the inclusion of specific radiotherapy checklist items in the NCCPs. Ongoing efforts are needed to promote the inclusion of radiotherapy in future iterations of NCCPs in order to improve global access to radiation treatment.
Background Mechanical ventilation is a common therapy in operating rooms and intensive care units. When ill-adapted, it can lead to ventilator-induced lung injury (VILI), which is associated with poor outcomes. Excessive regional pulmonary strain is thought to be a major mechanism responsible for VILI. Scarce bedside methods exist to measure regional pulmonary strain. We propose a novel way to measure regional pleural strain using ultrasound elastography. The objective of this study was to assess the feasibility and reliability of pleural strain measurement by ultrasound elastography and to determine if elastography parameters would correlate with varying tidal volumes. Methods A single-blind randomized crossover proof of concept study was conducted July to October 2017 at a tertiary care referral center. Ten patients requiring general anesthesia for elective surgery were recruited. After induction, patients received tidal volumes of 6, 8, 10, and 12 mL.kg –1 in random order, while pleural ultrasound cineloops were acquired at 4 standardized locations. Ultrasound radiofrequency speckle tracking allowed computing various pleural translation, strain and shear components. We screened 6 elastography parameters (lateral translation, lateral absolute translation, lateral strain, lateral absolute strain, lateral absolute shear and Von Mises Strain) to identify those with the best dose-response with tidal volumes using linear mixed effect models. Goodness-of-fit was assessed by the coefficient of determination. Intraobserver, interobserver and test-retest reliability were calculated using intraclass correlation coefficients. Results Analysis was possible in 90.7% of ultrasound cineloops. Lateral absolute shear, lateral absolute strain and Von Mises strain varied significantly with tidal volume and offered the best dose-responses and data modeling fits. Point estimates for intraobserver reliability measures were excellent for all 3 parameters (0.94, 0.94, and 0.93, respectively). Point estimates for interobserver (0.84, 0.83, and 0.77, respectively) and test-retest (0.85, 0.82, and 0.76, respectively) reliability measures were good. Conclusion Strain imaging is feasible and reproducible. Future studies will have to investigate the clinical relevance of this novel imaging modality. Clinical trial registration www.Clinicaltrials.gov , identifier NCT03092557.
Background Cardiopulmonary resuscitation (CPR) decreases lung volume below the functional residual capacity and can generate intrathoracic airway closure. Conversely, large insufflations can induce thoracic distension and jeopardize circulation. The capnogram (CO 2 signal) obtained during continuous chest compressions can reflect intrathoracic airway closure, and we hypothesized here that it can also indicate thoracic distension. Objectives To test whether a specific capnogram may identify thoracic distension during CPR and to assess the impact of thoracic distension on gas exchange and hemodynamics. Methods (1) In out-of-hospital cardiac arrest patients, we identified on capnograms three patterns: intrathoracic airway closure, thoracic distension or regular pattern. An algorithm was designed to identify them automatically. (2) To link CO 2 patterns with ventilation, we conducted three experiments: (i) reproducing the CO 2 patterns in human cadavers, (ii) assessing the influence of tidal volume and respiratory mechanics on thoracic distension using a mechanical lung model and (iii) exploring the impact of thoracic distension patterns on different circulation parameters during CPR on a pig model. Measurements and main results (1) Clinical data: 202 capnograms were collected. Intrathoracic airway closure was present in 35%, thoracic distension in 22% and regular pattern in 43%. (2) Experiments: (i) Higher insufflated volumes reproduced thoracic distension CO 2 patterns in 5 cadavers. (ii) In the mechanical lung model, thoracic distension patterns were associated with higher volumes and longer time constants. (iii) In six pigs during CPR with various tidal volumes, a CO 2 pattern of thoracic distension, but not tidal volume per se, was associated with a significant decrease in blood pressure and cerebral perfusion. Conclusions During CPR, capnograms reflecting intrathoracic airway closure, thoracic distension or regular pattern can be identified. In the animal experiment, a thoracic distension pattern on the capnogram is associated with a negative impact of ventilation on blood pressure and cerebral perfusion during CPR, not predicted by tidal volume per se.
Aim: The effectiveness and safety of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with stage III chronic kidney disease (CKD) are still subject to debate. We therefore assessed and compared the effectiveness and safety of DOACs vs. warfarin in this population. Methods: A cohort of patients with an inpatient or outpatient code for AF and stage III CKD who were newly prescribed an oral anticoagulant (OAC) was created using 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 on-treatment analysis using inverse probability of treatment weighting and Cox proportional hazards. Results. A total of 8,899 included patients filled a new OAC claim: 3,335 for warfarin and 5,564 DOACs. Compared with warfarin, rivaroxaban 15 mg and 20 mg 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), whereas 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). Conclusion: In comparison with warfarin, rivaroxaban and apixaban appear to be effective and safe in AF patients with stage III CKD.
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