Importance:Perioperative bleeding is common in general surgery. The POISE-3 (Perioperative Ischemic Evaluation-3) trial demonstrated efficacy of prophylactic tranexamic acid (TXA) compared with placebo in preventing major bleeding without increasing vascular outcomes in noncardiac surgery. Objective:To determine the safety and efficacy of prophylactic TXA, specifically in general surgery. Design, Setting, and Participants:Subgroup analyses were conducted that compared randomized treatment with TXA vs placebo according to whether patients underwent general surgery or nongeneral surgery in the POISE-3 blinded, international, multicenter randomized clinical trial. Participants were 45 years or older, were undergoing noncardiac surgery, had increased cardiovascular risk, and were expected to require at least an overnight hospital admission after surgery. Among 26 581 eligible patients identified, 17 046 were excluded, resulting in 9535 patients randomized to the POISE-3 trial. Participants were enrolled from June 2018 through July 2021. The data were analyzed during December 2023. Intervention:Prophylactic, 1-g bolus of intravenous TXA or placebo at the start and end of surgery. Main Outcomes and Measures:The primary efficacy outcome was a composite of life-threatening bleeding, major bleeding, or bleeding into a critical organ. The primary safety outcome was a composite of myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism at 30 days. Cox proportional hazards models were conducted, incorporating tests of interaction. Results:Among 9535 POISE-3 participants, 3260 underwent a general surgery procedure. Mean age was 68.6 (SD, 9.6) years, 1740 were male (53.4%), and 1520 were female (46.6%). Among general surgery patients, 8.0% and 10.5% in the TXA and placebo groups, respectively, had the primary efficacy outcome (hazard ratio [HR], 0.74; 95% CI, 0.59-0.93; P = .01) and 11.9% and 12.5% in the TXA and placebo groups, respectively, had the primary safety outcome (HR, 0.95; 95% CI, 0.78-1.16; P = .63). There was no significant interaction by type of surgery (general surgery vs nongeneral surgery) on the primary efficacy (P for interaction = .81) and safety (P for interaction = .37) outcomes. Across subtypes of general surgery, TXA decreased the composite bleeding outcome in hepatopancreaticobiliary surgery (HR, 0.55; 95% CI, 0.34-0.91 [n = 332]) and colorectal surgery (HR, 0.67; 95% CI, 0.45-0.98 [n = 940]). There was no significant interaction across subtypes of general surgery (P for interaction = .68). Conclusions and Relevance:In this study, TXA significantly reduced the risk of perioperative bleeding without increasing cardiovascular risk in patients undergoing general surgery procedures. Trial Registration:ClinicalTrials.gov Identifier: NCT03505723.

BACKGROUND:In several settings, therapeutic-dose non-vitamin K oral anticoagulants (NOACs) are superior to aspirin for the prevention of arterial and venous thromboembolism. PURPOSE:To estimate differences in bleeding risks between NOACs and single antiplatelet therapy. DATA SOURCES:MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to June 2024 without language restrictions. STUDY SELECTION:Randomized controlled trials (RCTs) comparing therapeutic-dose NOACs versus single antiplatelet therapy, with a minimum treatment duration of 3 months. DATA EXTRACTION:Data extraction was done independently and in duplicate. DATA SYNTHESIS:Nine RCTs with 26 224 participants were included. All studies used aspirin as antiplatelet therapy. Compared with aspirin, apixaban had similar rates of major bleeding (risk difference [RD], 0.0 percentage point [95% CI, -1.3 to 2.6 percentage points]; 5 trials) and intracranial hemorrhage (RD, -0.2 percentage point [CI, -0.6 to 1.4 percentage points]; 5 trials). Compared with aspirin, dabigatran had similar rates of major bleeding (RD, 0.5 percentage point [CI, -2.1 to 19.6 percentage points]; 2 trials) and intracranial hemorrhage (RD, 0.0 percentage point [CI, -1.1 to 24.5 percentage points]; 2 trials). Compared with aspirin, rivaroxaban had higher rates of major bleeding (RD, 0.9 percentage point [CI, -0.1 to 3.7 percentage points]; 2 trials) and intracranial hemorrhage (RD, 0.3 percentage point [CI, -0.1 to 79.7 percentage points]; 2 trials). The evidence certainty ranged from low to moderate. LIMITATION:Confidence intervals were wide and included the possibility of a null effect. CONCLUSION:In this systematic review of RCTs, rates of major bleeding for therapeutic-dose apixaban and dabigatran were similar to those for low-dose aspirin, whereas rates were higher for rivaroxaban. PRIMARY FUNDING SOURCE:None. (PROSPERO: CRD42024553683).

Importance:Delirium is common after cardiac surgery and associated with adverse outcomes. Intraoperative benzodiazepines may increase postoperative delirium but restricting intraoperative benzodiazepines has not yet been evaluated in a randomized trial. Objective:To determine whether an institutional policy of restricted intraoperative benzodiazepine administration reduced the incidence of postoperative delirium. Design, Setting, and Participants:This pragmatic, multiperiod, patient- and assessor-blinded, cluster randomized crossover trial took place at 20 North American cardiac surgical centers. All adults undergoing open cardiac surgery at participating centers during the trial period were included through a waiver of individual patient consent between November 2019 and December 2022. Intervention:Institutional policies of restrictive vs liberal intraoperative benzodiazepine administration were compared. Hospitals (clusters) were randomized to cross between the restricted and liberal benzodiazepine policies 12 to 18 times over 4-week periods. Main Outcomes and Measures:The primary outcome was the incidence of delirium within 72 hours of surgery as detected in routine clinical care, using either the Confusion Assessment Method-Intensive Care Unit or the Intensive Care Delirium Screening Checklist. Intraoperative awareness by patient report was assessed as an adverse event. Results:During the trial, 19 768 patients (mean [SD] age, 65 [12] years; 14 528 [73.5%] male) underwent cardiac surgery, 9827 during restricted benzodiazepine periods and 9941 during liberal benzodiazepine periods. During restricted periods, clinicians adhered to assigned policy in 8928 patients (90.9%), compared to 9268 patients (93.2%) during liberal periods. Delirium occurred in 1373 patients (14.0%) during restricted periods and 1485 (14.9%) during liberal periods (adjusted odds ratio [aOR], 0.92; 95% CI, 0.84-1.01; P = .07). No patient spontaneously reported intraoperative awareness. Conclusions and Relevance:In intention-to-treat analyses, restricting benzodiazepines during cardiac surgery did not reduce delirium incidence but was also not associated with an increase in the incidence of patient-reported intraoperative awareness. Given that smaller effect sizes cannot be ruled out, restriction of benzodiazepines during cardiac surgery may be considered. Research is required to determine whether restricting intraoperative benzodiazepines at the patient level can reduce the incidence of postoperative delirium. Trial Registration:ClinicalTrials.gov Identifier: NCT03928236.

BACKGROUND Inflammation is associated with adverse cardiovascular events. Data from recent trials suggest that colchicine reduces the risk of cardiovascular events. METHODS In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients who had myocardial infarction to receive either colchicine or placebo and either spironolactone or placebo. The results of the colchicine trial are reported here. The primary efficacy outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization, evaluated in a time-to-event analysis. C-reactive protein was measured at 3 months in a subgroup of patients, and safety was also assessed. RESULTS A total of 7062 patients at 104 centers in 14 countries underwent randomization; at the time of analysis, the vital status was unknown for 45 patients (0.6%), and this information was most likely missing at random. A primary-outcome event occurred in 322 of 3528 patients (9.1%) in the colchicine group and 327 of 3534 patients (9.3%) in the placebo group over a median follow-up period of 3 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.16; P=0.93). The incidence of individual components of the primary outcome appeared to be similar in the two groups. The least-squares mean difference in C-reactive protein levels between the colchicine group and the placebo group at 3 months, adjusted according to the baseline values, was -1.28 mg per liter (95% CI, -1.81 to -0.75). Diarrhea occurred in a higher percentage of patients with colchicine than with placebo (10.2% vs. 6.6%; P<0.001), but the incidence of serious infections did not differ between groups. CONCLUSIONS Among patients who had myocardial infarction, treatment with colchicine, when started soon after myocardial infarction and continued for a median of 3 years, did not reduce the incidence of the composite primary outcome (death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization).

Background: Delirium is an acute state of confusion associated with adverse postoperative outcomes. Delirium is diagnosed clinically using screening tools; most cases go undetected. Identifying a delirium biomarker would allow for accurate diagnosis, application of therapies, and insight into causal pathways. To agnostically discover novel biomarkers of delirium, we conducted a case-control sub-study using the VISION-Cardiac Surgery biobank. Our objective was to identify candidate biomarkers to investigate in future studies. Methods: We obtained a convenience sample of 30 patients with delirium on postoperative day 1 matched to 30 matched controls by age, sex, ethnicity, center and cardiopulmonary bypass time. The Olink Explore 3K platform was used to identify blood protein alterations on postoperative day 3. Protein concentrations were expressed as normalized protein expression (NPx) units (log2 fold scale). We compared protein expression between cases and controls using a paired t-test and reported significantly different biomarkers based on a False Discovery Rate (FDR)-adjusted p-value<0.05. Results: Of 2,865 unique serum proteins, 26 (0.9%) were significantly associated with delirium status; all were elevated in cases versus controls at an FDR<0.05. Pathway analysis identified “calcium-release channel activity” (Padj=0.02) and “Guanosine 5’ triphosphate (GTP)-binding” (Padj=0.005) functions as characteristic of proteins associated with delirium. The top three differentially expressed biomarkers were FKBP1B (Padj=0.003), C2CD2L (Padj=0.004), and RAB6B (Padj=0.004). The inflammatory biomarker IL-8 (CXCL8) (mean difference = 2.36; P=3.6x10-4) was also associated with delirium. Discussion: We identified 26 biomarkers significantly associated with delirium; all are novel except for IL-8. We did not identify an association between delirium and recognized neuro-inflammatory proteins and markers of brain injury, which supports using biomarkers to differentiate between delirium and other neurological conditions. While exploratory, our findings support using biomarkers to diagnose postoperative delirium and validate using agnostic screens to identify potential delirium biomarkers.

BACKGROUND:Timing to surgery for acute cholecystitis remains variable, ranging from early (< 7 d) to delayed surgery (> 7 d). Accelerated surgery may result in better outcomes owing to reduced exposure to hypercoagulable and inflammatory states. We sought to determine the feasibility of a trial comparing accelerated surgery with standard care among patients with calculous acute cholecystitis. METHODS:We conducted a multicentre pilot randomized controlled trial. We randomly assigned adult patients with acute cholecystitis to receive accelerated surgery (i.e., goal of surgery within 6 hours of diagnosis) or standard care. The primary feasibility outcome included recruitment of 60 patients, randomly assigning the equivalent of 1 patient per site per month, and 95% follow-up at 90 days. RESULTS:Sixty patients (mean age 61.7, standard deviation [SD] 13.5, yr; 27 [45%] female) were randomly assigned to accelerated surgery (n = 31) or standard care (n = 29) from December 2019 to December 2021, with 2 recruitment pauses due to the COVID-19 pandemic. The median time from diagnosis to surgery was 5.8 (interquartile range [IQR] 4.4-11.1) hours in the accelerated care arm and 20.3 (IQR 6.8-26.8) hours in the standard care arm. Across 4 sites, 4.6 patients per month were randomly assigned. All patients completed the 90-day follow up. CONCLUSION:In our pilot trial, we found that accelerated cholecystectomy was achievable. These results show the feasibility of a trial comparing accelerated and standard care among patients requiring surgery for acute cholecystitis and support a definitive trial. TRIAL REGISTRATION:ClinicalTrials.gov, no. NCT04033822.

BACKGROUND Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain. METHODS In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo. The results of the spironolactone trial are reported here. The two primary outcomes were a composite of death from cardiovascular causes or new or worsening heart failure, evaluated as the total number of events; and a composite of the first occurrence of myocardial infarction, stroke, new or worsening heart failure, or death from cardiovascular causes. Safety was also assessed. RESULTS We enrolled 7062 patients at 104 centers in 14 countries; 3537 patients were assigned to receive spironolactone and 3525 to receive placebo. At the time of our analyses, the vital status was unknown for 45 patients (0.6%). For the first primary outcome, there were 183 events (1.7 per 100 patient-years) in the spironolactone group as compared with 220 events (2.1 per 100 patient-years) in the placebo group over a median follow-up period of 3 years (hazard ratio adjusted for competing risk of death from noncardiovascular causes, 0.91; 95% confidence interval [CI], 0.69 to 1.21; P=0.51). With respect to the second primary outcome, an event occurred in 280 of 3537 patients (7.9%) in the spironolactone group and 294 of 3525 patients (8.3%) in the placebo group (hazard ratio adjusted for competing risk, 0.96; 95% CI, 0.81 to 1.13; P=0.60). Serious adverse events were reported in 255 patients (7.2%) in the spironolactone group and 241 (6.8%) in the placebo group. CONCLUSIONS Among patients with myocardial infarction, spironolactone did not reduce the incidence of death from cardiovascular causes or new or worsening heart failure or the incidence of a composite of death from cardiovascular causes, myocardial infarction, stroke, or new or worsening heart failure.

Background RBT-1 is a combination drug of stannic protoporfin (SnPP) and iron sucrose (FeS) that elicits a preconditioning response through activation of antioxidant, anti-inflammatory, and iron-scavenging pathways, as measured by heme oxygenase-1 (HO -1), interleukin-10 (IL -10), and ferritin, respectively. Our primary aim was to determine whether RBT-1 administered before surgery would safely and effectively elicit a preconditioning response in patients undergoing cardiac surgery. Methods This phase 2, double-blind, randomised, placebo-controlled, parallel-group, adaptive trial, conducted in 19 centres across the USA, Canada, and Australia, enrolled patients scheduled to undergo non-emergent coronary artery bypass graft (CABG) and/or heart valve surgery with cardiopulmonary bypass. Patients were randomised (1:1:1) to receive either a single intravenous infusion of high -dose RBT-1 (90 mg SnPP/240 mg FeS), low-dose RBT-1 (45 mg SnPP/240 mg FeS), or placebo within 24-48 h before surgery. The primary outcome was a preoperative preconditioning response, measured by a composite of plasma HO -1, IL -10, and ferritin. Safety was assessed by adverse events and laboratory parameters. Prespecified adaptive criteria permitted early stopping and enrichment. This trial is registered with ClinicalTrials.gov, NCT04564833. Findings Between Aug 4, 2021, and Nov 9, 2022, of 135 patients who were enrolled and randomly allocated to a study group (46 high -dose, 45 low-dose, 44 placebo), 132 (98%) were included in the primary analysis (46 high -dose, 42 low dose, 44 placebo). At interim, the trial proceeded to full enrollment without enrichment. RBT-1 led to a greater preconditioning response than did placebo at high -dose (geometric least squares mean [GLSM] ratio, 3.58; 95% CI, 2.91-4.41; p < 0.0001) and low -dose (GLSM ratio, 2.62; 95% CI, 2.11-3.24; p < 0.0001). RBT-1 was generally well tolerated by patients. The primary drug -related adverse event was dose -dependent photosensitivity, observed in 12 (26%) of 46 patients treated with high -dose RBT-1 and in six (13%) of 45 patients treated with low -dose RBT-1 (safety population). Interpretation RBT-1 demonstrated a statistically significant cytoprotective preconditioning response and a manageable safety profile. Further research is needed. A phase 3 trial is planned. Funding Renibus Therapeutics, Inc. Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Cardiac surgery may lead to myocardial damage and release of cardiac biomarkers through various mechanisms such as cardiac manipulation, systemic inflammation, myocardial hypoxia, cardioplegic arrest and ischaemia caused by coronary or graft occlusion. Defining perioperative myocardial infarction (PMI) after cardiac surgery presents challenges, and the association between the current PMI definitions and postoperative outcomes remains uncertain. To address these challenges, the European Association of Cardio-Thoracic Surgery (EACTS) facilitated collaboration among a multidisciplinary group to evaluate the existing evidence on the mechanisms, diagnosis and prognostic implications of PMI after cardiac surgery. The review found that the postoperative troponin value thresholds associated with an increased risk of mortality are markedly higher than those proposed by all the current definitions of PMI. Additionally, it was found that large postoperative increases in cardiac biomarkers are prognostically relevant even in absence of additional supportive signs of ischaemia. A new algorithm for PMI detection after cardiac surgery was also proposed, and a consensus was reached within the group that establishing a prognostically relevant definition of PMI is critically needed in the cardiovascular field and that PMI should be included in the primary composite outcome of coronary intervention trials.

ObjectiveThe incidence and factors associated with chronic postsurgical pain (CPSP) after ambulatory surgeries have not been well studied. Our primary objective was to determine the incidence of CPSP and secondary objectives included assessment of intensity of CPSP, incidence of moderate-to-severe CPSP, and exploration of factors associated with CPSP.MethodsThis is a prospective cohort study of ambulatory surgery patients having procedures with a potential to cause moderate-to-severe postoperative pain. All patients had participated in a randomized controlled trial (RCT) showing no difference in achieving satisfactory analgesia in a recovery unit with either morphine or hydromorphone. CPSP was defined as chronic pain that developed or increased in intensity after the surgical procedure and is localized to the surgical field or within the innervation territory of a nerve in the surgical field, and has persisted for 3 months post-surgery, with the exclusion of other causes of pain. Incidences of CPSP were reported as rate (%) with 95% CI, and intensity using a 0-10 numerical rating scale (95% CI). We used logistic regression to explore factors associated with CPSP adjusting for baseline catastrophizing and depression.ResultsAmong 402 RCT patients, 208 provided data for the 3-month outcome. Incidence of CPSP was 18.8% (39/208), 95% CI = 13.7%-24.7% and 78% (28/39) of them had moderate-to-severe CPSP. Average CPSP intensity was 5.5, 95% CI = 4.7-6.4. Every unit increase in pain over the first 24 h was significantly associated with increased odds of moderate-to-severe CPSP at 3 months; odds ratio = 1.28, 95% CI = 1.04-1.58.ConclusionsNearly one in five patients develop CPSP after ambulatory surgeries with the majority of them having moderate-to-severe pain. Considering that acute pain after discharge is associated with CPSP and that there are no formal care pathways to address this need, studies need to focus on evaluating feasible strategies to provide continuing care.

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

Background/Objectives: New-onset atrial fibrillation (AF) after cardiac surgery is associated with patient-important outcomes. Uncertainty persists regarding its prevention, detection, and management. This review seeks to identify, compile, and describe ongoing registered research studies involving patients with or at risk for post-operative AF (POAF) after cardiac surgery. Methods: We searched clinical trial registries in January 2023 for studies focusing on POAF prediction, prevention, detection, or management. We extracted data from each record and performed descriptive analyses. Results: In total, 121 studies met the eligibility criteria, including 82 randomized trials. Prevention studies are the most common (n = 77, 63.6%), followed by prediction (n = 21, 17.4%), management (n = 16, 13.2%), and detection studies (n = 7, 5.8%). POAF after cardiac surgery is an area of active research. Conclusions: There are many ongoing randomized prevention studies. However, two major clinical gaps persist; future randomized trials should compare rate and rhythm control in patients who develop POAF, and long-term follow-up studies should investigate strategies to monitor for AF recurrence in patients with POAF.

Background For patients with perioperative atrial fibrillation (POAF) after noncardiac surgery, earlier conversion to sinus rhythm may improve outcomes. The efficacy of a rhythm versus rate control strategy for the acute management of POAF remains uncertain. Methods We searched databases for randomized controlled trials (RCTs) and observational studies that included patients with POAF after noncardiac surgery and reported outcomes for patients acutely treated with a rhythm control strategy versus either a rate control or no treatment strategy. Studies were pooled using random-effects models. Results Of the observational studies, a rhythm control strategy was associated with higher conversion rates to sinus rhythm compared to a rate control or no treatment strategy (Risk Ratio (RR) 1.93, 95% Confidence Interval (CI) 1.25 to 2.97; 9 studies, N=591). Compared to a rate control or no treatment strategy, a rhythm control strategy was not associated with differences in length of hospital stay (mean difference -1.67 days, 95%CI -7.10 to 3.76; 2 studies), length of intensive care stay (mean difference -1.90 days, 95%CI -7.62 to 3.82; 1 study), or all-cause mortality (RR 1.12, 95%CI 0.62-2.00; 5 studies). In an RCT comparing amiodarone versus magnesium, the RR was 0.56 for conversion to sinus rhythm (95%CI 0.31 to 1.03; N=34). Conclusion A rhythm control strategy was associated with greater success rates for conversion to sinus rhythm compared to a rate control or no treatment strategy. However, the observational studies were of low quality and only one small RCT was identified, and few data were available for other outcomes.

Abstract Background New-onset post-operative atrial fibrillation (AF) affects approximately 1 in 3 patients after cardiac surgery and is associated with adverse outcomes. Whether the amount of time spent in AF is associated with outcomes is unknown. Methods VISION Cardiac Surgery was an international, prospective cohort of patients who underwent cardiac surgery in 12 countries. We divided participants according to their pattern of AF: no new-onset AF, duration <24 h, duration 24-48 h, duration 48-72 h, duration >72 h and discharged in AF. We created a separate category for those who received electrical cardioversion. We excluded participants with a history of AF before surgery and participants with unknown duration of AF. We assessed the association of different patterns of AF, as compared to no AF, with clinical events occurring between 30 days post-operatively and 1 year of follow up. For each outcome, we created a Cox proportional hazards model adjusted for CHA2DS2-VASc score, smoking, hemodialysis, prior cardiac surgery, surgery type and antithrombotic use at hospital discharge (oral anticoagulation alone, oral anticoagulation plus antiplatelet, antiplatelet alone, or none). Results Among 12,234 eligible participants, 3,887 (30.3%) had new-onset post-operative AF and 3,711 had a known duration of AF. The proportion of patients with new-onset AF who were discharged from hospital on oral anticoagulation was 39%. Table 1 displays event rates by AF pattern. Compared to participants without AF, we observed a higher risk of a composite of stroke or vascular death at one year in participants with estimated AF duration >72 h (3.9%, adjusted hazard ratio (aHR) 1.72; 95% CI 1.03-2.87) and in those who underwent electrical cardioversion (3.7%, aHR 2.18; 95%CI 1.16-4.11). Only AF duration >72 h was associated with an increased risk of stroke (2.1%; aHR 2.42; 95%CI 1.15-5.09). We observed a higher risk of all-cause mortality in participants who were in AF at hospital discharge (4.1%, aHR 1.83; 95%CI 1.10-3.05) and in participants who received electrical cardioversion (5.8%, aHR 2.81; 95%CI 1.67-4.73). Only being in AF at discharge was associated with an increased risk of heart failure (3.8%; aHR 2.63; 95% CI 1.49-4.63). All patterns of AF were associated with AF detection in follow-up, with the strongest associations observed in participants who were in AF at hospital discharge (31.8%, aHR 73.4; 95%CI 51.4- 105.0) and in those who received electrical cardioversion (12.5%, aHR 17.9; 95%CI 11.1-28.8). Conclusions Among patients with new-onset post-operative AF following cardiac surgery, duration of AF >72 h, electrical cardioversion and being in AF at discharge are all markers of adverse events in the year following surgery. All patterns of AF confer a higher risk of AF detection in follow-up. Duration and treatment of early post-operative AF may have implications regarding the longer-term risk of adverse outcomes and recurrent AF.

We describe our experience in setting up the UK arm of the ARTS trial and highlight regulatory and funding challenges in relation to an international multicentre setting for an investigational medicinal product.

Background: Preoperative anaemia is common in patient undergoing colorectal surgery. Understanding the population-level costs of preoperative anaemia will inform development and evaluation of anaemia management at health system levels. Methods: This was a population-based cohort study using linked, routinely collected data, including residents from Ontario, Canada, aged >= 18 yr who underwent an elective colorectal resection between 2012 and 2022. Primary exposure was preoperative anaemia (haemoglobin < 130 g L (- 1) in males; < 120 g L (- 1) in females). Primary outcome was 30-day costs in 2022 Canadian dollars (CAD), from the perspective of a publicly funded healthcare system. Secondary outcomes included red blood cell transfusion, major adverse events (MAEs), length of stay (LOS), days alive at home (DAH), and readmissions. Results: We included 54,286 patients, with mean 65.3 (range 18 - 102) years of age and 49.0% females, among which 21264 (39.2%) had preoperative anaemia. There was an absolute adjusted cost increase of $2671 per person at 30 days after surgery attributable to preoperative anaemia (ratio of means [RoM] 1.05, 95% confidence interval [CI] 1.04 - 1.06). Compared with the control group, 30-day risks of transfusion (odds ratio [OR] 4.34, 95% CI 4.04 - 4.66), MAEs (OR 1.14, 95% CI 1.03 - 1.27), LOS (RoM 1.08, 95% CI 1.07 - 1.10), and readmissions (OR 1.16, 95% CI 1.08 - 1.24) were higher in the anaemia group, with reduced DAH (RoM 0.95, 95% CI 0.95 - 0.96). Conclusions: Approximately $2671 CAD per person in 30-day health system costs are attributable to preoperative anaemia after colorectal surgery in Ontario, Canada.

ABSTRACT Background and hypothesis Heart failure is characterized as cardiac dysfunction resulting in elevated cardiac filling pressures with symptoms and signs of congestion. Distinguishing heart failure from other causes of similar presentations in patients with kidney failure is challenging but necessary, and is needed in randomized controlled trials (RCTs) to accurately estimate treatment effects. The objective of this study was to review heart failure events, their diagnostic criteria, and adjudication in RCTs of patients with kidney failure treated with dialysis. We hypothesized that heart failure events, diagnostic criteria, and adjudication were infrequently reported in RCTs in dialysis. Methods We conducted a meta-epidemiologic systematic review of RCTs from high-impact medical, nephrology, and cardiology journals from 2000 to 2020. RCTs were eligible if they enrolled adults receiving maintenance dialysis for kidney failure and evaluated any intervention. Results Of 561 RCTs in patients receiving dialysis, 36 (6.4%) reported heart failure events as primary (10, 27.8%) or secondary (31, 86.1%) outcomes. Ten of the 36 (27.8%) RCTs provided heart failure event diagnostic criteria and five of these (50%) adjudicated heart failure events. These 10 RCTs included event diagnostic criteria for heart failure or heart failure hospitalizations, and their criteria included dyspnoea (5/10), oedema (2/10), rales/crackles (4/10), chest X-ray pulmonary oedema or vascular redistribution (4/10), treatment in an acute setting (6/10), and ultrafiltration or dialysis (4/10). No study explicitly distinguished heart failure from volume overload secondary to non-adherence or underdialysis. Conclusion Overall, we found that heart failure events are infrequently reported in RCTs in dialysis and are heterogeneously defined. Further research is required to develop standardized diagnostic criteria that are practical and meaningful to patients and clinicians.