Transcatheter-Based Interventions for Tetralogy of Fallot Across All Age Groups.

Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease. Palliative procedures, either surgical or transcatheter, aim to improve oxygen saturation, affording definitive procedures at a later stage. Transcatheter interventions have been used before and after surgical palliative or definitive repair in children and adults. This review aims to provide an overview of the different catheter-based interventions for TOF across all age groups, with an emphasis on palliative interventions, such as patent arterial duct stenting, right ventricular outflow tract stenting, or balloon pulmonary valvuloplasty in infants and children and transcatheter pulmonary valve replacement in adults with repaired TOF, including the available options for a large, dilated native right ventricular outflow tract.

Balloon valvuloplasty for annular- and leaflet-level tricuspid stenosis: Report of cases and literature review.

Congenital tricuspid valve stenosis is extremely rare. We describe 2 cases of patients with adult congenital heart disease with hypoplastic tricuspid valve annulus who were symptomatic from annular- and leaflet-level tricuspid stenosis. The patients underwent transcatheter balloon valvuloplasty with good clinical outcomes. An extensive literature review and analysis of various procedural strategies suggests that percutaneous balloon valvuloplasty may be a reasonable therapeutic choice as a first-line therapy or when open surgical repair is associated with prohibitively high mortality. This procedure can be performed either as a destination therapy or as a bridge to valve replacement.

Cost-Utility Analysis of Geriatric Assessment and Management in Older Adults With Cancer: Economic Evaluation Within 5C Trial.

PURPOSE: Geriatric assessment (GA) is a guideline-recommended approach to optimize cancer management in older adults. We conducted a cost-utility analysis alongside the 5C randomized controlled trial to compare GA and management (GAM) plus usual care (UC) against UC alone in older adults with cancer. METHODS: The economic evaluation, conducted from societal and health care payer perspectives, used a 12-month time horizon. The Canadian 5C study randomly assigned patients to receive GAM or UC. Quality-adjusted life-years (QALYs) were measured using the EuroQol five dimension-5L questionnaire and health care utilization using cost diaries and chart reviews. We evaluated the incremental net monetary benefit (INMB) for the full sample and preselected subgroups. RESULTS: A total of 350 patients were included, of whom 173 received GAM and 177 UC. At 12 months, the average QALYs per patient were 0.728 and 0.751 for GAM and UC, respectively (ΔQALY, -0.023 [95% CI, -0.076 to 0.028]). Considering a societal perspective, the total average costs (in 2021 Canadian dollars) per patient were $46,739 and $45,177 for GAM and UC, respectively (ΔCost, $1,563 [95% CI, -$6,583 to $10,403]). At a cost-effectiveness threshold of $50,000/QALY, GAM was not cost-effective compared with UC (INMB, -$2,713 [95% CI, -$11,767 to $5,801]). The INMB was positive ($2,984 [95% CI, -$7,050 to $14,179]; probability of being cost-effective, 72%) for patients treated with curative intent, but remained negative for patients treated with palliative intent (INMB, -$9,909 [95% CI, -$24,436 to $4,153]). Findings were similar considering a health care payer perspective. CONCLUSION: To our knowledge, this is the first cost-utility analysis of GAM in cancer. GAM was cost-effective for patients with cancer treated with curative but not with palliative intent. The study provides further considerations for future adoption of GAM in practice.

Transcatheter left atrial appendage occlusion in patients with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Chronic kidney disease (CKD) is a risk factor for embolic stroke, and many nonvalvular atrial fibrillation (NVAF) patients have concomitant CKD. Anticoagulation therapy can be challenging in CKD due to increased bleeding risk, and left atrial appendage occlusion (LAAO) may be a promising alternative. OBJECTIVE: This systematic review aimed to consolidate current evidence on the safety and effectiveness of transcatheter LAAO in patients with CKD and end-stage renal disease (ESRD). METHODS: Medline, Cochrane, and Embase databases were searched from inception to September 2, 2022. We conducted a meta-analysis if an outcome was evaluated in at least two similar studies. RESULTS: We included 15 studies with 77,780 total patients. Of the 15 studies, 11 had a cohort design (five prospective and six retrospective), and four were case series. Patients with CKD were older and had a higher prevalence of comorbidities than non-CKD patients. The two groups did not differ in procedural failure rate, vascular complications, or pericardial tamponade. CKD patients exhibited higher odds of in-hospital acute kidney injury (AKI) and bleeding, longer-term bleeding, and mortality than those without CKD. The risk of in-hospital and longer-term cardioembolic events was similar between CKD and non-CKD populations (odds ratio = 1.01 [95% CI 0.70-1.15] and 1.05 [95% CI 0.55-2.00], respectively). Patients with ESRD had higher odds of in-hospital mortality and cardioembolic events than non-ESRD patients, with no differences in risk of pericardial tamponade. CONCLUSIONS: Based on observational studies, LAAO may be an effective option to prevent cardioembolic events in CKD. However, CKD patients may have higher odds of AKI and in-hospital and long-term bleeding and mortality. The adverse clinical outcomes observed in CKD patients may be attributed to this population's high burden of comorbidities, especially among those with ERSD, rather than the LAAO procedure itself. To ensure maximum clinical benefit, careful patient selection, management, and surveillance involving multidisciplinary teams are essential for CKD patients undergoing LAAO. Transcatheter Left Atrial Appendage Occlusion (laao) Can Prevent Cardioembolic Events In Chronic Kidney Disease (ckd) Patients. However, Ckd Patients, Particularly Those With End-stage Renal Disease/dialysis (esrd), May Face Increased Odds Of Acute Kidney Injury, In-hospital And Long-term Bleeding, And Mortality. Notably, These Adverse Outcomes In Ckd Patients May Be Linked To Their High Comorbidity Burden, Particularly In Those With Esrd, Rather Than The Laao Procedure Itself. Careful Patient Selection, Management, And Surveillance Involving Multidisciplinary Teams Are Essential For Ckd Patients Undergoing Laao To Ensure Maximum Clinical Benefit Transcatheter left atrial appendage occlusion (LAAO) can prevent cardioembolic events in chronic kidney disease (CKD) patients. However, CKD patients, particularly those with end-stage renal disease/dialysis (ESRD), may face increased odds of acute kidney injury, in-hospital and long-term bleeding, and mortality. Notably, these adverse outcomes in CKD patients may be linked to their high comorbidity burden, particularly in those with ESRD, rather than the LAAO procedure itself. Careful patient selection, management, and surveillance involving multidisciplinary teams are essential for CKD patients undergoing LAAO to ensure maximum clinical benefit.

Aortic luminal remodeling after intravascular stent therapy for coarctation of the aorta: intermediate results.

OBJECTIVE: Outcomes after adult coarctation of the aorta (CoA) stenting is scant. We explored predictors of aortic remodeling after stent implantation and report early- and intermediate-term clinical outcomes. METHODS: Adult patients who underwent stenting between July 2003 and December 2017 were included in this single-center retrospective study. We created a novel index of aortic volumetric and diameter changes using computed tomography (CT)/magnetic resonance (MR) images measured through TeraRecon and AngioQ. Predictors of aortic remodeling were explored using univariable linear regression analysis. RESULTS: One hundred and thirty-four patients (mean age 35.2 years, 58.2% men) underwent CoA stenting. Paired aortic diameter measurements were available in 20 patients, and 40 paired patients in volumetric measurements. There was significant reduction in aortic diameter immediately proximal to the left carotid and subclavian arteries, and the aorta distal to the stenosis (P less than .05) at follow-up. There was a significant volumetric reduction in the ascending aorta, aortic arch, and the aortic segment most proximal to the top of the stent (P less than .05). Univariate predictors of aortic remodeling included sex, age, presence of previous surgical repair, aortic valve morphology, and the number of antihypertensive medications. Mean follow-up time was 4.0 ± 3.8 years, where 5% of patients underwent reintervention due to complications, 3% developed aneurysms, and 3% had stent fractures. CONCLUSIONS: This study is the first to examine the anatomical changes that occur in the aorta post stent repair through analysis of serial imaging. Patients with stent-repaired coarctation demonstrated negative remodeling in multiple areas of the aorta with regards to the aortic diameter and volumetric measurements.

Cold-stored platelets for acute bleeding in cardiac surgical patients: a narrative review.

PURPOSE: Cold-stored platelets (CSP) are an increasingly active topic of international research. They are maintained at 1-6 °C, in contrast to standard room-temperature platelets (RTP) kept at 20-24 °C. Recent evidence suggests that CSP have superior hemostatic properties compared with RTP. This narrative review explores the application of CSP in adult cardiac surgery, summarizes the preclinical and clinical evidence for their use, and highlights recent research. SOURCE: A targeted search of MEDLINE and other databases up to 24 February 2022 was conducted. Search terms combined concepts such as cardiac surgery, blood, platelet, and cold-stored. Searches of trial registries ClinicalTrials.gov and WHO International Clinical Trials Registry Platform were included. Articles were included if they described adult surgical patients as their population of interest and an association between CSP and clinical outcomes. References of included articles were hand searched. PRINCIPAL FINDINGS: When platelets are stored at 1-6 °C, their metabolic rate is slowed, preserving hemostatic function for increased storage duration. Cold-stored platelets have superior adhesion characteristics under physiologic shear conditions, and similar or superior aggregation responses to physiologic agonists. Cold-stored platelets undergo structural, metabolic, and molecular changes which appear to "prime" them for hemostatic activity. While preliminary, clinical evidence supports the conduct of trials comparing CSP with RTP for patients with platelet-related bleeding, such as those undergoing cardiac surgery. CONCLUSION: Cold-stored platelets may have several advantages over RTP, including increased hemostatic capacity, extended shelf-life, and reduced risk of bacterial contamination. Large clinical trials are needed to establish their potential role in the treatment of acutely bleeding patients.

RéSUMé: OBJECTIF: Les plaquettes conservées au froid (PCF) sont un sujet de recherche internationale de plus en plus populaire. Ces plaquettes sont maintenues à une température de 1-6 °C, contrairement aux plaquettes standard conservées à température ambiante (PTA), maintenues à 20­24 °C. Des données probantes récentes suggèrent que les PCF ont des propriétés hémostatiques supérieures aux PTA. Ce compte rendu narratif explore l'application de PCF en chirurgie cardiaque chez l'adulte, résume les données probantes précliniques et cliniques de leur utilisation, et met en évidence les recherches récentes. SOURCES: Une recherche ciblée dans MEDLINE et d'autres bases de données jusqu'au 24 février 2022 a été effectuée. Les termes de recherche combinaient des concepts en anglais tels que cardiac surgery, blood, platelet et cold-stored (soit chirurgie cardiaque, plaquette, et entreposage frigorifique). Des recherches dans les registres d'études ClinicalTrials.gov et le système d'enregistrement international des essais cliniques (ICTRP) de l'OMS ont été incluses. Les articles ont été inclus s'ils décrivaient des patient·es adultes de chirurgie en tant que population d'intérêt et une association entre les PCF et les issues cliniques. Les références des articles inclus ont fait l'objet d'une recherche manuelle. CONSTATATIONS PRINCIPALES: Lorsque les plaquettes sont conservées entre 1 et 6 °C, leur taux métabolique est ralenti, préservant la fonction hémostatique pour une durée d'entreposage accrue. Les plaquettes conservées au froid ont des caractéristiques d'adhésion supérieures dans des conditions de cisaillement physiologique et des réponses d'agrégation similaires ou supérieures aux agonistes physiologiques. Les plaquettes conservées au froid subissent des changements structurels, métaboliques et moléculaires qui semblent les « amorcer ¼ pour une activité hémostatique. Bien que préliminaires, les données probantes cliniques appuient la réalisation d'études comparant les PCF aux PTA chez la patientèle présentant des saignements liés aux plaquettes, tels que les personnes bénéficiant d'une chirurgie cardiaque. CONCLUSION: Les plaquettes conservées au froid peuvent présenter plusieurs avantages par rapport aux PTA, notamment une capacité hémostatique accrue, une durée de conservation prolongée et un risque réduit de contamination bactérienne. De grands essais cliniques sont nécessaires pour établir leur rôle potentiel dans le traitement de la patientèle en hémorragie aiguë.

Effectiveness of geriatric assessment and management in older cancer patients: a systematic review and meta-analysis.

BACKGROUND: Frailty and multimorbidity among older cancer patients affect treatment tolerance and efficacy. Comprehensive geriatric assessment and management is recommended to optimize cancer treatment, but its effect on various outcomes remains uncertain. OBJECTIVE: Our objective was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) and cost-effectiveness studies comparing comprehensive geriatric assessment (with or without implementation of recommendations) to usual care in older cancer patients. METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane trials from inception to January 27, 2023, for RCTs and cost-effectiveness studies. Pooled estimates for outcomes were calculated using random-effects models. RESULTS: A total of 19 full-text articles representing 17 RCTs were included. Average participant age was 72-80 years, and 31%-62% were female. Comprehensive geriatric assessment type, mode of delivery, and evaluated outcomes varied across studies. Meta-analysis revealed no difference in risk of mortality (risk ratio [RR] = 1.08. 95% confidence interval [CI] = 0.91 to 1.29), hospitalization (RR = 0.92, 95% CI = 0.77 to 1.10), early treatment discontinuation (RR = 0.89, 95% CI = 0.67 to 1.19), initial dose reduction (RR = 0.99, 95% CI = 0.99 to 1.26), and subsequent dose reduction (RR = 0.87, 95% CI = 0.70 to 1.09). However, the risk of treatment toxicity was statistically significantly lower in the comprehensive geriatric assessment group (RR = 0.78, 95% CI = 0.70 to 0.86). No cost-effectiveness studies were identified. CONCLUSION: Compared with usual care, comprehensive geriatric assessment was not associated with a difference in risk of mortality, hospitalization, treatment discontinuation, and dose reduction but was associated with a lower risk of treatment toxicity indicating its potential to optimize cancer treatment in this population. Further research is needed to evaluate cost-effectiveness.

A systematic review of contrast-enhanced computed tomography calcium scoring methodologies and impact of aortic valve calcium burden on TAVI clinical outcomes.

Different methodologies have been used to assess the role of AV calcification (AVC) on TAVI outcomes. This systematic review aims to describe the burden of AVC, synthesize the different methods of calcium score quantification, and evaluate the impact of AVC on outcomes after TAVI. We included studies of TAVI patients who had reported AV calcium scoring by contrast-enhanced multidetector CT and the Agatston method. The impact of calcification on TAVI outcomes without restrictions on follow-up time or outcome type was evaluated. Results were reported descriptively, and a meta-analysis was conducted when feasible. Sixty-eight articles were included, with sample sizes ranging from 23 to 1425 patients. Contrast-enhanced calcium scoring was reported in 30 studies, calcium volume score in 28 studies, and unique scoring methods in two. All studies with calcium volume scores had variable protocols, but most utilized a modified Agatston method with variable attenuation threshold values of 300-850 HU. Eight studies used the Agatston method, with the overall mean AV calcium score in studies published from 2010 to 2012 of 3342.9 AU [95%CI: 3150.4; 3535.4, I2 â€‹= â€‹0%]. The overall mean score was lower and heterogenous in studies published from 2014 to 2020 (2658.9 AU [95% CI: 2517.3; 2800.5, I2 â€‹= â€‹79%]. Most studies reported a positive association between calcium burden and increased risk of adverse outcomes, including implantation of permanent pacemaker (7/8 studies), paravalvular leak (13/13 studies), and risk of aortic rupture (2/2 studies). AVC quantification methodology with contrast-enhanced CT is still variable. AVC negatively impacts TAVI outcomes independently of the quantification method.

Long-Term Outcomes of Unrepaired Isolated Partial Anomalous Pulmonary Venous Connection With an Intact Atrial Septum.

The natural history of an unrepaired isolated partial anomalous pulmonary venous connection(s) (PAPVC) and the absence of other congenital anomalies remains unclear. This study aimed to expand the understanding of the clinical outcomes in this population. Isolated PAPVC with an intact atrial septum is a relatively uncommon condition. There is the perception that patients with isolated PAPVC are usually asymptomatic, that the lesion generally has a limited hemodynamic impact, and that surgical repair is rarely justified. For this retrospective study, we reviewed our institutional database to identify patients with either 1 or 2 anomalous pulmonary veins that drain a portion of but not the complete ipsilateral lung. Patients with previous surgical cardiac repair, coexistence of other congenital cardiac anomalies that would result in either pretricuspid or post-tricuspid loading of the right ventricle (RV), or scimitar syndrome were excluded. We reviewed their clinical course over the follow-up period. We identified 53 patients; 41 with a single and 12 with 2 anomalous PAPVC. A total of 30 patients (57%) were men, with a mean age at the latest clinic visit of 47 ± 19 years (18 to 84 years). Turner syndrome (6 of 53, 11.3%), bicuspid aortic valve (6 of 53, 11.3%), and coarctation of the aorta (5 of 53, 9.4%) were commonly associated anomalies. A single anomalous left upper lobe vein was the most commonly identified variation. More than half of the patients were asymptomatic. Cardiopulmonary exercise test demonstrated a maximal oxygen consumption of 73 ± 20% expected (36 to 120). Transthoracic echocardiography demonstrated a mean RV basal diameter of 4.4 ± 0.8 cm, RV systolic pressure of 38 ± 13 (16 to 84) mm Hg. A total of 8 patients (14.8%) had ≥moderate tricuspid regurgitation. Cardiac magnetic resonance in 42 patients demonstrated a mean RV end-diastolic volume index of 122 ±3 0 ml/m2 (66 to 188 ml/m2), of which in 8 (14.8%), it was >150 ml/m2. Magnetic resonance imaging-based Qp:Qs was 1.6 ± 0.3. A total of 5 patients (9.3%) had established pulmonary hypertension (mean pulmonary artery pressure ≥25 mm Hg). In conclusion, isolated single or dual anomalous pulmonary venous connection is not necessarily a benign congenital anomaly because a proportion of patients develop pulmonary hypertension and/or RV dilation. Regular follow-up and on-going patient surveillance with cardiac imaging is advised.

Factors Affecting Referral and Patient Access to Heart Function Clinics in Ontario: A Qualitative Study of Stakeholders.

Background: Though heart failure patients benefit from multidisciplinary care in heart function clinics (HFCs), utilization is suboptimal and inequitable. This study investigated factors influencing referral and patient access to HFCs from multiple stakeholders' perspectives, namely policy-makers (PM), providers at HFCs and patients. Methods: In this qualitative study, semi-structured interviews with a purposive sample of Ontario stakeholders were conducted between February-June 2020 and July-December 2022 (paused due to pandemic) via Teams. Interview transcripts were concurrently analyzed using systematic text condensation with Nvivo. Two authors coded individually, with disagreements discussed with senior author. Results: Interviews with 7 HFCs (6 physicians, 1 nurse), 6 PM and 4 patients were completed before saturation; 5 themes emerged. First, with regard to health system organization, stakeholders reported gaps related to continuity of care, limited capacity and insufficient funding. Second, with regard to referral appropriateness and timeliness, sub-themes related to unclear referral criteria, varying clinic scope, and delays in triage, testing and time-to-visit. The third theme related to clinic characteristics, raised issues of varying clinic services and composition of healthcare professions/expertise. The fourth theme regarding patient factors related to comorbidity/frailty, socioeconomic status, barriers due to location (parking, traffic) and affinity to specific providers. The final theme related to the COVID-19 pandemic concerned increased referral volumes, loss to follow-up care, transition to online delivery modalities and patient refusal of in-person visits. Many facilitators to improve HFC referral and access were raised. Conclusions: Resources must be provided, and stakeholders brought together to standardize and integrate the HF care continuum.

Contexte: Bien que les patients souffrant d'insuffisance cardiaque bénéficient de soins multidisciplinaires dans des cliniques de fonction cardiaque, l'utilisation de ces dernières est sous-optimale et inéquitable. Cette étude visait à examiner les facteurs influençant l'orientation et l'accès des patients aux cliniques de fonction cardiaque du point de vue de plusieurs parties prenantes, à savoir les décideurs politiques, les professionnels de la santé travaillant dans ces cliniques et les patients. Méthodologie: Dans le cadre de cette étude qualitative, des entretiens semi-structurés ont été menés de février à juin 2020 et de juillet à décembre 2022 (interruption en raison de la pandémie) sur la plateforme Teams avec un échantillon d'intervenants choisis à dessein. Les transcriptions des entretiens ont été analysées simultanément en utilisant la condensation systématique de l'information à l'aide du logiciel Nvivo. Deux auteurs ont effectué individuellement l'encodage, et les divergences ont fait l'objet de discussions avec l'auteur principal. Résultats: Des entretiens avec des professionnels de sept cliniques de fonction cardiaque (6 médecins, 1 infirmière), six décideurs politiques et quatre patients ont été réalisés avant l'atteinte de la saturation des réponses, ce qui a permis de dégager cinq thèmes. Premièrement, en ce qui concerne l'organisation du système de santé, les intervenants ont signalé des lacunes liées à la continuité des soins, une capacité limitée et à financement insuffisant. Deuxièmement, sur le plan de l'adéquation et de la rapidité de l'orientation, les sous-thèmes étaient liés à des critères d'orientation mal définis, à des champs variables d'application clinique et à des retards dans le triage, les tests et les consultations. Le troisième thème portait sur les caractéristiques des cliniques et les questions relatives à la diversité des services cliniques et à la composition du personnel et des experts en santé. Le quatrième thème avait trait aux patients, notamment leurs troubles concomitants, leur fragilité, leur statut socio-économique, les difficultés d'accès (stationnement, circulation) et l'affinité avec certains professionnels. Le dernier thème découlait de la pandémie de COVID- 19 et concernait l'augmentation du nombre de patients, la perte de contact durant le suivi, la transition vers des modalités de prestation en ligne et le refus des patients de se présenter en personne. La question de la nécessité d'un grand nombre de facilitateurs pour améliorer l'orientation et l'accès aux cliniques de fonction cardiaque a également a été soulevée. Conclusions: Des ressources supplémentaires sont requises, et les intervenants doivent travailler de concert afin d'assurer un continuum de soins normalisé et intégré pour les patients atteints d'insuffisance cardiaque.

Short- and Long-Term Outcomes in Patients With Thrombophilia Undergoing Transcatheter Closure of Patent Foramen Ovale.

BACKGROUND: Patients with thrombophilia are underrepresented in studies evaluating outcomes after closure of patent foramen ovale (PFO). Real-world data on long term outcomes in this population are very limited. OBJECTIVES: This study compared outcomes in patients with and without thrombophilia undergoing PFO closure, using data from a large, clinical database linked to population-based databases. METHODS: This retrospective cohort study included consecutive patients who had a transcatheter PFO closure and had preprocedural thrombophilia screening. Data from a retrospective, clinical registry were linked to population-based administrative databases in Ontario Canada to evaluate outcomes. Outcomes were reported as rates per 100 person-years and compared using Poisson regression. RESULTS: We included 669 patients, with a mean age of 56.4 years, 97.9% of whom underwent PFO closure for a cryptogenic stroke. Thrombophilia was diagnosed among 174 (26.0%), of which 86% had inherited mutations. In-hospital, procedural complications were observed in 3.1% of patients with no difference by thrombophilia status. Similarly, no differences were observed in 30-day emergency department visits and readmissions. Over the median follow-up of 11.6 years, the most common adverse outcome was new-onset atrial fibrillation (1.0 per 100 person-years; 95% CI: 0.8-1.2), followed by recurrent cerebrovascular events (0.8 per 100 person-years; 95% CI: 0.6-1.1) with no differences between the groups (P > 0.05). CONCLUSIONS: After PFO closure, no differences were observed in long-term adverse outcomes between patients with and without thrombophilia. Though these patients have been excluded from randomized clinical trials of PFO closure in the past, real-world evidence supports their eligibility for the procedure.

Sex differences in the prevalence and factors associated with anxiety disorders in Canada: A population-based study.

The prevalence of anxiety disorders continues to increase in Canada. The study aimed to evaluate sex differences in the prevalence of anxiety disorders, associated identity factors and social determinants, and their interactions among the Canadian population. We used data from the 2017-2018 Canadian Community Health Survey (CCHS), a nationally representative survey. We evaluated associations between sex, other identity characteristics and social determinants, and anxiety disorders using multivariable logistic regression. To account for the complex sampling design, we applied sampling and bootstrap weights. The CCHS included 113,290 respondents, representative of 98% of the Canadian population over 12 years old. The prevalence of self-reported anxiety disorders was higher among females than males (11.6% vs 6.3%, p < 0.001). Adjusted regression analysis revealed higher odds of having mood disorders for those who were female, non-White, non-immigrant, homosexual or bisexual, unemployed, had lower income or food insecurity, had a disability and a weak sense of community belonging. Younger age was associated with higher odds of anxiety disorders among females (aOR: 1.50, 95%CI: 1.10-2.05) but not among males (aOR: 0.99, 95%CI: 0.64-1.56). An association between employment and higher income with lower odds of anxiety disorders, and bisexuality with higher odds of anxiety disorders, was stronger among males compared with females. Anxiety disorders are more prevalent among females than males in Canada. Age, employment, income, and sexual orientation have varying associations with anxiety disorders among the sexes. Strategies for improving mental health must recognize the complex links between sex and intersecting factors.

Cost-effectiveness analysis of genetic tools to predict treatment response in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapies show variable efficacy for patients with CF. Patient-derived predictive tools may identify individuals likely to respond to CFTRs, but are not in routine use. We aimed to determine the cost-utility of predictive tool-guided treatment with CFTRs as add-on to standard of care (SoC) for individuals with CF. METHODS: This economic evaluation compared two strategies using an individual level simulation: (i) Treat All, where all patients received CFTRs plus SoC and (ii) Test→Treat, where patients who tested positive on predictive tools received CFTRs plus SoC and those who tested negative received SoC only. We simulated 50,000 individuals over their lifetime, and estimated costs (2020 CAD) per quality-adjusted life year (QALY) from the healthcare payer's perspective, discounted at 1.5% annually. The model was populated using Canadian CF registry data and published literature. Probabilistic and deterministic sensitivity were conducted. RESULTS: The Treat All and Test→Treat and strategies yielded 22.41 and 21.36 QALYs, and cost $4.21 M and $3.15 M respectively. Results of probabilistic sensitivity analysis showed that Test→Treat was highly cost-effective compared to Treat All in 100% of simulations at cost-effectiveness thresholds as high as $500,000 per QALY. Test→Treat may save between $931 K to $1.1 M per QALY lost, depending on sensitivity and specificity of predictive tools. CONCLUSION: The use of predictive tools could optimize the health benefits of CFTR modulators while reducing costs. Our findings support the use of pre-treatment predictive testing and may help inform coverage and reimbursement policies for individuals with CF.

Evaluating sex-differences in the prevalence and associated factors of mood disorders in Canada.

BACKGROUND: We assessed the sex-differences in the prevalence and associated factors of mood disorders in Canada using a nationally representative survey, focusing on identity characteristics and socioeconomic factors. METHODS: A secondary analysis of the 2017-2018 Canadian Community Health Survey (CCHS) - Annual Component was conducted using Gender-Based Analysis Plus, which is an analytical process for incorporating various intersecting identity factors into research, programs, and policies. The presence of mood disorders was assessed through self-reporting. Factors associated with mood disorders were evaluated using multivariable logistic regression analysis after the application of sampling and bootstrap weights. RESULTS: The CCHS was completed by 113,290 Canadians, representative of 98 % of the population over the age of 12. Self-reported mood disorders were more prevalent among females than males (11.0 % vs 6.4 %, p < 0.001). Adjusted regression analysis revealed higher odds of reporting mood disorders for those who were female, unemployed, non-immigrant, non-White, smokers, homosexual or bisexual, had lower income, suffered from food insecurity, had a disability and weak sense of community belonging. Employment and higher income were more protective against mood disorders among males than females, and the association of older age with mood disorders was stronger in males than in females. LIMITATIONS: Mood disorders were assessed through self-reporting, and certain population groups were excluded from the survey. CONCLUSIONS: Females in Canada are affected by mood disorders at higher rates than males and certain factors have differential associations with mood disorders among the sexes. Strategies targeting mental disorders must be tailored towards the needs of specific groups.

Mismatch-repair deficiency, microsatellite instability, and lynch syndrome in ovarian cancer: A systematic review and meta-analysis.

OBJECTIVE: Investigating for mismatch repair protein deficiency (MMRd), microsatellite instability (MSI), and Lynch syndrome (LS) is widely accepted in endometrial cancer, but knowledge is limited on its value in epithelial ovarian cancer (EOC). The primary objective was to evaluate the prevalence of mismatch repair protein deficiency (MMRd), microsatellite instability (MSI)-high, and Lynch syndrome (LS) in epithelial ovarian cancer (EOC), as well as the diagnostic accuracy of LS screening tests. The secondary objective was to determine the prevalence of MMRd, MSI-high, and LS in synchronous ovarian endometrial cancer and in histological subtypes. METHODS: We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, and Embase databases. We included studies analysing MMR, MSI, and/or LS by sequencing. RESULTS: A total of 55 studies were included. The prevalence of MMRd, MSI-high, and LS in EOC was 6% (95% confidence interval (CI) 5-8%), 13% (95% CI 12-15%), and 2% (95% CI 1-3%) respectively. Hypermethylation was present in 76% of patients with MLH1 deficiency (95% CI 64-84%). The MMRd prevalence was highest in endometrioid (12%) followed by non-serous non-mucinous (9%) and lowest in serous (1%) histological subtypes. MSI-high prevalence was highest in endometrioid (12%) and non-serous non-mucinous (12%) and lowest in serous (9%) histological subtypes. Synchronous and endometrioid EOC had the highest prevalence of LS pathogenic variants at 7% and 3% respectively, with serous having lowest prevalence (1%). Synchronous ovarian and endometrial cancers had highest rates of MMRd (28%) and MSI-high (28%). Sensitivity was highest for IHC (91.1%) and IHC with MSI (92.8%), while specificity was highest for IHC with methylation (92.3%). CONCLUSION: MMRd and germline LS testing should be considered for non-serous non-mucinous EOC, particularly for endometrioid. PRECIS: The rates of mismatch repair deficiency, microsatellite instability high, and mismatch repair germline mutations are highest in endometrioid subtype and non-serous non-mucinous ovarian cancer. The rates are lowest in serous histologic subtype.

Cost-effectiveness of Fibrinogen Concentrate vs Cryoprecipitate for Treating Acquired Hypofibrinogenemia in Bleeding Adult Cardiac Surgical Patients.

Importance: Excessive bleeding requiring fibrinogen replacement is a serious complication of cardiac surgery. However, the relative cost-effectiveness of the 2 available therapies-fibrinogen concentrate and cryoprecipitate-is unknown. Objective: To determine cost-effectiveness of fibrinogen concentrate vs cryoprecipitate for managing active bleeding in adult patients who underwent cardiac surgery. Design, Setting, and Participants: A within-trial economic evaluation of the Fibrinogen Replenishment in Surgery (FIBERS) randomized clinical trial (February 2017 to November 2018) that took place at 4 hospitals based in Ontario, Canada, hospitals examined all in-hospital resource utilization costs and allogeneic blood product (ABP) transfusion costs incurred within 28 days of surgery. Participants included a subset of 495 adult patients from the FIBERS trial who underwent cardiac surgery and developed active bleeding and acquired hypofibrinogenemia requiring fibrinogen replacement. Interventions: Fibrinogen concentrate (4 g per dose) or cryoprecipitate (10 units per dose) randomized (1:1) up to 24 hours postcardiopulmonary bypass. Main Outcomes and Measures: Effectiveness outcomes included number of ABPs administered within 24 hours and 7 days of cardiopulmonary bypass. ABP transfusion (7-day) and in-hospital resource utilization (28-day) costs were evaluated and a multivariable net benefit regression model built for the full sample and predefined subgroups. Results: Patient level costs for 495 patients were evaluated (mean [SD] age 59.2 [15.4] years and 69.3% male.) Consistent with FIBERS, ABP transfusions and adverse events were similar in both treatment groups. Median (IQR) total 7-day ABP cost was CAD $2280 (US dollars [USD] $1697) (CAD $930 [USD $692]-CAD $4970 [USD $3701]) in the fibrinogen concentrate group and CAD $2770 (USD $1690) (IQR, CAD $1140 [USD $849]-CAD $5000 [USD $3723]) in the cryoprecipitate group. Median (interquartile range) total 28-day cost was CAD $38 180 (USD $28 431) $(IQR, CAD $26 350 [USD $19 622]-CAD $65 080 [USD $48 463]) in the fibrinogen concentrate group and CAD $38 790 (USD $28 886) (IQR, CAD $26 180 [USD $19 495]-CAD $70 380 [USD $52 409]) in the cryoprecipitate group. After exclusion of patients who were critically ill before surgery (11%) due to substantial variability in costs, the incremental net benefit of fibrinogen concentrate vs cryoprecipitate was positive (probability of being cost-effective 86% and 97% at $0 and CAD $2000 (USD $1489) willingness-to-pay, respectively). Net benefit was highly uncertain for nonelective and patients with critical illness. Conclusions and Relevance: Fibrinogen concentrate is cost-effective when compared with cryoprecipitate in most bleeding adult patients who underwent cardiac surgery with acquired hypofibrinogenemia requiring fibrinogen replacement. The generalizability of these findings outside the Canadian health system needs to be verified.

Risk factors of childhood cancer in Armenia: a case-control study.

INTRODUCTION: Childhood cancer (CC) is a leading cause of death among children aged 0-19 years worldwide. Each year, 400,000 new cases of CC are diagnosed globally. Given the between-country differences in CC incidence rates, types and trends, this study aimed to identify possible risk factors for CC in Armenia. METHODS: We used a case-control study design and enrolled participants from the only specialized pediatric hematology and oncology center in Armenia. Cases included patients ≤ 14 years old diagnosed and treated with a malignant disease between 2017 and 2020 in the centre. Controls included patients diagnosed and treated in the center during the same period for a non-malignant disease. We conducted telephone interviews with mothers of cases and controls. Independent risk factors of cancer were identified using multivariable logistic regression analysis. RESULTS: Overall, 234 participants (117 cases, 117 controls) were included in the study. Based on the fitted model, maternal usage of folic acid during pregnancy was protective against CC, almost twice decreasing its odds (OR = 0.54; 95% CI: 0.31-0.94). On the contrary, experiencing horrifying/terrifying event(s) during pregnancy (OR = 2.19; 95% CI: 1.18-4.07) and having induced abortions before getting pregnant with the given child (OR = 2.94; 95% CI: 1.45-5.96) were associated with higher odds for a child to develop cancer. CONCLUSION: Despite the limited sample size of the study, significant modifiable risk factors for CC in Armenia were identified, all of which were linked to the period of pregnancy. The data from this study adds to the limited information available from etiological CC research throughout the world, and it will increase understanding of CC risk factors in settings with small populations and low resources. Although these findings may be helpful for future research, they should be taken with caution unless validated from further larger-scale studies.

Real world long-term outcomes among adults undergoing transcatheter patent foramen closure with amplatzer PFO occluder.

BACKGROUND: Patent foramen ovale (PFO) is a congenital heart defect associated with an increased risk of cryptogenic stroke. We aimed to evaluate real-world outcomes of adult patients undergoing transcatheter PFO closure with the Amplatzer PFO Occluder. METHODS: In this single centre, retrospective cohort study, we linked a detailed clinical registry with provincial administrative databases to obtain short and long-term outcomes. Validated algorithms were used to established baseline comorbidities and adverse outcomes. RESULTS: Between 1999 and 2017, 479 patients had PFO closure with an Amplatzer PFO Occluder. The average age of the patients was 47.3 years (standard deviation (SD) = 12.4), and 54.7% were males. The procedural success was 100%, and 96% of patients were discharged on the same day. Any in-hospital complication was observed in 2.5% (n = 12) of patients. At 30 days post-discharge, 18% of patients had an ED visit and 5% a hospitalization. Over a mean follow-up of 9.1 (SD = 3.8) years, 4% experienced TIA, 1.5% stroke, and 7.6% atrial fibrillation. The composite outcome of stroke/TIA/death was observed in 10.9% of patients (1.22 events per 100 person-years). Patients >60 years old experienced higher rates of adverse events than younger patients. CONCLUSIONS: In this large real-world cohort of patients with cryptogenic stroke, we observed excellent safety and effectiveness outcomes for PFO closure conducted with Amplatzer PFO Occluder, similar to randomized controlled trials or other long-term cohort studies. New onset atrial fibrillation was one of the most commonly adverse events. Future studies should investigate early post-discharge management of patients to prevent readmissions.