Frailty inclusive care in acute and community-based settings: a systematic review protocol

Background Frailty is a known risk factor for an array of adverse outcomes including more frequent and prolonged health services use and high health care costs. Aging of the population has implications for care provision across the care continuum, particularly for people living with frailty. Despite known risks associated with frailty, there has been limited research on care pathways that address the needs of persons living with frailty. Our study aims to review and examine, in a rigorous way, the quality of evidence for multi-component interventions and care pathways focused on frailty. Methods A comprehensive electronic search strategy will be used to identify studies that evaluate multi-component interventions or care pathways for persons living with frailty. The search strategy will include terms for frailty, multi-component interventions, effectiveness, and cost effectiveness applied to the following databases: MEDLINE (OVID), EMBASE (OVID), CINAHL (EBSCO), Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews. An adapted search for Google Scholar and gray literature databases will also be used. References of included studies will be hand-searched for additional citations of frailty-inclusive care. Known experts and corresponding authors of identified articles will be contacted by email to identify further eligible studies. Risk of bias will be assessed using the Effective Public Health Practice Project Quality Assessment tool. Data will be extracted from eligible studies and it is anticipated that narrative analysis will be used. If studies with sufficient homogeneity are found, then pooled effects will be reported using meta-analysis. Discussion This review will appraise the evidence currently available on multi-component frailty interventions. Results will inform on clinical pathway development for people living with frailty across the care continuum and will guide future research to address gaps in the literature and areas in need of further development. Systematic review registration PROSPERO CRD42020166733 Supplementary Information The online version contains supplementary material available at 10.1186/s13643-021-01638-0.


Background
The general health and functional status of patients prior to acute illness and other stressors are accepted as important determinants of hospital outcomes [1,2]. This status can be captured by measuring frailty, an agerelated state of increased vulnerability with disproportionate changes in health status in response to stressors [3]. This creates the opportunity to develop and implement care protocols that are tailored to the health needs of persons who live with frailty.
As the worldwide population ages, the associated increase in prevalence of frailty across the care continuum presents urgent challenges to providing consistently appropriate care. Recent findings from cohort studies have shown prevalence of frailty in the Canadian adult community population is 8-24%, increasing as age advances from 2% (18-34 years) to 20% (≥65 years) [4,5]. Frailty is common in assisted living environments (29%), and among adults admitted to ICU (28-32%) [6][7][8][9]. Frailty in hospitalized patients has been associated with gradient increases in hospital mortality, intensity of organ support, frequency and duration of health services use, and cost, when compared to non-frail patients [8][9][10].
Despite knowledge that frailty presents high risk for suboptimal outcomes, development and evaluation of comprehensive frailty interventions appears limited to specific circumstances such as improving patient flow after surgery (enhanced recovery after surgery [ERAS]), addressing frailty-related diseases or disability (e.g., delirium, dementia, depression), and providing focused interventions (e.g., nutrition, exercise) in acute and community-based care settings. The opportunity to view frailty as a multi-system syndrome is often overlooked by generic pathways where aspects of frailty are entirely unnoticed or assumed to be addressed by broad criteria such as chronological age. Frailty inclusive care, as defined herein, is an approach to care in any setting that starts with authentic frailty case-finding, followed by further assessment of the underlying vulnerabilities (components), and then leading to advance care planning, general measures to prevent or slow progression, and specific steps to address frailty components. Frailty inclusive care interventions may be generic, or may be specific to medical condition or care setting.
The primary aim of this project is to rigorously examine and document the quality of evidence for multicomponent interventions (e.g., frailty-inclusive care pathways) encompassing the broader patient journey through both community and hospital care. In so doing, we will be mindful of a variety of frailty constructs and measures, and the ways that frailty inclusive care has been operationalized using different frailty assessment measures, evaluated based on any comparators and outcomes across patient populations. This will directly inform further development and implementation of frailty-specific recommendations as part of a larger program of work in this area.

Methods/design
The full systematic review protocol is registered with the International Prospective Register of Systematic Reviews (PROSPERO) (ID CRD42020166733, April 28, 2020). A recent search of PROSPERO and the Cochrane Library indicated there were no registered reviews focused on the proposed topic. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRIS MA-P) checklist is included as an additional file [11] (Additional file 1).

Search methodology and screening
The search strategy will be developed by an information specialist, in partnership with the broader review team and peer-reviewed by a second information specialist. The initial search strategy will be translated for use across bibliographic databases and web search engines. We will identify potentially relevant studies by searching the following bibliographic databases from 2000 onwards (i.e., when frailty became a term used in research) in all languages, using a combination of keywords (i.e., free text) and MeSH terms: MEDLINE (OVID), EMBASE (OVID), CINAHL (EBSCO), Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews (CDSR) ( Table 1).
Other searches and strategies will include Google Scholar; ProQuest Dissertation and Theses Global; World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and clinicaltrials.gov for ongoing trials; published abstracts; and conference proceedings for 2 years prior to search date. An a priori list of websites which may contain eligible studies that have not been indexed will also be reviewed (Table 2).
Citations identified by the searches will be deduplicated in EndNote (Clarivate Analytics, v.9.), then uploaded to a Covidence (Veritas Health Innovation, Melbourne, Australia) library. Studies reported in languages other than English will be translated to English using Google Translate [12]. Two reviewers will independently screen the titles and abstracts of studies identified by the search (i.e., primary screening). Studies that meet the predetermined eligibility criteria from title and abstract review will undergo screening of full text (i.e., secondary screening) by two independent reviewers. Any disagreements will be resolved by consensus or the decision of a third party.

Study selection
We will include studies in any clinical setting that use an established frailty measure for case-finding. To 6 (Fried* adj2 (definition or index or phenotyp* or scor*)).tw,kf. 7 (functional-status and (low or poor*)).tw,kf. 8 (geriatric adj2 (assess* or evaluat* or screen*)).tw,kf. improve consistency, a table of 93 eligible frailty measures was compiled from 13 literature reviews over the past decade, and classified based on the model of frailty (i.e., physical frailty, cumulative deficit, multidimensional, geriatric syndromes) and the method of administration (i.e., clinicianreport, clinician-judgment, self-report, performance-based, anthropometric, calculated) [13][14][15][16][17][18][19][20][21][22][23][24][25] (Table 3). To qualify as multi-component, more than one intervention must be present, targeting different components of frailty. The multicomponent intervention may include advance care planning, general measures to prevent or slow progression (e.g., a combined exercise and nutritional program), and detailed steps to address frailty. Specific interventions responding to components of frailty identified in particular individuals may include problems with cognition, mood, balance and mobility, continence, medications, and social support.

Eligibility criteria Population
The population of interest is all adult patients (≥18 years) defined as living with frailty, assessed by a validated frailty measurement, in acute, intermediate, or community-based care settings.

Intervention
We will identify multi-component interventions that have been developed and evaluated for their impact on individuals living with frailty, and the health services that comprise their care. Any intervention that can be applied to the broader patient journey through both community and hospital care will be included. Examples of interventions of interest include enhanced recovery after surgery (ERAS), multi-component fast track surgery programs or "prehabilitation," hospital to community transition processes, or care pathways that identify frailty and trigger comprehensive geriatric assessment (CGA) to address components of frailty. Interventions (e.g., pharmacological treatments, rehabilitative therapies, nutritional counseling) that are implemented independently or do not influence the overall care plan will be excluded, unless they are used in combination. Screening for frailty without intervention or CGA without the use of frailty measures to inform a personalized assessment or care plan will be excluded.

Comparisons
All comparisons will be included. We anticipate that in most cases usual care within hospital and/or the community will be compared to the intervention.

Outcomes
Outcomes include those associated with evaluation of multi-component frailty care implementation, including process measures (e.g., measures of fidelity; acceptability; feasibility) targeting any person living with frailty, health service utilization (i.e., readmission, contact with services), health outcomes (e.g., adverse events, morbidity, mortality, institutionalization), economic outcomes (e.g., cost, cost-effectiveness), and patient-oriented measures (e.g., quality of life, well-being, satisfaction with care, caregiver burden).

Study designs
We will consider all randomized trials (e.g., patient level or cluster), non-randomized controlled trials (e.g., before/after and time-series), observational studies, and cross-sectional studies. Publications will be excluded if a single intervention or no intervention was applied, no evaluation was conducted, if they contain no valid

Quality appraisal
Studies selected for inclusion will be assessed for risk of bias by two independent reviewers using the Effective Public Healthcare Practice Project instrument to assess the quality of quantitative studies [121]. This instrument has been considered suitable for assessment of risk of bias in systematic reviews where randomized and nonrandomized study designs were included [122,123]. Disagreements will be resolved by consensus or adjudication of a third party. Summary scores from the instrument will inform synthesis of information and exploration of heterogeneity in study results [121,124,125].

Data extraction
A data extraction form will be developed and piloted on a sample of included records in Microsoft Office Excel (v. 2016, Microsoft Corporation, Redmond, WA) to ensure adequate capture of characteristics and findings of included studies. One reviewer will extract the data from each primary study independently, then another will verify the accuracy of the extracted data. Disagreements will be settled through discussion with a third author.
The following information will be extracted from each included study:

Study characteristics
Author, year, publication type, trial registration number, funding source, setting (country, system of health care, acute/community/primary care), theoretical framing, research question(s), aims of study, design, population, sample, recruitment procedure, outcome measures, test statistics, key findings, limitations as noted by authors and reviewers, conclusions as noted by authors, reviewer notes.

Population
Sample size, inclusion/exclusion, number of enrolled and analyzed, description of cases/controls, reasons for withdrawal, missing data, age, proportion female, ethnicity, reason for admission, frailty definition, measure/instrument to identify of frailty, training for frailty instrument application, co-morbidities (dementia, mildcognitive impairment, known risk for/occurrence of post-treatment delirium, history of falls, occurrence/history of urinary infections/bedsores, other physical health diagnoses, malnutrition), subgroups analyzed in the study. Physical frailty Self-report and performance

Intervention/strategy
Intervention/strategy name, aim of intervention, intervention description, who delivered the intervention, professionals/others involved, intervention setting, intervention recipient, use of manual/guidelines for intervention, frequency of each intervention component, duration of each intervention component, assessment of fidelity, method of data collection, timing of data collection in relation to intervention, cost of intervention.

Data analysis
We anticipate a variety of study designs and methods of assessing complex interventions will pose challenges in conducting a meta-analysis. If a meta-analysis is not possible we will pool what data we can, reporting the limitations of our findings. In this case, we will describe findings in a narrative synthesis. To ensure a systematic approach to the narrative synthesis, the guidelines proposed by Cochrane will be adhered to [126]. The narrative will be structured according to study design, type and delivery of interventions, setting, and population. Similarities and differences between findings observed across studies and patterns in data will be outlined. Any data available will be transformed in attempts to find common descriptive and statistical formats for analysis. Within and between study differences will be explored for explanations of direction and size of effects of interventions. Effects of heterogeneity among studies will be discussed, particularly with respect to theoretical framing that may provide explanations for heterogeneity. Finally, the overall strength of the synthesis will be assessed by evaluating the risk of bias results, quality of the evidence, and an overall critical reflection on the synthesis methods [126].
If there are a sufficient number of similar interventions, effects will be pooled using random effects metaanalysis in RevMan (RevMan 5.3 Cochrane). Heterogeneity will be assessed both qualitatively to assess if metaanalysis should be used and measured formally using the I-squared statistic if possible with publication bias assessed using funnel plots. If meta-analysis is used, the following subgroup analyses will be considered: age, setting (e.g., community-based care vs. acute care, teaching vs. community hospitals), and acute ward types (e.g., ICU, medicine, surgical, specialist geriatric units, outpatient, emergency department).

Discussion
Frailty is a relatively new term, and describes both the state of exaggerated vulnerability associated with agerelated deficit accumulation, and the associated multidimensional syndrome. To be acceptable to clinicians and the patients they serve, frailty must meaningfully inform decisions about care. As the population ages, health care systems face growing numbers of patients with frailty who may derive less benefit or even more harm from aggressive interventions and invasive procedures while adding cost across the system [127,128]. In present circumstances, where specialist geriatrician resources are limited, the entire health care workforce needs to be empowered with valid methods of screening for frailty and delivering bespoke models of care [129]. Frailty inclusive care pathways may provide useful guidance in the care of older patients living with frailty in hospital, intermediate and community settings, where clinicians may benefit from presentation of precise considerations in specific patient populations (e.g., primary care, emergency department, surgery) who transition between care settings. Consistent frailty screening and application of frailty-inclusive interventions through existing care pathways and routine care may provide meaningful context to all associated decisions and care provided for this vulnerable population.

Limitations
Despite our aging population and expected increased incidence of frailty across the care continuum, we expect that there will be limited evidence of evaluation of multi-component interventions aimed to improve care and outcomes for people living with frailty. We expanded the search strategy to maximize findings, although results may demonstrate heterogeneous study designs and frailty assessment methods, limiting our ability to pool data and make inferences for practice. Moreover, we did not include patient or public input in our protocol development and may have focused on a limited perspective of frailty inclusive care. Regardless of the potential limitations we are committed to finding evidence of frailty pathways with rigorous evaluation to inform future practice where possible.

Conclusions
Frailty-inclusive care interventions that can be incorporated into existing pathways for any disease or clinical setting are an essential part of care continuity for people living with frailty. This review will inform future work to develop and implement pathways aiming to improve the care received by this vulnerable population.
Additional file 1: Additional Table 1. PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols) 2015 checklist CLM and GH contributed to writing the draft manuscript. All authors contributed to protocol development. All authors read and approved the final manuscript. All authors confirm their responsibility for its present form. CLM is guarantor of the review.

Funding
Funding to support this review was provided by a grant from the Alberta Health Services Critical Care Strategic Clinical Network (SCN) 2019 Systematic Review competition. The Government of Alberta provided partial support for involvement by Dr. Montgomery and Dr. Hopkin in the study through a grant to the Network of Alberta Health Economists. The terms of the grants mean they are unrestricted and there was no oversight from the Government of Alberta or Critical Care SCN on the topic, methods, results, or interpretation of the study. There was no involvement of funding organizations in the decision to publish.
Availability of data and materials Not applicable.

Declarations
Ethics approval and consent to participate Ethics review is not required by the University of Alberta. The review targets previously published articles. No personally identifiable information will be obtained.

Consent for publication
Not applicable.

Competing interests
All authors report no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work. Carmel Montgomery is supported by a Network of Alberta Health Economists fellowship award and was a 2017 Canadian Frailty Network Interdisciplinary Fellow. Dr. Bagshaw holds a Canada Research Chair in Critical Care Nephrology and is a scientific director for the Alberta Health Services Critical Care Strategic Clinical Network. Dr. Rolfson was a key member of the research group that developed and validated the Edmonton Frail Scale.

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