Evaluating the Value for Money of Precision Medicine from Early Cycle to Market Access: A Comprehensive Review of Approaches and Challenges.

OBJECTIVES: This study aimed to perform a comprehensive review of modeling approaches and methodological and policy challenges in the economic evaluation (EE) of precision medicine (PM) across clinical stages. METHODS: First, a systematic review was performed to assess the approaches of EEs in the past 10 years. Next, a targeted review of methodological articles was conducted for methodological and policy challenges in performing EEs of PM. All findings were synthesized into a structured framework that focused on patient population, Intervention, Comparator, Outcome, Time, Equity and ethics, Adaptability and Modeling aspects, named the "PICOTEAM" framework. Finally, a stakeholder consultation was conducted to understand the major determinants of decision making in PM investment. RESULTS: In 39 methodological articles, we identified major challenges to the EE of PM. These challenges include that PM applications involve complex and evolving clinical decision space, that clinical evidence is sparse because of small subgroups and complex pathways in PM settings, a one-time PM application may have lifetime or intergenerational impacts but long-term evidence is often unavailable, and that equity and ethics concerns are exceptional. In 275 EEs of PM, current approaches did not sufficiently capture the value of PM compared with targeted therapies, nor did they differentiate Early EEs from Conventional EEs. Finally, policy makers perceived the budget impact, cost savings, and cost-effectiveness of PM as the most important determinants in decision making. CONCLUSIONS: There is an urgent need to modify existing guidelines or develop a new reference case that fits into the new healthcare paradigm of PM to guide decision making in research and development and market access.

Group Model Building on causes and interventions for falls in Singapore: insights from a systems thinking approach.

BACKGROUND: Falls in older adults are the result of a complex web of interacting causes, that further results in other physical, emotional, and psychological sequelae. A conceptual framework that represents the reciprocal dynamics of these causal factors can enable clinicians, researchers, and policymakers to clarify goals in falls intervention in older adults. METHODS: A Group Model Building (GMB) exercise was conducted with researchers and clinicians from academic units and public healthcare institutes in Singapore. The aim of the exercise was to produce a shared visual representation of the causal structure for falls and engage in discussions on how current and future falls intervention programmes can address falls in the older adults, especially in the Asian context. It was conducted in four steps: 1) Outlining and prioritising desirable patient outcomes, 2) Conceptual model building, 3) Identifying key intervention elements of effective falls intervention programmes, 4) Mapping of interventions to outcomes. This causal loop diagram (CLD) was then used to generate insights into the current understanding of falls causal relationships, current efforts in falls intervention in Singapore, and used to identify gaps in falls research that could be further advanced in future intervention studies. RESULTS: Four patient outcomes were identified by the group as key in falls intervention: 1) Falls, 2) Injurious falls, 3) Fear of falling, and 4) Restricted mobility and life space. A CLD of the reciprocal relationships between risk factors and these outcomes are represented in four sub-models: 1) Fear of falling, 2) Injuries associated with falls, 3) Caregiver overprotectiveness, 4) Post-traumatic stress disorder and psychological resilience. Through this GMB exercise, the group gained the following insights: (1) Psychological sequelae of falls is an important falls intervention outcome. (2) The effects of family overprotectiveness, psychological resilience, and PTSD in exacerbating the consequences of falls are not well understood. (3) There is a need to develop multi-component falls interventions to address the multitude of falls and falls related sequelae. CONCLUSION: This work illustrates the potential of GMB to promote shared understanding of complex healthcare problems and to provide a roadmap for the development of more effective preventive actions.

Development of a real-world database for asthma and COPD: The SingHealth-Duke-NUS-GSK COPD and Asthma Real-World Evidence (SDG-CARE) collaboration.

PURPOSE: The SingHealth-Duke-GlaxoSmithKline COPD and Asthma Real-world Evidence (SDG-CARE) collaboration was formed to accelerate the use of Singaporean real-world evidence in research and clinical care. A centerpiece of the collaboration was to develop a near real-time database from clinical and operational data sources to inform healthcare decision making and research studies on asthma and chronic obstructive pulmonary disease (COPD). METHODS: Our multidisciplinary team, including clinicians, epidemiologists, data scientists, medical informaticians and IT engineers, adopted the hybrid waterfall-agile project management methodology to develop the SingHealth COPD and Asthma Data Mart (SCDM). The SCDM was developed within the organizational data warehouse. It pulls and maps data from various information systems using extract, transform and load (ETL) pipelines. Robust user testing and data verification was also performed to ensure that the business requirements were met and that the ETL pipelines were valid. RESULTS: The SCDM includes 199 data elements relevant to asthma and COPD. Data verification was performed and found the SCDM to be reliable. As of December 31, 2019, the SCDM contained 36,407 unique patients with asthma and COPD across the spectrum from primary to tertiary care in our healthcare system. The database updates weekly to add new data of existing patients and to include new patients who fulfil the inclusion criteria. CONCLUSIONS: The SCDM was systematically developed and tested to support the use RWD for clinical and health services research in asthma and COPD. This can serve as a platform to provide research and operational insights to improve the care delivered to our patients.

Incentives for Uptake of and Adherence to Outpatient Stroke Rehabilitation Services: A 3-Arm Randomized Controlled Trial.

OBJECTIVE: To determine if rehabilitation uptake and adherence can be increased by providing coordinated transportation (increased convenience) and eliminating out-of-pocket costs (reduced expense). DESIGN: Three-arm randomized controlled trial. SETTING: Stroke units of 2 Singapore tertiary hospitals. PARTICIPANTS: Singaporeans or permanent residents 21 years or older who were diagnosed as having stroke and were discharged home with physician's recommendation to continue outpatient rehabilitation (N=266). INTERVENTIONS: A Transportation Incentives arm (T), which provides free transportation services, a Transportation & Sessions Incentives arm (T&S), offering free transportation and prescribed stroke rehabilitation sessions, and a control arm, Education (E), consisting of a stroke rehabilitation educational program. MAIN OUTCOME MEASURES: The primary study outcome was uptake of outpatient rehabilitation services (ORS) among patients poststroke and key predefined secondary outcomes being number of sessions attended and adherence to prescribed sessions. RESULTS: Uptake rate of ORS was 73.0% for E (confidence interval [CI], 63.8%-82.3%), 81.8% for T (CI, 73.8%-89.8%), and 84.3% for T&S (CI, 76.7%-91.8%). Differences of T and T&S vs E were not statistically significant (P=.22 and P=.10, respectively). However, average number of rehabilitation sessions attended were significantly higher in both intervention arms: 5.50±7.65 for T and 7.51±9.52 for T&S vs 3.26±4.22 for control arm (E) (T vs E: P=.017; T&S vs E: P<.001). Kaplan-Meier analysis indicated that persistence was higher for T&S compared with E (P=.029). CONCLUSIONS: This study has demonstrated a possibility in increasing the uptake of and persistence to stroke ORS with free transportation and sessions. Incentivizing survivors of stroke to take up ORS is a new strategy worthy of further exploration for future policy change in financing ORS or other long-term care services.

Developing integration among stakeholders in the primary care networks of Singapore: a qualitative study.

BACKGROUND: Integrating healthcare services across and between the different health system levels can be achieved in a few ways; however, examining the social side of integration is essential and challenging. This paper explores the concept of integration perceived by general practitioners (GPs) and primary care network (PCN) representatives from the regional health systems (RHS) in a GP-RHS PCN and their perceived partnership success. METHODS: In this study, we explored three GP-RHS PCNs in Singapore. We used a qualitative research design and, overall, performed 17 semi-structured in-depth interviews with GPs (n = 11) and PCN representatives (n = 6) from the RHS. All interviews were audiotaped and transcribed verbatim. We conducted thematic analysis to inductively identify themes from the data. Singer's conceptual model of integration types was used as guiding principles to derive relevant and salient themes for integration. RESULTS: GPs and the RHS perceived the concept of integration through a series of interrelated strategies. Within the normative dimension, a sense of urgency motivated GPs to integrate improvements into their general practice. Participants perceived teamwork and relational climate as appropriate enablers for achieving interpersonal integration in a primary care partnership. While developing a trusted relationship was a perceived success of this partnership across the network, developing camaraderie and gaining knowledge in chronic disease management through the components of functional integration was a perceived success at an individual general practice level. The data also revealed some operational challenges within the structural dimension and some inabilities of the PCN to achieve complete process integration. CONCLUSIONS: Our study points to multi-faceted integration, comprising various forms that need to be manifested at all levels of care to achieve coordinated, seamless, and comprehensive care for patients suffering from chronic conditions. The present iteration of the PCN has been shown to offer integration at a level that warrants praise but still requires structural and process integration improvement.

Population Segmentation Based on Healthcare Needs: Validation of a Brief Clinician-Administered Tool.

BACKGROUND: As populations age with increasingly complex chronic conditions, segmenting populations into clinically meaningful categories of healthcare and related service needs can provide healthcare planners with crucial information to optimally meet needs. However, while conventional approaches typically involve electronic medical records (EMRs), such records do not always capture information reliably or accurately. OBJECTIVE: We describe the inter-rater reliability and predictive validity of a clinician-administered tool, the Simple Segmentation Tool (SST) for categorizing older individuals into one of six Global Impression (GI) segments and eight complicating factors (CFs) indicative of healthcare and related social needs. DESIGN: Observational study ( ClinicalTrials.gov , number NCT02663037). PARTICIPANTS: Patients aged 55 years and above. MAIN MEASURES: Emergency department (ED) subjects (between May and June 2016) had baseline SST assessment by two physicians and a nurse concurrently seeing the same individual. General medical (GM) ward subjects (February 2017) had a SST assessment by their principal physician. Adverse events (ED visits, hospitalizations, and mortality over 90 days from baseline) were determined by a blinded reviewer. Inter-rater reliability was measured using Cohen's kappa. Predictive validity was evaluated using Cox hazard ratios based on time to first adverse event. KEY RESULTS: Cohen's kappa between physician-physician, service physician-nurse, and physician-nurse pairs for GI were 0.60, 0.71, and 0.68, respectively. Cox analyses demonstrated significant predictive validity of GI and CFs for adverse outcomes. CONCLUSIONS: With modest training, clinicians can complete a brief instrument to segment their patient into clinically meaningful categories of healthcare and related service needs. This approach can complement and overcome current limitations of EMR-based instruments, particularly with respect to whole-patient care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02663037.

Long-term quality of life, sexual health and gastrointestinal function following colorectal cancer resection in an Asian cohort.

AIM: As populations age and cancer management improves, long-term survivorship and quality-of-life (QOL) outcomes are becoming equally important as oncological results. Data from Asian populations are scarce. We aimed to evaluate the sexual health, gastrointestinal function and QOL amongst colorectal cancer survivors in a tertiary referral centre in Singapore. METHOD: Adults who had undergone elective curative surgery for non-metastatic colorectal cancer at least 2 years prior were included. Exclusion criteria were cognitive disease, serious postoperative complications or recurrent cancer. Participants were invited to complete the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires EORTC-QLQ-C30 and QLQ-CR29. Using multiple bivariate analysis, r scores were used to examine relationship trends between QOL domains and survivor sociodemographic and disease-specific characteristics. RESULTS: From February 2017 to July 2019, 400 responses were recorded. Median age and follow-up duration were 64 years (range 32-90) and 78 months (interquartile range 49-113) respectively. Patients who had Stage III cancer had better overall QOL scores compared to Stage I/II. Rectal (vs. colon) cancer negatively influenced sexual health and gastrointestinal function, but did not appear to affect overall QOL. Amongst our cohort, 57% (n = 129) of men and 43% (n = 75) of women were sexually active. Markers of socioeconomic status, including employment, education and housing type, were found to significantly impact perception of various aspects of QOL. CONCLUSION: Knowledge of factors which influence well-being can identify individuals who may benefit from tailored management strategies. Regular patient-doctor contact may play a role in building and maintaining positive perspectives of cancer survivors. Normative data should be obtained from local populations to facilitate future comparative research.

Coronavirus disease 2019 (COVID-19): an evidence map of medical literature.

BACKGROUND: Since the beginning of the COVID-19 outbreak in December 2019, a substantial body of COVID-19 medical literature has been generated. As of June 2020, gaps and longitudinal trends in the COVID-19 medical literature remain unidentified, despite potential benefits for research prioritisation and policy setting in both the COVID-19 pandemic and future large-scale public health crises. METHODS: In this paper, we searched PubMed and Embase for medical literature on COVID-19 between 1 January and 24 March 2020. We characterised the growth of the early COVID-19 medical literature using evidence maps and bibliometric analyses to elicit cross-sectional and longitudinal trends and systematically identify gaps. RESULTS: The early COVID-19 medical literature originated primarily from Asia and focused mainly on clinical features and diagnosis of the disease. Many areas of potential research remain underexplored, such as mental health, the use of novel technologies and artificial intelligence, pathophysiology of COVID-19 within different body systems, and indirect effects of COVID-19 on the care of non-COVID-19 patients. Few articles involved research collaboration at the international level (24.7%). The median submission-to-publication duration was 8 days (interquartile range: 4-16). CONCLUSIONS: Although in its early phase, COVID-19 research has generated a large volume of publications. However, there are still knowledge gaps yet to be filled and areas for improvement for the global research community. Our analysis of early COVID-19 research may be valuable in informing research prioritisation and policy planning both in the current COVID-19 pandemic and similar global health crises.

Do healthcare needs-based population segments predict outcomes among the elderly? Findings from a prospective cohort study in an urbanized low-income community.

BACKGROUND: A rapidly ageing population with increasing prevalence of chronic disease presents policymakers the urgent task of tailoring healthcare services to optimally meet changing needs. While healthcare needs-based segmentation is a promising approach to efficiently assessing and responding to healthcare needs at the population level, it is not clear how available schemes perform in the context of community-based surveys administered by non-medically trained personnel. The aim of this prospective cohort, community setting study is to evaluate 4 segmentation schemes in terms of practicality and predictive validity for future health outcomes and service utilization. METHODS: A cohort was identified from a cross-sectional health and social characteristics survey of Singapore public rental housing residents aged 60 years and above. Baseline survey data was used to assign individuals into segments as defined by 4 predefined population segmentation schemes developed in Singapore, Delaware, Lombardy and North-West London. From electronic data records, mortality, hospital admissions, emergency department visits, and specialist outpatient clinic visits were assessed for 180 days after baseline segment assignment and compared to segment membership for each segmentation scheme. RESULTS: Of 1324 residents contacted, 928 agreed to participate in the survey (70% response). All subjects could be assigned an exclusive segment for each segmentation scheme. Individuals in more severe segments tended to have lower quality of life as assessed by the EQ-5D Index for health utility. All population segmentation schemes were observed to exhibit an ability to differentiate different levels of mortality and healthcare utilization. CONCLUSIONS: It is practical to assign individuals to healthcare needs-based population segments through community surveys by non-medically trained personnel. The resulting segments for all 4 schemes evaluated in this way have an ability to predict health outcomes and utilization over the medium term (180 days), with significant overlap for some segments. Healthcare needs-based segmentation schemes which are designed to guide action hold particular promise for promoting efficient allocation of services to meet the needs of salient population groups. Further evaluation is needed to determine if these schemes also predict responsiveness to interventions to meet needs implied by segment membership.

Associations between superoxide dismutase, malondialdehyde and all-cause mortality in older adults: a community-based cohort study.

BACKGROUND: Oxidative stress is an important theory of aging but population-based evidence has been lacking. This study aimed to evaluate the associations between biomarkers of oxidative stress, including plasma superoxide dismutase (SOD) activity and malondialdehyde (MDA), with all-cause mortality in older adults. METHODS: This is a community-based cohort study of 2224 participants (women:1227, median age: 86 years). We included individuals aged 65 or above and with plasma SOD activity and/or MDA tests at baseline. We evaluated the hazard ratios (HRs) and 95% confidence intervals (CIs) by multivariable Cox models. RESULTS: We documented 858 deaths during six years of follow-up. There was a significant interaction effect of sex with the association between SOD activity and mortality (P < 0.001). Compared with the lowest quintile, the risk of all-cause mortality was inversely associated with increasing quintiles of plasma SOD activity in women(P-trend< 0.001), with adjusted HRs for the second through fifth quintiles of 0.73 (95% CI 0.53-1.02), 0.52(95% CI 0.38-0.72), 0.53(95% CI 0.39-0.73), and 0.48(95% CI 0.35-0.66). There were no significant associations between SOD activity and mortality in men (P-trend = 0.64), and between MDA and mortality in all participants (P-trend = 0.79). CONCLUSIONS: Increased activity of SOD was independently associated with lower all-cause mortality in older women but not in men. This epidemiological study lent support for the free radical/oxidative stress theory of aging.

Can acute clinical outcomes predict health-related quality of life after stroke: a one-year prospective study of stroke survivors.

BACKGROUND: Health-related quality of life (HRQoL) is a key metric to understand the impact of stroke from patients' perspective. Yet HRQoL is not readily measured in clinical practice. This study aims to investigate the extent to which clinical outcomes during admission predict HRQoL at 3 months and 1 year post-stroke. METHODS: Stroke patients admitted to five tertiary hospitals in Singapore were assessed with Shah-modified Barthel Index (Shah-mBI), National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), Mini-Mental State Examination (MMSE), and Frontal Assessment Battery (FAB) before discharge, and the EQ-5D questionnaire at 3 months and 12 months post-stroke. Association of clinical measures with the EQ index at both time points was examined using multiple linear regression models. Forward stepwise selection was applied and consistently significant clinical measures were analyzed for their association with individual dimensions of EQ-5D in multiple logistic regressions. RESULTS: All five clinical measures at baseline were significant predictors of the EQ index at 3 months and 12 months, except that MMSE was not significantly associated with the EQ index at 12 months. NIHSS (3-month standardized ß = - 0.111; 12-month standardized ß = - 0.109) and mRS (3-month standardized ß = - 0.122; 12-month standardized ß = - 0.080) were shown to have a larger effect size than other measures. The contribution of NIHSS and mRS as significant predictors of HRQoL was mostly explained by their association with the mobility, self-care, and usual activities dimensions of EQ-5D. CONCLUSIONS: HRQoL at 3 months and 12 months post-stroke can be predicted by clinical outcomes in the acute phase. NIHSS and mRS are better predictors than BI, MMSE, and FAB.

Short-Term Trajectories of Depressive Symptoms in Stroke Survivors and Their Family Caregivers.

GOAL: We utilize group-based trajectory modeling (GBTM) to delineate depressive symptom trajectories among stroke survivor-caregiver dyads, to identify predictors of the delineated trajectories, and to assess the influence of time-varying covariates (stroke survivor depressive symptoms and functional disability, caregiver depressive symptoms, and foreign domestic worker [FDW] assistance) on the level of the depressive symptom trajectories. METHODS: Data on 172 stroke survivor-caregiver dyads in Singapore, for whom depressive symptoms were assessed thrice (baseline/3 months/6 months), were utilized. GBTM was applied to delineate depressive symptom trajectories, and to identify their predictors and time-varying covariates. FINDINGS: Three stroke survivor depressive symptom trajectories (low and decreasing [47.6%], low and increasing [43.1%], and high and increasing [9.3%]) and 2 caregiver depressive symptom trajectories (low and stable [71.5%] and high and decreasing [28.5%]) were delineated. Caregivers with chronic diseases were more likely (odds ratio [95% confidence interval]: 8.09[2.04-32.07]) and those caring for older stroke survivors (0.94[0.90-0.98]) were less likely to follow the high and decreasing than the low and stable depressive symptom trajectory. An increase in stroke survivor functional disability and caregiver depressive symptoms led to a rise (~worsening) in stroke survivor depressive symptom trajectories. Whereas an increase in stroke survivor depressive symptoms led to a rise in caregiver depressive symptom trajectories, FDW assistance led to a decline (~improvement). CONCLUSION: Care professionals should be mindful of heterogeneity in depressive symptom patterns over time among stroke survivor-caregiver dyads. Reciprocal association of depressive symptoms in the stroke survivor-caregiver dyad suggests that addressing mood problems in 1 member may benefit the other member, and calls for dyadic mental health interventions.

A Causal View of the Role and Potential Limitations of Capitation in Promoting Whole Health System Performance.

For several decades, health systems in developed countries have faced rapidly rising healthcare costs without concomitant improvements in health outcomes. Fee for service (FFS) reimbursement mechanisms (RMs), where health systems are paid based on volume, contribute to this trend. In Singapore, the public health service is trying to curb rising healthcare costs by transitioning from a volume-based RM to a capitated payment for a population within a geographical catchment area. To provide insight into the implications of this transition, we developed a causal loop diagram (CLD) to represent a causal hypothesis of the complex relationship between RM and health system performance. The CLD was developed with input from government policymakers, healthcare institution administrators, and healthcare providers. This work highlights that the causal relationships between government, provider organizations, and physicians involve numerous feedback loops that drive the mix of health services. The CLD clarifies that a FFS RM incentivizes high margin services irrespective of their health benefits. While capitation has the potential to mitigate this reinforcing phenomenon, it is not sufficient to promote service value. This suggests the need to establish robust mechanisms to govern common pool resources while minimizing adverse secondary effects.

Health System Transformation Playbook and Unified Care Model: an integrated design, systems & complexity thinking approach to health system transformation.

Health system transformation is a complex journey that often results in unintended consequences. Existing methods to drive health system transformation have intrinsic limitations which impede successful implementation in local contexts. The Health System Transformation Playbook is a design-, systems-, and complexity-thinking enabled methodology to systematically design, prioritize and test health system and services transformation actions, anchored on iterative story telling, model building and pathfinding processes that tackles the scale of socially and technologically complex adaptive systems through time. The Unified Care Model and its associated cascade of models are examples of ongoing application of Health System Transformation Playbook in a regional population health system in Singapore. Use of Health System Transformation Playbook enables stewards of health systems to gain a more systematic and coherent understanding of health systems and services planning and organization development, to accelerate transformation towards people-centered, integrated and value-driven health systems.

Mapping the value for money of precision medicine: a systematic literature review and meta-analysis.

Objective: This study aimed to quantify heterogeneity in the value for money of precision medicine (PM) by application types across contexts and conditions and to quantify sources of heterogeneity to areas of particular promises or concerns as the field of PM moves forward. Methods: A systemic search was performed in Embase, Medline, EconLit, and CRD databases for studies published between 2011 and 2021 on cost-effectiveness analysis (CEA) of PM interventions. Based on a willingness-to-pay threshold of one-time GDP per capita of each study country, the net monetary benefit (NMB) of PM was pooled using random-effects meta-analyses. Sources of heterogeneity and study biases were examined using random-effects meta-regressions, jackknife sensitivity analysis, and the biases in economic studies checklist. Results: Among the 275 unique CEAs of PM, publicly sponsored studies found neither genetic testing nor gene therapy cost-effective in general, which was contradictory to studies funded by commercial entities and early stage evaluations. Evidence of PM being cost-effective was concentrated in a genetic test for screening, diagnosis, or as companion diagnostics (pooled NMBs, $48,152, $8,869, $5,693, p < 0.001), in the form of multigene panel testing (pooled NMBs = $31,026, p < 0.001), which only applied to a few disease areas such as cancer and high-income countries. Incremental effectiveness was an essential value driver for varied genetic tests but not gene therapy. Conclusion: Precision medicine's value for money across application types and contexts was difficult to conclude from published studies, which might be subject to systematic bias. The conducting and reporting of CEA of PM should be locally based and standardized for meaningful comparisons.

Association of quality-of-care indicators with asthma outcomes: A retrospective observational study for asthma care in Singapore.

Introduction: Asthma guidelines have advocated for the use of quality-of-care indicators (QCIs) in asthma management. To improve asthma care, it is important to identify effective QCIs that are actionable. This study aimed to evaluate the effect of the presence of 3 QCIs: asthma education, Asthma Control Test (ACT) and spirometry testing on the time to severe exacerbation (TTSE). Method: Data collected from the SingHealth COPD and Asthma Data Mart (SCDM), including asthma patients managed in 9 SingHealth polyclinics and Singapore General Hospital from January 2015 to December 2020, were analysed. Patients receiving Global Initiative for Asthma (GINA) Steps 3-5 treatment, with at least 1 QCI recorded, and at least 1 severe exacerbation within 1 year before the first QCI record, were included. Data were analysed using multivariate Cox regression and quasi-Poisson regression models. Results: A total of 3849 patients in the registry fulfilled the criteria. Patients with records of asthma education or ACT assessment have a lower adjusted hazard ratio (HR) for TTSE (adjusted HR=0.88, P=0.023; adjusted HR=0.83, P<0.001). Adjusted HR associated with spirometry is higher (adjusted HR=1.22, P=0.026). No QCI was significantly associated with emergency department (ED)/inpatient visits. Only asthma education and ACT showed a decrease in the number of exacerbations for multivariate analysis (asthma education estimate: -0.181, P<0.001; ACT estimate: -0.169, P<0.001). No QCI was significant for the number of exacerbations associated with ED/inpatient visits. Conclusion: Our study suggests that the perfor-mance of asthma education and ACT was associated with increased TTSE and decreased number of exacerbations, underscoring the importance of ensuring quality care in clinical practice.

Pragmatic multicentre stepped-wedge cluster randomised trial to investigate the effectiveness of community-based falls prevention programme for older adults with falls risk in Singapore: a protocol paper.

INTRODUCTION: Falls are an important public health issue with consequences that include injuries, quality of life reduction and high healthcare costs. Studies show that falls prevention strategies are effective in reducing falls rate among community-dwelling older adults. However, the evaluation for effectiveness was usually done in a controlled setting with homogeneous population, and thus may not be generalisable to a wider population. This study aims to evaluate the impact of community falls prevention programmes with group-based strength and balance exercises, on falls risk and health outcomes for older adults with falls risk in Singapore. METHODS AND ANALYSIS: This is a pragmatic closed cohort stepped-wedge cluster randomised trial design study, which involves sequential crossover of clusters from the waitlist control condition to the intervention condition, with the sequence of crossover randomly determined. The intervention will be sequentially rolled out to 12 clusters (a minimum of 5 participants/cluster), over 6 time periods with 8-week intervals in Central and North regions of Singapore. The primary analysis will be conducted under the intention-to-treat principle. A general linear mixed model or generalised estimating equation analysis appropriate for a multilevel longitudinal study incorporating an appropriate error distribution and link function will be used. Markov model will be developed to estimate the incremental cost per quality-adjusted life years and incremental cost per fall prevented from the implementation of falls prevention strategies from a societal perspective. Conditional on there being clinically relevant differences in short-term outcomes, we will implement simulation modelling to project the long-term divergence in trajectories for outcomes and costs using the Markov model. ETHICS AND DISSEMINATION: Ethics approval has been obtained. Results will be disseminated in publications and other relevant platforms. TRIAL REGISTRATION NUMBER: NCT04788251.

Systems modelling as an approach for eliciting the mechanisms for hip fracture recovery among older adults in a participatory stakeholder engagement setting.

Introduction: Due to an aging population, the rising prevalence and incidence of hip fractures and the associated health and economic burden present a challenge to healthcare systems worldwide. Studies have shown that a complex interplay of physiological, psychological, and social factors often affects the recovery trajectories of older adults with hip fractures, often complicating the recovery process. Methods: This research aims to actively engage stakeholders (including doctors, physiotherapists, hip fracture patients, and caregivers) using the systems modeling methodology of Group Model Building (GMB) to elicit the factors that promote or inhibit hip fracture recovery, incorporating a feedback perspective to inform system-wide interventions. Hip fracture stakeholder engagement was facilitated through the Group Model Building approach in a two-half-day workshop of 25 stakeholders. This approach combined different techniques to develop a comprehensive qualitative whole-system view model of the factors that promote or inhibit hip fracture recovery. Results: A conceptual, qualitative model of the dynamics of hip fracture recovery was developed that draws on stakeholders' personal experiences through a moderated interaction. Stakeholders identified four domains (i.e., expectation formation, rehabilitation, affordability/availability, and resilience building) that play a significant role in the hip fracture recovery journey.. Discussion: The insight that recovery of loss of function due to hip fracture is attributed to (a) the recognition of a gap between pre-fracture physical function and current physical function; and (b) the marshaling of psychological resilience to respond promptly to a physical functional loss via uptake of rehabilitation services is supported by findings and has several policy implications.

The associations between caregivers' psychosocial characteristics and caregivers' depressive symptoms in stroke settings: a cohort study.

BACKGROUND: Studies have found that caregivers can influence stroke survivors' outcomes, such as mortality. It is thus pertinent to identify significant factors associated with caregivers' outcomes. The study objective was to examine the associations between caregivers' psychosocial characteristics and caregivers' depressive symptoms. METHODS: The analysis obtained three-month and one-year post-stroke data from the Singapore Stroke Study, which was collected from hospital settings. Caregivers' depressive symptoms were assessed via the Center for Epidemiologic Studies Depression instrument. Psychosocial characteristics of caregivers included subjective burden (Zarit Burden Interview), quality of care-relationship (a modified 3-item scale from the University of Southern California Longitudinal Study of Three-Generation Families) and expressive social support (an 8-item scale from Pearlin et al.). Mixed effect Tobit regressions were used to examine the associations between these study variables. RESULTS: A total of 214 caregivers of stroke patients hospitalized were included in the final analysis. Most caregivers were Chinese women with secondary school education, unemployed and married to the patients. Caregivers' subjective burden was positively associated with their depressive symptoms (Partial regression coefficient: 0.18, 95% CI 0.11-0.24). Quality of care-relationship (Partial regression coefficient: - 0.35, 95% CI - 0.63 to - 0.06) and expressive social support (partial regression coefficient: - 0.28, 95% CI - 0.37 to - 0.19) were negatively associated with caregivers' depressive symptoms. Caregivers' depressive symptoms were higher at three-month post-stroke than one-year post-stroke (Partial regression coefficient: - 1.00, 95% CI - 1.80 to - 0.20). CONCLUSION: The study identified subjective burden, quality of care-relationship and expressive social support as significantly associated with caregivers' depressive symptoms. Caregivers' communication skills may also play a role in reducing caregivers' depressive symptoms.

Plasma acylcarnitines as metabolic signatures of declining health-related quality of life measure in community-dwelling older adults: a combined cross-sectional and longitudinal pilot study.

BACKGROUND: Health-related quality of life (HRQoL) measures are predictors of adverse health outcomes in older adults. Studies have demonstrated cross-sectional associations between HRQoL measures and blood-based biochemical markers. Acylcarnitines (ACs) are a class of metabolites generated in the mitochondria and are predictive of multiple geriatric syndromes. Changes in ACs reflect alterations in central carbon metabolic pathways. However, the prospective relationship between plasma acylcarnitines and declining HRQoL has not been examined. This study aimed to investigate both cross-sectional and longitudinal associations of baseline ACs with baseline and declining EuroQol-5 Dimension/ EuroQol Visual Analogue Scale (EQ-5D/ EQ-VAS) in community-dwelling older adults. METHODS: 120 community-dwelling older adults with EQ-5D/ EQ-VAS measurements at baseline and follow-up were included. We quantified ACs at baseline using targeted plasma metabolomics profiling. Multivariate regressions were performed to examine cross-sectional and longitudinal associations between the measures. RESULTS: Cross-sectionally, ACs showed no significant associations with either EQ-5D index or EQ-VAS scores. Longitudinally, multiple baseline short-chain ACs were significantly and inversely associated with declining EQ-5D index score, explaining up to 8.5% of variance in the decline. CONCLUSIONS: Within a cohort of community-dwelling older adults who had high HRQoL at baseline, we showed that short-chain acylcarnitines are independent predictors of declining HRQoL. These findings reveal a novel association between central carbon metabolic pathways and declining HRQoL. Notably, dysregulation in mitochondrial central carbon metabolism could be detected prior to clinically important decline in HRQoL, providing the first evidence of objective biomarkers as novel predictors to monitor HRQoL in non-pharmacological interventions and epidemiology.