A Study Protocol of Realist Evaluation of Palliative Home Care Program for Non-Cancer Patients in Singapore.

Introduction: Violet Program (ViP) was developed to address the current home palliative service gap for individuals with life limiting non-cancer conditions residing in the Eastern part of Singapore. While its basic principles and processes have been planned and implemented, how ViP works, for whom and in what circumstances are not yet well understood. Therefore, we propose for a realist evaluation (RE) - a theory-based evaluation, to address the current knowledge gaps. Evaluation findings may guide, support further development and broader uptake of ViP. Methods and Analysis: This study will be conducted in three phases: 1. development of initial program theory (IPT), 2. testing of programme theory, and 3. refinement of IPT. First, IPT will be elicited through review of programme documents, scoping review of reviews and in-depth interviews with stakeholders involved in the conceptualization of ViP. Then, a convergent mixed method study will be conducted to assess contexts (C), mechanisms (M) and outcomes (O) to test the IPT through interviews with stakeholders, surveys and analysis of program and administrative databases. Based on findings gathered and through consultation with respective stakeholders, IPT will be refined to highlight what works (outcomes), how (mechanisms) and for whom under what conditions (contexts).

A community-based single fall prevention exercise intervention for older adults (STEADY FEET): Study protocol for a randomised controlled trial.

BACKGROUND: Falls and fall-related injuries in older adults are a leading cause of disability and death. Evidence has shown the benefits of exercises in improving functional outcomes and reducing fall rates among community-dwelling older adults. However, there is lack of effective community-based single exercise intervention for a broad population of older adults who are at high risk for falls. We aim to evaluate the effectiveness of Steady Feet (SF), a 6-month tailored community fall prevention exercise programme for improving functional outcomes. SF classes are facilitated by community fitness instructors and an exercise video. The main outcome is between-group changes in short physical performance battery (SPPB) scores. Secondary outcomes include balance confidence, fear of falling, quality of life, fall rates, and cost effectiveness. METHODS: We present the design of a 6-month randomised controlled trial of 260 older adults (≥ 60 years old). Individuals will be randomised in a 1:1 allocation ratio to the SF group or usual care group. Participants will be assessed at baseline, 3-month, and 6-month. Data on socio-demographics, co-morbidities, balance confidence, fear of falling, quality of life, physical activity level, rate of perceived exertion, fall(s) history, healthcare utilisation and cost, and satisfaction levels will be collected. Participants will also undergo functional assessments such as SPPB. Moreover, providers' satisfaction and feedback will be obtained at 3-month. DISCUSSION: An effective community fall prevention programme may lead to improved functional outcomes and reduced fall rates. Findings will also help inform the implementation and scaling of SF nation-wide. TRIAL REGISTRATION: Clinicaltrials.gov registration: NCT04801316. Registered on 15th March 2021.

Exploring the dimensions of patient experience for community-based care programmes in a multi-ethnic Asian context.

INTRODUCTION: The aim of this study is to explore patients' experiences with community-based care programmes (CCPs) and develop dimensions of patient experience salient to community-based care in Singapore. Most countries like Singapore are transforming its healthcare system from a hospital-centric model to a person-centered community-based care model to better manage the increasing chronic disease burden resulting from an ageing population. It is thus critical to understand the impact of hospital to community transitions from the patients' perspective. The exploration of patient experience will guide the development of an instrument for the evaluation of CCPs for quality improvement purposes. METHODS: A qualitative exploratory study was conducted where face-to-face in-depth interviews were conducted using a purposive sampling method with patients enrolled in CCPs. In total, 64 participants aged between 41 to 94 years were recruited. A deductive framework was developed using the Picker Patient Experience instrument to guide our analysis. Inductive coding was also conducted which resulted in emergence of new themes. RESULTS: Our findings highlighted eight key themes of patient experience: i) ensuring care continuity, ii) involvement of family, iii) access to emotional support, vi) ensuring physical comfort, v) coordination of services between providers, vi) providing patient education, vii) importance of respect for patients, and viii) healthcare financing. CONCLUSION: Our results demonstrated that patient experience is multi-faceted, and dimensions of patient experience vary according to healthcare settings. As most patient experience frameworks were developed based on a single care setting in western populations, our findings can inform the development of a culturally relevant instrument to measure patient experience of community-based care for a multi-ethnic Asian context.

Mixed-method evaluation of CARITAS: a hospital-to-community model of integrated care for dementia.

OBJECTIVES: The capability and capacity of the primary and community care (PCC) sector for dementia in Singapore may be enhanced through better integration. Through a partnership involving a tertiary hospital and PCC providers, an integrated dementia care network (CARITAS: comprehensive, accessible, responsive, individualised, transdisciplinary, accountable and seamless) was implemented. The study evaluated the process and extent of integration within CARITAS. DESIGN: Triangulation mixed-methods design and analyses were employed to understand factors underpinning network mechanisms. SETTING: The study was conducted at a tertiary hospital in the northern region of Singapore. PARTICIPANTS: We recruited participants who were involved in the conceptualisation, design, development and implementation of the CARITAS Programme from a tertiary hospital and PCC providers. INTERVENTION: We used the Rainbow Model of Integrated Care-Measurement Tool (RMIC-MT) to assess integration from managerial perspectives. RMIC-MT comprises eight dimensions that play interconnected roles on a macro-level, meso-level and micro-level. We administered RMIC-MT to healthcare providers and conducted in-depth interviews with key CARITAS stakeholders. PRIMARY AND SECONDARY OUTCOME MEASURES: We assessed integration scores across eight dimensions of the RMIC-MT and factors underpinning network mechanisms. RESULTS: Compared with other dimensions, functional integration (mechanisms by which information and management modalities are linked) achieved the lowest mean score of 55. Other dimensions (eg, clinical, professional and organisational integration) scored about 70. Presence of inspiring clinical leaders and tacit interdependencies among partners strengthened the network. However, the lack of structured documentation and a shared information-technology platform hindered functional integration. CONCLUSION: CARITAS has reached maturity in micro-levels and meso-levels of integration, while macro-integration needs further development. Integration can be enhanced by assessing service gaps, increasing engagement with stakeholders and providing a shared communication system.

Shifting care from hospital to community, a strategy to integrate care in Singapore: process evaluation of implementation fidelity.

BACKGROUND: Accessibility to efficient and person-centered healthcare delivery drives healthcare transformation in many countries. In Singapore, specialist outpatient clinics (SOCs) are commonly congested due to increasing demands for chronic care. To improve this situation, the National University Health System (NUHS) Regional Health System (RHS) started an integrated care initiative,the Right-Site Care (RSC) program in 2014. Through collaborations between SOCs at the National University Hospital and primary and community care (PCC) clinics in the western region of the county, the program was designed to facilitate timely discharge and appropriate transition of patients, who no longer required specialist care, to the community. The aim of this study was to evaluate the implementation fidelity of the NUHS RHS RSC program using the modified Conceptual Framework for Implementation Fidelity (CFIF), at three distinct levels; providers, organizational, and system levels to explain outcomes of the program and to inform further development of (similar) programs. METHODS: A convergent parallel mixed methods study using the realist evaluation approach was used. Data were collected between 2016 and 2018 through non-participatory observations, reviews of medical records and program database, together with semi-structured interviews with healthcare providers. Triangulation of data streams was applied guided by the modified CFIF. RESULTS: Our findings showed four out of six program components were implemented with low level of fidelity, and 9112 suitable patients were referred to the program while 3032 (33.3%) declined to be enrolled. Moderating factors found to influence fidelity included: (i) complexity of program, (ii) evolving providers' responsiveness, (iii) facilitation through synergistic partnership, training of PCC providers by specialists and supportive structures: care coordinators, guiding protocols, shared electronic medical record and shared pharmacy, (iv) lack of organization reinforcement, and (v) mismatch between program goals, healthcare financing and providers' reimbursement. CONCLUSION: Functional integration alone is insufficient for a successful right-site care program implementation. Improvement in relationships between providers, organizations, and patients are also warranted for further development of the program.

Conducting a Cost-Benefit Analysis of Transitional Care Programmes: The Key Challenges and Recommendations.

Transitional care encompasses a range of services designed to promote care integration as patients transfer between different locations or different levels of care. Transitional care programmes have been proven to produce positive outcomes in reducing hospital readmissions and improving patients' health outcomes. However, little is known about the benefits of the programmes on healthcare cost and the published results have been inconsistent. With increasing healthcare expenditures and limited public healthcare resources, cost-benefit analyses become paramount in informing healthcare resource allocation decisions. This perspective paper describes the approaches used in estimating the total costs of a bundle of transitional care services from an academic medical centre, identifies the key methodological challenges encountered in the process of cost-benefit analysis, and recommends potential solutions to tackle these challenges. By providing a comprehensive perspective on the methodological challenges, this paper encourages program evaluators to take these possible challenges into consideration for future cost-benefit analyses.

Clinical determinants of physical activity and sedentary behaviour in individuals with schizophrenia.

INTRODUCTION: Modifiable lifestyle factors such as physical activity (PA) have ameliorative effects on commonly reported health conditions in schizophrenia like cardiovascular diseases and diabetes. Similarly, reduction in sedentary behaviour (SB) promotes better physical health. However, engaging individuals with schizophrenia in PA and less SB can be challenging because of symptoms of schizophrenia. The aims of the present study are (i) to examine the profiles of PA and SB in individuals with schizophrenia; and (ii) to identify their respective clinical determinants. METHOD: 157 individuals with schizophrenia were recruited. PA and SB were examined via the Global Physical Activity Questionnaire (GPAQ). Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Potential clinical predictors of PA and SB were identified via univariate regression analyses and subsequently included in the final multiple regression models for PA and SB respectively. RESULTS: 63.7% met the WHO PA guidelines. Work-related activity was the largest domain specific contribution towards PA. Mean duration of SB was approximately 9 h and about 57.3% reported at least 8 h or more of SB daily. Positive symptom was associated with engagement in PA and reduced duration of SB. Negative symptom was associated with greater SB. CONCLUSION: With emerging evidence of deleterious health effects of SB independent of PA, it is important to monitor SB in individuals with schizophrenia, particularly those presenting with negative symptoms. While the lack of treatment response for negative symptoms remains a challenge, effort should be made to reduce duration of SB.

Retrospective evaluation of healthcare utilisation and mortality of two post-discharge care programmes in Singapore.

OBJECTIVE: To evaluate the impact on healthcare utilisation frequencies and charges, and mortality of a programme for frequent hospital utilisers and a programme for patients requiring high acuity post-discharge care as part of an integrated healthcare model. DESIGN: A retrospective quasi-experimental study without randomisation where patients who received post-discharge care interventions were matched 1:1 with unenrolled patients as controls. SETTING: The National University Health System (NUHS) Regional Health System (RHS), which was one of six RHS in Singapore, implemented the NUHS RHS Integrated Interventions and Care Extension (NICE) programme for frequent hospital utilisers and the NUHS Transitional Care Programme (NUHS TCP) for high acuity post-discharge care. The programmes were supported by the Ministry of Health in Singapore, which is a city-state nation located in Southeast Asia with a 5.6 million population. PARTICIPANTS: Linked healthcare administrative data, for the time period of January 2013 to December 2016, were extracted for patients enrolled in NICE (n=554) or NUHS TCP (n=270) from June 2014 to December 2015, and control patients. INTERVENTIONS: For both programmes, teams conducted follow-up home visits and phone calls to monitor and manage patients' post-discharge. PRIMARY OUTCOME MEASURES: One-year pre- and post-enrolment healthcare utilisation frequencies and charges of all-cause inpatient admissions, emergency admissions, emergency department attendances, specialist outpatient clinic (SOC) attendances, total inpatient length of stay and mortality rates were compared. RESULTS: Patients in NICE had lower mortality rate, but higher all-cause inpatient admission, emergency admission and emergency department attendance charges. Patients in NUHS TCP did not have lower mortality rate, but had higher emergency admission and SOC attendance charges. CONCLUSIONS: Both NICE and NUHS TCP had no improvements in 1 year healthcare utilisation across various setting and metrics. Singular interventions might not be as impactful in effecting utilisation without an overhauling transformation and restructuring of the hospital and healthcare system.

Implementation fidelity of a strategy to integrate service delivery: learnings from a transitional care program for individuals with complex needs in Singapore.

BACKGROUND: To cope with rising demand for healthcare services in Singapore, Regional Health Systems (RHS) comprising of health and social care providers across care settings were set up to integrate service delivery. Tasked with providing care for the western region, in 2012, the National University Health System (NUHS) - RHS developed a transitional care program for elderly patients with complex healthcare needs who consumed high levels of hospital resources. Through needs assessment, development of personalized care plans and care coordination, the program aimed to: (i) improve quality of care, (ii) reduce hospital utilization, and (iii) reduce healthcare-related costs. In this study, recognizing the need for process evaluation in conjunction with outcome evaluation, we aim to evaluate the implementation fidelity of the NUHS-RHS transitional care program to explain the outcomes of the program and to inform further development of (similar) programs. METHODS: Guided by the modified version of the Conceptual Framework for Implementation Fidelity (CFIF), adherence and moderating factors influencing implementation were assessed using non-participatory observations, reviews of medical records and program databases. RESULTS: Most (10 out of 14) components of the program were found to be implemented with low or moderate level of fidelity. The frequency or duration of the program components were observed to vary based on the needs of users, availability of care coordinators (CC) and their confidence. Variation in fidelity was influenced predominantly by: (1) complexity of the program, (2) extent of facilitation through guiding protocols, (3) facilitation of program implementation through CCs' level of training and confidence, (4) evolving healthcare participant responsiveness, and (5) the context of suboptimal capability among community providers. CONCLUSION: This is the first study to assess the context-specific implementation process of a transitional care program in the context of Southeast Asia. It provides important insights to facilitate further development and scaling up of transitional care programs within the NUHS-RHS and beyond. Our findings highlight the need for greater focus on engaging both healthcare providers and users, training CCs to equip them with the relevant skills required for their jobs, and building the capability of the community providers to implement such programs.

The effects of clinical illness severity and physical activity on health-related quality of life in schizophrenia.

BACKGROUND: Quality of life is an important clinical outcome in individuals with schizophrenia. Illness severity and physical activity (PA) were independently reported to influence health-related quality of life (HRQoL) in people with schizophrenia. This study attempts to examine the intensity and types of PA and their impact on HRQoL, as well as the relative contributions of illness severity, PA, and sedentary behavior (SB) to HRQoL in people with schizophrenia. METHODS: Demographic information was collected from 297 community-dwelling individuals with schizophrenia. Severity of illness was assessed on the Clinical Global Impression-Severity (CGI-S); PA and SB were assessed on the Global Physical Activity Questionnaire (GPAQ); HRQoL was assessed on the RAND-36. Regression analyses were conducted to examine the impact of different types and intensities of PA on HRQoL, and the relative impact of CGI-S, GPAQ-PA, and GPAQ-SB on HRQoL. RESULTS: Most participants had low PA level, and travel is the main type of PA adopted. Leisure time, travel-related, work-related, moderate-, and vigorous-intensity PA were all not associated with HRQoL. Lower severity of illness was significantly associated with better physical (PHC), mental (MHC) and global (GHC) health composites of the RAND-36 (GHC: t = - 5.628, p < 0.001, PHC: t = - 4.026, p < 0.001, MHC: t = - 5.534, p < 0.001). Both PA and SB were not significantly associated with PHC, MHC, and GHC. CONCLUSION: Severity of illness has a significant impact on HRQoL in people with schizophrenia. However, we found no evidence to support the association between physical activity and sedentary behavior with HRQoL.

Right-Site Care Programme with a community-based family medicine clinic in Singapore: secondary data analysis of its impact on mortality and healthcare utilisation.

OBJECTIVE: Stable patients with chronic conditions could be appropriately cared for at family medicine clinics (FMC) and discharged from hospital specialist outpatient clinics (SOCs). The Right-Site Care Programme with Frontier FMC emphasised care organised around patients in community rather than hospital-based providers, with one identifiable primary provider. This study evaluated impact of this programme on mortality and healthcare utilisation. DESIGN: A retrospective study without randomisation using secondary data analysis of patients enrolled in the intervention matched 1:1 with unenrolled patients as controls. SETTING: Programme was supported by the Ministry of Health in Singapore, a city-state nation in Southeast Asia with 5.6 million population. PARTICIPANTS: Intervention group comprises patients enrolled from January to December 2014 (n=684) and control patients (n=684) with at least one SOC and no FMC attendance during same period. INTERVENTIONS: Family physician in Frontier FMC managed patients in consultation with relevant specialist physicians or fully managed patients independently. Care teams in SOCs and FMC used a common electronic medical records system to facilitate care coordination and conducted regular multidisciplinary case conferences. PRIMARY OUTCOME MEASURES: Deidentified linked healthcare administrative data for time period of January 2011 to December 2017 were extracted. Three-year postenrolment mortality rates and utilisation frequencies and charges for SOC, public primary care centres (polyclinic), emergency department attendances and emergency, non-day surgery inpatient and all-cause admissions were compared. RESULTS: Intervention patients had lower mortality rate (HR=0.37, p<0.01). Among those with potential of postenrolment polyclinic attendance, intervention patients had lower frequencies (incidence rate ratio (IRR)=0.60, p<0.01) and charges (mean ratio (MR)=0.51, p<0.01). Among those with potential of postenrolment SOC attendance, intervention patients had higher frequencies (IRR=2.06, p<0.01) and charges (MR=1.86, p<0.01). CONCLUSIONS: Intervention patients had better survival, probably because their chronic conditions were better managed with close monitoring, contributing to higher total outpatient attendance frequencies and charges.

Implementation of Integrated Care in Singapore: A Complex Adaptive System Perspective.

BACKGROUND: Integrated care that focuses on organising healthcare services around people and their communities rather than their diseases is promoted as the strategy to overcome the challenges associated with growing complexity in healthcare needs, demand for healthcare services and inadequate supply of services due to fragmentation in the provision of services. While conceptually appears to be simple, integrated care is made up of multicomponent delivery strategies targeting various levels of the healthcare system while engaging various stakeholders in their execution. METHODS: We applied the complex adaptive system (CAS) perspective to two different initiatives that exemplify approaches towards integrating care in Singapore: the Regional Health System (RHS) model, implemented across healthcare institutions at the national level, and CARITAS Integrated Dementia Care implemented in the northern region of Singapore. We adopted an inductive approach in our analysis in which we studied the RHS and CARITAS Integrated Dementia Care according to the components of the CAS. We applied the typical characteristics of CAS: (i) diverse, interdependent and semi-autonomous actors (ii) self-organizing capacity and simple rules (iii) relationship with the bigger system, emergent behaviour and non-linearity in our analysis of key drivers behind the implementation of both the RHS and CARITAS integrated dementia care. RESULTS: By considering the RHS and CARITAS as whole networks each comprising of interacting and adaptive components instead of separate entities within a bigger system, the CAS provided a new mind-set in surfacing issues associated to the implementation of these integrated care networks. In addition to important actors, systems, it informed understanding of relationships and dependencies between different parts of the network - revealing the lack of homogeneity, conformity and difficulties in designing any optimal system in advance given the many moving parts. CONCLUSIONS: Drawing on the two examples of integrated care networks, this paper highlights the significance of effective collaboration built on a common focus, responsiveness to emergent behaviours, simple rules, the ability to self-organize and adapt in response to unexpected situations in further development of integrated care in the Singapore context and beyond.

Realist evaluation of a complex integrated care programme: protocol for a mixed methods study.

INTRODUCTION: The lack of understanding of how complex integrated care programmes achieve their outcomes due to the lack of acceptable methods leads to difficulties in the development, implementation, adaptation and scaling up of similar interventions. In this study, we evaluate an integrated care network, the National University Health System (NUHS) Regional Health System (RHS), consisting of acute hospitals, step down care, primary care providers, social services and community partners using a theory-driven realist evaluation approach. This study aims to examine how and for whom the NUHS-RHS works to improve healthcare utilisations, outcomes, care experiences and reduce healthcare costs. By using a realist approach that balances the needs of context-specific evaluation with international comparability, this study carries the potential to address current research gaps. METHODS AND ANALYSIS: This evaluation will be conducted in three research phases: (1) development of initial programme theory (IPT) underlying the NUHS-RHS; (2) testing of programme theory using empirical data; and (3) refinement of IPT. IPT was elicited and developed through reviews of programme documents, informal discussions and in-depth interviews with relevant stakeholders. Then, a convergent parallel mixed method study will be conducted to assess context (C), mechanisms (M) and outcomes (O) to test the IPT. Findings will then be analysed according to the realist evaluation formula of CMO in which findings on the context, mechanisms will be used to explain the outcomes. Finally, based on findings gathered, IPT will be refined to highlight how to improve the NUHS-RHS by detailing what works (outcome), as well as how (mechanisms) and under what conditions (context). ETHICS AND DISSEMINATION: The National Healthcare Group, Singapore, Domain Specific Review Board reviewed and approved this study protocol. Study results will be published in international peer-reviewed journals and presented at conferences and internally to NUHS-RHS and Ministry of Health, Singapore.

Peripheral blood gene expression of acute phase proteins in people with first episode psychosis.

BACKGROUND: There is a growing interest in the association between schizophrenia and the activation of inflammatory system with signs of acute phase (AP) response. Majority of such studies had focused on C-reactive protein (CRP). The aims of the present study were (i) to examine the gene expression profiles of other acute phase proteins (APP), namely haptoglobin (HP), alpha-1 antitrypsin (A1T), and alpha-2 macroglobulin (A2M) in patients with first episode psychosis (FEP) over a period of three months and (ii) to explore the association between APP levels and severity of symptoms. METHODS: In this study, HP, A1T and A2M gene expression levels from whole blood were measured at recruitment, 1- and 3-month follow-up visits using quantitative PCR (qPCR) in 43 patients with FEP and in 57 healthy controls. Diagnoses was ascertained on the Structured Clinical Interview for DSM-IV-TR. Severity of symptoms in patients was assessed on the Positive and Negative Syndrome Scale (PANSS) and a previously validated 5-factor PANSS structure was applied in the subsequent analyses. RESULTS: The FEP sample comprised of 28 (65.1%) individuals with schizophrenia, 12 (27.9%) with schizophreniform disorder and 3 (7%) with schizoaffective disorder. HP gene expression level was noted to be significantly higher in patients than controls at all three time points: recruitment (P=0.049), 1-month follow up (P=0.002) and 3-month follow up (P=0.005). PANSS positive, depression, and excitement symptom factors showed significant associations with HP (P=0.002), A1T (P=0.016) and A2M (P=0.034), respectively. These findings remained significant after controlling for age, gender, smoking status and accumulated chlorpromazine dosage. CONCLUSION: The current study provides information on HP, A1T and A2M gene expression profiles in FEP patients and their associations with psychopathology. This provides support for the hypothesis that inflammation is related to schizophrenia and further encourages studies on immune-inflammatory markers to understand the relationship between inflammation and schizophrenia.

GAD1 Gene Expression in Blood of Patients with First-Episode Psychosis.

γ-Aminobutyric acid (GABA), the primary inhibitory neurotransmitter, has often been studied in relation to its role in the pathophysiology of schizophrenia. GABA is synthesized from glutamate by glutamic acid decarboxylase (GAD), derived from two genes, GAD1 and GAD2. GAD1 is expressed as both GAD67 and GAD25 mRNA transcripts with the former reported to have a lower expression level in schizophrenia compared to healthy controls and latter was reported to be predominantly expressed fetally, suggesting a role in developmental process. In this study, GAD67 and GAD25 mRNA levels were measured by quantitative PCR (qPCR) in peripheral blood of subjects with first-episode psychosis (FEP) and from healthy controls. We observed low GAD25 and GAD67 gene expression levels in human peripheral blood. There was no difference in GAD25 and GAD67 gene expression level, and GAD25/GAD67 ratio between patients with FEP and healthy controls. PANSS negative symptoms were associated with levels of GAD25 mRNA transcripts in patients with FEP. While the current study provides information on GAD25 and GAD67 mRNA transcript levels in whole blood of FEP patients, further correlation and validation work between brain regions, cerebrospinal fluid and peripheral blood expression profiling are required to provide a better understanding of GAD25 and GAD67.

Instruments Measuring Integrated Care: A Systematic Review of Measurement Properties.

Policy Points: Investigations on systematic methodologies for measuring integrated care should coincide with the growing interest in this field of research. A systematic review of instruments provides insights into integrated care measurement, including setting the research agenda for validating available instruments and informing the decision to develop new ones. This study is the first systematic review of instruments measuring integrated care with an evidence synthesis of the measurement properties. We found 209 index instruments measuring different constructs related to integrated care; the strength of evidence on the adequacy of the majority of their measurement properties remained largely unassessed. CONTEXT: Integrated care is an important strategy for increasing health system performance. Despite its growing significance, detailed evidence on the measurement properties of integrated care instruments remains vague and limited. Our systematic review aims to provide evidence on the state of the art in measuring integrated care. METHODS: Our comprehensive systematic review framework builds on the Rainbow Model for Integrated Care (RMIC). We searched MEDLINE/PubMed for published articles on the measurement properties of instruments measuring integrated care and identified eligible articles using a standard set of selection criteria. We assessed the methodological quality of every validation study reported using the COSMIN checklist and extracted data on study and instrument characteristics. We also evaluated the measurement properties of each examined instrument per validation study and provided a best evidence synthesis on the adequacy of measurement properties of the index instruments. FINDINGS: From the 300 eligible articles, we assessed the methodological quality of 379 validation studies from which we identified 209 index instruments measuring integrated care constructs. The majority of studies reported on instruments measuring constructs related to care integration (33%) and patient-centered care (49%); fewer studies measured care continuity/comprehensive care (15%) and care coordination/case management (3%). We mapped 84% of the measured constructs to the clinical integration domain of the RMIC, with fewer constructs related to the domains of professional (3.7%), organizational (3.4%), and functional (0.5%) integration. Only 8% of the instruments were mapped to a combination of domains; none were mapped exclusively to the system or normative integration domains. The majority of instruments were administered to either patients (60%) or health care providers (20%). Of the measurement properties, responsiveness (4%), measurement error (7%), and criterion (12%) and cross-cultural validity (14%) were less commonly reported. We found <50% of the validation studies to be of good or excellent quality for any of the measurement properties. Only a minority of index instruments showed strong evidence of positive findings for internal consistency (15%), content validity (19%), and structural validity (7%); with moderate evidence of positive findings for internal consistency (14%) and construct validity (14%). CONCLUSIONS: Our results suggest that the quality of measurement properties of instruments measuring integrated care is in need of improvement with the less-studied constructs and domains to become part of newly developed instruments.

A Prospective Validation Study of a Rainbow Model of Integrated Care Measurement Tool in Singapore.

INTRODUCTION: The conceptual ambiguity of the integrated care concept precludes a full understanding of what constitutes a well-integrated health system, posing a significant challenge in measuring the level of integrated care. Most available measures have been developed from a disease-specific perspective and only measure certain aspects of integrated care. Based on the Rainbow Model of Integrated Care, which provides a detailed description of the complex concept of integrated care, a measurement tool has been developed to assess integrated care within a care system as a whole gathered from healthcare providers' and managerial perspectives. This paper describes the methodology of a study seeking to validate the Rainbow Model of Integrated Care measurement tool within and across the Singapore Regional Health System. The Singapore Regional Health System is a recent national strategy developed to provide a better-integrated health system to deliver seamless and person-focused care to patients through a network of providers within a specified geographical region. METHODS: The validation process includes the assessment of the content of the measure and its psychometric properties. CONCLUSION: If the measure is deemed to be valid, the study will provide the first opportunity to measure integrated care within Singapore Regional Health System with the results allowing insights in making recommendations for improving the Regional Health System and supporting international comparison.

Levels of Serum Brain-Derived Neurotrophic Factor in Schizophrenia.

Recent meta-analyses of serum brain-derived neurotrophic factor (BDNF) have reported lower levels in patients with schizophrenia. However, most studies did not consider the potential confounding effects of time of collection, age, sex, smoking, and obesity. Here, we sought to examine differences in serum BDNF between medicated patients with schizophrenia compared with control subjects, taking into consideration the potential confounders of serum BDNF. Serum was obtained from a sample of fasted blood collected from all participants, and BDNF was assayed on a commercially available kit. After adjusting for potential confounders, there was no statistically significant difference between cases and control subjects (p = 0.261). In the model, body mass index emerged as the most significant predictor of serum BDNF (ß = 0.22, p = 0.009). The present study did not support a role for serum BDNF as a biomarker in schizophrenia. This could be due to the nonspecific nature of serum BDNF and its association with both mental and physical conditions.

Clioquinol Improves Cognitive, Motor Function, and Microanatomy of the Alpha-Synuclein hA53T Transgenic Mice.

The abnormal accumulation of alpha-synuclein (α-syn) has been linked to a number of neurodegenerative disorders, the most noteworthy of which is Parkinson's disease. Alpha-synuclein itself is not toxic and fulfills various physiological roles in the central nervous system. However, specific types of aggregates have been shown to be toxic, and metals have been linked to the assembly of these toxic aggregates. In this paper, we have characterized a transgenic mouse that overexpresses the A53T mutation of human α-syn, specifically assessing cognition, motor performance, and subtle anatomical markers that have all been observed in synucleinopathies in humans. We hypothesized that treatment with the moderate-affinity metal chelator, clioquinol (CQ), would reduce the interaction between metals and α-syn to subsequently improve the phenotype of the A53T animal model. We showed that CQ prevents an iron-synuclein interaction, the formation of urea-soluble α-syn aggregates, α-syn-related substantia nigra pars compacta cell loss, reduction in dendritic spine density of hippocampal and caudate putamen medium spiny neurons, and the decline in motor and cognitive function. In conclusion, our data suggests that CQ is capable of mitigating the pathological metal/α-syn interactions, suggesting that the modulation of metal ions warrants further study as a therapeutic approach for the synucleinopathies.

Effects of Neonatal Iron Feeding and Chronic Clioquinol Administration on the Parkinsonian Human A53T Transgenic Mouse.

Increased nigral iron (Fe) is a cardinal feature of Parkinson's disease, as is the accumulation of aggregates comprising α-synuclein. We used wild-type mice and transgenic mice overexpressing the human A53T mutation to α-synuclein to examine the influence of increased Fe (days 10-17 postpartum) on the parkinsonian development phenotype of these animals (including abnormal nigral Fe levels and deficits in both cell numbers and locomotor activity), and to explore the impact of the Fe chelator clioquinol in the model. Both untreated and Fe-loaded A53T mice showed similar levels of nigral cell loss, though 5 months of clioquinol treatment was only able to prevent the loss in the non-Fe-loaded A53T group. Iron levels in the Fe-loaded A53T mice returned to normal at 8 months, though effects of dopamine denervation remained, demonstrated by limited locomotor activity and sustained neuron loss. These data suggest that Fe exposure during a critical developmental window, combined with the overexpression mutant α-synuclein, presents a disease phenotype resistant to intervention using clioquinol later in life.