Therapeutic Interventions for Frail Elderly Patients: Part II. Ongoing and Unpublished Randomized Trials

There is increasing momentum to measure frailty in clinical practice given its proven value as a predictor of outcomes, particularly in elderly patients with cardiovascular disease. The number of randomized clinical trials targeting frail older adults has been modest to date. Therefore, we systematically searched the ClinicalTrials.gov registry in order to review the frailty intervention trials that had been actively initiated or completed but not yet published. The interventions studied were exercise training in 2 trials, nutritional supplementation in 3 trials, combined exercise plus nutritional supplementation in 5 trials, pharmaceutical agents in 5 trials, multi-dimensional programs in 2 trials, and home-based services in 3 trials. Their respective study designs, populations, interventions, and planned outcomes are presented in this article.     

Physical Frailty Phenotype and the Development of Geriatric Syndromes in Older Adults with Coronary Heart Disease

BackgroundFrailty, a clinical state of vulnerability, is associated with subsequent adverse geriatric syndromes in the general population. We examined the long-term impact of frailty on geriatric outcomes among older patients with coronary heart disease.MethodsWe used the National Health and Aging Trends Study, a prospective cohort study linked to a Medicare sample. Coronary heart disease was identified by self-report or International Classification of Diseases (ICD) codes 1-year prior to the baseline visit. Frailty was measured using the Fried physical frailty phenotype. Geriatric outcomes were assessed annually during a 6-year follow-up.ResultsOf the 4656 participants, 1213 (26%) had a history of coronary heart disease 1-year prior to their baseline visit. Compared to those without frailty, subjects with frailty were older (ages ≥75: 80.9% vs 68.9%, P < 0.001), more likely to be female, and belong to an ethnic minority. The prevalence of hypertension, stroke, falls, disability, anxiety/depression, and multimorbidity were much higher in the frail, than nonfrail, participants. In a discrete time survival model, the incidence of geriatric syndromes during 6-year follow-up including 1) dementia, 2) loss of independence, 3) activities of daily living disability, 4) instrumental activities of daily living disability, and 5) mobility disability were significantly higher in the frail than in the nonfrail older patients with coronary heart disease.ConclusionIn patients with coronary heart disease, frailty is a risk factor for the accelerated development of geriatric outcomes. Efforts to identify frailty in the context of coronary heart disease are needed, as well as interventions to limit or reverse frailty status for older patients with coronary heart disease.     

The Clinical Potential of Senolytic Drugs

Senolytic drugs are agents that selectively induce apoptosis of senescent cells. These cells accumulate in many tissues with aging and at sites of pathology in multiple chronic diseases. In studies in animals, targeting senescent cells using genetic or pharmacological approaches delays, prevents, or alleviates multiple age‐related phenotypes, chronic diseases, geriatric syndromes, and loss of physiological resilience. Among the chronic conditions successfully treated by depleting senescent cells in preclinical studies are frailty, cardiac dysfunction, vascular hyporeactivity and calcification, diabetes mellitus, liver steatosis, osteoporosis, vertebral disk degeneration, pulmonary fibrosis, and radiation‐induced damage. Senolytic agents are being tested in proof‐of‐concept clinical trials. To do so, new clinical trial paradigms for testing senolytics and other agents that target fundamental aging mechanisms are being developed, because use of long‐term endpoints such as lifespan or healthspan is not feasible. These strategies include testing effects on multimorbidity, accelerated aging‐like conditions, diseases with localized accumulation of senescent cells, potentially fatal diseases associated with senescent cell accumulation, age‐related loss of physiological resilience, and frailty. If senolytics or other interventions that target fundamental aging processes prove to be effective and safe in clinical trials, they could transform geriatric medicine by enabling prevention or treatment of multiple diseases and functional deficits in parallel, instead of one at a time.     

Rehabilitation of the elderly patient on dialysis

Rehabilitation for geriatric patients, as well as rehabilitation for patients with a chronic disease, strives to mobilize individuals' residual capacity for optimal function in their usual environment. It is clear from observational studies that chronic dialysis patients often experience marked limitations in physical functioning, and these limitations tend to increase with patients' age. However, both prospective studies and controlled trials conducted with elderly persons demonstrate that muscle strengthening and cardiovascular exercise are related to improved physical functioning, and there is evidence that dialysis patients can also benefit from many of these interventions. Inpatient rehabilitation in a specialized geriatric unit has been shown to be associated with better functional outcomes and decreased need for institutionalization among elderly persons; the process of comprehensive geriatric assessment may also have beneficial outcomes. More controlled studies are needed in order to better specify the effectiveness of various geriatric interventions, for elderly subjects in general and for elderly dialysis patients specifically.     

Impact of functional status on 6-month mortality in elderly patients with acute venous thromboembolism: results from a prospective cohort

The benefits and harms of telehealth interventions compared to usual care for oral anticoagulation management are unclear. A systematic review and meta-analysis was conducted to assess their impact on clinically important outcomes. A search was conducted through MEDLINE, EMBASE and CENTRAL databases, and the retrieved citations were independently screened and extracted by two review authors. Cochrane Collaboration-recommended tools were used to assess for risk of bias. Co-primary outcomes were major bleeding and major thromboembolic events. Of 2145 retrieved citations, 7 were included for qualitative synthesis (1 randomized controlled trial, 1 prospective cohort and 5 retrospective cohorts). None addressed direct oral anticoagulants. Telehealth interventions were mainly consisted of telephone visits by clinicians, pharmacists and specialists. Meta-analysis of 3 studies (n?=?6955) showed significant improvements in the telehealth group for major thromboembolic events (RR 0.43, 95% CI 0.25–0.74, p?=?0.002), but no significant difference for major bleeding events (RR 0.83, 95% CI 0.52–1.33, p?=?0.44). There was no significant difference in any of the secondary outcomes. The overall GRADE quality of evidence was rated very low due to high risk of bias and low precision. Based on very low quality evidence, telehealth interventions may lower the risk of major thromboembolic events, but not other clinically important outcomes. A high quality study is likely to strongly influence these results. High quality randomized trials are recommended to better assess the benefits and harms of telehealth interventions for anticoagulation management.     

The clinical care of frail, older adults

Frailty and its management represent an emerging area of clinical care in older adults. Geriatricians have long recognized a syndrome of multiple comorbid conditions, immobility, weakness, and poor tolerance of physiologic stressors in older adults. Patients with these characteristics are described as frail and suffer increased adverse clinical outcomes. This article reviews the clinical spectrum of frailty in older adults, its biologic etiology, and potential clinical interventions. Several operational definitions of frailty and the associated clinical signs, symptoms, and outcomes are outlined. The biologic mechanisms hypothesized to underlie frailty are explored, particularly in the musculoskeletal, endocrine, and immune systems. Treatment options for frail, older adults are discussed, including physiologic system-targeted interventions and geriatric models of care.     

Does exercise aid smoking cessation? A systematic review

Aims: To assess the effectiveness of exercise-based interventions in smoking cessation. Design: A systematic review was conducted of articles published between 1980 and 1999. The review focused on randomized controlled trials (RCTs) in which the specific effects of exercise on smoking abstinence were examined. The primary dependent variable was smoking abstinence. Other studies which had both exercise programming as an independent variable and smoking behaviour as a dependent variable are briefly discussed. Participants: The review included interventions targeting both healthy individuals and those with specific medical conditions. Settings: The interventions were delivered in both community and inpatient settings. Measurements: Information extracted from each article included details of the participants, exercise and smoking cessation programmes, control conditions, exercise adherence rates, length of follow-up and outcomes. Findings: Of the eight trials satisfying our inclusion criteria, only two trials found a positive effect for exercise on smoking abstinence. The others showed no effect. Conclusions: There is some evidence for exercise aiding smoking cessation. Of the two trials finding a positive effect one was rigorously designed, the other was found to have numerous methodological limitations. Trials showing no effect lacked sensitivity. This was principally because of small sample sizes and inadequate measurement and control of exercise adherence. There is a need for more rigorously designed studies in this area.     

Screening of the frail patient in the emergency department: A systematic review

BackgroundSeveral frailty rating scales have been developed to detect and screen for the level of frailty. It is uncertain what diagnostic value screening of frailty level have in the emergency department.AimTo assess the accuracy of the screening tools used in the emergency department to detect frailty in patients ≥ 65 years by their ability to identify the risk of adverse outcomes.MethodsAn extensive medical literature search of Embase and PubMed was conducted, to identify studies using frailty screening scales in the emergency department. Data was subsequently extracted and evaluated from the results of the included studies.ResultsFour studies met the exact inclusion criteria. Four different frailty screening scales: Clinical Frailty Scale, Deficit Accumulation Index, Identification of Seniors At Risk and The Study of Osteoporotic Fracture frailty index used in the emergency department were described and compared. Predictive values for various outcomes are represented and discussed.ConclusionsThe results suggest that frailty successfully predicts increased risk of hospitalization, nursing home admission, mortality and prolonged length of stay after an initial emergency department visit. Frailty does however not predict increased risk of 30 day emergency department revisit. Further research highlighting the value of screening for frailty level in elderly emergency department patients is needed.Learning pointsAlthough frail elders in need of further geriatric assessment should be identified as soon as possible, this systematic review only identified four cohort studies of frailty assessment in emergency departments.Although frailty screening appeared to predict the risk of mortality and of admission to hospital/nursing home, these four studies did not show that it could predict return visits to emergency departments within 30 days.Randomized clinical trials of frailty screening tools compared to usual care or other methods of assessment are clearly needed.     

Old or frail: what tells us more?

BACKGROUND: Selecting elderly persons who need geriatric interventions and making accurate treatment decisions are recurring challenges in geriatrics. Chronological age, although often used, does not seem to be the best selection criterion. Instead, the concept of frailty, which indicates several concurrent losses in resources, can be used. METHODS: The predictive values of chronological age and frailty were investigated in a large community sample of persons aged 65 years and older, randomly drawn from the register of six municipalities in the northern regions of the Netherlands (45% of the original addressees). The participants' generative capacity to sustain well-being (i.e., self-management abilities) was used as the main outcome measure. RESULTS: When using chronological age instead of frailty, both too many and too few persons were selected. Furthermore, frailty related more strongly (with beta values ranging from -.25 to -.39) to a decline in the participants' self-management abilities than did chronological age (with beta values ranging from -.06 to -.14). Chronological age added very little to the explained variances of all outcomes once frailty was included. CONCLUSIONS: Using frailty as the criterion to select older persons at risk for interventions may be better than selecting persons based only on their chronological age.     

The effectiveness and costs of comprehensive geriatric evaluation and management

Comprehensive geriatric assessment (CGA) is a multidimensional interdisciplinary diagnostic process focused on determining a frail elderly person's medical, psychological, and functional capabilities in order to develop a coordinated and integrated plan for treatment and long-term follow-up. Geriatrics interventions building on CGA are defined from their historical emergence to the present day in a discussion of their complexity, goals and normative components. Through literature review, questions of the effectiveness and costs of these interventions are addressed. Evidence of effectiveness is derived from individual trials and, particularly, recent systematic reviews. While the trial evidence lends support to the proposition that geriatric interventions can be effective, the results have not been uniform. Review of meta-regression studies suggests that much of this outcome variability is related to identifiable program design parameters. In particular, targeting the frail, an interdisciplinary team structure with clinical control of care, and long-term follow-up, tend to be associated with effective programs. Answers to cost-effectiveness questions also vary and are more rare. With some exceptions, existing evidence as exists suggest that geriatrics interventions can be effective without raising total costs of care. Despite the attention given to these questions in recent years, there is still much room for clinical and scientific advance as we move to better understand what CGA interventions do well and in whom.     

Therapeutic Interventions for Frail Elderly Patients: Part I. Published Randomized Trials

The body of literature for frailty as a prognostic marker continues to grow, yet the evidence for frailty as a therapeutic target is less well defined. In the setting of cardiovascular disease, the prevalence of frailty is elevated and its impact on mortality and major morbidity is substantial. Therapeutic interventions aimed at improving frailty may impart gains in functional status and survival. Randomized clinical trials that tested one or more therapeutic interventions in a population of frail older adults were reviewed. The interventions studied were exercise training in 13 trials, nutritional supplementation in 4 trials, combined exercise plus nutritional supplementation in 7 trials, pharmaceutical agents in 8 trials, multi-dimensional programs in 5 trials, and home-based services in 1 trial. The main findings of these trials are explored along with a discussion of their relative merits and limitations.     

A systematic review of income generation interventions,including microfinance and vocational skills training,for HIV prevention

Income generation interventions, such as microfinance or vocational skills training, address structural factors associated with HIV risk. However, the effectiveness of these interventions on HIV-related outcomes in low- and middle-income countries has not been synthesized. The authors conducted a systematic review by searching electronic databases from 1990 to 2012, examining secondary references, and hand-searching key journals. Peer-reviewed studies were included in the analysis if they evaluated income generation interventions in low- or middle-income countries and provided pre-post or multi-arm measures on behavioral, psychological, social, care, or biological outcomes related to HIV prevention. Standardized forms were used to abstract study data in duplicate and study rigor was assessed. Of the 5218 unique citations identified, 12 studies met criteria for inclusion. Studies were geographically diverse, with six conducted in sub-Saharan Africa, three in South or Southeast Asia, and three in Latin America and the Caribbean. Target populations included adult women (N = 6), female sex workers/bar workers (N = 3), and youth/orphans (N = 3). All studies targeted females except two among youth/orphans. Study rigor was moderate, with two group-randomized trials and two individual-randomized trials. All interventions except three included some form of microfinance. Only a minority of studies found significant intervention effects on condom use, number of sexual partners, or other HIV-related behavioral outcomes; most studies showed no significant change, although some may have had inadequate statistical power. One trial showed a 55% reduction in intimate partner violence (adjusted risk ratio 0.45, 95% confidence interval 0.23–0.91). No studies measured incidence/prevalence of HIV or sexually transmitted infections among intervention recipients. The evidence that income generation interventions influence HIV-related behaviors and outcomes is inconclusive. However, these interventions may have important effects on outcomes beyond HIV prevention. Further studies examining not only HIV-related outcomes but also causal pathways and intermediate variables, are needed. Additional studies among men are also needed.     

Effect of Choline Supplementation on Neurological,Cognitive, and Behavioral Outcomes in Offspring Arising from Alcohol Exposure During Development: A Quantitative Systematic Review of Clinical and Preclinical Studies

Prenatal alcohol exposure results in cognitive, behavioral, and neurological deficits in offspring. There is an urgent need for safe and effective treatments to overcome these effects. Maternal choline supplementation has been identified as a potential intervention. Our objective was to review preclinical and clinical studies using choline supplementation in known cases of fetal alcohol exposure to determine its effectiveness in ameliorating deficits in offspring. A systematic search of 6 electronic databases was conducted and studies selected by reviewing titles/abstracts against specific inclusion/exclusion criteria. Study characteristics, population demographics, alcohol exposure, and intervention methods were tabulated, and quality of reporting was assessed. Data on cognitive, behavioral, and neurological outcomes were extracted and tabulated. Quantitative analysis was performed to determine treatment effects for individual study outcomes. A total of 189 studies were retrieved following duplicate removal. Of these, 22 studies (2 randomized controlled trials, 2 prospective cohort studies, and 18 preclinical studies) met the full inclusion/exclusion criteria. Choline interventions were administered at different times relative to alcohol exposure, impacting on their success to prevent deficits for specific outcomes. Only 1 clinical study showed significant improvements in information processing in 6‐month‐old infants from mothers treated with choline during pregnancy. Preclinical studies showed significant amelioration of deficits due to prenatal alcohol exposure across a wide variety of outcomes, including epigenetic/molecular changes, gross motor, memory, and executive function. This review suggests that choline supplementation has the potential to ameliorate specific behavioral, neurological, and cognitive deficits in offspring caused by fetal alcohol exposure, at least in preclinical studies. As only 1 clinical study has shown benefit, we recommend more clinical trials be undertaken to assess the effectiveness of choline in preventing deficits across a wider range of cognitive domains in children.     

Organization of care for persons with HIV-infection: a systematic review

The objective of this systematic review was to examine the effectiveness of the organization of care: case management, multidisciplinary care, multi-faceted treatment, hours of service, outreach programs and health information systems on medical, immunological, virological, psychosocial and economic outcomes for persons living with HIV/AIDS. We searched PubMed (MEDLINE) and 10 other electronic databases from 1 January 1980 to April, 2012 for both experimental and controlled observational studies. Thirty-three studies met the inclusion criteria. Eleven studies were randomized controlled trials (RCTs), three of which were conducted in low–middle income settings. Patient characteristics, study design, organization measures and outcomes data were abstracted independently by two reviewers from all studies. A risk of bias tool was applied to RCTs and a separate tool was used to assess the quality of observational studies. This review concludes that case management interventions were most consistently associated with improvements in immunological outcomes but case management demonstrates no clear association with other outcome measures. The same mixed results were also identified for multidisciplinary and multi-faceted care interventions. Eight studies with an outreach intervention were identified and demonstrated improvements or non-inferiority with respect to mortality, receipt of antiretroviral medications, immunological outcomes, improvements in healthcare utilization and lower reported healthcare costs when compared to usual care. Of the interventions examined in this review, sustained in-person case management and outreach interventions were most consistently associated with improved medical and economic outcomes, in particular antiretroviral prescribing, immunological outcomes and healthcare utilization. No firm conclusions can be reached about the impact of any one intervention on patient mortality.     

Efficacy of group psychotherapy for geriatric depression: A systematic review

BackgroundGeriatric depression is a common and debilitating psychopathology, but evidence supports the efficacy of psychotherapy in its treatment. Group therapy provides advantages over individual interventions. However, only three systematic reviews have focused specifically on the efficacy of group therapy for geriatric depression.ObjectiveTo ascertain the effects of group psychotherapy on geriatric depression in people aged 60 years and older, compared with alternative treatments or no treatment.Data sourcesA systematic review of English, Portuguese, and Spanish studies using the EBSCOhost Research and Science Direct databases (2011–2017). Additional studies were identified through reference lists. Search terms included group therapy, group psychotherapy, older adults, elderly, depressive disorder, geriatric depression, and depression in the elderly.Review methodsThe researcher screened any study designs concerning the effects of any paradigm of group therapy on geriatric depression versus alternative interventions or no treatment. Relevant data, including indicators of risk of bias, were extracted.Data synthesisNine studies were reviewed. Reminiscence therapy and cognitive-behavioral therapy are viable group interventions for geriatric depression, and were significantly superior to most controls. Conclusions about the long-term effects were unclear. Significant improvements were obtained for different intervention durations and facilitators, and with participants of different nationalities and age. Most studies recruited participants from the community, which limited generalizability. Group therapy also resulted in improvements in other psychological variables.ConclusionsGroup therapy can significantly improve geriatric depression. Improvements were found across a variety of settings, protocols, participant characteristics, and for several psychological domains.     

Are we measuring the right end-points? Variables that affect the impact of computerised decision support on patient outcomes: a systematic review

Previous reviews of electronic decision-support systems (EDSS) have often treated them as a single category, and factors that may modify their effectiveness of EDSS have not been examined. The objective was to summarise the evidence associating the use of computerised decision support and improved patient outcomes. PubMed/Medline and the Database of Abstracts were searched for randomised controlled trials (RCT) of EDSS from 1 January 1994 to 31 January 2006. Twenty-four RCT studies from 97 reviewed were selected, eight of them examined systems supporting decisions for patients who presented with an acute illness, and 16 studies enrolled patients with chronic conditions. Overall, 13 (54%) of the studies showed a positive result, and 11 (46%) were with no impact. Critiquing and consultative systems showed the impact in 71% and 47% of studies, respectively. All systems targeting decisions related to acute disease improved patient outcomes compared with 38% of systems focused on the management of chronic conditions (P = 0.005). Provision of EDSS improves prescribing practices and treatment outcomes of patients with acute illnesses; however, EDSS were less effective in primary care. Complex interventions as clinical EDSS may require new metrics of assessment to describe the impact on patient outcomes.     

Impact of geriatric nutritional risk index on prognosis in peripheral artery disease patients undergoing endovascular therapy

The prevalence of peripheral artery disease continues to rise, with major amputations and mortality remaining prominent. Frailty is a significant risk factor for adverse outcomes in the management of the vascular disease. The geriatric nutritional risk index has been used to predict adverse outcomes in lower extremity peripheral artery disease and is a nutrition-based surrogate for frailty. The authors recruited 126 patients with peripheral artery disease who underwent endovascular stent implantation. As in previous reports, malnutrition was diagnosed by the geriatric nutritional risk index. The authors used Kaplan-Meier and multivariate Cox proportional hazards regression analyses to analyze the risk of major adverse limb events, which included mortality, major amputation, and target limb revascularization. There were 67 major adverse limb events during a median follow-up of 480 days. Malnutrition on the basis of the geriatric nutritional risk index was present in 31% of patients. Cox regression analysis showed that malnutrition based on the geriatric nutritional risk index was an independent predictor of major adverse limb events. Kaplan-Meier analysis showed that major adverse limb events increased with worsening malnutrition. Our single-center, retrospective evaluation of geriatric nutritional risk index (as a synonym for body health) correlates with an increased risk of major adverse limb events. Future directions should focus not only on identifying these patients but also on modifying risk factors to optimize long-term outcomes.     

Operationalizing a frailty index from a standardized comprehensive geriatric assessment

OBJECTIVES: To construct and validate a frailty index (FI) that is clinically sensible and practical for geriatricians by basing it on a routinely used comprehensive geriatric assessment (CGA) instrument. DESIGN: Secondary analysis of a 3-month randomized, controlled trial of a specialized mobile geriatric assessment team. SETTING: Rural Nova Scotia. Participants were seen in their homes. PARTICIPANTS: Frail older adults, of whom 92 were in the intervention group and 77 in the control group. MEASUREMENTS: A standard CGA form that accounts for impairment, disability, and comorbidity burden was scored and summed as a frailty index (FI-CGA). The FI-GCA was stratified to describe three levels of frailty. Patients were followed for up to 12 months to determine how well the index predicted adverse outcomes (institutionalization or mortality, whichever came first). RESULTS: The three levels of frailty were mild (FI-CGA 0-7), moderate (FI-CGA 7-13), and severe (FI-CGA>13). Demographic and social traits were similar across groups, but greater frailty was associated with worse function (r=0.55) and mental status (r=0.33). Those with moderate and severe frailty had a greater risk of adverse outcomes than those with mild frailty (unadjusted hazard ratio=1.9 and 5.5, respectively). There was no difference between frailty groups in mean 3-month goal-attainment scaling scores. Intrarater reliability was 0.95. CONCLUSION: The FI-CGA is a valid, reliable, and sensible clinical measure of frailty that permits risk stratification of future adverse outcomes.     

老年危重症患者预后预测模型的研究进展

急性生理学与慢性健康状况评分(APACHE)和简化急性生理评分(SAPS)等传统模型虽然预测危重症患者的死亡较可靠,但预测老年危重症患者的预后却可能会出现预测偏移或群体校准不良,而针对老年人研发出的专用预测模型不具有足够的准确性和可靠性。因此,衰弱综合征成为了目前老年综合评估的核心,研究表明衰弱指数(FI)、衰弱分级(CFS)可作为衡量衰弱综合征的客观模型,已成为老年危重症预后评估的研究热点。本文综述了这些评估模型的发展进程及研究进展,以期临床医师能够更好地应用它们。     

Advances in antithrombin and antiplatelet therapy for percutaneous coronary intervention

Recent advances in anticoagulant and antiplatelet therapy have made significant improvements in patient outcomes in percutaneous coronary interventions. Direct thrombin inhibitors have found an increasing role in coronary interventions as more trials validate their efficacy and safety. Further refinements of glycoprotein IIb/IIIa inhibitors are enabling tailoring of these medications for the appropriate populations. While heparin alone had been the mainstay of anticoagulant therapy for many years, increasing studies with low molecular weight heparins, such as enoxaparin, and glycoprotein IIb/IIIa inhibitors have altered the landscape of percutaneous coronary interventions. The development of antiplatelet agents has been accelerated to improve long-term results. Over the past year, many exciting new developments in antithrombotic therapy with coronary intervention have evolved, providing improvement in patient care.