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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.

ObjectivesThe 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.DesignTriangulation mixed-methods design and analyses were employed to understand factors underpinning network mechanisms.SettingThe study was conducted at a tertiary hospital in the northern region of Singapore.ParticipantsWe recruited participants who were involved in the conceptualisation, design, development and implementation of the CARITAS Programme from a tertiary hospital and PCC providers.InterventionWe 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 measuresWe assessed integration scores across eight dimensions of the RMIC-MT and factors underpinning network mechanisms.ResultsCompared 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.ConclusionCARITAS 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.

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

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.

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

Topic Guide for Interviews. (DOCX 18 kb)

In this chapter, we describe the development of integrated care ecosystems known as the “Regional Health System(s) (RHS)” in Singapore. Singapore’s challenges associated with rapidly aging population, increasing complexity of needs, demands for healthcare services and fragmentation in the provision of healthcare services were the key factors driving the need to break down the silos and improve integration within and across the Singapore healthcare system. Initially developed in 2012 and re-organized in 2017, the RHS was designed to bring together different actors across disciplines, organizations and sectors to optimize quality, outcomes of care while keeping cost of healthcare affordable. The ecosystem provides the avenue for collaboration between different providers, and integrates different components of the system. In order to better meet future healthcare need while keeping the mandates, the RHS was re-organized from 6 into 3 in 2017. Every RHS ecosystem is led by a major public hospital working in collaboration with health and social care providers within the same geographical region. Together, the RHS ecosystems focus on (i) building partnerships (ii) strengthening primary care and (iii) fostering collaborative learnings to facilitate continual improvements. Four design principles, three overall strategies and three factors enabling ecosystem integration are described as factors facilitating integration. To date, RHS ecosystems have demonstrated good first steps in fostering integrated care in Singapore. In retrospect, it has become clear that the RHS ecosystem model reflects the characteristics of a typical complex adaptive system (CAS), in which relationships and dependencies of actors change with different agendas, working styles and time. The need to increase their adaptive capacity while constantly moving towards greater levels of integrated care is identified as the main ongoing challenge for care delivery innovation.

Introduction: The growing prevalence of dementia is of concern in Singapore as it poses significant health, social and economic burden on individuals, families and the healthcare system. While it widely known that dementia is best managed by a multidisciplinary team of healthcare providers working together across different healthcare settings, dementia care has been primarily delivered by tertiary hospitals in Singapore. Hospital-centric dementia care is insufficient because needs of persons with dementia PWDs and their caregivers extend beyond medical needs and are best provided for in the community. As demand continues to rise, the healthcare system now faces the challenges of ensuring sustainability, appropriateness and quality of dementia care. To cope with these, the CARITAS network was established in 2012 to foster integrated, person centered care across different healthcare settings through i formation of primary care and community PCC providers network ii empowerment of PCC to manage PWD in the community iii empowerment of caregivers and iv integration between tertiary hospital and PCC through clinical, professional and functional integration. With these strategies, the CARITAS aims to provide a comprehensive, accessible, responsive, individualized, trans-disciplinary, accountable and seamless care for PWDs in the northern part of Singapore within their community. Methods: To support further development of the CARITAS network, this study was designed as a formative evaluation. Using sequential exploratory mixed methods, we aim to examine the degree of care integration within the CARITAS network, identify moderating factors that affect its implementation by taking into consideration the context in which it operationalized so as to identify areas for improvements. Guided by the Rainbow Model of Integrated Care RMIC, the RMIC measurement tool RMIC-MT was first administered to 100 healthcare providers within the CARITAS network. Then, based on the findings from the RMIC-MT, 30 healthcare providers and caregivers were invited to participate in interviews to gather insights into the moderating factors of the implementation of the CARITAS network. Data from the various sources will initially be analyzed according to their data types and subsequently triangulated according to the RMIC. Recommendations for improvements will then be made. Results & Discussions: The results which will be presented at the conference have significant implications on a few levels. It will potentially i provide information for improvement of the CARITAS network, ii provide insights to other countries that are experimenting with new models of dementia care and iii contribute significantly to the international literature on improvement science. Lessons Learned: In the evaluation of complex healthcare intervention such as the CARITAS network, it is essential to conduct process evaluation in conjunction with outcome evaluation so as to account for variability in implementation. Without process evaluation, it would be difficult to determine actions to take for improving the intervention. Limitations: As this is a single site study, findings gathered from this study needs to be interpreted with consideration of the context in which the CARITAS network is implemented. Suggestions for future research Future research should be conducted to examine the effectiveness of the CARITAS network in improving its intended outcomes.

Introduction : Frequent admitters FA, defined as patients with three or more inpatient acute hospital admissions within one year, account for about 27% of episodes and incur high healthcare costs. National University Health System Regional Health System NUHS-RHS Integrated Interventions and Care Extension NICE, launched in 2014, targeted FA with the aim of reducing avoidable hospital utilisation. NICE patients were assigned a case manager who customised their care plan based on holistic needs assessment. NICE provided post-discharge home visits and/or phone calls to monitor patients’ progress, appropriate referrals to community health and social services, and consolidated care under one team. We retrospectively evaluated NICE’s effect on reducing utilisation over 1-year post-enrolment: all-cause admissions ADM, emergency admissions EM, emergency department visits ED, specialist outpatient clinic visits SOC, and total inpatient length of stay LOS. Methods : NICE patients enrolled between June 2014 to December 2015 were grouped as cases n=668. Unenrolled patients who were FA during the same period were designated as potential controls n=5,714, taking their third admission date during this period as proxy date of enrolment. Propensity score matching was conducted with the following: gender, race, age, residential housing type, number of comorbidities at enrolment, date of enrolment and pre-enrolment utilisation 1-year prior. This resulted in 604 matched case-control pairs. As the variance of each measure of utilisation is greater than its mean, negative binomial regression was used to model post-enrolment utilisation, adjusting for log-transformed pre-enrolment levels and matching propensity score, with an offset term to account for potential mortality during follow-up. We report incidence rate ratios IRR of cases to controls, with 95% confidence intervals 95%CI. Results : Cases unadjusted mean=6.7 had significantly fewer post-enrolment SOC than controls unadjusted mean=8.6, IRR=0.86 95%CI: 0.77-0.97. No statistically significant differences were observed for post-enrolment ADM, EM, ED, and LOS. Discussion : The results suggest that NICE provided adequate post-discharge follow-up care that patients would otherwise seek from SOC, thus potentially decreasing patients’ time and cost burden. For a significant proportion of patients in both groups, post-enrolment ADM, EM, ED, and LOS may have regressed to a low mean following an acute period of high admissions, resulting in floor effects which limit any further reductions in a 1-year period. Conclusion : NICE had an impact in reducing patients’ SOC post-discharge. Lessons Learned : The higher than expected variability in the utilisation patterns suggest FA are a heterogeneous group, and stratification could allow for more targeted interventions that better cater to care needs. Limitations : Patients were not randomised into cases and controls, but inherent bias from confounding factors was mitigated with matching. Different patient profiles and needs possibly also led to implementation inconsistencies. Suggestions for Future Research : Future research could stratify FA into subgroups and explore programme effects in reducing readmissions within patient subsets over a longer follow-up period. Targeted interventions for various subsets could be tested and inform future iterations of such programmes. Cost-benefit analysis should be conducted to determine if the savings from reduced SOC that are attributable to NICE outweighs the cost to run the programme.

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.

Introduction: Patients with multiple morbidities and complex needs are putting a strain on the resources of the health system, particularly on hospitals. The current fragmented hospital and disease centric care is unable to cope with the growing healthcare needs facing the modern day health system [1,2]. Therefore, integrated care interventions have been developed to improve the quality and efficiency of care by coordinating healthcare services in a person-centric manner with the aims of reducing health and social burden on the healthcare systems including hospitals [2]. However, the methods and outcomes of interventions used are different and evidence of the effectiveness of the interventions are not consistent. There is also a lack of understanding on why and how integrated care interventions work or do not work under certain circumstances. Based on the CMO (context, mechanism and outcomes) [3] model, we aim to summarise and compare the existing evidence of the context, mechanism and outcomes of hospital-led integrated care interventions from published peer-reviewed systematic reviews. Methods: A review of existing systematic reviews is being conducted to find out what works, for whom, and under what circumstances hospitals can provide effective integrated care interventions. The review will address the following questions: (1) what are the programmes available? (2) Who is the target population? (3) In what respect of integrated care (i.e., patient, system, organisation)? (4) What are the outcomes measured (e.g. healthcare utilizations, healthcare outcomes (QoL, quality of care mortality rates, etc.), costs) and how effective are they? (5) If they are effective, how do they work in different settings and for different populations? (6) What are the underlying mechanisms of these interventions? (7) What causes the heterogeneity in outcomes of hospital-led integrated care programmes? Based on the WHO definition of integrated care [4] and Rainbow Model of Integrated Care (RMIC) definition of system and organisation integration [5], articles are searched through PubMed, Scopus, Web of Science and Cochrane Database of Systematic Reviews for the period 2006-2016 (N=2290). A systematic review is included if it describes hospital-led interventions that involve system or organisation integration, involve an acute care setting as the lead, and have the outcomes of the interventions evaluated. Titles for inclusion are screened independently by three reviewers using predetermined criteria. Data are extracted and quality of review is assessed according to the Joanna-Briggs Institute guidelines.[6] Findings on context and mechanism are analysed to explain about outcomes. Complete findings will be presented during ICIC17. Discussion: The findings from the review will help inform policy-makers and healthcare professionals on the design of integrated care programmes that will most likely yield their desired outcomes, based on their target populations and context of the health system. The review will also provide an overview of how to bridge the gap between the development of interventions and successful implementation of hospital-led integrated care [2]. For researchers, the review will indicate the strength of existing evidence and identify directions for future research.

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.

The neurotrophin, brain-derived neurotrophic factor (BDNF), characterises a probable neurobiochemical explanation of maldevelopments in schizophrenia and is a candidate biomarker of the illness. A paucity of studies examining neurobiochemical predictors of remission in schizophrenia exists. In this study, we seek to examine if serum BDNF level is associated with remission status in a sample of Chinese patients with schizophrenia. This study did not find a significant relationship between serum BDNF and remission in patients with schizophrenia. Identification of a suitable biomarker for diagnosis, management, and prognostic outcome is crucial and warrants further study.

The 4th Schizophrenia International Research Society Conference was held in Florence, Italy, April 5-9, 2014 and this year had as its emphasis, "Fostering Collaboration in Schizophrenia Research". Student travel awardees served as rapporteurs for each oral session, summarized the important contributions of each session and then each report was integrated into a final summary of data discussed at the entire conference by topic. It is hoped that by combining data from different presentations, patterns of interest will emerge and thus lead to new progress for the future. In addition, the following report provides an overview of the conference for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research. Published by Elsevier B.V.

Background & hypothesis Schizophrenia is associated with increased mortality rates, which has been attributed to the greater incidence of cardiovascular disease (CVD) events. The Framingham risk score (FRS) is a widely-used age- and gender-specific algorithm to estimate 10-year CVD risk and vascular age. The main aim of this study was to determine the cardiovascular risk profile in schizophrenia and examine the effect of metabolic syndrome (MetS) as a predictor of CVD risk. We hypothesized that patients with schizophrenia have an increased 10-year CVD risk. Methods 83 Chinese patients with schizophrenia and 243 Chinese community controls were recruited. Their medical and smoking histories were obtained, and anthropometric parameters measured. All subjects provided fasted venous blood samples for lipid and glucose measurements. 10-year CVD risk and the difference between vascular and actual age (VA diff ) for each participant were computed using the FRS and compared between patients and controls. Results Schizophrenia patients had a higher mean 10-year CVD risk of 4.6%, as compared with 3.1% in controls, and a greater VA diff of 4.6 years vs. 0.6 years. Both smoking and MetS contributed significantly to the 10-year CVD risk in patients with schizophrenia, with smoking having a greater effect than MetS on this risk. Conclusion This study found a significantly elevated mean 10-year CVD risk and VA diff in patients with schizophrenia compared with controls. Findings point towards the importance of smoking cessation and screening for MetS to decrease the excess CVD risk in patients with schizophrenia.

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.

Brain-derived neurotrophic factor (BDNF), a neurotrophin known to be responsible for development, regeneration, survival and maintenance of neurons has been implicated in the pathophysiology of schizophrenia. This review seeks to complement previous reviews on biological roles of BDNF and summarizes evidence on the involvement of BDNF in the pathophysiology of schizophrenia with an emphasis on clinical relevance. The expressions of BDNF were altered in patients with schizophrenia and were found to be correlated with psychotic symptomatology. Antipsychotics appeared to have differential effects on expression of BDNF but did not restore BDNF expression of patients with schizophrenia to normal levels. In addition, evidence suggests that BDNF is involved in the major neurotransmitter systems and is associated with disruptions in brain structure, neurodevelopmental process, cognitive function, metabolic and immune systems commonly associated with schizophrenia. Besides that, BDNF has been demonstrated to be tightly regulated with estrogen which has also been previously implicated in schizophrenia. Evidence gathered in this review confirms the relevance of BDNF in the pathophysiology of schizophrenia and the potential utility of BDNF as a suitable biomarker for diagnostic and prognostic purposes for disease outcome and other co-morbidities. However, further investigations are warranted to examine the specificity of BDNF in schizophrenia compared to other neurodegenerative disorders and other neuropsychiatric illness. Longitudinal prospective studies will also be of added advantage for evaluation of prognostic utility of BDNF in schizophrenia.

Aims This study aims to examine and compare the predictive utility of blood pressure (BP), waist circumference (WC) and body mass index (BMI), and to determine optimal cut-off values in prediction of metabolic syndrome (MetS) in patients with chronic schizophrenia. Methods About 100 patients with chronic schizophrenia were recruited. BMI and BP were measured and laboratory tests to evaluate patients’ high-density lipoprotein cholesterol, triglycerides and glucose levels were performed. Presence of MetS was examined according to AHA/NHLBI guidelines. Predictive utility of BP, WC and BMI was examined using receiver operating curve and discriminant indices were determined accordingly. Results Forty-six (46%) patients were identified to have MetS. BMI of ≥23 kg m−2 was most accurate (AUC = 0.83, P

Parkinson's disease (PD) is a severe neurodegenerative disorder characterised by loss of dopaminergic neurons of the substantia nigra. The pathological hallmarks are cytoplasmic inclusions termed Lewy bodies consisting primarily of aggregated alpha-synuclein (alphaSN). Different lines of transgenic mice have been developed to model PD but have failed to recapitulate the hallmarks of this disease. Since treatment of rodents with the pesticide rotenone can reproduce nigrostriatal cell loss and other features of PD, we aimed to test chronic oral administration of rotenone to transgenic mice over-expressing human alphaSN with the A53T mutation. Initial assessment of this transgenic line for compensatory molecular changes indicated decreased brain beta-synuclein expression and significantly increased levels of the PD-associated oxidative stress response protein, DJ-1, and the E3 ubiquitin ligase enzyme, Parkin. Rotenone treatment of 30 mg/kg for 25 doses over a 35-day period was tolerated in the transgenic mice and resulted in decreased spontaneous locomotor movement and increased cytoplasmic alphaSN expression. The mitochondrial Parkinson's-associated PTEN-induced kinase 1 protein levels were also increased in transgenic mouse brain after rotenone treatment; there was no change in brain dopamine levels or nigrostriatal cell loss. These hA53T alphaSN transgenic mice provide a useful model for presymptomatic Parkinson's features and are valuable for study of associated compensatory changes in early Parkinson's disease stages.

Cognitive decline in Alzheimer's disease (AD) involves pathological accumulation of synaptotoxic amyloid-β (Aβ) oligomers and hyperphosphorylated tau. Because recent evidence indicates that glycogen synthase kinase 3β (GSK3β) activity regulates these neurotoxic pathways, we developed an AD therapeutic strategy to target GSK3β. The strategy involves the use of copper- bis (thiosemicarbazonoto) complexes to increase intracellular copper bioavailability and inhibit GSK3β through activation of an Akt signaling pathway. Our lead compound Cu II (gtsm) significantly inhibited GSK3β in the brains of APP/PS1 transgenic AD model mice. Cu II (gtsm) also decreased the abundance of Aβ trimers and phosphorylated tau, and restored performance of AD mice in the Y-maze test to levels expected for cognitively normal animals. Improvement in the Y-maze correlated directly with decreased Aβ trimer levels. This study demonstrates that increasing intracellular copper bioavailability can restore cognitive function by inhibiting the accumulation of neurotoxic Aβ trimers and phosphorylated tau.

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.

Integrated care has been suggested as a means to improve the accessibility and quality of healthcare, with the ultimate end of enhancing the health and wellbeing of patients and communities. However, the variations in the concept of integrated care across different stakeholders pose a considerable challenge to an otherwise expanding research area. Despite such promising views, information on standardized and validated tools to measure integrated care is limited. Against this backdrop, a systematic review on the measurement properties of instruments measuring integrated care will be conducted to provide insights on the state of the art in measuring integrated care and related concepts. The systematic review aims to answer three main questions: (1) what instruments are currently available to measure integrated care and how can they be categorized; (2) what measures were used to describe the degree of healthcare integration; and (3) what is the strength of evidence supporting the value of the measures reported (i.e., measurement properties)? Building on existing conceptual frameworks from previous research, a preliminary literature search was conducted to develop a search strategy in PubMed and Medline. The study selection criteria were developed and pilot tested in a sample of the main search results (N=8,095). Selection of articles and subsequent data extraction will be performed to evaluate the methodological quality of eligible articles. The systematic review will then identify instruments measuring integrated care and evaluate their measurement properties using the Consensus based standards for the selection of health based Measurement Instruments (COSMIN) manual and checklist. The expected results – to be presented at the conference – will provide an overall picture of the available instruments for measuring integrated care and contribute in positioning newly developed and validated instruments in the evolving landscape of integrated care. World Congress on Integrated Care 2014, Sydney, November 23-26, 2014. International Journal of Integrated Care – Volume 14, 8 December – URN:NBN:NL:UI:10-1-116586– http://www.ijic.org/

Brain derived neurotrophic factor (BDNF), which has been implicated in the pathogenesis of schizophrenia, has been recently shown to be involved in the regulation of metabolism and energy homeostasis. This study seeks to examine the relationship between BDNF, metabolic indices and cardiovascular (CVD) risk in patients with schizophrenia. Medical histories, demographic information and anthropometric measurements were collected and analyzed from 61 participants with schizophrenia. Fasting glucose and lipids were measured in a central laboratory, and serum BDNF was analyzed using commercially available enzyme-linked immunosorbent assay (ELISA). The 10-year CVD risk for each participant was computed using the Framingham risk score (FRS). Linear regressions were performed to examine the relationships between serum BDNF with body mass index (BMI), blood pressure (BP), triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C) and glucose. To examine the relationship between serum BDNF and FRS, serum BDNF was categorized into quartiles, and a multiple regression was performed. After adjusting for age, gender and current smoking status, diastolic BP (dBP) (p=0.045) and TG (p=0.015) were found to be significantly associated with serum BDNF. Participants in the highest quartile of serum BDNF had a 3.3 times increase in FRS over those in the lowest quartile. Our findings support the possible regulatory role of BDNF in metabolism and cardiovascular homeostasis among patients with schizophrenia similar to that observed among the non-mentally ill. Serum BDNF not only present itself as a candidate biomarker of schizophrenia but also might be a viable marker of metabolic co-morbidities associated with schizophrenia.

This study aims to examine and compare the predictive utility of blood pressure (BP), waist circumference (WC) and body mass index (BMI), and to determine optimal cut-off values in prediction of metabolic syndrome (MetS) in patients with chronic schizophrenia.About 100 patients with chronic schizophrenia were recruited. BMI and BP were measured and laboratory tests to evaluate patients' high-density lipoprotein cholesterol, triglycerides and glucose levels were performed. Presence of MetS was examined according to AHA/NHLBI guidelines. Predictive utility of BP, WC and BMI was examined using receiver operating curve and discriminant indices were determined accordingly.Forty-six (46%) patients were identified to have MetS. BMI of ≥23 kg m(-2) was most accurate (AUC = 0.83, P0.001), with sensitivity of 93.5%, specificity of 48.1%, positive predictive value of 60.6% and negative predictive value of 92.9% in identifying MetS.This finding has immediate and significant clinical implications in the local population with schizophrenia.

We have previously demonstrated that brief treatment of APP transgenic mice with metal ionophores (PBT2, Prana Biotechnology) rapidly and markedly improves learning and memory. To understand the potential mechanisms of action underlying this phenomenon we examined hippocampal dendritic spine density, and the levels of key proteins involved in learning and memory, in young (4 months) and old (14 months) female Tg2576 mice following brief (11 days) oral treatment with PBT2 (30 mg/kg/d). Transgenic mice exhibited deficits in spine density compared to littermate controls that were significantly rescued by PBT2 treatment in both the young (+17%, p