OBJECTIVE:To compare the accuracy of the modified Fried Index (mFI) and the Clinical Frailty Scale (CFS) to predict death or patient-reported new disability 90 days after major elective surgery.
...BACKGROUND:The association of frailty with patient-reported outcomes, and comparisons between preoperative frailty instruments are poorly described.
METHODS:This was a prospective multicenter cohort study. We determined frailty status in individuals ≥65 years having elective noncardiac surgery using the mFI and CFS. Outcomes included death or patient-reported new disability (primary); safety incidents, length of stay (LOS), and institutional discharge (secondary); ease of use, usefulness, benefit, clinical importance, and feasibility (tertiary). We measured the adjusted association of frailty with outcomes using regression analysis and compared true positive and false positive rates (TPR/FPR).
RESULTS:Of 702 participants, 645 had complete follow up. The CFS identified 297 (42.3%) with frailty, the mFI 257 (36.6%); 72 (11.1%) died or experienced a new disability. Frailty was significantly associated with the primary outcome (CFS adjusted odds ratio, OR, 2.51, 95% confidence interval, CI, 1.50–4.21; mFI adjusted-OR 2.60, 95% CI 1.57–4.31). TPR and FPR were not significantly different between instruments. Frailty was the only significant predictor of death or new disability in a multivariable analysis. Need for institutional discharge, costs and LOS were significantly increased in individuals with frailty. The CFS was easier to use, required less time and had less missing data.
CONCLUSIONS:Older people with frailty are significantly more likely to die or experience a new patient-reported disability after surgery. Clinicians performing frailty assessments before surgery should consider the CFS over the mFI as accuracy was similar, but ease of use and feasibility were higher.
BACKGROUND:Guidelines recommend routine preoperative frailty assessment for older people. However, the degree to which frailty instruments improve predictive accuracy when added to traditional risk ...factors is poorly described. Our objective was to measure the accuracy gained in predicting outcomes important to older patients when adding the Clinical Frailty Scale (CFS), Fried Phenotype (FP), or Frailty Index (FI) to traditional risk factors.
METHODS:This was an analysis of a multicenter prospective cohort of elective noncardiac surgery patients ≥65 years of age. Each frailty instrument was prospectively collected. The added predictive performance of each frailty instrument beyond the baseline model (age, sex, American Society of Anesthesiologists’ score, procedural risk) was estimated using likelihood ratio test, discrimination, calibration, explained variance, and reclassification. Outcomes analyzed included death or new disability, prolonged length of stay (LoS, >75th percentile), and adverse discharge (death or non-home discharge).
RESULTS:We included 645 participants (mean age, 74 standard deviation, 6); 72 (11.2%) participants died or experienced a new disability, 164 (25.4%) had prolonged LoS, and 60 (9.2%) had adverse discharge. Compared to the baseline model predicting death or new disability (area under the curve AUC, 0.67; R, 0.08, good calibration), prolonged LoS (AUC, 0.73; R, 0.18, good calibration), and adverse discharge (AUC, 0.78; R, 0.16, poor calibration), the CFS improved fit per the likelihood ratio test (P < .02 for death or new disability, <.001 for LoS, <.001 for discharge), discrimination (AUC = 0.71 for death or new disability, 0.76 for LoS, 0.82 for discharge), calibration (good for death or new disability, LoS, and discharge), explained variance (R = 0.11 for death or new disability, 0.22 for LoS, 0.25 for discharge), and reclassification (appropriate directional reclassification) for all outcomes. The FP improved discrimination and R for all outcomes, but to a lesser degree than the CFS. The FI improved discrimination for death or new disability and R for all outcomes, but to a lesser degree than the CFS and the FP. These results were consistent in internal validation.
CONCLUSIONS:Frailty instruments provide meaningful increases in accuracy when predicting postoperative outcomes for older people. Compared to the FP and FI, the CFS appears to improve all measures of predictive performance to the greatest extent and across outcomes. Combined with previous research demonstrating that the CFS is easy to use and requires less time than the FP, clinicians should consider its use in preoperative practice.
Frailty is associated with early postoperative outcomes. How frailty influences long-term postoperative recovery is poorly described. Our objective was to evaluate the association of frailty with ...postoperative disability trajectories in the year after surgery.
Prespecified 1-yr follow-up of a prospective multicentre cohort study. Patients ≥65 yr were assessed for frailty before major elective noncardiac surgery (Clinical Frailty Scale CFS and Fried Phenotype FP). The primary outcome was patient-reported disability score (using the WHO Disability Assessment Schedule 2.0) at baseline, 30, 90, and 365 days after surgery. Repeated measures linear regression estimated the association of preoperative frailty with changes in disability scores over time, adjusted for procedure. Group-based trajectory modelling was used to identify subgroup trajectories of people with frailty.
One-year follow-up was complete for 687/702 (97.9%) participants. Frailty was associated with a significant difference in disability trajectory (P<0.0001). Compared with baseline, people with frailty experienced a decrease in disability score at 365 days (CFS frailty: −7.3 points, 95% confidence interval CI −10.2 to −4.5); (FP frailty: −5.4 points, 95% CI −8.5 to −2.3); people without frailty had no significant change in their disability score from baseline (no CFS frailty: +0.8 points, 95% CI −1.7 to 3.2; no FP frailty: +1.1 points, 95% CI −3.5 to 1.3). More than one-third of people with frailty experienced an early increase in disability before achieving a net decrease in disability.
Decision-making and care planning should integrate the possible trade-offs between early adverse outcomes with longer-term benefit when frailty is present in older surgical patients.
When learning rule-based categories, sufficient cognitive resources are needed to test hypotheses, maintain the currently active rule in working memory, update rules after feedback, and to select a ...new rule if necessary. Prior research has demonstrated that conjunctive rules are more complex than unidimensional rules and place greater demands on executive functions like working memory. In our study, event-related potentials (ERPs) were recorded while participants performed a conjunctive rule-based category learning task with trial-by-trial feedback. In line with prior research, correct categorization responses resulted in a larger stimulus-locked late positive complex compared to incorrect responses, possibly indexing the updating of rule information in memory. Incorrect trials elicited a pronounced feedback-locked P300 elicited which suggested a disconnect between perception, and the rule-based strategy. We also examined the differential processing of stimuli that were able to be correctly classified by the suboptimal single-dimensional rule (“easy” stimuli) versus those that could only be correctly classified by the optimal, conjunctive rule (“difficult” stimuli). Among strong learners, a larger, late positive slow wave emerged for difficult compared with easy stimuli, suggesting differential processing of category items even though strong learners performed well on the conjunctive category set. Overall, the findings suggest that ERP combined with computational modelling can be used to better understand the cognitive processes involved in rule-based category learning.
Lipid droplets (LD) play a central role in lipid homeostasis by controlling transient fatty acid (FA) storage and release from triacylglycerols stores, while preventing high levels of cellular toxic ...lipids. This crucial function in oxidative tissues is altered in obesity and type 2 diabetes. Perilipin 5 (PLIN5) is a LD protein whose mechanistic and causal link with lipotoxicity and insulin resistance has raised controversies. We investigated here the physiological role of PLIN5 in skeletal muscle upon various metabolic challenges. We show that PLIN5 protein is elevated in endurance-trained (ET) subjects and correlates with muscle oxidative capacity and whole-body insulin sensitivity. When overexpressed in human skeletal muscle cells to recapitulate the ET phenotype, PLIN5 diminishes lipolysis and FA oxidation under basal condition, but paradoxically enhances FA oxidation during forskolin- and contraction- mediated lipolysis. Moreover, PLIN5 partly protects muscle cells against lipid-induced lipotoxicity. In addition, we demonstrate that down-regulation of PLIN5 in skeletal muscle inhibits insulin-mediated glucose uptake under normal chow feeding condition, while paradoxically improving insulin sensitivity upon high-fat feeding. These data highlight a key role of PLIN5 in LD function, first by finely adjusting LD FA supply to mitochondrial oxidation, and second acting as a protective factor against lipotoxicity in skeletal muscle.
Key points
Acute nicotinamide riboside (NR) supplementation does not alter substrate metabolism at rest, during or in recovery from endurance exercise.
NR does not alter NAD+‐sensitive signalling ...pathways in human skeletal muscle.
NR supplementation and acute exercise influence the NAD+ metabolome.
Oral supplementation of the NAD+ precursor nicotinamide riboside (NR) has been reported to alter metabolism alongside increasing sirtuin (SIRT) signalling and mitochondrial biogenesis in rodent skeletal muscle. However, whether NR supplementation can elicit a similar response in human skeletal muscle is unclear. This study assessed the effect of 7‐day NR supplementation on whole‐body metabolism and exercise‐induced mitochondrial biogenic signalling in skeletal muscle. Eight male participants (age: 23 ± 4 years, V̇O2peak 46.5 ± 4.4 ml kg–1 min–1) received 1 week of NR or cellulose placebo (PLA) supplementation (1000 mg day–1). Muscle biopsies were collected from the medial vastus lateralis prior to supplementation and pre‐, immediately post‐ and 3 h post‐exercise (1 h of 60% Wmax cycling) performed following the supplementation period. There was no effect of NR supplementation on substrate utilisation at rest or during exercise or on skeletal muscle mitochondrial respiration. Global acetylation, auto‐PARylation of poly ADP‐ribose polymerase 1 (PARP1), acetylation of Tumour protein 53 (p53)Lys382 and Manganese superoxide dismutase (MnSOD)Lys122 were also unaffected by NR supplementation or exercise. NR supplementation did not increase skeletal muscle NAD+ concentration, but it did increase the concentration of deaminated NAD+ precursors nicotinic acid riboside (NAR) and nicotinic acid mononucleotide (NAM) and methylated nicotinamide breakdown products (Me2PY and Me4PY), demonstrating the skeletal muscle bioavailability of NR supplementation. In summary, 1 week of NR supplementation does not alter whole‐body metabolism or skeletal muscle signal transduction pathways implicated in the mitochondrial adaptation to endurance exercise.
Key points
Acute nicotinamide riboside (NR) supplementation does not alter substrate metabolism at rest, during or in recovery from endurance exercise.
NR does not alter NAD+‐sensitive signalling pathways in human skeletal muscle.
NR supplementation and acute exercise influence the NAD+ metabolome.
Abstract Objective Recent data suggest that adipose triglyceride lipase (ATGL) plays a key role in providing energy substrate from triglyceride pools and that alterations of its expression/activity ...relate to metabolic disturbances in skeletal muscle. Yet little is known about its regulation. We here investigated the role of the protein G0/G1 Switch Gene 2 (G0S2), recently described as an inhibitor of ATGL in white adipose tissue, in the regulation of lipolysis and oxidative metabolism in skeletal muscle. Methods We first examined G0S2 protein expression in relation to metabolic status and muscle characteristics in humans. We next overexpressed and knocked down G0S2 in human primary myotubes to assess its impact on ATGL activity, lipid turnover and oxidative metabolism, and further knocked down G0S2 in vivo in mouse skeletal muscle. Results G0S2 protein is increased in skeletal muscle of endurance-trained individuals and correlates with markers of oxidative capacity and lipid content. Recombinant G0S2 protein inhibits ATGL activity by about 40% in lysates of mouse and human skeletal muscle. G0S2 overexpression augments (+49%, p < 0.05) while G0S2 knockdown strongly reduces (−68%, p < 0.001) triglyceride content in human primary myotubes and mouse skeletal muscle. We further show that G0S2 controls lipolysis and fatty acid oxidation in a strictly ATGL-dependent manner. These metabolic adaptations mediated by G0S2 are paralleled by concomitant changes in glucose metabolism through the modulation of Pyruvate Dehydrogenase Kinase 4 (PDK4) expression (5.4 fold, p < 0.001). Importantly, downregulation of G0S2 in vivo in mouse skeletal muscle recapitulates changes in lipid metabolism observed in vitro. Conclusion Collectively, these data indicate that G0S2 plays a key role in the regulation of skeletal muscle ATGL activity, lipid content and oxidative metabolism.
Adiposopathy, or sick fat, refers to adipose tissue dysfunction that can lead to several complications such as dyslipidemia, insulin resistance, and hyperglycemia. The relative contribution of ...adiposopathy in predicting insulin resistance remains unclear. We investigated the relationship between adiposopathy, as assessed as a low plasma adiponectin/leptin ratio, with anthropometry, body composition (hydrostatic weighing), insulin sensitivity (hyperinsulinemic-euglycemic clamp), inflammation, and fitness level (ergocycle VO
2max
, mL/kgFFM/min) in 53 men (aged 34–53 years) from four groups: sedentary controls without obesity (body mass index BMI <25 kg/m
2
), sedentary with obesity (BMI > 30 kg/m
2
), sedentary with obesity and glucose intolerance, and endurance trained active without obesity. The adiponectin/leptin ratio was the highest in trained men (4.75 ± 0.82) and the lowest in glucose intolerant subjects with obesity (0.27 ± 0.06; ANOVA
p
< 0.0001) indicating increased adiposopathy in those with obesity. The ratio was negatively associated with adiposity (e.g., waist circumference,
r
= −0.59,
p
< 0.01) and positively associated with VO
2max
(
r
= 0.67,
p
< 0.01) and insulin sensitivity (M/I,
r
= 0.73,
p
< 0.01). Multiple regression analysis revealed fitness as the strongest independent predictor of insulin sensitivity (partial
R
2
= 0.61). While adiposopathy was also an independent and significant contributor (partial
R
2
= 0.10), waist circumference added little power to the model (partial
R
2
= 0.024). All three variables remained significant independent predictors when trained subjects were excluded from the model. Plasma lipids were not retained in the model. We conclude that low fitness, adiposopathy, as well as adiposity (and in particular abdominal obesity) are independent contributors to insulin resistance in men without diabetes.
Research has shown that models of care involving geriatric care in orthopedics decrease hospitalizations, mortality, length of stay and post-operative complications. This article presents an example ...of a nurse practitioner-led orthogeriatric model of care in a large academic hospital in Ontario. The overall goal was to explore staff perspectives regarding the nurse practitioner-led orthogeriatric model of care.
We conducted a mixed methods approach consisting of an online questionnaire, semi-structured interviews, and a focus group with staff.
Questionnaire of staff showed overall support for functions of the NP within the model. Interviews with healthcare providers, and leadership as well as one focus group with orthopedic surgeons showed that despite the lack of formal awareness of the NP-led orthogeriatric model of care, staff felt that the model provided better care for the geriatric hip fracture population.
In the current context of geriatricians’ shortages to provide post-surgical care to geriatric patients, the staff described that geriatric care of hip fracture patients can be well accomplished by a NP. Further improvement efforts to create better awareness of the NP-led orthogeriatric model among the care team is needed.
IntroductionFrailty is a strong predictor of adverse postoperative outcomes. Prehabilitation may improve outcomes after surgery for older people with frailty by addressing physical and physiologic ...deficits. The objective of this trial is to evaluate the efficacy of home-based multimodal prehabilitation in decreasing patient-reported disability and postoperative complications in older people with frailty having major surgery.Methods and analysisWe will conduct a multicentre, randomised controlled trial of home-based prehabilitation versus standard care among consenting patients >60 years with frailty (Clinical Frailty Scale>4) having elective inpatient major non-cardiac, non-neurologic or non-orthopaedic surgery. Patients will be partially blinded; clinicians and outcome assessors will be fully blinded. The intervention consists of >3 weeks of prehabilitation (exercise (strength, aerobic and stretching) and nutrition (advice and protein supplementation)). The study has two primary outcomes: in-hospital complications and patient-reported disability 30 days after surgery. Secondary outcomes include survival, lower limb function, quality of life and resource utilisation. A sample size of 750 participants (375 per arm) provides >90% power to detect a minimally important absolute difference of 8 on the 100-point patient-reported disability scale and a 25% relative risk reduction in complications, using a two-sided alpha value of 0.025 to account for the two primary outcomes. Analyses will follow intention to treat principles for all randomised participants. All participants will be followed to either death or up to 1 year.Ethics and disseminationEthical approval has been granted by Clinical Trials Ontario (Project ID: 1785) and our ethics review board (Protocol Approval #20190409-01T). Results will be disseminated through presentation at scientific conferences, through peer-reviewed publication, stakeholder organisations and engagement of social and traditional media.Trial registration numberNCT04221295.
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