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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 hours and about 57.3% reported at least 8 hours 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.

IntroductionThe 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.MethodsA 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.ResultsOur 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.ConclusionOur 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.

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

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.

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.

ObjectiveTo 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.DesignA retrospective quasi-experimental study without randomisation where patients who received post-discharge care interventions were matched 1:1 with unenrolled patients as controls.SettingThe 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.ParticipantsLinked 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.InterventionsFor both programmes, teams conducted follow-up home visits and phone calls to monitor and manage patients’ post-discharge.Primary outcome measuresOne-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.ResultsPatients 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.ConclusionsBoth 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.

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. Electronic supplementary material The online version of this article (10.1186/s12913-019-3980-x) contains supplementary material, which is available to authorized users.

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

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.

IntroductionThe 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 analysisThis 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 disseminationThe 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.

Objective Immune-inflammatory mediators play a pivotal role in brain signaling and have been increasingly associated with the pathophysiology of schizophrenia. Many studies have indicated an increased level of immune-inflammatory interleukin-6 (IL-6) in schizophrenia. IL-6 is a well-known chief stimulator of inflammation. Of late leptin has also been implicated in the inflammatory pathway of schizophrenia. In this study we measured and compared serum levels of IL-6 and leptin in patients with schizophrenia to healthy controls, and investigated the relationship between IL-6 and leptin. Methods Serum IL-6 and leptin were determined in 20 patients diagnosed with schizophrenia and in 19 healthy controls matched by gender, age and body mass index (BMI) using commercial Bioplex assays. Results Using Mann-Whitney U-test, significantly increased IL-6 levels were found in the patients but there was no significant difference in leptin levels though a trend towards higher leptin was observed in the patients. Spearman correlations did not show any correlation between IL-6 and clinical variables except antipsychotic dosage. Leptin significantly correlated with gender and BMI. A large effect size correlation was observed between IL-6 and leptin in the patients but not in the controls. Multiple regression analysis performed on patients, after adjusting for gender and BMI, revealed there was no significant association between IL-6 and leptin. Conclusion IL-6 and leptin levels may reflect the chronic inflammatory state associated with schizophrenia but further evaluation is required. Also, it is important to consider the confounding effects of obesity in any examination of relationships between groups with regard to cytokines and adipokines.

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.

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.

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 (β = 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.

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.

Background: Integrated care is an important strategy for improving the process and outcome of healthcare delivery for patients with complex needs. Until now, there has been no universally accepted and validated measurement tool for integrated care. This study aimed to validate The Rainbow Model of Integrated Care Measurement Tool (RMIC-MT) which assesses, using a self-administered questionnaire, micro level (clinical), meso level (professional and organisational), macro level (system) and enabling (functional and normative) aspects of integrated care. Methods: Potentially relevant items were developed on the basis of a literature review and qualitative synthesis process. Three modified Delphi studies were used to asses the content validity of the items. Primary survey data were collected from healthcare providers and managers participating in integrated care projects from The Netherlands, Singapore and Australia. The RMIC-MT was validated for face validity, internal consistency, construct validity and reliability. Results and conclusions: The RMIC-MT is one of the first attempts to systematically measure different aspects of integrated care across the care continuum. Preliminary results suggest that the RMIC-MT is both a reliable and valid tool for assessing integrated care in different integrated care settings. The results of the construct and reliability analysis across countries will be presented, interpreted and discussed.

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.