Building resilience and reversing frailty: a randomised controlled trial of a primary care intervention for older adults.

BACKGROUND: There is a need for effective primary care interventions that help older people combat frailty and build resilience. OBJECTIVE: To study the effectiveness of an optimised exercise and dietary protein intervention. DESIGN: Multicentre, randomised-controlled, parallel-arm trial. SETTING: Six primary care practices, Ireland. METHODS: Six general practitioners enrolled adults aged 65+ with Clinical Frailty Scale score ≤5 from December 2020 to May 2021. Participants were randomised to intervention or usual care with allocation concealed until enrolment. Intervention comprised a 3-month home-based exercise regime, emphasising strength, and dietary protein guidance (1.2 g/kg/day). Effectiveness was measured by comparing frailty levels, based on the SHARE-Frailty Instrument, on an intention-to-treat basis. Secondary outcomes included bone mass, muscle mass and biological age measured by bioelectrical impedance analysis. Ease of intervention and perceived health benefit were measured on Likert scales. RESULTS: Of the 359 adults screened, 197 were eligible and 168 enrolled; 156 (92.9%) attended follow-up (mean age 77.1; 67.3% women; 79 intervention, 77 control). At baseline, 17.7% of intervention and 16.9% of control participants were frail by SHARE-FI. At follow-up, 6.3 and 18.2% were frail, respectively. The odds ratio of being frail between intervention and control groups post-intervention was 0.23 (95% confidence interval: 0.07-0.72; P = 0.011), adjusting for age, gender and site. Absolute risk reduction was 11.9% (CI: 0.8%-22.9%). Number needed to treat was 8.4. Grip strength (P < 0.001) and bone mass (P = 0.040) improved significantly. 66.2% found the intervention easy, 69.0% reported feeling better. CONCLUSION: A combination of exercises and dietary protein significantly reduced frailty and improved self-reported health.

Involving older people in co-designing an intervention to reverse frailty and build resilience.

BACKGROUND: An essential consideration in health research is to conduct research with members of the public rather than for them. Public and patient involvement (PPI) of older people in research can improve enrolment, relevance and impact. However, few studies with PPI in frailty research have been identified. PPI has fallen during the Covid-19 pandemic. OBJECTIVE: We aimed to involve older people in co-designing a randomised control trial (RCT) intervention to reverse frailty and build resilience. We also wished to encourage wider use of PPI with older people by outlining our approach. METHODS: Involvement of older people was undertaken in three stages. Eighteen over 65-year-olds helped co-design an exercise intervention in two group discussions using the Socratic education method. Ninety-four contributed intervention feedback in one-on-one telephone interviews over nine months. Ten contributors helped optimise the intervention in three online workshops. Multidisciplinary team input and systematic review supported co-design. RESULTS: Eleven home-based resistance exercises were co-designed by group discussion contributors (mean age 75, 61% female). Frailty intervention format, gender balance and GP follow-up were shaped in telephone interviews (mean age 77, 63% female). Dietary guidance and patient communication were co-designed in workshops (mean age 71, 60% females). Technology proved no barrier to PPI. The co-designed frailty intervention is being evaluated in a definitive RCT. CONCLUSIONS: We enabled meaningful the involvement of 112 older people in the co-design of an intervention to reverse frailty and build resilience in diverse ways. Inclusive involvement can be achieved during a pandemic. Feedback enhanced intervention feasibility for real-world primary-care.

Our research paper describes how we involved 112 older adults in the co-design of an intervention aiming to reverse frailty and build resilience. Involving participants in research can improve its feasibility and impact. However, there have been few studies involving older people in frailty research and involvement has fallen further during the Covid-19 pandemic. Involvement of older people was undertaken in three stages. Eighteen over 65-year-olds helped co-design an exercise intervention in two group discussions. Ninety-four older adults contributed intervention feedback in one-on-one telephone interviews over nine months. Ten contributors helped optimise the intervention in three online workshops. The co-designed intervention involved resistance exercises and dietary guidance and will be tested in a full randomised control trial. We enabled the meaningful involvement of 112 older people in our research in diverse ways. Inclusive involvement can be achieved during a pandemic.

What are the mechanisms that support healthcare professionals to adopt assisted decision-making practice? A rapid realist review.

BACKGROUND: The United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) establishes a right to legal capacity for all people, including those with support needs. People with disabilities have a legal right to be given the appropriate supports to make informed decisions in all aspects of their lives, including health. In Ireland, the Assisted Decision-Making (Capacity) Act (2015) ratifies the Convention and has established a legal framework for Assisted Decision Making (ADM). The main provisions of the Act are not yet implemented. Codes of Practice to guide health and social care professionals are currently being developed. Internationally, concerns are expressed that ADM implementation is poorly understood. Using realist synthesis, this study aims to identify Programme Theory (PT) that will inform ADM implementation in healthcare. METHODS: A Rapid Realist Review using collaborative methods was chosen to appraise relevant literature and engage knowledge users from Irish health and social care. The review was led by an expert panel of relevant stakeholders that developed the research question which asks, 'what mechanisms enable healthcare professionals to adopt ADM into practice?' To ensure the PT was inclusive of local contextual influences, five reference panels were conducted with healthcare professionals, family carers and people with dementia. PT was refined and tested iteratively through knowledge synthesis informed by forty-seven primary studies, reference panel discussions and expert panel refinement and consensus. RESULTS: The review has developed an explanatory PT on ADM implementation in healthcare practice. The review identified four implementation domains as significant. These are Personalisation of Health & ADM Service Provision, Culture & Leadership, Environmental & Social Re-structuring and Education, Training & Enablement. Each domain is presented as an explanatory PT statement using realist convention that identifies context, mechanism and outcome configurations. CONCLUSIONS: This realist review makes a unique contribution to this field. The PT can be applied by policymakers to inform intervention development and implementation strategy. It informs the imminent policy and practice developments in Ireland and has relevance for other worldwide healthcare systems dealing with similar legislative changes in line with UNCRPD.

Enabling public, patient and practitioner involvement in co-designing frailty pathways in the acute care setting.

BACKGROUND: Although not an inevitable part of ageing, frailty is an increasingly common condition in older people. Frail older patients are particularly vulnerable to the adverse effects of hospitalisation, including deconditioning, immobility and loss of independence (Chong et al, J Am Med Dir Assoc 18:638.e7-638.e11, 2017). The 'Systematic Approach to improving care for Frail older patients' (SAFE) study co-designed, with public and patient representatives, quality improvement initiatives aimed at enhancing the delivery of care to frail older patients within an acute hospital setting. This paper describes quality improvement initiatives which resulted from a co-design process aiming to improve service delivery in the acute setting for frail older people. These improvement initiatives were aligned to five priority areas identified by patients and public representatives. METHODS: The co-design work was supported by four pillars of effective and meaningful public and patient representative (PPR) involvement in health research (Bombard et al, Implement Sci 13:98, 2018; Black et al, J Health Serv Res Policy 23:158-67, 2018). These pillars were: research environment and receptive contexts; expectations and role clarity; support for participation and inclusive representation and; commitment to the value of co-learning involving institutional leadership. RESULTS: Five priority areas were identified by the co-design team for targeted quality improvement initiatives: Collaboration along the integrated care continuum; continence care; improved mobility; access to food and hydration and improved patient information. These priority areas and the responding quality improvement initiatives are discussed in relation to patient-centred outcomes for enhanced care delivery for frail older people in an acute hospital setting. CONCLUSIONS: The co-design approach to quality improvement places patient-centred outcomes such as dignity, identity, respectful communication as well as independence as key drivers for implementation. Enhanced inter-personal communication was consistently emphasised by the co-design team and much of the quality improvement initiatives target more effective, respectful and clear communication between healthcare personnel and patients. Measurement and evaluation of these patient-centred outcomes, while challenging, should be prioritised in the implementation of quality improvement initiatives. Adequate resourcing and administrative commitment pose the greatest challenges to the sustainability of the interventions developed along the SAFE pathways. The inclusion of organisational leadership in the co-design and implementation teams is a critical factor in the success of interventions targeting service delivery and quality improvement.

Using geographic information systems to map older people's emergency department attendance for future health planning.

OBJECTIVES: This study aimed to assess the pattern of use of EDs, factors contributing to the visits, geographical distribution and outcomes in people aged 65 years or older to a large hospital in Dublin. METHODS: A retrospective analysis of 2 years of data from an urban university teaching hospital ED in the southern part of Dublin was reviewed for the period 2014-2015 (n=103 022) to capture the records of attenders. All ED presentations by individuals 65 years and older were extracted for analysis. Address-matched records were analysed using QGIS, a geographic information systems (GIS) analysis and visualisation tool to determine straight-line distances travelled to the ED by age. RESULTS: Of the 49 538 non-duplicate presentations in the main database, 49.9% of the total are women and 49.1% are men. A subset comprised of 40 801 had address-matched records. When mapped, the data showed a distinct clustering of addresses around the hospital site but this clustering shows different patterns based on age cohort. Average distances travelled to ED are shorter for people 65 and older compared with younger patients. Average distances travelled for those aged 65-74 was 21 km (n=4177 presentations); for the age group 75-84, 18 km (n=2518 presentations) and 13 km for those aged 85 and older (n=2104 presentations). This is validated by statistical tests on the clustered data. Self-referral rates of about 60% were recorded for each age group, although this varied slightly, not significantly, with age. CONCLUSIONS: Health planning at a regional level should account for the significant number of older patients attending EDs. The use of GIS for health planning in particular can assist hospitals to improve their understanding of the origin of the cohort of older ED patients.

Dyslipidemias in the prevention of cardiovascular disease: risks and causality.

Atherosclerotic cardiovascular disease is now the major global cause of death, despite reductions in CVD deaths in developed societies. Dyslipidemias are a major contributor, but the mass occurrence of CVD relates to the combined effects of hyperlipidemia, hypertension, and smoking. Total blood cholesterol and LDL-cholesterol relate to CVD risk in an independent and graded manner and fulfill the criteria for causality. Therapeutic reduction of these lipid fractions is associated with improved outcomes. There is good evidence that HDL-cholesterol, triglycerides, and Lp(a) relate to CVD although the evidence for a causal relationship is weaker. The HDL association with CVD is largely independent of other risk factors whereas triglycerides may be more important as signaling a need to look intensively for other measures of risk such as central obesity, hypertension, low HDL-cholesterol, and glucose intolerance. Lp(a) is an inherited risk marker. The benefit of lowering it is uncertain, but it may be that its impact on risk is attenuated if LDL-cholesterol is low.

Testing the feasibility of a primary-care exercise intervention to prevent and reverse early frailty and build resilience in community-dwelling older adults.

Background: Resistance exercises have been shown to prevent and reverse frailty but their application in clinical practice is low. We wished to test the feasibility of an optimised exercise intervention for mild or pre-frailty in a primary-care setting and inform the design of a definitive randomised control trial. Methods: The intervention was co-designed with eighteen older adults in two group workshops, informed by systematic review and meta-analysis. Eligible patients aged 65+, mildly frail or less, presenting to an Irish primary-care centre over 6 months from January 2020 were invited to participate. They were offered an exercise guide and educational discussion. Demographics, health indicators and frailty scores were recorded. Feasibility was assessed using the Bowen model for acceptability; participation; demand; implementation; practicality; adaptation; integration; expansion; and limited-efficacy. Half of the randomly selected participants were telephoned after one month, and all the participants were called after two to measure effects on adherence. Findings: 94 of 107 eligible people (88%) participated (average age 77, 59 women (63%)). Only 15% had previously considered resistance exercises. The intervention satisfied all Bowen feasibility criteria. At one month, 65% of participants were exercising. At two months, adherence amongst those previously called was higher: 78%. 87% described exercises as 'very easy' or 'somewhat easy'. 66% felt 'much better' or 'slightly better'. Interpretation: Frailty intervention uptake and adherence were high. A single telephone call appeared to help increase adherence. Participants reported meaningful physical and mental health benefits. Funding: Roman Romero-Ortuno is funded by a grant from Science Foundation Ireland (SFI), grant number 18/FRL/6188.

Hypertension Pharmacological Treatment in Adults: A World Health Organization Guideline Executive Summary.

Hypertension is a major cause of cardiovascular disease and deaths worldwide especially in low- and middle-income countries. Despite the availability of safe, well-tolerated, and cost-effective blood pressure (BP)-lowering therapies, <14% of adults with hypertension have BP controlled to a systolic/diastolic BP <140/90 mm Hg. We report new hypertension treatment guidelines, developed in accordance with the World Health Organization Handbook for Guideline Development. Overviews of reviews of the evidence were conducted and summary tables were developed according to the Grading of Recommendations, Assessment, Development, and Evaluations approach. In these guidelines, the World Health Organization provides the most current and relevant evidence-based guidance for the pharmacological treatment of nonpregnant adults with hypertension. The recommendations pertain to adults with an accurate diagnosis of hypertension who have already received lifestyle modification counseling. The guidelines recommend BP threshold to initiate pharmacological therapy, BP treatment targets, intervals for follow-up visits, and best use of health care workers in the management of hypertension. The guidelines provide guidance for choice of monotherapy or dual therapy, treatment with single pill combination medications, and use of treatment algorithms for hypertension management. Strength of the recommendations was guided by the quality of the underlying evidence; the tradeoffs between desirable and undesirable effects; patient's values, resource considerations and cost-effectiveness; health equity; acceptability, and feasibility consideration of different treatment options. The goal of the guideline is to facilitate standard approaches to pharmacological treatment and management of hypertension which, if widely implemented, will increase the hypertension control rate world-wide.

Total cardiovascular disease risk assessment: a review.

PURPOSE OF REVIEW: The high risk strategy for the prevention of cardiovascular disease (CVD) requires an assessment of an individual's total CVD risk so that the most intensive risk factor management can be directed towards those at highest risk. Here we review developments in the assessment and estimation of total CVD risk. RECENT FINDINGS: Recent advances have focused on newer approaches to expressing risk, including lifetime risk and risk age; these are particularly useful in communicating risk to younger individuals. Additionally, increased emphasis has been placed on the role of body weight and abdominal obesity in CVD risk. Several recent large studies have clarified a number of issues relevant to the management of CVD risk, a matter of growing global concern. SUMMARY: Simple risk estimation systems utilizing only easily measured variables have a role in improving the accessibility and cost effectiveness of risk estimation. The addition of newer variables to risk estimation systems may be particularly useful for those at intermediate risk, in order to more correctly reclassify such individuals into appropriate risk categories.

Relationships between body mass index, cardiovascular mortality, and risk factors: a report from the SCORE investigators.

BACKGROUND: Although cardiovascular disease (CVD) is the biggest global cause of death, CVD mortality is falling in developed countries. There is concern that this trend may be offset by increasing levels of obesity. DESIGN: We used the Systematic Coronary Risk Evaluation (SCORE) data set to examine relationships between body mass index (BMI), conventional risk factors and CVD mortality. METHODS: The SCORE data set comprises data from 12 European cohort studies. The relationship between BMI and CVD mortality was examined in each BMI category using univariable and multivariable (Cox) analyses. The SCORE population was also divided into gender and age strata: under 40, 40-49, 50-59, and over 60. The rate of CVD mortality in each BMI category was calculated within each gender and age stratum. Relationships between BMI and other CVD risk factors were also examined. RESULTS: There was a strong, graded but J-shaped univariable relationship between BMI and CVD mortality in both genders. Each 5-unit increase in BMI was associated with an increase in CVD mortality of 34% in men and 29% in women. The hazard ratios remained significant when adjusted for age, self-reported smoking status, total cholesterol, and systolic blood pressure (SBP). On additional adjustment for diabetes and high-density lipoprotein cholesterol (HDL), the association between BMI and CVD mortality did not persist. In all age groups except those over 60 there were significant relationships between increased BMI and CVD mortality. In the over-60 age group the only significant relationships with mortality were in underweight and severely overweight women and mildly obese men. After adjustment for age, each 1-unit increase in BMI was associated with a 1.14 mmHg increase in SBP, 0.055 mmol/l increase in total cholesterol, and a 0.024 mmol/l decrease in HDL in men. Figures were slightly lower in women. CONCLUSIONS: Overall, overweight and obesity relate to CVD mortality in a strong and graded manner. The effects are greater in women and markedly so in younger persons. It is likely that a substantial part of the BMI-associated risk of CVD mortality is mediated through other known CVD risk factors. This increases the public health importance of BMI as both a simple indicator and mediator of CVD risk.

Integrin α(IIb)ß3 exists in an activated state in subjects with elevated plasma homocysteine levels.

Elevated levels of plasma homocysteine (Hcy) are an independent risk factor for cardiovascular disease and thrombosis. The molecular basis for this phenomenon is not known but may relate to modification of cell surface thiols. The platelet specific integrin α(IIb)ß3 is a cysteine-rich cell adhesion molecule that plays a critical role in platelet aggregation and adhesion in haemostasis and thrombosis. In this study, we looked for evidence of a homocysteine-induced modification of α(IIb)ß3 using a fluorescently labeled PAC-1 antibody that recognizes the activated conformation of the integrin on the platelet surface. We show that exogenous Hcy (10-100 µM) and homocysteine thiolactone (HcyTL) (10-100 µM) increased PAC-1 binding to platelets in a concentration dependent manner in vitro. In parallel, we show subjects with clinical hyperhomocysteinemia exhibit a greater degree of activation of α(IIb)ß3 compared to age-matched controls. These findings demonstrate that circulating Hcy can modulate the activation state of the platelet integrin α(IIb)ß3, a key player in platelet aggregation and thrombosis.

Simplifying cardiovascular risk estimation using resting heart rate.

AIMS: Elevated resting heart rate (RHR) is a known, independent cardiovascular (CV) risk factor, but is not included in risk estimation systems, including Systematic COronary Risk Evaluation (SCORE). We aimed to derive risk estimation systems including RHR as an extra variable and assess the value of this addition. METHODS AND RESULTS: The National FINRISK study (including 14,997 men and 15,861 women) was used to derive two formulas for estimation of 10 year risk of CV disease (CVD) mortality. The first formula contained current SCORE variables-total cholesterol, systolic blood pressure, smoking, age and gender. Inclusion of RHR resulted in only minor improvements in discrimination, based on both area under receiver operating characteristic curve (AUROC, men: 0.840 from 0.838, P = 0.5038; women: 0.87 from 0.865, P = 0.0522) and net reclassification index (NRI). The second, simplified formula contained only, age, smoking, gender, and body mass index. Addition of RHR to this simplified formula resulted in a statistically significant and meaningful improvement in AUROC (men: 0.819 from 0.812, P = 0.037; women: 0.862 from 0.827, P = 0.023) and NRI (0.05). Calibration also improved. A simple chart for estimating 10 year risk of fatal CVD including RHR is presented. CONCLUSION: Addition of RHR to formulas already containing lipid and blood pressure measures does not appreciably improve risk estimation. However, inclusion of RHR in simple systems, which can potentially enhance cost-effectiveness and accessibility of risk estimation, is useful.

Systematic Coronary Risk Evaluation (SCORE): JACC Focus Seminar 4/8.

Clinical estimation of the combined effect of several risk factors is unreliable and this resulted in the development of a number of risk estimation systems to guide clinical practice. Here, after defining general principles of risk estimation, the authors describe the evolution of the European Society of Cardiology's (ESC) Systematic COronary Risk Evaluation (SCORE) risk estimation system and some learnings from the data. They move on to describe the establishment of the ESC's Cardiovascular Risk Collaboration and outline its proposed research directions. First among these is the evolution of SCORE 2, which provides updated, calibrated risk estimates for total cardiovascular events for low, moderate, high, and very high-risk regions of Europe. The authors conclude by considering that the future of risk estimation may be to express risk as years of exposure to a cardiovascular risk factor profile rather than risk over a fixed time period, such as 10 years, and how advances in genetics may permit individualized lifetime risk estimation from childhood on.

Elevated resting heart rate is an independent risk factor for cardiovascular disease in healthy men and women.

BACKGROUND: Elevated resting heart rate (RHR) is known to be associated with reduced survival but inconsistencies remain, including lack of significance in most studies of healthy women, lack of independence from systolic blood pressure (SBP) in some, and the suggestion that RHR is merely functioning as a marker of physical inactivity or other comorbidities. We aimed to clarify these inconsistencies. METHODS: We analyzed the effect of RHR on end points in the National FINRISK Study; a representative, prospective study using Cox proportional hazards model. Ten-thousand five-hundred nineteen men and 11,334 women were included, excluding those with preexisting coronary heart disease, angina, heart failure, or on antihypertensive therapy. RESULTS: The hazard ratios for cardiovascular disease (CVD) mortality for each 15 beats/min increase in RHR were 1.24 (1.11-1.40) in men and 1.32 (1.08-1.60) in women, adjusted for age, gender, total cholesterol, physical activity (categorical), SBP, body mass index, and high-density lipoprotein cholesterol. This relationship remained significant after exclusion of those with comorbidities and events occurring within first 2 years of observation. Relationship with coronary mortality was stronger and with total mortality was slightly weaker. Inclusion of nonfatal end points weakened the relationship. CONCLUSIONS: A strong, graded, independent relationship between RHR and incident CVD was demonstrated. This was consistent in healthy men and women. We have clarified that the relationship is independent of SBP and that the temporal sequence would be compatible with a causal relationship. New findings include independence from both a validated measure of physical activity and comorbidities and the demonstration of a stronger effect for fatal than nonfatal events, supporting increased arrhythmogenicity of one of the mechanisms.

Italian cardiovascular mortality charts of the CUORE project: are they comparable with the SCORE charts?

BACKGROUND: The aim of this study was to build risk charts for the assessment of cardiovascular mortality of the CUORE project, an Italian longitudinal study, and to compare them with the systematic coronary risk evaluation (SCORE) project charts for low risk European countries. DESIGN: Random population samples enrolled in the 1980s and 1990s in Italy were included in the analysis: 7,520 men and 13,127 women aged 35-69 years without previous cardiovascular events and with a mean follow-up period of 10 years for cardiovascular disease. ICD-9 codes of death certificates similar to those of the SCORE project were considered when they appear as first cause of death. METHODS: Sex-stratified Cox proportional hazard model including age, systolic blood pressure, ratio between total and HDL cholesterol, and smoking habit as risk factors was used to assess cardiovascular mortality. RESULTS: Analysis showed that all risk factors included in the model were statistically significant. The corresponding area under the receiver operating characteristic curve was 0.825 (95% confidence interval: 0.803-0.846) for men and 0.850 (0.823-0.877) for women. The CUORE project charts yielded similar results to the corresponding charts of the SCORE project: Lin's coefficient was 0.929 for men and 0.935 for women. CONCLUSION: The comparison between CUORE and SCORE mortality risk charts shows that SCORE charts reflect quite well the Italian cardiovascular mortality and, correspondingly, Italian cohorts of the CUORE project are quite representative of European countries at low risk for cardiovascular mortality.

Assessment of cardiovascular risk.

Atherosclerotic cardiovascular disease (CVD) is the most common cause of death worldwide. Usually atherosclerosis is caused by the combined effects of multiple risk factors. For this reason, most guidelines on the prevention of CVD stress the assessment of total CVD risk. The most intensive risk factor modification can then be directed towards the individuals who will derive the greatest benefit. To assist the clinician in calculating the effects of these multiple interacting risk factors, a number of risk estimation systems have been developed. This review address several issues regarding total CVD risk assessment: Why should total CVD risk be assessed? What risk estimation systems are available? How well do these systems estimate risk? What are the advantages and disadvantages of the current systems? What are the current limitations of risk estimation systems and how can they be resolved? What new developments have occurred in CVD risk estimation?

Primary care interventions to address physical frailty among community-dwelling adults aged 60 years or older: A meta-analysis.

INTRODUCTION: The best interventions to address frailty among older adults have not yet been fully defined, and the diversity of interventions and outcome measures makes this process challenging. Consequently, there is a lack of guidance for clinicians and researchers regarding which interventions are most likely to help older persons remain robust and independent. This paper uses meta-analysis to assess effectiveness of primary care interventions for physical frailty among community-dwelling adults aged 60+ and provides an up-to-date synthesis of literature in this area. METHODS: PubMed, CINAHL, Cochrane Register of Controlled Trials, and PEDro databases were searched, and RCTs, controlled pilot studies, or trials with similar study designs addressing frailty in the primary care setting among persons aged 60+ were chosen. Study data was abstracted following PRISMA guidelines, then meta-analysis was performed using the random effects model. RESULTS: 31 studies with a total of 4794 participants were analysed. Interventions using predominantly resistance-based exercise and nutrition supplementation seemed to improve frailty status versus control (RR = 0.62 (CI 0.48-0.79), I2 = 0%). Exercise plus nutrition education also reduced frailty (RR = 0.69 (CI 0.58-0.82), I2 = 0%). Exercise alone seemed effective in reducing frailty (RR = 0.63 (CI 0.47-0.84), I2 = 0%) and improving physical performance (RR = 0.43 (CI 0.18-0.67), I2 = 0%). Exercise alone also appeared superior to control in improving gait speed (SMD = 0.36 (CI 0.10-0.61, I2 = 74%), leg strength (SMD = 0.61 (CI 0.09-1.13), I2 = 87%), and grip strength (Mean Difference = 1.08 (CI 0.02-2.15), I2 = 71%) though a high degree of heterogeneity was observed. Comprehensive geriatric assessment (RR = 0.77 (CI 0.64-0.93), I2 = 0%) also seemed superior to control in reducing frailty. CONCLUSION: Exercise alone or with nutrition supplementation or education, and comprehensive geriatric assessment, may reduce physical frailty. Individual-level factors and health systems resource availability will likely determine configuration of future interventions.