Personalised perioperative dosing of ivabradine in noncardiac surgery: a single-centre, randomised, placebo-controlled, double-blind feasibility pilot trial.

BACKGROUND: Perioperative myocardial injury after noncardiac surgery is associated with postoperative mortality. Heart rate (HR) is an independent risk factor for perioperative myocardial injury. In this pilot trial we tested the feasibility of a randomised, placebo-controlled trial of personalised HR-targeted perioperative ivabradine. METHODS: This was a single-centre, randomised, placebo-controlled, double-blind, parallel group, feasibility pilot trial conducted at Geneva University Hospitals. We included patients ≥75 yr old or ≥45 yr old with cardiovascular risk factors planned for intermediate- or high-risk surgery. Patients were randomised to receive ivabradine (2.5, 5.0, or 7.5 mg) or placebo according to their HR, twice daily, from the morning of surgery until postoperative day 2. Primary outcomes were appropriate dosage and blinding success rates. RESULTS: Between October 2020 and January 2022, we randomised 78 patients (recruitment rate of 1.3 patients week-1). Some 439 of 444 study drug administrations were adequate (99% appropriate dosage rate). The blinding success rate was 100%. There were 137 (31%) administrations of Pill A (placebo in both groups for HR ≤70 beats min-1). Nine (11.5%) patients had a high-sensitive cardiac troponin T elevation ≥14 ng L-1 between any two measurements. The number of bradycardia episodes was eight in the placebo group and nine in the ivabradine group. CONCLUSIONS: This pilot study demonstrates the feasibility of, and provides guidance for, a future trial testing the efficacy of personalised perioperative ivabradine. Future studies should include patients at higher risk of cardiac complications. CLINICAL TRIAL REGISTRATION: NCT04436016.

ESAIC focused guideline for the use of cardiac biomarkers in perioperative risk evaluation.

BACKGROUND: In recent years, there has been increasing focus on the use of cardiac biomarkers in patients undergoing noncardiac surgery. AIMS: The aim of this focused guideline was to provide updated guidance regarding the pre-, post- and combined pre-and postoperative use of cardiac troponin and B-type natriuretic peptides in adult patients undergoing noncardiac surgery. METHODS: The guidelines were prepared using Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. This included the definition of critical outcomes, a systematic literature search, appraisal of certainty of evidence, evaluation of biomarker measurement in terms of the balance of desirable and undesirable effects including clinical outcomes, resource use, health inequality, stakeholder acceptance, and implementation. The panel differentiated between three different scopes of applications: cardiac biomarkers as prognostic factors, as tools for risk prediction, and for biomarker-enhanced management strategies. RESULTS: In a modified Delphi process, the task force defined 12 critical outcomes. The systematic literature search resulted in over 25,000 hits, of which 115 full-text articles formed the body of evidence for recommendations. The evidence appraisal indicated heterogeneity in the certainty of evidence across critical outcomes. Further, there was relevant gradient in the certainty of evidence across the three scopes of application. Recommendations were issued and if this was not possible due to limited evidence, clinical practice statements were produced. CONCLUSION: The ESAIC focused guidelines provide guidance on the perioperative use of cardiac troponin and B-type natriuretic peptides in patients undergoing noncardiac surgery, for three different scopes of application.

Three-Minute Diagnostic Assessment for Delirium using the Confusion Assessment Method (3D-CAM): French translation and cultural adaptation.

PURPOSE: The routine use of validated diagnostic instruments is key to identifying delirious patients early and expediting care. The 3-Minute Diagnostic Assessment for Delirium using the Confusion Assessment Method (3D-CAM) instrument is a brief, easy to use, sensitive, and specific delirium assessment tool for hospitalized patients. We aimed to translate the original English version into French, and then adapt it to older high-risk patients. METHODS: Translation and adaptation of the questionnaire were guided by an expert committee and the 3D-CAM instrument developer. During the translation phase, we achieved semantic and conceptual equivalence of the instrument by conducting forward and backward translations. During the adaptation phase, we assessed the face validity, clarity of wording, and ease of use of the translated questionnaire by administering it to 30 patients and their caregivers in peri-interventional and medical intermediate care units. During both phases, we used qualitative (goal and adequacy of the questionnaire) and quantitative (Sperber score, clarity score) criteria. RESULTS: Translation: four items were judged inadequate and were revised until all reached a Sperber score of < 3/7. Face validity: 91% of patients thought the questionnaire was designed to assess memory, thoughts, or reasoning. Clarity: eight items required adjustments until all scored ≥ 9/10 for clarity. Ease of use: all bedside caregivers reported that the questionnaire was easy to complete after receiving brief instructions. CONCLUSIONS: We produced a culturally adapted French version of the 3D-CAM instrument that is well understood and well-received by older high-risk patients and their caregivers.

RéSUMé: OBJECTIF: L'administration systématique d'instruments diagnostiques validés est essentielle pour identifier précocement les patients confus. Le questionnaire 3D-CAM (3 Minute Diagnostic Confusion Assessment Method) est un outil d'évaluation bref, facile à administrer en milieu hospitalier, sensible et spécifique pour l'état confusionnel. Notre objectif était de le traduire en français, puis de l'adapter à une population de patients âgés à haut risque. MéTHODE: La traduction et l'adaptation ont été guidées par un comité d'experts et le développeur de l'instrument. Nous avons atteint une équivalence sémantique et conceptuelle en menant des traductions antérogrades, puis rétrogrades. Nous avons évalué la validité de contenu, la clarté lexicale, et la facilité d'administration du questionnaire en le soumettant à 30 patients et 30 soignants dans des unités de soins intermédiaires médicaux et péri-interventionnels. Durant les phases de traduction et d'adaptation, nous avons utilisé des critères qualitatifs et quantitatifs. RéSULTATS: Traduction : quatre questions ont été jugées inadéquates et ont été révisées pour atteindre un score de Sperber < 3/7. Validité de contenu : 91% des patients pensaient que le questionnaire était conçu pour évaluer la mémoire, les pensées, ou le raisonnement. Clarté : huit questions ont dû être modifiées pour atteindre un score de clarté ≥ 9/10. Facilité d'administration : tous les soignants pensaient que le questionnaire était facile à utiliser après une brève formation. CONCLUSIONS: Nous avons produit une version française du questionnaire 3D-CAM qui est adaptée aux patients âgés à haut risque et aux soignants en milieu de soins aigus.

Effect of ivabradine on major adverse cardiovascular events and mortality in critically ill patients: a systematic review and meta-analyses of randomised controlled trials with trial sequential analyses.

BACKGROUND: Ivabradine lowers heart rate (HR) without affecting contractility or vascular tone. It is licensed for HR control in chronic heart diseases. We performed a systematic review and meta-analyses to examine whether ivabradine could decrease major adverse cardiovascular events (MACE) and mortality in critically ill patients. METHODS: We searched Medline, Embase, Cochrane Library, and Web of Science for RCTs. Trial quality was assessed using the Cochrane risk of bias tool. Random-effects meta-analyses were performed if at least three trials or 100 patients were available. Results are reported as weighted mean difference (WMD), odds ratio (OR), and 95% confidence intervals (CIs). Trial sequential analyses were performed to estimate the sample size needed to reach definitive conclusions of efficacy or futility. RESULTS: We included 13 RCTs (n=1497 patients). We found no evidence of an impact of ivabradine on MACE (three RCTs, 819 patients; OR=0.77; 95% CI, 0.53-1.11) or mortality (10 RCTs, 1356 patients; OR=1.07; 95% CI, 0.63-1.82), but sample sizes were not reached to allow definitive conclusions. Compared with placebo or standard care, ivabradine reduced HR (eight RCTs, 464 patients; WMD, -9.5 beats min-1; 95% CI, -13.3 to -5.8). Risk of bradycardia was not different between ivabradine and control (five RCTs, 434 patients; OR=1.2; 95% CI, 0.60-2.38). Risk of bias was overall high or unclear. CONCLUSIONS: Ivabradine reduces HR compared with placebo or standard care. The effect on MACE or mortality in acute care remains unclear. Further RCTs powered to detect changes in clinically relevant outcomes are warranted. CLINICAL TRIAL REGISTRATION: Prospero CRD42018086109.

Prediction of long-term quality of life after severe traumatic brain injury based on variables at hospital admission.

Objectives: Variables collected early after severe traumatic brain injury (sTBI) could predict health-related quality of life (HRQoL). Our aim was to determine the prevalence of patients with a low HRQoL 4 years after sTBI and to develop a prediction model including early variables.Methods: Adult patients with both sTBI [abbreviated injury score of the head region (HAIS) >3] and disease-specific HRQoL assessments using the 'Quality of Life after Brain Injury' (QOLIBRI) were included. The outcome was the total score (TS) of QOLIBRI; cutoff for low HRQoL: <60 points. A multivariate logistic regression model and prediction model were performed.Results: One hundred-sixteen patients [median age 50.8 years (IQR 25.9-62.8; 21.6% >65 years)] were included; 68 (58.6%) with HAIS = 4, 48 (41.4%) with HAIS = 5. Median Glasgow Coma Scale (GCS) was 13 (IQR 3-15). Median TS was 77 (IQR 60-88). Low HRQoL was observed in 28 patients (24.1%). Two variables were associated with low HRQoL: GCS <13, working situation other than employed or retired. The prediction model had an AUROC of 0.765; calibration was moderate (Hosmer Lemeshow Chi2 6.82, p = .556).Conclusion: One in four patients had a low HRQoL after 4 years. A lower GCS and working situations were associated with low HRQoL.

Comparison of two prehospital predictive models for mortality and impaired consciousness after severe traumatic brain injury.

BACKGROUND: The primary aim was to investigate the performance of a National Advisory Committee for Aeronautics based predictive model (NACA-BM) for mortality at 14 days and a reference model using motor GCS (GCS-RM). The secondary aim was to compare the models for impaired consciousness of survivors at 14 days (IC-14; GCS ≤ 13). METHODS: Patients ≥16 years having sustained TBI with an abbreviated injury scale score of head region (HAIS) of >3 were included. Multivariate logistic regression models were used to test models for death and IC-14. The discrimination was assessed using area under the receiver-operating curves (AUROCs); noninferiority margin was -5% between the AUROCs. Calibration was assessed using the Hosmer Lemeshow goodness-of-fit test. RESULTS: Six hundred and seventy seven patients were included. The median age was 54 (IQR 32-71). The mortality rate was 31.6%; 99 of 438 surviving patients (22.6%) had an IC-14. Discrimination of mortality was 0.835 (95%CI 0.803-0.867) for the NACA-BM and 0.839 (0.807-0.872) for the GCS-RM; the difference of the discriminative ability was -0.4% (-2.3% to +1.7%). Calibration was appropriate for the NACA-BM (χ2 8.42; P = 0. 393) and for the GCS-RM (χ2 3.90; P = 0. 866). Discrimination of IC-14 was 0.757 (0.706-0.808) for the NACA-BM and 0.784 (0.734-0.835) for the GCS-RM; the difference of the discriminative ability was -2.5% (-7.8% to +2.6%). Calibration was appropriate for the NACA-BM (χ2 10.61; P = 0.225) and for the GCS-RM (χ2 6.26; P = 0.618). CONCLUSIONS: Prehospital prediction of mortality after TBI was good with both models, and the NACA-BM was not inferior to the GCS-RM. Prediction of IC-14 was moderate in both models.

Validation of the clinical frailty score (CFS) in French language.

BACKGROUND: Very old critical ill patients are a rapid expanding group. To better understand the magnitude of the challenges involved in intensive care practice for an ageing population and discuss a rational allocation of resources, healthcare practitioners need a reliable evaluation of frailty. In order to promote the adequate use of the Clinical Frailty Scale (CFS) in a wider panel of countries, we aimed to develop, validate and characterise a French (FR) version from the original English (EN) CFS. METHODS: We included participants recruited prospectively for the observational "The very old intensive care patient: A multinational prospective observation study" (VIP Study) at Geneva University Hospitals (FR speaking hospital). A FR version of the CFS was obtained by translation (EN- > FR) and back translation (FR- > EN). The final CFS-FR was then evaluated twice on the same participants with at least a 2-week interval by FR-speaking doctors and nurses. RESULTS: Inter-rater reliability was 0.87 (95%CI: 0.76-0.93) between doctors for the original CFS version and 0.76 (95%CI: 0.57-0.87) between nurses for the FR version. Inter-rater variability between doctor and nurse was 0.75 (95%CI: 0.56-0.87) for the original version, and 0.73 (95%CI: 0.52-0.85) for the FR version. Test-retest (stability) with the original vs the FR version was 0.86 (95%CI: 0.72-0.93) for doctors and 0.87 (95%CI: 0.76-0.93) for nurses. Differences between the evaluations of the CFS-EN and CSF-FR were not different from 0, with a mean difference of 0.06 (95%CI -0.24, 0.36) for the EN version and - 0.03 (95%CI -0.47, 0.41) for the FR version. Average original version ratings were slightly lower than FR version ratings, though this difference did not reach significance: -0.29 (95%CI -0.54, 0.04). CONCLUSION: In this prospective cohort of very old intensive care participants we developed and tested the basic psychometric properties (internal consistency, reproducibility) of a French version of the CFS. This manuscript provides clinically meaningful psychometric properties that have not been previously reported in any other language, including in the original EN version. The French cultural adaptation of this CFS has adequate psychometric properties for doctors or nurses to evaluate frailty in very old intensive care patients.

The concept of peri-operative medicine to prevent major adverse events and improve outcome in surgical patients: A narrative review.

: Peri-operative Medicine is the patient-centred and value-based multidisciplinary peri-operative care of surgical patients. Peri-operative stress, that is the collective response to stimuli occurring before, during and after surgery, is, together with pre-existing comorbidities, the pathophysiological basis of major adverse events. The ultimate goal of Peri-operative Medicine is to promote high quality recovery after surgery. Clinical scores and/or biomarkers should be used to identify patients at high risk of developing major adverse events throughout the peri-operative period. Allocation of high-risk patients to specific care pathways with peri-operative organ protection, close surveillance and specific early interventions is likely to improve patient-relevant outcomes, such as disability, health-related quality of life and mortality.

Patient-Controlled Versus Clinician-Controlled Sedation With Propofol: Systematic Review and Meta-analysis With Trial Sequential Analyses.

BACKGROUND: Sedation with propofol is frequently used to facilitate diagnostic and therapeutic procedures. Propofol can be administrated by the patient (patient-controlled sedation [PCS]) or by a clinician (clinician-controlled sedation [CCS]). We aimed to compare these 2 techniques. METHODS: PubMed, Embase, CENTRAL, and trial registries were searched up to October 2017 for randomized controlled trials comparing PCS with CCS with propofol. The primary end points were the risks of presenting at least 1 episode of oxygen desaturation, arterial hypotension, and bradycardia, and the risk of requiring a rescue intervention (pharmacologic therapies or physical maneuvers) for sedation-related adverse events. Secondary end points were the dose of propofol administrated, operator and patient satisfaction, and the risk of oversedation. A random-effects model and an α level of .02 to adjust for multiple analyses were used throughout. Trial sequential analyses were performed for primary outcomes. Quality of evidence was assessed according to the Grades of Recommendation, Assessment, Development, and Evaluation system. RESULTS: Thirteen trials (1103 patients; median age, 47 years; American Society of Anesthesiologists physical status I-III) describing various diagnostic and therapeutic procedures with propofol sedation were included. PCS had no impact on the risk of oxygen desaturation (11 trials, 31/448 patients [6.9%] with PCS versus 46/481 [9.6%] with CCS; risk ratio, 0.74 [98% confidence interval, 0.35-1.56]) but decreased the risk of requiring a rescue intervention for adverse events (11 trials, 29/449 patients [6.5%] with PCS versus 74/482 [15.4%] with CCS; risk ratio, 0.45 [98% confidence interval, 0.25-0.81]). For both outcomes, Trial sequential analyses suggested that further trials were unlikely to change the results, although the quality of evidence was graded very low for all primary outcomes. For the risk of arterial hypotension and bradycardia, the required sample size for a definitive conclusion had not been reached. Analysis of secondary outcomes suggested that PCS decreased the risk of oversedation and had no impact on propofol dose administrated, or on operator or patient satisfaction. CONCLUSIONS: PCS with propofol, compared with CCS with propofol, had no impact on the risk of oxygen desaturation, but significantly decreased the risk of rescue interventions for sedation-related adverse events. Further high-quality trials are required to assess the risks and benefits of PCS.

Integrated Health Care Management of Moderate to Severe TBI in Older Patients-A Narrative Review.

PURPOSE OF REVIEW: Traumatic brain injuries are common, especially within the elderly population, which is typically defined as age 65 and older. This narrative review aims at summarizing and critically evaluating important aspects of their health care management in covering the entire pathway from prehospital care to rehabilitation and beyond. RECENT FINDINGS: The number of older patients with traumatic brain injury (TBI) is increasing, and there seem to be differences in all aspects of care along their pathway when compared to younger patients. Despite a higher mortality and a generally less favorable outcome, the current literature shows that older TBI patients have the potential to make significant improvements over time. More research is needed to evaluate the most efficient and integrated clinical pathway from prehospital interventions to rehabilitation as well as the optimal treatment of older TBI patients. Most importantly, they should not be denied access to specific treatments and therapies only based on age.

Trajectory of disability and quality-of-life in non-geriatric and geriatric survivors after severe traumatic brain injury.

OBJECTIVE: The objective was to investigate disability and health-related quality-of-life (HRQoL) 3, 6 and 12 months after traumatic brain injury (TBI) in non-geriatric (≤ 65 years) and geriatric patients (> 65 years). METHODS: Patients ≥ 16 years who sustained a severe TBI (Abbreviated Injury Scale of the head region > 3) were included in this prospective, multi-centre study. Outcome measures were Glasgow Outcome Scale Extended (GOSE; disability), SF-12 (HRQoL). Mixed linear model analyses were performed. RESULTS: Three hundred and fifty-one patients (median age = 50 years; interquartile range (IQR) = 27-67) were included; 73.2% were male and 27.6% were geriatric patients. Median GOSE at 3, 6 and 12 months was 5 (IQR = 3-7), 6 (IQR = 4-8) and 7 (IQR = 5-8); this increase (slopetime = 0.22, p < 0.0001) was age dependent (slopeage*time = -0.06, p = 0.003). Median SF-12 physical component scale score at 3, 6 and 12 months was 42.1 (IQR = 33.6-50.7), 46.6 (IQR = 37.4-53.9) and 50.4 (IQR = 39.2-55.1); this increase (slopetime = 1.52, p < 0.0001) was not age dependent (slopeage*time = -0.30, p = 0.083). SF-12 mental component scale scores were unchanged. CONCLUSIONS: Disability decreased and HRQoL improved after TBI between 3-12 months. In geriatric patients this improvement was relevant for HRQoL only.

Predictors of inpatient (neuro)rehabilitation after acute care of severe traumatic brain injury: An epidemiological study.

OBJECTIVE: To describe the discharge destination of patients with severe traumatic brain injury (sTBI) after acute care. To identify predictors associated with inpatient rehabilitation (vs discharge home) and to identify predictors associated with neurorehabilitation (vs general rehabilitation). METHODS: A national, multi-centre, prospective study with adult survivors after sTBI (abbreviated injury scale head score > 3). Univariate and multivariate logistic regression models included patient characteristics, pre-injury conditions, initial neuro-physiological assessment, trauma mechanisms, severity of TBI and pre-hospital conditions to find predictors of discharge destination. RESULTS: Out of the 566 included patients, 341 (60%) were referred to inpatient rehabilitation, thereof 249 (73%) to neurorehabilitation; 225 (40%) were discharged home or to a nursing home. Lower scores on the Glasgow Coma Scale at admission/at 14 days, higher injury severity scores and older age were predictors for inpatient rehabilitation. Younger age and male gender were predictors for neurorehabilitation. CONCLUSIONS: Patients' pathways after acute care are not only determined by the severity of their brain injury, but also by their overall injury severity and socio-biological factors. More than half of the patients after sTBI are not discharged to specialized inpatient neurorehabilitation and, therefore, efforts should be taken to optimize post-acute care.

Real-time monitoring of exhaled drugs by mass spectrometry.

Future individualized patient treatment will need tools to monitor the dose and effects of administrated drugs. Mass spectrometry may become the method of choice to monitor drugs in real time by analyzing exhaled breath. This review describes the monitoring of exhaled drugs in real time by mass spectrometry. The biological background as well as the relevant physical properties of exhaled drugs are delineated. The feasibility of detecting and monitoring exhaled drugs is discussed in several examples. The mass spectrometric tools that are currently available to analyze breath in real time are reviewed. The technical needs and state of the art for on-site measurements by mass spectrometry are also discussed in detail. Off-line methods, which give support and are an important source of information for real-time measurements, are also discussed. Finally, some examples of drugs that have already been successfully detected in exhaled breath, including propofol, fentanyl, methadone, nicotine, and valproic acid are presented. Real-time monitoring of exhaled drugs by mass spectrometry is a relatively new field, which is still in the early stages of development. New technologies promise substantial benefit for future patient monitoring and treatment.

Preoperative and early postoperative quality of life after major surgery - a prospective observational study.

BACKGROUND: Changes in health-related quality of life (HRQoL) several days after surgery have rarely been investigated. We aimed to estimate the perioperative change of HRQoL, to identify patients with clinically relevant decrease in postoperative HRQoL and to establish factors associated with this decrease in HRQoL at day 30 after major surgery. METHODS: Patients scheduled for major surgery at a university hospital were enrolled. Based on the HRQoL SF-12 questionnaire, the preoperative physical component summary (PCS) score, preoperative mental component summary (MCS) score, and postoperative PCS and MCS scores at day 30 were recorded. Minimal clinically important difference (MCID) was defined as those with a decrease of at least one half of the standard deviation (SD) of preoperative PCS or MCS scores. Differences between the groups with or without decreased HRQoL were investigated using univariate comparisons. A multiple logistic regression model was performed to evaluate the predictive value of potential perioperative variables. RESULTS: The mean ± SD preoperative PCS score was 38.5 ± 10.6, postoperative score was 35.1 ± 7.8 (p = .004) in 85 patients. Thirty-five patients (41.2%) had a clinically relevant decrease of the postoperative PCS score. A normal to high preoperative exercise metabolic capacity measured with metabolic equivalent of task (MET) (p = .01) was a predictor of the decrease in postoperative PCS. The mean preoperative MCS scores (p = .395) were 42.2 (SD 12.8) preoperative, and 43.45 (SD 12.4) postoperative, respectively. CONCLUSIONS: Major surgery decreases postoperative PCS scores of HRQoL at 30 days. A normal to high exercise capacity was a predictor of a clinically relevant decrease of postoperative PCS scores. TRIAL REGISTRATION: 07-107 (Ethical Committee NAC of Geneva University Hospitals).

Association between impulsivity, emotional/behavioural hyperactivation and functional outcome one year after severe traumatic brain injury.

OBJECTIVE: To examine impulsivity changes after a severe traumatic brain injury (TBI) and to explore the relationships between impulsivity dimensions (urgency, lack of premeditation, lack of perseverance, sensation seeking), emotional/behavioural hyperactivation and 12-month outcome. METHODS: Measures of emotional/behavioural hyperactivation and functional outcome were administered to 60 patients with severe TBI 12 months after the trauma. A scale designed to assess impulsivity changes after TBI was completed by the patients' significant others at the same time. RESULTS: Scores on urgency and lack of perseverance were higher after the trauma, whereas the score on sensation seeking was lower and the score on lack of premeditation remained stable. Urgency was the only dimension of impulsivity related to both emotional/behavioural hyperactivation and functional outcome. The relationship between urgency and functional outcome was mediated by emotional/behavioural hyperactivation, suggesting that a high level of urgency results in emotional/behavioural hyperactivation, which in turn impacts functional outcome. Lack of perseverance was significantly associated with functional outcome, indicating that the higher the lack of perseverance, the lower the functional outcome. CONCLUSION: The results contribute to a better understanding of the 12-month outcome in patients with severe TBI. They also open interesting perspectives on management strategies for implementing targeted psychological interventions to decrease impulsive manifestations.

Standards for definitions and use of outcome measures for clinical effectiveness research in perioperative medicine: European Perioperative Clinical Outcome (EPCO) definitions: a statement from the ESA-ESICM joint taskforce on perioperative outcome measures.

There is a need for large trials that test the clinical effectiveness of interventions in the field of perioperative medicine. Clinical outcome measures used in such trials must be robust, clearly defined and patient-relevant. Our objective was to develop standards for the use of clinical outcome measures to strengthen the methodological quality of perioperative medicine research. A literature search was conducted using PubMed and opinion leaders worldwide were invited to nominate papers that they believed the group should consider. The full texts of relevant articles were reviewed by the taskforce members and then discussed to reach a consensus on the required standards. The report was then circulated to opinion leaders for comment and review. This report describes definitions for 22 individual adverse events with a system of severity grading for each. In addition, four composite outcome measures were identified, which were designed to evaluate postoperative outcomes. The group also agreed on standards for four outcome measures for the evaluation of healthcare resource use and quality of life. Guidance for use of these outcome measures is provided, with particular emphasis on appropriate duration of follow-up. This report provides clearly defined and patient-relevant outcome measures for large clinical trials in perioperative medicine. These outcome measures may also be of use in clinical audit. This report is intended to complement and not replace other related work to improve assessment of clinical outcomes following specific surgical procedures.

Effectiveness of the surgical safety checklist in a high standard care environment.

BACKGROUND: Use of surgical safety checklists has been associated with significant reduction in postoperative surgical site infection (SSI), morbidity, and mortality. OBJECTIVE: To evaluate the effectiveness of an intraoperative checklist in high-risk surgical patients in a high standard care environment with long-standing regular perioperative safety control programs. RESEARCH DESIGN: Quasi-experiment pre-post checklist implementation. SUBJECTS: Surgical patients above 16 years with an American Society of Anesthesiologists (ASA) score 3-5 operated upon at a large tertiary hospital. MEASURES: Unplanned return to operating room for any reason, reoperation for SSI, unplanned admission to intensive care unit, and in-hospital death within 30 days. RESULTS: A total of 609 patients (53% elective, 85% ASA 3, mean age 70 y) were included before and 1818 after implementation (52% elective, 87% ASA 3, mean age 69 y), the latter with 552, 558, and 708 in period I, II, and III, respectively. Comparing preimplementation to postimplementation periods: unplanned return to operating room occurred in 45/609 (7.4%) versus 109/1818 (6.0%) interventions [adjusted risk ratios (RR) 0.82; 95% confidence interval (CI), 0.59-1.14]; reoperation for SSI in 18/609 (3.0%) versus 109/1818 (1.7%) interventions (adjusted RR 0.56; 95% CI, 0.32-1.00); unplanned admission to intensive care unit in 17 (2.8%) versus 48 (2.6%) interventions (adjusted RR 0.90; 95% CI, 0.52-1.55); and in-hospital death occurred in 26 (4.3%) versus 108 (5.9%) patients (adjusted RR 1.44; 95% CI, 0.97-2.14). Checklist use during 77 interventions prevented 1 reoperation for SSI. CONCLUSIONS: A trend toward reduced reoperation rates for SSI was observed after checklist implementation in this high standard care environment; no influence on other outcome measures was observed.

Changes of health-related quality of life 6 months after high-risk oncological upper gastrointestinal and hepatobiliary surgery: a single-centre prospective observational study (ChangeQol Study).

INTRODUCTION: Postoperative health-related quality of life (HRQoL) is an essential outcome in oncological surgery, particularly for elderly patients undergoing high-risk surgery. Previous studies have suggested that, on average, HRQoL returns to premorbid normal levels in the months following major surgery. However, the averaging of effect over a studied cohort may hide the variation of individual HRQoL changes. The proportions of patients who have a varied HRQoL response (stable, improvement, or a deterioration) after major oncological surgery is poorly understood. The study aims to describe the patterns of these HRQoL changes at 6 months after surgery, and to assess the patients and next-of-kin regret regarding the decision to undergo surgery. METHODS AND ANALYSIS: This prospective observational cohort study is carried out at the University Hospitals of Geneva, Switzerland. We include patients over 18 years old undergoing gastrectomy, esophagectomy, pancreas resection or hepatectomy. The primary outcome is the proportion of patients in each group with changes in HRQoL (improvement, stability or deterioration) 6 months after surgery, using a validated minimal clinically important difference of 10 points in HRQoL. The secondary outcome is to assess whether patients and their next-of-kin may regret their decision to undergo surgery at 6 months. We measure the HRQoL using the EORTC QLQ-C30 questionnaire before and 6 months after surgery. We assess regret with the Decision Regret Scale (DRS) at 6 months after surgery. Key other perioperative data include preoperative and postoperative place of residence, preoperative anxiety and depression (HADS scale), preoperative disability (WHODAS V.2.0), preoperative frailty (Clinical Frailty Scale), preoperative cognitive function (Mini-Mental State Examination) and preoperative comorbidities. A follow-up at 12 months is planned. ETHICS AND DISSEMINATION: The study was first approved by the Geneva Ethical Committee for Research (ID 2020-00536) on 28 April 2020. The results of this study will be presented at national and international scientific meetings, and publications will be submitted to an open-access peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04444544.