Synthesizing regulatory guidance for demonstrating preclinical efficacy and translating promising cell therapies to early phase clinical trials: a scoping review.

BACKGROUND: Regulatory applications for cell therapy face more objections compared to conventional small molecule or biological drugs, leading to delays in market approval and clinical adoption. Increased regulatory objections frequently relate to issues regarding preclinical evidence, such as experimental design of animal studies, selection of animal models, endpoints, and determination of mechanism of action. Synthesis and clarification of the preclinical evidence necessary to demonstrate treatment efficacy and advance into early-phase clinical trials is needed to help researchers avoid regulatory objections. METHODS: We conducted a scoping review in which we searched repositories of the International Council for Harmonisation and all national member organizations (N = 38) for documents related to preclinical studies of cell therapies. Active guidance documents related to cell therapy were included, with no restrictions based on the year or language of publication. Data extraction was conducted in duplicate with conflicts resolved through consensus discussion. RESULTS: From 1215 identified documents, a total of 182 were included and analyzed, with 71% originating from ten major regulatory agencies. The most prevalent preclinical item addressed was the mechanism of action (n = 161, 88% of documents), underscoring its importance in bridging preclinical findings to clinical application. Most documents (n = 140, 77%) emphasized the importance of using clinically relevant preclinical models, though specific recommendations on models of disease were less common (n = 81, 45%). Selection of clinically relevant intervention parameters (n = 136, 75%) and outcome measures (n = 121, 66%) were also frequently recommended, but selection of relevant comparator groups appeared less frequently (n = 35, 19%). Furthermore, robust study design elements such as randomization and blinding were less frequently recommended, appearing in 31% of documents (n = 57). Comparison with clinical trial guidance revealed a significant gap in the rigor of study design recommendations for preclinical research. CONCLUSIONS: Regulatory guidance for preclinical efficacy studies often recommends a strong emphasis on the clinical relevance of animal models, intervention parameters, outcomes, and mechanism of action. Incorporating these recommendations into early preclinical studies should improve the acceptability of preclinical evidence for approval by the relevant national regulators and can be used as a guide to ensure that all evidence that regulators say they expect is efficiently assembled into new clinical trial applications.

Adherence to guideline-recommended care of late-onset hypertension in females versus males: A population-based cohort study.

BACKGROUND: Sex-based disparities in cardiovascular outcomes may be improved with appropriate hypertension management. OBJECTIVE: To compare the evidence-based evaluation and management of females with late-onset hypertension compared to males in the contemporary era. METHODS: Design: Retrospective population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Residents aged ≥66 years with newly diagnosed hypertension between January 1, 2010, and December 31, 2017. EXPOSURE: Sex (female vs. male). OUTCOMES AND MEASURES: We used Poisson and logistic regression to estimate adjusted sex-attributable differences in the performance of guideline-recommended lab investigations. We estimated adjusted differences in time to the prescription of, and type of, first antihypertensive medication prescribed between females and males, using Cox regression. RESULTS: Among 111,410 adults (mean age 73 years, 53% female, median follow-up 6.8 years), females underwent a similar number of guideline-recommended investigations (adjusted incidence rate ratio, 0.997 [95% confidence interval [CI] 0.99-1.002]) compared to males. Females were also as likely to complete all investigations (0.70% females, 0.77% males; adjusted odds ratio, 0.96 [95% CI 0.83-1.11]). Females were slightly less likely to be prescribed medication (adjusted hazard ratio [aHR] 0.98 [95% CI 0.96-0.99]) or, among those prescribed, less likely to be prescribed first-line medication (aHR, 0.995 [95% CI 0.994-0.997]). CONCLUSIONS: Compared to males, females with late-onset hypertension were equally likely to complete initial investigations with comparable prescription rates. These findings suggest that there may be no clinically meaningful sex-based differences in the initial management of late-onset hypertension to explain sex-based disparities in cardiovascular outcomes.

Association between anaesthesia-surgery team sex diversity and major morbidity.

BACKGROUND: Team diversity is recognized not only as an equity issue but also a catalyst for improved performance through diversity in knowledge and practices. However, team diversity data in healthcare are limited and it is not known whether it may affect outcomes in surgery. This study examined the association between anaesthesia-surgery team sex diversity and postoperative outcomes. METHODS: This was a population-based retrospective cohort study of adults undergoing major inpatient procedures between 2009 and 2019. The exposure was the hospital percentage of female anaesthetists and surgeons in the year of surgery. The outcome was 90-day major morbidity. Restricted cubic splines were used to identify a clinically meaningful dichotomization of team sex diversity, with over 35% female anaesthetists and surgeons representing higher diversity. The association with outcomes was examined using multivariable logistic regression. RESULTS: Of 709 899 index operations performed at 88 hospitals, 90-day major morbidity occurred in 14.4%. The median proportion of female anaesthetists and surgeons was 28 (interquartile range 25-31)% per hospital per year. Care in hospitals with higher sex diversity (over 35% female) was associated with reduced odds of 90-day major morbidity (OR 0.97, 95% c.i. 0.95 to 0.99; P = 0.02) after adjustment. The magnitude of this association was greater for patients treated by female anaesthetists (OR 0.92, 0.88 to 0.97; P = 0.002) and female surgeons (OR 0.83, 0.76 to 0.90; P < 0.001). CONCLUSION: Care in hospitals with greater anaesthesia-surgery team sex diversity was associated with better postoperative outcomes. Care in a hospital reaching a critical mass with over 35% female anaesthetists and surgeons, representing higher team sex-diversity, was associated with a 3% lower odds of 90-day major morbidity.

Risk Factors for Surgical Site Infection after Lower Limb Revascularisation Surgery: a Systematic Review and Meta-Analysis of Prognostic Studies.

OBJECTIVE: To systematically review and meta-analyse adjusted risk factors for surgical site infection (SSI) after lower limb revascularisation surgery. DATA SOURCES: MEDLINE, Embase, Evidence Based Medicine Reviews, and the Cochrane Central Register of Controlled Trials (inception to 28 April 2022). REVIEW METHODS: Systematic review and meta-analysis conducted according to PRISMA guidelines. After protocol registration, databases were searched. Studies reporting adjusted risk factors for SSI in adults who underwent lower limb revascularisation surgery for peripheral artery disease were included. Adjusted odds ratios (ORs) were pooled using random effects models. GRADE was used to assess certainty. RESULTS: Among 6 377 citations identified, 50 studies (n = 271 125 patients) were included. The cumulative incidence of SSI was 12 (95% confidence interval [CI] 10 - 13) per 100 patients. Studies reported 139 potential SSI risk factors adjusted for a median of 12 (range 1 - 69) potential confounding factors. Risk factors that increased the pooled adjusted odds of SSI included: female sex (pooled OR 1.41, 95% CI 1.20 - 1.64; high certainty); dependent functional status (pooled OR 1.18, 95% CI 1.03 - 1.35; low certainty); being overweight (pooled OR 1.82, 95% CI 1.29 - 2.56; moderate certainty), obese (pooled OR 2.20, 95% CI 1.44 - 3.36; high certainty), or morbidly obese (pooled OR 1.65, 95% CI 1.08 - 2.52; moderate certainty); chronic obstructive pulmonary disease (pooled OR 1.42, 95% CI 1.17 - 1.71; high certainty); chronic limb threatening ischaemia (pooled OR 1.67, 95% CI 1.22 - 2.29; moderate certainty); chronic kidney disease (pooled OR 2.13, 95% CI 1.18 - 3.83; moderate certainty); intra-operative (pooled OR 1.23, 95% CI 1.02 - 1.49), peri-operative (pooled OR 1.92, 95% CI 1.27 - 2.90), or post-operative (pooled OR 2.21, 95% CI 1.44 - 3.39) blood transfusion (moderate certainty for all); urgent or emergency surgery (pooled OR 2.12, 95% CI 1.22 - 3.70; moderate certainty); vein bypass and or patch instead of endarterectomy alone (pooled OR 1.86, 95% CI 1.33 - 2.59; moderate certainty); an operation lasting ≥ 3 hours (pooled OR 1.86, 95% CI 1.33 - 2.59; moderate certainty) or ≥ 5 hours (pooled OR 1.60, 95% CI 1.18 - 2.17; moderate certainty); and early or unplanned re-operation (pooled OR 4.50, 95% CI 2.18 - 9.32; low certainty). CONCLUSION: This systematic review identified evidence informed SSI risk factors following lower limb revascularisation surgery. These may be used to develop improved SSI risk prediction tools and to identify patients who may benefit from evidence informed SSI prevention strategies.

Frailty and decisional regret after elective noncardiac surgery: a multicentre prospective cohort study.

BACKGROUND: Frailty is associated with morbidity and mortality after surgery. The association of frailty with decisional regret is poorly defined. Our objective was to estimate the association of preoperative frailty with decisional regret status in the year after surgery. METHODS: We conducted a secondary analysis of a prospective, multicentre cohort study of patients aged ≥65 years who underwent elective noncardiac surgery. Decisional regret about having undergone surgery was ascertained at 30, 90, and 365 (primary time point) days after surgery using a 3-point ordinal scale. Bayesian ordinal logistic regression was used to estimate the association of frailty with decisional regret, adjusted for surgery type, age, sex, and mental health conditions. Subgroup and sensitivity analyses were conducted. RESULTS: We identified 669 patients; 293 (43.8%) lived with frailty. At 365 days after surgery, the unadjusted odds ratio (OR) associating frailty with greater decisional regret was 2.21 (95% credible interval [CrI] 0.98-5.09; P(OR>1)=0.97), which was attenuated after confounder adjustment (adjusted OR 1.68, 95% CrI 0.84-3.36; P(OR>1)=0.93). Similar results were estimated at 30 and 90 days. Additional adjustment for baseline comorbidities and disability score substantially altered the OR at 365 days (0.89, 95% CrI 0.37-2.12; P(OR>1)=0.39). There was a high probability that surgery type was an effect modifier (non-orthopaedic: OR 1.90, 95% CrI 1.00-3.59; P(OR>1)=0.98); orthopaedic: OR 0.87, 95% CrI 0.41-1.91; P(OR>1)=0.36). CONCLUSIONS: Among older surgical patients, there appears to be a complex association with frailty and decisional regret, with substantial heterogeneity based on assumed causal pathways and surgery type. Future studies are required to untangle the complex interplay between these factors.

Associations of preoperative anaemia with healthcare resource use and outcomes after colorectal surgery: a population-based cohort study.

BACKGROUND: Preoperative anaemia is common in patient undergoing colorectal surgery. Understanding the population-level costs of preoperative anaemia will inform development and evaluation of anaemia management at health system levels. METHODS: This was a population-based cohort study using linked, routinely collected data, including residents from Ontario, Canada, aged ≥18 yr who underwent an elective colorectal resection between 2012 and 2022. Primary exposure was preoperative anaemia (haemoglobin <130 g L-1 in males; <120 g L-1 in females). Primary outcome was 30-day costs in 2022 Canadian dollars (CAD), from the perspective of a publicly funded healthcare system. Secondary outcomes included red blood cell transfusion, major adverse events (MAEs), length of stay (LOS), days alive at home (DAH), and readmissions. RESULTS: We included 54,286 patients, with mean 65.3 (range 18-102) years of age and 49.0% females, among which 21 264 (39.2%) had preoperative anaemia. There was an absolute adjusted cost increase of $2671 per person at 30 days after surgery attributable to preoperative anaemia (ratio of means [RoM] 1.05, 95% confidence interval [CI] 1.04-1.06). Compared with the control group, 30-day risks of transfusion (odds ratio [OR] 4.34, 95% CI 4.04-4.66), MAEs (OR 1.14, 95% CI 1.03-1.27), LOS (RoM 1.08, 95% CI 1.07-1.10), and readmissions (OR 1.16, 95% CI 1.08-1.24) were higher in the anaemia group, with reduced DAH (RoM 0.95, 95% CI 0.95-0.96). CONCLUSIONS: Approximately $2671 CAD per person in 30-day health system costs are attributable to preoperative anaemia after colorectal surgery in Ontario, Canada.

Towards a common definition of surgical prehabilitation: a scoping review of randomised trials.

BACKGROUND: There is no universally accepted definition for surgical prehabilitation. The objectives of this scoping review were to (1) identify how surgical prehabilitation is defined across randomised controlled trials and (2) propose a common definition. METHODS: The final search was conducted in February 2023 using MEDLINE, Embase, PsycINFO, Web of Science, CINAHL, and Cochrane. We included randomised controlled trials (RCTs) of unimodal or multimodal prehabilitation interventions (nutrition, exercise, and psychological support) lasting at least 7 days in adults undergoing elective surgery. Qualitative data were analysed using summative content analysis. RESULTS: We identified 76 prehabilitation trials of patients undergoing abdominal (n=26, 34%), orthopaedic (n=20, 26%), thoracic (n=14, 18%), cardiac (n=7, 9%), spinal (n=4, 5%), and other (n=5, 7%) surgeries. Surgical prehabilitation was explicitly defined in more than half of these RCTs (n=42, 55%). Our findings consolidated the following definition: 'Prehabilitation is a process from diagnosis to surgery, consisting of one or more preoperative interventions of exercise, nutrition, psychological strategies and respiratory training, that aims to enhance functional capacity and physiological reserve to allow patients to withstand surgical stressors, improve postoperative outcomes, and facilitate recovery.' CONCLUSIONS: A common definition is the first step towards standardisation, which is needed to guide future high-quality research and advance the field of prehabilitation. The proposed definition should be further evaluated by international stakeholders to ensure that it is comprehensive and globally accepted.

Outcomes reported in randomised trials of surgical prehabilitation: a scoping review.

BACKGROUND: Heterogeneity of reported outcomes can impact the certainty of evidence for prehabilitation. The objective of this scoping review was to systematically map outcomes and assessment tools used in trials of surgical prehabilitation. METHODS: MEDLINE, EMBASE, PsychInfo, Web of Science, CINAHL, and Cochrane were searched in February 2023. Randomised controlled trials of unimodal or multimodal prehabilitation interventions (nutrition, exercise, psychological support) lasting at least 7 days in adults undergoing elective surgery were included. Reported outcomes were classified according to the International Society for Pharmacoeconomics and Outcomes Research framework. RESULTS: We included 76 trials, mostly focused on abdominal or orthopaedic surgeries. A total of 50 different outcomes were identified, measured using 184 outcome assessment tools. Observer-reported outcomes were collected in 86% of trials (n=65), with hospital length of stay being most common. Performance outcomes were reported in 80% of trials (n=61), most commonly as exercise capacity assessed by cardiopulmonary exercise testing. Clinician-reported outcomes were included in 78% (n=59) of trials and most frequently included postoperative complications with Clavien-Dindo classification. Patient-reported outcomes were reported in 76% (n=58) of trials, with health-related quality of life using the 36- or 12-Item Short Form Survey being most prevalent. Biomarker outcomes were reported in 16% of trials (n=12) most commonly using inflammatory markers assessed with C-reactive protein. CONCLUSIONS: There is substantial heterogeneity in the reporting of outcomes and assessment tools across surgical prehabilitation trials. Identification of meaningful outcomes, and agreement on appropriate assessment tools, could inform the development of a prehabilitation core outcomes set to harmonise outcome reporting and facilitate meta-analyses.

Effectiveness of dexmedetomidine on patient-centred outcomes in surgical patients: a systematic review and Bayesian meta-analysis.

BACKGROUND: Dexmedetomidine is increasingly used for surgical patients requiring general anaesthesia. However, its effectiveness on patient-centred outcomes remains uncertain. Our main objective was to evaluate the patient-centred effectiveness of intraoperative dexmedetomidine for adult patients requiring surgery under general anaesthesia. METHODS: We conducted a systematic search of MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL from inception to October 2023. Randomised controlled trials (RCTs) comparing intraoperative use of dexmedetomidine with placebo, opioid, or usual care in adult patients requiring surgery under general anaesthesia were included. Study selection, data extraction, and risk of bias assessment were performed by two reviewers independently. We synthesised data using a random-effects Bayesian regression framework to derive effect estimates and the probability of a clinically important effect. For continuous outcomes, we pooled instruments with similar constructs using standardised mean differences (SMDs) and converted SMDs and credible intervals (CrIs) to their original scale when appropriate. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Our primary outcome was quality of recovery after surgery. To guide interpretation on the original scale, the Quality of Recovery-15 (QoR-15) instrument was used (range 0-150 points, minimally important difference [MID] of 6 points). RESULTS: We identified 49,069 citations, from which 44 RCTs involving 5904 participants were eligible. Intraoperative dexmedetomidine administration was associated with improvement in postoperative QoR-15 (mean difference 9, 95% CrI 4-14, n=21 RCTs, moderate certainty of evidence). We found 99% probability of any benefit and 88% probability of achieving the MID. There was a reduction in chronic pain incidence (odds ratio [OR] 0.42, 95% CrI 0.19-0.79, n=7 RCTs, low certainty of evidence). There was also increased risk of clinically significant hypotension (OR 1.98, 95% CrI 0.84-3.92, posterior probability of harm 94%, n=8 RCTs) and clinically significant bradycardia (OR 1.74, 95% CrI 0.93-3.34, posterior probability of harm 95%, n=10 RCTs), with very low certainty of evidence for both. There was limited evidence to inform other secondary patient-centred outcomes. CONCLUSIONS: Compared with placebo or standard of care, intraoperative dexmedetomidine likely results in meaningful improvement in the quality of recovery and chronic pain after surgery. However, it might increase clinically important bradycardia and hypotension. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023439896).

Intraoperative pharmacologic opioid minimisation strategies and patient-centred outcomes after surgery: a scoping review.

BACKGROUND: Postoperative patient-centred outcome measures are essential to capture the patient's experience after surgery. Although a large number of pharmacologic opioid minimisation strategies (i.e. opioid alternatives) are used for patients undergoing surgery, it remains unclear which strategies are most promising in terms of patient-centred outcome improvements. This scoping review had two main objectives: (1) to map and describe evidence from clinical trials assessing the patient-centred effectiveness of pharmacologic intraoperative opioid minimisation strategies in adult surgical patients, and (2) to identify promising pharmacologic opioid minimisation strategies. METHODS: We searched MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL databases from inception to February 2023. We included trials investigating the use of opioid minimisation strategies in adult surgical patients and reporting at least one patient-centred outcome. Study screening and data extraction were conducted independently by at least two reviewers. RESULTS: Of 24,842 citations screened for eligibility, 2803 trials assessed the effectiveness of intraoperative opioid minimisation strategies. Of these, 457 trials (67,060 participants) met eligibility criteria, reporting at least one patient-centred outcome. In the 107 trials that included a patient-centred primary outcome, patient wellbeing was the most frequently used domain (55 trials). Based on aggregate findings, dexmedetomidine, systemic lidocaine, and COX-2 inhibitors were promising strategies, while paracetamol, ketamine, and gabapentinoids were less promising. Almost half of the trials (253 trials) did not report a protocol or registration number. CONCLUSIONS: Researchers should prioritise and include patient-centred outcomes in the assessment of opioid minimisation strategy effectiveness. We identified three potentially promising pharmacologic intraoperative opioid minimisation strategies that should be further assessed through systematic reviews and multicentre trials. Findings from our scoping review may be influenced by selective outcome reporting bias. STUDY REGISTRATION: OSF - https://osf.io/7kea3.

Prediction Models for Forecasting Risk of Development of Surgical Site Infection after Lower Limb Revascularization Surgery: A Systematic Review.

BACKGROUND: Surgical site infections (SSIs) are a common and potentially preventable complication of lower limb revascularization surgery associated with increased healthcare resource utilization and patient morbidity. We conducted a systematic review to evaluate multivariable prediction models designed to forecast risk of SSI development after these procedures. METHODS: After protocol registration (CRD42022331292), we searched MEDLINE, EMBASE, CENTRAL, and Evidence-Based Medicine Reviews (inception to April 4th, 2023) for studies describing multivariable prediction models designed to forecast risk of SSI in adults after lower limb revascularization surgery. Two investigators independently screened abstracts and full-text articles, extracted data, and assessed risk of bias. A narrative synthesis was performed to summarize predictors included in the models and their calibration and discrimination, validation status, and clinical applicability. RESULTS: Among the 6,671 citations identified, we included 5 studies (n = 23,063 patients). The included studies described 5 unique multivariable prediction models generated through forward selection, backward selection, or Akaike Information Criterion-based methods. Two models were designed to predict any SSI and 3 Szyilagyi grade II (extending into subcutaneous tissue) SSI. Across the 5 models, 18 adjusted predictors (10 of which were preoperative, 3 intraoperative, and 5 postoperative) significantly predicted any SSI and 14 adjusted predictors significantly predict Szilagyi grade II SSI. Female sex, obesity, and chronic obstructive pulmonary disease significantly predicted SSI in more than one model. All models had a "good fit" according to the Hosmer-Lemeshow test (P > 0.05). Model discrimination was quantified using the area under the curve, which ranged from 0.66 to 0.75 across models. Two models were internally validated using non-exhaustive twofold cross-validation and bootstrap resampling. No model was externally validated. Three studies had a high overall risk of bias according to the Prediction model Risk Of Bias ASsessment Tool (PROBAST). CONCLUSIONS: Five multivariable prediction models with moderate discrimination have been developed to forecast risk of SSI development after lower limb revascularization surgery. Given the frequency and consequences of SSI after these procedures, development and external validation of novel prediction models and comparison of these models to the existing models evaluated in this systematic review is warranted.

"It's a stressful, trying time for the caretaker": an interpretive description qualitative study of postoperative transitions in care for older adults with frailty from the perspectives of informal caregivers.

BACKGROUND: Older adults with frailty have surgery at a high rate. Informal caregivers often support the postoperative transition in care. Despite the growing need for family and caregiver support for this population, little is known about the experience of providing informal care to older adults with frailty during the postoperative transition in care. The purpose of this study was to explore what is important during a postoperative transition in care for older adults with frailty from the perspective of informal caregivers. METHODS: This was a qualitative study using an interpretive description methodology. Seven informal caregivers to older adults [aged ≥ 65 years with frailty (Clinical Frailty Scale score ≥ 4) who had an inpatient elective surgery] participated in a telephone-based, semi-structured interview. Audio files were transcribed and analyzed using reflexive thematic analysis. RESULTS: Four themes were constructed: (1) being informed about what to expect after surgery; (2) accessible communication with care providers; (3) homecare resources are needed for the patient; and (4) a support network for the caregivers. Theme 4 included two sub-themes: (a) respite and emotional support and (b) occupational support. CONCLUSIONS: Transitions in care present challenges for informal caregivers of older adults with frailty, who play an important role in successful transitions. Future postoperative transitional care programs should consider making targeted information, accessible communication, and support networks available for caregivers as part of facilitating successful transitions in care.

A quasi-experimental evaluation of the association between implementation of Quality-Based Procedures funding for hip fractures and improvements in processes and outcomes for hip fracture patients in Ontario: an interrupted time series analysis.

PURPOSE: In 2013, Ontario introduced a patient-based funding model for hip fracture care (Quality-Based Procedures [QBP]). The association of QBP implementation with changes in processes and outcomes has not been evaluated. METHODS: We conducted a quasi-experimental study using linked health data for adult hip fractures as an interrupted time series. The pre-QBP period was from 2008 to 2012 and the post-QBP period was from 2014 to 2018; 2013 was excluded as a wash-in period. We used segmented regression analyses to estimate the association of QBP implementation with changes in processes (surgery in less than two days from admission, use of echocardiography, use of nerve blocks, and provision of geriatric care) and clinical outcomes (90-day mortality, 90-day readmissions, length of stay, and days alive at home). We estimated the immediate (level) change, trend (slope) postimplementation, and total counterfactual differences. Sensitivity analyses included case-mix adjustment and stratification by hospital type and procedure. RESULTS: We identified 45,500 patients in the pre-QBP period and 41,256 patients in the post-QBP period. There was a significant total counterfactual increase in the use of nerve blocks (11.1%; 95% confidence interval [CI], 6.2 to 16.0) and a decrease in the use of echocardiography (-2.5%; 95% CI, -3.7 to -1.3) after QBP implementation. The implementation of QBP was not associated with a clinically or statistically meaningful change in 90-day mortality, 90-day readmission, length of stay, or number of days alive at home. CONCLUSION: Evaluation of the QBP program is crucial to inform ongoing and future changes to policy and funding for hip fracture care. The introduction of the QBP Hip Fracture program, supported by evidence-based recommendations, was associated with improved application of some evidence-based processes of care but no changes in clinical outcomes. There is a need for ongoing development and evaluation of funding models to identify optimal strategies to improve the value and outcomes of hip fracture care. STUDY REGISTRATION: Open Science Framework ( https://osf.io/2938h/ ); first posted 13 June 2022.

RéSUMé: OBJECTIF: En 2013, l'Ontario a mis en place un modèle de financement axé sur les patient·es pour les soins suivant une fracture de la hanche (procédures fondées sur la qualité [PFQ]). L'association entre la mise en œuvre des PFQ et les changements dans les processus et les devenirs n'a pas été évaluée. MéTHODE: Nous avons mené une étude quasi expérimentale en utilisant des données de santé couplées pour les fractures de la hanche chez l'adulte comme une série chronologique interrompue. La période précédant les PFQ s'étendait de 2008 à 2012, et la période subséquente à l'implantation des PFQ allait de 2014 à 2018. L'année 2013 a été exclue en tant que période de rodage. Nous avons utilisé des analyses de régression segmentées pour estimer l'association entre la mise en œuvre des PFQ avec des changements aux processus (chirurgie en moins que deux jours suivant l'admission, utilisation de l'échocardiographie, utilisation de blocs nerveux et prestation de soins gériatriques) et des issues cliniques (mortalité à 90 jours, réadmissions à 90 jours, durée de séjour et jours de vie à domicile). Nous avons estimé le changement immédiat (niveau), la tendance (pente) après la mise en œuvre et les différences contrefactuelles totales. Les analyses de sensibilité comprenaient l'ajustement et la stratification de la combinaison de cas par type d'hôpital et par procédure. RéSULTATS: Nous avons identifié 45 500 patient·es dans la période pré-PFQ et 41 256 patient·es dans la période post-PFQ. Il y a eu une augmentation contrefactuelle totale significative de l'utilisation de blocs nerveux (11,1 %; intervalle de confiance [IC] à 95 %, 6,2 à 16,0) et une diminution de l'utilisation de l'échocardiographie (−2,5 %; IC 95 %, −3,7 à −1,3) après la mise en œuvre des PFQ. La mise en œuvre des PFQ n'a pas été associée à un changement cliniquement ou statistiquement significatif de la mortalité à 90 jours, de la réadmission à 90 jours, de la durée de séjour ou du nombre de jours de vie à domicile. CONCLUSION: L'évaluation du programme de PFQ est cruciale pour guider les changements actuels et futurs aux politiques et au financement des soins suivant une fracture de la hanche. La mise en place du programme de PFQ pour les fractures de la hanche, appuyée par des recommandations fondées sur des données probantes, a été associée à une meilleure application de certains processus de soins fondés sur des données probantes, mais à aucun changement dans les devenirs cliniques. Il est nécessaire d'élaborer et d'évaluer continuellement des modèles de financement afin de déterminer les stratégies optimales pour améliorer la valeur et les devenirs des soins suivant une fracture de la hanche. ENREGISTREMENT DE L'éTUDE: Open Science Framework ( https://osf.io/2938h/ ); première publication le 13 juin 2022.

Perioperative quality indicators specific to the practice of anesthesia in noncardiac surgery: an umbrella review.

PURPOSE: Improvement in delivery of perioperative care depends on the ability to measure outcomes that can direct meaningful changes in practice. We sought to identify and provide an overview of perioperative quality indicators specific to the practice of anesthesia in noncardiac surgery. SOURCE: We conducted an umbrella review (a systematic review of systematic reviews) according to Joanna Briggs Institute methodology. We included systematic reviews examining perioperative indicators in patients ≥ 18 yr of age undergoing noncardiac surgery. Our primary outcome was any quality indicator specific to anesthesia. Indicators were classified by the Donabedian system and perioperative phase of care. The quality of systematic reviews was assessed using AMSTAR 2 criteria. Level of evidence of quality indicators was stratified by the Oxford Centre for Evidence-Based Medicine Classification. PRINCIPAL FINDINGS: Our search returned 1,475 studies. After removing duplicates and screening of abstracts and full texts, 23 systematic reviews encompassing 3,164 primary studies met our inclusion criteria. There were 330 unique quality indicators. Process indicators were most common (n = 169), followed by outcome (n = 114) and structure indicators (n = 47). Few identified indicators were supported by high-level evidence (45/330, 14%). Level 1 evidence supported indicators of antibiotic prophylaxis (1a), venous thromboembolism prophylaxis (1a), postoperative nausea/vomiting prophylaxis (1b), maintenance of normothermia (1a), and goal-directed fluid therapy (1b). CONCLUSION: This umbrella review highlights the scarcity of perioperative quality indicators that are supported by high quality evidence. Future development of quality indicators and recommendations for outcome measurement should focus on metrics that are supported by level 1 evidence. Potential targets for evidence-based quality-improvement programs in anesthesia are identified herein. STUDY REGISTRATION: PROSPERO (CRD42020164691); first registered 28 April 2020.

RéSUMé: OBJECTIF: L'amélioration de la prestation des soins périopératoires dépend de la capacité de mesurer les résultats qui peuvent orienter des changements significatifs dans la pratique. Nous avons cherché à identifier et à fournir une vue d'ensemble des indicateurs périopératoires de qualité spécifiques à la pratique de l'anesthésie en chirurgie non cardiaque. SOURCES: Nous avons mené une revue d'ensemble (une revue systématique des revues systématiques) selon la méthodologie de l'Institut Joanna Briggs. Nous avons inclus des revues systématiques examinant les indicateurs périopératoires chez les patient·es âgé·es de 18 ans ou plus bénéficiant d'une chirurgie non cardiaque. Notre critère d'évaluation principal était tout indicateur de qualité spécifique à l'anesthésie. Les indicateurs ont été classés en fonction du système de Donabedian et de la phase périopératoire des soins. La qualité des revues systématiques a été évaluée à l'aide des critères AMSTAR 2. Le niveau de donnée probante des indicateurs de qualité a été stratifié selon l'Oxford Centre for Evidence-Based Medicine Classification. CONSTATATIONS PRINCIPALES: Notre recherche a permis de trouver 1475 études. Après avoir éliminé les doublons et examiné les résumés et les textes intégraux, 23 revues systématiques englobant 3164 études primaires ont répondu à nos critères d'inclusion. Il y avait 330 indicateurs de qualité uniques. Les indicateurs de processus étaient les plus courants (n = 169), suivi des indicateurs de résultats (n = 114) et des indicateurs de structure (n = 47). Peu d'indicateurs identifiés étaient étayés par des données probantes de haut niveau (45/330, 14 %). Les données probantes de niveau 1 ont confirmé les indicateurs de l'antibioprophylaxie (1a), de la prophylaxie pour la thromboembolie veineuse (1a), de la prophylaxie postopératoire pour les nausées/vomissements (1b), du maintien de la normothermie (1a) et de la fluidothérapie ciblée (1b). CONCLUSION: Cet examen d'ensemble met en évidence la rareté des indicateurs périopératoires de qualité qui sont étayés par des données probantes de haute qualité. L'élaboration future d'indicateurs de qualité et de recommandations pour la mesure des résultats devrait être axée sur des paramètres étayés par des données probantes de niveau 1. Les cibles potentielles des programmes d'amélioration de la qualité de l'anesthésie fondés sur des données probantes sont identifiées dans le présent manuscrit. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42020164691); premier enregistrement le 28 avril 2020.

Nonclinical factors affecting intraoperative red blood cell transfusion: a systematic review.

PURPOSE: There is significant variability in intraoperative red blood cell (RBC) transfusion practice. We aimed to use the theoretical domains framework (TDF) to categorize nonclinical and behavioural factors driving intraoperative RBC transfusion practice in a systematic review of the literature. SOURCE: We searched electronic databases from inception until August 2021 to identify studies evaluating nonclinical factors affecting intraoperative RBC transfusion. Using the Mixed Methods Appraisal Tool, we assessed the quality of included studies and identified relevant nonclinical factors, which were coded into TDF domains by two independent reviewers using NVivo (Lumivero, QSR International, Burlington, MA, USA). We identified common themes within domains and sorted domains based on the frequency of reported factors. PRINCIPAL FINDINGS: Our systematic review identified 18 studies: nine retrospective cohort studies, six cross-sectional surveys, and three before-and-after studies. Factors related to the social influences, behavioural regulation, environmental context/resources, and beliefs about consequences domains of the TDF were the most reported factors. Key factors underlying the observed variability in transfusion practice included the social effects of peers, patients, and institutional culture on decision-making (social influences), and characteristics of the practice environment including case volume, geographic location, and case start time (environmental context/resources). Studies reported variable beliefs about the consequences of both intraoperative transfusion and anemia (beliefs about consequences). Provider- and institutional-level audits, educational sessions, and increased communication between surgeons/anesthesiologists were identified as strategies to optimize intraoperative transfusion decision-making (behavioural regulation). CONCLUSION: Our systematic review has synthesized the literature on nonclinical and behavioural factors impacting intraoperative transfusion decision-making, categorized using the TDF. These findings can inform evidence-based interventions to reduce intraoperative RBC transfusion variability. STUDY REGISTRATION: Open Science Framework ( https://osf.io/pm8zs/?view_only=166299ed28964804b9360c429b1218c1 ; first posted, 3 August 2022).

RéSUMé: OBJECTIF: Il existe une variabilité importante dans les pratiques de transfusion peropératoire de culots sanguins. Nous avons cherché à utiliser le cadre des domaines théoriques (TDF, pour theoretical domains framework) pour catégoriser les facteurs non cliniques et comportementaux motivant les pratiques de transfusion peropératoire de culots sanguins dans une revue systématique de la littérature. SOURCES: Nous avons réalisé des recherches dans les bases de données électroniques de leur création jusqu'en août 2021 pour identifier les études évaluant les facteurs non cliniques affectant la transfusion peropératoire de culots sanguins. À l'aide de l'outil d'évaluation des méthodes mixtes, nous avons évalué la qualité des études incluses et identifié les facteurs non cliniques pertinents, qui ont été codés dans les domaines TDF par deux personnes les révisant de manière indépendante utilisant NVivo (Lumivero, QSR International, Burlington, MA, États-Unis). Nous avons identifié des thèmes communs au sein des domaines et trié les domaines en fonction de la fréquence des facteurs signalés. CONSTATATIONS PRINCIPALES: Notre revue systématique a identifié 18 études : neuf études de cohorte rétrospectives, six sondages transversaux et trois études avant-après. Les facteurs liés aux influences sociales, à la régulation comportementale, au contexte et aux ressources environnementaux et les croyances concernant les domaines de conséquences du TDF étaient les facteurs les plus rapportés. Les principaux facteurs sous-jacents à la variabilité observée dans la pratique transfusionnelle comprenaient les effets sociaux des pairs, de la patientèle et de la culture de l'établissement sur la prise de décision (influences sociales) et les caractéristiques de l'environnement de pratique, y compris le volume de cas, l'emplacement géographique et l'heure de début des cas (contexte/ressources environnementaux). Des études ont fait état de croyances variables sur les conséquences de la transfusion peropératoire et de l'anémie (croyances sur les conséquences). Des vérifications au niveau des prestataires et des établissements, des séances de formation et une communication accrue entre les chirurgien·nes et les anesthésiologistes ont été identifiées comme des stratégies pouvant optimiser la prise de décision transfusionnelle peropératoire (régulation comportementale). CONCLUSION: Notre revue systématique a synthétisé la littérature sur les facteurs non cliniques et comportementaux ayant une incidence sur la prise de décision transfusionnelle peropératoire, classés à l'aide du TDF. Ces résultats peuvent éclairer les interventions fondées sur des données probantes pour réduire la variabilité de transfusion peropératoire de culots sanguins. ENREGISTREMENT DE L'éTUDE: Open Science Framework ( https://osf.io/pm8zs/?view_only=166299ed28964804b9360c429b1218c1 ; soumis pour la première fois, 3 août 2022).

Home-based exercise prehabilitation to improve disease-free survival and return to intended oncologic treatment after cancer surgery in older adults with frailty: a secondary analysis of a randomized trial.

BACKGROUND: Improving survivorship for patients with cancer and frailty is a priority. We aimed to estimate whether exercise prehabilitation improves disease-free survival and return to intended oncologic treatment for older adults with frailty undergoing cancer surgery. METHODS: We conducted a secondary analysis of the oncologic outcomes of a randomized trial of patients ≥ 60 yr of age with frailty undergoing elective cancer surgery. Participants were randomized either to a supported, home-based exercise program plus nutritional guidance or to usual care. Outcomes for this analysis were one-year disease-free survival and return to intended oncologic treatment. We estimated complier average causal effects to account for intervention adherence. RESULTS: We randomized 204 participants (102 per arm); 182 were included in our modified intention-to-treat population and, of these participants, 171/182 (94%) had complete one-year follow up. In the prehabilitation group, 18/94 (11%) died or experienced cancer recurrence, compared with 19/88 (11%) in the control group (hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.66 to 2.34; P = 0.49). Return to intended oncologic treatment occurred in 24/94 (29%) patients the prehabilitation group vs 20/88 (23%) in the usual care group (HR, 1.53; 95% CI, 0.84 to 2.77; P = 0.16). Complier average causal effects directionally diverged for disease-free survival (HR, 0.91; 95% CI, 0.20 to 4.08; P = 0.90) and increased the point estimate for return to treatment (HR, 2.04; 95% CI, 0.52 to 7.97; P = 0.30), but in both cases the CIs included 1. CONCLUSIONS: Randomization to home-based exercise prehabilitation did not lead to significantly better disease-free survival or earlier return to intended oncologic treatment in older adults with frailty undergoing cancer surgery. Our results could inform future trials powered for more plausible effect sizes, especially for the return to intended oncologic treatment outcome. STUDY REGISTRATION: ClinicalTrials.gov ( NCT02934230 ); first submitted 22 August 2016.

RéSUMé: CONTEXTE: L'amélioration de la survie des personnes atteintes de cancer et de fragilité est une priorité. Nous avons cherché à estimer si la préadaptation physique améliore la survie sans maladie et le retour au traitement oncologique prévu pour les personnes âgées fragiles bénéficiant d'une chirurgie du cancer. MéTHODE: Nous avons effectué une analyse secondaire des issues oncologiques d'une étude randomisée de patient·es âgé·es de 60 ans ou plus atteint·es de fragilité bénéficiant d'une chirurgie carcinologique non urgente. Nous avons randomisé les personnes participantes à un programme d'exercice à domicile accompagné de conseils nutritionnels ou à recevoir les soins habituels. Les critères d'évaluation de cette analyse étaient la survie sans maladie à un an et le retour au traitement oncologique prévu. Nous avons estimé les effets moyens causaux d'observance pour tenir compte de l'adhérence à l'intervention. RéSULTATS: Nous avons randomisé 204 participant·es (102 par bras); 182 personnes ont été incluses dans notre population modifiée en intention de traiter et, parmi ces participant·es, 171/182 (94%) ont fait l'objet d'un suivi complet à un an. Dans le groupe préadaptation, 18/94 (11%) personnes sont décédées ou ont connu une récidive du cancer, contre 19/88 (11 %) dans le groupe témoin (rapport de risque [HR], 1,25; intervalle de confiance [IC] à 95%, 0.66 à 2.34; P = 0.49). Le retour au traitement oncologique prévu a eu lieu chez 24 patient·es sur 94 (29 %) dans le groupe préadaptation vs 20/88 (23 %) dans le groupe de soins habituels (RR, 1.53; IC 95%, 0.84 à 2.77; P = 0.16). Les effets moyens causaux d'observance ont divergé directionnellement pour la survie sans maladie (RR, 0.91; IC 95%, 0.20 à 4.08; P = 0.90) et augmenté l'estimation ponctuelle du retour au traitement (RR, 2.04; IC 95%, 0.52 à 7.97; P = 0.30), mais dans les deux cas, les IC comprenaient 1. CONCLUSION: La randomisation pour la préadaptation physique à domicile n'a pas entraîné d'amélioration significative de la survie sans maladie ou de retour plus précoce au traitement oncologique prévu chez les personnes âgées fragiles bénéficiant d'une chirurgie du cancer. Nos résultats pourraient éclairer de futures études alimentées par des tailles d'effet plus plausibles, en particulier pour le critère de retour prévu au traitement oncologique. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov ( NCT02934230 ); première soumission le 22 août 2016.

Use of opioids and opioid alternatives during general anesthesia: a pan-Canadian survey among anesthesiologists.

PURPOSE: While there is limited patient-centred evidence (i.e., evidence that is important for patients and end-users) to inform the use of pharmacologic opioid minimization strategies (i.e., the use of opioid alternatives) for adult surgical patients requiring general anesthesia, such strategies are increasingly being adopted into practice. Our objectives were to describe anesthesiologists' beliefs regarding intraoperative opioid minimizing strategies use and utility, and to explore important clinical decision-making factors. METHODS: We conducted a pan-Canadian web-based survey of anesthesiologists that was distributed using a modified Dillman technique. Our multidisciplinary team, including a patient partners panel, participated in the process of domains and items generation, items reduction, formatting, and composition. Our sampling frames were members of the Canadian Anesthesiologists' Society and members of the Association des Anesthésiologistes du Québec. We used the newsletters of each organization to distribute our survey, which was available in English and French and housed on the LimeSurvey (LimeSurvey GmbH, Hamburg, Germany) platform. RESULTS: From our eligible sampling frame, 18% completed the survey (356 respondents out of 2,008 eligible participants). Most of the respondents believed that using opioid minimization strategies during general anesthesia could improve postoperative clinical outcomes, including pain control (84% agree or strongly agree, n = 344/409). Reported use of pharmacologic opioid minimization strategies was variable; however, most respondents believed that nonsteroidal anti-inflammatory drugs, acetaminophen, N-methyl-D-aspartate receptor antagonists (ketamine), α2-adrenoceptor agonists (dexmedetomidine), corticosteroids, and intravenous lidocaine improve prostoperative clinical outcomes. The primary factors guiding decision-making regarding the use of opioid minimization strategies were postoperative acute pain intensity, the impact of acute pain on functioning, patient well-being (i.e., quality of recovery) and patient satisfaction with care. A lack of evidence was the most important barrier limiting the use of opioid minimization strategies. CONCLUSION: In our survey of Canadian anesthesiologists, several opioid minimization strategies were believed to be effective complements to general anesthesia, although there was substantial variation in their reported use. Future randomized controlled trials and systematic reviews evaluating the effectiveness of opioid minimization strategies should prioritize patient-centred outcome measures assessment such as the quality of recovery or the impact of acute pain on functioning.

RéSUMé: OBJECTIF: Bien qu'il existe peu de données probantes centrées sur le/la patient·e (c.-à-d. des données probantes importantes pour les patient·es et les utilisateurs et utilisatrices) pour éclairer l'utilisation de stratégies pharmacologiques de minimisation des opioïdes (c.-à-d. l'utilisation d'alternatives aux opioïdes) pour la patientèle chirurgicale adulte nécessitant une anesthésie générale, de telles stratégies sont de plus en plus adoptées par les cliniciens. Nos objectifs étaient de décrire les croyances des anesthésiologistes concernant l'utilisation et l'utilité des stratégies peropératoires de minimisation des opioïdes, et d'explorer les facteurs importants pour la prise de décision clinique. MéTHODE: Nous avons mené un sondage pancanadien en ligne auprès des anesthésiologistes, distribué à l'aide d'une technique Dillman modifiée. Notre équipe multidisciplinaire, comprenant un panel de patient·es partenaires, a participé au processus de génération de domaines et d'éléments, de réduction des éléments, de formatage et de composition. Nos bases d'échantillonnage étaient les membres de la Société canadienne des anesthésiologistes et de l'Association des anesthésiologistes du Québec. Nous avons utilisé les bulletins d'information de chaque organisation pour distribuer notre sondage, disponible en anglais et en français et hébergé sur la plateforme LimeSurvey (LimeSurvey GmbH, Hambourg, Allemagne). RéSULTATS: De notre base d'échantillonnage admissible, 18 % ont répondu au sondage (356 personnes sur 2008 personnes admissibles). La plupart des répondant·es étaient d'avis que l'utilisation de stratégies de minimisation des opioïdes pendant l'anesthésie générale pourrait améliorer les issues cliniques postopératoires, notamment le contrôle de la douleur (84 % d'accord ou tout à fait d'accord, n = 344/409). L'utilisation déclarée de stratégies pharmacologiques de minimisation des opioïdes était variable; cependant, la plupart des répondant·es croyaient que les anti-inflammatoires non stéroïdiens, l'acétaminophène, les antagonistes des récepteurs N-méthyl-D-aspartate (kétamine), les agonistes α2­adrénergiques (dexmédétomidine), les corticostéroïdes et la lidocaïne intraveineuse améliorent les issues cliniques postopératoires. Les principaux facteurs guidant la prise de décision concernant l'utilisation de stratégies de minimisation des opioïdes étaient l'intensité de la douleur aiguë postopératoire, l'impact de la douleur aiguë sur le fonctionnement, le bien-être du patient ou de la patiente (c.-à-d. la qualité du rétablissement) et la satisfaction de la patiente ou du patient à l'égard des soins. Le manque de données probantes était l'obstacle le plus important à l'utilisation des stratégies de réduction des opioïdes. CONCLUSION: Dans notre sondage auprès des anesthésiologistes au Canada, plusieurs stratégies de minimisation des opioïdes étaient considérées comme des compléments efficaces à l'anesthésie générale, bien qu'il y avait des variations importantes dans leur utilisation déclarée. Les futures essais cliniques randomisés et revues systématiques évaluant l'efficacité des stratégies de minimisation des opioïdes devraient prioriser l'évaluation d'issues orientées vers le/la patient·e, comme la qualité du rétablissement ou la mesure de l'impact de la douleur aiguë sur le fonctionnement.

A systematic review and meta-analysis of outcomes associated with development of surgical site infection after lower-limb revascularization surgery.

OBJECTIVES: Although surgical site infection (SSI) is a commonly used quality metric after lower-limb revascularization surgery, outcomes associated with development of this complication are poorly characterized. We conducted a systematic review and meta-analysis of studies reporting associations between development of an SSI after these procedures and clinical outcomes and healthcare resource use. METHODS: We searched MEDLINE, Embase, CENTRAL, and Evidence-Based Medicine Reviews (inception to April 4th, 2023) for studies examining adjusted associations between development of an SSI after lower-limb revascularization surgery and clinical outcomes and healthcare resource use. Two investigators independently screened abstracts and full-text citations, extracted data, and assessed risk of bias. Data were pooled using random-effects models. Heterogeneity was assessed using I2 statistics. GRADE was used to assess estimate certainty. RESULTS: Among 6671 citations identified, we included 11 studies (n = 61,628 total patients) that reported adjusted-associations between development of an SSI and 13 different outcomes. Developing an SSI was associated with an increased adjusted-risk of hospital readmission (pooled adjusted-risk ratio (aRR) = 3.55; 95% CI (confidence interval) = 1.40-8.97; n = 4 studies; n = 13,532 patients; I2 = 99.0%; moderate certainty), bypass graft thrombosis within 30-days (pooled aRR = 2.09; 95% CI = 1.41-3.09; n = 2 studies; n = 23,240 patients; I2 = 51.1%; low certainty), reoperation (pooled aRR = 2.69; 95% CI = 2.67-2.72; n = 2 studies; n = 23,240 patients; I2 = 0.0%; moderate certainty), bleeding requiring a transfusion or secondary procedure (aRR = 1.40; 95% CI = 1.26-1.55; n = 1 study; n = 10,910 patients; low certainty), myocardial infarction or stroke (aRR = 1.21; 95% CI = 1.02-1.43; n = 1 study; n = 10,910 patients; low certainty), and major (i.e., above-ankle) amputation (pooled aRR = 1.93; 95% CI = 1.26-2.95; n = 4 studies; n = 32,859 patients; I2 = 83.0; low certainty). Development of an SSI >30-days after the index operation (aRR = 2.20; 95% CI = 1.16-4.17; n = 3 studies; n = 21,949 patients; low certainty) and prosthetic graft infection (aRR = 6.72; 95% CI = 3.21-12.70; n = 1 study; n = 272 patients; low certainty) were both associated with an increased adjusted-risk of major amputation. Prosthetic graft infection was also associated with an increased adjusted-risk of mortality >30-days after the index procedure (aRR = 6.40; 95% CI = 3.32-12.36; n = 1 study; n = 272 patients; low certainty). CONCLUSIONS: This systematic review and meta-analysis suggests that development of an SSI after lower-limb revascularization surgery significantly increases patient morbidity and healthcare resource use. SSI is therefore a valuable quality metric after these surgeries. However, current estimates are based on heterogenous, low-to-moderate certainty evidence and should be confirmed by large, multicenter, cohort studies.

Measuring the Predictive Accuracy of Preoperative Clinical Frailty Instruments Applied to Electronic Health Data in Older Patients Having Emergency General Surgery: A Retrospective Cohort Study.

OBJECTIVE: To compare predictive accuracy of frailty instruments operationalizable in electronic data for prognosticating outcomes among older adults undergoing emergency general surgery (EGS). BACKGROUND: Older patients undergoing EGS are at higher risk of perioperative morbidity and mortality. Preoperative frailty is a common and strong perioperative risk factor in this population. Despite this, existing barriers preclude routine preoperative frailty assessment. METHODS: We conducted a retrospective cohort study of adults above 65 undergoing EGS from 2012 to 2018 using Institute for Clinical Evaluative Sciences (ICES) provincial healthcare data in Ontario, Canada. We compared 4 frailty instruments: Frailty Index (FI), Hospital Frailty Risk Score (HFRS), Risk Analysis Index-Administrative (RAI), ACG Frailty-defining diagnoses indicator (ACG). We compared predictive accuracy beyond baseline risk models (age, sex, American Society of Anesthesiologists' score, procedural risk). Predictive performance was measured using discrimination, calibration, explained variance, net reclassification index and Brier score (binary outcomes); using explained variance, root mean squared error and mean absolute prediction error (continuous outcomes). Primary outcome was 30-day mortality. Secondary outcomes were 365-day mortality, nonhome discharge, days alive at home, length of stay, and 30-day and 365-day health systems cost. RESULTS: A total of 121,095 EGS patients met inclusion criteria. Of these, 11,422 (9.4%) experienced death 30 days postoperatively. Addition of FI, HFRS, and RAI to the baseline model led to improved discrimination, net reclassification index, and R2 ; RAI demonstrated the largest improvements. CONCLUSIONS: Adding 4 frailty instruments to typically assessed preoperative risk factors demonstrated strong predictive performance in accurately prognosticating perioperative outcomes. These findings can be considered in developing automated risk stratification systems among older EGS patients.

Efficacy of Strategies Intended to Prevent Surgical Site Infection After Lower Limb Revascularization Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: The objective of this study is to evaluate the efficacy of strategies intended to prevent surgical site infection (SSI) after lower limb revascularization surgery. BACKGROUND: SSIs are common, costly complications of lower limb revascularization surgery associated with significant morbidity and mortality. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and Evidence-Based Medicine Reviews (inception to April 28, 2022). Two investigators independently screened abstracts and full-text articles, extracted data, and assessed the risk of bias. We included randomized controlled trials (RCTs) that evaluated strategies intended to prevent SSI after lower limb revascularization surgery for peripheral artery disease. We used random-effects models to pool data and GRADE to assess certainty. RESULTS: Among 6258 identified citations, we included 26 RCTs (n=4752 patients) that evaluated 12 strategies to prevent SSI. Preincision antibiotics [risk ratio (RR)=0.25; 95% CI, 0.11-0.57; n=4 studies; I2 statistic=7.1%; high certainty] and incisional negative-pressure wound therapy (iNPWT) (RR=0.54; 95% CI, 0.38-0.78; n=5 studies; I2 statistic=7.2%; high certainty) reduced pooled risk of early (≤30 days) SSI. iNPWT also reduced the risk of longer-term (>30 days) SSI (pooled-RR=0.44; 95% CI, 0.26-0.73; n=2 studies; I2 =0%; low certainty). Strategies with uncertain effects on risk of SSI included preincision ultrasound vein mapping (RR=0.58; 95% CI, 0.33-1.01; n=1 study); transverse groin incisions (RR=0.33; 95% CI, 0.097-1.15; n=1 study), antibiotic-bonded prosthetic bypass grafts (RR=0.74; 95% CI, 0.44-1.25; n=1 study; n=257 patients), and postoperative oxygen administration (RR=0.66; 95% CI, 0.42-1.03; n=1 study) (low certainty for all). CONCLUSIONS: Preincision antibiotics and iNPWT reduce the risk of early SSI after lower limb revascularization surgery. Confirmatory trials are required to determine whether other promising strategies also reduce SSI risk.