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Introduction: Troponin elevation after noncardiac surgery is associated with an elevated risk of 30-day mortality. Little is known about relative merit of using a high-sensitivity Troponin T (hsTnT), the fifth-generation assay, vs the nonhigh sensitivity Troponin T (non-hsTnT), the fourth-generation assay, in the noncardiac surgery setting. We aimed to identify whether hsTnT can identify additional patients at risk that would have gone undetected with non-hsTnT measurement., Methods: The VISION Study included 40,004 noncardiac surgery patients with postoperative troponin measurements. Among them, 1,806 patients had both fourth-generation non-hsTnT and fifth-generation hsTnT concomitant measurements (4,451 paired results). We compared the absolute concentrations, the timing, and the impact of different thresholds on predicting 30-day major cardiovascular complications (composite of death, nonfatal cardiac arrest, coronary revascularization, and congestive heart failure)., Results: Based on the manufacturers' threshold of 14 ng/L, 580 (32.1%) patients had postoperative hsTnT concentrations greater than the threshold, while their non-hsTnT concentrations were below the manufacturer's threshold. These 580 patients had higher risk of major cardiovascular events (OR 2.33; CI 95% 1.04-5.23; P = .049) than patients with hsTnT concentrations below the manufacturer threshold. Among patients with myocardial injury after noncardiac surgery, only 50% would be detected by the fourth-generation non-hsTnT assay at 6 to 12 hours postoperative as compared to 85% with the fifth-generation hsTnT assay (P-value < .001)., Conclusions: Within the first 3 postoperative days, fifth-generation hsTnT identified at least 1 in 3 patients with troponin elevation that would have gone undetected by fourth-generation non-hsTnT using published thresholds in this setting. Furthermore, fifth-generation hsTnT identified patients with an elevation earlier than fourth-generation non-hsTnT, indicating potential to improve postoperative risk stratification., Competing Interests: Disclosures FKB holds a Research Early Career Award from Hamilton Health Sciences, and has received grants from Roche Diagnostics and SIEMENS for investigator initiated research grants, and honorarium for lectures or participation in as advisory board from Roche Diagnostics and Novartis. ED reports research grants for investigator-initiated studies and honoraria for participation in advisory board from Roche Diagnostics and research grant for investigator-initiated study from Abbott Laboratories. PK has received grants/reagents/consultant/advisor/ honoraria from Abbott Laboratories, Abbott Point of Care, Beckman Coulter, Ortho Clinical Diagnostics, Quidel, Randox Laboratories, Roche Diagnostics, Siemens Healthcare Diagnostics, and Thermo Fisher Scientific . McMaster University has filed patents with PK listed as an inventor in the acute cardiovascular biomarker field. OB Received research grants from AstraZeneca, Pfizer, Bayer, Amgen, Servier, Novartis, BMS and Boeheringer-Ingelheim unrelated to the submitted work PJD reports grants from Canadian Institutes of Health Research and from Ontario Strategy for Patient Oriented Research Support Unit/Ministry of Health and Long-Term Care during the conduct of the study; and grants from Abbott Diagnostics, Roche Diagnostics, and Siemens, CloudDX, Philips Healthcare, outside the submitted work. Declares to be consultant for Abbott Canada, Renibus, Roche Canada and Trimedic. Declares be a member of advisory board of Bayer, Quidel and speaker for Velocit. DIS, MT, AP, YL, DH, SS, WC, CC, SNO, SP, AK, AT and ACT declare no conflict of interest, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Hip fractures carry a substantial risk of complications and death. This study aimed to report the 90-day incidence of mortality, major perioperative complications and in-hospital timelines after a hip fracture in the Spanish HIP ATTACK-1 trial cohort, comparing with the non-Spanish cohort., Methods: Prospective cohort study of Spanish patients nested in the HIP ATTACK-1 trial. The HIP ATTACK-1 was an international, randomized, controlled trial (17 countries, 69 hospitals, 7 in Spain, highest recruiting country). Patients were randomized to either accelerated surgery (goal of surgery within 6 h of diagnosis) or standard care. Participants were ≥45 years of age who presented with a low-energy hip fracture requiring surgery., Results: Among 534 patients in the Spanish cohort, 69 (12.9 %) patients died at 90 days follow-up, compared to 225 (9.2 %) in the non-Spanish cohort (p = 0.009), mostly due to higher nonvascular related mortality. A composite of major postoperative complication occurred in 126 patients (23.6 %). The most common perioperative complications were myocardial injury (189 patients, 35.4 %), infection with no sepsis (86 patients, 16.1 %) and perioperative delirium (84 patients, 15.7 %); all these complication rates in Spain were significantly higher than the non-Spanish patients (29.2 % p = 0.005; 11.9 % p = 0.008 and 9.2 % p < 0.0001, respectively). Spanish cohort patients were older and had more comorbidities than the non-Spanish cohort, evidencing their greater frailty at baseline. Among Spanish patients, the median time from hip fracture diagnosis to surgery was 30.0 h (IQR 21.1-53.9) in the standard-care group, with 68.8 % of patients receiving surgery within 48 h of diagnosis. This median time was lower in the non-Spanish cohort (22.8 h, IQR 9.5-37.0), where 82.1 % of patients were operated within 48 h., Conclusions: In the HIP ATTACK-1 trial, 1 in 8 patients died 90 days after a hip fracture in Spain. The most common complication after a hip fracture was myocardial injury, followed by infection and delirium. Spanish patients had worse outcomes than non-Spanish patients. Research needs to focus on new interventions such as accelerated surgery and perioperative troponin measurement with the appropriate investment of resources, to prevent and identify early these complications with a goal of improving mortality for this high-risk population., Level of Evidence: II., Competing Interests: Declaration of competing interest Dr. Ernesto Guerra-Farfán and Dr. PJ Devereaux received research grants from Smith & Nephew for this investigator-initiated trial. Based on study questions Dr. PJ Devereaux originated and grants he has written, he has received grants from Abbott Diagnostics, Roche Diagnostics, and Siemens. Dr. Flavia K Borges received investigator-initiated research grants from Roche diagnostics and SIEMENS. Mohit Bhandari (g), Yaiza Garcia-Sanchez (h), Jorge H. Nuñez (c,i), Jaume Mestre-Torres (j), Jordi Tomas-Hernandez (a), Jordi Teixidor-Serra (a), Mariano Balaguer-Castro (k), Pablo Castillón (i), Alfred Dealbert (l), Julio De Caso Rodriguez (m), Hector J. Aguado (n), Enrique Guerado (o), Ekaterine Popova(m), Ana Claudia Tonelli (p), Kumar Balasubramanian (e), Jessica Vincent (e), Valerie Harvey (e), Etri Kocaqi (q) and Gerard Slobogean (r s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Myocardial injury after a hip fracture is common and has a poor prognosis. Patients with a hip fracture and myocardial injury may benefit from accelerated surgery to remove the physiological stress associated with the hip fracture. This study aimed to determine if accelerated surgery is superior to standard care in terms of the 90-day risk of death in patients with a hip fracture who presented with an elevated cardiac biomarker/enzyme measurement at hospital arrival., Methods: The HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) trial was a randomized controlled trial designed to determine whether accelerated surgery for hip fracture was superior to standard care in reducing death or major complications. This substudy is a post-hoc analysis of 1392 patients (from the original study of 2970 patients) who had a cardiac biomarker/enzyme measurement (>99.9% had a troponin measurement and thus "troponin" is the term used throughout the paper) at hospital arrival. The primary outcome was all-cause mortality. The secondary composite outcome included all-cause mortality and non-fatal myocardial infarction, stroke, and congestive heart failure 90 days after randomization., Results: Three hundred and twenty-two (23%) of the 1392 patients had troponin elevation at hospital arrival. Among the patients with troponin elevation, the median time from hip fracture diagnosis to surgery was 6 hours (interquartile range [IQR] = 5 to 13) in the accelerated surgery group and 29 hours (IQR = 19 to 52) in the standard care group. Patients with troponin elevation had a lower risk of mortality with accelerated surgery compared with standard care (17 [10%] of 163 versus 36 [23%] of 159; hazard ratio [HR] = 0.43 [95% confidence interval (CI) = 0.24 to 0.77]) and a lower risk of the secondary composite outcome (23 [14%] of 163 versus 47 [30%] of 159; HR = 0.43 [95% CI = 0.26 to 0.72])., Conclusions: One in 5 patients with a hip fracture presented with myocardial injury. Accelerated surgery resulted in a lower mortality risk than standard care for these patients; however, these findings need to be confirmed., Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The HIP ATTACK-1 trial was supported by the Canadian Institutes of Health Research, the Ontario Strategy for Patient Oriented Research Support Unit, the Ontario Ministry of Health and Long-Term Care, the Hamilton Health Sciences Foundation, the Physicians’ Services Incorporated Foundation, the Michael G. DeGroote Institute for Pain Research and Care, Smith & Nephew (to recruit patients in Spain), and Indiegogo Crowdfunding. This substudy received funding from a McMaster General Internal Medicine Research Grant. Funders had no role in the study design, conduct, analyses, or manuscript preparation. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/I117)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Surgical patients are often transfused to manage bleeding and anemia. Best practices for red blood cell (RBC) transfusion administration in patient having noncardiac surgery remains controversial and a robust evaluation and description of perioperative transfusion practices is lacking. We characterized perioperative hemoglobin concentrations and transfusion practices from the prospective VISION cohort which included 39,222 patients aged ≥45 years who had inpatient noncardiac surgery. Variations in transfusion practices were analyzed using hierarchical mixed models, and associations with mortality and complications were evaluated using a nested frailty survival model. Within the cohort, 16.1% (n = 6296) were given perioperative RBC transfusions, with the fraction declining from 20% to 13% over the 6-year study period. The proportion of patients transfused varied by surgery type from 6.4% for low-risk operations (i.e., minor surgery) to 31.5% for orthopedic surgeries. Variations were largely associated with patient hemoglobin concentrations, but also with center (range: 3.7%-27.3%) and country (0.4%-25.3%). Even after adjusting for baseline hemoglobin, comorbidities and type of surgery, both center and country were significant sources of variation in transfusion practices. Among transfused participants, 60.4% (n = 3728/6170) had at least 1 hemoglobin concentration ≤80g/L and 86.0% (n = 5305/6170) had at least 1 hemoglobin concentration ≤90g/L, suggesting that relatively restrictive transfusion strategies were used in most. The proportion of patients receiving at least 1 RBC transfusion declined from 20% to 13% over 6 years. However, there was considerable unexplained variation in transfusion practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Smoking cessation interventions are underutilized in the surgical setting. We aimed to systematically identify the barriers and facilitators to smoking cessation in the surgical setting., Methods: Following the Joanna Briggs Institute (JBI) framework for scoping reviews, we searched 5 databases (MEDLINE, Embase, Cochrane CENTRAL, CINAHL, and PsycINFO) for quantitative or qualitative studies published in English (since 2000) evaluating barriers and facilitators to perioperative smoking cessation interventions. Data were analyzed using thematic analysis and mapped to the theoretical domains framework (TDF)., Results: From 31 studies, we identified 23 unique barriers and 13 facilitators mapped to 11 of the 14 TDF domains. The barriers were within the domains of knowledge (e.g., inadequate knowledge of smoking cessation interventions) in 23 (74.2%) studies; environmental context and resources (e.g., lack of time to deliver smoking cessation interventions) in 19 (61.3%) studies; beliefs about capabilities (e.g., belief that patients are nervous about surgery/diagnosis) in 14 (45.2%) studies; and social/professional role and identity (e.g., surgeons do not believe it is their role to provide smoking cessation interventions) in 8 (25.8%) studies. Facilitators were mainly within the domains of environmental context and resources (e.g., provision of quit smoking advice as routine surgical care) in 15 (48.4%) studies, reinforcement (e.g., surgery itself as a motivator to kickstart quit attempts) in 8 (25.8%) studies, and skills (e.g., smoking cessation training and awareness of guidelines) in 5 (16.2%) studies., Conclusion: The identified barriers and facilitators are actionable targets for future studies aimed at translating evidence informed smoking cessation interventions into practice in perioperative settings. More research is needed to evaluate how targeting these barriers and facilitators will impact smoking outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ofori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To determine the epidemiology of post-operative complications among general surgery patients, inform their relationships with 30-day mortality, and determine the attributable fraction of death of each postoperative complication., Background: The contemporary causes of post-operative mortality among general surgery patients are not well characterized., Methods: VISION is a prospective cohort study of adult non-cardiac surgery patients across 28 centres in 14 countries, who were followed for 30 days after surgery. For the subset of general surgery patients, a cox proportional hazards model was used to determine associations between various surgical complications and post-operative mortality. The analyses were adjusted for preoperative and surgical variables. Results were reported in adjusted hazard ratios (HR) with 95% confidence intervals (CI)., Results: Among 7950 patients included in the study, 240 (3.0%) patients died within 30 days of surgery. Five post-operative complications (myocardial injury after non-cardiac surgery [MINS], major bleeding, sepsis, stroke, and acute kidney injury resulting in dialysis) were independently associated with death. Complications associated with the largest attributable fraction (AF) of post-operative mortality (i.e., percentage of deaths in the cohort that can be attributed to each complication, if causality were established) were major bleeding (n=1454, 18.3%, HR 2.49 95%CI 1.87-3.33, P<0.001, AF 21.2%), sepsis (n=783, 9.9%, HR 6.52, 95%CI 4.72-9.01, P<0.001, AF 15.6%), and MINS (n=980, 12.3%, HR 2.00, 95%CI 1.50-2.67, P<0.001, AF 14.4%)., Conclusion: The complications most associated with 30-day mortality following general surgery are major bleeding, sepsis, and MINS. These findings may guide the development of mitigating strategies, including prophylaxis for perioperative bleeding., Competing Interests: Conflict of Interest Statement: Based on study questions Dr. Devereaux has originated and grants he has written, he has received grants from Abbott Diagnostics, AOP Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers-Squibb, CloudDX, Coviden, Octapharma, Philips Healthcare, Roche Diagnostics, Siemens and Stryker. Dr. Devereaux has participated in advisory board meetings for GlaxoSmithKline, Boehringer Ingelheim, Bayer and Quidel Canada. He attended an expert panel meeting with AstraZeneca and Boehringer Ingelheim and he was Consultant for a call with Roche Pharma and consultant work with Abbott Diagnostics, Astra Zeneca, Renibus, Roche Canada and Trimedic. He has also been invited as a speaker with Bayer Inc, Novartis Pharma Canada, and Abbott Diagnostics. Dr. Rosen has no conflicts of interest relevant to this work but discloses the following: ACHQC Medical Director, Telabio grant support, Ariste Medical Stock options., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Hip fracture is a common serious injury among older adults, yet the management of hip fractures for patients taking direct oral anticoagulants remains inconsistent worldwide. Drawing from a synthesis of available evidence and expert opinion, best practice approaches for managing patients with a hip fracture and who are taking direct oral anticoagulants pre-operatively were considered by a working group of the Fragility Fracture Network Hip Fracture Audit Special Interest Group. The literature and related clinical guidelines were reviewed and a two-round modified Delphi study was conducted with a panel of experts from 16 countries and involved seven clinical specialities. Four consensus statements were achieved: peripheral nerve blocks can reasonably be performed on presentation for patients with hip fracture who are receiving direct oral anticoagulants; hip fracture surgery can reasonably be performed for patients taking direct oral anticoagulants < 36 h from last dose; general anaesthesia could reasonably be administered for patients with hip fracture and who are taking direct oral anticoagulants < 36 h from last dose (assuming eGFR > 60 ml.min -1 .1.73 m -2 ); and it is generally reasonable to consider recommencing direct oral anticoagulants (considering blood loss and haemoglobin) < 48 h after hip fracture surgery. No consensus was achieved regarding timing of spinal anaesthesia. The consensus statements were developed to aid clinicians in their decision-making and to reduce practice variations in the management of patients with hip fracture and who are taking direct oral anticoagulants. Each statement will need to be considered specific to each individual patient's treatment., (© 2024 Association of Anaesthetists.)

Objective: To determine timing and risk factors associated with readmission within 30 days of discharge following noncardiac surgery., Background: Hospital readmission after noncardiac surgery is costly. Data on the drivers of readmission have largely been derived from single-center studies focused on a single surgical procedure with uncertainty regarding generalizability., Methods: We undertook an international (28 centers, 14 countries) prospective cohort study of a representative sample of adults ≥45 years of age who underwent noncardiac surgery. Risk factors for readmission were assessed using Cox regression (ClinicalTrials.gov, NCT00512109)., Results: Of 36,657 eligible participants, 2744 (7.5%; 95% confidence interval [CI], 7.2-7.8) were readmitted within 30 days of discharge. Rates of readmission were highest in the first 7 days after discharge and declined over the follow-up period. Multivariable analyses demonstrated that 9 baseline characteristics (eg, cancer treatment in past 6 months; adjusted hazard ratio [HR], 1.44; 95% CI, 1.30-1.59), 5 baseline laboratory and physical measures (eg, estimated glomerular filtration rate or on dialysis; HR, 1.47; 95% CI, 1.24-1.75), 7 surgery types (eg, general surgery; HR, 1.86; 95% CI, 1.61-2.16), 5 index hospitalization events (eg, stroke; HR, 2.21; 95% CI, 1.24-3.94), and 3 other factors (eg, discharge to nursing home; HR, 1.61; 95% CI, 1.33-1.95) were associated with readmission., Conclusions: Readmission following noncardiac surgery is common (1 in 13 patients). We identified perioperative risk factors associated with 30-day readmission that can help frontline clinicians identify which patients are at the highest risk of readmission and target them for preventive measures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: In previous analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these deaths occurred during the index hospitalization for surgery. The authors set out to describe outcomes after discharge from hospital up to 1 yr after inpatient noncardiac surgery and associations between predischarge complications and postdischarge death up to 1 yr after surgery., Methods: This study was an analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007 to 2013 of patients aged 45 yr or older followed to 1 yr after surgery. The study estimated (1) the cumulative postdischarge incidence of death and other outcomes up to a year after surgery and (2) the adjusted time-varying associations between postdischarge death and predischarge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis., Results: Among 38,898 patients discharged after surgery, the cumulative 1-yr incidence was 5.8% (95% CI, 5.5 to 6.0%) for all-cause death and 24.7% (95% CI, 24.2 to 25.1%) for all-cause hospital readmission. Predischarge complications were associated with 33.7% (95% CI, 27.2 to 40.2%) of deaths up to 30 days after discharge and 15.0% (95% CI, 12.0 to 17.9%) up to 1 yr. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [95% CI, 9.3 to 21.9%] of deaths within 30 days, 6.4% [95% CI, 4.1 to 8.7%] within 1 yr), major bleeding (15.0% [95% CI, 8.3 to 21.7%] within 30 days, 4.7% [95% CI, 2.2 to 7.2%] within 1 yr), and sepsis (5.4% [95% CI, 2.2 to 8.6%] within 30 days, 2.1% [95% CI, 1.0 to 3.1%] within 1 yr)., Conclusions: One in 18 patients 45 yr old or older discharged after inpatient noncardiac surgery died within 1 yr, and one quarter were readmitted to the hospital. The risk of death associated with predischarge perioperative complications persists for weeks to months after discharge., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Purpose: Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery. Although the evidence suggests that beta blockers prevent POAF, they often cause hypotension. Landiolol, an ultra-short-acting β 1 blocker, may prevent POAF, without adverse hemodynamic consequences., Source: We searched MEDLINE, CENTRAL, Embase, and trial registries between January 1970 and March 2022. We included randomized controlled trials (RCTs) that evaluated the effect of landiolol for the prevention of POAF after cardiac surgery. Two reviewers independently assessed eligibility, extracted data, and assessed risk of bias using the Risk of Bias 2.0 tool. We pooled data using random-effects models. We used the Grading of Recommendations, Assessment, Development and Evaluations framework to assess certainty of evidence., Principal Findings: Nine RCTs including 868 participants met the eligibility criteria. Patients randomized to landiolol (56/460) had less POAF compared with controls (133/408) with a relative risk (RR) of 0.40 (95% confidence interval [CI], 0.30 to 0.54; I 2  = 0%;) and an absolute risk of 12.2% vs 32.6% (absolute risk difference, 20.4%; 95% CI, 15.0 to 25.0). Landiolol resulted in a shorter hospital length-of-stay (LOS) (268 patients; mean difference, -2.32 days; 95% CI, -4.02 to -0.57; I 2  = 0%). We found no significant difference in bradycardia (RR, 1.11; 95% CI, 0.48 to 2.56; I 2  = 0%). No hypotension was reported with landiolol. We judged the certainty of evidence as moderate for POAF (because of indirectness as outcomes were not clearly defined) and low for LOS (because of imprecision and concern of reporting bias)., Conclusion: In patients undergoing cardiac surgery, landiolol likely reduces POAF and may reduce LOS. A definitive large RCT is needed to confirm these findings., Study Registration: PROSPERO (CRD42021262703); registered 25 July 2021., (© 2023. The Author(s).)

Background: Benzodiazepine use is associated with delirium, and guidelines recommend avoiding them in older and critically ill patients. Their perioperative use remains common because of perceived benefits., Methods: We searched CENTRAL, MEDLINE, CINAHL, PsycInfo, and Web of Science from inception to June 2021. Pairs of reviewers identified randomised controlled trials and prospective observational studies comparing perioperative use of benzodiazepines with other agents or placebo in patients undergoing surgery. Two reviewers independently abstracted data, which we combined using a random-effects model. Our primary outcomes were delirium, intraoperative awareness, and mortality., Results: We included 34 randomised controlled trials (n=4354) and nine observational studies (n=3309). Observational studies were considered separately. Perioperative benzodiazepines did not increase the risk of delirium (n=1352; risk ratio [RR] 1.43; 95% confidence interval [CI]: 0.9-2.27; I 2 =72%; P=0.13; very low-quality evidence). Use of benzodiazepines instead of dexmedetomidine did, however, increase the risk of delirium (five studies; n=429; RR 1.83; 95% CI: 1.24-2.72; I 2 =13%; P=0.002). Perioperative benzodiazepine use decreased the risk of intraoperative awareness (n=2245; RR 0.26; 95% CI: 0.12-0.58; I 2 =35%; P=0.001; very low-quality evidence). When considering non-events, perioperative benzodiazepine use increased the probability of not having intraoperative awareness (RR 1.07; 95% CI: 1.01-1.13; I 2 =98%; P=0.03; very low-quality evidence). Mortality was reported by one randomised controlled trial (n=800; RR 0.90; 95% CI: 0.20-3.1; P=0.80; very low quality)., Conclusions: In this systematic review and meta-analysis, perioperative benzodiazepine use did not increase postoperative delirium and decreased intraoperative awareness. Previously observed relationships of benzodiazepine use with delirium could be explained by comparisons with dexmedetomidine., Systematic Review Protocol: PROSPERO CRD42019128144., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Myocardial injury due to ischaemia within 30 days of non-cardiac surgery is prognostically relevant. We aimed to determine the discrimination, calibration, accuracy, sensitivity and specificity of single-layer and multiple-layer neural networks for myocardial injury and death within 30 postoperative days. We analysed data from 24,589 participants in the Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation study. Validation was performed on a randomly selected subset of the study population. Discrimination for myocardial injury by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.70 (0.69-0.72) vs. 0.71 (0.70-0.73) with variables available before surgical referral, p < 0.001; 0.73 (0.72-0.75) vs. 0.75 (0.74-0.76) with additional variables available on admission, but before surgery, p < 0.001; and 0.76 (0.75-0.77) vs. 0.77 (0.76-0.78) with the addition of subsequent variables, p < 0.001. Discrimination for death by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.71 (0.66-0.76) vs. 0.74 (0.71-0.77) with variables available before surgical referral, p = 0.04; 0.78 (0.73-0.82) vs. 0.83 (0.79-0.86) with additional variables available on admission but before surgery, p = 0.01; and 0.87 (0.83-0.89) vs. 0.87 (0.85-0.90) with the addition of subsequent variables, p = 0.52. The accuracy of the multiple-layer model for myocardial injury and death with all variables was 70% and 89%, respectively., (© 2023 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Background: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively., Objective: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery., Design: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723)., Setting: 110 hospitals in 22 countries., Patients: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications., Intervention: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery., Measurements: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment., Results: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P  = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term., Limitation: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels., Conclusion: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications., Primary Funding Source: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-3157.

Background: The association between growth differentiation factor-15 concentrations and cardiovascular disease has been well described. The study hypothesis was that growth differentiation factor-15 may help cardiac risk stratification in noncardiac surgical patients, in addition to clinical evaluation., Methods: The objective of the study was to determine whether preoperative serum growth differentiation factor-15 is associated with the composite primary outcome of myocardial injury after noncardiac surgery and vascular death at 30 days and can improve cardiac risk prediction in noncardiac surgery. This is a prospective cohort study of patients 45 yr or older having major noncardiac surgery. The association between preoperative growth differentiation factor-15 and the primary outcome was determined after adjusting for the Revised Cardiac Risk Index. Preoperative N-terminal-pro hormone brain natriuretic peptide was also added to compare predictive performance with growth differentiation factor-15., Results: Between October 27, 2008, and October 30, 2013, a total of 5,238 patients were included who had preoperative growth differentiation factor-15 measured (median, 1,325; interquartile range, 880 to 2,132 pg/ml). The risk of myocardial injury after noncardiac surgery and vascular death was 99 of 1,705 (5.8%) for growth differentiation factor-15 less than 1,000 pg/ml, 161 of 1,332 (12.1%) for growth differentiation factor-15 1,000 to less than 1,500 pg/ml, 302 of 1476 (20.5%) for growth differentiation factor-15 1,500 to less than 3,000 pg/ml, and 247 of 725 (34.1%) for growth differentiation factor-15 concentrations 3,000 pg/ml or greater. Compared to patients who had growth differentiation factor-15 concentrations less than 1,000 pg/ml, the corresponding adjusted hazard ratio for each growth differentiation factor-15 category was 1.93 (95% CI, 1.50 to 2.48), 3.04 (95% CI, 2.41 to 3.84), and 4.8 (95% CI, 3.76 to 6.14), respectively. The addition of growth differentiation factor-15 improved cardiac risk classification by 30.1% (301 per 1,000 patients) compared to Revised Cardiac Risk Index alone. It also provided additional risk classification beyond the combination of preoperative N-terminal-pro hormone brain natriuretic peptide and Revised Cardiac Risk Index (16.1%; 161 per 1,000 patients)., Conclusions: Growth differentiation factor-15 is strongly associated with 30-day risk of major cardiovascular events and significantly improved cardiac risk prediction in patients undergoing noncardiac surgery., (Copyright © 2023, the American Society of Anesthesiologists. All Rights Reserved.)

Background: Myocardial injury after non-cardiac surgery (MINS), based on measurement of troponin T, is associated with perioperative major adverse cardiovascular events (MACE). We therefore determined the high-sensitivity troponin I (hsTnI) thresholds associated with 30 day MACE after non-cardiac surgery., Methods: We performed a nested biobank cohort study of 4553 patients from the Vascular Events in Non-Cardiac Surgery Patients Cohort Evaluation (VISION) Study. We measured hsTnI (ADVIA Centaur® hsTnI assay) on postoperative days 1 to 3 in patients ≥45 years undergoing non-cardiac surgery. An iterative Cox proportional hazard model determined peak postoperative hsTnI thresholds independently associated with MACE (i.e., death, myocardial infarction occurring on postoperative day 4 or after, non-fatal cardiac arrest, or congestive heart failure) within 30 days after surgery., Results: MACE occurred in 89/4545 (2.0%) patients. Peak hsTnI values of <75 ng/L, 75 ng/L to <1000 ng/L, and ≥1000 ng/L were associated with 1.2% (95% CI, 0.9-1.6), 7.1% (95% CI, 4.8-10.5), and 25.9% (95% CI, 16.3-38.4) MACE, respectively. Compared to peak hsTnI <75 ng/L, values 75 ng/L to <1000 ng/L and ≥1000 ng/L were associated with adjusted hazard ratios (aHR) of 4.53 (95% CI, 2.75-7.48) and 16.17 (95% CI, 8.70-30.07), respectively. MACE was observed in 9% of patients with peak hsTnI ≥75 ng/L vs 1% in patients with peak hsTnI <75 ng/L (aHR 5.76; 95% CI, 3.64-9.11). A peak hsTnI ≥75 ng/L was associated with MACE in the presence (aHR 9.35; 95% CI, 5.28-16.55) or absence (aHR 3.99; 95% CI, 2.19-7.25) of ischemic features of myocardial injury., Conclusion: A peak postoperative hsTnI ≥75 ng/L was associated with >5-fold increase in the risk of 30 days MACE compared to levels <75 ng/L. This threshold could be used for MINS diagnosis when the ADVIA Centaur hsTnI assay is used.Clinicaltrials.gov Registration Number: NCT00512109., (© American Association for Clinical Chemistry 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Myocardial injury after noncardiac surgery (MINS) is common and associated with short- and long-term major cardiovascular events. Diagnostic criteria for MINS using Abbott high-sensitivity cardiac troponin I (hs-cTnI) are unknown., Methods: We performed a prospective cohort study of adults who had in-patient noncardiac surgery and measured hs-cTnI (Abbott Laboratories) on postoperative serum samples collected up to postoperative day 3. The objective was to determine prognostically important hs-cTnI thresholds associated with major cardiac events and death at 30 days after noncardiac surgery. Using Cox proportional iterative analyses, we determined peak postoperative hs-cTnI thresholds associated with the occurrence of the 30-day composite of major cardiac events (ie, nonfatal myocardial infarction after 3 postoperative days, cardiac arrest, and congestive heart failure) and death., Results: Of 3953 included patients, 66 (1.7%) experienced the primary outcome at 30 days. Peak hs-cTnI values and associated incidence of major cardiac events and death were as follows: < 60 ng/L: 1.0% (95% CI 0.7-1.3); 60 to < 700 ng/L: 8.6% (5.6-13.0); and ≥ 700 ng/L: 27.3% (16.4-41.9). Compared with peak hs-cTnI < 60 ng/L, adjusted hazard ratios were 7.54 (95% CI% 4.27-13.32) for hs-cTnI values of 60 to < 700 ng/L and 26.87 (13.27-54.41) for values ≥ 700 ng/L., Conclusions: Hs-cTnI elevation within the first 3 days after noncardiac surgery independently predicts major cardiac events and death at 30 days. A postoperative hs-cTnI ≥ 60 ng/L was associated with a > 7-fold increase in the risk of subsequent major cardiac events and mortality at 30 days., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Some studies suggest that patients with pulmonary hypertension (PH) may be at higher risk of complications and death after noncardiac surgery. However, the magnitude of these associations is unclear., Objectives: To determine the associations between PH and adverse outcomes after noncardiac surgery., Methods: We searched PUBMED and EMBASE for studies published from January 1970 to April 2022. We included studies that reported the association between PH and one or more outcomes of interest occurring after noncardiac surgery. Data were pooled using random-effects models and reported as summary odds ratios (ORs) with 95% confidence intervals (CIs)., Results: Eighteen studies met eligibility criteria (n=18,214,760). PH was independently associated with mortality (adjusted odds ratio [OR] 2.09; 95% CI, 1.51-2.90; I 2 =98%; 8 studies). PH was associated with a higher unadjusted risk of deep venous thrombosis (OR 4.02; 95% CI, 2.14-7.54; I 2 =85%; 3 studies), pulmonary embolism (OR 4.16; 95% CI, 3.23-5.36; I 2 =69%; 7 studies), myocardial infarction (OR 1.49; 95% CI, 1.44-1.54; I 2 =0%; 5 studies), congestive heart failure or cardiogenic shock (OR 3.37; 95% CI, 1.73-6.60; I 2 =34%; 5 studies), length of hospital stay (mean difference 1.97 days; 95% CI, 0.81-3.12; I 2 =99%; 5 studies), and delayed extubation (OR 5.98; 95% CI, 1.70-21.02; I 2 =3%; 3 studies). PH was associated with lower unadjusted risk of postoperative stroke (OR 0.93; 95% CI, 0.88-0.98; I 2 =0%; 3 studies)., Conclusion: PH is a predictor of morbidity and mortality after noncardiac surgery. High quality studies are needed to determine effective strategies for reducing postoperative complications in this population., Competing Interests: Declaration of Competing Interest The author declare no conflicts of interest with the contents of this manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To determine the association of elevated troponin levels with time to surgery and the risk of mortality and other key clinical outcomes among elderly patients with hip fracture who had measured troponin levels at hospital admission., Design: Retrospective cohort study., Setting: Single academic trauma center., Patients: We included 299 consecutive patients 60 years of age or older with a hip fracture and cardiac troponin levels measured at the time of hospital admission., Intervention: Patients with elevated cardiac troponin levels at hospital admission (n = 43) compared with patients with normal troponin levels at admission (n = 256)., Main Outcome Measures: Time to surgery, 90-day mortality, and major complications within 90 days of injury., Results: The median age of the cohort was 80 years (interquartile range, 70-87 years), 59% were female, and 86% were living independently before their injury. Elevated troponin levels were associated with a 21-hour [95% confidence interval (CI), 12 to 32, P < 0.001] increase in the median time from admission to surgery (43 vs. 22 hours). Elevated troponin levels were also associated with a 14% (95% CI, 0% to 29%, P = 0.01) absolute increase in 90-day mortality (28% vs. 14%). Patients with elevated troponins were 15% (95% CI, -1% to 30%, P = 0.06) more likely to have a major complication (37% vs. 23%); however, the difference did not reach statistical significance., Conclusions: Among patients with a hip fracture and measured troponin levels, elevated troponin levels were associated with significant delays in surgery and increased 90-day mortality., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: N. N. O'Hara reported receiving stock or stock options from Arbutus Medical, Inc. unrelated to this research. G. P. Slobogean reported receiving research funding from the Patient-Centered Outcomes Research Institute, the US Department of Defense, and the National Institutes of Health unrelated to this research; and serving as a paid consultant with Nuvasive Orthopedics, Smith & Nephew, and Zimmer Biomet unrelated to this research. The remaining authors report no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Centralized statistical monitoring is sometimes employed as an alternative to onsite monitoring for randomized control trials. Current central monitoring methods have limitations, in that they are relatively resource intensive and do not necessarily generalize to studies where an irregularity pattern has not been observed before. Machine learning has been effective in detecting irregularities in industries such as finance and manufacturing, but to date none have been applied to clinical trials. We conducted a pilot study for the use of machine learning to identify center-level irregularities in data from multicenter clinical trials. We employed unsupervised machine learning methods, which do not rely on labelled data, and therefore allow for the automated discovery of previously unseen irregularity patterns while maintaining flexibility when applied to new data with different structures. This pilot study employs unsupervised machine learning to compute distance matrices between centres, which we used to produce centre-level continuous features. We then used a one-class support vector machine to learn the underlying distribution of each data set to identify data that was substantially different from these distributions. We evaluated our approach against current automatable centralized monitoring methods on two trials with known irregularities. While current approaches performed well on one trial (AUROC 0.752 for monitoring vs. 0.584 for machine learning), our techniques performed substantially better on the other (AUROC 0.140 for monitoring vs 0.728 for machine learning). The results of this pilot study suggest both the feasibility and the potential value of a machine learning-based approach to irregularity detection in RCTs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Tobacco smoking is a leading preventable cause of death and increases perioperative risk. Determinants of smoking abstinence after noncardiac surgery and the association between smoking and 1-yr vascular outcomes are not fully elucidated., Methods: We did a prospective cohort study of 40 004 patients, aged ≥45 yr, enrolled between August 2007 and November 2013, and followed for 1 yr after surgery. Patients were categorised as never smokers, ex-smokers (quit >4 weeks preoperatively), and current smokers (smoking ≤4 weeks preoperatively). Primary outcome was abstinence at 1 yr. Secondary outcome was a composite of all-cause death, non-fatal myocardial infarction, and non-fatal stroke at 1 yr., Results: Of 4658 current smokers, 1838 (39.5%) were abstinent 1 yr after surgery. Median (inter-quartile range) time to resumption was 7 (3-23) days post-surgery. Perioperatively, 7.2% of current smokers obtained smoking cessation pharmacotherapy. Older age (adjusted risk ratio [aRR] 1.21; 95% confidence interval [CI]: 1.12-1.32); having recent coronary artery disease (aRR 1.41; 95% CI: 1.29-1.55); cancer (aRR 1.37; 95% CI: 1.18-1.59); and undergoing major vascular (aRR 1.20; 95% CI: 1.02-1.41), urgent/emergent (aRR 1.14; 95% CI: 1.05-1.23), or thoracic (aRR 1.41; 95% CI: 1.26-1.56) surgeries increased abstinence. One-year abstinence was less likely when patients stopped smoking 0-1 day (aRR 0.53; 95% CI: 0.43-0.66) and 2-14 days (aRR 0.76; 95% CI: 0.71-0.82) before surgery compared with >14 days before surgery. Current smokers (adjusted hazard ratio [aHR] 1.14; 95% CI: 1.01-1.29) and ex-smokers (aHR 1.11; 95% CI: 1.03-1.21) had higher risk of the 1-yr vascular outcome compared with never smokers., Conclusions: Long-term tobacco abstinence is more likely after major surgery in those with serious medical comorbidities. Interventions to prevent smoking resumption after surgery remain a priority. Clinical trial registration NCT00512109., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding., Methods: We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025., Results: A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority)., Conclusions: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.)., (Copyright © 2022 Massachusetts Medical Society.)

Background: Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to ≥70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations., Methods: We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery. High-sensitivity cardiac troponin I measurements (upper reference limit, 26 ng per liter) were obtained 3 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II (which estimates the risk of death after cardiac surgery on the basis of 18 variables, including age and sex)., Results: Of 13,862 patients included in the study, 296 (2.1%) died within 30 days after surgery. Among patients who underwent isolated coronary-artery bypass grafting or aortic-valve replacement or repair, the threshold troponin level, measured within 1 day after surgery, that was associated with an adjusted hazard ratio of more than 1.00 for death within 30 days was 5670 ng per liter (95% confidence interval [CI], 1045 to 8260), a level 218 times the upper reference limit. Among patients who underwent other cardiac surgery, the corresponding threshold troponin level was 12,981 ng per liter (95% CI, 2673 to 16,591), a level 499 times the upper reference limit., Conclusions: The levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury. (Funded by the Canadian Institutes of Health Research and others; VISION Cardiac Surgery ClinicalTrials.gov number, NCT01842568.)., (Copyright © 2022 Massachusetts Medical Society.)

Background: Wearable continuous monitoring biosensor technologies have the potential to transform postoperative care with early detection of impending clinical deterioration., Objective: Our aim was to validate the accuracy of Cloud DX Vitaliti continuous vital signs monitor (CVSM) continuous noninvasive blood pressure (cNIBP) measurements in postsurgical patients. A secondary aim was to examine user acceptance of the Vitaliti CVSM with respect to comfort, ease of application, sustainability of positioning, and aesthetics., Methods: Included participants were ≥18 years old and recovering from surgery in a cardiac intensive care unit (ICU). We targeted a maximum recruitment of 80 participants for verification and acceptance testing. We also oversampled to minimize the effect of unforeseen interruptions and other challenges to the study. Validation procedures were according to the International Standards Organization (ISO) 81060-2:2018 standards for wearable, cuffless blood pressure (BP) measuring devices. Baseline BP was determined from the gold-standard ICU arterial catheter. The Vitaliti CVSM was calibrated against the reference arterial catheter. In static (seated in bed) and supine positions, 3 cNIBP measurements, each 30 seconds, were taken for each patient with the Vitaliti CVSM and an invasive arterial catheter. At the conclusion of each test session, captured cNIBP measurements were extracted using MediCollector BEDSIDE data extraction software, and Vitaliti CVSM measurements were extracted to a secure laptop through a cable connection. The errors of these determinations were calculated. Participants were interviewed about device acceptability., Results: The validation analysis included data for 20 patients. The average times from calibration to first measurement in the static position and to first measurement in the supine position were 133.85 seconds (2 minutes 14 seconds) and 535.15 seconds (8 minutes 55 seconds), respectively. The overall mean errors of determination for the static position were -0.621 (SD 4.640) mm Hg for systolic blood pressure (SBP) and 0.457 (SD 1.675) mm Hg for diastolic blood pressure (DBP). Errors of determination were slightly higher for the supine position, at 2.722 (SD 5.207) mm Hg for SBP and 2.650 (SD 3.221) mm Hg for DBP. The majority rated the Vitaliti CVSM as comfortable. This study was limited to evaluation of the device during a very short validation period after calibration (ie, that commenced within 2 minutes after calibration and lasted for a short duration of time)., Conclusions: We found that the Cloud DX's Vitaliti CVSM demonstrated cNIBP measurement in compliance with ISO 81060-2:2018 standards in the context of evaluation that commenced within 2 minutes of device calibration; this device was also well-received by patients in a postsurgical ICU setting. Future studies will examine the accuracy of the Vitaliti CVSM in ambulatory contexts, with attention to assessment over a longer duration and the impact of excessive patient motion on data artifacts and signal quality., Trial Registration: ClinicalTrials.gov NCT03493867; https://clinicaltrials.gov/ct2/show/NCT03493867., (©Michael H McGillion, Nazari Dvirnik, Stephen Yang, Emilie Belley-Côté, Andre Lamy, Richard Whitlock, Maura Marcucci, Flavia K Borges, Emmanuelle Duceppe, Carley Ouellette, Marissa Bird, Sandra L Carroll, David Conen, Jean-Eric Tarride, Prathiba Harsha, Ted Scott, Amber Good, Krysten Gregus, Karla Sanchez, Pamela Benoit, Julian Owen, Valerie Harvey, Elizabeth Peter, Jeremy Petch, Jessica Vincent, Michelle Graham, P J Devereaux. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 28.02.2022.)

The pursuit of more efficient patient-friendly health systems and reductions in tertiary health services use has seen enormous growth in the application and study of remote patient monitoring systems for cardiovascular patient care. While there are many consumer-grade products available to monitor patient wellness, the regulation of these technologies varies considerably, with most products having little to no evaluation data. As the science and practice of virtual care continues to evolve, clinicians and researchers can benefit from an understanding of more comprehensive solutions capable of monitoring multiple biophysical parameters (eg, oxygen saturation, heart rate) continuously and simultaneously. These devices, herein referred to as continuous multiparameter remote automated monitoring (CM-RAM) devices, have the potential to revolutionise virtual patient care. Through seamless integration of multiple biophysical signals, CM-RAM technologies can allow for the acquisition of high-volume big data for the development of algorithms to facilitate early detection of negative changes in patient health status and timely clinician response. In this article, we review key principles, architecture, and components of CM-RAM technologies. Work to date in this field and related implications are also presented, including strategic priorities for advancing the science and practice of CM-RAM., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes., Methods: The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization., Discussion: Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality., Trial Registration: ClinicalTrials.gov NCT03505723. Registered on 23 April 2018., (© 2022. The Author(s).)

Background: Most patients who take antihypertensive medications continue taking them on the morning of surgery and during the perioperative period. However, growing evidence suggests this practice may contribute to perioperative hypotension and a higher risk of complications. This protocol describes an acute kidney injury substudy of the Perioperative Ischemic Evaluation-3 (POISE-3) trial, which is testing the effect of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy in patients undergoing noncardiac surgery., Objective: To conduct a substudy of POISE-3 to determine whether a perioperative hypotension-avoidance strategy reduces the risk of acute kidney injury compared with a hypertension-avoidance strategy., Design: Randomized clinical trial with 1:1 randomization to the intervention (a perioperative hypotension-avoidance strategy) or control (a hypertension-avoidance strategy)., Intervention: If the presurgery systolic blood pressure (SBP) is <130 mmHg, all antihypertensive medications are withheld on the morning of surgery. If the SBP is ≥130 mmHg, some medications (but not angiotensin receptor blockers [ACEIs], angiotensin receptor blockers [ARBs], or renin inhibitors) may be continued in a stepwise manner. During surgery, the patients' mean arterial pressure (MAP) is maintained at ≥80 mmHg. During the first 48 hours after surgery, some antihypertensive medications (but not ACEIs, ARBs, or renin inhibitors) may be restarted in a stepwise manner if the SBP is ≥130 mmHg., Control: Patients receive their usual antihypertensive medications before and after surgery. The patients' MAP is maintained at ≥60 mmHg from anesthetic induction until the end of surgery., Setting: Recruitment from 108 centers in 22 countries from 2018 to 2021., Patients: Patients (~6800) aged ≥45 years having noncardiac surgery who have or are at risk of atherosclerotic disease and who routinely take antihypertensive medications., Measurements: The primary outcome of the substudy is postoperative acute kidney injury, defined as an increase in serum creatinine concentration of either ≥26.5 μmol/L (≥0.3 mg/dL) within 48 hours of randomization or ≥50% within 7 days of randomization., Methods: The primary analysis (intention-to-treat) will examine the relative risk and 95% confidence interval of acute kidney injury in the intervention versus control group. We will repeat the primary analysis using alternative definitions of acute kidney injury and examine effect modification by preexisting chronic kidney disease, defined as a prerandomization estimated glomerular filtration rate <60 mL/min/1.73 m 2 ., Results: Substudy results will be analyzed in 2022., Limitations: It is not possible to mask patients or providers to the intervention; however, objective measures will be used to assess acute kidney injury., Conclusions: This substudy will provide generalizable estimates of the effect of a perioperative hypotension-avoidance strategy on the risk of acute kidney injury., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Objective: To determine if virtual care with remote automated monitoring (RAM) technology versus standard care increases days alive at home among adults discharged after non-elective surgery during the covid-19 pandemic., Design: Multicentre randomised controlled trial., Setting: 8 acute care hospitals in Canada., Participants: 905 adults (≥40 years) who resided in areas with mobile phone coverage and were to be discharged from hospital after non-elective surgery were randomised either to virtual care and RAM (n=451) or to standard care (n=454). 903 participants (99.8%) completed the 31 day follow-up., Intervention: Participants in the experimental group received a tablet computer and RAM technology that measured blood pressure, heart rate, respiratory rate, oxygen saturation, temperature, and body weight. For 30 days the participants took daily biophysical measurements and photographs of their wound and interacted with nurses virtually. Participants in the standard care group received post-hospital discharge management according to the centre's usual care. Patients, healthcare providers, and data collectors were aware of patients' group allocations. Outcome adjudicators were blinded to group allocation., Main Outcome Measures: The primary outcome was days alive at home during 31 days of follow-up. The 12 secondary outcomes included acute hospital care, detection and correction of drug errors, and pain at 7, 15, and 30 days after randomisation., Results: All 905 participants (mean age 63.1 years) were analysed in the groups to which they were randomised. Days alive at home during 31 days of follow-up were 29.7 in the virtual care group and 29.5 in the standard care group: relative risk 1.01 (95% confidence interval 0.99 to 1.02); absolute difference 0.2% (95% confidence interval -0.5% to 0.9%). 99 participants (22.0%) in the virtual care group and 124 (27.3%) in the standard care group required acute hospital care: relative risk 0.80 (0.64 to 1.01); absolute difference 5.3% (-0.3% to 10.9%). More participants in the virtual care group than standard care group had a drug error detected (134 (29.7%) v 25 (5.5%); absolute difference 24.2%, 19.5% to 28.9%) and a drug error corrected (absolute difference 24.4%, 19.9% to 28.9%). Fewer participants in the virtual care group than standard care group reported pain at 7, 15, and 30 days after randomisation: absolute differences 13.9% (7.4% to 20.4%), 11.9% (5.1% to 18.7%), and 9.6% (2.9% to 16.3%), respectively. Beneficial effects proved substantially larger in centres with a higher rate of care escalation., Conclusion: Virtual care with RAM shows promise in improving outcomes important to patients and to optimal health system function., Trial Registration: ClinicalTrials.gov NCT04344665., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare: support from Roche, McMaster University, the Research Institute of St Joseph’s Healthcare Hamilton, Ottawa Hospital Academic Medical Association, Queen’s University, Hamilton Health Sciences, Kingston Health Sciences, London Health Sciences, St Joseph’s Healthcare Hamilton, the Ottawa Hospital, and the University of Alberta Hospital for the submitted work; a financial relationship with Cloud Diagnostics Canada for purchase of devices and data plans used in this trial; and a relationship with Cloud Diagnostics Canada, which undertook training sessions for virtual nurses and perioperative doctors and surgeons on how to use their technology., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Perioperative risk factors predicting major cardiovascular events (MACE) and the performance of the Revised Cardiac Risk Index (RCRI) in a retrospective cohort of 325 consecutive adult patients undergoing kidney transplant from deceased donor grafts were assessed. Primary outcome was a composite of MACE up to 30 days post-transplant. Incidence of MACE was 5.8% at 30 days. Overall proportion of patients with RCRI ≥ 4 was 5%, but was higher (28%) among those who developed MACE. Patients with RCRI ≥ 4 had lower survival free of MACE compared to those with RCRI < 4 (P <0.001); however, in multivariable analysis, RCRI was not a predictor of cardiovascular events. The RCRI demonstrated poor discrimination to predict MACE at 30 days [area under the curve 0.64 (95% CI 0.49-0.78)]. Revised Cardiac Risk Index was not associated with reduced MACE-free survival adjusted analysis and its predictive ability was poor., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: After nonelective (i.e., semiurgent, urgent and emergent) surgeries, patients discharged from hospitals are at risk of readmissions, emergency department visits or death. During the coronavirus disease 2019 (COVID-19) pandemic, we are undertaking the Post Discharge after Surgery Virtual Care with Remote Automated Monitoring Technology (PVC-RAM) trial to determine if virtual care with remote automated monitoring (RAM) compared with standard care will increase the number of days adult patients remain alive at home after being discharged following nonelective surgery., Methods: We are conducting a randomized controlled trial in which 900 adults who are being discharged after nonelective surgery from 8 Canadian hospitals are randomly assigned to receive virtual care with RAM or standard care. Outcome adjudicators are masked to group allocations. Patients in the experimental group learn how to use the study's tablet computer and RAM technology, which will measure their vital signs. For 30 days, patients take daily biophysical measurements and complete a recovery survey. Patients interact with nurses via the cellular modem-enabled tablet, who escalate care to preassigned and available physicians if RAM measurements exceed predetermined thresholds, patients report symptoms, a medication error is identified or the nurses have concerns they cannot resolve. The primary outcome is number of days alive at home during the 30 days after randomization., Interpretation: This trial will inform management of patients after discharge following surgery in the COVID-19 pandemic and offer insights for management of patients who undergo nonelective surgery in a nonpandemic setting. Knowledge dissemination will be supported through an online multimedia resource centre, policy briefs, presentations, peer-reviewed journal publications and media engagement., Trial Registration: ClinicalTrials.gov, no. NCT04344665., Competing Interests: Competing interests: CloudDX undertook training sessions for study nurses, perioperative physicians and surgeons regarding how to use their technology. David Conen has received personal fees from Servier Canada, outside of the current work. Emil Schemitsch has received personal fees from Stryker, Smith & Nephew, ITS Implants, Acumed, Swemac and DePuy Synthes, outside the present work. Emilie Belley-Cote has received grants from Bayer and Roche, outside the present work. Richard Whitlock has received grants from Bayer, Roche and Boehringer Ingelheim, an honorarium from Boehringer Ingeheim and consulting fees from AtriCure and PhaseBio, outside the present work. P.J. Devereaux has received a grant from Roche Diagnostics for the present work and grants from Abbott Diagnostics, Boehringer Ingeheim, Roche Diagnostics and Siemens, outside the present work, as well as patient monitors from Philips Healthcare and troponin assays from Siemens, outside the present work., (© 2021 Joule Inc. or its licensors.)

Myocardial injury after noncardiac surgery (MINS) includes patients with traditional myocardial infarction and those with ischemic myocardial injury after surgery. This study evaluated the prognostic value of MINS on major cardiovascular events and 30-day mortality, and determined independent preoperative predictors of MINS in patients after noncardiac surgery. This multicenter prospective cohort study was part of the VISION Study. The sample consisted of 2504 patients who underwent noncardiac surgery at 2 tertiary hospitals in Brazil between September 2008 and July 2012. Troponin Ts were measured 6-12 hours, and on days 1-3 after surgery. Cox regression analyses were performed to identify independent variables of major outcomes. A total of 314 (13%) patients were diagnosed with MINS, of which 26 (8%) died. Length-of-hospital stay of MINS patients was 3 times higher (18 ± 22 days vs 5.8 ± 11 days). In multivariate analysis, 30-day mortality was significantly higher among patients with MINS (hazard ratio [HR] 3.17 (95% confidence interval [CI] 1.56-6.41)), and major bleeding (HR 5.76 (95% CI 2.75-12.05)), sepsis (HR 5.08 (95% CI 2.25-11.46)), active cancer (HR 4.22 (95% CI 1.98-8.98)), and general surgery (HR 3.11 (95% CI 1.51-6.41)). Multivariable analysis indicated a higher chance of MINS in patients ≥75 years of age, history of diabetes mellitus, hypertension, heart failure, coronary disease, and end-stage renal failure. The incidence of MINS within 30 days after noncardiac surgery is related to higher mortality. Postoperative troponin monitoring in elder patients and with risk factors for atherosclerotic disease may help reduce postoperative cardiovascular events., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: We aimed to establish diagnostic criteria for bleeding independently associated with mortality after noncardiac surgery (BIMS) defined as bleeding during or within 30 days after noncardiac surgery that is independently associated with mortality within 30 days of surgery, and to estimate the proportion of 30-day postoperative mortality potentially attributable to BIMS., Methods: This was a prospective cohort study of participants ≥45 yr old having inpatient noncardiac surgery at 12 academic hospitals in eight countries between 2007 and 2011. Cox proportional hazards models evaluated the adjusted relationship between candidate diagnostic criteria for BIMS and all-cause mortality within 30 days of surgery., Results: Of 16 079 participants, 2.0% (315) died and 36.1% (5810) met predefined screening criteria for bleeding. Based on independent association with 30-day mortality, BIMS was identified as bleeding leading to a postoperative haemoglobin <70 g L -1 , transfusion of ≥1 unit of red blood cells, or that was judged to be the cause of death. Bleeding independently associated with mortality after noncardiac surgery occurred in 17.3% of patients (2782). Death occurred in 5.8% of patients with BIMS (161/2782), 1.3% (39/3028) who met bleeding screening criteria but not BIMS criteria, and 1.1% (115/10 269) without bleeding. BIMS was associated with mortality (adjusted hazard ratio: 1.87; 95% confidence interval: 1.42-2.47). We estimated the proportion of 30-day postoperative deaths potentially attributable to BIMS to be 20.1-31.9%., Conclusions: Bleeding independently associated with mortality after noncardiac surgery (BIMS), defined as bleeding that leads to a postoperative haemoglobin <70 g L -1 , blood transfusion, or that is judged to be the cause of death, is common and may account for a quarter of deaths after noncardiac surgery., Clinical Trial Registration: NCT00512109., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Diagnostic criteria for Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS) have been defined as bleeding that leads to a postoperative haemoglobin <70 g L -1 , leads to blood transfusion, or is judged to be the direct cause of death. Preoperative prediction guides for BIMS can facilitate informed consent and planning of perioperative care., Methods: In a prospective cohort study of 16 079 participants aged ≥45 yr having inpatient noncardiac surgery at 12 academic hospitals in eight countries between 2007 and 2011, 17.3% (2782) experienced BIMS. An electronic risk calculator for BIMS was developed and internally validated by logistic regression with bootstrapping, and further simplified to a risk index. Decision curve analysis assessed the potential utility of each prediction guide compared with a strategy of identifying risk of BIMS based on preoperative haemoglobin <120 g L -1 ., Results: With information about the type of surgery, preoperative haemoglobin, age, sex, functional status, kidney function, history of high-risk coronary artery disease, and active cancer, the risk calculator accurately predicted BIMS (bias-corrected C-statistic, 0.84; 95% confidence interval, 0.837-0.852). A simplified index based on preoperative haemoglobin <120 g L -1 , open surgery, and high-risk surgery also predicted BIMS, but less accurately (C-statistic, 0.787; 95% confidence interval, 0.779-0.796). Both prediction guides could improve decision making compared with knowledge of haemoglobin <120 g L -1 alone., Conclusions: BIMS, defined as bleeding that leads to a postoperative haemoglobin <70 g L -1 , leads to blood transfusion, or that is judged to be the direct cause of death, can be predicted by a simple risk index before surgery., Clinical Trial Registration: NCT00512109., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Physicians commonly judge whether a myocardial infarction (MI) is type 1 (thrombotic) vs type 2 (supply/demand mismatch) based on clinical information. Little is known about the accuracy of physicians' clinical judgement in this regard. We aimed to determine the accuracy of physicians' judgement in the classification of type 1 vs type 2 MI in perioperative and nonoperative settings., Methods: We performed an online survey using cases from the Op tical Coherence T omographic Im aging of Thromb us (OPTIMUS) Study, which investigated the prevalence of a culprit lesion thrombus based on intracoronary optical coherence tomography (OCT) in patients experiencing MI. Four MI cases, 2 perioperative and 2 nonoperative, were selected randomly, stratified by etiology. Physicians were provided with the patient's medical history, laboratory parameters, and electrocardiograms. Physicians did not have access to intracoronary OCT results. The primary outcome was the accuracy of physicians' judgement of MI etiology, measured as raw agreement between physicians and intracoronary OCT findings. Fleiss' kappa and Gwet's AC1 were calculated to correct for chance., Results: The response rate was 57% (308 of 536). Respondents were 62% male; median age was 45 years (standard deviation ± 11); 45% had been in practice for > 15 years. Respondents' overall accuracy for MI etiology was 60% (95% confidence interval [CI] 57%-63%), including 63% (95% CI 60%-68%) for nonoperative cases, and 56% (95% CI 52%-60%) for perioperative cases. Overall chance-corrected agreement was poor (kappa = 0.05), consistent across specialties and clinical scenarios., Conclusions: Physician accuracy in determining MI etiology based on clinical information is poor. Physicians should consider results from other testing, such as invasive coronary angiography, when determining MI etiology., (© 2020 Canadian Cardiovascular Society. Published by Elsevier Inc.)

Background: Preliminary data suggest that preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) may improve risk prediction in patients undergoing noncardiac surgery., Objective: To determine whether preoperative NT-proBNP has additional predictive value beyond a clinical risk score for the composite of vascular death and myocardial injury after noncardiac surgery (MINS) within 30 days after surgery., Design: Prospective cohort study., Setting: 16 hospitals in 9 countries., Patients: 10 402 patients aged 45 years or older having inpatient noncardiac surgery., Measurements: All patients had NT-proBNP levels measured before surgery and troponin T levels measured daily for up to 3 days after surgery., Results: In multivariable analyses, compared with preoperative NT-proBNP values less than 100 pg/mL (the reference group), those of 100 to less than 200 pg/mL, 200 to less than 1500 pg/mL, and 1500 pg/mL or greater were associated with adjusted hazard ratios of 2.27 (95% CI, 1.90 to 2.70), 3.63 (CI, 3.13 to 4.21), and 5.82 (CI, 4.81 to 7.05) and corresponding incidences of the primary outcome of 12.3% (226 of 1843), 20.8% (542 of 2608), and 37.5% (223 of 595), respectively. Adding NT-proBNP thresholds to clinical stratification (that is, the Revised Cardiac Risk Index [RCRI]) resulted in a net absolute reclassification improvement of 258 per 1000 patients. Preoperative NT-proBNP values were also statistically significantly associated with 30-day all-cause mortality (less than 100 pg/mL [incidence, 0.3%], 100 to less than 200 pg/mL [incidence, 0.7%], 200 to less than 1500 pg/mL [incidence, 1.4%], and 1500 pg/mL or greater [incidence, 4.0%])., Limitation: External validation of the identified NT-proBNP thresholds in other cohorts would reinforce our findings., Conclusion: Preoperative NT-proBNP is strongly associated with vascular death and MINS within 30 days after noncardiac surgery and improves cardiac risk prediction in addition to the RCRI., Primary Funding Source: Canadian Institutes of Health Research.

Background: Among adults undergoing contemporary noncardiac surgery, little is known about the frequency and timing of death and the associations between perioperative complications and mortality. We aimed to establish the frequency and timing of death and its association with perioperative complications., Methods: We conducted a prospective cohort study of patients aged 45 years and older who underwent inpatient noncardiac surgery at 28 centres in 14 countries. We monitored patients for complications until 30 days after surgery and determined the relation between these complications and 30-day mortality using a Cox proportional hazards model., Results: We included 40 004 patients. Of those, 715 patients (1.8%) died within 30 days of surgery. Five deaths (0.7%) occurred in the operating room, 500 deaths (69.9%) occurred after surgery during the index admission to hospital and 210 deaths (29.4%) occurred after discharge from the hospital. Eight complications were independently associated with 30-day mortality. The 3 complications with the largest attributable fractions (AF; i.e., potential proportion of deaths attributable to these complications) were major bleeding (6238 patients, 15.6%; adjusted hazard ratio [HR] 2.6, 95% confidence interval [CI] 2.2-3.1; AF 17.0%); myocardial injury after noncardiac surgery [MINS] (5191 patients, 13.0%; adjusted HR 2.2, 95% CI 1.9-2.6; AF 15.9%); and sepsis (1783 patients, 4.5%; adjusted HR 5.6, 95% CI 4.6-6.8; AF 12.0%)., Interpretation: Among adults undergoing noncardiac surgery, 99.3% of deaths occurred after the procedure and 44.9% of deaths were associated with 3 complications: major bleeding, MINS and sepsis. Given these findings, focusing on the prevention, early identification and management of these 3 complications holds promise for reducing perioperative mortality. Study registration: ClinicalTrials.gov, no. NCT00512109., Competing Interests: Competing interests: Clara Chow received support from the National Health and Medical Research Council of Australia and The Heart Foundation (Australia) for a career development fellowship. Robert Sapsford received nonfinancial support in the form of a research nurse funded by the National Institutes of Health Research, and lecture fees from Eli Lilly, MSD and Novo Nordisk. Denis Xavier received grants from Cadila Pharmaceuticals, Boehringer Ingelheim, Astra Zeneca India, Sanofi Aventis, Pfizer, Bristol–Myers Squibb, Medical Research Council (United Kingdom) and Wellcome Trust outside the submitted work. Emmanuelle Duceppe received a grant as a coapplicant on an investigator-initiated study and lecture fees from Roche Diagnostics. Philip J. Devereaux is a member of a research group with a policy of not accepting honorariums or other payments from industry for their own personal financial gain. They do accept honorariums or payments from industry to support research endeavours and costs to participate in meetings. Based on study questions Dr. Devereaux has originated and grants he has written, he has received grants from Abbott Diagnostics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers-Squibb, Coviden, Octapharma, Philips Healthcare, Roche Diagnostics, Siemens and Stryker. Dr Devereaux has participated in advisory board meetings for GlaxoSmithKline and Boehringer Ingelheim. He also attended an expert panel meeting with AstraZeneca and Boehringer Ingelheim. Roche Diagnostics provided Troponin T assays and financial support for the Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) Study. No other competing interests were declared., (© 2019 Joule Inc. or its licensors.)

Introduction: Annually, millions of adults suffer hip fractures. The mortality rate post a hip fracture is 7%-10% at 30 days and 10%-20% at 90 days. Observational data suggest that early surgery can improve these outcomes in hip fracture patients. We designed a clinical trial-HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) to determine the effect of accelerated surgery compared with standard care on the 90-day risk of all-cause mortality and major perioperative complications., Methods and Analysis: HIP ATTACK is a multicentre, international, parallel group randomised controlled trial (RCT) that will include patients ≥45 years of age and diagnosed with a hip fracture from a low-energy mechanism requiring surgery. Patients are randomised to accelerated medical assessment and surgical repair (goal within 6 h) or standard care. The co-primary outcomes are (1) all-cause mortality and (2) a composite of major perioperative complications (ie, mortality and non-fatal myocardial infarction, pulmonary embolism, pneumonia, sepsis, stroke, and life-threatening and major bleeding) at 90 days after randomisation. All patients will be followed up for a period of 1 year. We will enrol 3000 patients., Ethics and Dissemination: All centres had ethics approval before randomising patients. Written informed consent is required for all patients before randomisation. HIP ATTACK is the first large international trial designed to examine whether accelerated surgery can improve outcomes in patients with a hip fracture. The dissemination plan includes publishing the results in a policy-influencing journal, conference presentations, engagement of influential medical organisations, and providing public awareness through multimedia resources., Trial Registration Number: NCT02027896; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Introduction: Various definitions of bleeding have been used in perioperative studies without systematic assessment of the diagnostic criteria for their independent association with outcomes important to patients. Our proposed definition of bleeding impacting mortality after noncardiac surgery (BIMS) is bleeding that is independently associated with death during or within 30 days after noncardiac surgery. We describe our analysis plan to sequentially 1) establish the diagnostic criteria for BIMS, 2) estimate the independent contribution of BIMS to 30-day mortality and 3) develop and internally validate a clinical prediction guide to estimate patient-specific risk of BIMS., Methods: In the Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) study, we prospectively collected bleeding data for 16 079 patients aged 45 years or more who had noncardiac inpatient surgery between 2007 and 2011 at 12 centres in 8 countries across 5 continents. We will include bleeding features independently associated with 30-day mortality in the diagnostic criteria for BIMS. Candidate features will include the need for reoperation due to bleeding, the number of units of erythrocytes transfused, the lowest postoperative hemoglobin concentration, and the absolute and relative decrements in hemoglobin concentration from the preoperative value. We will then estimate the incidence of BIMS and its independent association with 30-day mortality. Last, we will construct and internally validate a clinical prediction guide for BIMS., Interpretation: This study will address an important gap in our knowledge about perioperative bleeding, with implications for the 200 million patients who undergo noncardiac surgery globally every year. Trial registration: ClinicalTrials.gov, no NCT00512109., Competing Interests: Competing interests: See the end of the article., (Copyright 2017, Joule Inc. or its licensors.)