Howard Bergman

A global clinical measure of fitness and frailty in elderly people

Background: There is no single generally accepted clinical definition of frailty. Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians. We aimed to develop a tool that would be both predictive and easy to use. Methods: We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging (CSHA). We followed this cohort prospectively; after 5 years, we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care, and correlated the results with those obtained from other established tools. Results: The CSHA Clinical Frailty Scale was highly correlated (r = 0.80) with the Frailty Index. Each 1-category increment of our scale significantly increased the medium-term risks of death (21.2% within about 70 mo, 95% confidence interval [CI] 12.5%–30.6%) and entry into an institution (23.9%, 95% CI 8.8%–41.2%) in multivariable models that adjusted for age, sex and education. Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition, function or comorbidity in assessing risk for death (area under the curve 0.77 for 18-month and 0.70 for 70-month mortality). Interpretation: Frailty is a valid and clinically important construct that is recognizable by physicians. Clinical judgments about frailty can yield useful predictive information.

The I.A.N.A. task force on frailty assessment of older people in clinical practice

Frailty is a commonly used term indicating older persons at increased risk for adverse outcomes such as onset of disability, morbidity, institutionalisation or mortality or who experience a failure to integrate adequate responses in the face of stress. Although most physicians caring for older people recognize the importance of frailty, there is still a lack of both consensus definition and consensual clinical assessment tools. The aim of the present manuscript was to perform a comprehensive review of the definitions and assessment tools on frailty in clinical practice and research, combining evidence derived from a systematic review of literature along with an expert opinion of a European, Canadian and American Geriatric Advisory Panel (GAP). There was no consensus on a definition of frailty but there was agreement to consider frailty as a pre-disability stage. Being disability a consequence rather than the cause of frailty, frail older people do not necessary need to be disabled. The GAP considered that disability (as a consequence of frailty) should not be included in frailty definitions and assessment tools. Although no consensual assessment tool could be proposed, gait speed could represent the most suitable instrument to be implemented both in research and clinical evaluation of older people, as assessment of gait speed at usual pace is a quick, inexpensive and highly reliable measure of frailty.

Searching for an Operational Definition of Frailty: A Delphi Method Based Consensus Statement. The Frailty Operative Definition-Consensus Conference Project

BACKGROUND There is no consensus regarding the definition of frailty for clinical uses. METHODS A modified Delphi process was used to attempt to achieve consensus definition. Experts were selected from different fields and organized into five Focus Groups. A questionnaire was developed and sent to experts in the area of frailty. Responses and comments were analyzed using a pre-established strategy. Statements with an agreement more than or equal to 80% were accepted. RESULTS Overall, 44% of the statements regarding the concept of frailty and 18% of the statements regarding diagnostic criteria were accepted. There was consensus on the value of screening for frailty and about the identification of six domains of frailty for inclusion in a clinical definition, but no agreement was reached concerning a specific set of clinical/laboratory biomarkers useful for diagnosis. CONCLUSIONS There is agreement on the usefulness of defining frailty in clinical settings as well as on its main dimensions. However, additional research is needed before an operative definition of frailty can be established.

Gait Speed as an Incremental Predictor of Mortality and Major Morbidity in Elderly Patients Undergoing Cardiac Surgery

OBJECTIVES The purpose of this study was to test the value of gait speed, a clinical marker for frailty, to improve the prediction of mortality and major morbidity in elderly patients undergoing cardiac surgery. BACKGROUND It is increasingly difficult to predict the elderly patients risk posed by cardiac surgery because existing risk assessment tools are incomplete. METHODS A multicenter prospective cohort of elderly patients undergoing cardiac surgery was assembled at 4 tertiary care hospitals between 2008 and 2009. Patients were eligible if they were 70 years of age or older and were scheduled for coronary artery bypass and/or valve replacement or repair. The primary predictor was slow gait speed, defined as a time taken to walk 5 m of ≥ 6 s. The primary end point was a composite of in-hospital post-operative mortality or major morbidity. RESULTS The cohort consisted of 131 patients with a mean age of 75.8 ± 4.4 years; 34% were female patients. Sixty patients (46%) were classified as slow walkers before cardiac surgery. Slow walkers were more likely to be female (43% vs. 25%, p = 0.03) and diabetic (50% vs. 28%, p = 0.01). Thirty patients (23%) experienced the primary composite end point of mortality or major morbidity after cardiac surgery. Slow gait speed was an independent predictor of the composite end point after adjusting for the Society of Thoracic Surgeons risk score (odds ratio: 3.05; 95% confidence interval: 1.23 to 7.54). CONCLUSIONS Gait speed is a simple and effective test that may identify a subset of vulnerable elderly patients at incrementally higher risk of mortality and major morbidity after cardiac surgery.

The Identification of Frailty: A Systematic Literature Review

An operational definition of frailty is important for clinical care, research, and policy planning. The literature on the clinical definitions, screening tools, and severity measures of frailty were systematically reviewed as part of the Canadian Initiative on Frailty and Aging. Searches of MEDLINE from 1997 to 2009 were conducted, and reference lists of retrieved articles were pearled, to identify articles published in English and French on the identification of frailty in community‐dwelling people aged 65 and older. Two independent reviewers extracted descriptive information on study populations, frailty criteria, and outcomes from the selected papers, and quality rankings were assigned. Of 4,334 articles retrieved from the searches and 70 articles retrieved from the pearling, 22 met study inclusion criteria. In the 22 articles, physical function, gait speed, and cognition were the most commonly used identifying components of frailty, and death, disability, and institutionalization were common outcomes. The prevalence of frailty ranged from 5% to 58%. Despite significant work over the past decade, a clear consensus definition of frailty does not emerge from the literature. The definition and outcomes that best suit the unique needs of the researchers, clinicians, or policy‐makers conducting the screening determine the choice of a screening tool for frailty. Important areas for further research include whether disability should be considered a component or an outcome of frailty. In addition, the role of cognitive and mood elements in the frailty construct requires further clarification.

Role of Frailty in Patients With Cardiovascular Disease

Frailty is a geriatric syndrome of increased vulnerability to stressors that has been implicated as a causative and prognostic factor in patients with cardiovascular disease (CVD). The American Heart Association and the Society of Geriatric Cardiology have called for a better understanding of frailty as it pertains to cardiac care in the elderly. The aim of this study was to systematically review studies of frailty in patients with CVD. A search was conducted of Ovid MEDLINE, EMBASE, the Cochrane Database, and unpublished sources. Inclusion criteria were an assessment of frailty using systematically defined criteria and a study population with prevalent or incident CVD. Nine studies were included, encompassing 54,250 elderly patients with a mean weighted follow-up of 6.2 years. In community-dwelling elders, CVD was associated with an odds ratio (OR) of 2.7 to 4.1 for prevalent frailty and an OR of 1.5 for incident frailty in those who were not frail at baseline. Gait velocity (a measure of frailty) was associated with an OR of 1.6 for incident CVD. In elderly patients with documented severe coronary artery disease or heart failure, the prevalence of frailty was 50% to 54%, and this was associated with an OR of 1.6 to 4.0 for all-cause mortality after adjusting for potential confounders. In conclusion, there exists a relation between frailty and CVD; frailty may lead to CVD, just as CVD may lead to frailty. The presence of frailty confers an incremental increase in mortality. The role of frailty assessment in clinical practice may be to refine estimates of cardiovascular risk, which tend to be less accurate in the heterogenous elderly patient population.

Addition of Frailty and Disability to Cardiac Surgery Risk Scores Identifies Elderly Patients at High Risk of Mortality or Major Morbidity

Background— Cardiac surgery risk scores perform poorly in elderly patients, in part because they do not take into account frailty and disability which are critical determinants of health status with advanced age. There is an unmet need to combine established cardiac surgery risk scores with measures of frailty and disability to provide a more complete model for risk prediction in elderly patients undergoing cardiac surgery. Methods and Results— This was a prospective, multicenter cohort study of elderly patients (≥70 years) undergoing coronary artery bypass and/or valve surgery in the United States and Canada. Four different frailty scales, 3 disability scales, and 5 cardiac surgery risk scores were measured in all patients. The primary outcome was the STS composite end point of in-hospital postoperative mortality or major morbidity. A total of 152 patients were enrolled, with a mean age of 75.9±4.4 years and 34% women. Depending on the scale used, 20–46% of patients were found to be frail, and 5–76% were found to have at least 1 disability. The most predictive scale in each domain was: 5-meter gait speed ≥6 seconds as a measure of frailty (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.17–5.90), ≥3 impairments in the Nagi scale as a measure of disability (OR, 2.98; 95% CI, 1.35–6.56) and either the Parsonnet score (OR, 1.08; 95% CI, 1.04–1.13) or Society of Thoracic Surgeons Predicted Risk of Mortality or Major Morbidity (STS-PROMM) (OR, 1.05; 95% CI, 1.01–1.09) as a cardiac surgery risk score. Compared with the Parsonnet score or STS-PROMM alone, (area under the curve, 0.68–0.72), addition of frailty and disability provided incremental value and improved model discrimination (area under the curve, 0.73–0.76). Conclusions— Clinicians should use an integrative approach combining frailty, disability, and risk scores to better characterize elderly patients referred for cardiac surgery and identify those that are at increased risk.

Tetrahydroaminoacridine-lecithin combination treatment in patients with intermediate-stage Alzheimer's disease. Results of a Canadian double-blind, crossover, multicenter study.

We studied the efficacy and safety of oral tetrahydroaminoacridine (THA) combined with lecithin in 52 patients with Alzheimers disease. The maximal tolerated dose of THA (up to 100 mg per day) was determined during an eight-week titration period, after which the tolerated dose of THA or placebo was given during two sequential randomized periods of treatment lasting eight weeks each. Highly purified lecithin (4.7 g per day) was administered during all phases of the study. Efficacy was expressed in terms of scores on the Mini-Mental State (MMS) test, the modified MMS test, the Hierarchic Dementia Scale, the Rapid Disability Rating Scale-II, and the behavioral scale of Reisberg et al. Safety was assessed by careful clinical monitoring as well as serial measurements of liver aminotransferases. Forty-six patients completed the titration period, and 39 completed the double-blind period, during which only the MMS score showed a small but significant increase (P less than 0.05) after four weeks of treatment with THA. Autonomic side effects of THA were common but mild. Reversible elevations of serum aspartate and alanine aminotransferase levels to three or more times the upper limit of normal occurred in 17 percent of patients; most of the patients affected were women. A liver biopsy performed in one patient showed resolving focal liver-cell necrosis. These studies fail to demonstrate a significant clinical benefit of THA given orally in a maximal dose of 100 mg per day over a period of eight weeks in combination with lecithin.

Rivastigmine and donepezil treatment in moderate to moderately-severe Alzheimer's disease over a 2-year period

ABSTRACT Objectives: Randomised controlled trials that directly compare cholinesterase inhibitors for the treatment of Alzheimers disease have been characterised by significant methodological limitations. As a consequence, they have failed to establish whether there are differences between agents in this class. To help address this question, a double-blind, randomised, controlled, multicentre trial was designed to evaluate the efficacy and tolerability of cholinesterase inhibitor treatment in patients with moderate to moderately-severe Alzheimers disease over a 2-year period. Methods: Patients were randomly assigned to rivastigmine 3–12 mg/day or donepezil 5–10 mg/day. Efficacy measures comprised assessments of cognition, activities of daily living, global functioning and behavioural symptoms. Safety and tolerability assessments included adverse events and measurement of vital signs. Results: In total, 994 patients received cholinesterase inhibitor treatment (rivastigmine, n = 495; donepezil, n = 499), and 57.9% of patients completed the study. The most frequent reason for premature discontinuation in both treatment groups was adverse events, primarily gastrointestinal. Adverse events were more frequent in the rivastigmine group during the titration phase, but similar in the maintenance phase. Serious adverse events were reported by 31.7% of rivastigmine- and 32.5% of donepezil-treated patients, respectively. Rivastigmine and donepezil had similar effects on measures of cognition and behaviour, but rivastigmine showed a statistically significant advantage on measures of activities of daily living and global functioning in the ITT–LOCF population. However, this was not maintained in the non-ITT–LOCF populations. In secondary sub-group analyses, AD patients who had genotypes that encoded for full expression of the butyrylcholinesterase enzyme (BuChE wt/wt; n = 226/340), who were < 75 years of age (n = 362/994) or who had symptoms suggestive of concomitant Lewy body disease (n = 49/994) showed significantly greater benefits from rivastigmine treatment. Conclusions: Cholinesterase inhibitor treatment may offer continued therapeutic benefit for up to 2 years in patients with moderate AD. Although both drugs performed similarly on cognition and behaviour, rivastigmine may provide greater benefit in activities of daily living and global functioning.

ADVANCING GERIATRIC NURSING PRACTICE: Randomized Controlled Trial of Nurse Case Management of Frail Older People

OBJECTIVES: To compare the effects of nurse case management with usual care provided to community‐dwelling frail older people in regard to quality of life, satisfaction with care, functional status, admission to hospital, length of hospital stay, and readmission to emergency department.