A Hospital-Wide Open-Label Cluster Crossover Pragmatic Comparative Effectiveness Randomized Trial Comparing Normal Saline to Ringer's Lactate: Protocol and Statistical Analysis Plan of The FLUID Trial.

BACKGROUND: Normal saline (NS) and Ringer's lactate (RL) are the most common crystalloids given to hospitalized patients. Despite concern about possible harm associated with NS (eg, hyperchloremic metabolic acidosis, impaired kidney function, and death), few large multicenter randomized trials focused on critically ill patients have compared these fluids. Uncertainty exists about the effects of these fluids on clinically important outcomes across all hospitalized patients. OBJECTIVE: The FLUID trial is a pragmatic, multicenter, 2×2 cluster crossover comparative effectiveness randomized trial that aims to evaluate the effectiveness of a hospital-wide policy that stocks either NS or RL as the main crystalloid fluid in 16 hospitals across Ontario, Canada. METHODS: All hospitalized adult and pediatric patients (anticipated sample size 144,000 patients) with an incident admission to the hospital over the course of each study period will be included. Either NS or RL will be preferentially stocked throughout the hospital for 12 weeks before crossing to the alternate fluid for the subsequent 12 weeks. The primary outcome is a composite of death and hospital readmission within 90 days of hospitalization. Secondary outcomes include death, hospital readmission, dialysis, reoperation, postoperative reintubation, length of hospital stay, emergency department visits, and discharge to a facility other than home. All outcomes will be obtained from health administrative data, eliminating the need for individual case reports. The primary analysis will use cluster-level summaries to estimate cluster-average treatment effects. RESULTS: The statistical analysis plan has been prepared "a priori" in advance of receipt of the trial data set from ICES and any analyses. CONCLUSIONS: We describe the protocol and statistical analysis plan for the evaluation of primary and secondary outcomes for the FLUID trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04512950; https://classic.clinicaltrials.gov/ct2/show/NCT04512950. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51783.

A model to predict level of adherence to prehabilitation in older adults with frailty having cancer surgery.

PURPOSE: Preoperative exercise could improve postoperative outcomes for people with frailty; however, little is known about how to predict older people's adherence to exercise before surgery (i.e., prehabilitation) programs. Our objective was to derive and validate a model to predict prehabilitation adherence in older adults living with frailty before cancer surgery. METHODS: This was a nested prospective cohort study of older adults with frailty having cancer surgery who participated in a randomized controlled trial of home-based prehabilitation compared with standard perioperative care. We constructed a multivariable ordinary least squares linear regression model to predict adherence. Covariates were selected a priori based on clinical expertise and systematic review. Optimism was estimated through internal validation using bootstrap resampling. RESULTS: The derivation cohort consisted of 95 participants in the intervention arm of the trial. Percent adherence ranged from 0% to 100%, with a mean (standard deviation) of 61 (34)%. Previous physical activity and age were the only predictors significant at the 5% level. CONCLUSION: A prespecified multivariable model may help to explain a modest degree of variation in prehabilitation adherence in older people with frailty. While this model is an important step toward personalizing prehabilitation support, this study was limited by a small sample size and future research is needed to better understand personalized prediction of prehabilitation adherence in older people with frailty.

RéSUMé: OBJECTIF: L'exercice préopératoire pourrait améliorer les issues postopératoires pour les personnes fragilisées; cependant, on ne sait que peu de choses sur la façon de prédire l'observance des personnes âgées à faire de l'exercice avant leur chirurgie (c.-à-d. à suivre des programmes de préadaptation). Notre objectif était de définir et de valider un modèle pour prédire l'observance de la préadaptation chez les personnes âgées fragilisées avant une chirurgie oncologique. MéTHODE: Il s'agissait d'une étude de cohorte prospective imbriquée auprès de personnes âgées fragilisées subissant une chirurgie oncologique qui ont participé à une étude randomisée contrôlée sur la préadaptation à domicile par rapport aux soins périopératoires standard. Nous avons construit un modèle de régression linéaire des moindres carrés ordinaires multivariés pour prédire l'observance. Les covariables ont été sélectionnées a priori sur la base de notre expertise clinique et d'une revue systématique. L'optimisme a été estimé par validation interne à l'aide d'une méthode de rééchantillonnage type « bootstrap ¼. RéSULTATS: La cohorte de dérivation comprenait 95 participant·es dans le volet intervention de l'étude. Le pourcentage d'observance variait de 0 % à 100 %, avec une moyenne (écart type) de 61 (34) %. L'activité physique antérieure et l'âge étaient les seuls prédicteurs significatifs au seuil de 5 %. CONCLUSION: Un modèle multivarié prédéfini peut aider à expliquer un degré modeste de variation dans l'observance de la préadaptation chez les personnes âgées fragilisées. Bien que ce modèle soit une étape importante vers la personnalisation du soutien à la préadaptation, cette étude a été limitée par un échantillon de petite taille; des recherches futures sont nécessaires pour mieux comprendre la prédiction personnalisée de l'observance de la préadaptation chez les personnes âgées fragilisées.

"My Biggest Fear Is She'll Die Alone": Care Partner Perspectives of Institutional COVID-19 Visitor Restrictions in Ontario, Canada.

In March 2020, the Government of Ontario, Canada implemented public health measures, including visitor restrictions in institutional care settings, to protect vulnerable populations, including older adults (> 65 years), against COVID-19 infection. Prior research has shown that visitor restrictions can negatively influence older adults' physical and mental health and can cause increased stress and anxiety for care partners. This study explores the experiences of care partners separated from the person they care for because of institutional visitor restrictions during the COVID-19 pandemic. We interviewed 14 care partners between the ages of 50 and 89; 11 were female. The main themes that emerged were changing public health and infection prevention and control policies, shifting care partner roles as a result of visitor restrictions, resident isolation and deterioration from the care partner perspective, communication challenges, and reflections on the impacts of visitor restrictions. Findings may be used to inform future health policy and system reforms.

Predictors of adherence to prescribed exercise programs for older adults with medical or surgical indications for exercise: a systematic review.

BACKGROUND AND OBJECTIVES: Prescribed exercise to treat medical conditions and to prepare for surgery is a promising intervention to prevent adverse health outcomes for older adults; however, adherence to exercise programs may be low. Our objective was to identify and grade the quality of predictors of adherence to prescribed exercise in older adults. METHODS: Prospective observational and experimental studies were identified using a peer-reviewed search strategy applied to MEDLINE, EMBASE, Cochrane, and CINAHL from inception until October 6, 2020. Following an independent and duplicate review of titles, abstracts, and full texts, we included prospective studies with an average population age >65 years, where exercise was formally prescribed for a medical or surgical condition. We excluded studies where exercise was prescribed for a chronic musculoskeletal condition. Risk of bias was assessed using the Quality in Prognostic studies tool or Cochrane risk of bias tool, as appropriate. Predictors of adherence were identified and graded for quality using an adaptation of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework for predictor studies. RESULTS: We included 19 observational studies and 4 randomized controlled trials (n=5785) Indications for exercise included cardiac (n=6), pulmonary rehabilitation (n=7), or other (n=10; surgical, medical, and neurologic). Of the 10 studies that reported adherence as the percent of prescribed sessions completed, average adherence was 80% (range 60-98%; standard deviation (SD) 11%). Of the 10 studies that reported adherence as a categorical threshold demarking adherent vs not adherent, average adherence was 57.5% (range 21-83%; SD 21%). Moderate-quality evidence suggested that positive predictors of adherence were self-efficacy and good self-rated mental health; negative predictors were depression (high quality) and distance from the exercise facility. Moderate-quality evidence suggested that comorbidity and age were not predictive of adherence. CONCLUSIONS: These findings can inform the design of future exercise programs as well as the identification of individuals who may require extra support to benefit from prescribed exercise. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018108242.

Association between frailty and patient outcomes after cancer surgery: a population-based cohort study.

BACKGROUND: Frailty is associated with poor postoperative outcomes, but existing data do not describe frailty's interaction with tumour characteristics at the time of cancer surgery. Our objective was to estimate the association between frailty and long-term survival, and to explore any interaction with tumour stage and grade. METHODS: This was a population-based cohort study conducted using linked provincial health administrative data in Ontario, Canada (2009-20). Using a cancer registry, we identified adults having elective cancer surgery. Frailty was measured using a validated index (range 0-1; higher score=greater frailty). Associations between frailty and long-term postoperative survival (primary outcome) were estimated using proportional hazards regression. Secondary outcomes were length of stay, discharge destination, days alive at home, and healthcare costs. RESULTS: We identified and included 52 012 patients. Mean frailty score was 0.13 (standard deviation 0.07). During follow-up, 19 378 (37.3%) patients died. After adjustment for risk factors, each 10% increase in frailty was associated with a 1.60-fold relative decrease in survival (95% confidence interval: 1.56-1.64). The frailty-survival association was strongest for patients with lower stage and grade cancers. Increased frailty was associated with longer hospital stays (3 days), fewer days alive and at home (42 days yr-1), more frequent discharge to a nursing facility (2.38-fold), and increased healthcare costs ($6048). CONCLUSIONS: Patient frailty is associated with decreased long-term survival after cancer surgery. The association is stronger for early-stage and -grade cancers, which would otherwise have a better survival prognosis.

The Association of Frailty with Outcomes after Cancer Surgery: A Systematic Review and Metaanalysis.

BACKGROUND: Cancer is common in older adults, who often have concurrent frailty. Frailty is a strong predictor of adverse outcomes in surgical patients. Our objective is to systematically review the association of frailty with postoperative mortality and other adverse outcomes in adult patients who have undergone nonemergency cancer surgery. METHODS: After registration (CRD42020171163), we systematically reviewed PubMed, MEDLINE, EMBASE, and CINAHL databases to identify all studies reporting an association between a preoperative frailty measurement and a relevant outcome (primary: all-cause mortality in-hospital or within 30 days of surgery; secondary outcomes: postoperative complications, length of stay, discharge disposition, mortality between 30 days and 1 year, postoperative function, and delirium). All stages of the review were completed in duplicate. Risk of bias was assessed using the Quality in Prognostic Studies (QUIPS) tool. Metaanalysis was used to pool effect estimates using random-effects models. RESULTS: A total of 2877 studies were identified, and 71 were included. Frailty was significantly associated with mortality within 30 days (adjusted odds ratio (OR) 3.02, 95% confidence interval (CI) 1.77-5.15), adverse discharge disposition (adjusted OR 2.14, 95% CI 1.52-3.02), postoperative complications (adjusted OR 2.39, 95% CI 1.64-3.49), longer-term mortality (unadjusted OR 4.32, 95% CI 2.15-8.67), and length of stay (mean difference 2.30, 95% CI 1.10-3.50). The number of studies presenting adequately adjusted estimates was small. Findings may be limited due to publication bias. CONCLUSIONS: In adults having elective cancer surgery, frailty is strongly associated with adverse health outcomes. Preoperative frailty assessment should be considered in prognostication.

A Systematic Review and Meta-Analysis of Preoperative Frailty Instruments Derived From Electronic Health Data.

BACKGROUND: Frailty is a strong predictor of adverse outcomes in the perioperative period. Given the increasing availability of electronic medical data, we performed a systematic review and meta-analysis with primary objectives of describing available frailty instruments applied to electronic data and synthesizing their prognostic value. Our secondary objectives were to assess the construct validity of frailty instruments that have been applied to perioperative electronic data and the feasibility of electronic frailty assessment. METHODS: Following protocol registration, a peer-reviewed search strategy was applied to Medline, Excerpta Medica dataBASE (EMBASE), Cochrane databases, and the Comprehensive Index to Nursing and Allied Health literature from inception to December 31, 2019. All stages of the review were completed in duplicate. The primary outcome was mortality; secondary outcomes included nonhome discharge, health care costs, and length of stay. Effect estimates adjusted for baseline illness, sex, age, procedure, and urgency were of primary interest; unadjusted and adjusted estimates were pooled using random-effects models where appropriate or narratively synthesized. Risk of bias was assessed. RESULTS: Ninety studies were included; 83 contributed to the meta-analysis. Frailty was defined using 22 different instruments. In adjusted data, frailty identified from electronic data using any instrument was associated with a 3.57-fold increase in the odds of mortality (95% confidence interval [CI], 2.68-4.75), increased odds of institutional discharge (odds ratio [OR], 2.40; 95% CI, 1.99-2.89), and increased costs (ratio of means, 1.54; 95% CI, 1.46-1.63). Most instruments were not multidimensional, head-to-head comparisons were lacking, and no feasibility data were reported. CONCLUSIONS: Frailty status derived from electronic data provides prognostic value as it is associated with adverse outcomes, even after adjustment for typical risk factors. However, future research is required to evaluate multidimensional instruments and their head-to-head performance and to assess their feasibility and clinical impact.

The Association of Frailty With Adverse Outcomes After Multisystem Trauma: A Systematic Review and Meta-analysis.

BACKGROUND: Frailty strongly predicts adverse outcomes in a variety of clinical settings; however, frailty-related trauma outcomes have not been systematically reviewed and quantitatively synthesized. Our objective was to systematically review and meta-analyze the association between frailty and outcomes (mortality-primary; complications, health resource use, and patient experience-secondary) after multisystem trauma. METHODS: After registration (CRD42018104116), we applied a peer-reviewed search strategy to MEDLINE, EMBASE, and Comprehensive Index to Nursing and Allied Health Literature (CINAHL) from inception to May 22, 2019, to identify studies that described: (1) multisystem trauma; (2) participants ≥18 years of age; (3) explicit frailty instrument application; and (4) relevant outcomes. Excluded studies included those that: (1) lacked a comparator group; (2) reported isolated injuries; and (3) reported mixed trauma and nontrauma populations. Criteria were applied independently, in duplicate to title/abstract and full-text articles. Risk of bias was assessed using the Risk of Bias in Nonrandomized Studies-of Interventions (ROBINS-I) tool. Effect measures (adjusted for prespecified confounders) were pooled using random-effects models; otherwise, narrative synthesis was used. RESULTS: Sixteen studies were included that represented 5198 participants; 9.9% of people with frailty died compared to 4.2% of people without frailty. Frailty was associated with increased mortality (adjusted odds ratio [OR], 1.53; 95% confidence interval [CI], 1.37-1.71), complications (adjusted OR, 2.32; 95% CI, 1.72-3.15), and adverse discharge (adjusted OR, 1.78; 95% CI, 1.29-2.45). Patient function, experience, and resource use outcomes were rarely reported. CONCLUSIONS: The presence of frailty is significantly associated with mortality, complications, and adverse discharge disposition after multisystem trauma. This provides important prognostic information to inform discussions with patients and families and highlights the need for trauma system optimization to meet the complex needs of older patients.