Haptoglobin genotype is a risk factor for coronary artery disease in prediabetes: A case-control study.

Objective: Coronary artery disease (CAD) prediction remains inconsistent with many unappreciated risk factors. Haptoglobin genotype determines the haptoglobin protein's effectiveness to bind free hemoglobin and prevent oxidative stress, a contributor to atherosclerosis. The haptoglobin 2-2 genotype increases the prevalence of cardiovascular disease (CVD) approximately five times compared to the 1-1 genotype in individuals with diabetes. The risk is unknown in prediabetes. The purpose of this study was to determine an association between haptoglobin genotype and CAD in prediabetes. Methods: The researchers used case-control convenience sampling from two cardiovascular disease prevention clinics in Memphis, TN, and Spokane, WA, from January 1, 2016 to March 31, 2020. Participants were ages 35-70, had prediabetes, and free of chronic inflammatory or infectious diseases. Cases had a history of subclinical or clinical CAD, while controls did not have a history of CAD. Differences between cases and controls and among haptoglobin genotypes were analyzed using t-tests and ANOVA for continuous variables and chi-square or Fisher's exact tests for categorical variables. Associations among Hp genotypes and CAD were estimated using logistic regression. Results: The sample (N = 178; 72 cases and 106 controls) was 96 % white and 64 % male. Cases had lower total cholesterol (p = 0.0001) and high-sensitivity C-reactive protein (p = 0.021). Except for CAD, haptoglobin genotype was independent of any demographic or clinical variable. Haptoglobin 2-2 genotype had 4.0 times higher odds of CAD than haptoglobin 1-1 (p = 0.01). Conclusion: Haptoglobin 2-2 genotype had approximately four times higher odds of having CAD compared to the haptoglobin 1-1 genotype. Cases had more desirable clinical profiles, likely attributable to more aggressive treatment of traditional risk factors than controls. Haptoglobin genotype is a potentially important CAD risk factor in prediabetes (88 million Americans). Further studies are needed for interventions to reduce the oxidative stress associated with the Hp 2-2 genotype and glycosylated hemoglobin and for CAD reduction.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A molecular epidemiological study on Escherichia coli in young chicks with colibacillosis identified two possible outbreaks across farms.

Avian pathogenic Escherichia coli (APEC) is the cause of colibacillosis outbreaks in young poultry chicks, resulting in acute to peracute death. The high morbidity and mortality caused by colibacillosis results in poor animal welfare, reduced sustainability and economical loss worldwide. To advance the understanding of the molecular epidemiology, genomic relatedness and virulence traits of APEC, we performed systematic sampling from 45 confirmed colibacillosis broiler flocks with high first week mortality (FWM) during 2018-2021. From these flocks, 219 APEC isolates were whole genome sequenced (WGS) and bioinformatic analyses were performed. The bioinformatic analyses included sequence typing (ST), serotyping, detection of virulence-associated genes (VAGs) and phylogenetic analysis. Our results showed a high prevalence of ST23, ST429 and ST95 among APEC isolates from Norwegian broiler flocks, and identified ST23, ST429, ST117 and ST371 to cause disease more often alone, compared to ST95, ST69 and ST10. Phylogenetic analyses, together with associated metadata, identified two distinct outbreaks of colibacillosis across farms caused by ST429 and ST23 and gave insight into expected SNP distances within and between flocks identified with the same ST. Further, our results highlighted the need for combining two typing methods, such as serotyping and sequence typing, to better discriminate strains of APEC. Ultimately, systematic sampling of APEC from multiple birds in a flock, together with WGS as a diagnostic tool is important to identify the disease-causing APEC within a flock and to detect outbreaks of colibacillosis across farms.

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

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

Intentions and willingness to engage in risky driving behaviour among high school adolescents: evaluating the bstreetsmart road safety programme.

OBJECTIVE: To investigate the impact of a road safety programme on adolescents' willingness to engage in risky behaviour as probationary drivers, adjusted for covariates of interest. METHOD: The bstreetsmart is a road safety programme delivered to around 25 000 adolescent students annually in New South Wales. Using a smartphone-based app, student and teacher participation incentives, students were surveyed before and after programme attendance. Mixed-methods linear regression analysed pre/post-modified Behaviour of Young Novice Driver (BYNDS_M) scores. RESULTS: 2360 and 1260 students completed pre-event and post-event surveys, respectively. Post-event BYNDS_M scores were around three points lower than pre-event scores (-2.99, 95% CI -3.418 to -2.466), indicating reduced intention to engage in risky driving behaviours. Covariates associated with higher stated intentions of risky driving were exposure to risky driving as a passenger (1.21, 95% CI 0.622 to 2.011) and identifying as non-binary gender (2.48, 95% CI 1.879 to 4.085), adjusting for other predictors. CONCLUSIONS: Trauma-informed, reality-based injury prevention programmes can be effective in changing short-term stated intentions to engage in risky driving, among a pre-independent driving student population. The adolescent novice driver age group is historically challenging to engage, and injury prevention action must be multipronged to address the many factors influencing their behaviour.

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

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

Negative and positive experiences of caregiving among family caregivers of older blunt trauma patients.

OBJECTIVES: Family caregivers play a fundamental role in the care of the older blunt trauma patient. We aim to identify risk factors for negative and positive experiences of caregiving among family caregivers. DESIGN: Prospective, nationwide, multi-center cohort study. SETTING AND PARTICIPANTS: 110 family caregivers of Singaporeans aged≥55 admitted for unintentional blunt trauma with an Injury Severity Score (ISS) or New Injury Severity Score (NISS)≥10 were assessed for caregiving-related negative (disturbed schedule and poor health, lack of family support, lack of finances) and positive (esteem) experiences using the modified-Caregiver Reaction Assessment (m-CRA) three months post-injury. METHODS: The association between caregiver and patient factors, and the four m-CRA domains were evaluated via linear regression. RESULTS: Caregivers of retired patients and caregivers of functionally dependent patients (post-injury Barthel score <80) reported a worse experience in terms of disturbed schedule and poor health (ß-coefficient 0.42 [95% Confidence Interval 0.10, 0.75], p = .01; 0.77 [0.33, 1.21], p = .001), while male caregivers and caregivers who had more people in the household reported a better experience (-0.39 [-0.73, -0.06], p = .02; -0.16 [-0.25, -0.07], p = .001). Caregivers of male patients, retired patients, and patients living in lower socioeconomic housing were more likely to experience lack of family support (0.28, [0.03, -0.53], p = .03; 0.26, [0.01, 0.52], p = .05; 0.34, [0.05, -0.66], p = .02). In the context of lack of finances, caregivers of male patients and caregivers of functionally dependent patients reported higher financial strain (0.74 [0.31, 1.17], p = .001; 0.84 [0.26, 1.43], p = .01). Finally, caregivers of male patients reported higher caregiver esteem (0.36 [0.15, 0.57], p = .001). CONCLUSIONS AND IMPLICATIONS: Negative and positive experiences of caregiving among caregivers of older blunt trauma patients are associated with pre-injury disability and certain patient and caregiver demographics. These factors should be considered when planning the post-discharge support of older blunt trauma patients.

ULTRASTRUCTURE OF EGG ENVELOPES AND EARLY EMBRYOS OF ROHDELLA AMAZONICA (TREMATODA: ASPIDOGASTREA) PARASITIC IN BANDED PUFFER FISH, COLOMESUS PSITTACUS.

Egg structure and early embryonic development of the aspidogastrean, Rohdella amazonica, a basal trematode, were studied by transmission electron microscopy (TEM) to gain insight into functional, developmental, and phylogenetic characteristics. Gravid worms were removed from the intestine of naturally infected banded puffer fish Colomesus psittacus, collected from the Bay of Marajó, Paracauari River (Pará, Brazil) and processed by standard TEM methods. By the time of pronuclear fusion, the fertilized zygote was already enclosed in a thick, electron-dense pre-operculate eggshell and an underlying layer of vitellocytes that fused into a vitelline syncytium as they were still secreting their shell granules. When cleavage commenced, a small number of macromeres moved to the area just underneath the eggshell, where they fused to form a single syncytial embryonic envelope. Simultaneously, the smaller blastomeres continued to divide as they maintained contact with each other, but remained separate from the vitelline syncytium. Concurrent with these cellular changes, a thickened knob expanded at one pole of the eggshell and began to form an opercular suture. By the time the operculum was fully formed, the vitelline syncytium had mostly degenerated, while the smaller blastomeres had become cohesive as a single mass that preceded the differentiation and morphogenesis of the cotylocidium larva. The general pattern of cleavage and eggshell formation resembles that of other trematodes and polylecithal cestodes, but the single embryonic envelope has been reported only in a few basal taxa. The only other aspidogastrean studied in detail to date is very similar, indicating close phylogenetic affinity and conservatism within this basal neodermatan and neoophoran group.

Tannic Acid-Modified Silver Nanoparticles in Conjunction with Contact Lens Solutions Are Useful for Progress against the Adhesion of Acanthamoeba spp. to Contact Lenses.

Acanthamoeba spp. are amphizoic amoebae that are widely distributed in the environment and capable of entering the human body. They can cause pathogenic effects in different tissues and organs, including Acanthamoeba keratitis (AK), which may result in a loss of visual acuity and blindness. The diagnostics, treatment, and prevention of AK are still challenging. More than 90% of AK cases are related to the irresponsible wearing of contact lenses. However, even proper lens care does not sufficiently protect against this eye disease, as amoebae have been also found in contact lens solutions and contact lens storage containers. The adhesion of the amoebae to the contact lens surface is the first step in developing this eye infection. To limit the incidence of AK, it is important to enhance the anti-adhesive activity of the most popular contact lens solutions. Currently, silver nanoparticles (AgNPs) are used as modern antimicrobial agents. Their effectiveness against Acanthamoeba spp., especially with the addition of plant metabolites, such as tannic acid, has been confirmed. Here, we present the results of our further studies on the anti-adhesion potential of tannic acid-modified silver nanoparticles (AgTANPs) in combination with selected contact lens solutions against Acanthamoeba spp. on four groups of contact lenses. The obtained results showed an increased anti-adhesion activity of contact lens solutions in conjunction with AgTANPs with a limited cytotoxicity effect compared to contact lens solutions acting alone. This may provide a benefit in improving the prevention of amoebae eye infections. However, there is still a need for further studies on different pathogenic strains of Acanthamoeba in order to assess the adhesion of the cysts to the contact lens surface and to reveal a more comprehensive picture of the activity of AgTANPs and contact lens solutions.

An Agile Systems Modeling Framework for Bed Resource Planning During COVID-19 Pandemic in Singapore.

Background: The COVID-19 pandemic has had a major impact on health systems globally. The sufficiency of hospitals' bed resource is a cornerstone for access to care which can significantly impact the public health outcomes. Objective: We describe the development of a dynamic simulation framework to support agile resource planning during the COVID-19 pandemic in Singapore. Materials and Methods: The study data were derived from the Singapore General Hospital and public domain sources over the period from 1 January 2020 till 31 May 2020 covering the period when the initial outbreak and surge of COVID-19 cases in Singapore happened. The simulation models and its variants take into consideration the dynamic evolution of the pandemic and the rapidly evolving policies and processes in Singapore. Results: The models were calibrated against historical data for the Singapore COVID-19 situation. Several variants of the resource planning model were rapidly developed to adapt to the fast-changing COVID-19 situation in Singapore. Conclusion: The agility in adaptable models and robust collaborative management structure enabled the quick deployment of human and capital resources to sustain the high level of health services delivery during the COVID-19 surge.

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

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

ULTRASTRUCTURE AND CYTOCHEMISTRY OF LATE EMBRYOS AND COTYLOCIDIUM LARVAE OF ROHDELLA AMAZONICA (TREMATODA: ASPIDOGASTREA), FROM THE TROPICAL ESTUARINE FISH, COLOMESUS PSITTACUS.

Developmental ultrastructure of late embryos and cotylocidium larval morphogenesis of Rohdella amazonica, an aspidogastrean parasite of fish, were studied to reveal the functional aspects of larvigenesis within the egg as well as phylogenetically relevant characteristics of the embryos and larvae in this basal trematode group. Gravid worms were removed from the intestine of naturally infected banded puffer fish Colomesus psittacus, collected from the Bay of Marajó, Paracauari River (Pará, Brazil) and processed by standard methods of transmission electron microscopy (TEM) and cytochemistry. During late cleavage and rearrangement of the blastomeres, the vitelline syncytium that plays a role in eggshell formation and nutrient provision to the embryo completes its apoptotic degeneration as the embryonic mass grows substantially. Early larval morphogenesis involves cellular positioning that defines the anteroposterior polarity of the differentiating larva. Progressing through larvigenesis, the anterior end forms a muscular oral sucker surrounding the mouth, which leads inward into the pharynx and expanding digestive cavity. At the posterior end, a large disc forms as a precursor to the eventual ventral disc. The fully formed cotylocidium, still within the eggshell, is flexed ventrally, bringing the 2 poles into near juxtaposition. The neodermatan tegument with outwardly projecting small microvilli becomes fully formed, as myocytons, a protonephridial system, and 2 glandular regions occupy the body's interior. The ultrastructural features described here are very similar to those reported for Aspidogaster limacoides from fish and somewhat similar to those reported for Cotylogaster occidentalis from molluscs, but differ from the more diverse larvae of neodermatan taxa that have been studied more extensively.

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

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