Miat and interacting protein Metadherin maintain a stem-like niche to promote medulloblastoma tumorigenesis and treatment resistance.

Long noncoding RNAs (lncRNAs) play essential roles in the development and progression of many cancers. However, the contributions of lncRNAs to medulloblastoma (MB) remain poorly understood. Here, we identify Miat as an lncRNA enriched in the sonic hedgehog group of MB that is required for maintenance of a treatment-resistant stem-like phenotype in the disease. Loss of Miat results in the differentiation of tumor-initiating, stem-like MB cells and enforces the differentiation of tumorigenic stem-like MB cells into a nontumorigenic state. Miat expression in stem-like MB cells also facilitates treatment resistance by down-regulating p53 signaling and impairing radiation-induced cell death, which can be reversed by therapeutic inhibition of Miat using antisense oligonucleotides. Mechanistically, the RNA binding protein Metadherin (Mtdh), previously linked to resistance to cytotoxic therapy in cancer, binds to Miat in stem-like MB cells. Like the loss of Miat, the loss of Mtdh reduces tumorigenicity and increases sensitivity to radiation-induced death in stem-like MB cells. Moreover, Miat and Mtdh function to regulate the biogenesis of several microRNAs and facilitate tumorigenesis and treatment resistance. Taken together, these data reveal an essential role for the lncRNA Miat in sustaining a treatment-resistant pool of tumorigenic stem-like MB cells.

Stroke risk in women with atrial fibrillation.

BACKGROUND AND AIMS: Female sex is associated with higher rates of stroke in atrial fibrillation (AF) after adjustment for other CHA2DS2-VASc factors. This study aimed to describe sex differences in age and cardiovascular care to examine their relationship with stroke hazard in AF. METHODS: Population-based cohort study using administrative datasets of people aged ≥66 years diagnosed with AF in Ontario between 2007 and 2019. Cause-specific hazard regression was used to estimate the adjusted hazard ratio (HR) for stroke associated with female sex over a 2-year follow-up. Model 1 included CHA2DS2-VASc factors, with age modelled as 66-74 vs. ≥ 75 years. Model 2 treated age as a continuous variable and included an age-sex interaction term. Model 3 further accounted for multimorbidity and markers of cardiovascular care. RESULTS: The cohort consisted of 354 254 individuals with AF (median age 78 years, 49.2% female). Females were more likely to be diagnosed in emergency departments and less likely to receive cardiologist assessments, statins, or LDL-C testing, with higher LDL-C levels among females than males. In Model 1, the adjusted HR for stroke associated with female sex was 1.27 (95% confidence interval 1.21-1.32). Model 2 revealed a significant age-sex interaction, such that female sex was only associated with increased stroke hazard at age >70 years. Adjusting for markers of cardiovascular care and multimorbidity further decreased the HR, so that female sex was not associated with increased stroke hazard at age ≤80 years. CONCLUSION: Older age and inequities in cardiovascular care may partly explain higher stroke rates in females with AF.

Evaluating the safety of high-intensity focused ultrasound treatment for rectal endometriosis: results from a French prospective multicentre study including 60 patients.

STUDY QUESTION: Is increasing the intensity of high-intensity focused ultrasound (HIFU) by 30% in the treatment of rectal endometriosis a safe procedure? SUMMARY ANSWER: This study demonstrates the safety of a 30% increase in the intensity of HIFU in the treatment of rectal endometriosis, with no Clavien-Dindo Grade III complications overall, and namely no rectovaginal fistulae. WHAT IS KNOWN ALREADY: A feasibility study including 20 patients with rectal endometriosis demonstrated, with no severe complications, a significant improvement in digestive disorders, dysmenorrhoea, dyspareunia, and health status, although the volume of the endometriosis nodule did not appear to be reduced. STUDY DESIGN, SIZE, DURATION: A prospective multicentre cohort study was conducted between 2020 and 2022 with 60 patients with symptomatic rectal endometriosis. Following the failure of medical treatment, HIFU treatment was offered as an alternative to surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS: As the main objective of this study was to examine safety, all adverse events observed during the 6 months of follow-up were analysed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) and Clavien-Dindo classifications. Secondary objectives included evaluating the evolution of symptoms using validated questionnaires: gynaecological and digestive pain symptoms with a visual analogue scale, health status with the Medical Outcomes Study 36-item Short Form (SF-36) questionnaire, average post-operative daily pain level, and analgesic medication required in the 10 days following treatment. MRI was also performed at Day 1 to detect early complications. Finally, we performed a blinded MRI review of the evolution of the nodule at 6 months post-treatment. MAIN RESULTS AND THE ROLE OF CHANCE: The procedure was performed under spinal anaesthesia for 30% of the patients. The median duration of treatment was 32 min. Fifty-five patients left the hospital on Day 1. MRI scans performed on Day 1 did not highlight any early-onset post-operative complication. Using the Clavien-Dindo classification, we listed 56.7% Grade I events, 3.4% Grade II events, and no events Grade III or higher. At 1, 3, and 6 months, all gynaecologic, digestive and general symptoms, as well as health status, had significantly improved. The evolution of the nodule was also significant (P < 0.001) with a 28% decrease in volume. LIMITATIONS, REASONS FOR CAUTION: The main objective was safety and not effectiveness. The study was not randomized and there was no control group. WIDER IMPLICATIONS OF THE FINDINGS: HIFU treatment for rectal endometriosis results in an improvement of symptoms with low morbidity; as such, for selected patients, it could be a valuable alternative to surgical approaches following the failure of medical treatment. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the company EDAP TMS. Professors Dubernard and Rousset are consultants for EDAP TMS. Dubernard received travel support from EDAP-TMS. Dr F. Chavrier received industrial grants from EDAP-TMS. He has developed a device for generating focused ultrasonic waves with reduced treatment time. This device has been patented by EDAP-TMS. Dr Lafon received industrial grants from EDAP-TMS; he declares that EDAP-TMS provided funding directly to INSERM to support a young researcher chair in therapeutic ultrasound, which is unrelated to the current study. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT04494568.

Days alive and out of hospital for adult female and male cardiac surgery patients: a population-based cohort study.

BACKGROUND: Research shows women experience higher mortality than men after cardiac surgery but information on sex-differences during postoperative recovery is limited. Days alive and out of hospital (DAH) combines death, readmission and length of stay, and may better quantify sex-differences during recovery. This main objective is to evaluate (i) how DAH at 30-days varies between sex and surgical procedure, (ii) DAH responsiveness to patient and surgical complexity, and (iii) longer-term prognostic value of DAH. METHODS: We evaluated 111,430 patients (26% female) who underwent one of three types of cardiac surgery (isolated coronary artery bypass [CABG], isolated non-CABG, combination procedures) between 2009 - 2019. Primary outcome was DAH at 30 days (DAH30), secondary outcomes were DAH at 90 days (DAH90) and 180 days (DAH180). Data were stratified by sex and surgical group. Unadjusted and risk-adjusted analyses were conducted to determine the association of DAH with patient-, surgery-, and hospital-level characteristics. Patients were divided into two groups (below and above the 10th percentile) based on the number of days at DAH30. Proportion of patients below the 10th percentile at DAH30 that remained in this group at DAH90 and DAH180 were determined. RESULTS: DAH30 were lower for women compared to men (22 vs. 23 days), and seen across all surgical groups (isolated CABG 23 vs. 24, isolated non-CABG 22 vs. 23, combined surgeries 19 vs. 21 days). Clinical risk factors including multimorbidity, socioeconomic status and surgical complexity were associated with lower DAH30 values, but women showed lower values of DAH30 compared to men for many factors. Among patients in the lowest 10th percentile at DAH30, 80% of both females and males remained in the lowest 10th percentile at 90 days, while 72% of females and 76% males remained in that percentile at 180 days. CONCLUSION: DAH is a responsive outcome to differences in patient and surgical risk factors. Further research is needed to identify new care pathways to reduce disparities in outcomes between male and female patients.

Trajectories of P2Y12 inhibitor adherence in patients with acute coronary syndromes.

PURPOSE: P2Y12 inhibitors (P2Y12i) reduce cardiac events after acute coronary syndromes (ACS). However, suboptimal P2Y12i adherence persists. We aimed to examine P2Y12i non-adherence using group-based trajectory methods and to identify adherence predictors. METHODS: We conducted a population-based, retrospective cohort study using administrative data in Ontario, Canada of patients ≥65 years admitted for ACS between April 2014 and March 2018 with a P2Y12i dispensed within 7 days of discharge. We used group-based trajectory models to characterize longitudinal 1-year adherence patterns. Predictors associated with each adherence trajectory were identified by multinomial logistic regression. RESULTS: We included 11 917 patients using clopidogrel and 9763 using ticagrelor, aged [mean ± SD]: 77.33 ± 8.31/73.59 ± 6.79 years; men: 56.2%/65.4%, respectively. We identified 3 longitudinal adherence trajectories, that differed by agent: 75% of clopidogrel and 68% of ticagrelor patients showed a consistently adherent trajectory, while 13%/17% were gradually, and 12%/15% were rapidly non-adherent, respectively (p < 0.001). Differing baseline characteristics in each cohort were associated with observed adherence trajectories. Concomitant atrial fibrillation and prior bleeding history were associated with non-adherence among clopidogrel users. Among ticagrelor users, women and older persons were more likely to be rapidly non-adherent, adherence declining steeply starting 1 month post-ACS. CONCLUSIONS: We identified distinct adherence trajectories for clopidogrel and ticagrelor post-ACS, with 3 out of 4 clopidogrel patients but only 2 out of 3 ticagrelor patients in the consistently adherent trajectory. Intensive interventions targeted to the period of steep adherence decline post-ACS, particularly for women and older persons initiating ticagrelor, and patients with atrial fibrillation on clopidogrel should be considered and investigated further.

Development and Validation of the CANHEART Population-Based Laboratory Prediction Models for Atherosclerotic Cardiovascular Disease.

BACKGROUND: Prediction of atherosclerotic cardiovascular disease (ASCVD) in primary prevention assessments exclusively with laboratory results may facilitate automated risk reporting and improve uptake of preventive therapies. OBJECTIVE: To develop and validate sex-specific prediction models for ASCVD using age and routine laboratory tests and compare their performance with that of the pooled cohort equations (PCEs). DESIGN: Derivation and validation of the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) Lab Models. SETTING: Population-based cohort study in Ontario, Canada. PARTICIPANTS: A derivation and internal validation cohort of adults aged 40 to 75 years without cardiovascular disease from April 2009 to December 2015; an external validation cohort of primary care patients from January 2010 to December 2014. MEASUREMENTS: Age and laboratory predictors measured in the outpatient setting included serum total cholesterol, high-density lipoprotein cholesterol, triglycerides, hemoglobin, mean corpuscular volume, platelets, leukocytes, estimated glomerular filtration rate, and glucose. The ASCVD outcomes were defined as myocardial infarction, stroke, and death from ischemic heart or cerebrovascular disease within 5 years. RESULTS: Sex-specific models were developed and internally validated in 2 160 497 women and 1 833 147 men. They were well calibrated, with relative differences less than 1% between mean predicted and observed risk for both sexes. The c-statistic was 0.77 in women and 0.71 in men. External validation in 31 697 primary care patients showed a relative difference less than 14% and an absolute difference less than 0.3 percentage points in mean predicted and observed risks for both sexes. The c-statistics for the laboratory models were 0.72 for both sexes and were not statistically significantly different from those for the PCEs in women (change in c-statistic, -0.01 [95% CI, -0.03 to 0.01]) or men (change in c-statistic, -0.01 [CI, -0.04 to 0.02]). LIMITATION: Medication use was not available at the population level. CONCLUSION: The CANHEART Lab Models predict ASCVD with similar accuracy to more complex models, such as the PCEs. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Treatment techniques for rectovaginal fistulas after low rectal resection for deep endometriosis.

Endometriosis is a benign gynecologic affection that may lead to major surgeries, such as colorectal resections. Rectovaginal fistulas (RVF) are among the possible complications. When they occur, it is necessary to adapt the repair surgery as best as possible to limit their functional consequences. This video shows three different techniques for correcting RVF after rectal resection for endometriosis, with a combination of perineal surgery and laparoscopy: a mucosal flap, a transanal transection and single stapled anastomosis (TTSS) and a pull through. Supplementary file1 (MP4 469658 KB).

Association of Neighborhood-Level Material Deprivation With Atrial Fibrillation Care in a Single-Payer Health Care System: A Population-Based Cohort Study.

BACKGROUND: There are limited data on the association of material deprivation with clinical care and outcomes after atrial fibrillation (AF) diagnosis in jurisdictions with universal health care. METHODS: This was a population-based cohort study of individuals ≥66 years of age with first diagnosis of AF between April 1, 2007, and March 31, 2019, in the Canadian province of Ontario, which provides public funding and prohibits private payment for medically necessary physician and hospital services. Prescription medications are subsidized for residents >65 years of age. The primary exposure was neighborhood material deprivation, a metric derived from Canadian census data to estimate inability to attain basic material needs. Neighborhoods were categorized by quintile from Q1 (least deprived) to Q5 (most deprived). Cause-specific hazards regression was used to study the association of material deprivation quintile with time to AF-related adverse events (death or hospitalization for stroke, heart failure, or bleeding), clinical services (physician visits, cardiac diagnostics), and interventions (anticoagulation, cardioversion, ablation) while adjusting for individual characteristics and regional cardiologist supply. RESULTS: Among 347 632 individuals with AF (median age 79 years, 48.9% female), individuals in the most deprived neighborhoods (Q5) had higher prevalence of cardiovascular disease, risk factors, and noncardiovascular comorbidity relative to residents of the least deprived neighborhoods (Q1). After adjustment, Q5 residents had higher hazards of death (hazard ratio [HR], 1.16 [95% CI, 1.13-1.20]) and hospitalization for stroke (HR, 1.16 [95% CI, 1.07-1.27]), heart failure (HR, 1.14 [95% CI, 1.11-1.18]), or bleeding (HR, 1.16 [95% CI, 1.07-1.25]) relative to Q1. There were small differences across quintiles in primary care physician visits (HR, Q5 versus Q1, 0.91 [95% CI, 0.89-0.92]), echocardiography (HR, Q5 versus Q1, 0.97 [95% CI, 0.96-0.99]), and dispensation of anticoagulation (HR, Q5 versus Q1, 0.97 [95% CI, 0.95-0.98]). There were more prominent disparities for Q5 versus Q1 in cardiologist visits (HR, 0.84 [95% CI, 0.82-0.86]), cardioversion (HR, 0.80 [95% CI, 0.76-0.84]), and ablation (HR, 0.45 [95% CI, 0.30-0.67]). CONCLUSIONS: Despite universal health care and prescription medication coverage, residents of more deprived neighborhoods were less likely to visit cardiologists or receive rhythm control interventions after AF diagnosis, even though they exhibited higher cardiovascular disease burden and higher risk of adverse outcomes.

Noninvasive Plaque Imaging to Accelerate Coronary Artery Disease Drug Development.

Coronary artery disease (CAD) remains the leading cause of adult mortality globally. Targeting known modifiable risk factors has had substantial benefit, but there remains a need for new approaches. Improvements in invasive and noninvasive imaging techniques have enabled an increasing recognition of distinct quantitative phenotypes of coronary atherosclerosis that are prognostically relevant. There are marked differences in plaque phenotype, from the high-risk, lipid-rich, thin-capped atheroma to the low-risk, quiescent, eccentric, nonobstructive calcified plaque. Such distinct phenotypes reflect different pathophysiologic pathways and are associated with different risks for acute ischemic events. Noninvasive coronary imaging techniques, such as computed tomography, positron emission tomography, and coronary magnetic resonance imaging, have major potential to accelerate cardiovascular drug development, which has been affected by the high costs and protracted timelines of cardiovascular outcome trials. This may be achieved through enrichment of high-risk phenotypes with higher event rates or as primary end points of drug efficacy, at least in phase 2 trials, in a manner historically performed through intravascular coronary imaging studies. Herein, we provide a comprehensive review of the current technology available and its application in clinical trials, including implications for sample size requirements, as well as potential limitations. In its effort to accelerate drug development, the US Food and Drug Administration has approved surrogate end points for 120 conditions, but not for CAD. There are robust data showing the beneficial effects of drugs, including statins, on CAD progression and plaque stabilization in a manner that correlates with established clinical end points of mortality and major adverse cardiovascular events. This, together with a clear mechanistic rationale for using imaging as a surrogate CAD end point, makes it timely for CAD imaging end points to be considered. We discuss the importance of global consensus on these imaging end points and protocols and partnership with regulatory bodies to build a more informed, sustainable staged pathway for novel therapies.

Predicting left main stenosis in stable ischemic heart disease using logistic regression and boosted trees.

BACKGROUND: The ISCHEMIA trial showed similar cardiovascular outcomes of an initial conservative strategy as compared with invasive management in patients with stable ischemic heart disease without left main stenosis. We aim to assess the feasibility of predicting significant left main stenosis using extensive clinical, laboratory and non-invasive tests data. METHODS: All adult patients who had stress testing prior to undergoing an elective coronary angiography for stable ischemic heart disease in Ontario, Canada, between April 2010 and March 2019, were included. Candidate predictors included comprehensive demographics, comorbidities, laboratory tests, and cardiac stress test data. The outcome was stenosis of 50% or greater in the left main coronary artery. A traditional model (logistic regression) and a machine learning algorithm (boosted trees) were used to build prediction models. RESULTS: Among 150,423 patients included (mean age: 64.2 ± 10.6 years; 64.1% males), there were 9,225 (6.1%) with left main stenosis. The final logistic regression model included 24 predictors and 3 interactions, had an optimism-adjusted c-statistic of 0.72 and adequate calibration (optimism-adjusted Integrated Calibration Index 0.0044). These results were consistent in subgroups of males and females, diabetes and non-diabetes, and extent of ischemia. The boosted tree algorithm had similar accuracy, also resulting in a c-statistic of 0.72 and adequate calibration (Integrated Calibration Index 0.0054). CONCLUSIONS: In this large population-based study of patients with stable ischemic heart disease using extensive clinical data, only modest prediction of left main coronary artery disease was possible with traditional and machine learning modelling techniques.

Risk Factors for Major Cardiovascular Events in Adult Sepsis Survivors: A Population-Based Cohort Study.

OBJECTIVES: To describe risk factors for major cardiovascular events in adults following hospital discharge after sepsis. DESIGN: Population-based cohort study. SETTING: Ontario, Canada (2008-2017). PATIENTS: Adult patients (age 18 yr or older) who survived a first sepsis hospitalization without preexisting cardiovascular disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary composite outcome was myocardial infarction, stroke, or cardiovascular death up to 5 years following hospital discharge. We used cause-specific Cox proportional hazards models that accounted for the competing risk of noncardiovascular death to describe factors associated with major cardiovascular events. We identified 268,259 adult patients without cardiovascular disease (median age, 72 yr), of whom 10.4% experienced a major cardiovascular event during a median follow-up of 3 years. After multivariable adjustment, age (hazard ratio [HR], 1.53 for every 10 yr; 95% CI, 1.51-1.54), male sex (HR, 1.23; 95% CI, 1.20-1.26), diabetes mellitus (HR, 1.24; 95% CI, 1.21-1.27), hypertension (HR, 1.34; 95% CI, 1.30-1.38), prevalent atrial fibrillation (HR, 1.46; 95% CI, 1.40-1.52), and chronic kidney disease (HR, 1.11; 95% CI, 1.06-1.16) were associated with major cardiovascular events during long-term follow-up. Sepsis characteristics such as site of infection (pneumonia vs other: HR, 1.09; 95% CI, 1.05-1.12), septic shock (HR, 1.08; 95% CI, 1.05-1.11), and renal replacement therapy (HR, 1.51; 95% CI, 1.38-1.64) were also associated with subsequent cardiovascular events. In an analysis restricting to patients with troponin values measured during the hospitalization (26,400 patients), an elevated troponin was also associated with subsequent cardiovascular events (HR, 1.23; 95% CI, 1.13-1.33). CONCLUSIONS: Classic cardiovascular risk factors, comorbid conditions, and characteristics of the sepsis episode were associated with a higher hazard of major cardiovascular events in adult sepsis survivors. These findings may inform enrichment strategies for future studies.

Weight strategy in older adults with obesity: calorie restriction or not?

PURPOSE OF REVIEW: Along with the marked increase in the population of older adults with obesity is the need for effective strategies to treat aging- and obesity-related complications. This review highlights recent progress in obesity management in older adults. RECENT FINDINGS: Although calorie restriction is needed to significantly reduce fat mass, an exercise protocol is crucial to ameliorate functional outcomes. The addition of a resistance exercise protocol improves the response of muscle protein synthesis to anabolic stimuli, preventing the calorie restriction-induced reduction in muscle and bone mass. The addition of an aerobic exercise protocol improves cardiorespiratory fitness and cognitive function. However, the addition of both aerobic and resistance exercise protocols to calorie restriction provides the greatest improvements in myocellular quality, frailty, and cardiometabolic and cognitive outcomes, translating into the greatest improvement in quality of life. Such comprehensive lifestyle intervention effectively improves glucometabolic control and age-relevant outcomes in older adults with diabetes. When combined with testosterone therapy, such lifestyle intervention also preserves muscle and bone mass in older, men with obesity and hypogonadism. SUMMARY: We conclude that calorie restriction among older adults with obesity should be prescribed in combination with both aerobic and resistance exercise to maximize benefits on overall health.

Inter-software and inter-scan variability in measurement of epicardial adipose tissue: a three-way comparison of a research-specific, a freeware and a coronary application software platform.

OBJECTIVES: Epicardial adipose tissue (EAT) is a proposed marker of cardiovascular risk; however, clinical application may be limited by variability in post-processing software platforms. We assessed inter-vendor agreement of EAT volume (EATv) and attenuation on both contrast-enhanced (CE) and non-contrast CT (NCT) using a standard coronary CT reporting software (Vitrea), an EAT research-specific software (QFAT) and a freeware imaging software (OsiriX). METHODS: Seventy-six consecutive patients undergoing simultaneous CE and NCT had complete volumetric EAT measurement. Between-software, within-software NCT vs. CE, and inter- and intra-observer agreement were evaluated with analysis by ANOVA (with post hoc adjustment), Bland-Altman with 95% levels of agreement (LoA) and intraclass correlation coefficient (ICC). RESULTS: Mean EATv (freeware 53 ± 31 mL vs. research 93 ± 43 mL vs. coronary 157 ± 64 mL) and attenuation (freeware - 72 ± 25 HU vs. research - 75 ± 3 HU vs. coronary - 61 ± 10 HU) were significantly different between all vendors (ANOVA p < 0.001). EATv was consistently higher in NCT vs. CE for all software packages, with most reproducibility found in research software (bias 26 mL, 95% LoA: 2 to 56 mL), compared to freeware (bias 11 mL 95% LoA: - 46 mL to 69 mL) and coronary software (bias 10 mL 95% LoA: - 127 to 147 mL). Research software had more comparable NCT vs. CE attenuation (- 75 vs. - 72 HU) compared to freeware (- 72 vs. - 57 HU) and coronary (- 61 vs. - 39 HU). Excellent inter-observer agreement was seen with research (ICC 0.98) compared to freeware (ICC 0.73) and coronary software (ICC 0.75) with narrow LoA on Bland-Altman analysis. CONCLUSION: There are significant inter-vendor differences in EAT assessment. Our study suggests that research-specific software has better agreement and reproducibility compared to freeware or coronary software platforms. KEY POINTS: • There are significant differences between EAT volume and attenuation values between software platforms, regardless of scan type. • Non-contrast scans routinely have higher mean EAT volume and attenuation; however, this finding is only consistently seen with research-specific software. • Of the three analyzed packages, research-specific software demonstrates the highest reproducibility, agreement, and reliability for both inter-scan and inter-observer agreement.

Variation and clinical consequences of wait-times for atrial fibrillation ablation: population level study in Ontario, Canada.

AIMS: Atrial fibrillation (AF) is the most common cardiac rhythm disorder. Emerging evidence supporting the efficacy of catheter ablation in managing AF has led to increased demand for this therapy, potentially outpacing the capacity to perform this procedure. Mismatch between demand and capacity for AF ablation results in wait-times which have not been comprehensively evaluated at a population level. Additionally, the consequences of such delays in AF ablation, namely the risk of hospitalization or adverse events, have not been studied. METHODS AND RESULTS: This observational cohort study included adults referred for catheter ablation to treat AF in Ontario, Canada, between 1 April 2016 and 31 March 2020. Wait-time was defined from referral to the earliest of ablation, death, off-list, or the study endpoint of 31 March 2022. The outcomes of interest included a composite of death, hospitalization for AF/heart failure, and emergency department visit for AF/heart failure. Our study cohort included 6253 patients referred for de novo AF ablation. The median wait-time for patients who received and who did not receive ablation was 218 days (IQR: 112-363) and 520 days (IQR: 270-763), respectively. Wait-time increased consistently for patients referred between October 2017 and March 2020. Mortality was rare, but significant morbidity was observed, affecting 19.2% of patients on the waitlist for AF ablation. Paroxysmal AF was associated with a statistically significant greater risk for adverse outcomes on the waitlist (HR 1.51, 95% CI 1.18-1.93). CONCLUSION: Wait-times for AF ablation are increasing and are associated with significant morbidity.

Depressive Symptoms are Associated With C-Reactive Protein in Older Adults With Obesity.

OBJECTIVES: To test the hypothesis that depressive symptoms vary with high-sensitivity C-reactive protein (hs-CRP), among older adults with obesity. METHODS: This was a cross-sectional, secondary analysis of baseline data from two related lifestyle intervention trials. The study sample comprises 148 consecutively recruited, community-dwelling older adults (age >=65 years) without severe psychiatric illness and with body mass index >=30 kg/m2. Logarithmically transformed GDS was analyzed as the dependent variable. Independent variables included log-transformed hs-CRP and covariates: sex, age, and concurrent use of antidepressant medication at baseline. An additional analysis was performed using binary conversion of the GDS scores, wherein a cutoff score of 5 was considered positive for depressive symptoms. RESULTS: Sample mean GDS score was 2.7 (SD 3.0, range 0 - 14). A significant multivariate model of GDS scores (R2 = .089, F = 3.5, P = .010) revealed log-transformed hs-CRP (P = .017) and male sex (P = .012) as associated with depressive symptoms. Supplemental analysis demonstrated associations between depressive symptoms and log-transformed hs-CRP (OR 2.17, P = .001) and between depressive symptoms and male sex (OR 3.78, P = .013). Univariate logistic regression found hs-CRP to be associated with depressive symptoms. CONCLUSIONS: In older adults with obese BMI, male sex and higher hs-CRP are associated with depression, even in a group with relatively minimal depressive symptoms. Hs-CRP may offer clinical utility as a biomarker for depression among older adults with obese BMI, even among those with non-severe psychiatric symptomatology.

A review of the use of propensity score methods with multiple treatment groups in the general internal medicine literature.

BACKGROUND: Propensity score (PS) methods with two treatment groups (e.g., treated vs. control) is a well-established technique for reducing the effects of confounding in nonrandomized studies. However, researchers are often interested in comparing multiple interventions. PS methods have been modified to incorporate multiple exposures. We described available techniques for PS methods in multicategory exposures (≥3 groups) and examined their use in the medical literature. METHODS: A comprehensive search was conducted for studies published in PubMed, Embase, Google Scholar, and Web of Science until February 27, 2023. We included studies using PS methods for multiple groups in general internal medicine research. RESULTS: The literature search yielded 4088 studies (2616 from PubMed, 86 from Embase, 85 from Google Scholar, 1671 from Web of Science, five from other sources). In total, 264 studies using PS method for multiple groups were identified; 61 studies were on general internal medicine topics and included. The most commonly used method was that of McCaffrey et al., which was used in 26 studies (43%), where the Toolkit for Weighting and Analysis of Nonequivalent Groups (TWANG) method and corresponding inverse probabilities of treatment weights were estimated via generalized boosted models. The next most commonly used method was pairwise propensity-matched comparisons, which was used in 20 studies (33%). The method by Imbens et al. using a generalized propensity score was implemented in six studies (10%). Four studies (7%) used a conditional probability of being in a particular group given a set of observed baseline covariates where a multiple propensity score was estimated using a non-parsimonious multinomial logistic regression model. Four studies (7%) used a technique that estimates generalized propensity scores and then creates 1:1:1 matched sets, and one study (2%) used the matching weight method. CONCLUSIONS: Many propensity score methods for multiple groups have been adopted in the literature. The TWANG method is the most commonly used method in the general medical literature.

Association Between Hospital Postoperative Troponin Use and Patient Outcomes After Vascular Surgery.

BACKGROUND: Acute myocardial injury after noncardiac surgery, which is most often symptomatically silent, is associated with increased mortality and morbidity. However, it is not known if routine postoperative troponin testing will affect patient outcomes. METHODS: We assembled a cohort of patients who underwent carotid endarterectomy or abdominal aortic aneurysm repair in Ontario, Canada, from 2010 to 2017. Hospitals were categorized into high, medium, and low troponin testing intensity based on the proportion of patients who received postoperative troponin testing. Cox proportional hazards modeling was used to assess the association between hospital-specific testing intensity and 30-day and 1-year major adverse cardiovascular events (MACEs) while adjusting for patient-, surgery-, and hospital-level factors. RESULTS: The cohort consisted of 18,467 patients from 17 hospitals. Mean age was 72 years, and 74.0% were men. Rates of postoperative troponin testing were 77.5%, 35.8%, and 21.6% in the high-, medium-, and low-testing intensity hospitals, respectively. At 30 days, 5.3%, 5.3%, and 6.5% of patients in high-, medium-, and low-testing intensity hospitals experienced MACE, respectively. Higher troponin testing rate was associated with lower adjusted hazard ratios (HRs) for MACE at 30 days (0.94; 95% confidence interval [CI], 0.89-0.98) and at 1 year (0.97; 95% CI, 0.94-0.99) for each 10% increase in hospital troponin rate. Hospitals with high-testing intensity had higher rates of postoperative cardiology referrals, cardiovascular testing, and rates of new cardiovascular prescriptions. CONCLUSIONS: Patients undergoing vascular surgery at hospitals with higher postoperative troponin testing intensity experienced fewer adverse outcomes than patients who had surgery at hospitals with lower testing intensity.

Differences in Treatment Patterns and Outcomes of Acute Myocardial Infarction for Low- and High-Income Patients in 6 Countries.

Importance: Differences in the organization and financing of health systems may produce more or less equitable outcomes for advantaged vs disadvantaged populations. We compared treatments and outcomes of older high- and low-income patients across 6 countries. Objective: To determine whether treatment patterns and outcomes for patients presenting with acute myocardial infarction differ for low- vs high-income individuals across 6 countries. Design, Setting, and Participants: Serial cross-sectional cohort study of all adults aged 66 years or older hospitalized with acute myocardial infarction from 2013 through 2018 in the US, Canada, England, the Netherlands, Taiwan, and Israel using population-representative administrative data. Exposures: Being in the top and bottom quintile of income within and across countries. Main Outcomes and Measures: Thirty-day and 1-year mortality; secondary outcomes included rates of cardiac catheterization and revascularization, length of stay, and readmission rates. Results: We studied 289 376 patients hospitalized with ST-segment elevation myocardial infarction (STEMI) and 843 046 hospitalized with non-STEMI (NSTEMI). Adjusted 30-day mortality generally was 1 to 3 percentage points lower for high-income patients. For instance, 30-day mortality among patients admitted with STEMI in the Netherlands was 10.2% for those with high income vs 13.1% for those with low income (difference, -2.8 percentage points [95% CI, -4.1 to -1.5]). One-year mortality differences for STEMI were even larger than 30-day mortality, with the highest difference in Israel (16.2% vs 25.3%; difference, -9.1 percentage points [95% CI, -16.7 to -1.6]). In all countries, rates of cardiac catheterization and percutaneous coronary intervention were higher among high- vs low-income populations, with absolute differences ranging from 1 to 6 percentage points (eg, 73.6% vs 67.4%; difference, 6.1 percentage points [95% CI, 1.2 to 11.0] for percutaneous intervention in England for STEMI). Rates of coronary artery bypass graft surgery for patients with STEMI in low- vs high-income strata were similar but for NSTEMI were generally 1 to 2 percentage points higher among high-income patients (eg, 12.5% vs 11.0% in the US; difference, 1.5 percentage points [95% CI, 1.3 to 1.8 ]). Thirty-day readmission rates generally also were 1 to 3 percentage points lower and hospital length of stay generally was 0.2 to 0.5 days shorter for high-income patients. Conclusions and Relevance: High-income individuals had substantially better survival and were more likely to receive lifesaving revascularization and had shorter hospital lengths of stay and fewer readmissions across almost all countries. Our results suggest that income-based disparities were present even in countries with universal health insurance and robust social safety net systems.

Experimental Search for Neutron to Mirror Neutron Oscillations as an Explanation of the Neutron Lifetime Anomaly.

An unexplained >4σ discrepancy persists between "beam" and "bottle" measurements of the neutron lifetime. A new model proposed that conversions of neutrons n into mirror neutrons n^{'}, part of a dark mirror sector, can increase the apparent neutron lifetime by 1% via a small mass splitting Δm between n and n^{'} inside the 4.6 T magnetic field of the National Institute of Standards and Technology Beam Lifetime experiment. A search for neutron conversions in a 6.6 T magnetic field was performed at the Spallation Neutron Source which excludes this explanation for the neutron lifetime discrepancy.

The Effectiveness of a Specialized Primary Care Medical Home for Patients with Serious Mental Illness.

BACKGROUND: There are unmet primary care needs among people with serious mental illness that might be improved with integrated care and medical care management. Many healthcare organizations have attempted to address this problem, but few interventions have been rigorously studied and found to be effective. OBJECTIVE: Study the implementation and effectiveness of a novel, specialized primary care medical home designed to improve the healthcare of patients with serious mental illness. DESIGN, SETTING, AND PARTICIPANTS: Clustered controlled trial for a median of 401 days. One Veterans Health Administration medical center was assigned to intervention and two were assigned to usual care (control). Thirty-nine clinicians and managers were included in the study, as well as 331 patients who met eligibility criteria. INTERVENTION: A specialized medical home with systematic patient engagement, proactive nurse panel management, a collaborative care psychiatrist, and a primary care physician providing care that included psychiatric treatment. MAIN MEASURES: Quality of care, chronic illness care and care experience, symptoms, and quality of life. KEY RESULTS: Sixty-five intervention patients (40%) moved all psychiatric care to the primary care team. No adverse events were attributable to the intervention. Compared with control, intervention patients had greater improvement over time in appropriate screening for body mass index, lipids, and glucose (χ2 = 6.9, 14.3, and 3.9; P's < .05); greater improvement in all domains of chronic illness care (activation, decision support, goal-setting, counseling, coordination) and care experience (doctor-patient interaction, shared decision-making, care coordination, access; F for each 10-24, P's < .05); and greater improvement in mental health-related quality of life (F = 3.9, P = .05) and psychotic symptoms (F = 3.9, P = .05). CONCLUSION: A primary care medical home for serious mental illness can be feasible to implement, safe, and more effective than usual care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01668355.