Characterization of Peripheral Artery Disease and Associations with Traditional Risk Factors, Mobility, and Biomarkers in the Project Baseline Health Study.

BACKGROUND: There is a dearth of research on immunophenotyping in peripheral artery disease (PAD). This study aimed to describe the baseline characteristics, immunophenotypic profile, and quality of life (QoL) of participants with PAD in the Project Baseline Health Study (PBHS). METHODS: The PBHS study is a prospective, multi-center, longitudinal cohort study that collected clinical, molecular, and biometric data from participants recruited between 2017 and 2018. In this analysis, baseline demographic, clinical, mobility, QoL, and flow cytometry data were stratified by the presence of PAD (ankle brachial index [ABI] ≤0.90). RESULTS: Of 2,209 participants, 58 (2.6%) had lower-extremity PAD, and only 2 (3.4%) had pre-existing PAD diagnosed prior to enrollment. Comorbid smoking (29.3% vs. 14%, p<0.001), hypertension (54% vs. 30%, p<0.001), diabetes (25% vs. 14%, p=0.031), and at least moderate coronary calcifications (Agatston score >100: 32% vs. 17%, p=0.01) were significantly higher in participants with PAD than in those with normal ABIs, as were high-sensitivity C-reactive protein levels (5.86 vs. 2.83, p<0.001). After adjusting for demographic and risk factors, participants with PAD had significantly fewer circulating CD56-high natural killer cells, IgM+ memory B cells, and CD10/CD27 double-positive B cells (p<0.05 for all). CONCLUSIONS: This study reinforces existing evidence that a large proportion of PAD without claudication may be underdiagnosed, particularly in female and Black or African American participants. We describe a novel immunophenotypic profile of participants with PAD that could represent a potential future screening or diagnostic tool to facilitate earlier diagnosis of PAD. GOV IDENTIFIER: NCT03154346, https://clinicaltrials.gov/ct2/show/NCT03154346.

Culprit-Only Revascularization, Single-Setting Complete Revascularization, and Staged Complete Revascularization in Acute Myocardial Infarction: Insights From a Mixed Treatment Comparison Meta-Analysis of Randomized Trials.

BACKGROUND: Complete revascularization improves cardiovascular outcomes compared with culprit-only revascularization in patients with acute myocardial infarction ([MI]; ST-segment-elevation MI or non-ST-segment-elevation MI) and multivessel coronary artery disease. However, the timing of complete revascularization (single-setting versus staged revascularization) is uncertain. The aim was to compare the outcomes of single-setting complete, staged complete, and culprit vessel-only revascularization in patients with acute MI and multivessel disease. METHODS: PubMed, EMBASE, and clinicaltrials.gov databases were searched for randomized controlled trials that compared 3 revascularization strategies. RESULTS: From 16 randomized controlled trials that randomized 11 876 patients with acute MI and multivessel disease, both single-setting complete and staged complete revascularization reduced primary outcome (cardiovascular mortality/MI; odds ratio [OR], 0.52 [95% CI, 0.41-0.65]; OR, 0.74 [95% CI, 0.62-0.88]), composite of all-cause mortality/MI (OR, 0.52 [95% CI, 0.40-0.67]; OR, 0.78 [95% CI, 0.67-0.91]), major adverse cardiovascular event (OR, 0.42 [95% CI, 0.32-0.56]; OR, 0.62 [95% CI, 0.47-0.82]), MI (OR, 0.39 [95% CI, 0.26-0.57]; OR, 0.73 [95% CI, 0.59-0.90]), and repeat revascularization (OR, 0.30 [95% CI, 0.18-0.47]; OR, 0.46 [95% CI, 0.30-0.71]) compared with culprit-only revascularization. Single-setting complete revascularization reduced cardiovascular mortality/MI (OR, 0.70 [95% CI, 0.55-0.91]), major adverse cardiovascular event (OR, 0.67 [95% CI, 0.50-0.91]), and all-cause mortality/MI driven by a lower risk of MI (OR, 0.53 [95% CI, 0.36-0.77]) compared with staged complete revascularization. Single-setting complete revascularization ranked number 1, followed by staged complete revascularization (number 2) and culprit-only revascularization (number 3) for all outcomes. The results were largely consistent in subgroup analysis comparing ST-segment-elevation MI versus non-ST-segment-elevation MI cohorts. CONCLUSIONS: Single-setting complete revascularization may offer the greatest reductions in cardiovascular events in patients with acute MI and multivessel disease. A large-scale randomized trial of single-setting complete versus staged complete revascularization is warranted to evaluate the optimal timing of complete revascularization.

American Heart Association Cardiogenic Shock Registry: Design and Implementation.

BACKGROUND: Cardiogenic shock is a morbid complication of heart disease that claims the lives of more than 1 in 3 patients presenting with this syndrome. Supporting a unique collaboration across clinical specialties, federal regulators, payors, and industry, the American Heart Association volunteers and staff have launched a quality improvement registry to better understand the clinical manifestations of shock phenotypes, and to benchmark the management patterns, and outcomes of patients presenting with cardiogenic shock to hospitals across the United States. METHODS: Participating hospitals will enroll consecutive hospitalized patients with cardiogenic shock, regardless of etiology or severity. Data are collected through individual reviews of medical records of sequential adult patients with cardiogenic shock. The electronic case record form was collaboratively designed with a core minimum data structure and aligned with Shock Academic Research Consortium definitions. This registry will allow participating health systems to evaluate patient-level data including diagnostic approaches, therapeutics, use of advanced monitoring and circulatory support, processes of care, complications, and in-hospital survival. Participating sites can leverage these data for onsite monitoring of outcomes and benchmarking versus other institutions. The registry was concomitantly designed to provide a high-quality longitudinal research infrastructure for pragmatic randomized trials as well as translational, clinical, and implementation research. An aggregate deidentified data set will be made available to the research community on the American Heart Association's Precision Medicine Platform. On March 31, 2022, the American Heart Association Cardiogenic Shock Registry received its first clinical records. At the time of this submission, 100 centers are participating. CONCLUSIONS: The American Heart Association Cardiogenic Shock Registry will serve as a resource using consistent data structure and definitions for the medical and research community to accelerate scientific advancement through shared learning and research resulting in improved quality of care and outcomes of shock patients.

Association Between Frailty and Management and Outcomes of Acute Myocardial Infarction Complicated by Cardiogenic Shock.

Background: Cardiogenic shock (CS) in the setting of acute myocardial infarction (AMI) is associated with high morbidity and mortality. Frailty is a common comorbidity in patients with cardiovascular disease and is also associated with adverse outcomes. The impact of preexisting frailty at the time of CS diagnosis following AMI has not been studied. Objectives: The purpose of this study was to examine the prevalence of frailty in patients admitted with AMI complicated by CS (AMI-CS) hospitalizations and its associations with in-hospital outcomes. Methods: We retrospectively analyzed the National Inpatient Sample from 2016 to 2020 and identified all hospitalizations for AMI-CS. We classified them into frail and nonfrail groups according to the hospital frailty risk score cut-off of 5 and compared in-hospital outcomes. Results: A total of 283,700 hospitalizations for AMI-CS were identified. Most (70.8%) occurred in the frail. Those with frailty had higher odds of in-hospital mortality (adjusted OR [aOR]: 2.17, 95% CI: 2.07 to 2.26, P < 0.001), do-not-resuscitate status, and discharge to a skilled nursing facility compared with those without frailty. They also had higher odds of in-hospital adverse events, including intracranial hemorrhage, gastrointestinal hemorrhage, acute kidney injury, and delirium. Importantly, AMI-CS hospitalizations in the frail had lower odds of coronary revascularization (aOR: 0.55, 95% CI: 0.53-0.58, P < 0.001) or mechanical circulatory support (aOR: 0.89, 95% CI: 0.85-0.93, P < 0.001). Lastly, hospitalizations for AMI-CS showed an overall increase from 53,210 in 2016 to 57,065 in 2020 (P trend <0.001), with this trend driven by a rise in the frail. Conclusions: A high proportion of hospitalizations for AMI-CS had concomitant frailty. Hospitalizations with AMI-CS and frailty had higher rates of in-hospital morbidity and mortality compared to those without frailty.

Polyvascular Disease: A Narrative Review of Risk Factors, Clinical Outcomes and Treatment.

PURPOSE OF REVIEW: Polyvascular disease has a significant global burden and is associated with increased risk of major adverse cardiac events with each additional vascular territory involved. The purpose of this review is to highlight the risk factors, associated outcomes, emerging genetic markers, and evidence for screening and treatment of polyvascular disease. RECENT FINDINGS: Polyvascular disease is the presence of atherosclerosis in two or more vascular beds. It has a significant global burden, with a prevalence of 30-70% in patients with known atherosclerosis. Patients with polyvascular disease experience elevated rates of cardiovascular death, myocardial infarction and stroke, especially among high-risk subgroups like those with type 2 diabetes mellitus and there is a step-wise increased risk of adverse outcomes with each additional vascular territory involved. Genetic analyses demonstrate that some individuals may carry a genetic predisposition, while others exhibit higher levels of atherogenic lipoproteins and inflammatory markers. Routine screening for asymptomatic disease is not currently recommended by major cardiovascular societies unless patients are high-risk. While there are no established protocols for escalating treatment, existing guidelines advocate for lipid-lowering therapy. Additionally, recent studies have demonstrated benefit from antithrombotic agents, such as P2Y12 inhibitors and low-dose anticoagulation, but the optimal timing and dosage of these agents has not been established, and the ischemic benefit must be balanced against the increased risk of bleeding in the polyvascular population. Due to the high prevalence and risks associated with polyvascular disease, early identification and treatment intensification are crucial to reduce disease progression. Future research is needed to develop screening protocols and determine the optimal timing and dosing of therapy to prevent ischemic events.

Case Volumes and Outcomes Among Early-Career Interventional Cardiologists in the United States.

BACKGROUND: Little is known about the procedural characteristics, case volumes, and mortality rates for early- vs non-early-career interventional cardiologists in the United States. OBJECTIVES: This study examined operator-level data for patients who underwent percutaneous coronary intervention (PCI) between April 2018 and June 2022. METHODS: Data were collected from the National Cardiovascular Data Registry CathPCI Registry, American Board of Internal Medicine certification database, and National Plan and Provider Enumeration System database. Early-career operators were within 5 years of the end of training. Annual case volume, expected mortality and bleeding risk, and observed/predicted mortality and bleeding outcomes were evaluated. RESULTS: A total of 1,451 operators were early career; 1,011 changed their career status during the study; and 6,251 were non-early career. Overall, 514,540 patients were treated by early-career and 2,296,576 patients by non-early-career operators. The median annual case volume per operator was 59 (Q1-Q3: 31-97) for early-career and 57 (Q1-Q3: 28-100) for non-early-career operators. Early-career operators were more likely to treat patients presenting with ST-segment elevation myocardial infarction and urgent indications for PCI (both P < 0.001). The median predicted mortality risk was 2.0% (Q1-Q3: 1.5%-2.7%) for early-career and 1.8% (Q1-Q3: 1.2%-2.4%) for non-early-career operators. The median predicted bleeding risk was 4.9% (Q1-Q3: 4.2%-5.7%) for early-career and 4.4% (Q1-Q3: 3.7%-5.3%) for non-early-career operators. After adjustment, an increased risk of mortality (OR: 1.08; 95% CI: 1.05-1.17; P < 0.0001) and bleeding (OR: 1.08; 95% CI: 1.05-1.12; P < 0.0001) were associated with early-career status. CONCLUSIONS: Early-career operators are caring for patients with more acute presentations and higher predicted risk of mortality and bleeding compared with more experienced colleagues, with modestly worse outcomes. These data should inform institutional practices to support the development of early-career proceduralists.

Impact of anemia on outcomes and resource utilization in patients with myocardial infarction: A national database analysis.

BACKGROUND: Although anemia is common in patients with myocardial infarction (MI), management remains controversial. We quantified the association of anemia with in-hospital outcomes and resource utilization in patients admitted with MI using a large national database. METHODS: All hospitalizations with a primary diagnosis code for acute MI in the National Inpatient Sample (NIS) between 2014 and 2018 were identified. Among these hospitalizations, patients with anemia were identified using a secondary diagnosis code. Data on demographic and clinical variables were collected. Outcomes of interest included in-hospital adverse events, length of stay (LOS), and total cost. Multivariable logistic regression and generalized linear models were used to evaluate the relationship between anemia and outcomes. RESULTS: Among 1,113,181 MI hospitalizations, 254,816 (22.8%) included concomitant anemia. Anemic patients were older and more likely to be women. After adjustment for demographics and comorbidities, anemia was associated with higher mortality (7.1 vs. 4.3%; odds ratio 1.09; 95% confidence interval [CI] 1.07-1.12, p < 0.001). Anemia was also associated with a mean of 2.71 days longer LOS (average marginal effects [AME] 2.71; 95% CI 2.68-2.73, p < 0.05), and $ 9703 mean higher total costs (AME $9703, 95% CI $9577-$9829, p < 0.05). Anemic patients who received blood transfusions had higher mortality as compared with those who did not (8.2% vs. 7.0, p < 0.001). CONCLUSION: In MI patients, anemia was associated with higher in-hospital mortality, adverse events, total cost, and length of stay. Transfusion was associated with increased mortality, and its role in MI requires further research.

The impact of robotic rectal cancer surgery at a Canadian regional cancer centre: a retrospective cohort study.

BACKGROUND: Although robotic surgery has several advantages over other minimally invasive surgery (MIS) techniques for rectal cancer surgery, the uptake in Canada has been limited owing to a perceived increase in cost and lack of training. The objective of this study was to determine the impact of access to robotic surgery in a Canadian setting. METHODS: We conducted a retrospective cohort study involving consecutive adults undergoing surgical resection for rectal cancer between 2017 and 2020. The primary exposure was access to robotic surgery. Outcomes included MIS utilization, short-term outcomes, total cost of care, and quality of surgical resection. We completed univariate and multivariate analyses. RESULTS: We included 171 individuals in this cohort study (85 in the prerobotic period and 86 in the robotic period). The 2 groups had similar baseline characteristics. A higher proportion of individuals underwent successful MIS in the robotic phase (86% v. 46%, p < 0.001). Other benefits included a shorter mean length of hospital stay (5.1 d v. 9.2 d, p < 0.001). The quality of surgical resection was similar between groups. The total cost of care was $16 746 in the robotic period and $18 808 in the prerobotic period (mean difference -$1262, 95% confidence interval -$4308 to $1783; p = 0.4). CONCLUSION: Access to robotic rectal cancer surgery increased successful completion of MIS and shortened hospital stay, with a similar total cost of care. Robotic rectal cancer surgery can enhance patient outcomes in the Canadian setting.

Emergency Colorectal Surgery in Those with Cirrhosis: A Population-based Study Assessing Practice Patterns, Outcomes and Predictors of Mortality.

Background: Those with cirrhosis who require emergency colorectal surgery are at risk for poor outcomes. Although risk predictions models exists, these tools are not specific to colorectal surgery, nor were they developed in a contemporary setting. Thus, the objective of this study was to assess the outcomes in this population and determine whether cirrhosis etiology and/or the Model for End Stage Liver Disease (MELD-Na) is associated with mortality. Methods: This population-based study included those with cirrhosis undergoing emergent colorectal surgery between 2009 and 2017. All eligible individuals in Ontario were identified using administrative databases. The primary outcome was 90-day mortality. Results: Nine hundred and twenty-seven individuals (57%) (male) were included. The most common cirrhosis etiology was non-alcoholic fatty liver disease (NAFLD) (50%) and alcohol related (32%). Overall 90-day mortality was 32%. Multivariable survival analysis demonstrated those with alcohol-related disease were at increased risk of 90-day mortality (hazards ratio [HR] 1.53, 95% confidence interval [CI] 1.2-2.0 vs. NAFLD [ref]). Surgery for colorectal cancer was associated with better survival (HR 0.27, 95%CI 0.16-0.47). In the subgroup analysis of those with an available MELD-Na score (n = 348/927, 38%), there was a strong association between increasing MELD-Na and mortality (score 20+ HR 6.6, 95%CI 3.9-10.9; score 10-19 HR 1.8, 95%CI 1.1-3.0; score <10 [ref]). Conclusion: Individuals with cirrhosis who require emergent colorectal surgery have a high risk of postoperative complications, including mortality. Increasing MELD-Na score is associated with mortality and can be used to risk stratify individuals.

Evaluating the Use of Unfractionated Heparin with Intra-Aortic Balloon Counterpulsation.

BACKGROUND: Evidence supporting anticoagulation with unfractionated heparin (UFH) in patients with an intra-aortic balloon pump (IABP) to prevent limb ischaemia remains limited, while bleeding risks remain high. Monitoring heparin in this setting with anti-factor Xa (anti-Xa) is not previously described. OBJECTIVES: The study objective is to describe the incidence of thromboembolic and bleeding events with the use of UFH in patients with an IABP utilising monitoring with both anti-Xa and activated partial thromboplastin time (aPTT). METHODS: This is a retrospective study of adults who received an IABP and UFH for ≥24 hours. Electronic medical records were reviewed for pertinent data. The primary outcome was the incidence of limb ischaemia during IABP. Secondary outcomes included myocardial infarction, thrombus on IABP, or stroke. Exploratory outcomes included any venous thromboembolism and bleeding events. RESULTS: Of 159 patients, 88% received an IABP for cardiogenic shock and median duration of IABP support was 118 hours (interquartile range, 67-196). Limb ischaemia occurred in four of 159 patients (2.5%). Strokes occurred in 3.8% of the cohort, and bleeding events occurred in 33%. Despite anticoagulation use in all patients, 11% experienced a venous thromboembolism, with most identified upon asymptomatic screening with concern for heparin-induced thrombocytopenia. We found no differences in outcomes that occurred with a hybrid anti-Xa and aPTT versus aPTT monitoring alone. CONCLUSIONS: We observed a high rate of thrombotic and bleeding complications with the use of UFH in patients with an IABP. Use of anti-Xa versus aPTT for monitoring was not associated with complications. These data suggest safer anticoagulation strategies are needed in this setting.

Spontaneous Coronary Artery Dissection in a Healthy Man With Non-ST Elevation Myocardial Infarction.

This case report discusses a diagnosis of spontaneous coronary artery dissection in an otherwise healthy man with non­ST elevation myocardial infarction.

A systematic review and meta-analysis of oncological outcomes with transanal total mesorectal excision for rectal cancer.

AIM: Transanal total mesorectal (taTME) excision is a method used to assist in the radical removal of the rectum. By adopting the concept of natural orifice surgery, it offers potential benefits over conventional techniques. Early enthusiasm for this strategy led to its rapid and widespread adoption. The imposing of a local moratorium was precipitated by the discovery in Norway of an uncommon multifocal pattern of locoregional recurrence. The aim of this systematic review and meta-analysis was to determine the incidence of local recurrence after taTME for rectal cancer. METHOD: Conforming to the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines checklist, a systematic review and meta-analysis was conducted. This included case series and comparative studies between taTME and preferentially laparoscopic procedures published between 2010 and 2021. RESULTS: There were a total of 1175 studies retrieved. After removal and screening for quality and relevance, the final analysis contained 40 studies. The local recurrence rate following taTME was 3.4% (95% CI 2.9%-3.9%, I2 = 0%) in 4987 patients with follow-up durations ranging from 0.7 to 5.5 years. Compared with laparoscopic TME, local recurrence was not statistically different for the taTME group (p = 0.076); however, it was less probable (OR = 0.51, 95% CI 0.24-1.09, I2 = 0%). Systemic recurrence and circumferential resection margin status were secondary outcomes; however, the differences were not statistically significant. CONCLUSION: Our data suggest that the local recurrence for regular laparoscopic and transanal TME surgeries may be comparable, suggesting that taTME can be performed without influencing locoregional oncological outcomes in patients treated at specialized institutions and who have been cautiously selected.

Frailty and In-Hospital Outcomes for Management of Cardiogenic Shock without Acute Myocardial Infarction.

(1) Background: Cardiogenic shock (CS) is associated with high morbidity and mortality. Frailty and cardiovascular diseases are intertwined, commonly sharing risk factors and exhibiting bidirectional relationships. The relationship of frailty and non-acute myocardial infarction with cardiogenic shock (non-AMI-CS) is poorly described. (2) Methods: We retrospectively analyzed the National Inpatient Sample from 2016 to 2020 and identified all hospitalizations for non-AMI-CS. We classified them into frail and non-frail groups according to the hospital frailty risk score cut-off of 5 and compared in-hospital outcomes. (3) Results: A total of 503,780 hospitalizations for non-AMI-CS were identified. Most hospitalizations involved frail adults (80.0%). Those with frailty had higher odds of in-hospital mortality (adjusted odds ratio [aOR] 2.11, 95% confidence interval [CI] 2.03-2.20, p < 0.001), do-not-resuscitate status, and discharge to a skilled nursing facility compared with those without frailty. They also had higher odds of in-hospital adverse events, such as acute kidney injury, delirium, and longer length of stay. Importantly, non-AMI-CS hospitalizations in the frail group had lower use of mechanical circulatory support but not rates of cardiac transplantation. (4) Conclusions: Frailty is highly prevalent among non-AMI-CS hospitalizations. Those accompanied by frailty are often associated with increased rates of morbidity and mortality compared to those without frailty.

Smartphone Application Versus Standard Instruction for Colonoscopic Preparation: A Randomized Controlled Trial.

OBJECTIVE: To compare smartphone application (Colonoscopic Preparation) instructions versus paper instructions for bowel preparation for colonoscopy. BACKGROUND: Adhering to bowel preparation instructions is important to ensure a high-quality colonoscopy. PATIENTS AND METHODS: This randomized controlled trial included individuals undergoing colonoscopy at a tertiary care hospital. Individuals were randomized (1:1) to receive instructions through a smartphone application or traditional paper instructions. The primary outcome was the quality of the bowel preparation as measured by the Boston Bowel Preparation Score. Secondary outcomes included cecal intubation and polyp detection. Patient satisfaction was assessed using a previously developed questionnaire. RESULTS: A total of 238 individuals were randomized (n = 119 in each group), with 202 available for the intention-to-treat analysis (N = 97 in the app group and 105 in the paper group). The groups had similar demographics, indications for colonoscopy, and type of bowel preparation. The primary outcome (Boston Bowel Preparation Score) demonstrated no difference between groups (Colonoscopic Preparation app mean: 7.26 vs paper mean: 7.28, P = 0.91). There was no difference in cecal intubation (P = 0.37), at least one polyp detected (P = 0.43), or the mean number of polyps removed (P = 0.11). A higher proportion strongly agreed or agreed that they would use the smartphone app compared with paper instructions (89.4% vs 70.1%, P = 0.001). CONCLUSIONS: Smartphone instructions performed similarly to traditional paper instructions for those willing to use the application. Local patient preferences need to be considered before making changes in the method of delivery of medical instructions.

One-month DAPT with ticagrelor and aspirin for patients undergoing coronary artery bypass grafting: rationale and design of the randomised, multicentre, double-blind, placebo-controlled ODIN trial.

The optimal antiplatelet strategy after coronary artery bypass graft (CABG) surgery in patients with chronic coronary syndromes (CCS) is unclear. Adding the P2Y12 inhibitor, ticagrelor, to low-dose aspirin for 1 year is associated with a reduction in graft failure, particularly saphenous vein grafts, at the expense of an increased risk of clinically important bleeding. As the risk of thrombotic graft failure and ischaemic events is highest early after CABG surgery, a better risk-to-benefit profile may be attained with short-term dual antiplatelet therapy followed by single antiplatelet therapy. The One Month Dual Antiplatelet Therapy With Ticagrelor in Coronary Artery Bypass Graft Patients (ODIN) trial is a prospective, randomised, double-blind, placebo-controlled, international, multicentre study of 700 subjects that will evaluate the effect of short-term dual antiplatelet therapy with ticagrelor plus low-dose aspirin after CABG in patients with CCS. Patients will be randomised 1:1 to ticagrelor 90 mg twice daily or matching placebo, in addition to aspirin 75-150 mg once daily for 1 month; after the first month, antiplatelet therapy will be continued with aspirin alone. The primary endpoint is a hierarchical composite of all-cause death, stroke, myocardial infarction, revascularisation and graft failure at 1 year. The key secondary endpoint is a hierarchical composite of all-cause death, stroke, myocardial infarction, Bleeding Academic Research Consortium (BARC) type 3 bleeding, revascularisation and graft failure at 1 year (net clinical benefit). ODIN will report whether the addition of ticagrelor to low-dose aspirin for 1 month after CABG reduces ischaemic events and provides a net clinical benefit in patients with CCS. (ClinicalTrials.gov: NCT05997693).

Bleeding Outcomes in Patients Treated With Asundexian in Phase II Trials.

BACKGROUND: Phase II trials of asundexian were underpowered to detect important differences in bleeding. OBJECTIVES: The goal of this study was to obtain best estimates of effects of asundexian vs active control/placebo on major and clinically relevant nonmajor (CRNM) and all bleeding, describe most common sites of bleeding, and explore association between asundexian exposure and bleeding. METHODS: We performed a pooled analysis of 3 phase II trials of asundexian in patients with atrial fibrillation (AF), recent acute myocardial infarction (AMI), or stroke. Bleeding was defined according to the International Society on Thrombosis and Hemostasis (ISTH) criteria. RESULTS: In patients with AF (n = 755), both asundexian 20 mg and 50 mg once daily vs apixaban had fewer major/CRNM events (3 of 249; incidence rate [IR] per 100 patient-years 5.47 vs 1 of 254 [IR: not calculable] vs 6 of 250 [IR: 11.10]) and all bleeding (12 of 249 [IR: 22.26] vs 10 of 254 [IR: 18.21] vs 26 of 250 [IR: 50.56]). In patients with recent AMI or stroke (n = 3,409), asundexian 10 mg, 20 mg, and 50 mg once daily compared with placebo had similar rates of major/CRNM events (44 of 840 [IR: 7.55] vs 42 of 843 [IR: 7.04] vs 56 of 845 [IR: 9.63] vs 41 of 851 [IR: 6.99]) and all bleeding (107 of 840 [IR: 19.57] vs 123 of 843 [IR: 22.45] vs 130 of 845 [IR: 24.19] vs 129 of 851 [IR: 23.84]). Most common sites of major/CRNM bleeding with asundexian were gastrointestinal, respiratory, urogenital, and skin. There was no significant association between asundexian exposure and major/CRNM bleeding. CONCLUSIONS: Analyses of phase II trials involving >500 bleeds highlight the potential for improved safety of asundexian compared with apixaban and similar safety compared with placebo. Further evidence on the efficacy of asundexian awaits the results of ongoing phase III trials.

Evaluating registry-based trial economics: Results from the STRESS clinical trial.

Background: Registry-based trials have the potential to reduce randomized clinical trial (RCT) costs. However, observed cost differences also may be achieved through pragmatic trial designs. A systematic comparison of trial costs across different designs has not been previously performed. Methods: We conducted a study to compare the current Steroids to Reduce Systemic inflammation after infant heart surgery (STRESS) registry-based RCT vs. two established designs: pragmatic RCT and explanatory RCT. The primary outcome was total RCT design costs. Secondary outcomes included: RCT duration and personnel hours. Costs were estimated using the Duke Clinical Research Institute's pricing model. Results: The Registry-Based RCT estimated duration was 31.9 weeks greater than the other designs (259.5 vs. 227.6 weeks). This delay was caused by the Registry-Based design's periodic data harvesting that delayed site closing and statistical reporting. Total personnel hours were greatest for the Explanatory design followed by the Pragmatic design and the Registry-Based design (52,488 vs 29,763 vs. 24,480 h, respectively). Total costs were greatest for the Explanatory design followed by the Pragmatic design and the Registry-Based design ($10,140,263 vs. $4,164,863 vs. $3,268,504, respectively). Thus, Registry-Based total costs were 32 % of the Explanatory and 78 % of the Pragmatic design. Conclusion: Total costs for the STRESS RCT with a registry-based design were less than those for a pragmatic design and much less than an explanatory design. Cost savings reflect design elements and leveraging of registry resources to improve cost efficiency, but delays to trial completion should be considered.

Applying the fragility index to randomized controlled trials evaluating total neoadjuvant therapy for rectal cancer: A methodological survey.

BACKGROUND: Recently, there has been significant interest in, and adoption of, total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC). We designed the present study to assess the robustness of the randomized controlled trials (RCTs) evaluating contemporary TNTs for LARC using the fragility index (FI). MATERIALS AND METHODS: Relevant articles were identified through a review article by Johnson et al. in the Canadian Journal of Surgery. Dichotomous outcomes within these RCTs were eligible for inclusion if the reported effect size had a p-value < 0.05. The main outcome was FI for each included outcome. Walsh et al.'s method of calculating FI was utilized. Correlations between FI and research characteristics were assessed using the Spearman's rank correlation coefficients. Risk of bias was assessed using Cochrane recommended tools. RESULTS: Ten RCTs were identified with 25 outcomes having statistically significant differences between groups. Eleven outcomes were time-to-event outcomes, while the remainder were dichotomous outcomes. Approximately half (n = 13) were oncologic outcomes. The median FI was 2 (interquartile range [IQR] 1-16). The number of patients lost to follow-up exceeded the FI in 17 outcomes (68.0 %) and thus these results were considered "fragile". Lower FI was associated with high risk of bias (rho = -0.5594) and greater loss to follow-up (rho = -0.4394), while higher FI was associated with large study size (rho = 0.5120). CONCLUSIONS: The robustness of outcomes from trials assessing TNT for LARC was found to be questionable. Most outcomes were fragile, as determined by the FI. This survey is limited by the number of included studies.

Burnout in cardiology: a narrative review.

The frequency of burnout is rising among cardiologists, affecting not only their well-being but also the quality of patient care. Computerization of practice, bureaucracy, excessive workload, lack of control/autonomy, hostile and hectic work environments, insufficient income, and work life imbalance are the main categories listed as contributing factors to cardiologists' burnout. Organization- and physician-directed interventions can be impactful; however, the effectiveness and feasibility of these interventions have rarely been assessed in cardiology. This review summarizes recent publications on burnout in cardiology, discusses the contributing factors and implications of burnout on physicians' health and patient safety, and explores possible interventions.