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Background: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common after noncardiac surgery. Postsurgical pain is frequent and can persist as chronic postsurgical pain (CPSP). The association between postsurgical pain and POD or POCD is biologically plausible. We conducted this systematic review to evaluate the association between acute postsurgical pain or CPSP and POD or POCD in adults undergoing noncardiac surgery., Methods: We followed Preferred Reporting Items for Systematic Review and Meta-Analyses. We searched MEDLINE, EMBASE, Cochrane, CINAHL and PSYCHINFO up to May 2023. We included cohort, case-control, and cross-sectional studies of any language. Pairs of reviewers independently screened studies, extracted data and assessed the risk of bias using the CLARITY tool and the Joanna Briggs Institute checklist. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. Where possible, we conducted random-effects meta-analyses to summarise our findings., Results: We analysed 30 studies (>9000 participants) that assessed the association between acute postoperative pain and POD/POCD. Dose-response meta-analyses found that postoperative pain intensity was associated with occurrence of POD (adjusted relative risk [aRR]/unit of pain intensity: 1.26; 95% confidence interval [CI]: 1.17-1.35; low certainty of evidence) and risk of developing POD (aRR/unit of pain intensity: 1.18; 95% CI: 1.08-1.30; low certainty of evidence). There was very low certainty of evidence regarding the association between postoperative pain and POCD. No studies assessed the association between CPSP and POCD. Residual confounding and substantial methodological variability between studies prevented pooling data from many of the included studies and lowered certainty of evidence., Conclusions: Dose-response meta-analyses found that postoperative pain intensity was associated with occurrence of and risk of developing POD., Systematic Review Protocol: PROSPERO-CRD42021192105., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

The science of pilot trials is evolving, and understanding of their role in medical research is increasing. Perioperative randomised controlled trials often test interventions that are inherently multidisciplinary and complex; therefore, there might be compelling reasons to conduct pilot studies to assess feasibility and inform trial design. As pilot studies themselves require resources, investigators should not squander this opportunity; they should design them so that they properly address the sources of uncertainty regarding the success of the definitive trial., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objectives: To determine, in a sample of noninferiority trials, the noninferiority margins (NIMs) and their relation to effect estimates in superiority trials, the rationale being that in general NIMs should be no larger than effects declared important in superiority trials., Study Design and Setting: To identify cardiovascular trials published in high-impact journals with a statistically significant primary outcome involving mortality, we systematically searched PubMed, Embase, and MEDLINE databases (January 2015-July 2020). We documented the NIMs and determined the proportion of trials with NIMs larger than the median effect estimates across superiority trials., Results: From 1,477 screened titles, 65 (39 noninferiority, 26 superiority) trials proved eligible. The NIMs ranged from risk difference of 0.54-10%. The effect estimate across superiority trials was a median risk difference of 2.1% (interquartile range 1.5-4.9); the NIM was larger than 2.1% in 28 (71.8%) noninferiority trials and larger than 1.5%, which was the lower bound of the interquartile range in 32 (82.1%) noninferiority trials., Conclusion: The very wide range of noninferiority margins and the proportion above a threshold that most would consider an important mortality reduction suggest that clinicians and guideline panels should focus on study results, paying little attention to authors' noninferiority margins., Competing Interests: Declaration of Competing Interest, (Copyright © 2023 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.)

Objectives: Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance to rate the certainty domain of imprecision is presently not fully operationalized for rating down by two levels and when different baseline risk or uncertainty in these risks are considered. In addition, there are scenarios in which lowering the certainty of evidence by three levels for imprecision is more appropriate than lowering it by two levels. In this article, we conceptualize and operationalize rating down for imprecision by one, two and three levels for imprecision using the contextualized GRADE approaches and making decisions., Methods: Through iterative discussions and refinement in online meetings and through email communication, we developed draft guidance to rating the certainty of evidence down by up to three levels based on examples. The lead authors revised the approach according to the feedback and the comments received during these meetings and developed GRADE guidance for how to apply it. We presented a summary of the results to all attendees of the GRADE Working Group meeting for feedback in October 2021 (approximately 80 people) where the approach was formally approved., Results: This guidance provides GRADE's novel approach for the considerations about rating down for imprecision by one, two and three levels based on serious, very serious and extremely serious concerns. The approach includes identifying or defining thresholds for health outcomes that correspond to trivial or none, small, moderate or large effects and using them to rate imprecision. It facilitates the use of evidence to decision frameworks and also provides guidance for how to address imprecision about implausible large effects and trivial or no effects using the concept of the 'review information size' and for varying baseline risks. The approach is illustrated using practical examples, an online calculator and graphical displays and can be applied to dichotomous and continuous outcomes., Conclusion: In this GRADE guidance article, we provide updated guidance for how to rate imprecision using the partially and fully contextualized GRADE approaches for making recommendations or decisions, considering alternate baseline risks and for both dichotomous and continuous outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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.)

Objectives: This study aimed to review the degree of personalization of benefit and harm in the reporting of recent high-profile randomized controlled trials (RCTs) involving pharmacological interventions., Study Design and Setting: This study is a systematic review of RCTs published between 2012 and 2017 with at least one intervention evaluating drug therapy and meeting the "high-profile" threshold in a premier academic literature abstraction service. Our primary outcome was the proportion of trials reporting subgroup analyses of a combined benefit-harm outcome. Secondary outcomes included the proportion of trials reporting subgroup analyses or clinical prediction guide for benefits or harms. We assessed the quality of the subgroup analyses using a modified version of previously published credibility criteria., Results: Of 296 eligible RCTs, nine studies (3%) reported a combined benefit-harm endpoint. We found subgroup analyses of a combined benefit-harm endpoint in three studies (1%), a benefit endpoint in 167 studies (56.4%), and a harm endpoint in 18 studies (6.1%). The overall quality of the subgroup analyses was poor. Only one study reported a clinical prediction guide for an outcome., Conclusion: Despite great interest in the personalization of therapies, it is rarely reported in high-profile trials. Lack of rigorous and widely accepted methods may be the major barrier., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Calculating the number needed to treat (NNT) has been widely used to help understand treatment effect results of randomized controlled trials (RCTs). Combined benefit and harm profiles from RCT results have to be taken into account to maximize benefits and minimize harms. Unfortunately, in the biomedical community, there is no easy and acceptable way to incorporate both benefit and harm information of treatments in a single summary statistic similar to an NNT. In this study, we propose a new metric, the "NNT for net effect" or NNTnet to present the combined benefit and harm effects of an intervention or therapy based on NNT-type information with the intention that it will advance decision-making for health professionals, researchers, and resource managers in real-world practice. Examples are provided to illustrate the calculation and application of the NNTnet in practice. An NNTnet is specifically applicable to the physicians and resource managers who interpret the data published in the literature to help with their decision-making and the researchers who present the trial data to the audiences in their studies and presentations, all of whom used to use NNT information to show and interpret beneficial and harmful effects separately., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Oncology guidelines suggest using the Khorana score to select ambulatory cancer patients receiving chemotherapy for primary venous thromboembolism (VTE) prevention, but its performance in different cancers remains uncertain., Objective: To examine the performance of the Khorana score in assessing 6-month VTE risk, and the efficacy and safety of low-molecular-weight heparin (LMWH) among high-risk Khorana score patients., Methods: This individual patient data meta-analysis evaluated (ultra)-LMWH in patients with solid cancer using data from seven randomized controlled trials., Results: A total of 3293 patients from the control groups with an available Khorana score had lung (n = 1913; 58%), colorectal (n = 452; 14%), pancreatic (n = 264; 8%), gastric (n = 201; 6%), ovarian (n = 184; 56%), breast (n = 164; 5%), brain (n = 84; 3%), or bladder cancer (n = 31; 1%). The 6-month VTE incidence was 9.8% among high-risk Khorana score patients and 6.4% among low-to-intermediate-risk patients (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2). The dichotomous Khorana score performed differently in lung cancer patients (OR 1.1; 95% CI, 0.72-1.7) than in the group with other cancer types (OR 3.2; 95% CI, 1.8-5.6; P interaction  = .002). Among high-risk patients, LMWH decreased the risk of VTE by 64% compared with controls (OR 0.36; 95% CI, 0.22-0.58), without increasing the risk of major bleeding (OR 1.1; 95% CI, 0.59-2.1)., Conclusion: The Khorana score was unable to stratify patients with lung cancer based on their VTE risk. Among those with other cancer types, a high-risk score was associated with a three-fold increased risk of VTE compared with a low-to-intermediate risk score. Thromboprophylaxis was effective and safe in patients with a high-risk Khorana score., (© 2020 International Society on Thrombosis and Haemostasis.)

Study Objective: To assess the effect of different intraoperative blood pressure targets on the development of POCD and test the feasibility of a larger trial., Design: Randomized controlled pilot trial., Setting: Perioperative care in a tertiary care teaching hospital with outpatient follow-up., Patients: One hundred one patients aged ≥75 years with ASA physical status <4, undergoing elective, non-cardiac surgery under general anesthesia and 33 age-matched healthy controls., Interventions: Randomization to a personalized intraoperative blood pressure target, mean arterial pressure (MAP) ≥ 90% of preoperative values (Target group), or to a more liberal intraoperative blood pressure management (No-Target group). Strategies to reach intraoperative blood pressure target were at discretion of anesthesiologists., Measurements: An experienced neuropsychologist performed a validated battery of neurocognitive tests preoperatively and 3 months after surgery. Incidence of POCD at three months and postoperative delirium were assessed. Intraoperative time spent with MAP ≥ 90% of preoperative values, recruitment and drop-out rate at 3 months were feasibility outcomes., Main Results: The Target group spent a higher percentage of intraoperative time with MAP ≥90% of preoperative values (65 ± 25% vs. 49 ± 28%, p < 0.01). Incidence of POCD (11% vs. 7%, relative risk 1.52; 95% CI, 0.41 to 6.3; p = 0.56) and delirium (6% vs. 14%, relative risk, 0.44; 95% CI, 0.12 to 1.60; p = 0.21) did not differ between groups. No correlation was found between intraoperative hypotension and postoperative cognitive performance (p = 0.75) or delirium (p = 0.19). Recruitment rate was of 6 patients/month (95% confidential interval (CI), 5 to 7) and drop-out rate at 3 months was 24% (95% CI, 14 to 33%)., Conclusions: Intraoperative hypotension did not correlate with postoperative cognitive dysfunction or delirium occurrence in elderly patients undergoing general anesthesia for non-cardiac surgery. A multicenter randomized controlled trial is needed in order to confirm the effect of intraoperative blood pressure on the development of POCD., Trial Registration Number: NCT02428062www.clinicaltrials.gov., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Worldwide, more than 230 million adults have major noncardiac surgery each year. Although surgery can improve quality and duration of life, it can also precipitate major complications. Moreover, a substantial proportion of deaths occur after discharge. Current systems for monitoring patients postoperatively, on surgical wards and after transition to home, are inadequate. On the surgical ward, vital signs evaluation usually occurs only every 4-8 hours. Reduced in-hospital ward monitoring, followed by no vital signs monitoring at home, leads to thousands of cases of undetected/delayed detection of hemodynamic compromise. In this article we review work to date on postoperative remote automated monitoring on surgical wards and strategy for advancing this field. Key considerations for overcoming current barriers to implementing remote automated monitoring in Canada are also presented., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Few studies describe oral anticoagulant (OAC) prescription practices in very elderly patients with atrial fibrillation (AF)., Methods: In this sub-analysis of the PREFER in AF study, performed in 2012, patients were stratified according to age (<80 [n=5565] and ≥80years [n=1660]) and OAC treatment. Factors associated with OAC prescription were analyzed in a multivariate logistic regression model with backward elimination of variables least associated with OAC use., Results: Patients ≥80years presented with permanent AF more often (p<0.0001) and reported fatigue and dyspnea more frequently (p<0.0001) and palpitations less frequently (p<0.0001) than patients <80years. Hypertension, stroke, heart failure, coronary heart disease, peripheral arterial disease, cancer, chronic kidney disease, and prior major bleeding were significantly more frequent in ≥80years. Most patients were treated with OACs in both age groups. The overall use of vitamin K antagonists was similar in both groups (78.2% vs.78.2% p=0.98), while the use of non-vitamin K antagonist OACs was lower in the ≥80years old group than in the <80years group (4.5% vs. 6.6% p=0.001). Among patients ≥80years, prior stroke and heart failure were significantly associated with OAC use, whereas higher age, prior bleeding, paroxysmal AF, chronic hepatic disease, and difficulties with self-care were associated with no OAC use., Conclusions: The current use of OAC in European AF patients was satisfactorily high in octogenarians, suggesting reasonable implementation of current guidelines. Interestingly, patients with poor quality of life were less often anticoagulated. This may warrant further studies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: How the adoption of prediction models to decide which patient with atrial fibrillation (AF) to anticoagulate can affect prescription rates and outcomes is unclear., Methods: We retrospectively analyzed data from Danish registries on patients with a first-time recorded AF from 2005 to 2010. We simulated the adoption of a decisional model based on the individual absolute risk reduction of stroke and absolute risk increase of bleeding with warfarin, as expected from the patient CHA2DS2-VASc and HAS-BLED, adjusted for a 0.6 relative value for bleeding versus stroke. We studied 3 different model versions and calculated for each of them the net benefit associated with its adoption, measured as the value-adjusted reduction in stroke and bleeding events at 1 year, compared with i) the actual practice, or ii) recommending warfarin consistently with the European Society of Cardiology (ESC) guidelines, irrespective of HAS-BLED., Results: We included 41,455 patients; 31.9% actually received warfarin. The expected treatment rate with the model ranged from 21% to 87% according to the version used. The model version resulting into the highest treatment rate (i.e. treating any patient with CHA2DS2-VASc ≥ 1) was associated with the greatest net benefit (0.98; 95% credible interval 0.72-1.23), compared with the actual practice, with a 1/3 reduction in overall mortality, as with the adoption of ESC guidelines., Conclusions: Preliminarily to a randomized impact study, our analysis suggests that individualizing anticoagulation for AF using a decisional model might have a clinical advantage over actual practice, and no added advantage over following ESC guidelines., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: It is unclear how to appropriately manage discontinuation and resumption of antiplatelet therapy in patients with coronary stents who need noncardiac surgery. We undertook a systematic review of the literature to identify practice guideline statements regarding antiplatelet therapy in patients with coronary stents undergoing noncardiac surgery., Methods: We used six search strategies to identify practice guideline statements that comment on perioperative antiplatelet management for patients with coronary stents undergoing noncardiac surgery. Two independent reviewers assessed study eligibility, abstracted data, and completed quality assessment., Results: We identified 11 practice guidelines that met the eligibility criteria; these were included in the review. These guidelines advised that elective noncardiac surgery be delayed for at least 4 weeks after bare-metal stent implantation and at least 6 months after drug-eluting stent implantation. For elective surgery, all guidelines advised continuing acetylsalicylic acid (ASA) therapy whenever possible. If interruption of antiplatelet therapy was required, four guidelines advised to discontinue ASA/clopidogrel at least 5 days before surgery, while two guidelines advised to discontinue 7 to 10 days before surgery. Five guidelines provided varying guidance for the use of perioperative bridging during antiplatelet therapy interruption., Conclusions: Most current recommendations are based on expert opinion. This review highlights the need for well-designed prospective studies to identify optimal management strategies in patients with coronary stents who are on antiplatelet therapy and who need noncardiac surgery.

Objective: We compared the performance of aggregate data (AD)--based and individual patient data (IPD)-based meta-analyses to synthesize evidence on the ability of D-dimer to distinguish recurrence risk in patients with unprovoked venous thromboembolism (VTE) who stopped anticoagulation., Study Design and Setting: We compared the results of the published AD-based rate ratio of VTE recurrence for positive vs. negative D-dimer, estimated by a mixed-effect Poisson model, with those of the IPD-based hazard ratio obtained by a Cox regression stratified by trial. We performed three additional analyses to investigate the methodological reasons for differences between the two approaches, comparing the IPD Cox regression with AD generated from IPD Poisson regression (to control for differences in population on study), AD time-to-event meta-analysis, and AD generated from IPD meta-regression., Results: Published analyses agreed in direction and statistical significance when estimating the prognostic value of D-dimer even if IPD estimates suggested a stronger effect. The additional analyses suggested that differences in study populations might explain this slight difference. Poor reporting in published studies precluded a true comparison of AD- and IPD-based assessments of heterogeneity sources., Conclusion: AD and IPD meta-analyses yielded similar estimates of D-dimer effect to distinguish risk for recurrent VTE. The IPD approach was justified by the need to investigate sources of heterogeneity., (Copyright © 2013 Elsevier Inc. All rights reserved.)