Impact on pulmonary, cardiac, and renal function and long-term quality of life after hospitalization for acute respiratory distress syndrome due to COVID-19: Protocol of the Post-COVID Brazil 3 study.

RATIONALE: Evidence about long-term sequelae after hospitalization for acute respiratory distress syndrome due to COVID-19 is still scarce. PURPOSE: To evaluate changes in pulmonary, cardiac, and renal function and in quality of life after hospitalization for acute respiratory distress syndrome secondary to COVID-19. METHODS: This will be a multicenter case-control study of 220 participants. Eligible are patients who are hospitalized for acute respiratory distress syndrome due to COVID-19. In the control group, individuals with no history of hospitalization in the last 12 months or long-term symptoms of COVID-19 will be selected. All individuals will be subjected to pulmonary spirometry with a carbon monoxide diffusion test, chest tomography, cardiac and renal magnetic resonance imaging with gadolinium, ergospirometry, serum and urinary creatinine, total protein, and urinary microalbuminuria, in addition to quality-of-life questionnaires. Patients will be evaluated 12 months after hospital discharge, and controls will be evaluated within 90 days of inclusion in the study. For all the statistical analyses, p < 0.05 is the threshold for significance. RESULTS: The primary outcome of the study will be the pulmonary diffusing capacity for carbon monoxide measured after 12 months. The other parameters of pulmonary, cardiac, and renal function and quality of life are secondary outcomes. CONCLUSION: This study aims to determine the long-term sequelae of pulmonary, cardiac, and renal function and the quality of life of patients hospitalized for acute respiratory distress syndrome due to COVID-19 in the Brazilian population.

The End Justifies the Means: Chagas Disease from a Perspective of the Host-Trypanosoma cruzi Interaction.

The neglected Chagas disease (CD) is caused by the protozoan parasite Trypanosoma cruzi. Despite CD dispersion throughout the world, it prevails in tropical areas affecting mainly poor communities, causing devastating health, social and economic consequences. Clinically, CD is marked by a mildly symptomatic acute phase, and a chronic phase characterized by cardiac and/or digestive complications. Current treatment for CD relies on medications with strong side effects and reduced effectiveness. The complex interaction between the parasite and the host outlines the etiology and progression of CD. The unique characteristics and high adaptability of T. cruzi, its mechanisms of persistence, and evasion of the immune system seem to influence the course of the disease. Despite the efforts to uncover the pathology of CD, there are many gaps in understanding how it is established and reaches chronicity. Also, the lack of effective treatments and protective vaccines constitute challenges for public health. Here, we explain the background in which CD is established, from the peculiarities of T. cruzi molecular biology to the development of the host's immune response leading to the pathophysiology of CD. We also discuss the state of the art of treatments for CD and current challenges in basic and applied science.

Association between acute disease severity and one-year quality of life among post-hospitalisation COVID-19 patients: Coalition VII prospective cohort study.

PURPOSE: To assess the association between acute disease severity and 1-year quality of life in patients discharged after hospitalisation due to coronavirus disease 2019 (COVID-19). METHODS: We conducted a prospective cohort study nested in 5 randomised clinical trials between March 2020 and March 2022 at 84 sites in Brazil. Adult post-hospitalisation COVID-19 patients were followed for 1 year. The primary outcome was the utility score of EuroQol five-dimension three-level (EQ-5D-3L). Secondary outcomes included all-cause mortality, major cardiovascular events, and new disabilities in instrumental activities of daily living. Adjusted generalised estimating equations were used to assess the association between outcomes and acute disease severity according to the highest level on a modified ordinal scale during hospital stay (2: no oxygen therapy; 3: oxygen by mask or nasal prongs; 4: high-flow nasal cannula oxygen therapy or non-invasive ventilation; 5: mechanical ventilation). RESULTS: 1508 COVID-19 survivors were enrolled. Primary outcome data were available for 1156 participants. At 1 year, compared with severity score 2, severity score 5 was associated with lower EQ-5D-3L utility scores (0.7 vs 0.84; adjusted difference, - 0.1 [95% CI - 0.15 to - 0.06]); and worse results for all-cause mortality (7.9% vs 1.2%; adjusted difference, 7.1% [95% CI 2.5%-11.8%]), major cardiovascular events (5.6% vs 2.3%; adjusted difference, 2.6% [95% CI 0.6%-4.6%]), and new disabilities (40.4% vs 23.5%; adjusted difference, 15.5% [95% CI 8.5%-22.5]). Severity scores 3 and 4 did not differ consistently from score 2. CONCLUSIONS: COVID-19 patients who needed mechanical ventilation during hospitalisation have lower 1-year quality of life than COVID-19 patients who did not need mechanical ventilation during hospitalisation.

Do Australian policies enable a primary health care system to identify family adversity and subsequently support these families-A scoping study.

ISSUE ADDRESSED: To determine if Australian policies support a primary health care system to identify family adversity and subsequently support these families. METHODS: Two methodological approaches were used: (i) a scoping review of Australian federal and two states (Victoria and New South Wales) policies related to family adversity (e.g., childhood maltreatment or household dysfunction, such as parental mental illness); (ii) thirteen semi-structured interviews with Victorian Community Health Service (CHS) staff and government policy makers, recruited via snowball sampling to understand the context of policy making and service implementation. Data collected were subsequently discussed in relation to the Stages Model of policy analysis. RESULTS: One hundred and eighty-eight policies referenced family adversity. Of these, 37 policies met all eligibility criteria including a focus on early intervention within primary care and were included in the review. Most policies were developed within health departments (78%) and included a wide range of adversities, with the majority based within maternal and child health and CHS platforms. Most policy development included consultation with stakeholders. Although most policies received some level of funding, few included funding details and only a third included evaluation. CONCLUSIONS: There are many policies related to family adversity in Australia, with most focused within existing primary care platforms. Given these policies, Australia should be well positioned to identify and respond to family adversity. SO WHAT: More work needs to be done to ensure policies are adequately implemented, evaluated and transparently and appropriately funded. The co-occurrence of adversity should focus policy action; and potentially lead to more effective and efficient outcomes.

Formulating Initial Programme Theories of the Healthy Homes and Neighbourhoods Integrated Care Initiative.

Introduction: The Healthy Homes and Neighbourhoods (HHAN) integrated care initiative was designed to break intergenerational cycles of social and health inequalities and enhance access to and engagement with health and social services for vulnerable families in the Sydney Local Health District. We sought to unearth the initial programme theory of the HHAN initiative to inform rollout to other relevant areas. Methods: We conducted a critical realist evaluation using steps. (1) Exploring the events around the HHAN initiative development. (2) Explore consumer experiences. (3) Identifying the entities and associations characterising the HHAN initiative and related outcomes. (4) Searching for different theoretical perspectives and explanations (abduction). (5) Hypothesising the mechanisms and [context] conditions that might have activated the generation of the HHAN outcomes (retroduction). Results: We identified three central mechanisms; trust, buy-in and motivation, and understanding family dynamics operating across consumer, provider and systems levels of the HHAN initiative. Discussion: These programme theories reveal that to achieve the goals of HHAN, interpersonal dynamics, fostering buy-in and ensuring motivation of both the consumers and care workers should be sought and sustained at all levels. Conclusion: The programme theories unveil that integrated care initiatives should foster positive relationships at all levels to ensure favourable consumer outcomes.

Unpacking the design, implementation and uptake of community-integrated health care services: a critical realist synthesis.

INTRODUCTION: Community-integrated care initiatives are increasingly being used for social and health service delivery and show promising outcomes. Nevertheless, it is unclear what structures and underlining causal agents (generative mechanisms) are responsible for explaining how and why they work or not. METHODS AND ANALYSIS: Critical realist synthesis, a theory-driven approach to reviewing and synthesising literature based on the critical realist philosophy of science, underpinned the study. Two lenses guided our evidence synthesis, the community health system and the patient-focused perspective of integrated care. The realist synthesis was conducted through the following steps: (1) concept mining and framework formulation, (2) searching for and scrutinising the evidence, (3) extracting and synthesising the evidence (4) developing the narratives from causal explanatory theories, and (5) disseminate, implement and evaluate. RESULTS: Three programme theories, each aligning with three groups of stakeholders, were unearthed. At the systems level, three bundles of mechanisms were identified, that is, (1) commitment and motivation, (2) willingness to address integrated health concerns and (3) shared vision and goals. At the provider level, five bundles of mechanisms critical to the successful implementation of integrated care initiatives were abstracted, that is, (1) shared vision and buy-in, (2) shared learning and empowerment, (3) perceived usefulness, (4) trust and perceived support and (5) perceived role recognition and appreciation. At the user level, five bundles of mechanisms were identified, that is, (1) motivation, (2) perceived interpersonal trust, (3) user-empowerment, (4) perceived accessibility to required services and (5) self-efficacy and self-determination. CONCLUSION: We systematically captured mechanism-based explanatory models to inform practice communities on how and why community-integrated models work and under what health systems conditions. PROSPERO REGISTRATION NUMBER: CRD42020210442.

Integrated Child and Family Hub models for detecting and responding to family adversity: protocol for a mixed-methods evaluation in two sites.

INTRODUCTION: Integrated community healthcare Hubs may offer a 'one stop shop' for service users with complex health and social needs, and more efficiently use service resources. Various policy imperatives exist to implement Hub models of care, however, there is a dearth of research specifically evaluating Hubs targeted at families experiencing adversity. To contribute to building this evidence, we propose to co-design, test and evaluate integrated Hub models of care in two Australian community health services in low socioeconomic areas that serve families experiencing adversity: Wyndham Vale in Victoria and Marrickville in New South Wales. METHODS AND ANALYSIS: This multisite convergent mixed-methods study will run over three phases to (1) develop the initial Hub programme theory through formative research; (2) test and, then, (3) refine the Hub theory using empirical data. Phase 1 involves co-design of each Hub with caregivers, community members and practitioners. Phase 2 uses caregiver and Hub practitioner surveys at baseline, and 6 and 12 months after Hub implementation, and in-depth interviews at 12 months. Two stakeholder groups will be recruited: caregivers (n=100-200 per site) and Hub practitioners (n=20-30 per site). The intervention is a co-located Hub providing health, social, legal and community services with no comparator. The primary outcomes are caregiver-reported: (i) identification of, (ii) interventions received and/or (iii) referrals received for adversity from Hub practitioners. The study also assesses child, caregiver, practitioner and system outcomes including mental health, parenting, quality of life, care experience and service linkages. Primary and secondary outcomes will be assessed by examining change in proportions/means from baseline to 6 months, from 6 to 12 months and from baseline to 12 months. Service linkages will be analysed using social network analysis. Costs of Hub implementation and a health economics analysis of unmet need will be conducted. Thematic analysis will be employed to analyse qualitative data. ETHICS AND DISSEMINATION: Royal Children's Hospital and Sydney Local Health District ethics committees have approved the study (HREC/62866/RCHM-2020). Participants and stakeholders will receive results through meetings, presentations and publications. TRIAL REGISTRATION NUMBER: ISRCTN55495932.

Understanding for whom, how and why Sydney Local Health District's Integrated Response was Effective in Addressing COVID-19: A Critical Realist Qualitative Study.

INTRODUCTION: Australia has been comparatively effective in preventing the transmission of COVID-19. The Sydney Local Health District [SLHD] used a "whole of health" integrated approach to respond to the pandemic. The aim of this study was to understand for whom, how and why this response worked, to inform a sustainable system transformation. METHODS: A critical realist qualitative study was conducted with 20 purposively selected key informants. Data were collected through in-depth interviews and analysed using thematic analysis guided by abduction and retroduction. The five strategies of the WHO integrated people-centred health services framework was used to guide the overall study. RESULTS: An enabling environment of a strong governance, emergency preparedness, a committed and adaptable workforce, and a strong core infrastructure underpinned SLHD's effective response. With a culture of embracing innovation, the district adapted virtual care to effectively quarantine people through their special health accommodation, and coordinate care across tertiary and community services. The established interagency relationships prior to the pandemic, enabled service directors to quickly integrate their services, which empowered and engaged the community [and staff], working across relevant sectors to provide care "where the people are"; reaching marginalised populations, and reducing community transmission. DISCUSSION AND CONCLUSION: The SLHD's progress towards a 'whole of health' approach, empowered and enabled the district to effectively work within and across sectors to address the pandemic in a people-centred manner. Sustaining the contextual conditions and mechanisms, that facilitated effective integration, will be beneficial beyond the pandemic.

Biofuel recovery from microalgae biomass grown in dairy wastewater treated with activated sludge: The next step in sustainable production.

Microalgae biofuel could be the next step in avoiding the excessive use of fossil fuels and reducing negative impacts on the environment. In the present study, two species of microalgae (Scenedesmus obliquus and Chlorella vulgaris) were used for biomass production, grown in dairy wastewater treated by activated sludge systems. The photobioreactors were operated in batch and in continuous mode. The dry biomass produced was in the range of 2.30 to 3.10 g L-1. The highest volumetric yields for lipids and carbohydrates were 0.068 and 0.114 g L-1 day-1. Maximum CO2 biofixation (750 mg L-1 day-1) was obtained in continuous mode. The maximum values for lipids (21%) and carbohydrates (39%) were recorded in the batch process with species Scenedesmus obliquus. In all of the experiments, the Linolenic acid concentration (C18:3) was greater than 12%, achieving satisfactory oxidative stability and good quality. Projected biofuel production could vary between 4,863,708 kg and 9,246,456 kg year-1 if all the dairy wastewater produced in Brazil were used for this purpose. Two hectares would be needed to produce 24,99 × 109 L year-1 of microalgae bioethanol, a far lower value than used in cultivating sugar cane. If all dairy wastewater generated annually in Brazil were used to produce microalgae biomass, it would be possible to obtain approximately 30,609 to 53,647 barrels of biodiesel per year. These data show that only by using dairy wastewater would biofuels be produced to replace 17% to 40% of the fossil fuels currently used in Brazil.

Enhanced Arthrospira platensis Biomass Production Combined with Anaerobic Cattle Wastewater Bioremediation.

Microalgae biomasses offer important benefits regarding macromolecules that serve as promising raw materials for sustainable production. In the present study, the microalgae Arthrospira platensis DHR 20 was cultivated in horizontal photobioreactors (HPBR), with and without temperature control, in batch mode (6 to 7 days), with anaerobically digested cattle wastewater (ACWW) as substrate. High dry biomass concentrations were observed (6.3-7.15 g L-1). Volumetric protein, carbohydrate, and lipid productivities were 0.299, 0.135, and 0.108 g L-1 day-1, respectively. Promising lipid productivities per area were estimated between 22.257 and 39.446 L ha-1 year-1. High CO2 bio-fixation rates were recorded (875.6-1051 mg L-1 day-1), indicating the relevant potential of the studied microalgae to mitigate atmospheric pollution. Carbon concentrations in biomass ranged between 41.8 and 43.6%. ACWW bioremediation was satisfactory, with BOD5 and COD removal efficiencies of 72.2-82.6% and 63.3-73.6%. Maximum values of 100, 95.5, 92.4, 80, 98, and 94% were achieved concerning the removal of NH4 +, NO3 -, Pt, SO4 2-, Zn, and Cu, respectively. Total and thermotolerant coliform removals reached 99-99.7% and 99.7-99.9%. This microalgae-mediated process is, thus, promising for ACWW bioremediation and valuation, producing a microalgae biomass rich in macromolecules that can be used to obtain friendly bio-based products and bioenergy. Supplementary Information: The online version contains supplementary material available at 10.1007/s12155-021-10258-4.

The Burden of Mental Illness Among Survivors of Critical Care-Risk Factors and Impact on Quality of Life: A Multicenter Prospective Cohort Study.

BACKGROUND: Survivors of critical care may demonstrate mental health disorders in the months after discharge. RESEARCH QUESTION: What are risk factors for mental health disorders after ICU discharge and is there an association between the burden of mental illness and health-related quality of life (HRQoL)? STUDY DESIGN AND METHODS: Multicenter prospective cohort study that included 579 adult ICU survivors with an ICU stay of > 72 h in 10 ICUs. RESULTS: The outcomes were anxiety and depression assessed by the Hospital Anxiety and Depression Scale, posttraumatic stress disorder (PTSD) assessed by the Impact Event Scale 6, and HRQoL assessed by the Short Form 12 version 2. The 6-month prevalences of any mental health disorder were 36.2% (the prevalences of anxiety, depression, and PTSD were 24.2%, 20.9%, and 15.4%, respectively). ICU survivors with mental health disorders showed worse HRQoL scores in both physical and mental dimensions than those without. The higher the number of psychiatric syndromes manifested, the worse the mental dimension of HRQoL. Age of < 65 years (P = .009), history of depression (P = .009), anxiety (P = .003) and depression (P = .02) symptoms at ICU discharge, physical dependence (P = .01), and decreased physical functional status (P = .04) at 6 months were associated with anxiety. History of depression (P = .001), depression symptoms at ICU discharge (P < .001), and decreased physical functional status at 6 months (P = .01) were associated with depression. Depression symptoms at ICU discharge (P = .01), physical dependence (P = .01), and decreased physical functional status (P = .02) at 6 months were associated with PTSD. INTERPRETATION: The network of potential risk factors for mental illness among patients discharged from an ICU is complex and involves multiple factors (age, premorbid mental health, acute emotional stress, and physical impairment after ICU stay). The negative impact of the burden of mental illness on HRQoL among critical care survivors is of concern.

Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial.

OBJECTIVE: To determine whether tocilizumab improves clinical outcomes for patients with severe or critical coronavirus disease 2019 (covid-19). DESIGN: Randomised, open label trial. SETTING: Nine hospitals in Brazil, 8 May to 17 July 2020. PARTICIPANTS: Adults with confirmed covid-19 who were receiving supplemental oxygen or mechanical ventilation and had abnormal levels of at least two serum biomarkers (C reactive protein, D dimer, lactate dehydrogenase, or ferritin). The data monitoring committee recommended stopping the trial early, after 129 patients had been enrolled, because of an increased number of deaths at 15 days in the tocilizumab group. INTERVENTIONS: Tocilizumab (single intravenous infusion of 8 mg/kg) plus standard care (n=65) versus standard care alone (n=64). MAIN OUTCOME MEASURE: The primary outcome, clinical status measured at 15 days using a seven level ordinal scale, was analysed as a composite of death or mechanical ventilation because the assumption of odds proportionality was not met. RESULTS: A total of 129 patients were enrolled (mean age 57 (SD 14) years; 68% men) and all completed follow-up. All patients in the tocilizumab group and two in the standard care group received tocilizumab. 18 of 65 (28%) patients in the tocilizumab group and 13 of 64 (20%) in the standard care group were receiving mechanical ventilation or died at day 15 (odds ratio 1.54, 95% confidence interval 0.66 to 3.66; P=0.32). Death at 15 days occurred in 11 (17%) patients in the tocilizumab group compared with 2 (3%) in the standard care group (odds ratio 6.42, 95% confidence interval 1.59 to 43.2). Adverse events were reported in 29 of 67 (43%) patients who received tocilizumab and 21 of 62 (34%) who did not receive tocilizumab. CONCLUSIONS: In patients with severe or critical covid-19, tocilizumab plus standard care was not superior to standard care alone in improving clinical outcomes at 15 days, and it might increase mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT04403685.

Care Coordination for Vulnerable Families in the Sydney Local Health District: What Works for Whom, under What Circumstances, and Why?

INTRODUCTION: Healthy Homes and Neighbourhoods (HHAN), an integrated care programme in the Sydney Local Health District (SLHD), seeks to address the needs of disadvantaged families through care coordination, as one of its components. This research aims to determine for whom, when and why the care coordination component of HHAN works, and establish the reported outcomes for clients, service-providers and partner organisations. METHODS: Critical realist methodology was utilised to undertake a qualitative evaluation of the impact of care coordination. Purposive sampling was used to select a total of 37 participants for interview, including consumers, service-providers and key stakeholders. Thematic analysis was undertaken to derive the major modes of intervention of HHAN, and data representing these elements was coded and summarised under contexts, mechanisms and outcomes. RESULTS: Analysis indicates that care coordination has a positive impact on clients' sense of independence, self-awareness and outlook on life. Trust and favourable interpersonal relations were identified as major underlying mechanisms for a successful client-provider working relationship. The identified modes of intervention facilitating positive consumer outcomes included accessibility, flexibility and service navigation. Persistent siloes in health and systemic resistance to collaboration was seen to hinder effective care delivery. CONCLUSIONS: This study suggests that a care coordination model may be effective in engaging disadvantaged families in healthcare, assist them in navigating the health system and can lead to beneficial health and social outcomes. Successful implementation of care coordination requires flexible programme design and experienced and skilful clinicians to fulfil the care coordinator role. There is a need to appreciate the negative impact that the complex and siloed health system can have on disadvantaged families.

Refining Program Theory for a Place-Based Integrated Care Initiative in Sydney, Australia.

INTRODUCTION: The Healthy Homes and Neighbourhoods (HHAN) Integrated Care Program seeks to enhance vulnerable family engagement with health and social services through a care coordination model. Besides servicing families in Sydney, HHAN has also established place-based initiatives (PBIs) in areas of disadvantage such as Redfern. The Redfern PBI co-locates HHAN with housing, drug and alcohol services, and financial and legal services. This integration aims to facilitate service access and multi-agency support for vulnerable families in Redfern. Hence, this study aims to evaluate for whom, when and why HHAN's PBI at Redfern works, or not, and what are its outcomes. METHODS: The project utilises critical realist methodology to undertake a qualitative evaluation of the impact of the PBI on clients, services and the community. Purposive sampling was used to identify 21 participants including HHAN clients, HHAN staff and stakeholders (HHAN partners). In-depth, semi-structured interviews were audio-recorded, transcribed, coded and analysed using a context (C), intervention (I), mechanism (M) outcome (O) (CIMO) approach to abductive analysis. RESULTS: Five key CIMO configurations of the Redfern PBI emerged - whole-of-family involvement, flexibility, trust, building connections and co-location. Whilst each theory had specific outcomes, overall client outcomes included improved access to services, better outlook, empowerment and engagement with services. Service outcomes included increased collaboration and foundation for integration between HHAN and other services. Negative outcomes included lack of full integration, the risk associated with integration and difficulty evaluating impact. CONCLUSION: This study successfully refined the program theory for subsequent use in later implementation of critical realist evaluation studies.

Early and Late Mortality Following Discharge From the ICU: A Multicenter Prospective Cohort Study.

OBJECTIVES: To identify the frequency, causes, and risk factors of early and late mortality among general adult patients discharged from ICUs. DESIGN: Multicenter, prospective cohort study. SETTING: ICUs of 10 tertiary hospitals in Brazil. PATIENTS: One-thousand five-hundred fifty-four adult ICU survivors with an ICU stay greater than 72 hours for medical and emergency surgical admissions or greater than 120 hours for elective surgical admissions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcomes were early (30 d) and late (31 to 365 d) mortality. Causes of death were extracted from death certificates and medical records. Twelve-month cumulative mortality was 28.2% (439 deaths). The frequency of early mortality was 7.9% (123 deaths), and the frequency of late mortality was 22.3% (316 deaths). Infections were the leading cause of death in both early (47.2%) and late (36.4%) periods. Multivariable analysis identified age greater than or equal to 65 years (hazard ratio, 1.65; p = 0.01), pre-ICU high comorbidity (hazard ratio, 1.59; p = 0.02), pre-ICU physical dependence (hazard ratio, 2.29; p < 0.001), risk of death at ICU admission (hazard ratio per 1% increase, 1.008; p = 0.03), ICU-acquired infections (hazard ratio, 2.25; p < 0.001), and ICU readmission (hazard ratio, 3.76; p < 0.001) as risk factors for early mortality. Age greater than or equal to 65 years (hazard ratio, 1.30; p = 0.03), pre-ICU high comorbidity (hazard ratio, 2.28; p < 0.001), pre-ICU physical dependence (hazard ratio, 2.00; p < 0.001), risk of death at ICU admission (hazard ratio per 1% increase, 1.010; p < 0.001), and ICU readmission (hazard ratios, 4.10, 4.17, and 1.82 for death between 31 and 60 days, 61 and 90 days, and greater than 90 days after ICU discharge, respectively; p < 0.001 for all comparisons) were associated with late mortality. CONCLUSIONS: Infections are the main cause of death after ICU discharge. Older age, pre-ICU comorbidities, pre-ICU physical dependence, severity of illness at ICU admission, and ICU readmission are associated with increased risk of early and late mortality, while ICU-acquired infections are associated with increased risk of early mortality.

A Critical Realist Translational Social Epidemiology Protocol for Concretising and Contextualising a "Theory of Neighbourhood Context, Stress, Depression, and the Developmental Origins of Health and Disease (DOHaD)", Sydney Australia.

BACKGROUND: We will describe here a translational social epidemiology protocol for confirming a critical realist "Theory of Neighbourhood Context, Stress, Depression, and the Developmental Origins of Health and Disease (DOHaD). The approach will include the concretising and contextualising of the above causal theory into programme theories for child and adolescent interventions that aim to break intergenerational cycles of disadvantage and poor life outcomes. In undertaking this work we seek to advance realist translational methodology within the discipline of applied perinatal and paediatric social epidemiology. THEORY AND METHODS: The research settings are in metropolitan Sydney. The design will be a longitudinal, multi-level, mixed method realist evaluation of applied programme interventions that seek to break the intergeneration cycle of social disadvantage and poor child health and developmental outcomes. The programme of research will consist of three components: 1) Operationalisation of the theory and designing of programme initiatives for implementation; 2) Evaluation of the translated programme and implementation theory using Theory of Change and critical realist evaluation; and 3) Theory Testing of realist hypotheses using both intensive and extensive critical realist research methods including realist structural modelling. DISCUSSION: The proposed programme of research will assist in translating empirical explanatory theory building to theory driven interventions. The research will be situated in socially disadvantaged regions of Sydney where the local child and family inter-agencies will collaborate to design and implement new initiatives that address significant disparities in childhood development and adolescent outcomes attributed to neighbourhood circumstances, family stress and intergenerational cycles of disadvantage and poor mental health.

Designing Initiatives for Vulnerable Families: From Theory to Design in Sydney, Australia.

INTRODUCTION: Intergenerational cycles of poverty, violence and crime, poor education and employment opportunities, psychopathology, and poor lifestyle and health behaviours require innovative models of health care delivery to break them. We describe a programme of research informed service development targeting vulnerable families in inner metropolitan Sydney, Australia that is designed to build and confirm a "Theory of Neighbourhood Context, Stress, Depression, and the Developmental Origins of Health and Disease (DOHaD)". We describe the development of an intervention design and business case that drew on earlier realist causal and programme theoretical work. METHODS: Realist causal and programme theory were used to inform the collaborative design of initiatives for vulnerable families. The collaborative design process included: identification of desirable and undesirable outcomes and contextual factors, consultation forums, interagency planning, and development of a service proposal. RESULTS: The design elements included: perinatal coordination, sustained home visiting, integrated service model development, two place-based hubs, health promotion and strengthened research and analysis capability. CONCLUSIONS: We demonstrate here the design of interventions for vulnerable families in Sydney utilising translational research from previous realist causal and program theory building to operational service design. We have identified the importance of our earlier analysis of underlying causal mechanisms and related programme mechanisms for identifying the elements for the full intervention design. The application of theory added rigour to the design of the integrated care initiatives. In applying the theory to the local situation the analysis took into account: the role of the local agencies; evidence of program effectiveness; determinants and outcomes for local children and their families; the current deployment of service resources; and insights from front-line staff and interagency partners.

Designing an Integrated Care Initiative for Vulnerable Families: Operationalisation of Realist Causal and Programme Theory, Sydney Australia.

INTRODUCTION: In July 2015 Sydney Local Health District (SLHD) implemented an integrated care initiative for vulnerable families in the Inner West region of Sydney, Australia. The initiative was designed as a cross-agency care coordination network that would ensure that vulnerable families: had their complex health and social needs met; kept themselves and their children safe; and were connected to society. We will describe the development of the design that drew on earlier realist causal and program theoretical work. METHODS: Realist causal and program theory were used to inform the collaborative design of an initiative for vulnerable families. The collaborative design process included: identification of desirable and undesirable outcomes and contextual factors, stakeholder consultation, interagency planning, and development of a service proposal. RESULTS: The design elements included: identification of vulnerable family cohorts; care coordination; evidence-informed intervention(s); general practice engagement and support; family health improvement; placed-based neighbourhood initiatives; interagency system change and collaborative planning; monitoring of individual and family outcomes; and evaluation. CONCLUSIONS: The design study described advances toward the implementation of a whole-of-government integrated health and social care initiative. The initiative was designed as a cross-agency care coordination network that would ensure that vulnerable families: had their complex health and social needs met; kept themselves and their children safe; and were connected to society. In so doing we aim to break intergenerational cycles of poverty, violence and crime, poor education and employment opportunities, psychopathology, and poor lifestyle and health behaviours, through strengthening family resilience, improving access to services, and addressing the social determinants of health and wellbeing.

Implementation, Mechanisms of Effect and Context of an Integrated Care Intervention for Vulnerable Families in Central Sydney Australia: A Research and Evaluation Protocol.

INTRODUCTION: In March 2014, the New South Wales (NSW) Government (Australia) announced the NSW Integrated Care Strategy. In response, a family-centred, population-based, integrated care initiative for vulnerable families and their children in Sydney, Australia was developed. The initiative was called Healthy Homes and Neighbourhoods. A realist translational social epidemiology programme of research and collaborative design is at the foundation of its evaluation. THEORY AND METHOD: The UK Medical Research Council (MRC) Framework for evaluating complex health interventions was adapted. This has four components, namely 1) development, 2) feasibility/piloting, 3) evaluation and 4) implementation. We adapted the Framework to include: critical realist, theory driven, and continuous improvement approaches. The modified Framework underpins this research and evaluation protocol for Healthy Homes and Neighbourhoods. DISCUSSION: The NSW Health Monitoring and Evaluation Framework did not make provisions for assessment of the programme layers of context, or the effect of programme mechanism at each level. We therefore developed a multilevel approach that uses mixed-method research to examine not only outcomes, but also what is working for whom and why.

Evolutionary analyses of myosin genes in trypanosomatids show a history of expansion, secondary losses and neofunctionalization.

Myosins are motor proteins that comprise a large and diversified family important for a broad range of functions. Two myosin classes, I and XIII, were previously assigned in Trypanosomatids, based mainly on the studies of Trypanosoma cruzi, T. brucei and Leishmania major, and important human pathogenic species; seven orphan myosins were identified in T. cruzi. Our results show that the great variety of T. cruzi myosins is also present in some closely related species and in Bodo saltans, a member of an early divergent branch of Kinetoplastida. Therefore, these myosins should no longer be considered "orphans". We proposed the classification of a kinetoplastid-specific myosin group into a new class, XXXVI. Moreover, our phylogenetic data suggest that a great repertoire of myosin genes was present in the last common ancestor of trypanosomatids and B. saltans, mainly resulting from several gene duplications. These genes have since been predominantly maintained in synteny in some species, and secondary losses explain the current distribution. We also found two interesting genes that were clearly derived from myosin genes, demonstrating that possible redundant or useless genes, instead of simply being lost, can serve as raw material for the evolution of new genes and functions.