Q. Roquebert1,4, J. Sicsic1, B. Santos-Eggimann2, N. Sirven1, T. Rapp1,3
1. LIRAES (EA4470), Université de Paris; Paris, France; 2. Centre universitaire de médecine générale et santé publique (Unisanté), Université de Lausanne, Switzerland; 3. LIEPP, Sciences Po, France; 4. Université de Strasbourg, Université de Lorraine, CNRS, BETA, 67000 Strasbourg, France
Corresponding author: Jonathan Sicsic (PhD), LIRAES, 45 rue des Saints-Pères, Université de Paris 75006 Paris, Jonathan.firstname.lastname@example.org. +33(0)177219361
J Frailty Aging 2021;in press
Published online March 15, 2021, http://dx.doi.org/10.14283/jfa.2021.7
This systematic literature review documents the link between frailty or sarcopenia, conceptualized as dimensions of physical health, and the use of long-term care services by older individuals. Long-term care services include formal and informal care provided at home as well as in institutions. A systematic review was performed according to PRISMA requirements using the following databases: PubMed-Medline, Embase, CINAHL, Web of Science, and Academic Search Premier. We included all quantitative studies published in English between January 2000 and December 2018 focusing on individuals aged 50 or more, using a relevant measurement of sarcopenia or physical frailty and a long-term care related outcome. A quality assessment was carried out using the questionnaire established by the Good Practice Task Force Report of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Five subsets of long-term care outcome were considered: 1/ nursing home placement (NHP), 2/ nursing home short stay (NHSS), 3/ formal personal care (FPC), 4/ formal home help (FHH), 5/ informal care (IC). Out of 1943 studies, 17 were finally included in the review. With some studies covering several LTC outcomes, frailty and / or sarcopenia were associated with increased LTC use in 17 out of 26 cases (NHP: 5/6, NHSS: 3/4, FPC: 5/7, FHH: 1/4, IC: 3/5) The association was not consistent in 5 cases (NHP: 1/6, NHSS: 1/4, FPC: 2/7, FHH: 0/4, IC: 1/5) and the association was either not significant or the results inconclusive in the remaining 9 cases. Overall, while results on sarcopenia are scarce, evidence support a positive association between frailty and LTC use. The evidence is stronger for the association of physical frailty with nursing home placement / short stay as well as on FPC. There is less (more heterogeneous) evidence regarding the correlation between physical frailty and FHH or IC use. Results need to be confirmed by more advanced statistical methods or design based on longitudinal data.
Key words: Frailty, sarcopenia, long-term care, systematic review, nursing home, informal care, formal care.
In a context of aging populations, the demand for long-term care (LTC) is increasing rapidly. Referring to the relatively large range of services needed in the long run to individuals because of their functional limitations, LTC can be provided in the community by relatives (informal care), professional nurses or care workers (formal care), or in specific institutions such as in nursing homes. LTC spending represents an increasing share of Western countries’ Gross Domestic Product (GDP) and most of these expenditures are funded by public mechanism schemes involving taxes and/or social insurance (1, 2). Projections suggest that LTC public expenditures should increase by 69% at least (in a healthy aging scenario) reaching 2.7 % of GDP in the European Union in 2070 (3).
Beyond disability status, increasing attention is being paid to the pre-disability condition as conceptualized by frailty and sarcopenia. While frailty is defined as a vulnerable health status resulting from the reduction of individuals’ physiological reserve, sarcopenia indicates the loss of muscle mass and muscle strength (4). In practice, frailty and sarcopenia are closely related, and it may be difficult to empirically distinguish these concepts. Indeed, frailty and sarcopenia often overlap; most frail older people exhibit sarcopenia, and some older people with sarcopenia are also frail (5). Frailty is relatively easy to measure in the clinical practice. Some readily accessible screening tests also exist for sarcopenia, such as the SARC-F (6). Yet precise measurement of sarcopenia involves more complex instruments such as dual x-ray absorptiometry scan to measure appendicular lean mass (ALM) and classify individuals according to pre-defined cut-points (7, 8). Overall, both are prevalent in old age and associated with adverse health events. Efforts to adapt healthcare and social systems to aging populations might benefit from taking into account the effects of frailty and sarcopenia on health and long-term care services utilization.
A growing literature has been exploring the relationship between frailty or sarcopenia and LTC use since the early 2000’s. However, it is difficult to have a clear perspective of the overall findings and the quality of evidence stemming from this literature. Indeed, publications used various measures of frailty, explored sometimes different LTC outcomes (formal care use, informal care use, nursing home use etc.), applied different statistical modelling techniques, sampling methods etc. Therefore, there is need for a systematic review to assess the quality of the methods, classify findings according to different outcomes, and provide an overall perspective of the relationship between frailty, sarcopenia and LTC use. To the best of our knowledge, such an analysis of the literature has not been done yet.
Three prior reviews of the literature have provided evidence that frailty is associated with a higher risk of hospitalization (9, 10) and nursing home placement (10, 11). These studies have found moderate evidence of the association between frailty and hospitalization or institutionalization. Results on sarcopenia are more limited: it was positively correlated with hospitalization in one study (12) but no study examined its link with nursing home entry.
The present review fills a gap in the literature by focusing on the link between frailty or sarcopenia and LTC, not only including nursing home admission but also formal and informal care provided in the community. Moreover, we evaluated the quality of evidence and summarized the current knowledge on frailty and sarcopenia as correlates of LTC use in populations aged 50 years and over. This article addresses the following question: are frailty and sarcopenia, conceptualized as dimensions of physical health, associated with the use of long-term care services by older individuals? Our systematic review is the first to focus on various LTC outcomes, and to provide an evaluation of both the results of the literature and the quality of the published evidence. The following aspects of LTC utilization are investigated: first, informal care, referring to the unpaid care provided by relatives; second, formal care, referring to the paid care provided by professionals, either nurses or personal care workers; finally, we also consider LTC provided in nursing homes.
The protocol for our systematic review was prepared and registered on the International Prospective Register of Systematic Reviews (PROSPERO; Ref CRD42020137212). The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and with close adherence to the Cochrane Handbook for Systematic Reviews of Interventions. The resulting PRISMA checklist (see Table A.1, Appendix A.1, in Supplemental Materials), and the flowchart (see Figure 1) depict the stages involved in the selection process. The following subsections briefly discuss the methodology.
Flowchart of screening phases
Data Sources and Search Strategy
The search was conducted from April 2019 to June 2019 on the following databases:
PubMed-Medline, Embase, CINAHL (Academic Search Premier/EconLit), Web of Science. A preliminary search was conducted in order to develop a search strategy. The final search strategy is described in Appendix A.2. We employed some methodological components of the Effective Practice and Organisation of Care (EPOC) group’s search strategy, combined with selected MeSH terms and free text terms related to the PICOS (i.e. population, intervention, comparator, outcome and study design) elements. Studies published in English between January 2000 and December 2018 were collected. Also, the reference lists of the retrieved articles were examined to look for further relevant literature (through a ‘pearling procedure’).
Two researchers independently screened the titles and abstracts of papers published in English between 2000-2018. The selection of relevant papers was completed according to predefined eligibility criteria: i) the population of interest was composed of people aged 50 or more; ii) sarcopenia or physical frailty were explicitly measured by an identified tool (phenotype, index, scale, indicator) measuring a physical or biomedical component (thus excluding papers focusing only on psychological or social conceptions of frailty); iii) the comparators were expected to be populations with different levels of frailty or sarcopenia, including the comparison of a frail (respectively sarcopenic) population and a non-frail (respectively non sarcopenic) population; iv) the outcome should be a long-term care outcome (formal care, informal care, nursing home admission); v) we focused on quantitative research papers and excluded case reports, qualitative works or other studies without design (discussion, commentary, workshop report, systematic review).
A pilot phase was conducted to check that these criteria were precise enough. In the selection process, the information regarding the paper (authorship, institutions, journal titles and year of publication) were not blinded: even though inclusion decisions could be affected by these parameters, blind assessment has been shown to be costly and have a limited value in the study selection (13). Differences in screening results were solved by dialogue between the five members of the research team involved in the preparation of the manuscript.
We searched for cross-sectional, cohort, and pre-post studies, using a validated measure of physical frailty or sarcopenia. There were no restrictions in terms of study setting, or characteristics of sample population (except the age condition).
Typology of LTC outcomes
The main outcomes were categorized as utilization of any type of LTC services, at the intensive (i.e., probability of use) or extensive (i.e., volume of use, volume of costs) margins. We considered five different categories: 1/ Nursing home placement (NHP), regrouping any long or permanent stay in a nursing home or LTC institution, 2/ Nursing home short stay (NHSS), 3/ Formal personal care (FPC), regrouping home care services explicitly stated (e.g., ‘home care’, ‘nursing care’), 4/ Formal home help (FHH), consisting in any type of non-care help (e.g., help with meals of household duties), and 5/ Informal care (IC), provided by spouse, children or relatives.
Data Extraction, Analysis and Synthesis
Two independent reviewers (QR, JS) screened each study to identify the abstract, title, keywords, and concepts reflecting both the study’s contribution and research context. Databases were searched for a combination of three groups of keywords, referring to the variables of interest (frailty and sarcopenia), the outcomes of interest (long-term care, included formal care provided by nurses and care workers, informal care and nursing homes), and a third group complementing the request with a condition relating to utilization (use, utilization, visits, consumption). The complete search strategy is described in Appendix A.2.
Once the search strategy was completed, the full text of the relevant studies was retrieved and assessed by the two review authors with respect to the inclusion/exclusion criteria. When consensus was difficult to reach, a third review author (TR) assessed the study. The data were extracted by one reviewer (QR or JS) and checked by a second reviewer (JS or QR). The raw data from each manuscript included authors’ names, year of publication, title, journal, country and regions (if specified), study setting, study design, study population, participant demographics (age, share of women), details on the physical frailty measure used, type of LTC outcome use, raw and adjusted estimates, and risk of bias assessment details. The collected data were organized manually and tabulated using standardized forms. Given the heterogeneity of studies in terms of type of outcome and reporting (i.e., odds ratio, risk ratio, hazard ratio, marginal effects, etc.) we were unable to pool the results and conduct a meta-analysis. Therefore, we provide a comparative summary of findings for the main outcomes, using measures of the association in the same way as they were reported.
Risk of bias and quality assessment
The risk of bias was assessed using the Report from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force which provides a questionnaire to assess the relevance and credibility of observational studies (14). The credibility of each study was assessed by scoring each study across six quality domains: Design (8 items), Data (4 items), Analysis (3 items), Reporting (7 items), Interpretation (8 items), and Conflict of Interest (2 items). Two independent reviewers assessed each study (QR and JS). When a difference persisted between them, a third reviewer (TR) assessed the study and came to an agreement. Details regarding the grid and the coding strategy for each item are provided in Appendix A.3: Table A.3.1 assesses the credibility with respect to the study design domain, Table A.3.2 with respect to the data, Table A.3.3 with respect to the analysis, Table A.3.4 with respect to reporting, Table A.3.5 with respect to interpretation.
The Task Force Report (14) identified two specific criteria, where failure to address these criteria would indicate a “fatal flaw” and require particular caution in interpreting the results. One criterion concerned the Data: “was exposure outcome valid?” and the second concerned the Analysis: “was there a thorough assessment and control of confounding?”. Because the first criterion was already included as a study selection criterion, we only considered the second criteria as a potential fatal flaw. In case no multivariate regression analysis was conducted (adjusting for potential confounders), we classified the study as providing “not enough evidence” to conclude on the relationship being investigated.
Results of screening phases
The literature search yielded 2,534 titles in the preliminary phase. Figure 1 depicts the flow chart associated to the screening procedure. Removal of duplicates resulted in 1,933 potentially relevant papers. Then, at the screening stage, 1,920 studies were removed after applying the exclusion criteria. The pearling procedure allowed us to identify 4 more relevant papers. In the end, our systematic review comprised 17 studies on the relationship between frailty and /or sarcopenia and LTC use (16 studies using frailty, and 1 study using sarcopenia as main independent variable). Main outcomes, descriptions, and statistics (when available) are presented in Table 1. A complete summary of findings is provided in Appendix A.4, including information on the frailty/sarcopenia measurements, outcomes considered and statistical uncertainty around point estimates.
Summary of study design and outcomes
a. Time frame only for longitudinal / cohort studies; *: Significant at the 5% level; b. OR calculated by authors based on raw coefficients (log OR); Abbreviations. HR: hazard ratio; OR: odds ratio; RR: risk ratio; ME: marginal effect; raw coefficient. NA: not available. ALM: appendicular lean mass; Note: details regarding measurements and statistical uncertainty around point estimates are provided in Appendix A.3.
As regard settings, 12 of the 17 reviewed studies took place in the general (community-dwelling) population, (15–26). Two studies considered residents of housing facilities or long-stay home care clients (27, 28) and two studies focused on the specific population of adults with intellectual disabilities (29) or cognitive impairments (30). One study focused on patients with diagnostic of Alzheimer disease (AD) (31). Interest in the association between physical frailty, sarcopenia, and LTC use seems to have arisen since 2008, with an increasing trend since. Most of the research was conducted in North America (n=4), Australia (n=2), and central Europe (n=11) (see Table A.5.1 and Figure A.5.1 for more details on the geographical distribution of studies).
Overall, the mean relative score achievement (quality) was 84% (min= 67%, max= 100%) for the subdomain design, 97% (min= 67%, max= 100%) for the subdomain data, 28% (min= 0%, max= 67%) for the subdomain analyses, 84% (min= 57%, max= 100%) for the subdomain reporting, and 82% (min= 75%, max= 100%) for the subdomain interpretation. Appendix A.3 provides details on the scoring of each paper according to each domain. In the quality assessment, an important issue lies in the way potential confounders are dealt with: few studies used of an appropriate design (Design, Question 5, 2 studies coded 1 out of 17) and they were scarcely discussed (Interpretation, Question 4, 5 studies coded 1 out of 17). Overall, no study had all criteria 100% fulfilled. There were no large discrepancies in terms of quality according to the class of LTC outcome, though studies investigating FHH had lower scores on average, and studies focusing on LTC placements (short or permanent) tended to have higher quality (see Figures A.3.1 in Appendix A.3).
A “fatal flaw” (assessed by the absence of control or assessment of potential confounders) was diagnosed for four studies (19, 25, 26, 29). Two of the studies focused on formal home care (19, 29), among which one study additionally focused on home care (19), and two studies focused on informal care (25, 26).
Association between frailty, sarcopenia and LTC use
Frailty and LTC use
Overall, 10 studies reported a positive association between frailty and LTC use (15–18, 23, 24, 27–29, 31) (Table 2). Conversely, only two studies showed no significant association between frailty and LTC use (21, 22). In three studies, there was not enough evidence to conclude on the relationship between frailty and LTC use (e.g., because no multivariate regression was run) (19, 25, 26). Among the 10 studies reporting positive associations, three found mixed results (17, 24, 31), which varied according to the frailty measure used (see Table 1 for a summary of results according to each frailty measure used).
Summary of results per class of outcome
Legend: NS nonsignificant; (+) Outcome increased significantly; NEE: not enough evidence (e.g., no adjusted multivariate regression conducted); (*) inconsistent association (the association varies according to the frailty measure considered); In each study, the LTC outcomes were groups into one of the five categories: 1/ Nursing home placement (NHP), 2/ Nursing home short stay (NHSS), 3/ Formal personal care (FPC), 4/ Formal home care (FHC), 5/ Informal care (IC). Several outcomes per study are possible.
Sarcopenia and LTC use
Only one study focused on the relationship between sarcopenia and LTC use . Using a 3-classes characterization of sarcopenia defined as sarcopenia I (i.e., low appendicular lean mass / ALM alone), sarcopenia II (low ALM with weakness), or sarcopenia III (low ALM with weakness and poor gait speed), the authors found a positive association between sarcopenia (either I, II, or III) and NHP. Moreover, the relationship was stronger when sarcopenia severity was higher (the effect size was higher for sarcopenia III compared to sarcopenia I or sarcopenia II).
Heterogeneity of results according to the LTC outcome
The number of studies having focused on each type of LTC outcome was distributed as follows (one study may have analysed multiple LTC outcomes): six studies on nursing home placement (NHP) (15, 20, 22, 27, 28, 31), four studies on nursing home short stay (NHSS) (16, 17, 21, 23), seven studies on formal personal care (FPC) (16–19, 24, 25, 29), four studies on formal home help (FHH) (16, 19, 25, 26), and five studies on informal care (IC) (17, 24–26, 30). Among the six studies investigating the association between frailty and NHP, 5 studies found a significant positive association, including one with mixed results (i.e., depending on frailty measurement) (see Table 1). Regarding NHSS, three studies confirmed a positive significant association, including one with mixed results. Regarding FPC, five studies confirmed a positive significant association, including two with mixed results. The evidence was less compelling for the two other LTC outcomes. Regarding FHH, only one study found a positive significant association; it was not possible to conclude for the other three studies because no multivariate regression models were estimated. Last, concerning IC, three studies found a positive significant association with frailty, including one with mixed results.
The purpose of this systematic review was to assess the association between physical frailty or sarcopenia and LTC use. Our paper is the first to systematically review the results of these studies and assess their strength and weaknesses using a validated quality assessment grid (14). We found that most of the reviewed studies reported a positive association of physical frailty and LTC outcomes. Moreover, there is evidence showing an association between frailty and LTC use for each class of LTC outcome. Specifically, there seems to be already reasonable evidence to conclude on a positive relationship of physical frailty with nursing home placement / short stay as well as on FPC. However, there is less (more heterogeneous) evidence regarding the association between physical frailty and FHH or IC use. Besides, only one study investigated the association between sarcopenia and LTC use, and found a positive association for NHP. Further studies should thus focus on the particular LTC use outcomes with insufficient evidence, and on sarcopenia.
We found important heterogeneity across studies in terms of i) type of frailty indicator used, ii) statistical analysis, and iii) reporting of results. This heterogeneity made it difficult to compare or transpose the results from one study to another. Overall, 12 different physical frailty measures and three sarcopenia indicators were used (altogether in one study). Almost all studies used multidimensional frailty indexes (most of which based on self-reported data), with a majority using either the original 5 items Fried frailty index (with categorisation into robust, pre-frail, frail) (16, 18, 21–24, 30), the Tilburg frailty indicator (17, 22, 26) or composite frailty indexes counting the number (or percentage) of deficits accumulated (27, 28, 31). In one study, sarcopenia was defined using clinical assessment of appendicular lean mass, muscle strength, and gait speed (20).
Most studies used multivariate regression analyses controlling for several of the following covariates: age, gender, morbidity, disability, and some basic sociodemographic characteristics such as education, living arrangements, or income. However, none of the studies included exactly the same number and types of controls, making the comparing of results difficult. Moreover, in only few instances the rationale for including specific controls was provided. One study performed sensitivity analysis with respect to the model specification. We conclude that future studies should carefully explain and justify their model, and perform sensitivity analyses regarding model specification (inclusion or exclusion of covariates). Despite the fact that a majority of studies relied on cohort data, very few used statistical methods designed to reduce unobserved confounding using longitudinal or panel data models (e.g. fixed effects or correlated random effects models). Specifically, only two studies analysed LTC outcome in relation with frailty transitions (19, 24), among which only one used fixed effect model to control for time invariant confounders (24). Future studies investigating the association between frailty and LTC use should consider using more advanced designs and more robust statistical methods such as the one suggested.
Finally, the studies were highly heterogeneous in terms of reporting of results. Studies using binary outcomes reported the results either in terms of raw estimates, odds ratio, or marginal effects. Studies using continuous outcomes (e.g., costs or time between events) reported either hazard ratio or risk ratio. We thus recommend that future studies report results that can be compared across settings, such as reporting average marginal effects, which can be computed using linear or non-linear (e.g., logit, probit) models.
In conclusion, our article is the first systematic literature review to focus on the relationship between frailty and sarcopenia, operationalized using existing validated measures, on various LTC outcomes among people worldwide. Overall, there is evidence suggesting that frailty is a key correlate of LTC use. But there is still a lack of evidence on the relationship between sarcopenia and LTC use, due an insufficient number of studies that investigated that issue. However, the strength of evidence is heterogeneous and varies according to the type of LTC outcome considered. Overall, the quality of studies was judged weak to moderate. Very few studies were considered as providing strong evidence, in particular because of weaknesses in statistical analyses performed, although many studies relied on cohort data. Future studies should address potential confounding using longitudinal models allowing integrating the effect of within-individual heterogeneity and assessing the effect of transitions into frailty (or sarcopenia) on LTC use. Moreover, the studies should perform sensitivity analyses by varying the control variables or using stratified analyses. In particular, it is of importance to know if the effect of frailty varies according to predefined socio-economic categories (32). This information would be useful for the definition of appropriate LTC policies aiming at ensuring equity of access.
With regards to the implications, our systematic literature review supports three main orientations for aging policies. First, eligibility criteria for public allowances should include frailty measures because evidence shows that regardless of the measure used, frailty is associated with increased LTC use. Second, the challenges associated with frailty among older people are global, since correlations between frailty measures and LTC use are similar across countries. This calls for global aging initiatives, to learn from each country’s experience. Third, frailty prevention in older populations is a policy priority. While many countries (France, Germany, Netherlands etc.) implemented disability reforms, future policies should also target frail populations, and enhance innovations to detect frailty in the 65-75 age group.
Funding and acknowledgements: The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n° 115621, resources of which are composed of financial contribution from the European Union’ Seventh Framework Programme (FP7 / 2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies’ in kind contribution.
Conflicts of Interest: None of the authors report any conflict of interest whatsoever.
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