When asked to define frailty, the image of a thin,

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1 PROGRESS IN GERIATRICS The Identification of Frailty: A Systematic Literature Review Shelley A. Sternberg, MD, MSCE, * Andrea Wershof Schwartz, MD, MPH, Sathya Karunananthan, MSc, Howard Bergman, MD, and A. Mark Clarfield, MD 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. J Am Geriatr Soc 59: , Key words: frailty; systematic review; clinical tool; operational definition From * Maccabi Healthcare Services, Jerusalem, Israel; Mount Sinai School of Medicine, New York, New York; Solidage Research Group on Frailty and Aging: McGill University and Université de Montréal, Montreal, Canada; Division of Geriatric Medicine, McGill University, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada; and Department of Geriatrics, Soroka Hospital and the Ben-Gurion University of the Negev, Beer Sheva, Israel. Address correspondence to Dr. Shelley A. Sternberg, Maccabi Healthcare Services, 45 Haim Toren Street, Pisgat Zeev, Jerusalem, Israel. sternb_sh@mac.org.il DOI: /j x When asked to define frailty, the image of a thin, stooped, slow octogenarian quickly comes to mind. Despite an intuitive understanding by clinicians, consensus on a definition of frailty has been much slower and more difficult to reach. 1 Frailty has variously been defined as physical disability, impairment in basic or instrumental activities of daily living, or simply an increased vulnerability to adverse outcomes. 2 The definition that Fried et al. proposed describes a wasting syndrome, with weight loss and negative energy balance as important elements. 3 Other criteria have emphasized a life course approach, taking into account mid- and early-life influences on late-life frailty. 2 Cognitive and social factors are a more-recent research focus. 4 7 An operational definition of frailty is important for clinical care, research, and policy planning Fried s definition based on data from the Cardiovascular Health Study includes three or more of weight loss, weakness, exhaustion, low activity level, and slow gait speed. 3 This syndrome of frailty, with its own underlying pathophysiology, is held to be a construct distinct from disability or comorbidity. This definition has been widely used for research purposes but has so far proven impractical in the clinical setting. 4 An accumulation of deficits model of frailty, which posits that, simply put, the more things go awry, the more likely frailty is to develop, has been described. 11 This mathematical model counts disabilities and comorbidities. Although well validated and investigated, this tool is more useful for policy planners than for clinicians. 12 A clinically usable definition of frailty would help physicians screen their patients for frailty and allow for stratification according to risk level before cancer treatment, coronary angiography, or surgery Just as clinicians need a uniform definition of frailty to screen and treat their patients appropriately, so too do researchers and policy-makers. Whether exploring the etiologies and predictors of frailty, or interventions to prevent and treat frailty, researchers need a clear definition to define their study populations and measure their results. 8,9,16 Similarly, policy decisions regarding the distribution of scarce resources to help frail older adults and planning for future needs of an aging society are also JAGS 59: , , Copyright the Authors Journal compilation 2011, The American Geriatrics Society /11/$15.00

2 2130 STERNBERG ET AL. NOVEMBER 2011 VOL. 59, NO. 11 JAGS Figure 1. Hypothesized pathway to frailty. dependent on a consensus definition. Studies of comprehensive geriatric assessments (CGA) that use a multidisciplinary team approach to develop a treatment plan for frail older adults have shown that targeted populations, namely those who are not too well but not too sick, are the most likely to benefit from this intervention. 17 A clear operational definition of frailty would thus enable the appropriate population to be targeted for interventions such as CGA that help to preserve functional status and prevent, delay, or decrease adverse outcomes such as recurrent hospitalization, institutionalization, and death (Figure 1). This study was developed as part of the Canadian Initiative on Frailty and Aging (CIFA), an international research initiative that aims to further understanding of the causes, characteristics, trajectory, and implications of frailty, with the ultimate goal of improving the lives of older people at risk of frailty by disseminating knowledge on its prevention, detection, treatment, and rehabilitation, as well as on the cost-effective organization of services. 18 As an initial step in the process, the investigators of the CIFA undertook a series of systematic reviews of the available literature on frailty. The purpose of this study was to systematically review the literature on the identification of frailty. The research questions were: 1. What are the clinical operational definitions of frailty? 2. What are the instruments used to screen for and identify frailty? 3. What are tools to measure the severity of frailty? METHODS The methods for this systematic review were based on a standardized approach that was established for the CIFA reviews and has been described elsewhere. 19 Because there is not yet a widely accepted definition of frailty in the literature, a central coordination group of CIFA investigators designed a search strategy to be used for all of the reviews that would be broad enough to capture the literature related to the concept of frailty and included the following general keywords: aged combined with frail or frailty, vulnerable or vulnerability, healthy aging or successful aging, and disability or disabled persons. Geriatrics (methods), risk assessment, risk factors, health status indicators, disability evaluation, forecasting, patient care planning, clinical markers, health surveys, and diagnosis were added. Two of the authors (SS and AWS) identified published articles through searches of Medline and Ageline databases for the period from January 1, 1997, through December 31, 2004, and then subsequently updated them to December 31, In addition, a manual search of reference lists from relevant retrieved articles was performed. Only English and French publications involving human subjects were considered. Studies were selected for inclusion if they examined patient populations of community-dwelling adults aged 65 and older and offered clinically relevant outcomes, such as hospitalization, death, or change in functional status. Only articles describing original tools were included, and not subsequent validation studies using the same tool Articles that focused on definitions, screening criteria or severity measures of disability that did not mention frailty were not included, because the conceptualization of frailty as a syndrome that may overlap with but is distinct from disability was of interest. 1,26 Review Process The review process has been described elsewhere. 19 Briefly, the abstracts of retrieved articles were blinded in terms of author and journal. Two of the authors of the current study (SS and AMC or AWS) then independently reviewed the abstracts for relevance. For abstracts that at least one of the authors selected as relevant, the full articles were retrieved. In a subsequent step, the authors read through the full articles, blinded in terms of author, journal, and acknowledgments, and selected original studies that met the inclusion criteria. Disagreements were resolved through discussion. The references in each of the selected articles were then pearled to identify additional references of potential relevance. All original studies were then retained for quality assessment and data abstraction. Pertinent editorials and review articles that emerged from the literature search were retained as background papers. Two assessors trained in the use of the quality assessment and data abstraction tool developed for this review independently assessed the methodological quality and abstracted data from all of the selected articles. Methodological criteria included appropriateness of the study population, inclusion and exclusion criteria, outcome definition and measurement, risk factor measurement, time frame of exposures, measurement of confounders, statistical analysis, and the follow-up of control and intervention groups. Each criterion was given a rating from 1 to 4, with 1 representing the poorest and 4 representing the highest quality. Assessors also ranked the overall methodological quality of the article from 1 to 4. A consensus ranking was then determined for all individual items and for the overall rating. Two authors performed a final review to ensure that each article was relevant to the study questions. RESULTS Four thousand three hundred forty-four abstracts were reviewed, from which 144 articles were chosen for further assessment. An additional 70 articles were identified by pearling the bibliographies of the 144 aforementioned articles and by consulting with experts, for a total of 214

3 JAGS NOVEMBER 2011 VOL. 59, NO. 11 THE IDENTIFICATION OF FRAILTY 2131 articles; 166 of these were eliminated for not being considered original research or not addressing the research question. This left 48 articles for quality assessment and data abstraction, of which a further 26 were eliminated for being of poor methodological quality or for being validation studies rather than presenting original tools, leaving 22 articles as the subject of the current article (Figure 2). Table 1 describes the characteristics of these 22 articles. With respect to quality, six articles (27%) received a score of 4, 6,7,11, (50%) were given a score of 3, 3,30 39 and five (23%) scored The reported prevalence of frailty ranged from 5% to 58%. Definitions and Screening Criteria The identifying components, such as activities of daily living (ADLs) or weight loss, mentioned in the frailty definitions or screening tools are displayed in Figure 3A. Physical function (17, 77%), gait speed or mobility (11, 50%), and cognition (11, 50%) were the most commonly mentioned categories. ADLs and IADLs were included as identifying components of frailty more frequently in the earlier years of this review, whereas gait speed and cognition have become more common in recent years. The outcomes that the frailty criteria or screening tool predicted in 17 of the 22 articles were categorized, as displayed in Figure 3B. Four articles that appear in Table 1 were excluded from Figure 3B because they were cross-sectional analyses and lacked outcome measures and a fifth article because it presented a clinical global impression of change over time without specific outcome measures. 36 The most common outcomes of frailty were death (13, 76%), disability (7, 41%), and institutionalization (6, 35%). A grouped outcome category of overall functional decline including disability, physical performance decline, and functional decline was present in 11 (65%) of the articles. The use of disability as an outcome measure of frailty was also more common in recent studies. Severity of Frailty Sixteen of 22 articles (73%) presented severity measures of frailty. 3,7,11,27 29,33,35 39,41 44 These severity measures defined participants as fit, prefrail, or frail or graded frailty using a numerical score. Inclusion of a severity measure of frailty was more common in recent studies. Two innovative analyses addressed frailty as a dynamic state over time. 27,36 One developed a clinical judgment tool to measure change in frailty over time, 36 whereas the other assessed the effect of static versus dynamic frailty on physical performance and functional decline. 27 DISCUSSION The current study has presented a systematic review of articles from 1997 to 2009 addressing the clinical operational definitions, screening criteria, and severity measures of frailty. The most-common identifying factors for frailty were physical functioning, gait speed, and cognition. Outcomes most commonly examined were death, disability, and institutionalization. A recent trend toward including gait speed and cognition as components of frailty, and disability as an outcome rather than a component of frailty, was evident. The choice of components to be included in the frailty definition continues to be a contentious issue with important implications. For example, although some authors have included disability and functional decline as a component of frailty, 11,28,30,33 37,39,40,43 others regard disability and functional decline as an outcome. 3,27,29,32,34,37,39 When disability is left out of the measure of frailty, a tool emerges that aims to identify risk in a population that is functionally independent. 6 Designing interventions to delay the onset of frailty in this population would be analogous to primary prevention (Figure 4). Because disability has itself been shown to be an important predictor of hospitalization and death, by combining it with other markers of Search of Medline articles published from 1997 to 2009 in English/French (N = 4,334) 1st selection based on abstracts blinded for author and journal Abstracts eliminated (N = 3,991) Abstracts selected (N = 343) 2nd selection based on articles blinded for author, abstract, journal, sponsors, acknowledgments Articles eliminated (N = 199) * Articles selected from reference lists of the selected articles. Articles retained (N = 144) Pearled articles* (N = 70) Pearled articles* eliminated (N = 44) Review or editorials retained as background papers (N = 122) Articles retained for quality assessment and data abstraction (N = 48) Articles eliminated (N = 26) Articles retained for review (N = 22) Figure 2. Article selection flowchart.

4 2132 STERNBERG ET AL. NOVEMBER 2011 VOL. 59, NO. 11 JAGS Table 1. Study Characteristics References Quality Rating (1 4) Recruitment Period Length of Follow-Up, Years Identifying Factors Assessed Brody Age 2. Bathing assistance 3. Medication assistance 4. Health conditions interfere with daily activities Strawbridge Cross-sectional Four domains: analysis in Physical functioning, 2. nutritive, 3. cognitive, 4. sensory Frail defined as problems or difficulties in 2 domains Chin Three definitions of frailty: Physical inactivity plus either 1. decreased energy intake, 2. 5-year weight loss, or 3. low BMI Rockwood Mobility 2. ADL 3. Continence 4. Cognition Scoring: 0 = independent; Brown 41 2 Not reported NA Cross-sectional 1 = incontinence only; 2 = assistance with 1 identifying factors; 3 = dependence in 2 identifying factors Modified physical performance test Score: 32 to 36 = fit; = mildly frail; = moderate frailty Source Population Analytical Sample Size, n Outcomes Social HMO 5,810 Nursing home certifiable or home care eligible or institutionalized Alameda County Study 574 Quality-of-life measures: activities, life satisfaction, mental health Zutphen Study, Holland 450 Death Disability Physical performance decline Canadian Study of Health and Aging 9,008 Death Institutionalization Communitydwelling older adults 107 Strength Range of motion Balance Gait parameters Coordination and reaction speed Sensation (Continued)

5 JAGS NOVEMBER 2011 VOL. 59, NO. 11 THE IDENTIFICATION OF FRAILTY 2133 Table 1. (Contd.) References Quality Rating (1 4) Recruitment Period Length of Follow-Up, Years Identifying Factors Assessed Fried 3 3 Cohort Cohort Weight loss 2. Grip strength 3. Exhaustion 4. Walking time 5. Physical activity Frail = 3 criteria Prefrail = 1 or 2 criteria Saliba Four models: Age, self-rated health, and: 1. function; 2. function and medical conditions; 3. function and expanded diagnoses; 4. self-reported diagnoses and conditions Brody Empirical method Clinical judgment method Mitnitski Frailty Index constructed statistically from self-report and observed data on 20 accumulated deficits Jones 35 3 NA 1 Frailty index CGA impairment, disability, comorbidity Number of problems and number of comorbidities/2 Mild 0 to 7, moderate 7 to 13, severe >13 Studenski 36 3 NA NA Clinical Global Impression of Change in Physical Frailty Physical frailty strength, balance, nutrition, stamina, neuromotor, mobility Consequences of frailty function, healthcare utilization Global frailty physical and consequences Source Population Analytical Sample Size, n Outcomes Cardiovascular Health Study 5,317 in cohort 1, 4, 735 in cohort 2 Incident falls, hospitalization, worsening mobility or ADL function, Death Medicare Current Beneficiary annual survey respondents 6,205 Functional decline, death Social HMO 5,810 Nursing home certifiable or home care eligible or institutionalized The Canadian Study of Health and Aging 2,914 Mortality Mobile Geriatric Assessment Team trial 182 Mortality or institutionalization Six expert panel members, 46 clinicians, 24 patients, and 12 caregivers based at an academic geriatric center NA NA (Continued)

6 2134 STERNBERG ET AL. NOVEMBER 2011 VOL. 59, NO. 11 JAGS Table 1. (Contd.) References Quality Rating (1 4) Recruitment Period Length of Follow-Up, Years Identifying Factors Assessed Carrière Mobility 2. Balance 3. Strength 4. Visual acuity 5. Body composition 6. Physical activity 7. Educational level 8. Perceived health 9. Fear of falling Score: Statistical Klein Gait speed 2. Peak expiratory flow 3. Grip strength 4. Not being able to stand from a sitting position in one try 5. Visual impairment Score: 0 (no frailty) to 5 (maximum frailty) Puts years 1. Static: BMI, peak expiratory flow, MMSE, vision, hearing, incontinence, mastery, depression, low physical activity 2. Dynamic: weight loss, decline in peak flow, decline in cognition, loss of vision or hearing, new incontinence, decline in mastery, activity Source Population Epidemiology of Osteoporosis Study, France Beaver Dam Eye Study Longitudinal Aging Study Amsterdam Analytical Sample Size, n Outcomes 545 Disability 2,515 Cardiovascular disease, hypertension, cancer Mortality 2,430 Decline in physical performance tests or self-reported ADL (Continued)

7 JAGS NOVEMBER 2011 VOL. 59, NO. 11 THE IDENTIFICATION OF FRAILTY 2135 Table 1. (Contd.) References Quality Rating (1 4) Recruitment Period Length of Follow-Up, Years Identifying Factors Assessed Rockwood years 1. Modified MMSE 2. Cumulative Illness Rating Scale 3. History of falls 4. Delirium 5. Cognitive impairment or dementia 6. Functional status 7. Urinary incontinence 8. ADL 9. Cognitive impairment, no dementia 10. Mobility Score: 1 (very fit) to 7 (severely frail) Rolfson 43 2 July weeks NA 1. Cognitive impairment Cross-sectional 2. Balance and mobility 3. Mood 4. Functional independence 5. Medication use 6. Social support 7. Nutrition 8. Health attitudes 9. Continence 10. Burden of medical illness 11. Quality of life Score: 0 to 17 (maximum frailty) Amici 42 2 NA NA Neurological, cardiac, respiratory, renal, peripheral vascular, cancer, gastrointestinal, locomotive, sensory, metabolic and nutrition, MMSE Ensrud Weight loss 2. Time to get up five times from a chair 3. Decreased energy level Score: 0 = robust; 1 = prefrail; 2+ =frail Source Population Analytical Sample Size, n Outcomes Canadian Study of Health and Aging 2,305 Death, institutionalization Referral population for comprehensive geriatric assessment, Canada 158 NA Italians aged NA Study of Osteoporotic Fractures 6,701 Death Fractures Falls Disability (Continued)

8 2136 STERNBERG ET AL. NOVEMBER 2011 VOL. 59, NO. 11 JAGS Table 1. (Contd.) References Quality Rating (1 4) Recruitment Period Length of Follow-Up, Years Identifying Factors Assessed Source Population Analytical Sample Size, n Outcomes Ravaglia Aged Male 3. Physical inactivity 4. Use of 3 drugs 5. Sensory deficits 6. Calf circumference 7. Instrumental ADL disability, 8. Gait and balance test score Pessimism about one s health Score: 0 to 2 normal; 3 to 9 increasing frailty Rothman Fried criteria+ 1. Cognitive impairment 2. Depressive symptoms Ávila-Funes Fried criteria+ 1. Cognitive impairment Hubbard 44 2 No data NA Cross-sectional 1. Weight loss 2. Weakness 3. Slow gait speed 4. Cognitive impairment 5. Decreased lung function Conselice Study of Brain Aging, Italy Precipitating Events Project Three-City Study, France Continuing care wards (frail), day hospital (intermediate), age-matched independent older adults (fit), South Wales 1,007 Death, Fractures, Falls, hospitalization Onset of new and worsening of preexisting disability 754 Chronic disability, nursing home placement Injurious falls, death 6,030 Incident disability, 30 frail, 40 intermediate, and 40 fit hospitalization, death, dementia Fried criteria Rockwood criteria ADL = activity of daily living; BMI = body mass index; HMO = health maintenance organization; MMSE = Mini Mental State Examination; NA = not addressed; CGA = comprehensive geriatric assessment.

9 JAGS NOVEMBER 2011 VOL. 59, NO. 11 THE IDENTIFICATION OF FRAILTY 2137 A B Figure 3. A. Prevalence of identifying factors for frailty in definitions and screening tools. B. Prevalence of outcomes of frailty predicted by definitions and screening tools. BMI = body mass index. vulnerability in assessing frailty, the level of risk in a group that has already been identified as vulnerable by virtue of their disability is being examined. Interventions in this group to prevent further deterioration in frailty status would be analogous to secondary prevention trials (Figure 4). The strengths of this study are its rigorous design and standardized systematic review protocol, including blinded review of abstracts and quality assessments, as part of the overarching CIFA. A recent report on the clinical assessment of frailty provided a review of the literature of definitions, clinical tools, and components of frailty combined with the expert opinion of an international panel of geriatricians. 45 Although it was a comprehensive review and update, it did not provide any indication of the quality of the studies reviewed. A limitation of the current study is that the search was restricted to identifying factors of frailty, by necessity leaving out the rich literature on tools to identify disability. Consensus does not yet exist regarding the component elements of frailty. The Fried phenotype of frailty has enjoyed the most attention from researchers because of its underlying physiological base and easily measurable Figure 4. Opportunities for prevention of frailty. components. Nonetheless, although lauding this approach, Ferrucci admitted our gerontological souls are still bleeding ; the definition feels incomplete. 46 Responding to this challenge, recent studies have examined the Fried components and added cognition and mood to the scale. 6,7 Questions regarding the relationship between frailty, aging, disability, and chronic disease require clarification. 16 The role of gait speed as a powerful predictor of adverse outcomes in nondisabled older people who are years away from entering the frailty cycle is an active area of research. 16,47 Focus is also shifting to the dynamic nature of frailty over time rather than assessing frailty as a static condition. 36 The definition and outcomes that best suit the needs of those doing the screening determine the choice of a screening tool for frailty. 10 For example, clinicians looking to streamline their office practice to target complicated patients may prefer a screening tool that is short and simple to use, predicts a decline in functional status, and is linked to quality-of-care measures for vulnerable elders, such as the tool proposed by Saliba. 34,48 Those more interested in researching the biology of frailty may prefer a definition based on a biologically plausible model, such as the Fried tool. 3 An administrator involved in planning services for older adults may turn to a tool that predicts hospital admission and avoids the debate as to how to define frailty. 49 Alternatively, the administrator may choose a frailty scale that can be derived from an administrative database such as the accumulated deficits approach of Mitnitski and Rockwood. 11 The pressing clinical, research, and public policy implications of a consensus definition of frailty underscore the need for further investigation into models of identifying frailty. ACKNOWLEDGMENTS Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Funding provided by the CIFA, supported by the Max Bell Foundation, Réseau Québécois de Recherche sur le

10 2138 STERNBERG ET AL. NOVEMBER 2011 VOL. 59, NO. 11 JAGS Vieillissement, Canadian Institutes of Health Research, and Gustav Levinschi Foundation. Author Contributions: All authors: Conception and design of the study and acquisition of data. Sternberg, Clarfield, and Wershof Schwartz: Analysis and interpretation of data. Sternberg and Wershof Schwartz: Drafting of the article. Bergman, Clarfield, and Karunananthan: Revision of the article for important intellectual content. All authors gave final approval of the current version of the article. Sponsor s Role: The sponsors had no role in the design, methods, data collection, analysis and preparation of paper. REFERENCES 1. Whitson HE, Purser JL, Cohen HJ. Frailty thy name is phrailty? J Gerontol A Biol Sci Med Sci 2007;62A: Hogan DB, MacKnight C, Bergman H. Models, definitions, and criteria of frailty. Aging Clin Exp Res 2003;15: Fried LP, Tangen CM, Walston J et al. Frailty in older adults: Evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56A:M146 M Rockwood K. Frailty and its definition: A worthy challenge. J Am Geriatr Soc 2005;53: Fisher AL. Just what defines frailty? J Am Geriatr Soc 2005;53: Rothman MD, Leo-Summers L, Gill TM. Prognostic significance of potential frailty criteria. J Am Geriatr Soc 2008;56: Avila-Funes JA, Amieva H, Barberger-Gateau P et al. Cognitive impairment improves the predictive validity of the phenotype of frailty for adverse health outcomes: The Three-City Study. J Am Geriatr Soc 2009;57: Ferrucci L, Guralnik JM, Studenski S et al. Designing randomized, controlled trials aimed at preventing or delaying functional decline and disability in frail, older persons: A consensus report. J Am Geriatr Soc 2004;52: Walston J, Hadley EC, Ferrucci L et al. Research agenda for frailty in older adults: Toward a better understanding of physiology and etiology: Summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults. J Am Geriatr Soc 2006;54: Martin FC, Brighton P. Frailty: Different tools for different purposes? Age Ageing 2008;37: Mitnitski AB, Graham JE, Mogilner AJ et al. Frailty, fitness and late-life mortality in relation to chronological and biological age. BMC Geriatr 2002;2: Searle SD, Mitnitski A, Gahbauer EA et al. A standard procedure for creating a frailty index. BMC Geriatr 2008;8: Puts MT, Monette J, Girre V et al. Are frailty markers useful for predicting treatment toxicity and mortality in older newly diagnosed cancer patients? Results from a prospective pilot study. Crit Rev Oncol Hematol 2011;78 (2): Freiheit EA, Hogan DB, Eliasziw M et al. Development of a frailty index for patients with coronary artery disease. J Am Geriatr Soc 2010;58: Makary MA, Segev DL, Pronovost PJ et al. Frailty as a predictor of surgical outcomes in older patients. J Am Coll Surgeons 2010;210: Bergman H, Ferrucci L, Guralnik J et al. Frailty: An emerging research and clinical paradigm: Issues and controversies. J Gerontol A Biol Sci Med Sci 2007;62A: Stuck AE, Siu AL, Wieland GD et al. Comprehensive geriatric assessment: A meta-analysis of controlled trials. Lancet 1993;342: Bergman H. The Canadian Initiative on Frailty and Aging. Aging Clin Exp Res 2003;15: Karunananthan S, Wolfson C, Bergman H et al. A multidisciplinary systematic literature review on frailty: Overview of the methodology used by the Canadian Initiative on Frailty and Aging. BMC Medical Res Methodol 2009;9: Bandeen-Roche K, Xue QL, Ferrucci L et al. Phenotype of frailty: Characterization in the Women s Health and Aging Studies. J Gerontol A Biol Sci Med Sci 2006;61A: Ottenbacher KJ, Ostir GV, Peek MK et al. Frailty in older Mexican Americans. J Am Geriatr Soc 2005;53: Woods NF, LaCroix AZ, Gray SL et al. Frailty: Emergence and consequences in women aged 65 and older in the Women s Health Initiative Observational Study. J Am Geriatr Soc 2005;53: Mitnitski A, Bao L, Skoog I et al. A cross-national study of transitions in deficit counts in two birth cohorts: Implications for modeling ageing. Exp Gerontol 2007;42: Min LC, Elliott MN, Wenger NS et al. Higher vulnerable elders survey scores predict death and functional decline in vulnerable older people. J Am Geriatr Soc 2006;54: Ho LS, Williams HG, Hardwick EAW. Discriminating characteristics of community dwelling elderly at high and low risk for frailty. J Aging Phys Activity 2002;10: Fried LP, Ferrucci L, Darer J et al. Untangling the concepts of disability, frailty, and comorbidity: Implications for improved targeting and care. J Gerontol A Biol Sci Med Sci 2004;59A: Puts MT, Lips P, Deeg DJ. Static and dynamic measures of frailty predicted decline in performance-based and self-reported physical functioning. J Clin Epidemiol 2005;58: Rockwood K, Song X, MacKnight C et al. A global clinical measure of fitness and frailty in elderly people. CMAJ 2005 Aug 30;173: Ensrud KE, Ewing SK, Taylor BC et al. Comparison of 2 frailty indexes for prediction of falls, disability, fractures, and death in older women. Arch Intern Med 2008;168: Brody KK, Johnson RE, Ried LD et al. A comparison of two methods for identifying frail Medicare-aged persons. J Am Geriatr Soc 2002;50: Strawbridge WJ, Shema SJ, Balfour JL et al. Antecedents of frailty over three decades in an older cohort. J Gerontol B Psychol Sci Soc Sci 1998;53B:S9 S Chin APM, Dekker JM, Feskens EJ et al. How to select a frail elderly population? A comparison of three working definitions. J Clin Epidemiol 1999;52: Rockwood K, Stadnyk K, MacKnight C et al. A brief clinical instrument to classify frailty in elderly people. [Comment]. Lancet 1999;353: Saliba D, Elliott M, Rubenstein LZ et al. The Vulnerable Elders Survey: A tool for identifying vulnerable older people in the community. J Am Geriatr Soc 2001;49: Jones DM, Song X, Rockwood K. Operationalizing a frailty index from a standardized comprehensive geriatric assessment. J Am Geriatr Soc 2004;52: Studenski S, Hayes RP, Leibowitz RQ et al. Clinical global impression of change in physical frailty: Development of a measure based on clinical judgment. J Am Geriatr Soc 2004;52: Carrière I, Colvez A, Favier F et al. Hierarchical components of physical frailty predicted incidence of dependency in a cohort of elderly women. J Clin Epidemiol 2005;58: Klein BE, Klein R, Knudtson MD et al. Frailty, morbidity and survival. Arch Gerontol Geriatr 2005;41: Ravaglia G, Forti P, Lucicesare A et al. Development of an easy prognostic score for frailty outcomes in the aged. Age Ageing 2008;37: Brody KK, Johnson RE, Douglas RL. Evaluation of a self-report screening instrument to predict frailty outcomes in aging populations. Gerontologist 1997;37: Brown M, Sinacore DR, Binder EF et al. Physical and performance measures for the identification of mild to moderate frailty. J Gerontol A Biol Sci Med Sci 2000;55A:M350 M Amici A, Baratta A, Linguanti A et al. The Marigliano-Cacciafesta polypathological scale: A tool for assessing fragility. Arch Gerontol Geriatr 2008;46: Rolfson DB, Majumdar SR, Tsuyuki RT et al. Validity and reliability of the Edmonton Frail Scale. Age Ageing 2006;35: Hubbard RE, O Mahony MS, Woodhouse KW. Characterising frailty in the clinical setting a comparison of different approaches. Age Ageing 2009;38: Abellan van Kan G, Rolland Y, Houles M et al. The assessment of frailty in older adults. Clin Geriatr Med 2010;6: Ferrucci L, Mahallati A, Simonsick EM. Frailty and the foolishness of Eos. J Gerontol A Biol Sci Med Sci 2006;61A: Studenski S, Perera S, Patel K et al. Gait speed and survival in older adults. JAMA 2011;305: Wenger NS, Roth CP, Shekelle P. Introduction to the assessing care of vulnerable elders-3 quality indicator measurement set. J Am Geriatr Soc 2007;55Suppl 2:S247 S Wagner JT, Bachmann LM, Boult C et al. Predicting the risk of hospital admission in older persons--validation of a brief self-administered questionnaire in three European countries. J Am Geriatr Soc 2006;54: