Early Prediction of Autistic Spectrum Disorder Using Developmental Surveillance Data.

Importance: With the continuous increase in the prevalence of autistic spectrum disorder (ASD), effective early screening is crucial for initiating timely interventions and improving outcomes. Objective: To develop predictive models for ASD using routinely collected developmental surveillance data and to assess their performance in predicting ASD at different ages and in different clinical scenarios. Design, Setting, and Participants: This retrospective cohort study used nationwide data of developmental assessments conducted between January 1, 2014, and January 17, 2023, with minimal follow-up of 4 years and outcome collection in March 2023. Data were from a national program of approximately 1000 maternal child health clinics that perform routine developmental surveillance of children from birth to 6 years of age, serving 70% of children in Israel. The study included all children who were assessed at the maternal child health clinics (N = 1 187 397). Children were excluded if they were born at a gestational age of 33 weeks or earlier, had no record of gestational age, or were followed up for less than 4 years without an ASD outcome. The data set was partitioned at random into a development set (80% of the children) and a holdout evaluation set (20% of the children), both with the same prevalence of ASD outcome. Exposures: For each child, demographic and birth-related covariates were extracted, as were per-visit growth measurements, quantified developmental milestone assessments, and referral summary covariates. Only information that was available before the prediction age was used for training and evaluating the models. Main Outcome and Measure: The main outcome was eligibility for a governmental disabled child allowance due to ASD, according to administrative data of the National Insurance Institute of Israel. The performance of the models that predict the outcome was evaluated and compared with previous work on the Modified Checklist for Autism in Toddlers (M-CHAT). Results: The study included 1 187 397 children (610 588 [51.4%] male). The performance of the ASD prediction models improved with prediction age, with fair accuracy already at 12 months of age. A model that combined longitudinal measures of developmental milestone assessments with a minimal set of demographic variables, which was applied at 18 to 24 months of age, achieved an area under the receiver operating characteristic curve of 0.83, with a sensitivity of 45.1% at a specificity of 95.0%. A model using single-visit assessments achieved an area under the receiver operating characteristic curve of 0.81 and a sensitivity of 41.2% at a specificity of 95.0%. The best performing prediction models surpassed the pooled performance of M-CHAT (sensitivity, 40%; specificity, 95%) reported in studies with a similar design. Conclusions and Relevance: This cohort study found that ASD can be predicted from routine developmental surveillance data at an accuracy surpassing M-CHAT screening. This tool may be seamlessly integrated in the clinical workflow to improve early identification of children who may benefit from timely interventions.

Increased rates of unattained developmental milestones among Israeli children between 2016 and 2020: a national report.

BACKGROUND: The early years of children's lives are critical for their healthy development. Although children's growth and development rates may vary, a significant delay during early childhood could indicate a medical or a developmental disorder. Developmental surveillance is used worldwide by healthcare providers in routine encounters, as well as by educators and parents, to elicit concerns about child development. In this work, we used a national dataset of developmental assessments to describe temporal trends of milestone attainment rates and associations between milestone attainment and various sociodemographic factors. METHODS: The study included 1,002,700 children ages birth until 6 years with 4,441,689 developmental visits between the years 2016 and 2020. We used the Israeli developmental scale to assess the annual rates of failure to attain language, social and motoric milestones by the entire population, as well as by subgroups stratified by sociodemographic factors. In addition, we evaluated the rates of parental concern for child development and of the nurse's report of development inadequate for age. We used multivariable logistic regression to analyze the impact of different sociodemographic factors on the odds of failure to attain milestones, while controlling for confounding. RESULTS: Milestone failure rates progressively increased over the examined years in all developmental domains, and most prominently in the language domain. Conversely, the rates of parental concern for developmental delay remained constant. In multivariable analysis, higher risk of milestone attainment failure was observed in children whose mothers were divorced, unemployed, immigrant, had lower education, of Bedouin origin or were over 40 years old when giving birth. CONCLUSIONS: This report describes national trends of child development in the gross motor, fine motor, language, and social domains. A periodic report of these trends should be published to objectively evaluate subgroups in need for intervention, and to assess the effectiveness of intervention programs in attempt to maximize the developmental potential of children in Israel.

A Developmental Surveillance Score for Quantitative Monitoring of Early Childhood Milestone Attainment: Algorithm Development and Validation.

BACKGROUND: Developmental surveillance, conducted routinely worldwide, is fundamental for timely identification of children at risk of developmental delays. It is typically executed by assessing age-appropriate milestone attainment and applying clinical judgment during health supervision visits. Unlike developmental screening and evaluation tools, surveillance typically lacks standardized quantitative measures, and consequently, its interpretation is often qualitative and subjective. OBJECTIVE: Herein, we suggested a novel method for aggregating developmental surveillance assessments into a single score that coherently depicts and monitors child development. We described the procedure for calculating the score and demonstrated its ability to effectively capture known population-level associations. Additionally, we showed that the score can be used to describe longitudinal patterns of development that may facilitate tracking and classifying developmental trajectories of children. METHODS: We described the Developmental Surveillance Score (DSS), a simple-to-use tool that quantifies the age-dependent severity level of a failure at attaining developmental milestones based on the recently introduced Israeli developmental surveillance program. We evaluated the DSS using a nationwide cohort of >1 million Israeli children from birth to 36 months of age, assessed between July 1, 2014, and September 1, 2021. We measured the score's ability to capture known associations between developmental delays and characteristics of the mother and child. Additionally, we computed series of the DSS in consecutive visits to describe a child's longitudinal development and applied cluster analysis to identify distinct patterns of these developmental trajectories. RESULTS: The analyzed cohort included 1,130,005 children. The evaluation of the DSS on subpopulations of the cohort, stratified by known risk factors of developmental delays, revealed expected relations between developmental delay and characteristics of the child and mother, including demographics and obstetrics-related variables. On average, the score was worse for preterm children compared to full-term children and for male children compared to female children, and it was correspondingly worse for lower levels of maternal education. The trajectories of scores in 6 consecutive visits were available for 294,000 children. The clustering of these trajectories revealed 3 main types of developmental patterns that are consistent with clinical experience: children who successfully attain milestones, children who initially tend to fail but improve over time, and children whose failures tend to increase over time. CONCLUSIONS: The suggested score is straightforward to compute in its basic form and can be easily implemented as a web-based tool in its more elaborate form. It highlights known and novel relations between developmental delay and characteristics of the mother and child, demonstrating its potential usefulness for surveillance and research. Additionally, it can monitor the developmental trajectory of a child and characterize it. Future work is needed to calibrate the score vis-a-vis other screening tools, validate it worldwide, and integrate it into the clinical workflow of developmental surveillance.

Postexposure-vaccine-prophylaxis against COVID-19.

During the COVID-19 pandemic, postexposure-vaccine-prophylaxis is not a practice. Following exposure, only patient isolation is imposed. Moreover, no therapeutic prevention approach is applied. We asked whether evidence exists for reduced mortality rate following postexposure-vaccine-prophylaxis. To estimate the effectiveness of postexposure-vaccine-prophylaxis, we obtained data from the Israeli Ministry of Health registry. The study population consisted of Israeli residents aged 12 years and older, identified for the first time as PCR-positive for SARS-CoV-2, between December 20th, 2020 (the beginning of the vaccination campaign) and October 7th, 2021. We compared "recently injected" patients-that proved PCR-positive on the same day or on 1 of the 5 consecutive days after first vaccination (representing an unintended postexposure-vaccine-prophylaxis)s-to unvaccinated control group. Among Israeli residents identified PCR-positive for SARS-CoV-2, 11 687 were found positive on the day they received their first vaccine injection (BNT162b2) or on 1 of the 5 days thereafter. In patients over 65 years, 143 deaths occurred among 1412 recently injected (10.13%) compared to 255 deaths among the 1412 unvaccinated (18.06%), odd ratio (OR) 0.51 (95% confidence interval [CI]: 0.41-0.64; p < 0.001). A significant reduction in the death toll was observed among the 55-64 age group, with 8 deaths occurring among the 1320 recently injected (0.61%) compared to 24 deaths among the 1320 unvaccinated control (1.82%), OR 0.33 (95% CI: 0.13-0.76; p = 0.007). Postexposure-vaccine-prophylaxis is effective against death in COVID-19 infection.

Assessing the Attainment Rates of Updated CDC Milestones Using a New Israeli Developmental Scale.

OBJECTIVES: Developmental milestones norms are widely used worldwide and are fundamental for early childhood developmental surveillance. We compared a new Israeli evidence-based national developmental scale with the recently updated Centers for Disease Control and Prevention (CDC) checklists. METHODS: We used a cohort of nearly 4.5 million developmental assessments of 758 300 full-term born children aged 0 to 6 years (ALL-FT cohort), who visited maternal child health clinics in Israel for routine developmental surveillance. Among the assessed milestones of 4 developmental domains (gross motor, fine motor, language, and personal-social) we identified milestones that had equivalents on the CDC checklists and assessed the attainment rates of the Israeli children at the ages recommended by the CDC, at which ≥75% of the children would be expected to achieve the milestone. The analysis was repeated on a subgroup of 658 958 children who were considered healthy, typically developing by their birth and growth characteristics (NORMAL-FT cohort). RESULTS: There were 29 milestones, across all developmental domains and assessment ages, whose definitions by both tools were compatible, and could be compared. The attainment rate at the CDC-recommended age was >90% for 22 (76%) and 23 (79%) milestones, and the median attainment rates were 95.2% and 96.3% in the ALL-FT and NORMAL-FT cohorts, respectively. CONCLUSIONS: For almost all comparable milestones of all domains and all ages, children of the Israeli cohorts achieved the milestones earlier than expected by the CDC-defined threshold age. Evidence-based analysis of milestone norms among different populations may enable adjustments of developmental scales and facilitate more personalized developmental surveillance.

Combining Inpatient and Outpatient Data for Diagnosis of Non-Valvular Atrial Fibrillation Using Electronic Health Records: A Validation Study.

PURPOSE: Previous studies have demonstrated differences in atrial fibrillation (AF) detection based on data from hospital sources without data from outpatient sources. We investigated the detection of documented diagnoses of non-valvular AF in a large Israeli health-care organization using electronic health record data from multiple sources. PATIENTS AND METHODS: This was an open-chart validation study. Three distinct algorithms for identifying AF in electronic health records, differing in the source of their International Classification of Diseases, Ninth Revision code and use of the associated free text, were defined. Algorithm 1 incorporated inpatient data with outpatient data and the associated free text. Algorithm 2 incorporated inpatient and outpatient data regardless of the free text associated with AF diagnosis. Algorithm 3 used only inpatient data source. These algorithms were compared to a gold standard and their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. To establish the gold standard (documentation of arrhythmia based on electrocardiography interpretation or a cardiologist's written diagnosis), 200 patients at highest risk for having non-valvular AF were randomly selected for open-chart validation by two physicians. RESULTS: The algorithm that included hospital settings, outpatient settings, and incorporated associated free text in the outpatient records had the optimal balance between all validation measures, with a high level of sensitivity (85.4%), specificity (95.0%), PPV (81.4%), and NPV (96.2%). The alternative algorithm that combined inpatient and outpatient data without free text also performed better than the algorithm that included only hospital data (82.9%, 95.0%, 81.0%, and 95.6%, compared to 70.7%, 96.9%, 85.3%, and 92.8%, sensitivity, specificity, PPV, and NPV, respectively). CONCLUSION: In this study, involving a comprehensive data collection from inpatient and outpatient sources, incorporating outpatient data with inpatient data improved the diagnosis of non-valvular AF compared to inpatient data alone.

Risk of Stroke, Bleeding, and Death in Patients with Nonvalvular Atrial Fibrillation and Chronic Kidney Disease.

INTRODUCTION: Atrial fibrillation (AF) and chronic kidney disease (CKD) are both associated with increased risk of stroke, and CKD carries a higher bleeding risk. Oral anticoagulation (OAC) treatment is used to reduce the risk of stroke in patients with nonvalvular AF (NVAF); however, the risk versus benefit of OAC for advanced CKD is continuously debated. We aim to assess the management and outcomes of NVAF patients with impaired renal function within a population-based cohort. METHODS: We conducted a retrospective observational cohort study using ICD-9 healthcare coding. Patients with incident NVAF between 2004 and 2015 were identified stratified by CKD stage. We compared treatment strategies and estimated risks of stroke, death, or any major bleeding based on CKD stages and OAC treatment. RESULTS: We identified 85,116 patients with incident NVAF. Patients with impaired renal function were older and had more comorbidities. OAC was most common among stage 2 CKD patients (49%) and least in stages 4-5 CKD patients (27.6%). Higher CKD stages were associated with worse outcomes. Stroke rates increased from 1.04 events per 100 person-years (PY) in stage 1 CKD to 3.72 in stages 4-5 CKD. Mortality increased from 3.42 to 32.95 events/100 PY, and bleeding rates increased from 0.89 to 4.91 events/100 PY. OAC was associated with reduced stroke and intracranial bleeding risk regardless of CKD stage, and with a reduced mortality risk in stages 1-3 CKD. CONCLUSION: Among NVAF patients, advanced renal failure is associated with higher risk of stroke, death, and bleeding. OAC was associated with reduced stroke and intracranial bleeding risk, and with improved survival in stages 1-3 CKD.

Translating clinical trial results into personalized recommendations by considering multiple outcomes and subjective views.

Currently, clinicians rely mostly on population-level treatment effects from RCTs, usually considering the treatment's benefits. This study proposes a process, focused on practical usability, for translating RCT data into personalized treatment recommendations that weighs benefits against harms and integrates subjective perceptions of relative severity. Intensive blood pressure treatment (IBPT) was selected as the test case to demonstrate the suggested process, which was divided into three phases: (1) Prediction models were developed using the Systolic Blood-Pressure Intervention Trial (SPRINT) data for benefits and adverse events of IBPT. The models were externally validated using retrospective Clalit Health Services (CHS) data; (2) Predicted risk reductions and increases from these models were used to create a yes/no IBPT recommendation by calculating a severity-weighted benefit-to-harm ratio; (3) Analysis outputs were summarized in a decision support tool. Based on the individual benefit-to-harm ratios, 62 and 84% of the SPRINT and CHS populations, respectively, would theoretically be recommended IBPT. The original SPRINT trial results of significant decrease in cardiovascular outcomes following IBPT persisted only in the group that received a "yes-treatment" recommendation by the suggested process, while the rate of serious adverse events was slightly higher in the "no-treatment" recommendation group. This process can be used to translate RCT data into individualized recommendations by identifying patients for whom the treatment's benefits outweigh the harms, while considering subjective views of perceived severity of the different outcomes. The proposed approach emphasizes clinical practicality by mimicking physicians' clinical decision-making process and integrating all recommendation outputs into a usable decision support tool.

Comparison of Stroke Risk Stratification Scores for Atrial Fibrillation.

Several stroke risk stratification scores have been developed to guide clinical decision-making in patients with nonvalvular atrial fibrillation (AF). The aim of this study was to compare the performance of the CHADS2, CHA2DS2-VASc and R2CHADS2 risk scores to predict stroke. This retrospective cohort study was based on electronic medical records from Clalit Health Services (CHS), the largest payer provider healthcare organization in Israel. Data of CHS members with AF diagnosis between 2004 and 2015 were extracted. Demographic and co-morbidity data were used to calculate the 3 risk scores, and the performance of the scores to predict stroke were compared using area under the curve and net reclassification index. Of the 89,213 CHS members with AF, 52.3% were women and median age was 76 years. The proportions of patients at high risk were 66.2%, 86.7%, and 71.1% in the CHADS2, CHA2DS2-VASc, and R2CHADS2, respectively, with stroke incidence rates of 2.91, 2.35, and 2.80 per 100 person-years, respectively. Area under the curves for stroke prediction were 0.61 for both CHADS2 and CHA2DS2-VASc and 0.59 for R2CHADS2. Net reclassification index analysis demonstrated a net improvement of 0.089 in the index when CHA2DS2-VASc was compared with CHADS2 and a net reduction of 0.083 when R2CHADS2 was compared with CHADS2. In conclusion, current stroke stratification scores have comparable but limited ability to predict stroke in patients with AF. Stroke prevention strategies may vary depending on the applied stratification. There is a need for a better stroke risk stratification score for patients with AF.

Net clinical benefit of anticoagulant treatments in elderly patients with nonvalvular atrial fibrillation: Experience from the real world.

BACKGROUND: Oral anticoagulation (OAC) is effective in stroke prevention in elderly patients with nonvalvular atrial fibrillation (AF), but older patients are also at higher risk of bleeding. OBJECTIVE: We aimed to examine whether OAC has net clinical benefit (NCB) in elderly patients with AF. METHODS: This is a retrospective cohort study of patients with AF, aged 75 years and older, who were diagnosed from January 1, 2013, through December 31, 2015. Incidences of stroke and intracranial hemorrhage (ICH) were estimated as the number of events per 100 person-years. The NCBs were estimated with respect to time in therapeutic range (TTR) (<60% or ≥60%) and treatment type (warfarin and low or high dose of direct oral anticoagulants [DOACs]). RESULTS: We included 11,760 patients, of whom 4982 (42.4%) were treated with OACs: 2042 (17.4%) with warfarin and 2940 (25.0%) with DOACs. Among patients treated with warfarin, those who achieved TTR ≥ 60% had a lower incidence of stroke (2.54 per 100 person-years vs 5.21 per 100 person-years; P = .01) but without a statistically significant lower incidence of ICH (0.68 per 100 person-years vs 1.10 per 100 person-years; P = .45) and a higher NCB (9.78 vs 6.52) than did those with TTR < 60%. Among patients treated with DOACs, patients treated with the high dose had a statistically significant similar incidence of stroke (8.40 per 100 person-years vs 9.81 per 100 person-years; P = .67), a statistically significant lower incidence of ICH (0.33 per 100 person-years vs 1.20 per 100 person-years; P = .02), and a higher NCB (4.42 vs 1.78) than did patients treated with the low dose. CONCLUSION: A large proportion of elderly patients are not treated with OACs. We found that the NCB of OAC in the elderly is positive, with the highest benefit in elderly patients treated with warfarin who achieved TTR ≥ 60% or high dose of DOACs.

Comparing Management and Outcomes in Men and Women With Nonvalvular Atrial Fibrillation: Data From a Population-Based Cohort.

OBJECTIVES: This study sought to identify the differences in stroke, mortality, and bleeding between men and women with atrial fibrillation (AF). BACKGROUND: There are inconsistent data regarding the thromboembolic risk difference between men and women with AF. The authors assessed the risk of stroke, death, and bleeding in men and women with incident AF. METHODS: The authors employed a prospective historical cohort using an electronic database from a large health maintenance organization. All members with incident AF between 2004 and 2015 were included. Primary endpoints were ischemic stroke, death, and major bleeding. RESULTS: The authors identified 89,213 members with incident nonvalvular atrial fibrillation (NVAF), 52.3% of whom were women. Women were older, with a higher prevalence of hypertension, whereas more men had diabetes, heart failure, and ischemic heart disease than the women did. Ischemic stroke occurred in 6.4% of the patients: 7.0% of women and 5.8% of men. Sex did not affect adjusted stroke risk (hazard ratio [HR]: 0.91; 95% confidence interval [CI]: 0.77 to 1.06; p = 0.22). However, women 75 years of age and older were at an increased risk (HR: 1.25; 95% CI: 1.17 to 1.34). Mortality rates were higher among women (33.5% vs. 32%; p < 0.001); however, women had a significantly lower adjusted mortality risk (HR: 0.78; 95% CI: 0.71 to 0.86). Women had lower risk of intracranial hemorrhage (HR: 0.81; 95% CI: 0.76 to 0.87) and major gastrointestinal bleeding (HR: 0.78; 95% CI: 0.70 to 0.87). CONCLUSIONS: Men and women with AF had a similar risk of ischemic stroke, except for women 75 years of age or older, who had a higher risk. Our findings support using a similar anticoagulation strategy for prevention of stroke in men and women with a similar number of risk factors.

Catheter ablation for the treatment of atrial fibrillation is associated with a reduction in health care resource utilization.

BACKGROUND: Catheter ablation (CA) is superior to antiarrhythmic therapy at reducing recurrence of atrial fibrillation (AF); however, there are limited data regarding whether this decrease translates into a reduction in health care resource utilization. OBJECTIVE: To evaluate the impact of AF ablation on long-term health care resource utilization. METHODS: A population-based cohort was constructed to include patients who underwent CA for AF in Quebec, Canada, between April 2005 and March 2011. Resource utilization was evaluated 24 months pre- and postindex CA procedure. RESULTS: In a cohort of 1,556 patients, resource utilization increased progressively over the 24-month period leading to index CA (P for trend <0.05 for hospitalizations, ER visits, outpatient visits, cardioversions, and echocardiograms). After index CA, all-cause hospitalizations, hospitalizations for AF, ER visits, cardioversions, and echocardiograms were reduced 12 months post-CA compared to 12 months prior (all-cause hospitalizations 0.8-0.6 per patient per year; hospitalizations for AF 0.4-0.3; ER visits 2.9-1.8; cardioversions 0.5-0.2; echocardiograms 0.8-0.5; P < 0.05 for all trends). Resource utilization continued to decline at 24 months post-CA (vs. 12 months prior) for all-cause hospitalizations (0.4), cardioversions (0.1), and echocardiograms (0.3) (per patient year; P < 0.05 for all trends). CONCLUSION: In conclusion, the pattern of increasing health care resource utilization preceding CA for AF reverses after CA to lower than preablation levels up to 24 months post-CA.

Dabigatran use in elderly patients with atrial fibrillation.

In elderly patients (≥ 75 years), evidence of dabigatran efficacy is lacking and increased vigilance is warranted. We aimed to assess dabigatran effectiveness and safety in elderly patients in real-world practice. We conducted a population-based study using administrative databases, in Quebec (1999-2013). Dabigatran users (110/150 mg) were compared with matched warfarin users with regard to stroke and bleeding events. Age was categorised into < 75 or ≥ 75 years. Propensity score adjusted models were used. The cohort consisted of 15,918 dabigatran users and 47,192 matched warfarin users, with 67.3% being elderly patients. The elderly predominantly used the lower dose (80.1%) while younger patients mainly used the higher dose (80.0%). In multivariable analyses adjusted for propensity score, the risk of stroke in elderly patients using dabigatran, was no different than the risk in warfarin users (HR 1.05, 95% CI: 0.93, 1.19) regardless of dabigatran dose. However, dabigatran was associated with lower rates of intracranial haemorrhage (HR 0.60, 95% CI: 0.47-0.76) and higher rates of gastrointestinal bleeding (HR 1.30 95% CI: 1.14-1.50) when compared to warfarin. Based on real-life experience, dabigatran can offer an alternative to warfarin in elderly patients, with fewer intracranial bleeding events. However, caution is warranted for gastrointestinal bleeding.

Sex Differences in Dabigatran Use, Safety, And Effectiveness In a Population-Based Cohort of Patients With Atrial Fibrillation.

BACKGROUND: Sex differences were observed with regard to warfarin treatment in patients with atrial fibrillation, with women having a higher risk of stroke compared with men. We aimed to compare sex differences in use, safety, and effectiveness of dabigatran. METHODS AND RESULTS: We conducted a population-based cohort study of patients with atrial fibrillation using administrative data in Quebec, Canada, 1999 to 2013. Men and women who filled a prescription for dabigatran (110 and 150 mg bid) were compared with matched warfarin users with respect to their rates of stroke, bleeding, and myocardial infarction events, using propensity score analysis. The cohort comprised 31 786 women (50.4%) and 31 324 men (49.6%). Women had a higher baseline stroke risk and lower baseline bleeding risk compared with men. Women filled more prescriptions for the lower dabigatran dose compared with men (adjusted OR, 1.35; 95% confidence interval, 1.24-1.48). In multivariable analyses adjusted for propensity scores, dabigatran use was associated with a lower risk of bleeding compared with warfarin in men (P for interaction=0.008). Dabigatran was associated with a trend toward lower risk of stroke in women treated with the 150-mg dose (HR, 0.79; 95% confidence interval, 0.56-1.04), but was not associated with a difference in the risk of myocardial infarction compared with warfarin in either sex. CONCLUSIONS: In real-life practice, women are more frequently treated with low-dose dabigatran, yet a trend toward lower stroke rates in women taking high-dose dabigatran was observed. Men benefit from lower bleeding rates with dabigatran compared with warfarin.

Temporal trends and sex differences in pulmonary vein isolation for patients with atrial fibrillation.

BACKGROUND: Indications for pulmonary vein isolation for the treatment of atrial fibrillation (AF) have expanded over the years. OBJECTIVE: We aimed to describe trends in demographic and clinical characteristics of patients undergoing ablation, with a particular focus on sex differences. METHODS: Patients who underwent first AF ablation between 2003 and 2012 were identified within an AF cohort by using Quebec administrative databases. Descriptive statistics and multivariable analysis were used to examine sex differences and temporal trends in demographic and clinical characteristics, as well as independent predictors of the ablation procedure. RESULTS: A total of 2438 of 173,689 patients in the AF cohort underwent AF ablation. In the span of 10 years, the rate of AF ablation increased from 8.5 to 57.2 per million persons-an almost 7-fold increase. Patients undergoing ablation were younger than patients in the general AF cohort (57.4 ± 12.2 years vs 75.3 ± 12.0 years) and had fewer baseline comorbidities (56.7% vs 88.4%). Representing 42.9% of the general AF cohort, the annual proportion of women in the AF ablation cohort has not surpassed 30%, and men had a higher likelihood of undergoing ablation than did women (odds ratio 1.54; 95% confidence interval 1.40-1.69). Over the decade of observation, there were slight increases in patient age, comorbidities, and CHADS2 score, some of which reached clinical significance for men and/or women. CONCLUSION: The uptake of AF ablation over 10 years has expanded, with an increasingly greater number of older patients and with increased presence of comorbidities; however, there has been no increase in the relatively low proportion of women undergoing AF ablation.

Warfarin Treatment and Outcomes of Patients With Atrial Fibrillation in Rural and Urban Settings.

BACKGROUND: Warfarin is an effective agent in the prevention of stroke in patients with atrial fibrillation (AF). However, it requires close monitoring with regular visits to health care facilities. To date, it is unknown whether there is a difference in warfarin utilization and outcomes between urban and rural settings. METHODS: We used administrative databases to compare warfarin utilization patterns and stroke and major bleeding outcomes in rural and urban settings in a population-based cohort study of patients ≥ 65 years admitted to hospital with a diagnosis of AF in the province of Quebec, Canada, from 1999 to 2007. Patients' postal codes were used to differentiate between rural and urban settings. RESULTS: The cohort comprised 18,198 rural (21.8%) and 65,315 urban (78.2%) patients, with similar mean age of 79 years and a similar burden of comorbidities. Overall, there was marked underutilization of warfarin in both rural and urban settings. Warfarin-filled prescription rates were slightly higher in the rural setting (adjusted OR: 1.16, 95% CI: 1.12-1.20). In multivariable Cox regression analyses, the risk for stroke and major bleeding in rural settings was similar to that in urban settings (stroke: adjusted HR: 1.01, 95% CI: 0.95-1.09; major bleeding: adjusted HR: 1.03, 95% CI: 0.95-1.12). CONCLUSIONS: Patients in rural settings were slightly more likely to fill a prescription for warfarin, but they experienced similar stroke and major bleeding rates to their urban counterparts.

Relation of digoxin use in atrial fibrillation and the risk of all-cause mortality in patients ≥65 years of age with versus without heart failure.

Previous studies on digoxin use in patients with atrial fibrillation (AF) and the risk of all-cause mortality found conflicting results. We conducted a population-based, retrospective, cohort study of patients aged ≥65 years admitted to a hospital with a primary or secondary diagnosis of AF, in Quebec province, Canada, from 1998 to 2012. The AF cohort was grouped into patients with and without heart failure (HF) and into digoxin and no-digoxin users according to the first prescription filled for digoxin within 30 days after AF hospital discharge. We derived propensity score-matched digoxin and no-digoxin treatment groups for the groups of patients with and without HF, respectively, and conducted multivariable Cox proportional hazards regression analyses to determine association between digoxin use and all-cause mortality. The AF propensity score-matched cohorts of patients with and without HF were well balanced on baseline characteristics. In the propensity score-matched HF group, digoxin use was associated with a 14% greater risk of all-cause mortality (adjusted hazard ratio 1.14, 95% confidence interval 1.10 to 1.17). In the propensity score-matched no-HF group, digoxin use was associated with a 17% greater risk of all-cause mortality (adjusted hazard ratio 1.17, 95% confidence interval 1.14 to 1.19). In conclusion, our retrospective analyses found that digoxin use was associated with a greater risk for all-cause mortality in patients aged ≥65 years with AF regardless of concomitant HF. Large, multicenter, randomized controlled trials or prospective cohort studies are required to clarify this issue.

Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis.

BACKGROUND: Current observational studies on warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation (AF) undergoing dialysis found conflicting results. METHODS AND RESULTS: We conducted a population-based retrospective cohort study of patients aged ≥65 years admitted to a hospital with a primary or secondary diagnosis of AF, in Quebec and Ontario, Canada from 1998 to 2007. The AF cohort was grouped into dialysis (hemodialysis and peritoneal dialysis) and nondialysis patients and into warfarin and no-warfarin users according to the first prescription filled for warfarin within 30 days after AF hospital discharge. We determined the association between warfarin use and the risk for stroke and bleeding in dialysis and nondialysis patients. The cohort comprised 1626 dialysis patients and 204 210 nondialysis patients. Among dialysis patients, 46% (756/1626) patients were prescribed warfarin. Among dialysis patients, warfarin users had more congestive heart failure and diabetes mellitus, but fewer prior bleeding events in comparison with the no-warfarin users. Among dialysis patients, warfarin use, in comparison with no-warfarin use, was not associated with a lower risk for stroke (adjusted hazard ratio, 1.14; 95% confidence interval, 0.78-1.67) but was associated with a 44% higher risk for bleeding (adjusted hazard ratio, 1.44; 95% confidence interval, 1.13-1.85) after adjusting for potential confounders. Propensity score-adjusted analyses yielded similar results. CONCLUSIONS: Our results suggest that warfarin use is not beneficial in reducing stroke risk, but it is associated with a higher bleeding risk in patients with AF undergoing dialysis.

Sex differences in stroke risk among older patients with recently diagnosed atrial fibrillation.

CONTEXT: Stroke is a serious complication associated with atrial fibrillation (AF). Women with AF are at higher risk of stroke compared with men. Reasons for this higher stroke risk in women remain unclear, although some studies suggest that undertreatment with warfarin may be a cause. OBJECTIVE: To compare utilization patterns of warfarin and the risk of subsequent stroke between older men and women with AF at the population level. DESIGN, SETTING, AND PATIENTS: Population-based cohort study of patients 65 years or older admitted to the hospital with recently diagnosed AF in the province of Quebec, Canada, 1998-2007, using administrative data with linkage between hospital discharge, physicians, and prescription drug claims databases. MAIN OUTCOME MEASURES: Risk of stroke. RESULTS: The cohort comprised 39,398 men (47.2%) and 44,115 women (52.8%). At admission, women were older and had a higher CHADS(2) (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack) score than men (1.99 [SD, 1.10] vs 1.74 [SD, 1.13], P < .001). At 30 days postdischarge, 58.2% of men and 60.6% of women had filled a warfarin prescription. In adjusted analysis, women appeared to fill more warfarin prescriptions compared with men (odds ratio, 1.07 [95% CI, 1.04-1.11]; P < .001). Adherence to warfarin treatment was good in both sexes. Crude stroke incidence was 2.02 per 100 person-years (95% CI, 1.95-2.10) in women vs 1.61 per 100 person-years (95% CI, 1.54-1.69) in men (P < .001). The sex difference was mainly driven by the population of patients 75 years or older. In multivariable Cox regression analysis, women had a higher risk of stroke than men (adjusted hazard ratio, 1.14 [95% CI, 1.07-1.22]; P < .001), even after adjusting for baseline comorbid conditions, individual components of the CHADS(2) score, and warfarin treatment. CONCLUSION: Among older patients admitted with recently diagnosed AF, the risk of stroke was greater in women than in men, regardless of warfarin use.