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Modelling the influence of different concentrations of lead and cadmium ions upon a laboratory culture of insects has not been adequately studied. In our research, we assessed the influence of cadmium and lead nitrates at different concentrations (10-2-10-9 М) upon the development of larvae, pupae and imagines of Calliphora vicina Robineau-Desvoidy, 1830 (Diptera: Calliphoridae). We found an acceleration in the development of larvae and an increase in mass of puparia when lead ions were added to the food of the larvae, and decrease in the mass of puparia when cadmium ions were added. We registered nanism and malformation of the fly imagines in experiments with lead and cadmium in the food substrate. We observed that under the influence of the studied heavy metal ions there was a reduced motor activity of the fly larvae at all stages of development, a delay in formation of puparia and a delay in the emergence of imagines in comparison with the control group.

Abstract Background Precise analysis of expression-regulating elements, such as enhancers and insulators, requires that they be tested under reproducible, isogenic conditions. The commonly used methods of transfecting DNA into cell lines and selecting for drug resistance lack the requisite precision, as they yield cell lines in which varying numbers of gene copies have inserted at varying and undefined sites. By contrast, recombination-mediated cassette exchange (RMCE), by which a site-specific recombinase is used to place a single copy of a transgene at a constant chromosomal site of a cell line, offers the necessary precision. Although RMCE is generally applicable, many regulatory elements of interest are tissue-specific in their function and so require cell lines in the appropriate ontogenetic state. Results As reported here, we have used RMCE in a mouse B hybridoma cell line to establish a system with several additional advantages. To avoid the non-physiological features of prokaryotic DNA, this system uses the immunoglobulin μ heavy chain (IgH) gene from the hybridoma as the reporter. Expression can be measured simply by bulk culture assays (ELISA, Northern blot) and single cell assays (flow cytometry). Expression of the IgH reporter gene varies only 1.5 fold among independent transfectants, and expression is greatly (> 50 fold) increased by inclusion of the IgH intronic enhancer. Conclusion This system is suitable for precise analysis of the regulatory elements of the immunoglobulin loci.

Objectives: Evaluate the utility of a joint model when analysing a patient-reported endpoint as part of a randomized controlled trial (RCT) in which censoring occurs when patients die during follow-up., Study Design and Setting: The present study comprises two parts as follows: first we reanalyzed data from a previously published RCT comparing two fluid regimens in the first 24 hours of major abdomino-pelvic surgery ('Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery [RELIEF]' trial). In this trial, patient-reported disability was measured at multiple timepoints before and after surgery. Next, we conducted a simulation study to jointly emulate patient-reported disability and survival, similar to the RELIEF trial, under nine treatment-outcome scenarios. In both parts, we compared a joint model analysis to a linear mixed-effect model combined with one of the several traditional methods of handling longitudinal missingness as follows: available data analysis, complete case analysis, last observation carried forward, and worst-case assumption., Results: In part one, the joint model revealed no between-group differences in patient-reported disability at 1, 3, 6, and 12 months after surgery. The worst-case approach consistently resulted in the largest deviation from the joint model estimates, although in this particular setting none of the approaches materially changed the study's conclusions. In part two, the simulations revealed that across all treatment-outcome scenarios, the joint model expectedly produced unbiased estimates of patient-reported disability. Similarly, employing an approach based on all available data (ie, relying on the maximum likelihood estimator for handling missingness) yielded disability estimates close to the simulated values, albeit with slight bias across some scenarios. The last observation carried forward approach that mirrored the joint model's estimates except when the treatment had a nonnull effect on patient-reported disability. The worst-case analysis resulted in high bias, which was particularly evident when the treatment had a large effect on survival. The complete case analysis resulted in high bias across all scenarios., Conclusion: In randomized trials that employ a patient-reported outcome as one of their endpoints, a joint model can address bias arising from informative missingness related to death. Methods for handling missingness based on all available data appear to be a reasonable alternative to joint models, with only slight bias across some simulated scenarios., Plain Language Summary: 'Patient-centered research' focuses on outcomes that are prioritized by patients. This approach often involves asking patients to complete questionnaires about their health experiences. However, if a patient does not finish a study, dealing with their missing answers can pose significant challenges. Joint models are a recent statistical method that may help address this issue. In this study, we used joint models in a real-world clinical trial, and in a series of simulated trials, to determine how well they handle missing questionnaire data from patients. We found that joint models offer significant benefits over most traditional methods used to analyze clinical trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Postoperative systemic inflammation is strongly associated with surgical outcomes, but its relationship with patient-centred outcomes is largely unknown. Detection of excessive inflammation and patient and surgical factors associated with adverse patient-centred outcomes should inform preventative treatment options to be evaluated in clinical trials and current clinical care. This retrospective cohort study analysed prospectively collected data from 3000 high-risk, elective, major abdominal surgery patients in the restrictive vs. liberal fluid therapy for major abdominal surgery (RELIEF) trial from 47 centres in seven countries from May 2013 to September 2016. The co-primary endpoints were persistent disability or death up to 90 days after surgery, and quality of recovery using a 15-item quality of recovery score at days 3 and 30. Secondary endpoints included: 90-day and 1-year all-cause mortality; septic complications; acute kidney injury; unplanned admission to intensive care/high dependency unit; and total intensive care unit and hospital stays. Patients were assigned into quartiles of maximum postoperative C-reactive protein concentration up to day 3, after multiple imputations of missing values. The lowest (reference) group, quartile 1, C-reactive protein ≤ 85 mg.l -1 , was compared with three inflammation groups: quartile 2 > 85 mg.l -1 to 140 mg.l -1 ; quartile 3 > 140 mg.l -1 to 200 mg.l -1 ; and quartile 4 > 200 mg.l -1 to 587 mg.l -1 . Greater postoperative systemic inflammation had a higher adjusted risk ratio (95%CI) of persistent disability or death up to 90 days after surgery, quartile 4 vs. quartile 1 being 1.76 (1.31-2.36), p < 0.001. Increased inflammation was associated with increasing decline in risk-adjusted estimated medians (95%CI) for quality of recovery, the quartile 4 to quartile 1 difference being -14.4 (-17.38 to -10.71), p < 0.001 on day 3, and -5.94 (-8.92 to -2.95), p < 0.001 on day 30. Marked postoperative systemic inflammation was associated with increased risk of complications, poor quality of recovery and persistent disability or death up to 90 days after surgery., (© 2023 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Background: Older patients are vulnerable to developing new or worsening disability after surgery. Despite this, patient or surgical characteristics predisposing to postoperative disability are poorly defined. The aim of the study was to develop and validate a model, subsequently transformed to point-score form, to predict 6-month death or disability in older patients after surgery., Methods: The authors built a prospective, single-center registry to develop and validate the prediction model. The registry included patients 70 yr of age or older undergoing elective and nonelective, cardiac and noncardiac surgery between May 25, 2017, and February 11, 2021, and combined clinical data from the electronic medical record, hospital administrative data (International Classification of Diseases, Tenth Revision, Australian Modification codes) and World Health Organization (Geneva, Switzerland) Disability Assessment Schedule data collected directly from the patients. Death or disability was defined as being dead or having a World Health Organization Disability Assessment Schedule score 16% or greater. Included patients were randomly divided into model development (70%) and internal validation (30%) cohorts. Once constructed, the logistic regression and point-score models were assessed using the internal validation cohort and an external validation cohort comprising data from a separate randomized trial., Results: Of 2,176 patients who completed the World Health Organization Disability Assessment Schedule immediately before surgery, 927 (43%) patients were disabled, and 413 (19%) had significant disability. By 6 months after surgery, 1,640 patients (75%) had data available for the primary outcome analysis. Of these patients, 195 (12%) patients had died, and 691 (42%) were dead or disabled. The developed point-score model included the preoperative World Health Organization Disability Assessment Schedule score, patient age, dementia, and chronic kidney disease. The point score model retained good discrimination in the internal (area under the curve, 0.74; 95% CI, 0.69 to 0.79) and external (area under the curve, 0.77; 95% CI, 0.74 to 0.80) validation data sets., Conclusions: The authors developed and validated a point score model to predict death or disability in older patients after surgery., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Intermediate and high-risk patients undergoing surgery are often managed on a surgical ward in the absence of haemodynamic or ventilatory support requirements necessitating intensive care unit or high dependency unit admission. We describe a model of care for the multidisciplinary management of selected postoperative patients and the epidemiology of patients managed using this model at a tertiary Australian hospital.Of 25,139 patients undergoing inpatient surgery at our institution over a two-year period, 506 (2%) were referred to the Perioperative Medicine team. The median age of patients referred was 74 years; 85% had an American Society of Anesthesiologists physical status ≥3, and 44% underwent emergency surgery. Major complication or death within 30 days was 44.2% (213/482). The most common complications, as defined by the American College of Surgeons National Surgical Quality Improvement Program were transfusion within 72 h (17.4%), pneumonia/aspiration pneumonitis (11.3%), and acute renal failure (10.6%); median time to Medical Emergency Team call was 146 (interquartile range 77-279) h.Sixty-six percent of referred patients (280/423) required an intervention during their time under the service. This high incidence indicates that this population of patients merits closer attention, including routine measurement and reporting of postoperative outcomes to monitor and improve quality of care at our institution as part of an integrated perioperative service. We believe that with so much current focus on perioperative medicine, it is important we translate this to clinical care by evolving traditional models of management into more innovative strategies to meet the complex demands of today's surgical patients.

Background: Expert recommendations propose the WHO Disability Assessment Schedule (WHODAS) 2.0 as a core outcome measure in surgical studies, yet data on its long-term measurement properties remain limited. These were evaluated in a secondary analysis of the Measurement of Exercise Tolerance before Surgery (METS) prospective cohort., Methods: Participants were adults (40 years of age or older) who underwent inpatient non-cardiac surgery. The 12-item WHODAS and EQ-5DTM-3L questionnaires were administered preoperatively (in person) and 1 year postoperatively (by telephone). Responsiveness was characterized using standardized response means (SRMs) and correlation coefficients between change scores. Construct validity was evaluated using correlation coefficients between 1-year scores and comparisons of WHODAS scores across clinically relevant subgroups., Results: The analysis included 546 patients. There was moderate correlation between changes in WHODAS and various EQ-5DTM subscales. The strongest correlation was between changes in WHODAS and changes in the functional domains of the EQ-5D-3L-for example, mobility (Spearman's rho 0.40, 95 per cent confidence interval [c.i.] 0.32 to 0.48) and usual activities (rho 0.45, 95 per cent c.i. 0.30 to 0.52). When compared across quartiles of EQ-5D index change, median WHODAS scores followed expected patterns of change. In subgroups with expected functional status changes, the WHODAS SRMs ranged from 'small' to 'large' in the expected directions of change. At 1 year, the WHODAS demonstrated convergence with the EQ-5D-3L functional domains, and good discrimination between patients with expected differences in functional status., Conclusion: The WHODAS questionnaire has construct validity and responsiveness as a measure of functional status at 1 year after major surgery., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Compared with anaemia before surgery, the underlying pathogenesis and implications of postoperative anaemia are largely unknown., Methods: This retrospective cohort study analysed prospective data obtained from 2983 adult patients across 47 centres enrolled in a clinical trial evaluating restrictive and liberal intravenous fluids. The primary endpoint was persistent disability or death up to 90 days after surgery. Secondary endpoints included major septic complications, hospital stay, and patient quality of recovery using a 15-item quality of recovery (QoR-15) score, hospital re-admissions, and disability-free survival up to 12 months after surgery. Anaemia and disability were defined according to the WHO definitions. Multivariable regression was used to adjust for baseline risk and surgery., Results: A total of 2983 patients met inclusion criteria for this study, of which 78.5% (95% confidence interval [CI], 76.7-80.1%) had postoperative anaemia. Patients with postoperative anaemia had a higher adjusted risk of death or disability up to 90 days after surgery when compared with those without anaemia: 18.2% vs 9.2% (risk ratio [RR]=1.51; 95% CI, 1.10-2.07, P=0.011); lower QoR-15 scores on Day 3 and Day 30, 105 (95% CI, 87-119) vs 114 (95% CI, 99-128; P<0.001), and 130 (95% CI, 112-140) vs 139 (95% CI, 121-144; P<0.011), respectively; higher adjusted risk of a composite of mortality/septic complications, 2.01 (95% CI, 1.55-42.67; P<0.001); unplanned admission to ICU (RR=2.65; 95% CI, 1.65-4.23; P<0.001); and longer median (inter-quartile range [IQR]) hospital stays, 6.6 (4.4-12.4) vs 3.7 (2.5-6.5) days (P<0.001)., Conclusions: Postoperative anaemia is common and is independently associated with poor outcomes after surgery. Optimal prevention and treatment strategies need to be investigated., Clinical Trial Registration: NCT04978285 (ClinicalTrials.gov)., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: There are very few patient-centred global outcome measures of recovery in the days or weeks after surgery. This meta-analysis evaluated the psychometric properties and clinical acceptability of the 15-item quality of recovery (QoR-15) scale., Methods: We searched bibliographic databases for studies undertaking psychometric evaluation of the QoR-15 or using the QoR-15 as an outcome measure after surgery. Record screening, data extraction, and quality assessments were independently done by two researchers. Weighted averages estimating overall summary statistics across all the studies were calculated using random-effects meta-analysis. Pooled correlation coefficients were transformed using a Fisher z-transformation and then back-transformed to calculate pooled results. The four co-primary endpoints were validity, reliability, responsiveness, and clinical utility of the QoR-15 scale., Results: A total of 26 unique studies met the eligibility criteria, yielding up to 22 847 patients across 16 countries, in 15 languages. A further 172 studies in a further 18 countries and six languages used the QoR-15 as an outcome measure. The QoR-15 had excellent discriminant validity, with the mean difference in QoR-15 scores in patients with and without postoperative complications (9.6; 95% confidence interval [CI], 5.9-13.3; P<0.001), and good convergent validity (for a global visual analogue recovery scale, pooled r=0.63; 95% CI, 0.54-0.71). There was excellent reliability: internal consistency (pooled α=0.85; 95% CI, 0.83-0.87), split-half reliability=0.80 (95% CI, 0.75-0.84), and test-retest reliability=0.97 (95% CI, 0.95-0.98). There was also high responsiveness (pooled standardised response mean=0.87; 95% CI, 0.65-1.08), patient recruitment into evaluation studies (96%; 95% CI, 93-99), and excellent completion and return rates (91%; 95% CI, 84-96). The mean time to complete the QoR-15 was 2.7 (95% CI, 2.2-3.1) min., Conclusions: The QoR-15 is a valid, reliable, and responsive patient-centred outcome metric in surgical patients. It is highly acceptable to both patients and clinicians., Registration: Open Science Framework Identifier: DOI 10.17605/OSF.IO/78HTA., Competing Interests: Declaration of interest PM was the co-developer of the QoR-15 scale, and is an editor of the Brtish Journal of Anaesthesia. PM, MAS and JK received grants from the Australian National Health and Medical Research Council. No other disclosures were reported., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

The most appropriate method to predict postoperative outcomes in patients with severe obesity undergoing elective non-bariatric surgery is not known. We conducted a single-centre prospective cohort study in patients with a body mass index of at least 35 kg/m 2 undergoing non-bariatric, non-cardiac surgery. Patients completed the six-minute walk test prior to surgery. Disability was measured before and six months after surgery using the World Health Organization disability assessment schedule. Primary outcome measures included quality of recovery at one month and significantly increased disability at six months after surgery. A total of 293 patients participated. The median body mass index was 41 kg/m 2 . Patients generally recovered well. Following surgery, 9% of patients experienced a poor quality of recovery and 7% developed a significant increase in disability. The proportion of patients free from clinically significant disability increased from 66% prior to surgery to 90% at six months after surgery. The distance walked in six minutes was weakly predictive of poor recovery at one month and significantly increased disability at six months; weight and body mass index were not. The area under the receiver operating characteristic curve was 0.65 (95% confidence intervals 0.51 to 0.78) for poor recovery and 0.64 (95% confidence intervals 0.51 to 0.77) for increased disability. A preoperative six-minute walk test distance of 308 m was the best cut-off value for predicting increased postoperative disability (sensitivity 0.68, specificity 0.63). The six-minute walk test was most discriminatory at shorter distances. This population of patients with severe obesity appeared to recover well and had few adverse outcomes. The degree of functional capacity was more important than the degree of obesity in predicting postoperative outcomes.

Background: There is a paucity of data on depression, anxiety and post-traumatic stress disorder after left ventricular assist device (LVAD) implantation. We designed an observational study to integrate these with functional capacity and health-related quality of life (HR-QOL) in surviving LVAD patients., Methods and Results: Consenting patients between 1 month and 9 years after LVAD implantation (n = 121) were screened for functional capacity (World Health Organization Disability Assessment Schedule 2.0 [WHODAS 2.0)]); HR-QOL (European Quality of Life [EQ-5D] and Visual Assessment Scales [EQ-VAS]), depression (Patient Health Questionnaire [PHQ-9], anxiety (Generalized Anxiety Disorder Scale [GAD-7]) and post-traumatic stress disorder (Impact of Event Scale Revised [IES-R]). Of the 94% of patients who consented, 34.7% reported impaired functional capacity (WHODAS 2.0 score of ≥25%), 23.1%-34.7% HR-QOL problems (domain EQ-5D of ≥3), 10.7% "poor health" (EQ-VAS of ≤40), 14.9% depression (PHQ-9 of >14), 11.7% suicidal ideation and 17.5% anxiety (GAD-7 of >10). Among these patients, 23.5% had a positive screen for post-traumatic stress disorder (IES-R of ≥24). An EQ-VAS of 80 or greater predicted good functional capacity (P < .001)., Conclusions: One-third of discharged LVAD patients reported impaired function, HR-QOL, and psychological issues. A standardized evaluation before and after LVAD implantation could facilitate psychologic prehabilitation, inform decision-making, and identify indications for mental health intervention., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The six-minute walk test (6MWT) is a simple and valid test for assessing cardiopulmonary fitness. Nevertheless, the relationship between preoperative 6MWT distance and postoperative complications is uncertain. We conducted a secondary analysis of the 6MWT nested cohort substudy of the Measurement of Exercise Tolerance before Surgery study to determine if 6MWT distance predicts postoperative complications or death., Methods: This analysis included 545 adults (≥ 40 yr) who were at elevated cardiac risk and had elective inpatient non-cardiac surgery at 15 hospitals in Canada, Australia, and New Zealand. Each participant performed a preoperative 6MWT and was followed for 30 days after surgery. The primary outcome was moderate or severe in-hospital complications. The secondary outcome was 30-day death or myocardial injury. Multivariable logistic regression modelling was used to characterize the adjusted association of 6MWT distance with these outcomes., Results: Seven participants (1%) terminated their 6MWT sessions early because of lower limb pain, dyspnea, or dizziness. Eighty-one (15%) participants experienced moderate or severe complications and 69 (13%) experienced 30-day myocardial injury or death. Decreased 6MWT distance was associated with increased odds of moderate or severe complications (adjusted odds ratio, 1.32 per 100 m decrease; 95% confidence interval, 1.01 to 1.73; P = 0.045). There was no association of 6MWT distance with myocardial injury or 30-day death (non-linear association; P = 0.49)., Conclusion: Preoperative 6MWT distance had a modest association with moderate or severe complications after inpatient non-cardiac surgery. Further studies are needed to determine the optimal role of the 6MWT as an objective exercise test for informing preoperative risk stratification.

Background: The World Health Organization Disability Assessment Schedule 2.0 has been used to measure postoperative disability in several clinical trials and cohort studies. It is uncertain what the minimal clinically important difference or patient-acceptable symptom state scores are for this scale in patients recovering from surgery., Methods: The authors analyzed prospectively collected data from three studies that measured disability 3 and 6 months after surgery. Three distribution-based methods (0.3 multiplied by SD, standard error of the measurement, and 5% range) and two anchor-based methods (anchored to two patient-rated health status questions and separately to unplanned hospital readmission) were averaged to estimate the minimal clinically important difference for the World Health Organization Disability Assessment Schedule 2.0 score converted to a percentage scale. Scores consistent with a patient-acceptable symptom state and clinically significant disability were determined by an anchored 75th centile method., Results: Data from 4,361 patients were analyzed. The average minimal clinically important difference estimate for the World Health Organization Disability Assessment Schedule 2.0 was 5%, with similar estimates in patients with or without preoperative disability. The patient-acceptable symptom state score was 16%, and the score consistent with at least moderate clinically significant disability was 35%. Using these estimates, between baseline and 6 months after surgery, 21% of patients had a significant increase in disability, and 73% achieved a patient-acceptable symptom state., Conclusions: A change in World Health Organization Disability Assessment Schedule 2.0 score of 5% or more after surgery is consistent with a clinically important change in disability. Patients with a score less than 16% after surgery have an acceptable symptom state and can be considered as disability-free, whereas patients with a score of 35% or more can be considered as having at least moderate clinically significant disability.

Accurately measuring the incidence of major postoperative complications is essential for funding and reimbursement of healthcare providers, for internal and external benchmarking of hospital performance and for valid and reliable public reporting of outcomes. Actual or surrogate outcomes data are typically obtained by one of three methods: clinical quality registries, clinical audit, or administrative data. In 2017 a perioperative registry was developed at the Alfred Hospital and mapped to administrative and clinical data. This study investigated the statistical agreement between administrative data (International Statistical Classification of Diseases and Related Health Problems (10th edition) Australian Modification codes) and clinical audit by anaesthetists in identifying major postoperative complications. The study population included 482 high-risk surgical patients referred to the Alfred Hospital anaesthesia postoperative service over two years. Clinical audit was conducted to determine the presence of major complications and these data were compared to administrative data. The main outcome was statistical agreement between the two methods, as defined by Cohen's kappa statistic. Substantial agreement was observed for five major complications, moderate agreement for three, fair agreement for six and poor agreement for two. Sensitivity and positive predictive value ranged from 0 to 100%. Specificity was above 90% for all complications. There was important variation in inter-rater agreement. For four of the five complications with substantial agreement between administrative data and clinical audit, sensitivity was only moderate (61.5%-75%). Using International Statistical Classification of Diseases and Related Health Problems (10th edition) Australian Modification codes to identify postoperative complications at our hospital has high specificity but is likely to underestimate the incidence compared to clinical audit. Further, retrospective clinical audit itself is not a highly reliable method of identifying complications. We believe a perioperative clinical quality registry is necessary to validly and reliably measure major postoperative complications in Australia for benchmarking of hospital performance and before public reporting of outcomes should be considered.

Background: The Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications., Methods: The analysis included 1546 participants (≥40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes., Results: The DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96-0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92-0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00-1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01-1.05)., Conclusions: A DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The 6-min walk test (6MWT) is a common means of functional assessment. Its relationship to disability-free survival (DFS) is uncertain., Methods: This sub-study of the Measurement of Exercise Tolerance for Surgery study had co-primary outcome measures: correlation of the preoperative 6MWT distance with 30 day quality of recovery (15-item quality of recovery) and 12 month WHO Disability Assessment Schedule scores. The prognostic utility of the 6MWT and other risk assessment tools for 12 month DFS was assessed with logistic regression and receiver-operating-characteristic-curve analysis., Results: Of 574 patients recruited, 567 (99%) completed the 6MWT. Twelve months after surgery, 16 (2.9%) patients had died and 444 (77%) had DFS. The 6MWT correlated weakly with 30 day 15-item quality of recovery (ρ=0.14; P=0.001) and 12 month WHO Disability Assessment Schedule (ρ=-0.23; P<0.0005) scores. When the cohort was split into 6MWT distance tertiles, the adjusted odds ratio of low vs high tertiles for DFS was 3.13 [95% confidence interval (CI): 1.54-6.35]. The only independent variable predictive of DFS was the Duke Activity Status Index (DASI) score (adjusted odds ratio: 1.06; P<0.0005). The area under the receiver-operating-characteristic curve for DFS was 0.63 (95% CI: 0.57-0.70) for the 6MWT, 0.60 (95% CI: 0.53-0.67) for cardiopulmonary-exercise-testing-derived peak oxygen consumption, and 0.70 (95% CI: 0.64-0.76) for the DASI score., Conclusions: Of the risk assessment tools analysed, the DASI was the most predictive of DFS. The 6MWT was safe and comparable with cardiopulmonary exercise testing for all predictive assessments. Future research should aim to determine the optimal 6MWT distance thresholds for risk prediction., (Copyright © 2018 British Journal of Anaesthesia. All rights reserved.)

Background: Functional capacity is an important component of risk assessment for major surgery. Doctors' clinical subjective assessment of patients' functional capacity has uncertain accuracy. We did a study to compare preoperative subjective assessment with alternative markers of fitness (cardiopulmonary exercise testing [CPET], scores on the Duke Activity Status Index [DASI] questionnaire, and serum N-terminal pro-B-type natriuretic peptide [NT pro-BNP] concentrations) for predicting death or complications after major elective non-cardiac surgery., Methods: We did a multicentre, international, prospective cohort study at 25 hospitals: five in Canada, seven in the UK, ten in Australia, and three in New Zealand. We recruited adults aged at least 40 years who were scheduled for major non-cardiac surgery and deemed to have one or more risk factors for cardiac complications (eg, a history of heart failure, stroke, or diabetes) or coronary artery disease. Functional capacity was subjectively assessed in units of metabolic equivalents of tasks by the responsible anaesthesiologists in the preoperative assessment clinic, graded as poor (<4), moderate (4-10), or good (>10). All participants also completed the DASI questionnaire, underwent CPET to measure peak oxygen consumption, and had blood tests for measurement of NT pro-BNP concentrations. After surgery, patients had daily electrocardiograms and blood tests to measure troponin and creatinine concentrations until the third postoperative day or hospital discharge. The primary outcome was death or myocardial infarction within 30 days after surgery, assessed in all participants who underwent both CPET and surgery. Prognostic accuracy was assessed using logistic regression, receiver-operating-characteristic curves, and net risk reclassification., Findings: Between March 1, 2013, and March 25, 2016, we included 1401 patients in the study. 28 (2%) of 1401 patients died or had a myocardial infarction within 30 days of surgery. Subjective assessment had 19·2% sensitivity (95% CI 14·2-25) and 94·7% specificity (93·2-95·9) for identifying the inability to attain four metabolic equivalents during CPET. Only DASI scores were associated with predicting the primary outcome (adjusted odds ratio 0·96, 95% CI 0·83-0·99; p=0·03)., Interpretation: Subjectively assessed functional capacity should not be used for preoperative risk evaluation. Clinicians could instead consider a measure such as DASI for cardiac risk assessment., Funding: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research, Innovation and Science, UK National Institute of Academic Anaesthesia, UK Clinical Research Collaboration, Australian and New Zealand College of Anaesthetists, and Monash University., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To evaluate 'days at home up to 30 days after surgery' (DAH 30 ) as a patient-centred outcome measure., Design: Prospective cohort study., Data Source: Using clinical trial data (seven trials, 2109 patients) we calculated DAH 30 from length of stay, readmission, discharge destination and death up to 30 days after surgery., Main Outcome: The association between DAH 30 and serious complications after surgery., Results: One or more complications occurred in 263 of 1846 (14.2%) patients, including 19 (1.0%) deaths within 30 days of surgery; 245 (11.6%) patients were discharged to a rehabilitation facility and 150 (7.1%) were readmitted to hospital within 30 days of surgery. The median DAH 30 was significantly less in older patients (p<0.001), those with poorer physical functioning (p<0.001) and in those undergoing longer operations (p<0.001). Patients with serious complications had less days at home than patients without serious complications (20.5 (95% CI 19.1 to 21.9) vs 23.9 (95% CI 23.8 to 23.9) p<0.001), and had higher rates of readmission (16.0% vs 5.9%; p<0.001). After adjusting for patient age, sex, physical status and duration of surgery, the occurrence of postoperative complications was associated with fewer days at home after surgery (difference 3.0(95% CI 2.1 to 4.0) days; p<0.001)., Conclusions: DAH 30 has construct validity and is a readily obtainable generic patient-centred outcome measure. It is a pragmatic outcome measure for perioperative clinical trials., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Preoperative functional capacity is considered an important risk factor for cardiovascular and other complications of major non-cardiac surgery. Nonetheless, the usual approach for estimating preoperative functional capacity, namely doctors' subjective assessment, may not accurately predict postoperative morbidity or mortality. 3 possible alternatives are cardiopulmonary exercise testing; the Duke Activity Status Index, a standardised questionnaire for estimating functional capacity; and the serum concentration of N-terminal pro-B-type natriuretic peptide (NT pro-BNP), a biomarker for heart failure and cardiac ischaemia., Methods and Analysis: The Measurement of Exercise Tolerance before Surgery (METS) Study is a multicentre prospective cohort study of patients undergoing major elective non-cardiac surgery at 25 participating study sites in Australia, Canada, New Zealand and the UK. We aim to recruit 1723 participants. Prior to surgery, participants undergo symptom-limited cardiopulmonary exercise testing on a cycle ergometer, complete the Duke Activity Status Index questionnaire, undergo blood sampling to measure serum NT pro-BNP concentration and have their functional capacity subjectively assessed by their responsible doctors. Participants are followed for 1 year after surgery to assess vital status, postoperative complications and general health utilities. The primary outcome is all-cause death or non-fatal myocardial infarction within 30 days after surgery, and the secondary outcome is all-cause death within 1 year after surgery. Both receiver-operating-characteristic curve methods and risk reclassification table methods will be used to compare the prognostic accuracy of preoperative subjective assessment, peak oxygen consumption during cardiopulmonary exercise testing, Duke Activity Status Index scores and serum NT pro-BNP concentration., Ethics and Dissemination: The METS Study has received research ethics board approval at all sites. Participant recruitment began in March 2013, and 1-year follow-up is expected to finish in 2016. Publication of the results of the METS Study is anticipated to occur in 2017., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Survival and freedom from disability are arguably the most important patient-centered outcomes after surgery, but it is unclear how postoperative disability should be measured. The authors thus evaluated the World Health Organization Disability Assessment Schedule 2.0 in a surgical population., Methods: The authors examined the psychometric properties of World Health Organization Disability Assessment Schedule 2.0 in a diverse cohort of 510 surgical patients. The authors assessed clinical acceptability, validity, reliability, and responsiveness up to 12 months after surgery., Results: Criterion and convergent validity of World Health Organization Disability Assessment Schedule 2.0 were supported by good correlation with the 40-item quality of recovery scale at 30 days after surgery (r = -0.70) and at 3, 6, and 12 months after surgery with physical functioning (The Katz index of independence in Activities of Daily Living; r = -0.70, r = -0.60, and rho = -0.47); quality of life (EQ-5D; r = -0.57, -0.60, and -0.52); and pain interference scores (modified Brief Pain Inventory Short Form; r = 0.72, 0.74, and 0.81) (all P < 0.0005). Construct validity was supported by increased hospital stay (6.9 vs. 5.3 days, P = 0.008) and increased day 30 complications (20% vs. 11%, P = 0.042) in patients with new disability. There was excellent internal consistency with Cronbach's α and split-half coefficients greater than 0.90 at all time points (all P < 0.0005). Responsiveness was excellent with effect sizes of 3.4, 3.0, and 1.0 at 3, 6, and 12 months after surgery, respectively., Conclusions: World Health Organization Disability Assessment Schedule 2.0 is a clinically acceptable, valid, reliable, and responsive instrument for measuring postoperative disability in a diverse surgical population. Its use as an endpoint in future perioperative studies can provide outcome data that are meaningful to clinicians and patients alike.

The in vitro activity of cefodizime (HR-221), a new cephalosporin antibiotic, was compared with the activities of selected antimicrobial agents against a broad spectrum of aerobic bacteria. Cefodizime concentrations of 2 micrograms/ml inhibited about 90% of Enterobacteriaceae studied. Serratia marcescens required 8 micrograms/ml to inhibit 90% of strains. Among gram-positive cocci, 50% of strains were inhibited by 2 micrograms/ml of cefodizime (including methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis, and penicillin-resistant Streptococcus pneumoniae). Pseudomonas aeruginosa was less susceptible to cefodizime. Cefotaxime, an antibiotic closely related to cefodizime structurally, was about fourfold more active.

The minimal inhibitory concentrations of cefmenoxime (SCE-1365), cefotaxime, cefoperazone, and moxalactam against various species of aerobic bacteria were determined. The activities of cefmenoxime, cefotaxime, and moxalactam were generally similar and slightly higher than the activity of cefoperazone.

The in vitro activity of U-57930E, a new clindamycin analog, against aerobic gram-positive cocci was studied by microdilution broth susceptibility tests and compared with the activities of clindamycin, vancomycin, oxacillin, and ampicillin. U-57930E inhibited methicillin-susceptible Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus viridans at concentrations of less than or equal to 1 microgram/ml. This degree of activity was generally slightly less than that of the other antimicrobial agents tested. Methicillin-resistant Staphylococcus aureus, coagulase-negative staphylococci, penicillin-resistant Streptococcus pneumoniae, and enterococci were resistant to U-57930E. At the concentrations used, U-57930E exhibited bactericidal activity against most susceptible organisms, and a minimal effect of inoculum size was noted.

The activities of 11 antimicrobial agents against 36 strains of Campylobacter fetus subsp. jejuni were studied by a broth microdilution method. All strains were susceptible to 7 of the 11 antimicrobial agents. Of the newer agents tested N-formimidoyl thienamycin (MK0787) and rosaramicin had very good activity, whereas cefotaxime, moxalactam, and cefoperazone had poorer activity.