The Impact of Frailty on Short-Term Outcomes After Elective Hip and Knee Arthroplasty in Older Adults: A Systematic Review.
ABSTRACT: Introduction:This systematic literature review evaluates (1) frailty in older adults as a risk factor for short-term adverse events and suboptimal clinical outcomes after total joint arthroplasty and (2) interventions to improve arthroplasty outcomes in these frail patients. Methods:PubMed, EMBASE, Cochrane Register of Controlled Trials, SCOPUS, AgeLine, and Web of Science were searched from database inception to November 22, 2017; gray literature and references were also searched. Studies including adults ≥65 years of age undergoing hip or knee arthroplasty and measuring preoperative frailty and postoperative adverse events or clinical outcomes within 90 days of surgery were included. Two investigators independently screened all abstracts and extracted data; disagreements were adjudicated by a third reviewer. Risk of bias was assessed using the Newcastle-Ottawa scale for cohort studies and the Cochrane Risk of Bias tool for randomized controlled trials. Study quality was assessed using a 5-point scale modified from the Oxford Centre for Evidence-Based Medicine tool. Results:Of 1913 abstracts identified, 82 full texts were reviewed, and 13 met inclusion criteria: 5 prospective cohort studies, 6 retrospective cohort studies, and 2 randomized controlled trials covering 382 763 total patients. These studies used 13 frailty instruments and assessed 32 distinct outcomes. Substantial heterogeneity precluded valid meta-analysis; results were qualitatively summarized by study design, frailty instrument, and outcome type. Of the 11 cohort studies, 10 found significant associations between frailty and poor postoperative outcomes. Trials of preoperative frailty-modifying interventions found no association between interventions and improved outcomes. Discussion:Standardizing frailty measurement would improve generalizability, permitting the assessment of associations with patient-reported and functional outcome measures, as well as the efficacy of interventions to improve outcomes, in frail patients undergoing arthroplasty. Conclusions:Frailty is associated with higher rates of short-term adverse events and worse clinical outcomes after elective hip and knee arthroplasty.
Project description:INTRODUCTION:Frailty is associated with reduced functional capacity, decreased resistance to stressors and is predictive of a range of adverse health outcomes, including dependency, hospitalisation and mortality. Early identification of frailty may prevent, reduce and postpone adverse health outcomes. However, there is a need for additional evidence to guide decision-making for the care of frail patients since frail persons are frequently excluded from studies, the differential impact of frailty is often not examined in clinical trials and few large-scale clinical trials examining frail cohorts have been conducted. Randomised control trials (RCTs) published to date have used a diverse range of definitions of frailty, as well as a variety of outcome measures. The objective of this systematic review is to comprehensively characterise the frail populations enrolled and the end points reported in frailty RCTs. METHODS AND ANALYSIS:We will identify all RCTs reporting on the outcome of interventions in adult (age ?18 years) frail populations as defined by authors, in all settings of care. Databases will include MEDLINE, CINAHL, EMBASE, PsycInfo, Global Health, the Joanna Briggs database and Cochrane Library. Two reviewers will independently determine trial eligibility. For each included trial, we will conduct duplicate independent data extraction, inter-rater reliability, risk of bias assessment and evaluation of the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. ETHICS AND DISSEMINATION:This systematic review will comprehensively identify RCTs including frail patients to identify how frailty is measured and which outcomes are reported. The results of this systematic review may inform clinicians caring for persons with frailty, facilitate conduct of future RCTs and inform future efforts to develop common data elements and core outcomes for frailty studies. Our findings will be disseminated through conference presentation and publication in peer-reviewed journals. PROSPERO REGISTRATION NUMBER:CRD42017065233.
Project description:Perioperative management of older adults is a complex field that is heavily influenced by the clinical heterogeneity of older adults. Frailty-a geriatric syndrome in which a patient is more vulnerable to stressors due to decreases in physical function and reserve-has been indicative of adverse postoperative outcomes. Many tools have been developed to measure frailty that incorporate a variety of factors including physical and cognitive function, comorbidities, self-reported measures of health, and clinical judgment. Most of these frailty assessment tools are able to identify a subset of patients at risk of adverse outcomes including postoperative complications, longer hospital length of stay, discharge to a higher level of care, and mortality. Frailty assessment before surgical interventions can also guide discussions among patients, their families, anesthesiologists, and surgeons to tailor operative plans for patients to mitigate this increased risk. Studies are ongoing to identify interventions in frail patients that can improve postoperative outcomes, but high-quality data in the form of randomized controlled trials are lacking at this time.
Project description:<h4>Introduction</h4>Frailty is a common condition affecting older adults and is associated with increased mortality and adverse outcomes. Identification of older adults at risk of adverse outcomes is central to subsequent resource planning and targeted interventions. This systematic review and meta-analysis will examine the: (1) diagnostic accuracy of the Clinical Frailty Scale (CFS) in identifying hospitalised adults ?65 years with frailty and a medical diagnosis compared with the reference standard Frailty Index or Frailty Phenotype and (2) predictive value of the CFS in determining those at increased risk of subsequent adverse outcomes.<h4>Methods and analysis</h4>We will include cross-sectional, retrospective and prospective cohort studies, and randomised controlled trials that assess either the diagnostic accuracy of the CFS when compared with the reference standard Frailty Index/Frailty Phenotype or the predictive validity of the CFS to predict subsequent adverse outcomes in hospitalised adults over 65 years with medical complaints. Adverse outcomes include falls, functional decline, unplanned Emergency Department attendance, emergency rehospitalisation, nursing home admission or death. A systematic search will be conducted in Embase, AMED, MEDLINE (Ebsco, Ovid, Pubmed), CINAHL, PsycINFO, Cochrane Library. Studies will be limited to those published from 2005 to 30 October 2019. Two independent reviewers will screen all titles and abstracts to identify relevant studies. The methodological quality of studies will be independently assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. A CFS score of >4?will be used to identify frailty. We will construct 2×2 tables and determine true positives, true negatives, false positives and false negatives for each study when compared with the reference standard and for each adverse outcome. A bivariate random effects model will be applied to generate pooled summary estimates of sensitivity and specificity.<h4>Ethics and dissemination</h4>Ethical approval is not required for this systematic review. We will disseminate our findings through a peer-reviewed journal.
Project description:BACKGROUND:Frailty is an important prognostic factor for adverse outcomes and increased resource use in the growing population of older surgical patients. We identified and appraised studies that tested interventions in populations of frail surgical patients to improve perioperative outcomes. METHODS:We systematically searched Cochrane, CINAHL, EMBASE and Medline to identify studies that tested interventions in populations of frail patients having surgery. All phases of study selection, data extraction, and risk of bias assessment were done in duplicate. Results were synthesized qualitatively per a prespecified protocol (CRD42016039909). RESULTS:We identified 2 593 titles; 11 were included for final analysis, representing 1 668 participants in orthopedic, general, cardiac, and mixed surgical populations. Only one study was multicenter and risk of bias was moderate to high in all studies. Interventions were applied pre- and postoperatively, and included exercise therapy (n = 4), multicomponent geriatric care protocols (n = 5), and blood transfusion triggers (n = 1); no specific surgical techniques were compared. Exercise therapy, applied pre-, or post-operatively, was associated with significant improvements in functional outcomes and improved quality of life. Multicomponent protocols suffered from poor compliance and difficulties in implementation. Transfusion triggers had no significant impact on mortality or other outcomes. CONCLUSIONS:Despite a growing literature that demonstrates strong independent associations between frailty and adverse outcomes, few interventions have been tested to improve the outcomes of frail surgical patients, and most available studies are at substantial risk of bias. Multicenter, low risk of bias, studies of perioperative exercise are needed, while substantial efforts are required to develop and test other interventions to improve the outcomes of frail people having surgery.
Project description:BACKGROUND:Frailty is the loss of ability to withstand a physiological stressor and is associated with multiple adverse outcomes in older people. Trials to prevent or ameliorate frailty are in their infancy. A range of different outcome measures have been proposed, but current measures require either large sample sizes, long follow-up, or do not directly measure the construct of frailty. METHODS:We propose a composite outcome for frailty prevention trials, comprising progression to the frail state, death, or being too unwell to continue in a trial. To determine likely event rates, we used data from the English Longitudinal Study for Ageing, collected 4?years apart. We calculated transition rates between non-frail, prefrail, frail or loss to follow up due to death or illness. We used Markov state transition models to interpolate one- and two-year transition rates and performed sample size calculations for a range of differences in transition rates using simple and composite outcomes. RESULTS:The frailty category was calculable for 4650 individuals at baseline (2226 non-frail, 1907 prefrail, 517 frail); at follow up, 1282 were non-frail, 1108 were prefrail, 318 were frail and 1936 had dropped out or were unable to complete all tests for frailty. Transition probabilities for those prefrail at baseline, measured at wave 4 were respectively 0.176, 0.286, 0.096 and 0.442 to non-frail, prefrail, frail and dead/dropped out. Interpolated transition probabilities were 0.159, 0.494, 0.113 and 0.234 at two years, and 0.108, 0.688, 0.087 and 0.117 at one year. Required sample sizes for a two-year outcome in a two-arm trial were between 1040 and 7242 for transition from prefrailty to frailty alone, 246 to 1630 for transition to the composite measure, and 76 to 354 using the composite measure with an ordinal logistic regression approach. CONCLUSION:Use of a composite outcome for frailty trials offers reduced sample sizes and could ameliorate the effect of high loss to follow up inherent in such trials due to death and illness.
Project description:Frail older adults are at increased risk of poor clinical outcomes. Frailty assessment is therefore important in clinical trials to understand the benefits and harms of interventions. However, consensus is lacking on how frailty should be assessed.We developed a prospectively specified index using a battery of formal tests and instruments and a retrospectively generated index using medical comorbidities and patient reported outcomes (PROs) within an adjuvanted recombinant zoster vaccine (RZV) trial (NCT02979639). For both frailty indices (FIs), a total deficit score was calculated as the accumulation of deficits and participants were categorized as non-frail, pre-frail and frail. We assessed (1) the feasibility and validity of both FIs; (2) the impact of RZV vaccine reactogenicity by frailty status on Short Form-36 [SF-36] physical functioning (PF) scores.Of 401 participants, aged ?50 years, 236 (58.9%) were categorized non-frail, 143 (35.7%), pre-frail, and 22 (5.5%) frail using the prospective FI. Corresponding numbers for the retrospective FI were 192 (47.9%), 169 (42.1%) and 40 (10.0%), respectively. Strong concordance was observed between the frailty status assessments (P < .001). The proportion defined as frail increased from 1.5%, to 10.4% in participants aged 50-59, and ?70 years, respectively, for the prospective FI. Corresponding numbers for the retrospective FI were 3.7%, and 17.2%, respectively. RZV vaccination was associated with a transient, non-clinically meaningful, decrease on the SF-36 PF score in frail participants.Both frailty indices provided similar results. The retrospectively generated FI offers the advantage of being easier to incorporate into vaccine clinical trials of older adults.
Project description:BACKGROUND:According to some studies, interventions can prevent or delay frailty, but their effect in preventing adverse outcomes in frail community-dwelling older people is unclear. The aim is to investigate the effect of an intervention on adverse outcomes in frail older adults. METHODS:A systematic review and meta-analysis of Medline, Embase, the Cochrane Library, and Social Sciences Citation Index. Randomized controlled studies that aimed to treat frail community-dwelling older adults, were included. The outcomes were mortality, hospitalization, formal health costs, accidental falls, and institutionalization. Several sub-analyses were performed (duration of intervention, average age, dimension, recruitment). RESULTS:Twenty-five articles (16 original studies) were included. Six types of interventions were found. The pooled odds ratios (OR) for mortality when allocated in the experimental group were 0.99 [95% CI: 0.79, 1.25] for case management and 0.78 [95% CI: 0.41, 1.45] for provision information intervention. For institutionalization, the pooled OR with case management was 0.92 [95% CI: 0.63, 1.32], and the pooled OR for information provision intervention was 1.53 [95% CI: 0.64, 3.65]. The pooled OR for hospitalization when allocated in the experimental group was 1.13 [95% CI: 0.95, 1.35] for case management. Further sub-analyses did not yield any significant findings. CONCLUSION:This systematic review and meta-analysis does not provide sufficient scientific evidence that interventions by frail older adults can be protective against the included adverse outcomes. A sub-analysis for some variables yielded no significant effects, although some findings suggested a decrease in adverse outcomes. TRIAL REGISTRATION:Prospero registration CRD42016035429 .
Project description:BACKGROUND:Frailty is common in clinical practice, but trials rarely report on participant frailty. Consequently, clinicians and guideline-developers assume frailty is largely absent from trials and have questioned the relevance of trial findings to frail people. Therefore, we examined frailty in phase 3/4 industry-sponsored clinical trials of pharmacological interventions for three exemplar conditions: type 2 diabetes mellitus (T2DM), rheumatoid arthritis (RA), and chronic obstructive pulmonary disease (COPD). METHODS:We constructed a 40-item frailty index (FI) in 19 clinical trials (7 T2DM, 8 RA, 4 COPD, mean age 42-65?years) using individual-level participant data. Participants with a FI >?0.24 were considered 'frail'. Baseline disease severity was assessed using HbA1c for T2DM, Disease Activity Score-28 (DAS28) for RA, and % predicted FEV1 for COPD. Using generalised gamma regression, we modelled FI on age, sex, and disease severity. In negative binomial regression, we modelled serious adverse event rates on FI and combined results for each index condition in a random-effects meta-analysis. RESULTS:All trials included frail participants: prevalence 7-21% in T2DM trials, 33-73% in RA trials, and 15-22% in COPD trials. The 99th centile of the FI ranged between 0.35 and 0.45. Female sex was associated with higher FI in all trials. Increased disease severity was associated with higher FI in RA and COPD, but not T2DM. Frailty was associated with age in T2DM and RA trials, but not in COPD. Across all trials, and after adjusting for age, sex, and disease severity, higher FI predicted increased risk of serious adverse events; the pooled incidence rate ratios (per 0.1-point increase in FI scale) were 1.46 (95% CI 1.21-1.75), 1.45 (1.13-1.87), and 1.99 (1.43-2.76) for T2DM, RA, and COPD, respectively. CONCLUSION:The upper limit of frailty in trials is lower than has been described in the general population. However, mild to moderate frailty was common, suggesting trial data may be harnessed to inform disease management in people living with frailty. Participants with higher FI experienced more serious adverse events, suggesting screening for frailty in trial participants would enable identification of those that merit closer monitoring. Frailty is identifiable and prevalent among middle-aged and older participants in phase 3/4 drug trials and has clinically important safety implications.
Project description:BACKGROUND:Frail older adults are predisposed to multiple comorbidities and adverse events. Recent interventional studies have shown that frailty can be improved and managed. In this study, effective individualized home-based exercise and nutrition interventions were developed for reducing frailty in older adults. METHODS:This study was a four-arm, single-blind, randomized controlled trial conducted between October 2015 and June 2017 at Miaoli General Hospital in Taiwan. Overall, 319 pre-frail or frail older adults were randomly assigned into one of the four study groups (control, exercise, nutrition, and exercise plus nutrition [combination]) and followed up during a 3-month intervention period and 3-month self-maintenance period. Improvement in frailty scores was the primary outcome. Secondary outcomes included improvements in physical performance and mental health. The measurements were performed at baseline, 1?month, 3?months, and 6?months. RESULTS:At the 6-month measurement, the exercise (difference in frailty score change from baseline: -?0.23; 95% confidence interval [CI]: -?0.41, -?0.05; p?=?0.012), nutrition (-?0.28; 95% CI: -?0.46, -?0.11; p?=?0.002), and combination (-?0.34; 95% CI: -?0.52, -?0.16; p?<? 0.001) groups exhibited significantly greater improvements in the frailty scores than the control group. Significant improvements were also observed in several physical performance parameters in the exercise, nutrition, and combination groups, as well as in the 12-Item Short Form Health Survey mental component summary score for the nutrition group. CONCLUSIONS:The designated home-based exercise and nutrition interventions can help pre-frail or frail older adults to improve their frailty score and physical performance. TRIAL REGISTRATION:Retrospectively registered at ClinicalTrials.gov (identifier: NCT03477097); registration date: March 26, 2018.
Project description:Frailty, a syndrome of physiological deficits, is prevalent among older adults and predicts elevated risk of adverse health outcomes. Although persistent pain predicts similar risk, it is seldom considered in frailty measurement. This article evaluated the construct and predictive validity of including persistent pain in phenotypic frailty measurement.Frailty and persistent pain were operationalized using data from the Health and Retirement Study (2006-2012 waves). Among a subset of adults aged 65 and older (n = 3,652), we used latent class analysis to categorize frailty status and to evaluate construct validity. Using Cox proportional hazards models, we compared time to incident adverse outcomes (death, fall, hospitalization, institutionalization, and functional disability) between frailty classes determined by either including or excluding persistent pain as a frailty component.In latent class models, persistent pain occurred with other frailty components in patterns consistent with a medical syndrome. Frail and intermediately frail classes determined by including persistent pain were more strongly associated with all adverse outcomes compared with frail and intermediately frail classes determined excluding persistent pain. Frail respondents had significantly greater risk of death compared with nonfrail respondents when frailty models included rather than excluded persistent pain (respectively, hazard ratio [HR] = 3.87, 95% confidence interval [CI] = 2.99-5.00 (including pain); HR = 2.10, 95% CI = 1.71-2.59 (excluding pain).Findings support consideration of persistent pain as a component of the frailty phenotype. Persistent pain assessment may provide an expedient method to enhance frailty measurement and improve prediction of adverse outcomes.