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Abstract Central nervous system germ cell tumors (CNS-GCT) are malignant neoplasms that arise predominantly during adolescence and young adulthood. These tumors are typically sensitive to treatment, but resulting long-term health deficits are common. Additional clinical challenges include surgical risks associated with tumor biopsy, and need to determine treatment response for adapting radiotherapy protocols. The aim of this study was to establish the detectability of circulating-tumor DNA (ctDNA) from cerebrospinal fluid (CSF) of children with CNS-GCT as a potential biomarker. We obtained CSF from patients with CNS-GCT by lumbar puncture or intra-operatively. Cell-free DNA (cfDNA) was extracted and subjected to low-pass whole genome sequencing (LP-WGS). Copy-number alterations (CNAs) were inferred and served as a marker of measurable residual disease (MRD). Comparisons with imaging findings and tumor marker levels were made. A total of 29 CSF samples from 21 patients (16 with germinoma, 5 with non-germinomatous GCT) were sequenced. Twenty samples from 19 patients were collected at diagnosis, and 9 samples from 7 patients were collected during or after therapy. Among the diagnostic samples, CNAs were detected in samples from 17/19 patients (89%), which included 8 with marker-negative tumors. Specific clinical scenarios suggested that serial cfDNA analysis may carry utility in tracking treatment responses as well as clarifying indeterminate imaging findings. Our results provide evidence for the high-sensitivity in detecting ctDNA from CSF of CNS-GCT patients using LP-WGS, with potential utility for non-invasive diagnosis and disease monitoring in upcoming CNS-GCT studies.

Abstract Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) have a syndemic relationship with shared risk factors and complex interplay between genetic, environmental, socioeconomic, and pathophysiological mechanisms. CVD is among the most common comorbidities in patients with COPD and vice versa. Patients with COPD, irrespective of their disease severity, are at increased risk of CVD morbidity and mortality, driven in part by COPD exacerbations. Despite these known interrelationships, CVD is underestimated and undertreated in patients with COPD. Similarly, COPD is an independent risk-enhancing factor for adverse cardiovascular (CV) events, yet it is not incorporated into current CV risk assessment tools, leading to under-recognition and undertreatment. There is a pressing need for systems change in COPD management to move beyond symptom control towards a comprehensive cardiopulmonary disease paradigm with proactive prevention of exacerbations and adverse cardiopulmonary outcomes and mortality. However, there is a dearth of evidence defining optimal cardiopulmonary care pathways. Fortunately, there is a precedent to support systems-level change in the field of diabetes, which evolved from glycemic control to comprehensive multi-organ risk assessment and management. Key elements included integrated multidisciplinary care, intensive risk factor management, coordination between primary and specialist care, care pathways and protocols, education and self management, and disease-modifying therapies. This commentary article draws parallels between the cardiometabolic and cardiopulmonary paradigms and makes a case for systems change towards multidisciplinary, integrated cardiopulmonary care, using the evolution in diabetes care as a potential framework.

Abstract Growth differentiation factor (GDF15) has been considered a biomarker and recently a hormonal driver for diseases in different populations. However, the role of GDF15 as a biomarker of health outcomes in obese men from different racial/ethnic background has not been evaluated. The objective of this study was to investigate the racial/ethnic differences on the relationship between GDF15 and markers of glucometabolic status, hormonal profile, body composition and bone mineral density (BMD) in obese men. One hundred ninety‐three obese men from diverse racial/ethnic backgrounds were enrolled. BMD and body composition were measured by dual energy X‐ray absorptiometry. Serum GDF15, osteocalcin, C‐terminal telopeptide, sclerostin, adiponectin, leptin, estradiol, testosterone, follicle‐stimulating hormone, luteinizing hormone, 25‐hydroxyvitamin D, lipid profile, and hemoglobin A1C (A1C) were measured. Non‐African Americans (NAA) had significantly higher GDF15 level than African Americans (AA). Level was also higher in patients with type 2 diabetes (T2DM). In both the groups GDF15 correlated with A1C and lean mass. However. GDF15 correlated with body fat, LDL total cholesterol and femoral neck BMD only in NAA and with appendicular lean mass only in AA. Ethnicity, total cholesterol and T2DM were found to be independent predictors of GDF15. We conclude that GDF15 may influence glucometabolic status, body composition and bone parameters which may affect cardiovascular risk and osteoporosis between races.

BackgroundTestosterone (T) therapy increases lean mass and reduces total body and truncal fat mass in hypogonadal men. However, the underlying molecular mechanisms for the reciprocal changes in fat and lean mass in humans are not entirely clear.MethodsSecondary analysis of specimens obtained from a single-arm, open-label clinical trial on pharmacogenetics of response to T therapy in men with late-onset hypogonadism, conducted between 2011 and 2016 involving 105 men (40-74 years old), who were given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subcutaneous fat (SCF), peripheral blood mononuclear cells (PBMC) and serum were obtained from the participants at different time points of the study. We measured transcription factors for adipogenesis and myogenesis in the SCF, and PBMC, respectively, by real-time quantitative PCR at baseline and 6 months. Serum levels of FOLLISTATIN, PAX7, MYOSTATIN, ADIPSIN, and PRDM16 were measured by ELISA.ResultsAs expected, there was a significant increase in T and estradiol levels after 6 months of T therapy. There was also a reduction in fat mass and an increase in lean mass after 6 months of T therapy. Gene-protein studies showed a significant reduction in the expression of the adipogenic markers PPARγ in SCF and ADIPSIN levels in the serum, together with a concomitant significant increase in the expression of myogenic markers, MYOD in PBMC and PAX7 and FOLLISTATIN levels in the serum after 6 months of T therapy compared to baseline. Interestingly, there was a significant increase in the adipo-myogenic switch, PRDM16, expression in SCF and PBMC, and in circulating protein levels in the serum after 6 months of T therapy, which is likely from increased estradiol.ConclusionOur study supports that molecular shift from the adipogenic to the myogenic pathway in men with hypogonadism treated with T could be mediated directly or indirectly by enhanced PRDM16 activity, in turn a result from increased estradiol level. This might have led to the reduction in body fat and increase in lean mass commonly seen in hypogonadal men treated with T.

Abstract 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.

We present the clinical course of a 4-year-old girl with neurofibromatosis type 1-associated, unresectable, symptomatic urinary bladder ganglioneuroma. She was initially trialed on sirolimus without response and subsequently responded to MEK inhibitor trametinib, with improvement clinically and radiographically over 10 months. This report broadens the repertoire of therapeutic strategies for MEK inhibition in diseases related to the MAPK pathway.

Background: “Secondary” atrial fibrillation (AF) denotes AF that is precipitated by short-term triggers and that may be reversible. Using administrative data to study secondary AF is of interest, but the ability of these data to verify secondary AF has not been studied. Methods: We conducted a cross-sectional analysis of 1000 randomly selected hospitalizations of patients discharged alive between January 1, 2016 and March 31, 2020, with AF coded as the most responsible diagnosis (type 1), post-admit comorbidity (type 2), or secondary diagnosis (type 3). We compared diagnosis types to AF category (secondary or not) as determined by a physician blinded to the discharge diagnosis type. We calculated the positive predictive value (PPV) of the designation of secondary AF in comparison to physician determination. Results: A total of 421 hospitalizations had AF documented as a type 2 diagnosis; this had a PPV of 94.8% for physician determination of secondary AF. After excluding hospitalizations with preexisting AF, and those for which AF type could not be determined by the physician, the PPV of a type 2 diagnosis (n = 391) for secondary AF was 99.7%. Type 3 diagnoses of AF (n = 222) mostly captured hospitalizations with preexisting AF (87.8% of type 3 diagnoses). Conclusions: A type 2 diagnosis can be used to verify secondary AF in people who were first diagnosed with AF while hospitalized for other causes. This verification facilitates cohort studies and clinical trial recruitment of people with this AF subtype, although it should not be used to determine the prevalence or incidence of secondary AF. Résumé: Contexte: Une fibrillation auriculaire (FA) « secondaire » signifie que la FA est précipitée par des déclencheurs apparus depuis peu et pouvant être réversibles. L’utilisation de données administratives en vue d’étudier la FA secondaire peut être pertinente, mais la possibilité que ces données permettent d’évaluer les FA secondaires n’a pas été étudiée. Méthodologie: Nous avons effectué une analyse transversale de 1 000 hospitalisations, sélectionnées au hasard, de patients ayant reçu leur congé alors qu’ils étaient en vie entre le 1er janvier 2016 et le 31 mars 2020, et dans le dossier desquels la FA était codée comme étant le diagnostic principal de l’hospitalisation (type 1), une affection concomitante diagnostiquée après l’admission à l’hôpital (type 2) ou un diagnostic secondaire (type 3). Nous avons comparé les types des diagnostics à la catégorie de FA (secondaire ou pas), déterminée par un médecin qui ignorait le type de diagnostic confirmé au moment du congé. Nous avons calculé la valeur prédictive positive (VPP) de la désignation de FA secondaire, comparativement à ce que le médecin a déterminé. Résultats: Au total, 421 hospitalisations étaient associées à un diagnostic confirmé de FA de type 2, ce qui a produit une VPP de 94,8 % pour ce que le médecin avait déterminé comme étant une FA se-condaire. Après l’exclusion des hospitalisations de patients qui présentaient une FA préexistante et de ceux pour qui le type de FA ne pouvait pas être déterminé par le médecin, la VPP d’un diagnostic de FA de type 2 (n = 391) pour une FA secondaire était de 99,7 %. Les diagnostics de FA de type 3 (n = 222) étaient principalement associés à des hospitalisations de patients présentant une FA préexistante (87,8 % des diagnostics de type 3). Conclusions: Un diagnostic de FA de type 2 peut servir à vérifier la présence d’une FA secondaire chez les personnes ayant reçu un premier diagnostic de FA alors qu’elles étaient hospitalisées pour d’autres causes. Cette vérification facilite les études de cohortes et le recrutement pour des essais cliniques de personnes atteintes de ce sous-type de FA, mais elle ne doit pas servir à déterminer la prévalence ou l’incidence de la FA secondaire.

Background Dyslipidemia management is a cornerstone in cardiovascular disease prevention and relies heavily on patient adherence to lifestyle modifications and medications. Numerous cholesterol patient education materials are available online, but it remains unclear whether these resources are suitable for the majority of North American adults given the prevalence of low health literacy. This review aimed to (1) identify printable cholesterol patient education materials through an online search, and (2) evaluate the readability, understandability, and actionability of each resource to determine its utility in practice. Methods and Results We searched the MEDLINE database for peer‐reviewed educational materials and the websites of Canadian and American national health organizations for gray literature. Readability was measured using the Flesch–Kincaid Grade Level, and scores between fifth‐ and sixth‐grade reading levels were considered adequate. Understandability and actionability were scored using the Patient Education Materials Assessment Tool and categorized as superior (>80%), adequate (50%–70%), or inadequate (

Background Transcatheter aortic valve implantation (TAVI) has seen indication expansion and thus exponential growth in demand over the past decade. In many jurisdictions, the growing demand has outpaced capacity, increasing wait times and preprocedural adverse events. In this study, we derived prediction models that estimate the risk of adverse events on the waitlist and developed a triage tool to identify patients who should be prioritized for TAVI. Methods and Results We included adult patients in Ontario, Canada referred for TAVI and followed up until one of the following events first occurred: death, TAVI procedure, removal from waitlist, or end of the observation period. We used subdistribution hazards models to find significant predictors for each of the following outcomes: (1) all‐cause death while on the waitlist; (2) all‐cause hospitalization while on the waitlist; (3) receipt of urgent TAVI; and (4) a composite outcome. The median predicted risk at 12 weeks was chosen as a threshold for a maximum acceptable risk while on the waitlist and incorporated in the triage tool to recommend individualized wait times. Of 13 128 patients, 586 died while on the waitlist, and 4343 had at least 1 hospitalization. A total of 6854 TAVIs were completed, of which 1135 were urgent procedures. We were able to create parsimonious models for each outcome that included clinically relevant predictors. Conclusions The Canadian TAVI Triage Tool (CAN3T) is a triage tool to assist clinicians in the prioritization of patients who should have timely access to TAVI. We anticipate that the CAN3T will be a valuable tool as it may improve equity in access to care, reduce preventable adverse events, and improve system efficiency.

BackgroundThe expanding population of older adults with obesity is a public health challenge, in part, because of the increased risk of fractures despite normal or high bone mineral density. Potential factors predisposing to fractures in this group include sarcopenia associated with obesity and impaired bone quality. We aimed to determine the contribution of sarcopenic obesity (SO) indices to bone strength as assessed by microfinite element analysis (μFEA) of high-resolution peripheral quantitative computed tomography (HR-pQCT).MethodsOne-hundred eighty-nine older (age ≥ 65 years) adults with obesity (BMI ≥ 30 kg/m2) participated in lifestyle intervention trials at our medical center. All underwent baseline measurements of bone strength (failure load and stiffness) using μFEA from HR-pQCT of the distal radius and tibia. In addition, SO indices [appendicular lean mass/weight (ALM/W) and percent body fat (FM%)] by dual-energy X-ray absorptiometry and handgrip strength (HGS) by dynamometry were assessed. SO was diagnosed and staged based on the 2022 ESPEN and EASO expert consensus statement.ResultsBoth ALM/W and HGS were positively correlated explaining 28% to 36% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). In contrast, FM% was negatively correlated explaining 22% to 31% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). The associations of SO indices with failure load and stiffness remained significant after controlling for age, sex, race/ethnicity, diabetes, and 25-OH vitamin D (ALM/W: R2 = 0.301 to 0.448, HGS: R2 = 0.346 to 0.472, FM%: R2 = 0.299 to 0.432) (p < 0.001 to 0.011). SO was diagnosed in 75/189 (40%) participants with 66/75 (88%) having functional or metabolic complications (stage II). Participants with SO had lower failure load and stiffness at the distal radius than participants with no SO (both p < 0.05).ConclusionThese findings demonstrate that lower muscle mass and strength and higher fat mass may impair bone quality. Therefore, interventions that focus on preserving muscle mass and strength while reducing fat mass may be important to decrease fracture risk when older adults with obesity undertake lifestyle intervention therapy.

Summary: Biological evidence supports plasma methemoglobin as a biomarker for anemia-induced tissue hypoxia. In this translational planned substudy of the multinational randomized controlled transfusion thresholds in cardiac surgery (TRICS-III) trial, which included adults undergoing cardiac surgery requiring cardiopulmonary bypass with a moderate-to-high risk of death, we investigated the relationship between perioperative hemoglobin concentration (Hb) and methemoglobin; and evaluated its association with postoperative outcomes. The primary endpoint was a composite of death, myocardial infarction, stroke, and severe acute kidney injury at 28 days. We observe weak non-linear associations between decreasing Hb and increasing methemoglobin, which were strongest in magnitude at the post-surgical time point. Increased levels of post-surgical methemoglobin were associated with a trend toward an elevated risk for stroke and exploratory neurological outcomes. Our generalizable study demonstrates post-surgical methemoglobin may be a marker of anemia-induced organ injury/dysfunction, and may have utility for guiding personalized approaches to anemia management. Clinicaltrials.gov registration NCT02042898.

Background: Although we had previously reported the cardiac and neurologic outcomes of Chinese and South Asian Ontarians in wave 1 of COVID-19, data on subsequent waves of COVID-19 remain unexamined. This is an extension study of this cohort in waves 2 and 3. Methods: We identified adult Ontarians with a positive COVID-19 polymerase chain reaction test from January 1, 2020 to June 30, 2021, and they were classified as being Chinese or South Asian using a validated surname algorithm; we compared their outcomes of mortality, and cardiac and neurologic complications with those of the general population using multivariable logistic regression models. Results: Compared to the general population (n = 439,977), the Chinese population (n = 15,208) was older (mean age 44.2 vs 40.6 years, P < 0.001) and the South Asian population (n = 46,333) was younger (39.2 years, P < 0.001). The Chinese population had a higher 30-day mortality (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.28-1.61) and more hospitalization or emergency department visits (OR, 1.14; 95% CI, 1.09-1.28), with a trend toward a higher incidence of cardiac complications (OR, 1.03; 95% CI, 0.87-1.12) and neurologic complications (OR, 1.23; 95% CI, 0.96-1.58). South Asians had a lower 30-day mortality (OR, 0.88; 95% CI, 0.78-0.98) but a higher incidence of hospitalization or emergency department visits (OR, 1.17; 95% CI, 1.14-1.20) with a trend toward a lower incidence of cardiac complications (OR, 0.76; 95% CI, 0.67-0.87) and neurologic complications (OR, 0.89; 95% CI, 0.73-1.09). There was also a significant difference in these outcomes between wave 1, 2 and 3, with a greater mortality in all groups in waves 2 and 3. Conclusions: Ethnicity continues to be an important determinant of mortality, cardiac and neurologic outcomes, and healthcare use among patients with COVID-19, requiring further studies to understand factors driving these differences. Résumé: Contexte: Nous avons déjà présenté les issues cliniques cardiaques et neurologiques chez les Ontariens de descendance chinoise ou sud-asiatique pour la première vague de la pandémie de COVID-19, mais les données au sujet des vagues ultérieures n’avaient pas encore été analysées. Nous présentons ici une prolongation de cette étude de cohortes pour la seconde et la troisième vague de COVID-19. Méthodologie: Notre analyse porte sur des adultes ontariens ayant obtenu un résultat positif à un test de COVID-19 par réaction en chaîne de la polymérase entre le 1er janvier 2020 et le 30 juin 2021. Un algorithme validé pour l’analyse des noms de famille a été utilisé pour isoler les sujets de descendance chinoise ou sud-asiatique, et leur taux de mortalité de même que les complications cardiaques et neurologiques ont été comparés à ceux de la population générale à l’aide de modèles de régression logistique multivariée. Résultats: En comparaison de la population générale (n = 439 977), les personnes de descendance chinoise (n = 15 208) se sont révélées plus âgées (âge moyen de 44,2 ans contre 40,6 ans, P < 0,001), tandis que les personnes de descendance sud-asiatique (n = 46 333) étaient plus jeunes (39,2 ans, P < 0,001). Dans la population de descendance chinoise, le taux de mortalité après 30 jours était plus élevé (rapport de cotes [RC] de 1,44; intervalle de confiance [IC] à 95 % de 1,28 à 1,61), et davantage d’hospitalisations ou de consultations aux urgences sont survenues (RC de 1,14; IC à 95 % de 1,09 à 1,28). L’incidence de complications cardiaques (RC de 1,03; IC à 95 % de 0,87 à 1,12) et de complications neurologiques (RC de 1,23; IC à 95 % de 0,96 à 1,58) avait également tendance à être plus élevée. Chez les personnes de descendance sud-asiatique, le taux de mortalité après 30 jours était plus faible (RC de 0,88; IC à 95 % de 0,78 à 0,98), mais l’incidence d’hospitalisations ou de consultations aux urgences était plus élevée (RC de 1,17; IC à 95 % de 1,14 à 1,20). Elles présentaient également une tendance vers une plus faible incidence de complications cardiaques (RC de 0,76; IC à 95 % de 0,67 à 0,87) et de complications neurologiques (RC de 0,89; IC à 95 % de 0,73 à 1,09). Des différences significatives ont également été observées pour ces paramètres entre les vagues 1, 2 et 3 de la maladie, et le taux de mortalité était plus élevé pour tous les groupes des vagues 2 et 3. Conclusions: L’origine ethnique demeure un déterminant important de la mortalité, des issues cliniques cardiaques et neurologiques ainsi que de l’utilisation des ressources en santé chez les patients atteints de la COVID-19. D’autres études sont toutefois nécessaires pour mieux comprendre les facteurs qui expliquent ces différences.

Background: A simplified Canadian definition was recently developed to enable identification of individuals with familial hypercholesterolemia (FH) and severe hypercholesterolemia in the general population. Our objective was to use a modified version of this new definition to assess contemporary disease prevalence, treatment patterns, and low-density lipoprotein cholesterol (LDL-C) control in Ontario, Canada. Methods: We identified individuals aged 66 to 105 years who were alive as of January 1, 2011, using the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) database, which was created by linking 19 population-based health databases in Ontario. Hypercholesterolemia was identified using LDL-C values. Cholesterol reduction and lipid-lowering treatment were assessed at time of diagnosis and after at least 2 and 5 years’ follow-up. Results: Among 922,464 individuals, 2440 (0.26%) met criteria for definite or probable FH, and 72,893 (7.90%) for severe hypercholesterolemia. At diagnosis, mean LDL-C concentration was 9.52 mmol/L for those with definite FH, 5.83 mmol/L for those with probable FH, 5.73 mmol/L for those with severe hypercholesterolemia, and 3.33 mmol/L for all other individuals. After > 5 years, LDL-C concentration remained elevated at 3.58 mmol/L for those with definite FH, 2.72 mmol/L for those with probable FH, and 2.93 mmol/L for those with severe hypercholesteremia. Use of statin therapy was initially high (83% of those with definite FH, 78% of those with probable FH, 62% of those with severe hypercholesterolemia); however, fewer patients remained on statins at follow-up at > 5 years (62% of those with definite FH, 67% of those with probable FH, 58% of those with severe hypercholesterolemia). Conclusions: Among older Ontarians, we estimated that 1 in 378 individuals had FH, and 1 in 13 had severe hypercholesterolemia. Despite being at substantially increased cardiovascular risk, these patients acheived suboptimal LDL-C level control and fewer were on medical therapy at follow-up. Résumé: Introduction: Une définition canadienne simplifiée a récemment été élaborée pour permettre la détection des personnes atteintes d’hypercholestérolémie familiale (HF) et d'hypercholestérolémie grave au sein de la population générale. Notre objectif était d’utiliser la version modifiée de cette nouvelle définition pour évaluer la prévalence contemporaine de la maladie, les schémas de traitement et la maîtrise du cholestérol à lipoprotéines de faible densité (cholestérol LDL) en Ontario, au Canada. Méthodes: Nous avons recensé les individus âgés de 66 à 105 ans qui étaient en vie au 1er janvier 2011 à partir de la base de données Cardiovascular Health in Ambulatory Care Research Team (CANHEART), qui a été créée par la liaison de 19 bases de données populationnelles de l’Ontario. L’hypercholestérolémie a été définie par les valeurs du cholestérol LDL. Nous avons évalué la diminution du cholestérol et le traitement hypolipémiant au moment du diagnostic et après au moins les suivis après 2 ans et après 5 ans. Résultats: Parmi les 922 464 personnes, 2 440 (0,26 %) répondaient aux critères de diagnostic définitif ou de diagnostic probable d’HF, et 72 893 (7,90 %), aux critères d’hypocholestérolémie grave. Au diagnostic, les concentrations moyennes de cholestérol LDL étaient de 9,52 mmol/l chez ceux qui avaient un diagnostic définitif d’HF, de 5,83 mmol/l chez ceux qui avaient un diagnostic probable d’HF, de 5,73 mmol/l chez ceux qui avaient un diagnostic d’hypercholestérolémie grave et de 3,33 mmol/l chez toutes les autres personnes. Après > 5 ans, les concentrations de cholestérol LDL étaient demeurées élevées : 3,58 mmol/l chez ceux qui avaient un diagnostic définitif d’HF, 2,72 mmol/l chez ceux qui avaient un diagnostic probable d’HF et 2,93 mmol/l chez ceux qui avaient un diagnostic d’hypercholestérolémie grave. L’utilisation du traitement par statines était initialement élevée (83 % de ceux qui avaient un diagnostic définitif d’HF, 78 % de ceux qui avaient un diagnostic probable d’HF, 62 % de ceux qui avaient un diagnostic d’hypercholestérolémie grave). Toutefois, moins de patients avaient conservé les statines au suivi > 5 ans (62 % de ceux qui avaient un diagnostic définitif d’HF, 67 % de ceux qui avaient un diagnostic probable d’HF, 58 % de ceux qui avaient un diagnostic d’hypercholestérolémie grave). Conclusions: Parmi les Ontariens âgés, nous avons estimé que 1 sur 378 personnes avaient une HF, et que 1 sur 13 avaient une hypercholestérolémie grave. Malgré le fait qu’ils sont exposés à un risque cardiovasculaire substantiellement élevé, ces patients ont atteint une maîtrise sous-optimale du taux de cholestérol LDL et moins d'entre eux étaient sous traitement médical au suivi.

Background Atherosclerotic disease is an important contributor to adverse outcomes in patients with atrial fibrillation (AF). There is limited recognition of the association between statin use and stroke rates in AF. We aimed to quantify the association between statin use and stroke rate in AF. Methods and Results Using linked administrative databases in Ontario, Canada, we conducted a population‐based retrospective cohort study of patients, aged ≥66 years, diagnosed with AF between 2009 and 2019. We used cause‐specific hazard regression to determine the association of statin use with stroke rate. We developed a second model to further adjust for lipid levels in the subset of patients with available measurements in the year before AF diagnosis. Both models adjusted for age, sex, heart failure, hypertension, diabetes, stroke/transient ischemic attack, vascular disease, and P2Y12 inhibitors at baseline, plus anticoagulation as a time‐varying covariate. We studied 261 659 qualifying patients (median age, 78 years; 49% women). Statins were used in 142 834 (54.6%) patients, and 145 673 (55.7%) had lipid measurement(s) in the preceding year. Statin use was associated with lower stroke rates, with adjusted hazard ratios of 0.83 (95% CI, 0.77–0.88; P1.5 mmol/L. Conclusions Statins were associated with lower stroke rates in patients with AF, whereas higher low‐density lipoprotein levels were associated with higher stroke rates, highlighting the importance of vascular risk factor treatment in AF.

Employee retention is one of the human resource management (HRM) issues. This study determines the factors that significantly influence employee retention amidst the COVID-19 pandemic. The study employs complete enumeration and uses primary data. After which, the results are analyzed using descriptive statistics and econometric modeling. Results reveal that employees are satisfied to do their respective jobs (M=4.09, SD=0.48). In addition, they show that the determinants such as other income (p-value=0.024), length of service (p-value=0.099), as well as reward and recognition (p-value=0.015), are significant influences to employees’ retention. Hence, these conclude that better remuneration (and the increase thereof) are more likely to retain existing employees and attract employees from other organizations. Furthermore, the study specifically recommends that employee retention be improved by further refining reward and recognition that surely meet the needs and well-being of the employees.

Abstract The atherogenic index of plasma (AIP) is a novel biomarker of atherogenic dyslipidaemia (AD), but its relationship with cardiac adipose tissue depots is unknown. We aimed to assess the association of AD with cardiac adipose tissue parameters on coronary computed tomography angiography (CCTA). We studied 161 patients who underwent CCTA between 2008 and 2011 (age 59.0 ± 14.0 years). AD was defined as triglyceride (TG) > 1.7 mmol/L and HDL

Abstract We aimed to determine whether early public health interventions in 2020 mitigated the association of sociodemographic and clinical risk factors with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a population-based cohort study of all adults in Ontario, Canada who underwent testing for SARS-CoV-2 through December 31, 2020. The outcome was laboratory-confirmed SARS-CoV-2 infection, determined by reverse transcription polymerase chain reaction testing. Adjusted odds ratios (ORs) were determined for sociodemographic and clinical risk factors before and after the first-wave peak of the pandemic to assess for changes in effect sizes. Among 3,167,753 community-dwelling individuals, 142,814 (4.5%) tested positive. The association between age and SARS-CoV-2 infection risk varied over time (P-interaction

Introduction: Loss of skeletal muscle mass and function (sarcopenia) is common in individuals with obesity due to metabolic changes associated with a sedentary lifestyle, adipose tissue derangements, comorbidities (acute and chronic diseases) and during the ageing process. Co-existence of excess adiposity and low muscle mass/function is referred to as sarcopenic obesity (SO), a condition increasingly recognized for its clinical and functional features that negatively influence important patient-centred outcomes. Effective prevention and treatment strategies for SO are urgently needed, but efforts are hampered by the lack of a universally established SO definition and diagnostic criteria. Resulting inconsistencies in the literature also negatively affect the ability to define prevalence as well as clinical relevance of SO for negative health outcomes. Aims and Methods: The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched an initiative to reach expert consensus on a definition and diagnostic criteria for SO. The jointly appointed international expert panel proposes that SO is defined as the co-existence of excess adiposity and low muscle mass/function. The diagnosis of SO should be considered in at-risk individuals who screen positive for a co-occurring elevated body mass index or waist circumference, and markers of low skeletal muscle mass and function (risk factors, clinical symptoms, or validated questionnaires). Diagnostic procedures should initially include assessment of skeletal muscle function, followed by assessment of body composition where presence of excess adiposity and low skeletal muscle mass or related body compartments confirm the diagnosis of SO. Individuals with SO should be further stratified into stage I in the absence of clinical complications or stage II if cases are associated with complications linked to altered body composition or skeletal muscle dysfunction. Conclusions: ESPEN and EASO, as well as the expert international panel, advocate that the proposed SO definition and diagnostic criteria be implemented into routine clinical practice. The panel also encourages prospective studies in addition to secondary analysis of existing data sets, to study the predictive value, treatment efficacy and clinical impact of this SO definition.

There is a long-standing interest in the development of patterning process for porous materials. Here, the authors report a solvent-free bottom-up approach for the patterning of zeolitic imidazolate frameworks; well-resolved patterns with features down to the scale of 100 nm can be achieved.

Aim: To evaluate the prognosis of 30-day survival post-cardiac arrest among patients receiving home care and nursing home residents. Methods: We conducted a population-level retrospective cohort study of community-dwelling adults (≥18 years) who received cardiac arrest care at a hospital in Ontario, Canada, between 2006 to 2018. We linked population-based health datasets using the Home Care Dataset to identify patients receiving home care and the Continuing Care Reporting System to identify nursing home residents. We included both out-of-hospital and in-hospital cardiac arrests. We determined unadjusted and adjusted associations using logistic regression after adjusting for age and sex. We converted relative measures to absolute risks. Results: Our cohort contained 86,836 individuals. Most arrests (55.5 %) occurred out-of-hospital, with 9,316 patients enrolled in home care and 2,394 residing in a nursing home. When compared to those receiving no support services, the likelihood of survival to 30-days was lower for those receiving home care (RD = −6.5; 95 %CI = −7.5 – −5.0), with similar results found within sub-groups of out-of-hospital (RD = −6.7; 95 %CI = −7.6 – −5.7) and in-hospital arrests (RD = −8.7; 95 %CI = −10.6 – −7.3). The likelihood of 30-day survival was lower for nursing home residents (RD = −7.2; 95 %CI = −9.3 - −5.3) with similar results found within sub-groups of out-of-hospital (RD = −8.6; 95 %CI = −10.6 – −5.7) and in-hospital arrests (RD = −5.0; 95 %CI = −7.8 – −2.1). Conclusion: Patients receiving home care and nursing home residents had worse overall prognoses of survival post-cardiac arrest compared to those receiving no pre-arrest support, highlighting two medically-complex groups likely to benefit from advance care planning.

Background The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial decreased major adverse cardiovascular events with very low‐dose rivaroxaban and aspirin in patients with coronary artery disease and peripheral artery disease. We examined the eligibility and potential real‐world impact of this strategy on the COMPASS‐eligible population. Methods and Results COMPASS eligibility criteria were applied to the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) registry, a population‐based cohort of Ontario adults. We compared 5‐year major adverse cardiovascular events and major bleeding rates stratified by COMPASS eligibility and by clinical risk factors. We applied COMPASS trial rivaroxaban/aspirin arm hazard ratios to estimate the potential impact on the COMPASS‐eligible cohort. Among 362 797 patients with coronary artery disease or peripheral artery disease, 38% were deemed eligible, 47% ineligible, and 15% indeterminate. Among eligible patients, a greater number of risk factors was associated with higher rates of cardiovascular outcomes, whereas bleeding rates increased minimally. Over 5 years, applying COMPASS treatment effects to eligible patients resulted in a 2.4% absolute risk reduction of major adverse cardiovascular events and a number needed to treat of 42, and a 1.3% absolute risk increase of major bleeding and number needed to harm (NNH) of 77. Those with at least 2 risk factors had a 3.0% absolute risk reduction of major adverse cardiovascular events (number needed to treat =34) and a 1.6% absolute risk increase of major bleeding (number needed to harm =61). Conclusions Implementation of very‐low‐dose rivaroxaban therapy would potentially impact ≈$$ \approx $$2 in 5 patients with atherosclerotic disease in Ontario. Eligible individuals with ≥$$ \ge $$2 comorbidities represent a high‐risk subgroup that may derive the greatest benefit‐to‐risk ratio. Selection of patients with high‐risk predisposing factors appears appropriate in routine practice.

Serial cardiac troponin (cTn) testing on patients with symptoms suggestive of acute coronary syndrome (ACS) is primarily to identify those patients with evolving myocardial injury. With the improved analytical performance of the high-sensitivity cTn (hs-cTn) assays, different change criteria have been proposed that are mostly assay dependent. Here, we developed and compared a new Common Change Criteria (3C for the combined criteria of >3 ng/L, >30%, or >15% based on the initial cTn concentration of 100 ng/L, respectively) method, versus the 2 h assay-dependent absolute change criteria endorsed by the European Society of Cardiology (ESC), versus the common relative >20% change criterion. These different analytical change criteria were evaluated in 855 emergency department (ED) patients with symptoms of ACS and who had two samples collected 3 h apart. The cTn concentrations were measured with four different assays (Abbott hs-cTnI, Roche hs-cTnT, Ortho cTnI-ES, and Ortho hs-cTnI). The outcomes evaluated were myocardial infarction (MI) and a composite outcome (MI, unstable angina, ventricular arrhythmia, heart failure, or cardiovascular death) within 7 days of ED presentation. The combined change criteria (3C) method yielded higher specificities (range: 93.9 to 97.2%) as compared to the >20% criterion (range: 42.3 to 88.1%) for all four assays for MI. The 3C method only yielded a higher specificity estimate for MI for the cTnI-ES assay (95.9%) versus the absolute change criteria (71.7%). Similar estimates were obtained for the composite outcome. There was also substantial agreement between hs-cTnT and the different cTnI assays for MI with the 3C method, with the percent agreement being ≥95%. The Common Change Criteria (3C) method combining both absolute and different percent changes may be used with cTnI, hs-cTnT, and different hs-cTnI assays to yield similar high-specificity (rule-in) estimates for adverse cardiovascular events for patients presenting to the ED with ACS symptoms.

ABSTRACT: Background: Given changes in the care and outcomes of acute myocardial infarction (AMI) patients over the past several decades, we sought to develop prediction models that could be used to generate accurate risk-adjusted mortality and readmission outcomes for hospitals in current practice across Canada. Methods: A Canadian national expert panel was convened to define appropriate AMI patients for reporting and develop prediction models. Preliminary candidate variable evaluation was conducted using Ontario patients hospitalized with a most responsible diagnosis of AMI from April 1, 2015 to March 31, 2018. National data from the Canadian Institute for Health Information was used to develop AMI prediction models. The main outcomes were 30-day all-cause in-hospital mortality and 30-day urgent all-cause readmission. Discrimination of these models (measured by c-statistics) was compared with that of existing Canadian Institute for Health Information models in the same study cohort. Results: The AMI mortality model was assessed in 54,240 Ontario AMI patients and 153,523 AMI patients across Canada. We observed a 30-day in-hospital mortality rate of 6.3%, and a 30-day all-cause urgent readmission rate of 10.7% in Canada. The final Canadian AMI mortality model included 12 variables and had a c-statistic of 0.834. For readmission, the model had 13 variables and a c-statistic of 0.679. Discrimination of the new AMI models had higher c-statistics compared with existing models (c-statistic 0.814 for mortality; 0.673 for readmission). Conclusions: In this national collaboration, we developed mortality and readmission models that are suitable for profiling performance of hospitals treating AMI patients in Canada. RÉSUMÉ: Contexte: Compte tenu des changements apportés au cours des dernières décennies aux soins des patients ayant subi un infarctus aigu du myocarde (IAM) et aux issues d'un tel événement, nous avons voulu élaborer des modèles prédictifs pouvant servir à calculer de façon précise les résultats relatifs à la mortalité et aux réadmissions, ajustés selon les risques, pour les hôpitaux dans la pratique actuelle au Canada. Méthodologie: Un groupe national d'experts canadiens a été mis sur pied et a reçu le mandat de définir les critères appropriés applicables aux patients ayant subi un IAM aux fins de déclaration des cas et d’élaborer des modèles prédictifs. L’évaluation préliminaire des variables proposées a été effectuée à partir de patients hospitalisés en Ontario entre le 1er avril 2015 et le 31 mars 2018 chez lesquels l'IAM était le diagnostic principal à l'origine de l'hospitalisation. Les données à l’échelle nationale de l'Institut canadien d'information sur la santé (ICIS) ont été utilisées pour élaborer des modèles prédictifs d'IAM. Les deux principales issues évaluées étaient la mortalité hospitalière toutes causes confondues à 30 jours et la réadmission urgente toutes causes confondues à 30 jours. Le pouvoir discriminant de ces modèles (mesuré par la statistique C) a été comparé à celui des modèles existants de l'ICIS dans la même cohorte de l’étude. Résultats: Le modèle de mortalité par IAM a été évalué auprès de patients ayant subi un IAM, dont 54 240 en Ontario et 153 523 dans l'ensemble du Canada. Nous avons observé un taux de mortalité hospitalière à 30 jours de 6,3 % et un taux de réadmission urgente à 30 jours toutes causes confondues de 10,7 % au Canada. Le modèle canadien final de prédiction de la mortalité par IAM était constitué de 12 variables et avait une statistique C de 0,834. Pour la réadmission, le modèle comportait 13 variables et présentait une statistique C de 0,679. Le pouvoir discriminant des nouveaux modèles d'IAM présentait une statistique C supérieure à celle des modèles existants (statistique C de 0,814 pour la mortalité et de 0,673 pour la réadmission). Conclusions: Dans le cadre de cette collaboration nationale, nous avons élaboré des modèles prédictifs de la mortalité et de la réadmission hospitalière qui permettent d’établir un profil des résultats obtenus par les hôpitaux traitant des patients ayant subi un IAM au Canada.

Abstract Aims Heart failure (HF) guidelines place patients into 3 discrete groups according to left ventricular ejection fraction (LVEF): reduced (

Study objective: Develop and evaluate a model that uses health administrative data to categorize cardiovascular (CV) cause of death (COD). Design: Population-based cohort. Setting: Ontario, Canada. Participants: Decedents ≥ 40 years with known COD between 2008 and 2015 in the CANHEART cohort, split into derivation (2008 to 2012; n = 363,778) and validation (2013 to 2015; n = 239,672) cohorts. Main outcome measures: Model performance. COD was categorized as CV or non-CV with ICD-10 codes as the gold standard. We developed a logistic regression model that uses routinely collected healthcare administrative to categorize CV versus non-CV COD. We assessed model discrimination and calibration in the validation cohort. Results: The strongest predictors for CV COD were history of stroke, history of myocardial infarction, history of heart failure, and CV hospitalization one month before death. In the validation cohort, the c-statistic was 0.80, the sensitivity 0.75 (95 % CI 0.74 to 0.75) and the specificity 0.71 (95 % CI 0.70 to 0.71). In the primary prevention validation sub-cohort, the c-statistic was 0.81, the sensitivity 0.71 (95 % CI 0.70 to 0.71) and the specificity 0.75 (95 % CI 0.75 to 0.75) while in the secondary prevention sub-cohort the c-statistic was 0.74, the sensitivity 0.81 (95 % CI 0.81 to 0.82) and the specificity 0.54 (95 % CI 0.53 to 0.54), Conclusion: Modelling approaches using health administrative data show potential in categorizing CV COD, though further work is necessary before this approach is employed in clinical studies.

IntroductionType 2 diabetes mellitus (T2DM) is well-known to be associated with normal bone density but, concurrently, low bone turnover and increased risk for fracture. One of the proposed mechanisms is possible derangement in bone precursor cells, which could be represented by deficiencies in circulating osteogenic progenitor (COP) cells and osteoclast precursors (OCP). The objective of our study is to understand whether extent of glycemic control has an impact on these cells, and to identify other factors that may as well.MethodsThis was a secondary analysis of baseline data from 51 male participants, aged 37-65 in an ongoing clinical trial at Michael E. DeBakey VA Medical Center, Houston, Texas, USA. At study entry serum Hemoglobin A1c was measured by high-performance liquid chromatography osteocalcin (OCN) and C-terminal telopeptide of type 1 collagen (CTx) were measured by ELISA, and testosterone and estradiol by liquid-chromatography/mass-spectrometry. Areal bone mineral density (BMD), trabecular bone score and body composition were measured by dual energy x-ray absorptiometry, while COP and OCP were measured by flow cytometry.ResultsWhen adjusted for serum testosterone, parathyroid hormone, and 25-hydroxyvitamin D, those with poor long-term glycemic control had significantly higher percentage of COP (p = 0.04). COP correlated positively with visceral adipose tissue (VAT) volume (r = 0.37, p = 0.01) and negatively with free testosterone (r = -0.28, p = 0.05) and OCN (r = -0.28, p = 0.07), although only borderline for the latter. OCP correlated positively with age, FSH, lumbar spine BMD, and COP levels, and negatively with glucose, triglycerides, and free estradiol. Multivariable regression analyses revealed that, in addition to being predictors for each other, another independent predictor for COP was VAT volume while age, glucose, and vitamin D for OCP.ConclusionOur results suggest that high COP could be a marker of poor metabolic control. However, given the complex nature and the multitude of factors influencing osteoblastogenesis/adipogenesis, it is possible that the increase in COP is a physiologic response of the bone marrow to increased osteoblast apoptosis from poor glycemic control. Alternatively, it is also likely that a metabolically unhealthy profile may retard the development of osteogenic precursors to fully mature osteoblastic cells.

Background: In 2017, the Canadian Cardiovascular Society (CCS) published guidelines recommending postoperative troponin surveillance in higher-risk patients having major noncardiac surgery. The objective of this study was to evaluate the proportion of major noncardiac surgery patients that would meet recommendations for troponin testing and to assess the rates of troponin testing before guideline adoption. Methods: We conducted a retrospective observational study of patients age 40 to 105 undergoing a subset of major noncardiac surgeries that included orthopedics, gynecology, general, urology, vascular, and thoracic surgeries in Ontario, Canada from January 1, 2010 to December 31, 2017. The primary outcomes were the proportion of patients recommended for testing based on the guidelines and rates of troponin testing within 2 days of surgery. Results: We identified 257,704 patients who underwent noncardiac surgery. Mean age was 66.4 ± 11.9 years, and 12.4% underwent urgent surgery. Applying the CCS guidelines, 71.2% of elective surgery patients and 81.0% of urgent surgery patients would have met recommendations for postoperative troponin screening, whereas 10.8% and 27.1% received postoperative troponin testing, respectively. Most elective surgery patients met recommendations for testing based on the age criterion (54.9%), followed by diabetes (24.6%) and high-risk surgery (22.7%) criteria. Troponin testing varied substantially by types of surgery: highest for open abdominal aortic aneurisms and lowest for hysterectomies. Conclusions: Based on the CCS guidelines, most patients undergoing the subset of surgeries assessed would have met recommendations for routine troponin testing. In contrast, routine troponin testing before guideline adoption was done infrequently in Ontario, with substantial variations based on the surgery type. Résumé: Introduction: En 2017, la Société canadienne de cardiologie (SCC) a publié des lignes directrices dont les recommandations portaient sur la surveillance de la troponine en phase postopératoire chez les patients exposés à un risque accru de subir une intervention chirurgicale non cardiaque importante. L'objectif de la présente étude était d’évaluer le nombre de patients subissant une intervention chirurgicale non cardiaque importante qui répondraient aux recommandations sur le dosage de la troponine et de déterminer la fréquence des dosages de la troponine avant l'adoption des lignes directrices. Méthodes: Nous avons mené une étude observationnelle rétrospective auprès de patients âgés de 40 à 105 ans subissant des interventions chirurgicales non cardiaques importantes, à savoir des interventions de chirurgie orthopédique, de chirurgie gynécologique, de chirurgie générale, de chirurgie urologique, de chirurgie vasculaire et de chirurgie thoracique en Ontario, au Canada, du 1er janvier 2010 au 31 décembre 2017. Les principaux critères d’évaluation étaient le nombre de patients pour qui le dosage était recommandé selon les lignes directrices, et la fréquence des dosages de la troponine dans les deux jours après l'intervention chirurgicale. Résultats: Nous avons relevé 257 704 patients qui avaient subi une intervention chirurgicale non cardiaque. L’âge moyen était de 66,4 ± 11,9 ans, et 12,4 % avaient subi une intervention chirurgicale urgente. En appliquant les lignes directrices de la SCC, 71,2 % des patients avaient subi une intervention chirurgicale élective et 81,0 % des patients qui avaient subi une intervention chirurgicale urgente répondaient aux recommandations de dépistage de la troponine en phase postopératoire, alors que respectivement 10,8 % et 27,1 % avaient reçu le dosage de la troponine en phase postopératoire. La plupart des patients qui avaient subi une intervention chirurgicale élective répondaient aux recommandations sur le dosage selon le critère d’âge (54,9 %), puis selon le critère de diabète (24,6 %) et le critère d'intervention chirurgicale à risque élevé (22,7 %). Le dosage de la troponine variait de façon substantielle selon le type d'intervention chirurgicale : le dosage le plus élevé lors des traitements chirurgicaux ouverts des anévrismes de l'artère abdominale et le dosage le plus faible lors d'hystérectomies. Conclusions: Selon les lignes directrices de la SCC, la plupart des patients qui subissaient les interventions chirurgicales évaluées avaient répondu aux recommandations de dosage systématique de la troponine. En revanche, le dosage systématique de la troponine avant l'adoption des lignes directrices était rarement réalisé en Ontario, et des variations substantielles selon le type d'intervention chirurgicale étaient observées.

Abstract Aims The LE index (Length of hospitalization plus number of Emergent visits ≤6 months) predicts 30 day all‐cause readmission or death following hospitalization for heart failure (HF). We combined N‐terminal pro‐B type natriuretic peptide (NT‐proBNP) levels with the LE index to derive and validate the LENT index for risk prediction at the point of care on the day of hospital discharge. Methods and results In this prospective cohort sub‐study of the Patient‐centred Care Transitions in HF clinical trial, we used log‐binomial regression models with LE index and either admission or discharge NT‐proBNP as the predictors and 30 day composite all‐cause readmission or death as the primary outcome. No other variables were added to the model. We used regression coefficients to derive the LENT index and bootstrapping analysis for internal validation. There were 772 patients (mean [SD] age 77.0 [12.4] years, 49.9% female). Each increment in the LE index was associated with a 25% increased risk of the primary outcome (RR 1.25, 95% CI 1.16–1.35; C‐statistic 0.63). Adjusted for the LE index, every 10‐fold increase in admission and discharge NT‐proBNP was associated with a 48% (RR 1.48; 95% CI 1.10, 1.99; C‐statistic 0.64; net reclassification index [NRI] 0.19) and 56% (RR 1.56; 95% CI 1.08, 2.25; C‐statistic 0.64; NRI 0.21) increased risk of the primary outcome, respectively. The predicted probability of the primary outcome increased to a similar extent with incremental LENT, regardless of whether admission or discharge NT‐proBNP level was used. Conclusions The point‐of‐care LENT index predicts 30 day composite all‐cause readmission or death among patients hospitalized with HF, with improved risk reclassification compared with the LE index. The performance of this simple, 3‐variable index ‐ without adjustment for comorbidities ‐ is comparable to complex risk prediction models in HF. Trial Registration: ClinicalTrials.gov Identifier: NCT02112227

ContextMale hypogonadism adversely affects body composition, bone mineral density (BMD), and metabolic health. A previous report showed that pre-treatment testosterone (T) levels of

Background Despite improved outcomes associated with ticagrelor compared with clopidogrel in acute coronary syndrome (ACS), many studies have demonstrated slow adoption of ticagrelor in the United States because of its increased cost. Less is known about how ticagrelor is adopted when there is no added cost consideration. Our objectives were to determine patterns of use of ticagrelor, hospital‐level adoption of ticagrelor use, and factors associated with its use after ACS in a publicly funded health care system. Methods and Results We conducted a population‐based cohort study including patients (≥65 years) hospitalized with their first ACS from April 2014 to March 2018 in Ontario, Canada. We determined temporal trends in ticagrelor use and hospital‐level adoption of its use post‐ACS discharge. Using hierarchical regression models, we identified significant predictors of ticagrelor use. There were 23 962 patients with ACS (mean age 76.3 years, 59.7% men) hospitalized in 156 hospitals. Overall ticagrelor use increased from 32.6% in 2014/2015 to 51.8% in 2017/2018. There was substantial variation in ticagrelor use post‐ACS across hospitals, with hospital‐specific prescribing rates ranging from 0% to 83.6%. Lower odds of ticagrelor use was associated with advanced age and the presence of comorbidities. Besides patient factors, being admitted to a rurally located hospital more than halved the odds of being prescribed ticagrelor (odds ratio [OR], 0.49; 95% CI, 0.32–0.77). Being managed by a cardiologist during the index ACS hospitalization was associated with higher odds of having a ticagrelor prescription after ACS (OR, 2.80; 95% CI, 2.36–3.33). Conclusions Ticagrelor use rates varied substantially across hospitals and were strongly associated with physician and hospital factors independent of patient characteristics.

Low-grade fibromyxoid sarcomas (LGFMSs) are typically adult-onset tumors that arise from the extremities. Here, we report an exceptional case of primary thoracic LGFMS in an 8-year-old girl that resulted in mediastinal syndrome. In reporting this case, we discuss the clinical challenges, role of molecular profiling and review reported cases of pediatric thoracic LGFMSs.

Background: The incidence of coronavirus disease 2019 (COVID-19) in patients with ST-segment elevation myocardial infarction (STEMI) has not been fully described. Methods: All patients with STEMI undergoing primary percutaneous coronary intervention (PCI) in Ontario, Canada between March 1 and September 30, 2020 were included. Rates of positive COVID-19 tests from January 1, 2020 to the date of STEMI presentation were ascertained. For comparison, COVID-19 results were also evaluated in the adult Ontario population between January 1, 2020 and September 30, 2020, using provincial laboratory testing data. Results: There were 3606 unique patients presenting with STEMI and receiving PCI in Ontario, Canada during the study period. Sixteen patients (0.44%) tested positive for COVID-19. The background infection rate among all 12,448,541 Ontario residents was similar, at 0.34%. Conclusions: The results of this population-based analysis suggest that proceeding with primary PCI with appropriate infection control practices is reasonable when community infection rates are low. Résumé: Contexte: L'incidence de la maladie à coronavirus 2019 (COVID-19) chez les patients présentant un infarctus du myocarde avec élévation du segment ST (STEMI) n'a pas été entièrement décrite. Méthodologie: Tous les patients atteints de STEMI ayant subi une intervention coronarienne percutanée (ICP) primaire en Ontario (Canada) entre le 1er mars et le 30 septembre 2020 ont été inclus. Les taux de tests positifs à la COVID entre le 1er janvier 2020 et le moment de la présentation du STEMI ont été vérifiés. Aux fins de comparaison, les résultats des tests de dépistage de la COVID-19 ont également été évalués au sein de la population adulte de l'Ontario entre le 1er janvier 2020 et le 30 septembre 2020 au moyen des données des laboratoires provinciaux. Résultats: Pendant la période d’étude, 3 606 patients présentant un STEMI et ayant subi une ICP en Ontario (Canada) ont été recensés. Seize patients (0,44 %) ont reçu un résultat positif au test de dépistage de la COVID-19. Le taux d'infection parmi les 12 448 541 résidents de l'Ontario était similaire, soit 0,34 %. Conclusions: Les résultats de cette analyse populationnelle portent à penser qu'il est raisonnable de procéder à une ICP primaire avec des mesures appropriées de contrôle des infections lorsque les taux d'infection dans la collectivité sont faibles.

Abstract Background We sought to evaluate the association of metabolic syndrome (MetS) and computed tomography (CT)-derived cardiometabolic biomarkers (non-alcoholic fatty liver disease [NAFLD] and epicardial adipose tissue [EAT] measures) with long-term risk of major adverse cardiovascular events (MACE) in asymptomatic individuals. Methods This was a post-hoc analysis of the prospective EISNER (Early-Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) study of participants who underwent baseline coronary artery calcium (CAC) scoring CT and 14-year follow-up for MACE (myocardial infarction, late revascularization, or cardiac death). EAT volume (cm3) and attenuation (Hounsfield units [HU]) were quantified from CT using fully automated deep learning software (

This white paper will summarize the key topics, outcomes, and recommendations from the Canada-India Healthcare Summit 2021 COVID-19 Pandemic Response and Initiatives sessions held on May 20–21, 2021. In particular, the authors have focused their attention on topics on the effect of COVID-19 on noncommunicable diseases, depression, research on substance abuse, and post COVID-19 pain management. The authors have developed a better understanding of these conditions' interplay with COVID-19 infection. The paper also deals with important topics around the effects of NCD on COVID-19 and vice versa, as well as key considerations around research and development, innovation, policy, and finally, summarizes the ways forward in which Canada and India could collaborate strategically. We also include key points raised during the summit.

Background: In response to the COVID-19 pandemic, Ontario issued a declaration of emergency, implementing public health interventions on March 16, 2020. Methods: We compared cardiac catheterization procedures for ST-elevation myocardial infarction (STEMI) between January 1 and May 10, 2020 to the same time frame in 2019. Results: From March 16 to May 10, 2020, after implementation of provincial directives, STEMI cases significantly decreased by up to 25%. The proportion of patients who achieved guideline targets for first medical contact balloon for primary percutaneous coronary intervention (PCI) decreased substantially to 28% (median, 101 minutes) for patients who presented directly to a PCI site and to 37% (median, 149 minutes) for patients transferred from a non-PCI site, compared with 2019. Conclusions: STEMI cases across Ontario have been substantially affected during the COVID-19 pandemic. Résumé: Introduction: En réponse à la pandémie de COVID-19, l’Ontario a déclaré l’état d’urgence et mis en place des interventions de santé publique le 16 mars 2020. Méthodes: Nous avons comparé les procédures de cathétérisme cardiaque lors d’infarctus du myocarde avec sus-décalage du segment ST (STEMI) du 1er janvier au 10 mai 2020 à la même période en 2019. Résultats: Du 16 mars au 10 mai 2020, après la mise en place des directives provinciales, les cas de STEMI ont connu une diminution significative pouvant atteindre jusqu’à 25 %. La proportion de patients qui ont atteint les objectifs prévus aux lignes directrices entre le premier contact médical et le ballonnet de l’intervention coronarienne percutanée (IPC) a connu une diminution considérable de 28 % (médiane, 101 minutes) pour ceux qui se présentaient directement dans un site d’IPC et de 37 % (médiane, 149 minutes) pour ceux qui étaient dirigés vers un site non-ICP, et ce, en comparaison à 2019. Conclusions: La pandémie de COVID-19 a considérablement nui aux cas de STEMI de l’Ontario.

PURPOSE Despite being the most common pediatric solid tumors, incidence and outcome of CNS tumors in Chinese children have not been systematically reported. We addressed this knowledge gap by comparing the epidemiology of pediatric CNS tumors in Hong Kong and the United States. PATIENTS AND METHODS Data between 1999 and 2016 from a population-based cancer registry in Hong Kong, China, on patients < 18 years old with CNS tumors (Hong Kong cohort) and from the US SEER Program (Asian/Pacific Islander and all ethnicities) were compared. Incidence and overall survival (OS) by histology were evaluated. RESULTS During the study period, 526 children were newly diagnosed with CNS tumors in Hong Kong (crude incidence rate, 2.47 per 100,000; 95% CI, 2.26 to 2.69). Adjusted incidences were significantly lower in the Hong Kong (2.51; 95% CI, 2.30 to 2.74) than in the SEER (Asian/Pacific Islander: 3.26; 95% CI, 2.97 to 3.57; P < .001; all ethnicities: 4.10 per 100,000; 95% CI, 3.99 to 4.22; P < .001) cohorts. Incidences of germ cell tumors (0.57 v 0.24; P < .001) were significantly higher, but those of glial and neuronal tumors (0.94 v 2.61; P < .001), ependymomas (0.18 v 0.31; P = .005), and choroid plexus tumors (0.08 v 0.16; P = .045) were significantly lower in Hong Kong compared with SEER (all ethnicities) cohorts. Compared with the SEER (Asian/Pacific Islander) cohort, histology-specific incidences were similar except for a lower incidence of glial and neuronal tumors in Hong Kong (0.94 v 1.74; P < .001). Among cohorts, OS differed only for patients with glial and neuronal tumors (5-year OS: Hong Kong, 52.5%; SEER [Asian/Pacific Islander], 73.6%; SEER [all ethnicities], 79.9%; P < .001). CONCLUSION We identified important ethnic differences in the epidemiology of CNS tumors in Chinese children. These results will inform the development of pediatric neuro-oncology services in China and aid further etiologic studies.

Background: For patients investigated for suspected acute coronary syndrome, there is uncertainty if a single measurement of high-sensitivity cardiac troponin I (hs-cTnI) at emergency department (ED) presentation can identify patients at both low and high risk for mortality. Methods: We included consecutive adult patients in the ED who had a Clinical Chemistry Score (CCS) taken at presentation (ie, combination of glucose, creatinine for estimated glomerular filtration rate determination, and hs-cTnI assay) in a Canadian city between 2012 and 2013. Outcomes were 3-month, 1-year, and 5-year all-cause mortality using the provincial death registry. Mortality rates and test performance (eg, sensitivity and specificity) with 95% confidence intervals (CIs) were obtained for the CCS or hs-cTnI assay alone using established cutoffs for these tests. Results: Our cohort included 5974 patients with a 1-year mortality rate of 17.2% (95% CI, 16.2-18.3). A CCS ≥ 1 yielded a sensitivity of 99.2% (95% CI, 98.4-99.6) compared with the hs-cTnI ≥ 5 ng/L cutoff sensitivity of 88.4% (95% CI, 86.3-90.3), with the mortality rate being significantly lower for patients with CCS < 1 (2.0%; 95% CI, 0.9-4.0) vs patients with hs-cTnI < 5 ng/L (5.0%; 95% CI, 4.2-6.0) at 1 year (P = 0.01). A CCS of 5 also yielded a higher specificity (88.5%; 95% CI, 87.5-89.3) compared with hs-cTnI > 26 ng/L (83.9%; 95% CI, 82.9-84.9), with no difference in mortality rates (37.4% vs 36.3%; P = 0.66). This trend was consistent at 3-month and 5-year mortality. Conclusion: For patients in the ED with a potential cardiac issue, using the CCS cutoffs can better identify patients at low and high risk for mortality than using published cutoffs for hs-cTnI alone. Résumé: Contexte: Dans le cas des patients chez qui l’on soupçonne un syndrome coronarien aigu, des doutes subsistent à savoir si la mesure de la troponine I cardiaque à haute sensibilité (TnIc-hs) à l’arrivée au service des urgences peut, à elle seule, permettre de repérer les patients présentant un risque de mortalité faible ou élevé. Méthodologie: L’étude portait sur les patients adultes qui se sont présentés consécutivement au service des urgences dans une ville canadienne entre 2012 et 2013 et pour lesquels un score CCS (Clinical Chemistry Score, ou score des paramètres biochimiques cliniques, c’est-à-dire glycémie, créatininémie [aux fins du calcul du débit de filtration glomérulaire estimé] et dosage de la TnIc-hs) a été établi à leur arrivée. Les critères d’évaluation étaient la mortalité toutes causes confondues à 3 mois, à 1 an et à 5 ans, déterminée à partir des actes de décès inscrits au registre provincial. Les taux de mortalité et la fiabilité des tests (sensibilité et spécificité) avec des intervalles de confiance (IC) à 95 % ont été déterminés pour le score CCS et pour le dosage de la TnIc-hs seulement au moyen des valeurs seuils établies pour ces tests. Résultats: La cohorte réunissait 5 974 patients, et le taux de mortalité à 1 an s’établissait à 17,2 % (IC à 95 % : 16,2-18,3). Un score CCS ≥ 1 a été associé à une sensibilité de 99,2 % (IC à 95 % : 98,4-99,6) comparativement à 88,4 % (IC à 95 % : 86,3-90,3) pour une valeur seuil de TnIc-hs ≥ 5 ng/l, le taux de mortalité à 1 an étant significativement plus bas chez les patients ayant un score CCS < 1 (2,0 %; IC à 95 % : 0,9-4,0) que chez ceux ayant un taux de TnIc-hs < 5 ng/l (5,0 %; IC à 95 % : 4,2-6,0) (p = 0,01). Un score CCS de 5 a en outre été associé à une plus grande spécificité (88,5 %; IC à 95 % : 87,5-89,3) qu’un taux de TnIc-hs > 26 ng/l (83,9 %; IC à 95 % : 82,9-84,9); il n’y avait pas de différence entre les taux de mortalité (37,4 % vs 36,3 %; p = 0,66). Les résultats relatifs à la mortalité à 3 mois et à 5 ans concordaient avec cette tendance. Conclusion: Dans le cas des patients admis au service des urgences en raison d’un problème cardiaque potentiel, les valeurs seuils du score CCS peuvent permettre de mieux repérer les patients qui présentent un risque de mortalité faible ou élevé, comparativement aux seules valeurs seuils publiées des taux de TnIc-hs.

Background: Patients with heart failure (HF) with concomitant ischemic heart disease (IHD) have not been well characterized. We examined survival of patients with ischemic HF syndrome (IHFS), defined as presentation with acute HF and concomitant features suggestive of IHD. Methods: Patients were included if they presented with acute HF to hospitals in Ontario, Canada. IHD was defined by any of the following criteria: angina/chest pain, prior myocardial infarction (MI), or troponin elevation that was above the upper limit of normal (mild) or suggestive of cardiac injury. Deaths were determined after hospital presentation. Results: Of 5353 patients presenting with acute HF, 4088 (76.4%) exhibited features of IHFS. Patients with IHFS demonstrated a higher rate of 30-day (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.33-2.68) and 1-year death (HR, 1.16, 95% CI, 1.00-1.35) compared with those with nonischemic HF. Troponin elevation demonstrated the strongest association with mortality. Mildly elevated troponin was associated with increased hazard over 30-day (HR, 1.77; 95% CI, 1.12-2.81) and 1-year (HR, 1.63; 95% CI, 1.38-1.93) mortality. Troponins indicative of cardiac injury were associated with increased hazard of death over 30 days (HR, 2.33; 95% CI, 1.63-3.33) and 1 year (HR, 1.40; 95% CI, 1.21-1.61). The association between elevated troponin and higher mortality at 30 days was similar in left ventricular ejection fraction subcategories of HF with reduced ejection fraction, HF with mildly reduced ejection fraction, or HF with preserved ejection fraction (P interaction = 0.588). After multivariable adjustment, prior MI and angina were not associated with higher mortality risk. Conclusions: In acute HF, elevated troponin, but not prior MI or angina, was associated with a higher risk of 30-day and 1-year mortality irrespective of left ventricular ejection fraction. Résumé: Contexte: Les patients présentant une insuffisance cardiaque et une cardiopathie ischémique (CI) concomitante ne sont pas bien caractérisés. Nous avons examiné les données sur la survie de patients atteints d’un syndrome d’insuffisance cardiaque ischémique (SICI), caractérisé par la présence d’une insuffisance cardiaque aiguë et de manifestations concomitantes évoquant une CI. Méthodologie: Les données examinées concernaient des patients atteints d’insuffisance cardiaque aiguë reçus en consultation dans des hôpitaux de l’Ontario, au Canada. Un patient était réputé atteint de CI s’il répondait à l’un des critères suivants : angine/douleur thoracique, antécédents d’infarctus du myocarde (IM) ou élévation de la concentration de troponine se situant au-delà de la limite supérieure de la normale (cas léger) ou évoquant une lésion cardiaque. La détermination des décès a été effectuée en aval des consultations hospitalières. Résultats: Parmi 5 353 patients atteints d’insuffisance cardiaque aiguë reçus en consultation, 4 088 (76,4 %) présentaient des caractéristiques de SICI. Chez les patients atteints d’un SICI, un taux plus élevé de mortalité à 30 jours (rapport des risques instantanés [RRI] : 1,89, intervalle de confiance [IC] à 95 % : 1,33-2,68) et à 1 an (RRI : 1,16, IC à 95 % : 1,00-1,35) a été noté comparativement aux patients atteints d’insuffisance cardiaque non ischémique. L’élévation de la concentration de troponine présentait la plus forte association avec la mortalité. Une légère élévation de la concentration de troponine se trouvait associée à un risque accru de mortalité à 30 jours (RRI : 1,77, IC à 95 % : 1,12-2,81) et à 1 an (RRI : 1,63, IC à 95 % : 1,38-1,93). Les concentrations de troponine témoignant de lésions cardiaques étaient associées à une augmentation du risque de mortalité à 30 jours (RRI : 2,33, IC à 95 % : 1,63-3,33) et à 1 an (RRI : 1,40, IC à 95 % : 1,21-1,61). L’association entre une concentration élevée de troponine et une augmentation du taux de mortalité à 30 jours était semblable dans les sous-catégories d’insuffisance cardiaque avec fraction d’éjection ventriculaire gauche réduite, légèrement réduite ou préservée (p = 0,588 pour l’interaction). Après correction multivariée, les antécédents d’IM et d’angine n’étaient pas associés à un risque accru de mortalité. Conclusions: Dans un contexte d’insuffisance cardiaque aiguë, l’élévation de la concentration de troponine était associée à un risque plus élevé de mortalité à 30 jours et à 1 an indépendamment de la fraction d’éjection ventriculaire gauche; les antécédents d’IM ou d’angine ne l’étaient toutefois pas.

Summary: Background: Atherosclerotic plaque quantification from coronary CT angiography (CCTA) enables accurate assessment of coronary artery disease burden and prognosis. We sought to develop and validate a deep learning system for CCTA-derived measures of plaque volume and stenosis severity. Methods: This international, multicentre study included nine cohorts of patients undergoing CCTA at 11 sites, who were assigned into training and test sets. Data were retrospectively collected on patients with a wide range of clinical presentations of coronary artery disease who underwent CCTA between Nov 18, 2010, and Jan 25, 2019. A novel deep learning convolutional neural network was trained to segment coronary plaque in 921 patients (5045 lesions). The deep learning network was then applied to an independent test set, which included an external validation cohort of 175 patients (1081 lesions) and 50 patients (84 lesions) assessed by intravascular ultrasound within 1 month of CCTA. We evaluated the prognostic value of deep learning-based plaque measurements for fatal or non-fatal myocardial infarction (our primary outcome) in 1611 patients from the prospective SCOT-HEART trial, assessed as dichotomous variables using multivariable Cox regression analysis, with adjustment for the ASSIGN clinical risk score. Findings: In the overall test set, there was excellent or good agreement, respectively, between deep learning and expert reader measurements of total plaque volume (intraclass correlation coefficient [ICC] 0·964) and percent diameter stenosis (ICC 0·879; both p

Background The degree of hospital‐level variation in the ratio of percutaneous coronary interventions to coronary artery bypass grafting procedures (PCI:CABG) and the association of the PCI:CABG ratio with clinical outcome are unknown. Methods and Results In a multicenter population‐based study conducted in Ontario, Canada, we identified 44 288 patients from 19 institutions who had nonemergent diagnostic angiograms indicating severe multivessel coronary artery disease (2013–2017) and underwent a coronary revascularization procedure within 90 days. Hospitals were divided into tertiles according to their adjusted PCI:CABG ratio into low (0.70–0.85, n=17 487), medium (1.01–1.17, n=15 275), and high (1.18–1.29, n=11 526) ratio institutions. Compared with low PCI:CABG ratio hospitals, hazard ratios (HRs) for major adverse cardiac and cerebrovascular events were higher at medium (HR, 1.19; 95% CI, 1.14–1.25) and high ratio (HR, 1.21; 95% CI, 1.15–1.27) hospitals during a median 3.3 (interquartile range 2.1–4.6) years follow‐up. When interventional cardiologists performed the diagnostic angiogram, the odds of the patient receiving PCI was higher (odds ratio, 1.37; 95% CI, 1.23–1.52) than when it was performed by noninterventional cardiologists, after accounting for patient characteristics. Having the diagnostic angiogram at an institution without cardiac surgical capabilities was independently associated with a higher risk of major adverse cardiac and cerebrovascular events (HR, 1.07; 95% CI, 1.02–1.11), death (HR, 1.09; 95% CI, 1.02–1.18), and myocardial infarction (HR, 1.10; 95% CI, 1.03–1.17). Conclusions Patients undergoing diagnostic angiography in hospitals with higher PCI:CABG ratio had higher rates of adverse outcomes, including major adverse cardiac and cerebrovascular events, myocardial infarction, and repeat revascularization. Presence of on‐site cardiac surgery was associated with better survival and lower major adverse cardiac and cerebrovascular events.

Objectives To identify patient, physician and geographic level factors that are associated with variation in initial stress testing strategy in patients evaluated for chest pain.Design Retrospective cohort study.Setting Population-based study of patients undergoing evaluation for chest pain in Ontario, Canada between 1 January 2011 and 31 March 2018.Participants 103 368 patients who underwent stress testing (graded exercise stress testing (GXT), stress echocardiography (stress echo) or myocardial perfusion imaging (MPI)) following evaluation for chest pain.Primary and secondary outcome measures To identify the patient, physician and geographic level factors associated with variation in initial test selection, we fit two separate 2-level hierarchical multinomial logistic regression models for which the outcome was initial stress testing strategy (GXT, MPI or stress echo).Results There was significant variability in the initial type of stress test performed, with approximately 50% receiving a GXT compared with approximately 36% who received MPI and 14% who received a stress echo. Physician-level factors were key drivers of this variation, accounting for up to 59.0% of the variation in initial testing. Physicians who graduated medical school >30 years ago were approximately 45% more likely to order an initial stress echo (OR 1.45, 95% CI 1.17 to 1.80) than a GXT. Cardiovascular disease specialists were approximately sevenfold more likely to order an initial MPI (OR 7.35, 95% CI 5.38 to 10.03) than a GXT. Patients aged >70 years were approximately fivefold more likely to receive an MPI (OR 4.74, 95% CI 4.42 to 5.08) and approximately 26% more likely to receive a stress echo (OR 1.26, 95% CI 1.15 to 1.38) than a GXT.Conclusions We report significant variability in initial stress testing strategy in Ontario. Much of that variability was driven by physician-level factors that could potentially be addressed through educational campaigns geared at reducing this variability and improving guideline adherence.

Background There are limited data on the association of diabetes duration and glycemic control with stroke risk in atrial fibrillation (AF). Our objective was to study the association of diabetes duration and glycated hemoglobin (HbA1c) with the rate of stroke in people with diabetes and newly diagnosed AF. Methods and Results This was a population‐based cohort study using linked administrative data sets. We studied 37 209 individuals aged ≥66 years diagnosed with AF in Ontario between April 2009 and March 2019, who had diabetes diagnosed 1 to 16 years beforehand. The primary outcome was hospitalization for stroke at 1 year. Cause‐specific hazard regression was used to model the association of diabetes duration and glycated hemoglobin (HbA1c) with the rate of stroke. Restricted cubic spline analyses showed increasing hazard ratios (HR) for stroke with longer diabetes duration that plateaued after 10 years and increasing HRs for stroke with HbA1c levels >7%. Relative to patients with

Dengue virus is an important circulating arbovirus in Brazil responsible for high morbidity and mortality worldwide, representing a huge economic and social burden, in addition to affecting public health. In this study, the biological activity, toxicity, and antiviral activity against dengue virus type 2 (DENV-2) of tizoxanide (TIZ) was evaluated in Vero cell culture. TIZ has a broad spectrum of action in inhibiting different pathogens, including bacteria, protozoa, and viruses. Cells were infected for 1 h with DENV-2 and then treated for 24 h with different concentrations of the drug. The quantification of viral production indicated the antiviral activity of TIZ. The protein profiles in infected Vero cells treated and not treated with TIZ were analyzed using the label-free quantitative proteomic approach. TIZ was able to inhibit virus replication mainly intracellularly after DENV-2 penetration and before the complete replication of the viral genome. Additionally, the study of the protein profile of infected not-treated and infected-treated Vero cells showed that TIZ interferes with cellular processes such as intracellular trafficking and vesicle-mediated transport and post-translational modifications when added after infection. Our results also point to the activation of immune response genes that would eventually lead to a decrease of DENV-2 production. TIZ is a promising therapeutic molecule for the treatment of DENV-2 infections.

BackgroundEmerging data suggest that type 2 diabetes mellitus (T2D) is associated with an increased risk for fractures despite relatively normal or increased bone mineral density (BMD). Although the mechanism for bone fragility in T2D patients is multifactorial, whether glycemic control is important in generating this impairment in bone metabolism remains unclear. The purpose of our study is to identify a hemoglobin A1c (A1c) threshold level by which reduction in bone turnover begins in men with T2D.MethodA cross-sectional analysis of baseline data was obtained from 217 men, ages 35–65, regardless of the presence or absence of hypogonadism or T2D, who participated in 2 clinical trials. The following data were obtained: A1c by HPLC, testosterone and estradiol by LC/MS, bone turnover markers Osteocalcin [OC], C-terminal telopeptide [CTx], and sclerostin by ELISA, and BMD by DXA. Patients were grouped into 4 categories based of A1c (group I:

Background Small observational studies have suggested that statin users have a lower risk of dying with COVID‐19. We tested this hypothesis in a large, population‐based cohort of adults in 2 of Canada’s most populous provinces: Ontario and Alberta. Methods and Results We examined reverse transcriptase–polymerase chain reaction swab positivity rates for SARS‐CoV‐2 in adults using statins compared with nonusers. In patients with SARS‐CoV‐2 infection, we compared 30‐day risk of all‐cause emergency department visit, hospitalization, intensive care unit admission, or death in statin users versus nonusers, adjusting for baseline differences in demographics, clinical comorbidities, and prior health care use, as well as propensity for statin use. Between January and June 2020, 2.4% of 226 142 tested individuals aged 18 to 65 years, 2.7% of 88 387 people aged 66 to 75 years, and 4.1% of 154 950 people older than 75 years had a positive reverse transcriptase–polymerase chain reaction swab for SARS‐CoV‐2. Compared with 353 878 nonusers, the 115 871 statin users were more likely to test positive for SARS‐CoV‐2 (3.6% versus 2.8%, P

Background The relationship between health care utilization and outcomes in patients with atrial fibrillation is unknown. The objective of this study was to investigate whether cardiologists’ billing amounts in a fee‐for‐service environment are associated with better patient‐level clinical outcomes. Methods and Results A retrospective cohort study was conducted using administrative claims data of cardiologists in Ontario, Canada between April 1, 2011 and March 31, 2016. The cardiologists were stratified into quintiles based on their median billing patterns per patient over the observation period. The primary outcomes were patient‐level receipt of repeat visits, cardiac diagnostic tests, and medications ≤1 year of index date. The secondary clinical outcomes were death, emergency department visits, and all‐cause hospitalization 1‐year post‐index visit. The patient cohort comprised 182 572 patients with atrial fibrillation (median age 74 years, 58% male) from 467 cardiologists. Patients with atrial fibrillation seen by higher‐billing cardiologists were 26% more likely to have an echocardiogram (adjusted odds ratio [aOR], 1.26 [95% CI, 1.10–1.43] for quintile 5 versus 2), 28% a stress test (aOR, 1.28 [1.12–1.46] for quintile 5 versus 2), 25% continuous electrocardiographic monitoring (aOR, 1.25 [1.08–1.46] for quintile 4 versus 2), and 79% more likely to get a stress echocardiogram (aOR, 1.79 [1.32–2.42] for quintile 5 versus 2). They also had a higher rate of all‐cause hospitalization (aOR, 1.13 [1.07–1.20]). Mortality rates were similar across cardiologists billing quintiles (eg, aOR, 0.98 [0.87–1.11] for quintile 4 versus 2). Conclusions Higher‐billing cardiologists ordered more diagnostic tests per patient with atrial fibrillation but these are not associated with improvements in outcomes.

Background The multidisciplinary Heart Team (HT) is recommended for management decisions for transcatheter aortic valve replacement (TAVR) candidates, and during TAVR procedures. Empiric evidence to support these recommendations is limited. We aimed to explore temporal trends, drivers, and outcomes associated with HT utilization. Methods and Results TAVR candidates were identified in Ontario, Canada, from April 1, 2012 to March 31, 2019. The HT was defined as having a billing code for both a cardiologist and cardiac surgeon during the referral period. The procedural team was defined as a billing code during the TAVR procedure. Hierarchical logistical models were used to determine the drivers of HT. Median odds ratios were calculated to quantify the degree of variation among hospitals. Of 10 412 patients referred for TAVR consideration, 5489 (52.7%) patients underwent a HT during the referral period, with substantial range between hospitals (median odds ratio of 1.78). Utilization of a HT for TAVR referrals declined from 69.9% to 41.1% over the years of the study. Patient characteristics such as older age, frailty and dementia, and hospital characteristics including TAVR program size, were found associated with lower HT utilization. In TAVR procedures, the procedural team included both cardiologists and cardiac surgeons in 94.9% of cases, with minimal variation over time or between hospitals. Conclusions There has been substantial decline in HT utilization for TAVR candidates over time. In addition, maturity of TAVR programs was associated with lower HT utilization.