Factors Impacting Physician Prognostic Accuracy in Heart Failure Patients With Reduced Left Ventricular Ejection Fraction.

BACKGROUND: A recent study showed that the accuracy of heart failure (HF) cardiologists and family doctors to predict mortality in outpatients with HF proved suboptimal, performing less well than models. OBJECTIVES: The authors sought to evaluate patient and physician factors associated with physician accuracy. METHODS: The authors included outpatients with HF from 11 HF clinics. Family doctors and HF cardiologists estimated patient 1-year mortality. They calculated predicted mortality using the Seattle HF Model and followed patients for 1 year to record mortality (or urgent heart transplant or ventricular assist device implant as mortality-equivalent events). Using multivariable logistic regression, the authors evaluated associations among physician experience and confidence in estimates, duration of patient-physician relationship, patient-physician sex concordance, patient race, and predicted risk, with concordant results between physician and model predictions. RESULTS: Among 1,643 patients, 1-year event rate was 10% (95% CI: 8%-12%). One-half of the estimates showed discrepant results between model and physician predictions, mainly owing to physician risk overestimation. Discrepancies were more frequent with increasing patient risk from 38% in low-risk to ∼75% in high-risk patients. When making predictions on male patients, female HF cardiologists were 26% more likely to have discrepant predictions (OR: 0.74; 95% CI: 0.58-0.94). HF cardiologist estimates in Black patients were 33% more likely to be discrepant (OR: 0.67; 95% CI: 0.45-0.99). Low confidence in predictions was associated with discrepancy. Analyses restricted to high-confidence estimates showed inferior calibration to the model, with risk overestimation across risk groups. CONCLUSIONS: Discrepant physician and model predictions were more frequent in cases with perceived increased risk. Model predictions outperform physicians even when they are confident in their predictions. (Predicted Prognosis in Heart Failure [INTUITION]; NCT04009798).

Increasing rates of screening and treatment of iron deficiency in ambulatory patients with heart failure with reduced ejection fraction: a quality improvement cohort study.

INTRODUCTION: Iron deficiency anaemia (IDA) is common in patients with heart failure (HF) and is associated with advanced HF and increased mortality. Intravenous iron supplementation increases exercise tolerance, improves quality of life, and decreases symptoms among patients with HF with reduced ejection fraction (HFrEF) and iron deficiency. Despite this, many patients are not screened or treated for IDA. We aimed to increase rates of screening and treatment of IDA among HF patients through the introduction of curated materials to aid HF clinicians with appropriate screening and treatment. METHODS: We conducted a retrospective chart review to identify the baseline number of HFrEF patients screened and treated for IDA at two ambulatory cardiology clinics in Toronto, Ontario. A quality improvement initiative was then introduced, which consisted of education and curated materials to aid clinicians in the screening and treatment of IDA among HFrEF patients. The proportion of patients screened and treated for IDA preintervention and postintervention were compared using χ2 tests of Independence. RESULTS: In the preintervention cohort, 36.3% (n=45) of patients with anaemia were screened for IDA. Among those screened, 64.4% (n=29) had IDA. Only 17.2% (n=5) of these were treated with IV iron. After implementation of the quality improvement initiative, 90.9% (n=60) of patients with anaemia were screened for IDA (p<0.001) and 90.3% (n=28) of those with IDA were treated with IV iron (p<0.001). CONCLUSION: The introduction of curated materials to aid clinicians was associated with increased rates of screening and treatment of IDA among ambulatory HFrEF patients. Further work is required to identify barriers and implement strategies to increase screening and treatment rates of IDA among HFrEF patients.

Emerging treatments for corneal endothelium decompensation - a systematic review.

PURPOSE: Endothelial keratoplasty (EK) is the conventional treatment to improve visual acuity of corneal endothelium decompensation (CED) patients, with other therapies mainly for symptomatic relief. However, the shortage of corneal grafts and other limitations to EK urge the development of novel alternative treatments. In the last decade, novel options have been proposed, yet only a limited number of reviews have systematically reported on outcomes. Therefore, this systematic review evaluates the existing clinical evidence of novel surgical approaches for CED. METHOD: We identified 24 studies that illustrated the clinical observations of the surgical approaches in interest. We included Descemet stripping only (DSO), Descemet membrane transplantation (DMT) where Descement membrane alone instead of corneal endothelium with cells is transplanted, and cell-based therapy. RESULTS: In general, these therapies may provide visual outcomes comparable with EK under specific conditions. DSO and DMT target CED with relatively healthy peripheral corneal endothelium like Fuchs' corneal endothelial dystrophy, while cell-based therapy offers more versatile applications. Side effects of DSO would decrease with modifications to surgical techniques. Moreover, Rho-associated protein kinase inhibitor adjuvant therapy could enhance clinical results in DSO and cell-based therapy. CONCLUSION: Long-term controlled clinical trials with larger sample size on the therapies are needed. The simplicity of DSO and the high translational potential of cell-based therapy to treat CED of most etiologies made these two treatment strategies promising.

Ocular manifestations and diagnosis of tuberculosis involving the uvea: a case series.

BACKGROUND: Ocular tuberculosis (TB) affects 1-2% of patients with TB, with TB uveitis being the most common. This series aims to look at different manifestations of tuberculosis associated uveitis and the different tests used to make a presumptive or definitive diagnosis. METHODS: Patients diagnosed with TB related uveitis in Hong Kong SAR between 2017 and 2020 were reviewed. Demographics, clinical features, investigations and treatments of patients were collected. RESULTS: Fifteen eyes in 10 patients with a mean age 57.30 ± 10.17 years were included. The ocular manifestations on presentation included anterior uveitis (50%), posterior uveitis (40%) and panuveitis (10%), where 70% of them were unilateral and 30% were bilaterally infected; on subsequent visits the manifestations further developed into posterior uveitis (40%), panuveitis (40%) and anterior uveitis (20%), where 50% of them were unilateral and 50% bilateral infected. Tuberculosis tests were positive in 5 out of 7 Mantoux tests, 4 out of 4 T-SPOT TB tests, 3 out of 4 QuantiFERON-TB gold tests, 1 out of 1 lymph node biopsy, 0 out of 9 chest x-rays, and no aqueous fluid polymerase chain reaction (PCR) was tested. Vision impairing complications were seen in 6 patients where retinal vasculitis was most commonly seen. With anti-TB treatment prescribed in 9 patients, side effects occurred in 5 patients, including ocular hypertension, disc swelling, and hepatitis. CONCLUSIONS: Ocular TB infections may manifest in various forms, and can involve different parts of the eye. Bilateral involvement of TB is commonly presented, and both eyes should be evaluated at every follow up. When TB is suspected in a patient, diagnostic confirmation requires multimodal investigations where a negative chest x-ray is not useful in ruling out ocular TB infections, especially in an endemic region like Hong Kong. In these patients, it is crucial to have a high index of suspicion for TB, even when they do not demonstrate classical respiratory signs and symptoms of TB.

3D Spheroid Invasion Assay for High-Throughput Screening of Small-Molecule Libraries.

Cancer metastasis is a complex cascade that involves the activation of cancer cell migration and invasion of the extracellular space. Cancer-associated fibroblasts (CAFs) are known inducers of cancer cell invasion. However, current in vitro invasion assays such as the Boyden chamber assay are cumbersome and low throughput. Therefore, there is an urgent need for new ex vivo, surrogate invasion assays that can faithfully recapitulate the cancer cell invasion process in vitro and are amenable to large-scale screening of small-molecule libraries in a high-throughput fashion. Here, we describe a well-established high-throughput three-dimensional (3D) spheroid invasion assay as a powerful tool to identify novel molecular targets that can potentially mediate CAF-dependent cancer cell invasion.

Access to Heart Failure Services in Canada: Findings of the Heart and Stroke National Heart Failure Resources and Services Inventory.

BACKGROUND: The rising incidence of heart failure (HF) in Canada necessitates commensurate resources dedicated to its management. Several health system partners launched an HF Action Plan to understand the current state of HF care in Canada and address inequities in access and resources. METHODS: A national Heart Failure Resources and Services Inventory (HF-RaSI) was conducted from 2020 to 2021 of all 629 acute care hospitals and 20 urgent care centres in Canada. The HF-RaSI consisted of 44 questions on available resources, service,s and processes across acute care hospitals and related ambulatory settings. RESULTS: HF-RaSIs were completed by 501 acute care hospitals and urgent care centres, representing 94.7% of all HF hospitalisations across Canada. Only 12.2% of HF care was provided by hospitals with HF expertise and resources, and 50.9% of HF admissions were in centres with minimal outpatient or inpatient HF capabilities. Across all Canadian hospitals, 28.7% did not have access to B-type natriuretic peptide testing, and only 48.1% had access to on-site echocardiography. Designated HF medical directors were present at 21.6% of sites (108), and 16.2% sites (81) had dedicated inpatient interdisciplinary HF teams. Among all of the sites, 28.1% (141) were HF clinics, and of those, 40.4% (57) had average wait times from referral to first appointment of more than 2 weeks. CONCLUSIONS: Significant gaps and geographic variation in delivery and access to HF services exist in Canada. This study highlights the need for provincial and national health systems changes and quality improvement initiatives to ensure equitable access to the appropriate evidence-based HF care.

Predicting 1-Year Mortality in Outpatients With Heart Failure With Reduced Left Ventricular Ejection Fraction: Do Empiric Models Outperform Physician Intuitive Estimates? A Multicenter Cohort Study.

BACKGROUND: Many studies have demonstrated that physicians often err in estimating patient prognosis. No studies have directly compared physician to model predictive performance in heart failure (HF). We aimed to compare the accuracy of physician versus model predictions of 1-year mortality. METHODS: This multicenter prospective cohort study on 11 HF clinics in 5 provinces in Canada included consecutive consented outpatients with HF with reduced left ventricular ejection fraction (<40%). By collecting clinical data, we calculated predicted 1-year mortality using the Seattle HF Model (SHFM), the Meta-Analysis Global Group in Chronic HF score, and the HF Meta-Score. HF cardiologists and family doctors, blinded to model predictions, estimated patient 1-year mortality. During 1-year follow-up, we recorded the composite end point of mortality, urgent ventricular assist device implant, or heart transplant. We compared physicians and model discrimination (C statistic), calibration (observed versus predicted event rate), and risk reclassification. RESULTS: The study included 1643 patients with ambulatory HF with a mean age of 65 years, 24% female, and mean left ventricular ejection fraction of 28%. Over 1-year follow-up, 9% had an event. The SHFM had the best discrimination (SHFM C statistic 0.76; HF Meta-Score 0.73; Meta-Analysis Global Group in Chronic Heart Failure 0.70) and calibration. Physicians' discrimination differed little (0.75 for HF cardiologists and 0.73 for family doctors) but both physician groups substantially overestimated risk by >10% in both low- and high-risk patients (poor calibration). In risk reclassification analysis, among patients without events, the SHFM better classified 51% in comparison to HF cardiologists and 43% in comparison to family doctors. In patients with events, the SHFM erroneously assigned lower risk to 44% in comparison to HF cardiologists and 34% in comparison to family doctors. CONCLUSIONS: Family doctors and HF cardiologists showed adequate risk discrimination, with however substantial overestimation of absolute risk. Predictive models showed higher accuracy. Incorporating models in family and HF cardiology practices may improve patient care and resource use in HF with reduced left ventricular ejection fraction. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04009798.

Canadian Cardiovascular Society-Canadian Heart Failure Society Focused Clinical Practice Update of Patients With Differing Heart Failure Phenotypes.

A number of societies produce heart failure (HF) management guidelines, comprising official recommendations on the basis of recent research discoveries, but their applicability to specific situations encountered in daily practice might be difficult. In this clinical practice update we aim to provide responses to fundamental questions that face health care providers, like appropriate timing for the introduction and optimization of different classes of medication according to specific patient phenotypes, when second-line therapies and valvular interventions should be considered, and management of difficult clinical scenarios such as cardiorenal syndrome and frailty. A consensus-based methodology was used. Approaches to 5 different phenotypes are presented: (1) The wet HF phenotype is the easiest to manage, decongestion being performed alongside introduction of guideline-directed medical therapy (GDMT); (2) The de novo HF phenotype requires the introduction of the 4 pillars of GDMT, personalizing the order on the basis of the individuals' biological and physiological characteristics; (3) The worsening HF phenotype is a marker of poor prognosis, and therefore should motivate optimization of GDMT, start second-line therapies, and/or reevaluate goals of care/advanced HF therapies; (4) The cardiorenal phenotypes require correct volume assessment, because renal function usually improves with decongestion; and (5) The frail HF phenotype require special attention, careful drug titration, and consideration of cardiac rehabilitation programs. In conclusion, specific common HF phenotypes call for a personalized approach to improve adoption of the HF guidelines into clinical practice.

Patient Eligibility for Established and Novel Guideline-Directed Medical Therapies After Acute Heart Failure Hospitalization.

BACKGROUND: Acute heart failure (AHF) hospitalization presents an opportunity to optimize pharmacotherapy to improve outcomes. OBJECTIVES: This study's aim was to define eligibility for initiation of guideline-directed medical therapy and newer heart failure (HF) agents from recent clinical trials in the AHF population. METHODS: The authors analyzed patients with an AHF admission within the CAN-HF (Canadian Heart Failure) registry between January 2017 and April 2020. Heart failure with reduced ejection fraction (HFrEF) was defined as left ventricular ejection fraction (LVEF) ≤40% and heart failure with preserved ejection fraction (HFpEF) as LVEF >40%. Eligibility was assessed according to the major society guidelines or enrollment criteria from recent landmark clinical trials. RESULTS: A total of 809 patients with documented LVEF were discharged alive from hospital: 455 with HFrEF and 354 with HFpEF; of these patients, 284 had a de novo presentation and 525 had chronic HF. In HFrEF patients, eligibility for therapies was 73.6% for angiotensin receptor-neprilysin inhibitors (ARNIs), 94.9% for beta-blockers, 84.4% for mineralocorticoid receptor antagonists (MRAs), 81.1% for sodium-glucose cotransporter-2 (SGLT2) inhibitors, and 15.6% for ivabradine. Additionally, 25.9% and 30.1% met trial criteria for vericiguat and omecamtiv mecarbil, respectively. Overall, 71.6% of patients with HFrEF (75.5% de novo, 69.5% chronic HF) were eligible for foundational quadruple therapy. In the HFpEF population, 37.6% and 59.9% were eligible for ARNIs and SGLT2 inhibitors based on recent trial criteria, respectively. CONCLUSIONS: The majority of patients admitted with AHF are eligible for foundational quadruple therapy and additional novel medications across a spectrum of HF phenotypes.

Trial of an Intervention to Improve Acute Heart Failure Outcomes.

BACKGROUND: Patients with acute heart failure are frequently or systematically hospitalized, often because the risk of adverse events is uncertain and the options for rapid follow-up are inadequate. Whether the use of a strategy to support clinicians in making decisions about discharging or admitting patients, coupled with rapid follow-up in an outpatient clinic, would affect outcomes remains uncertain. METHODS: In a stepped-wedge, cluster-randomized trial conducted in Ontario, Canada, we randomly assigned 10 hospitals to staggered start dates for one-way crossover from the control phase (usual care) to the intervention phase, which involved the use of a point-of-care algorithm to stratify patients with acute heart failure according to the risk of death. During the intervention phase, low-risk patients were discharged early (in ≤3 days) and received standardized outpatient care, and high-risk patients were admitted to the hospital. The coprimary outcomes were a composite of death from any cause or hospitalization for cardiovascular causes within 30 days after presentation and the composite outcome within 20 months. RESULTS: A total of 5452 patients were enrolled in the trial (2972 during the control phase and 2480 during the intervention phase). Within 30 days, death from any cause or hospitalization for cardiovascular causes occurred in 301 patients (12.1%) who were enrolled during the intervention phase and in 430 patients (14.5%) who were enrolled during the control phase (adjusted hazard ratio, 0.88; 95% confidence interval [CI], 0.78 to 0.99; P = 0.04). Within 20 months, the cumulative incidence of primary-outcome events was 54.4% (95% CI, 48.6 to 59.9) among patients who were enrolled during the intervention phase and 56.2% (95% CI, 54.2 to 58.1) among patients who were enrolled during the control phase (adjusted hazard ratio, 0.95; 95% CI, 0.92 to 0.99). Fewer than six deaths or hospitalizations for any cause occurred in low- or intermediate-risk patients before the first outpatient visit within 30 days after discharge. CONCLUSIONS: Among patients with acute heart failure who were seeking emergency care, the use of a hospital-based strategy to support clinical decision making and rapid follow-up led to a lower risk of the composite of death from any cause or hospitalization for cardiovascular causes within 30 days than usual care. (Funded by the Ontario SPOR Support Unit and others; COACH ClinicalTrials.gov number, NCT02674438.).

The State of Heart Failure Care in Canada: Minimal Improvement in Readmissions Over Time Despite an Increased Number of Evidence-Based Therapies.

Background: An unanswered question is whether the combination of advances in medical and device therapy over the past decade has translated into improved outcomes for patients with heart failure (HF) in Canada. Methods: The Canadian Institute for Health Information (CIHI) Hospital Morbidity Database was used to identify hospitalizations for HF among patients aged 18 years and older in Canadian hospitals during fiscal years 2009/2010 and 2018/2019. We assessed interprovincial differences in age, sex, length of stay (LOS), discharge disposition, type of admitting hospital, and most responsible service, for all HF admissions. National and provincial rates of HF admissions and all-cause 30-day readmissions were calculated. Results: After adjusting for age, the rate of HF admissions in Canada was 216 per 100,000 population in 2009/2010 and 2018/2019. The majority of patients with HF were admitted to general internal medicine and community hospitals in both 2009/2010 and 2018/2019. The national, crude, all-cause 30-day readmission rate stayed constant at 20.6%, and the majority of patients were readmitted with the diagnosis of HF in both 2009/2010 (62.5%) and 2018/2019 (59.0%). Median and interquartile range of HF LOS also remained unchanged at 7 days (3-14). Conclusions: The national rate of HF admissions, 30-day readmissions, and HF LOS have remained unchanged from 2009/2010 to 2018/2019, despite advances in medical and device therapy during this timeframe.

Introduction: La question demeure de savoir si, au cours de la dernière décennie au Canada, la combinaison des avancées dans les traitements médicaux et à l'aide d'un dispositif s'est traduite par de meilleurs résultats cliniques chez les patients atteints d'insuffisance cardiaque (IC). Méthodes: Nous avons utilisé la base de données sur la morbidité hospitalière de l'Institut canadien d'information sur la santé (ICIS) pour recenser les hospitalisations de patients atteints d'IC âgés de 18 ans et plus dans les hôpitaux du Canada au cours des années financières 2009/2010 et 2018/2019. Nous avons évalué les différences interprovinciales selon l'âge, le sexe, la durée du séjour (DDS), l'état à la sortie, le type d'hôpital à l'admission et le service le plus tenu à la prise en charge du patient, de toutes les admissions liées à l'IC. Nous avons calculé les taux provinciaux et national des admissions liées à l'IC et les réadmissions toutes causes confondues dans les 30 jours. Résultats: Après ajustement en fonction de l'âge, le taux d'admissions liées à l'IC au Canada était de 216 pour 100 000 habitants en 2009/2010 et en 2018/2019. La majorité des patients atteints d'IC avaient été admis en médecine interne générale et dans les hôpitaux communautaires en 2009/2010 et en 2018/2019. Le taux national, brut, toutes causes confondues de réadmissions dans les 30 jours était resté constant à 20,6 %, et la majorité des patients avaient eu des réadmissions liées au diagnostic d'IC en 2009/2010 (62,5 %) et en 2018/2019 (59,0 %). L'écart interquartile et la médiane de la DDS liée à l'IC étaient aussi demeurés inchangés après 7 jours (3-14). Conclusions: Le taux national des admissions liées à l'IC, les réadmissions dans les 30 jours et la DDS liée à l'IC étaient demeurés inchangés de 2009/2010 à 2018/2019, malgré les avancées des traitements médicaux et à l'aide d'un dispositif durant cette période de temps.

The Canadian Heart Failure (CAN-HF) Registry: A Canadian Multicentre, Retrospective Study of Inpatients With Heart Failure.

Background: Despite recent advances in the management of patients with heart failure (HF), national data regarding the quality of care provided are lacking. The Canadian Heart Failure (CAN-HF) Registry was designed to obtain contemporary, real-world data describing the management of patients with HF. Methods: Quality of care in patients admitted for acute HF (AHF), in relation to guidelines and national HF quality indicators, was assessed as part of the CAN-HF Registry study. Results: A total of 943 patients admitted to the hospital with AHF were included in this analysis. Patient weight was not recorded on admission for 26% of patients, with daily weight being captured in only 61% of patients. Only 54% of inpatients received left ventricular ejection fraction assessment while hospitalized. Patient education was documented in 31% of patients prior to discharge, with 51% receiving instructions to follow up with a specialist upon discharge, and 2% being referred to a cardiac rehabilitation program. Although use of guideline-directed medical therapy increased during hospitalization, the proportions of patients receiving renin-angiotensin-aldosterone inhibition (63%), beta-blockade (80%), and mineralocorticoid receptor antagonist (40%) upon discharge indicate that potential room for improvement exists. Conclusions: The CAN-HF Registry study demonstrated a potential quality-of-care gap in the management of patients admitted with AHF.

Contexte: Malgré les progrès récents dans la prise en charge des patients souffrant d'insuffisance cardiaque (IC), on note un manque flagrant de données nationales sur la qualité des soins prodigués. Le Registre canadien sur l'insuffisance cardiaque (Canadian Heart Failure Registry ou CAN-HF) a été conçu pour colliger des données contemporaines du monde réel décrivant la prise en charge des patients atteints d'IC. Méthodologie: Dans le cadre de l'étude CAN-HF Registry, on a évalué la qualité des soins prodigués aux patients hospitalisés pour cause d'IC aiguë (ICA) par rapport aux lignes directrices et aux indicateurs nationaux de qualité applicables à l'IC. Résultats: Notre analyse a porté sur 943 patients hospitalisés pour cause d'ICA. Le poids corporel n'avait pas été noté chez 26 % des patients au moment de leur admission à l'hôpital. Les mesures quotidiennes du poids avaient été prises chez 61 % des patients seulement. L'évaluation de la fraction d'éjection ventriculaire gauche avait été effectuée chez seulement 54 % des patients hospitalisés. Selon les documents consultés, 31 % des patients avaient reçu de l'information et des instructions avant de recevoir leur congé de l'hôpital; 51 % avaient reçu la directive de consulter un spécialiste pour assurer leur suivi après leur sortie de l'hôpital et 2 % avaient été orientés vers un programme de réadaptation cardiaque. Si le traitement médical administré durant l'hospitalisation était davantage conforme aux lignes directrices, les proportions de patients ayant reçu des inhibiteurs de la rénine-angiotensine-aldostérone (63 %), des bêtabloquants (80 %) et des antagonistes des récepteurs minéralocorticoïdes (40 %) à leur sortie de l'hôpital indiquent qu'il y a encore des progrès à faire. Conclusions: L'étude CAN-HF Registry a démontré qu'il pouvait y avoir des lacunes dans la qualité des soins prodigués aux patients hospitalisés pour cause d'ICA.

Increased Mortality in Patients With Acutely Decompensated Heart Failure During the COVID-19 Pandemic in Toronto, Canada.

Background: Coronavirus disease 2019 (COVID-19) has resulted in a reduction in patients seeking timely consultation for illnesses that are not related to COVID-19. Previously, we reported a decline in the number of emergency department (ED) visits and hospitalizations for acute decompensated heart failure (ADHF) during the 2020 COVID-19 pandemic vs that in 2019. We aimed to determine the consequences of these early trends on ADHF-patient morbidity and mortality. Methods: We compared consecutive patients presenting with ADHF to 3 academic medical centres in Toronto, Canada from March 1-September 28, 2020, vs those from the same time period in 2019. We used multivariate logistic regression models to evaluate whether the odds of hospitalization after presenting to the ED, recurrent ED visits or readmission within 30 days, and in-hospital all-cause mortality differed by timeframe. Results: We observed that, during the COVID-19 pandemic, a lower total number of patients presented to the hospital with ADHF, vs that in 2019. Despite this difference, the probability of being admitted to the hospital did not differ for patients seen in 2020 vs 2019. Among ADHF patients admitted to the hospital, however, we observed a significantly higher proportion being admitted to the intensive care unit, and a relative 66% increase in in-hospital mortality during the 2020 COVID-19 era, compared to that in 2019. Conclusions: Our findings suggest that improved messaging may be needed for patients living with chronic health conditions, including HF, during the pandemic, to educate and encourage them to present to hospital services when in need.

Contexte: La maladie à coronavirus 2019 (COVID-19) s'est traduite par une diminution du nombre de patients demandant des consultations médicales pour des états de santé sans lien avec la COVID-19. Nous avons précédemment décrit une diminution du nombre de consultations aux urgences et d'hospitalisations en raison d'une insuffisance cardiaque aiguë décompensée (ICAD) au cours de la pandémie de COVID-19 en 2020, par rapport à 2019. Nous avons voulu déterminer les conséquences de ces tendances précoces sur la morbidité et la mortalité chez les patients atteints d'ICAD. Méthodologie: Nous avons comparé les données pour les patients consécutifs atteints d'ICAD de trois centres médicaux hospitaliers de Toronto (Canada) traités entre le 1er mars et le 28 septembre 2020 et durant la même période en 2019. À l'aide de modèles de régression logistique multivariée, nous avons évalué les différences entre les probabilités d'hospitalisation après une consultation aux urgences, de consultations récurrentes aux urgences ou de réadmission dans les 30 jours suivant la visite initiale, ainsi que de mortalité hospitalière toutes causes confondues pour les patients vus durant ces deux périodes. Résultats: Durant la pandémie de COVID-19, le nombre total de patients atteints d'ICAD s'étant présentés à l'hôpital a été plus faible que celui relevé pour l'année 2019. Malgré cet écart, la probabilité d'admission à l'hôpital ne différait pas pour les patients vus en 2020 et en 2019. Parmi les patients atteints d'ICAD admis à l'hôpital, nous avons toutefois observé une proportion significativement plus élevée de séjours aux soins intensifs et une hausse relative de 66 % du taux de mortalité hospitalière, en comparant les données de 2020 (pandémie de COVID-19) et celles de 2019. Conclusions: Nos observations indiquent qu'il pourrait être nécessaire d'améliorer la communication avec les patients atteints de problèmes de santé chroniques (y compris l'IC) en situation de pandémie de façon à mieux les informer et à les encourager à consulter les services hospitaliers lorsque nécessaire.

Scaffold-Free Strategy Using a PEG-Dextran Aqueous Two-Phase-System for Corneal Tissue Repair.

Forming thin tissue constructs with minimal extracellular matrix surrounding them is important for tissue engineering applications. Here, we explore and optimize a strategy that enables rapid fabrication of scaffold-free corneal tissue constructs using the liquid-liquid interface of an aqueous two-phase system (ATPS) that is based on biocompatible polymers, dextran and polyethylene glycol. Intact tissue-like constructs, made of corneal epithelial or endothelial cells, can be formed on the interface between the two liquid phases of ATPS within hours and subsequently collected simply by removing the liquid phases. The formed corneal cell constructs express essential physiological markers and have preserved viability and proliferative ability in vitro. The corneal epithelial cell constructs are also able to re-epithelialize the corneal epithelial wound in vitro. The results suggest the promise of our reported strategy in corneal repair.

Virtual reality and augmented reality- emerging screening and diagnostic techniques in ophthalmology: A systematic review.

In health care, virtual reality (VR) and augmented reality (AR) have been applied extensively for many purposes. Similar to other technologies such as telemedicine and artificial intelligence, VR and AR may improve clinical diagnosis and screening services in ophthalmology by alleviating current problems, including workforce shortage, diagnostic error, and underdiagnosis. In the past decade a number of studies and products have used VR and AR concepts to build clinical tests for ophthalmology, but comprehensive reviews on these studies are limited. Therefore, we conducted a systematic review on the use of VR and AR as a diagnostic and screening tool in ophthalmology. We identified 26 studies that implemented a variety of VR and AR tests on different conditions, including VR cover tests for binocular vision disorder, VR perimetry for glaucoma, and AR slit lamp biomicroscopy for retinal diseases. In general, while VR and AR tools can become standardized, automated, and cost-effective tests with good user experience, several weaknesses, including unsatisfactory accuracy, weak validation, and hardware limitations, have prevented these VR and AR tools from having wider clinical application. Also, a comparison between VR and AR is made to explain why studies have predominantly used VR rather than AR.

Modeling the Role of Cancer-Associated Fibroblasts in Tumor Cell Invasion.

The major cause of cancer-related deaths can be attributed to the metastatic spread of tumor cells-a dynamic and complex multi-step process beginning with tumor cells acquiring an invasive phenotype to allow them to travel through the blood and lymphatic vessels to ultimately seed at a secondary site. Over the years, various in vitro models have been used to characterize specific steps in the cascade to collectively begin providing a clearer picture of the puzzle of metastasis. With the discovery of the TME's supporting role in activating tumor cell invasion and metastasis, these models have evolved in parallel to accommodate features of the TME and to observe its interactions with tumor cells. In particular, CAFs that reside in reactive tumor stroma have been shown to play a substantial pro-invasive role through their matrix-modifying functions; accordingly, this warranted further investigation with the development and use of invasion assays that could include these stromal cells. This review explores the growing toolbox of assays used to study tumor cell invasion, from the simple beginnings of a tumor cell and extracellular matrix set-up to the advent of models that aim to more closely recapitulate the interplay between tumor cells, CAFs and the extracellular matrix. These models will prove to be invaluable tools to help tease out the intricacies of tumor cell invasion.

A systematic review of multimodal clinical biomarkers in the management of thyroid eye disease.

Thyroid Eye Disease (TED) is an autoimmune disease that affects the extraocular muscles and periorbital fat. It most commonly occurs with Graves' Disease (GD) as an extrathyroidal manifestation, hence, it is also sometimes used interchangeably with Graves' Ophthalmopathy (GO). Well-known autoimmune markers for GD include thyroid stimulating hormone (TSH) receptor antibodies (TSH-R-Ab) which contribute to hyperthyroidism and ocular signs. Currently, apart from radiological investigations, detection of TED is based on clinical signs and symptoms which is largely subjective, with no established biomarkers which could differentiate TED from merely GD. We evaluated a total of 28 studies on potential biomarkers for diagnosis of TED. Articles included were published in English, which investigated clinical markers in tear fluid, orbital adipose-connective tissues, orbital fibroblasts and extraocular muscles, serum, thyroid tissue, as well as imaging biomarkers. Results demonstrated that biomarkers with reported diagnostic power have high sensitivity and specificity for TED, including those using a combination of biomarkers to differentiate between TED and GD, as well as the use of magnetic resonance imaging (MRI). Other biomarkers which were upregulated include cytokines, proinflammatory markers, and acute phase reactants in subjects with TED, which are however, deemed less specific to TED. Further clinical investigations for these biomarkers, scrutinising their specificity and sensitivity on a larger sample of patients, may point towards selection of suitable biomarkers for aiding detection and prognosis of TED in the future.

Automated digital counselling with social network support as a novel intervention for patients with heart failure: protocol for randomised controlled trial.

INTRODUCTION: Heart failure (HF) symptoms improve through self-care, for which adherence remains low among patients despite the provision of education for these behaviours by clinical teams. Open Access Digital Community Promoting Self-Care, Peer Support and Health Literacy (ODYSSEE-vCHAT) combines automated digital counselling with social network support to improve mortality and morbidity, engagement with self-care materials, and health-related quality of life. METHODS AND ANALYSIS: Use of ODYSSEE-vCHAT via Internet-connected personal computer by 162 HF patients will be compared with a control condition over 22 months. The primary outcome is a composite index score of all-cause mortality, all-cause emergency department visits, and HF-related hospitalisation at trial completion. Secondary outcomes include individual components of the composite index, engagement with self-care materials, and patient-reported measures of physical and psychosocial well-being, disease management, health literacy, and substance use. Patients are recruited from tertiary care hospitals in Toronto, Canada and randomised on a 1:1 ratio to both arms of the trial. Online assessments occur at baseline (t=0), months 4, 8 and 12, and trial completion. Ordinal logistic regression analyses and generalised linear models will evaluate primary and secondary outcomes. ETHICS AND DISSEMINATION: The trial has been approved by the research ethics boards at the University Health Network (20-5960), Sunnybrook Hospital (5117), and Mount Sinai Hospital (21-022-E). Informed consent of eligible patients occurs in person or online. Findings will be shared with key stakeholders and the public. Results will allow for the preparation of a Canada-wide phase III trial to evaluate the efficacy of ODYSSEE-vCHAT in improving clinical outcomes and raising the standard of outpatient care. TRIAL REGISTRATION NUMBER: NCT04966104.