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Introduction: Population health management is increasingly being used to support place-based models of care. This case study provides an account of the use of the Population Health Management - Maturity Index (PHM-MI) tool to inform the future development of a neighbourhood model of care for older people in the Central Coast region of Australia., Description: The PHM-MI tool comprises a set of six evidence-informed elements known to be important in enabling PHM in practice. As part of a joint strategic needs assessment, 17 selected stakeholders from key regional organizations were invited to undertake the PHM-MI tool survey. Three follow-up workshops were held to interpret the results and determine priority actions., Discussion: The PHM-MI scores revealed that the overall maturity of the Central Coast to successfully deliver PHM was low across all six elements, findings that were corroborated through participant workshops. Systemic fragmentations, most pertinently of funding and regulation, incentivised silo-based working. The need to formalise and strengthen regional collaborations, enable data integration, find creative ways to use existing funding streams, and promote community engagement were highlighted as core priorities., Conclusion: Using the PHM-MI tool was enabled by it being embedded within a pre-existing regional strategic process. The results were used to inform future regional priorities. The PHM-MI tool has the potential for use across regional or national contexts., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

A need exists to improve end-of-life care for people with advanced dementia, by integrating available services. Stakeholders on the Central Coast of New South Wales united to co-design an improved model of care that would integrate care across care settings. The aim of this project was to co-design a model of integrated, person-centred palliative care for people with dementia at the end of life. This case study describes seven co-design workshops which took place in 2023 to develop a program logic model. Workshops were run in a hybrid format, with stakeholders attending in person and online. Workshops were attended by an average of 26 stakeholders including people and carers with lived experience of dementia, healthcare workers from hospital and community-based services (public and private), primary care clinicians, and participants from the not-for-profit sector and academia. Stakeholders developed a shared mission and purpose and identified priority areas for improving palliative care for people with advanced dementia. This led to the development of a program logic model, which included components relating to education for people with dementia, carers, and professionals, care coordination and referrals, and regular multidisciplinary case conferences. Feedback on the model from a new audience identified areas for improvement. The stakeholder group participated in a survey to evaluate the effectiveness of the co-design. The survey found that stakeholders were satisfied with the model of care the group developed. This project highlighted the value of adopting a co-design approach with stakeholders to develop a new model of care.

Visually-induced dizziness (visual vertigo) is a core symptom of Persistent Perceptual Postural Dizziness (PPPD) and occurs in other conditions and general populations. It is difficult to treat and lacks new treatments and research. We incorporated the existing rehabilitation approach of visual desensitisation into an online game environment to enhance control over visual motion and complexity. We report a mixed-methods feasibility trial assessing: Usage and adherence; rehabilitation potential; system usability and enjoyment; relationship with daily dizziness. Participants played online with (intervention, N = 37) or without (control, N = 39) the visual desensitisation component for up to 5-10 min, twice daily for 6 weeks. Dropout was 45%. In the intervention group, N = 17 played for the recommended time while N = 20 played less. Decreases in visual vertigo symptoms, anxiety and depression correlated with playtime for the intervention but not control. System usability was high. Daily symptoms predicted playtime. Qualitative responses broadly supported the gamified approach. The data suggest gamified visual desensitisation is accessible, acceptable and, if adherence challenges can be overcome, could become a useful addition to rehabilitation schedules for visually-induced dizziness and associated anxiety. Further trials are needed., (© 2024. The Author(s).)

A key element of women's empowerment is the ability to participate in household decision-making. This study presents the qualitative results from the Shonjibon Cash and Counselling Trial baseline process evaluation with the aim of exploring the status of women's decision-making at the trial's outset and to facilitate the exploration of any changes in women's empowerment over the course of the trial. Between January and March 2021, we conducted forty-one in-depth interviews with pregnant women in rural Bangladesh. The research team translated, transcribed, coded, and discussed the interviews. We used thematic analysis to examine women's experience and perceptions on household decision-making. The key findings that emerged; women jointly participated in financial decision-making with their husbands; men made the final decision regarding seeking healthcare, and women solely made choices regarding infant and young child feeding. Our findings revealed that women felt that they needed to discuss their plans to go outside the house with their husbands, many perceived a lack of importance in the community towards women's participation in decision-making. This study documents current contextual information on the status of women's involvement in household decision-making and intrahousehold power dynamics at the start of the Shonjibon Cash and Counselling Trial., Competing Interests: The authors report there are no competing interests to declare., (Copyright: © 2024 Kirkwood et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Cognitive load impacts performance of debriefers and learners during simulations, but limited data exists examining debriefer cognitive load. The aim of this study is to compare the cognitive load of the debriefers during simulation-based team training (SbTT) with Rapid Cycle Deliberate Practice (RCDP) debriefing and Traditional Reflective Debriefing (TRD). We hypothesize that cognitive load will be reduced during RCDP compared to TRD., Methods: This study was part of a large-scale, interdisciplinary team training program at Children's Healthcare of Atlanta Egleston Pediatric Emergency Department, with 164 learners (physicians, nurses, medical technicians, paramedics, and respiratory therapists (RTs)). Eight debriefers (main facilitators and discipline-specific coaches) led 28 workshops, which were quasi-randomized to either RCDP or TRD. Each session began with a baseline medical resuscitation scenario and cognitive load measurement using the NASA Task Load Index (TLX), and the NASA TLX was repeated immediately following either TRD or RCDP debriefing. Raw scores of the NASA TLX before and after intervention were compared. ANOVA tests were used to compare differences in NASA TLX scores before and after intervention between the RCDP and TRD groups., Results: For all debriefers, mean NASA TLX scores for physical demands and frustration significantly decreased (- 0.8, p = 0.004 and - 1.3, p = 0.002) in TRD and mean perceived performance success significantly increased (+ 2.4, p < 0.001). For RCDP, perceived performance success increased post-debriefing (+ 3.6, p < 0.001), time demands decreased (- 1.0, p = 0.04), and frustration decreased (- 2.0, p < 0.001). Comparing TRD directly to RCDP, perceived performance success was greater in RCDP than TRD (3.6 vs. 2.4, p = 0.04). Main facilitators had lower effort and mental demand in RCDP and greater perceived success (p < 0.001)., Conclusion: RCDP had greater perceived success than TRD for debriefers. Main facilitators also report reduced effort and baseline mental demand in RCDP. For less experienced debriefers, newer simulation programs, or large team training sessions such as our study, RCDP may be a less mentally demanding debriefing methodology for facilitators., (© 2024. The Author(s).)

Objective: This scoping review has 3 objectives: to identify the literature on older adults' engagement with community music-making in which an experience of transformative change is noted; to explore the different ways transformation is described; and to identify factors that enable this experience., Introduction: Music has been shown to stimulate transformation (positive change) in individuals. Documented experiences of transformation fall into 3 broad areas: self-perception, quality of life, and personal growth. Yet the specific elements of musical experience that enable such effects remain little understood. Identifying the literature on this topic will enable deeper understanding and identify gaps in knowledge., Inclusion Criteria: The review will include peer-reviewed publications, systematic and scoping reviews, and gray literature, including theses and reports. Studies will focus on older community-dwelling adults (60 years or over) engaged in group music-making in community settings. The studies must include enquiry into transformative effects. Music used therapeutically in health settings; individual music-making; and listening (rather than active music-making) will be excluded. Any empirical methodology will be accepted., Methods: The review will follow the JBI guidelines for scoping reviews. Databases to be searched will include MEDLINE (Ovid), CINAHL (EBSCOhost), PsycINFO (Ovid), Scopus, Embase (Ovid), Informit, Cochrane Library, Campbell Collaboration, JBI EBP, Web of Science, JSTOR, Academic Search Ultimate (EBSCOhost), ProQuest Dissertations & Theses Global, and Google Scholar. Studies must be published in English, from 2000 until the present. Retrieved studies will be independently screened by at least 2 reviewers. Data will be extracted using a data extraction tool developed by the research team. The findings will be presented in tabular format, supported by a narrative summary., Details of the Review Are Available in Open Science Framework: https://osf.io/ftuhx., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 JBI.)

The rate of progression of Alzheimer's disease (AD) differs dramatically between patients. Identifying the most is critical because when their numbers differ between treated and control groups, it distorts the outcome, making it impossible to tell whether the treatment was beneficial. Much recent effort, then, has gone into identifying RPs. We pooled de-identified placebo-arm data of three randomized controlled trials (RCTs), EXPEDITION, EXPEDITION 2, and EXPEDITION 3, provided by Eli Lilly and Company. After processing, the data included 1603 mild-to-moderate AD patients with 80 weeks of longitudinal observations on neurocognitive health, brain volumes, and amyloid-beta (Aβ) levels. RPs were defined by changes in four neurocognitive/functional health measures. We built deep learning models using recurrent neural networks with attention mechanisms to predict RPs by week 80 based on varying observation periods from baseline (e.g., 12, 28 weeks). Feature importance scores for RP prediction were computed and temporal feature trajectories were compared between RPs and non-RPs. Our evaluation and analysis focused on models trained with 28 weeks of observation. The models achieved robust internal validation area under the receiver operating characteristic (AUROCs) ranging from 0.80 (95% CI 0.79-0.82) to 0.82 (0.81-0.83), and the area under the precision-recall curve (AUPRCs) from 0.34 (0.32-0.36) to 0.46 (0.44-0.49). External validation AUROCs ranged from 0.75 (0.70-0.81) to 0.83 (0.82-0.84) and AUPRCs from 0.27 (0.25-0.29) to 0.45 (0.43-0.48). Aβ plasma levels, regional brain volumetry, and neurocognitive health emerged as important factors for the model prediction. In addition, the trajectories were stratified between predicted RPs and non-RPs based on factors such as ventricular volumes and neurocognitive domains. Our findings will greatly aid clinical trialists in designing tests for new medications, representing a key step toward identifying effective new AD therapies., Competing Interests: PS is funded by the McCord Family Professorship in Neurology, the Umphrey Family Professorship in Neurodegenerative Disorders, multiple NIH grants and several foundation grants (1R01AG080137-01A1, 1RF1AG072491-01, 1R03AG077191-01, 1U01AG079847-01A1, 5R01AG66749-03, 1R01AG083039-01, 5R01AG067498-03, 1RF1AG055053-0A1, 1R01AG062690-01, 1R01AG059321-01A1, 1R01DE07027, 1R01AG082721-01, 2124789, AGT002985, AGT008724, AGT009122), and contracts with multiple pharmaceutical companies related to the performance of clinical trials (ALZ-80-AD301-AGT005383, AGT004414, AGT003423, AGT003882, AGT006620, AGT005768, AGT004564, AGT009188, AGT006056, AGT006764, AGT008197, AGT010139, AGT011949). He serves as a consultant and speaker for Eli Lilly, and Acadia Pharmaceuticals. No other authors have declarations to disclose., (Copyright: © 2024 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Nursing homes struggle to meet the needs of their residents as they become older and frailer, live with more complex co-morbidity, and are impacted by memory impairment and dementia. Moreover, the nursing home system is overwhelmed with significantly constraining organisational and regulatory demands that stand in the way of achieving resident-focused outcomes. These issues are compounded by the perceptions of poor working environments, poor remuneration, and poor satisfaction amongst staff. The system is beyond the state of 'reform' and requires a fundamental redesign based on first organisational systems understandings: a clearly defined purpose and goal, shared values, and system-wide agreed "simple (or operating) rules". A 'fit-for-purpose' future requires a complex adaptive nursing home system characterised by seamless 'bottom-up and top-down' information flows to ensure that the necessary 'work that needs to be done' is done, and a governance structure that focuses on quality improvement and holds the system accountable for the quality of care that is provided., (© 2024 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Nursing homes (also referred to as residential aged care facilities, or long-term care facilities) cater for older people on a respite or long-term basis for those who are no longer able to live independently at home. Globally the sector struggles to meet societal expectations since it is torn between three competing agendas-meeting the needs of residents, meeting the demands of regulators, and meeting the financial imperatives of nursing home proprietors. Competing demands indicate that the system lacks a clear understanding of its purpose-without a clearly understood purpose any system will become dysfunctional overall and across all its levels of organisation. This scoping study aims to summarise and synthesise what is already known about the systemic function and failures in the nursing home system, and the impact this has on the wider health and aged care system., Method: MEDLINE, EMBASE, PSYCHINFO, CINAHL and SCOPUS were searched using the terms: (nursing home care OR residential aged care OR nursing home) AND (organisational failure OR institutional failure OR systemic failure), limited to English language articles, including all years up to the end of February 2021. In addition, we used snowballing of article references and Google searches of the grey literature. System-focused articles were defined as those that explored how an issue at one system level impacted other system levels, or how an issue impacted at least two different agents at the same system level., Result: Thirty-eight articles addressed systemic issues as defined in four different contexts: United States (14), Canada (2), Australia (11) and European countries (11). Only four studies reported whole-of-system findings, whereas the remaining 34 more narrowly addressed systemic features of specific nursing home issues. The thematic analysis identified 29 key systemic issues across five system layers which consistently appear across every country/health system context. The negative outcomes of these systemic failings include: high rates of regulatory reprimands for unacceptable or unsafe practices; dissatisfaction in care experiences on the part of residents, families, and care staff-including a fear of being sent to a nursing home; and the perception amongst staff that nursing homes are not preferred places to work., Conclusions: The key issues affecting nursing home residents, and the care home sector more generally, are systemic in nature arising from two key issues: first, the lack of shared agreement on the care home system's purpose; and second, the lack of clear governance and accountability frameworks for system regulation and performance at a national level. Addressing these two key issues must be the starting point for any 'real' nursing home system redesign that can achieve a seamlessly integrated system that delivers the outcomes nursing home residents and their families expect. 'Systems thinking' is required to simultaneously improve care quality and outcomes for residents, strengthen regulation and accountability, and enable financial viability., (© 2024 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Introduction: Epilepsy is the most common neurological condition globally. Integrating health and social care is fundamental in epilepsy management, but the scope of progress in this area is unclear. This scoping review aimed to capture the range and type of integrated care components and models in epilepsy management., Methods: Four databases were searched for articles published since 2010 that reported on integrated care in epilepsy. Data were extracted and synthesised into components of integrated care that had been implemented or recommended only. Models of integrated care were identified, and their components tabulated., Results: Fifteen common and interrelated components of integrated care emerged that were aligned with four broad areas: healthcare staff and pathways (e.g., epilepsy nurses); tasks and services (e.g., care coordination); education and engagement (e.g., shared decision making); and technology for diagnosis and communication (e.g., telehealth). Twelve models of integrated care were identified; seven were implemented and five were recommended., Discussion: There is a growing evidence-base supporting integrated, person-centred epilepsy care, but implementation is challenged by entrenched silos, underdeveloped pathways for care, and deficits in epilepsy education., Conclusion: Integrating epilepsy care relies on changes to workforce development and policy frameworks to support whole-of-system vision for improving care., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Background: In simulation-based education, debriefing is necessary to promote knowledge acquisition and skill application. Rapid Cycle Deliberate Practice (RCDP) and Traditional Reflective Debriefing (TRD) are based in learning theories of deliberate practice and reflective learning, respectively. In this study, we compared the effectiveness of TRD versus RCDP on acquisition of conceptual knowledge and teamwork skills among interdisciplinary learners in the pediatric emergency department., Methods: One hundred sixty-four learners including emergency department attending physicians, fellows, nurses, medical technicians, paramedics, and respiratory therapists, participated in 28 in-situ simulation workshops over 2 months. Groups were quasi-randomized to receive RCDP or TRD debriefing. Learners completed a multiple-choice test to assess teamwork knowledge. The TEAM Assessment Tool assessed team performance before and after debriefing. Primary outcomes were teamwork knowledge and team performance., Results: Average pre-intervention baseline knowledge assessment scores were high in both groups (TRD mean 90.5 (SD 12.7), RCDP mean 88.7 (SD 15.5). Post-test scores showed small improvements in both groups (TRD mean 93.2 (SD 12.2), RCDP mean 89.9 (SD 13.8), as indicated by effect sizes (ES = 0.21 and 0.09, for TRD and RCDP, respectively). Assessment of team performance demonstrated a significant improvement in mean scores from pre-assessment to post-assessment for all TEAM Assessment skills in both TRD and RCDP arms, based on p-values (all p < 0.01) and effect sizes (all ES > 0.8). While pre-post improvements in TEAM scores were generally higher in the RCDP group based on effect sizes, analysis did not indicate either debriefing approach as meaningfully improved over the other., Conclusions: Our study did not demonstrate that either TRD versus RCDP was meaningfully better in teamwork knowledge acquisition or improving skill application and performance. As such, we propose Reflective Deliberate Practice as a framework for future study to allow learners to reflect on learning and practice in action., (© 2024. The Author(s).)

Introduction: People living with long-term neurological conditions (LTNCs) have complex needs that demand intensive care coordination between sectors. This review aimed to establish if integrated care improves outcomes for people, and what characterises successful interventions., Methods: A systematic review of the literature was undertaken evaluating multisectoral integrated care interventions in people living with Parkinson's disease (PD), Multiple Sclerosis (MS) and Huntington's disease (HD). Strength of evidence was rated for the different outcomes., Results: A total of 15 articles were included, reporting on 2095 patients and caregivers, finding that integrated care can improve people's access to resources and reduce patients' depression. UK studies indicated improvements in patients' quality of life, although the international literature was inconclusive. Few programmes considered caregivers' outcomes, reporting no difference or even worsening in depression, burden and quality of life. Overall, the evidence showed a mismatch between people's needs and outcomes measured, with significant outcomes (e.g., self-management, continuity of care, care experience) lacking. Successful programmes were characterised by expert knowledge, multisectoral care coordination, care continuity and a person-centred approach., Conclusions: The impact of integrated care programmes on people living with LTNCs is limited and inconclusive. For a more person-centred approach, future studies need to assess integrated care from a service-user perspective., Patient and Public Contribution: Thirty people living with LTNCs were involved in this review, through defining research questions, validating the importance of the project, and increasing the researchers' understanding on what matters to service users. A patient and public involvement subgroup of representatives with lived experience on PD, MS and HD identified the need for more person-centred integrated care, with specific concerns over care fragmentation, care duplication and care continuity. This was key to data analysis and formulating the characteristics of successful and unsuccessful integrated care programmes from the perspective of service users. The discrepancy between service users' needs and the outcomes assessed in the literature point to user-driven research as the solution to address what matters to patients and caregivers., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Background: Improving palliative and end-of-life care for people with dementia is a growing priority globally. This study aimed to integrate multiple perspectives on end-of-life care for people with dementia and carers, to identify clinically relevant areas for improvement., Methods: The mixed-methods study involved surveys, interviews, and workshops with two participant groups: healthcare professionals and carers (individuals who provided care and support to a family member or friend). Healthcare professionals were invited to complete an online adapted version of the Australian Commission on Safety and Quality in Health Care, End-of-Life Care Toolkit: Clinician Survey Questions. Carers completed a hard copy or online adapted version of the Views of Informal Carers-Evaluation of Services (Short form) (VOICES-SF) questionnaire. Interview schedules were semi-structured, and workshops followed a co-design format. Findings were integrated narratively using a weaving approach., Results: Five areas in which we can improve care for people with dementia at the end of life, were identified: 1) Timely recognition of end of life; 2) Conversations about palliative care and end of life; 3) Information and support for people with dementia and carers; 4) Person-and-carer-centred care; 5) Accessing quality, coordinated care., Conclusions: There are multiple areas where we can improve the quality of end-of-life care people with dementia receive. The findings demonstrate that the heterogeneous and challenging experiences of living with and caring for people with dementia necessitate a multidisciplinary, multifaceted approach to end-of-life care. The identified solutions, including care coordination, can guide local development of co-designed models of end-of-life care for people with dementia., (© 2024. The Author(s).)

Background: The need for better end-of-life care for people with dementia has been acknowledged. Existing literature suggests that people dying with dementia have less access to palliative care, yet little is known about the care provided to people with dementia at the end of life. This study aimed to establish evidence related to end-of-life care for people dying with dementia in hospital compared to other settings., Methods: A retrospective clinical audit of people who had a diagnosis of dementia and had accessed services within a local health district, who died between 2015 and 2019, was conducted. A total of 705 people were identified, and a subset of 299 people randomly selected for manual audit. Chi-square p-values were used to compare the place of death, and a t-test or non-parametric test was used to assess the significance of the difference, as appropriate. Measures of functional decline within one month of death were assessed using mixed effects logistic regression models., Results: The characteristics of people differed by place of death, with people who died in hospital more likely to be living at home and to not have a spouse. Less than 1 in 5 people had advance care directives or plans. Many were still being actively treated at the time of death: almost half of people who died in hospital had an investigation in their final 72 hours, less than half of people were coded as receiving palliative care at death, and more than 2 in 3 people did not get access to specialist palliative care. Declining function was associated with the terminal phase., Conclusion: This study provides novel insights for those providing end-of-life care for people with dementia. Healthcare professionals and policy makers should consider how demographic characteristics relate to the places people with dementia receive end-of-life care. The care provided to people with dementia in the last year of their life highlights the need for more support to prepare advance care documentation and timely consideration for palliative care. Changes in markers of nutritional status and function in people with advanced dementia may help with identification of terminal phases., (© 2024. The Author(s).)

Background: People with dementia have different care and support needs at their end of life compared to people with other life-limiting illnesses, and general palliative care models may not meet the needs of people with dementia and their carers and families. Some dementia-specific end-of-life care models have been implemented, and a summary of existing models was undertaken to inform development of a local model., Aim: To identify best-practice models of care for people in the advanced and end stages of dementia, and their families and carers., Design: A rapid review with narrative summary of peer-reviewed articles and grey literature was conducted., Data Sources: Ten databases were searched for articles published between January 2000 and April 2022. Inclusion criteria were: all care settings; AND the model focuses on people with end-stage or advanced dementia; AND contained multiple components., Results: Nineteen articles or reports, describing twelve dementia-specific models of end-of-life care in a range of care settings were identified for inclusion in the review. There is strong evidence that the principles of best practice palliative care for people with advanced dementia are well known, but limited examples of translation of this knowledge into integrated models of care. The key issues that emerged from the findings were: referral and admission to care, integration of care, sustainability and evaluation., Conclusions: Findings can be used to inform development of improved end-of-life care pathways for people with dementia, but well-designed research studies are needed to evaluate the effectiveness of integrated models of care for this vulnerable population.

Background: Accurately identifying cognitive changes in Mexican American (MA) adults using the Mini-Mental State Examination (MMSE) requires knowledge of population-based norms for the MMSE, a scale which has widespread use in research settings., Objective: To describe the distribution of MMSE scores in a large cohort of MA adults, assess the impact of MMSE requirements on their clinical trial eligibility, and explore which factors are most strongly associated with their MMSE scores., Methods: Visits between 2004-2021 in the Cameron County Hispanic Cohort were analyzed. Eligible participants were ≥18 years old and of Mexican descent. MMSE distributions before and after stratification by age and years of education (YOE) were assessed, as was the proportion of trial-aged (50-85- year-old) participants with MMSE <24, a minimum MMSE cutoff most frequently used in Alzheimer's disease (AD) clinical trials. As a secondary analysis, random forest models were constructed to estimate the relative association of the MMSE with potentially relevant variables., Results: The mean age of the sample set (n = 3,404) was 44.4 (SD, 16.0) years old and 64.5% female. Median MMSE was 28 (IQR, 28-29). The percentage of trial-aged participants (n = 1,267) with MMSE <24 was 18.6% overall and 54.3% among the subset with 0-4 YOE (n = 230). The five variables most associated with the MMSE in the study sample were education, age, exercise, C-reactive protein, and anxiety., Conclusion: The minimum MMSE cutoffs in most phase III prodromal-to-mild AD trials would exclude a significant proportion of trial-aged participants in this MA cohort, including over half of those with 0-4 YOE.

Patient-derived xenograft (PDX) models are an effective preclinical in vivo platform for testing the efficacy of novel drugs and drug combinations for cancer therapeutics. Here we describe a repository of 79 genomically and clinically annotated lung cancer PDXs available from The Jackson Laboratory that have been extensively characterized for histopathologic features, mutational profiles, gene expression, and copy-number aberrations. Most of the PDXs are models of non-small cell lung cancer (NSCLC), including 37 lung adenocarcinoma (LUAD) and 33 lung squamous cell carcinoma (LUSC) models. Other lung cancer models in the repository include four small cell carcinomas, two large cell neuroendocrine carcinomas, two adenosquamous carcinomas, and one pleomorphic carcinoma. Models with both de novo and acquired resistance to targeted therapies with tyrosine kinase inhibitors are available in the collection. The genomic profiles of the LUAD and LUSC PDX models are consistent with those observed in patient tumors from The Cancer Genome Atlas and previously characterized gene expression-based molecular subtypes. Clinically relevant mutations identified in the original patient tumors were confirmed in engrafted PDX tumors. Treatment studies performed in a subset of the models recapitulated the responses expected on the basis of the observed genomic profiles. These models therefore serve as a valuable preclinical platform for translational cancer research., Significance: Patient-derived xenografts of lung cancer retain key features observed in the originating patient tumors and show expected responses to treatment with standard-of-care agents, providing experimentally tractable and reproducible models for preclinical investigations., (©2022 The Authors; Published by the American Association for Cancer Research.)

COVID-19 has devastated global communities and economies. The pandemic has exposed socioeconomic disparities and weaknesses in health systems worldwide. Long-term health effects and economic recovery are major concerns. Ecosystem restoration-ie, the repair of ecosystems that have been degraded-relates directly to tackling the health and socioeconomic burdens of COVID-19, because stable and resilient ecosystems are fundamental determinants of health and socioeconomic stability. Here, we use COVID-19 as a case study, showing how ecosystem restoration can reduce the risk of infection and adverse sequelae and have an integral role in humanity's recovery from COVID-19. The next decade will be crucial for humanity's recovery from COVID-19 and for ecosystem repair. Indeed, in the absence of effective, large-scale restoration, 95% of the Earth's land could be degraded by 2050. The UN Decade on Ecosystem Restoration (2021-30) declaration reflects the growing urgency and scale at which we should repair ecosystems. Importantly, ecosystem restoration could also help to combat the health and socioeconomic issues that are associated with COVID-19, yet it is poorly integrated into current responses to the disease. Ecosystem restoration can be a core public health intervention and assist in COVID-19 recovery if it is closely integrated with socioeconomic, health, and environmental policies., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Health organisations are increasingly implementing 'embedded researcher' models to translate research into practice. This paper examines the impact of an embedded researcher model known as the embedded Economist (eE) Program that was implemented in an Australian Primary Health Network (PHN) located in regional New South Wales, Australia. The site, participants, program aims and design are described. Insights into the facilitators, challenges and barriers to the integration of economic evaluation perspectives into the work of the PHN are provided., Methods: The eE Program consisted of embedding a lead health economist on site, supported by offsite economists, part-time, for fifteen weeks to collaborate with PHN staff. Evaluation of the eE at the PHN included qualitative data collection via semi-structured interviews (N= 34), observations (N=8) and a field diary kept by the embedded economists. A thematic analysis was undertaken through the triangulation of this data., Results: The eE Program successfully met its aims of increasing PHN staff awareness of the value of economic evaluation principles in decision-making and their capacity to access and apply these principles. There was also evidence that the program resulted in PHN staff applying economic evaluations when commissioning service providers. Evaluation of the eE identified two key facilitators for achieving these results. First, a highly receptive organisational context characterised by a work ethic, and site processes and procedures that were dedicated to improvement. Second was the development of trusted relationships between the embedded economist and PHN staff that was enabled through: the commitment of the economist to bi-directional learning; facilitating access to economic tools and techniques; personality traits (likeable and enthusiastic); and because the eE provided ongoing support for PHN projects beyond the fifteen-week embedding period., Conclusions: This study provides the first detailed case description of an embedded health economics program. The results demonstrate how the process, context and relational factors of engaging and embedding the support of a health economist works and why. The findings reinforce international evidence in this area and are of practical utility to the future deployment of such programs., (© 2022. The Author(s).)

The greatly increased use of aquatic species to study disease over the past 20 years necessitates understanding their husbandry and housing requirements to optimize research and welfare and to ensure compliance with regulations. To achieve these goals, aquatic systems have expanded from pet shop and home aquaria to research-grade systems incorporating designs and features to increase their robustness, practicality, and flexibility. Moreover, these last decades have seen the increasing use of aquatic animals for infectious disease research using containment level 2 (CL2)/biosafety level 2 pathogens. In this study, we discuss the facility design requirements and modifications, which must be considered for the planning, construction, and use of an aquatic facility for zebrafish infected with CL2 pathogens. These include decontamination of water and equipment, racking and filtration design, personal protective equipment, and husbandry procedures. This guidance is based on our experience in the design and ongoing management of such facilities.

The development of integrated care initiatives to overcome service delivery fragmentation has become a global concern. Yet, the lack of guidance in their design and delivery has led to a high risk of project failure. Several authors have proposed driving ideas and strategies to foster care integration but a comprehensive conceptual framework building on the evidence and different perspectives of scientific contributions is still needed. The objective of this article is to explain the process of development and validation of a comprehensive framework that could be used either to standardize descriptions of existing care integration initiatives or as a conceptual basis for reflecting on the effective design of new programs or projects. In an initial phase, we used a comprehensive list of 175 items resulting from a literature review in order to identify a 'core set' of relevant framework items. subsequent phases, we validated the newly developed framework. External experts supported the validation phases. The iteration process resulted in a framework of 40 items grouped into seven dimensions: Person-centered care, Clinical integration, Professional integration, Organizational integration, Systemic integration, Functional integration, and Normative integration. The validated framework proved to be understandable and relevant to identify analytical aspects fostering care integration. It could be adapted as a useful tool to inform the design and implementation of new integrated care interventions as well as to generate standardized description of initiatives to perform insightful comparisons.

Territorial reactive aggression in mice is used to study the biology of aggression-related behavior and is also a critical component of procedures used to study mood disorders, such as chronic social defeat stress. However, quantifying mouse aggression in a systematic, representative, and easily adoptable way that allows direct comparison between cohorts within or between studies remains a challenge. Here, we propose a structural equation modeling approach to quantify aggression observed during the resident-intruder procedure. Using data for 658 sexually experienced CD-1 male mice generated by three research groups across three institutions over a 10-year period, we developed a higher-order confirmatory factor model wherein the combined contributions of latency to the first attack, number of attack bouts, and average attack duration on each trial day (easily observable metrics that require no specialized equipment) are used to quantify individual differences in aggression. We call our final model the Mouse Aggression Detector (MAD) model. Correlation analyses between MAD model factors estimated from multiple large datasets demonstrate generalizability of this measurement approach, and we further establish the stability of aggression scores across time within cohorts and demonstrate the utility of MAD for selecting aggressors which will generate a susceptible phenotype in social defeat experiments. Thus, this novel aggression scoring technique offers a systematic, high-throughput approach for aggressor selection in chronic social defeat stress studies and a more consistent and accurate study of mouse aggression itself., (© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Introduction: There is growing interest in assessing the impact of health interventions, particularly when women are the focus of the intervention, on women's empowerment. Globally, research has shown that interventions targeting nutrition, health and economic development can affect women's empowerment. Evidence suggests that women's empowerment is also an underlying determinant of nutrition outcomes. Depending on the focus of the intervention, different domains of women's empowerment will be influenced, for example, an increase in nutritional knowledge, or greater control over income and access to resources., Objective: This study evaluates the impact of the Shonjibon Cash and Counselling (SCC) Trial that combines nutrition counselling and an unconditional cash transfer, delivered on a mobile platform, on women's empowerment in rural Bangladesh., Methods and Analysis: We will use a mixed-methods approach, combining statistical analysis of quantitative data from 2840 women in a cluster randomised controlled trial examining the impact of nutrition behaviour change communications (BCCs) and cash transfers on child undernutrition. Pregnant participants will be given a smartphone with a customised app, delivering nutrition BCC messages, and will receive nutrition counselling via a call centre and an unconditional cash transfer. This study is a component of the SCC Trial and will measure women's empowerment using a composite indicator based on the Project-Level Women's Empowerment in Agriculture Index, with quantitative data collection at baseline and endline. Thematic analysis of qualitative data, collected through longitudinal interviews with women, husbands and mothers-in-law, will elicit a local understanding of women's empowerment and the linkages between the intervention and women's empowerment outcomes. This paper describes the study protocol to evaluate women's empowerment in a nutrition-specific and sensitive intervention using internationally validated, innovative tools and will help fill the evidence gap on pathways of impact, highlighting areas to target for future programming., Ethics and Dissemination: Ethical approval has been obtained from the International Centre for Diarrhoeal Disease Research (Ref. PR 17106) and The University of Sydney (Ref: 2019/840). Findings from this study will be shared in Bangladesh with dissemination sessions in-country and internationally at conferences, and will be published in peer-reviewed journals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Purpose: The purpose of this paper is to argue for an improved conceptualisation of health service research, using Stengers' (2018) metaphor of "slow science" as a critical yardstick., Design/methodology/approach: The paper is structured in three parts. It first reviews the field of health services research and the approaches that dominate it. It then considers the healthcare research approaches whose principles and methodologies are more aligned with "slow science" before presenting a description of a "slow science" project in which the authors are currently engaged., Findings: Current approaches to health service research struggle to offer adequate resources for resolving frontline complexity, principally because they set more store by knowledge generalisation, disciplinary continuity and integrity and the consolidation of expertise, than by engaging with frontline complexity on its terms, negotiating issues with frontline staff and patients on their terms and framing findings and solutions in ways that key in to the in situ dynamics and complexities that define health service delivery., Originality/value: There is a need to engage in a paradigm shift that engages health services as co-researchers, prioritising practical change and local involvement over knowledge production. Economics is a research field where the products are of natural appeal to powerful health service managers. A "slow science" approach adopted by the embedded Economist Program with its emphasis on pre-implementation, knowledge mobilisation and parallel site capacity development sets out how research can be flexibly produced to improve health services., (© Christine Jorm, Rick Iedema, Donella Piper, Nicholas Goodwin and Andrew Searles.)

Background: Renal medullary carcinoma (RMC) is a rare but aggressive tumor often complicated by early lung metastasis with few treatment options and very poor outcomes. There are currently no verified RMC patient-derived xenograft (PDX) mouse models established from metastatic pleural effusion (PE) available to study RMC and evaluate new therapeutic options., Methods: Renal tumor tissue and malignant PE cells from an RMC patient were successfully engrafted into 20 NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ (NSG) mice. We evaluated the histopathological similarity of the renal tumor and PE PDXs with the original patient renal tumor and PE, respectively. We then evaluated the molecular integrity of the renal tumor PDXs between passages, as well as the PE PDX compared to two generations of renal tumor PDXs, by microarray analysis. The therapeutic efficacy of sunitinib and temsirolimus was tested in a serially-transplanted generation of 27 PE PDX mice., Results: The pathologic characteristics of the patient renal tumor and patient PE were retained in the PDXs. Gene expression profiling revealed high concordance between the two generations of renal tumor PDXs (RMC-P0 vs. RMC-P1, r=0.865), as well as between the first generation PE PDX and each generation of the renal tumor PDX (PE-P0 vs. RMC-P0, r=0.919 and PE-P0 vs. RMC-P1, r=0.843). A low number (626) of differentially-expressed genes (DEGs) was seen between the first generation PE PDX and the first generation renal tumor PDX. In the PE-P1 xenograft, sunitinib significantly reduced tumor growth (p<0.001) and prolonged survival (p=0.004) compared to the vehicle control., Conclusions: A metastatic PE-derived RMC PDX model was established and shown to maintain histologic features of the patient cancer. Molecular integrity of the PDX models was well maintained between renal tumor and PE PDX as well as between two successive renal tumor PDX generations. Using the PE PDX model, sunitinib demonstrated therapeutic efficacy for RMC. This model can serve as a foundation for future mechanistic and therapeutic studies for primary and metastatic RMC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lee, Ijiri, Rodriguez, Gandour-Edwards, Lee, Tepper, Li, Beckett, Lam, Goodwin and Satake.)

Background: Systematic approaches to the inclusion of economic evaluation in national healthcare decision-making are usual. It is less common for economic evaluation to be routinely undertaken at the 'local-level' (e.g. in a health service or hospital) despite the largest proportion of health care expenditure being determined at this service level and recognition by local health service decision makers of the need for capacity building in economic evaluation skills. This paper describes a novel program - the embedded Economist (eE) Program. The eE Program aims to increase local health service staff awareness of, and develop their capacity to access and apply, economic evaluation principles in decision making. The eE program evaluation is also described. The aim of the evaluation is to capture the contextual, procedural and relational aspects that assist and detract from the eE program aims; as well as the outcomes and impact from the specific eE projects., Methods: The eE Program consists of a embedding a health economist in six health services and the provision of supported education in applied economic evaluation, provided via a community of practice and a university course. The embedded approach is grounded in co-production, embedded researchers and 'slow science'. The sites, participants, and program design are described. The program evaluation includes qualitative data collection via surveys, semi-structured interviews, observations and field diaries. In order to share interim findings, data are collected and analysed prior, during and after implementation of the eE program, at each of the six health service sites. The surveys will be analysed by calculating frequencies and descriptive statistics. A thematic analysis will be conducted on interview, observation and filed diary data. The Framework to Assess the Impact from Translational health research (FAIT) is utilised to assess the overall impact of the eE Program., Discussion: This program and evaluation will contribute to knowledge about how best to build capacity and skills in economic evaluation amongst decision-makers working in local-level health services. It will examine the extent to which participants are able to improve their ability to utilise evidence to inform decisions, avoid waste and improve the value of care delivery.

CHAPTER 1: RETAIL INITIATIVES TO IMPROVE THE HEALTHINESS OF FOOD ENVIRONMENTS IN RURAL, REGIONAL AND REMOTE COMMUNITIES: Objective: To synthesise the evidence for effectiveness of initiatives aimed at improving food retail environments and consumer dietary behaviour in rural, regional and remote populations in Australia and comparable countries, and to discuss the implications for future food environment initiatives for rural, regional and remote areas of Australia., Study Design: Rapid review of articles published between January 2000 and May 2020., Data Sources: We searched MEDLINE (EBSCOhost), Health and Society Database (Informit) and Rural and Remote Health Database (Informit), and included studies undertaken in rural food environment settings in Australia and other countries., Data Synthesis: Twenty-one articles met the inclusion criteria, including five conducted in Australia. Four of the Australian studies were conducted in very remote populations and in grocery stores, and one was conducted in regional Australia. All of the overseas studies were conducted in rural North America. All of them revealed a positive influence on food environment or consumer behaviour, and all were conducted in disadvantaged, rural communities. Positive outcomes were consistently revealed by studies of initiatives that focused on promotion and awareness of healthy foods and included co-design to generate community ownership and branding., Conclusion: Initiatives aimed at improving rural food retail environments were effective and, when implemented in different rural settings, may encourage improvements in population diets. The paucity of studies over the past 20 years in Australia shows a need for more research into effective food retail environment initiatives, modelled on examples from overseas, with studies needed across all levels of remoteness in Australia. Several retail initiatives that were undertaken in rural North America could be replicated in rural Australia and could underpin future research. CHAPTER 2: WHICH INTERVENTIONS BEST SUPPORT THE HEALTH AND WELLBEING NEEDS OF RURAL POPULATIONS EXPERIENCING NATURAL DISASTERS?: Objective: To explore and evaluate health and social care interventions delivered to rural and remote communities experiencing natural disasters in Australia and other high income countries., Study Design: We used systematic rapid review methods. First we identified a test set of citations and generated a frequency table of Medical Subject Headings (MeSH) to index articles. Then we used combinations of MeSH terms and keywords to search the MEDLINE (Ovid) database, and screened the titles and abstracts of the retrieved references., Data Sources: We identified 1438 articles via database searches, and a further 62 articles via hand searching of key journals and reference lists. We also found four relevant grey literature resources. After removing duplicates and undertaking two stages of screening, we included 28 studies in a synthesis of qualitative evidence., Data Synthesis: Four of us read and assessed the full text articles. We then conducted a thematic analysis using the three phases of the natural disaster response cycle., Conclusion: There is a lack of robust evaluation of programs and interventions supporting the health and wellbeing of people in rural communities affected by natural disasters. To address the cumulative and long term impacts, evidence suggests that continuous support of people's health and wellbeing is needed. By using a lens of rural adversity, the complexity of the lived experience of natural disasters by rural residents can be better understood and can inform development of new models of community-based and integrated care services. CHAPTER 3: THE IMPACT OF BUSHFIRE ON THE WELLBEING OF CHILDREN LIVING IN RURAL AND REMOTE AUSTRALIA: Objective: To investigate the impact of bushfire events on the wellbeing of children living in rural and remote Australia., Study Design: Literature review completed using rapid realist review methods, and taking into consideration the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement for systematic reviews., Data Sources: We sourced data from six databases: EBSCOhost (Education), EBSCOhost (Health), EBSCOhost (Psychology), Informit, MEDLINE and PsycINFO. We developed search terms to identify articles that could address the research question based on the inclusion criteria of peer reviewed full text journal articles published in English between 1983 and 2020. We initially identified 60 studies and, following closer review, extracted data from eight studies that met the inclusion criteria., Data Synthesis: Children exposed to bushfires may be at increased risk of poorer wellbeing outcomes. Findings suggest that the impact of bushfire exposure may not be apparent in the short term but may become more pronounced later in life. Children particularly at risk are those from more vulnerable backgrounds who may have compounding factors that limit their ability to overcome bushfire trauma., Conclusion: We identified the short, medium and long term impacts of bushfire exposure on the wellbeing of children in Australia. We did not identify any evidence-based interventions for supporting outcomes for this population. Given the likely increase in bushfire events in Australia, research into effective interventions should be a priority. CHAPTER 4: THE ROLE OF NATIONAL POLICIES TO ADDRESS RURAL ALLIED HEALTH, NURSING AND DENTISTRY WORKFORCE MALDISTRIBUTION: Objective: Maldistribution of the health workforce between rural, remote and metropolitan communities contributes to longstanding health inequalities. Many developed countries have implemented policies to encourage health care professionals to work in rural and remote communities. This scoping review is an international synthesis of those policies, examining their effectiveness at recruiting and retaining nursing, dental and allied health professionals in rural communities., Study Design: Using scoping review methods, we included primary research - published between 1 September 2009 and 30 June 2020 - that reported an evaluation of existing policy initiatives to address workforce maldistribution in high income countries with a land mass greater than 100 000 km 2 ., Data Sources: We searched MEDLINE, Ovid Embase, Ovid Emcare, Informit, Scopus, and Web of Science. We screened 5169 articles for inclusion by title and abstract, of which we included 297 for full text screening. We then extracted data on 51 studies that had been conducted in Australia, the United States, Canada, United Kingdom and Norway., Data Synthesis: We grouped the studies based on World Health Organization recommendations on recruitment and retention of health care workers: education strategies (n = 27), regulatory change (n = 11), financial incentives (n = 6), personal and professional support (n = 4), and approaches with multiple components (n = 3)., Conclusion: Considerable work has occurred to address workforce maldistribution at a local level, underpinned by good practice guidelines, but rarely at scale or with explicit links to coherent overarching policy. To achieve policy aspirations, multiple synergistic evidence-based initiatives are needed, and implementation must be accompanied by well designed longitudinal evaluations that assess the effectiveness of policy objectives. CHAPTER 5: AVAILABILITY AND CHARACTERISTICS OF PUBLICLY AVAILABLE HEALTH WORKFORCE DATA SOURCES IN AUSTRALIA: Objective: Many data sources are used in Australia to inform health workforce planning, but their characteristics in terms of relevance, accessibility and accuracy are uncertain. We aimed to identify and appraise publicly available data sources used to describe the Australian health workforce., Study Design: We conducted a scoping review in which we searched bibliographic databases, websites and grey literature. Two reviewers independently undertook title and abstract screening and full text screening using Covidence software. We then assessed the relevance, accessibility and accuracy of data sources using a customised appraisal tool., Data Sources: We searched for potential workforce data sources in nine databases (MEDLINE, Embase, Ovid Emcare, Scopus, Web of Science, Informit, the JBI Evidence-based Practice Database, PsycINFO and the Cochrane Library) and the grey literature, and examined several pre-defined websites., Data Synthesis: During the screening process we identified 6955 abstracts and examined 48 websites, from which we identified 12 publicly available data sources - eight primary and four secondary data sources. The primary data sources were generally of modest quality, with low scores in terms of reference period, accessibility and missing data. No single primary data source scored well across all domains of the appraisal tool., Conclusion: We identified several limitations of data sources used to describe the Australian health workforce. Establishment of a high quality, longitudinal, linked database that can inform all aspects of health workforce development is urgently needed, particularly for rural health workforce and services planning. CHAPTER 6: RAPID REALIST REVIEW OF OPIOID TAPERING IN THE CONTEXT OF LONG TERM OPIOID USE FOR NON-CANCER PAIN IN RURAL AREAS: Objective: To describe interventions, barriers and enablers associated with opioid tapering for patients with chronic non-cancer pain in rural primary care settings., Study Design: Rapid realist review registered on the international register of systematic reviews (PROSPERO) and conducted in accordance with RAMESES standards., Data Sources: English language, peer-reviewed articles reporting qualitative, quantitative and mixed method studies, published between January 2016 and July 2020, and accessed via MEDLINE, Embase, CINAHL Complete, PsycINFO, Informit or the Cochrane Library during June and July 2020. Grey literature relating to prescribing, deprescribing or tapering of opioids in chronic non-cancer pain, published between January 2016 and July 2020, was identified by searching national and international government, health service and peek organisation websites using Google Scholar., Data Synthesis: Our analysis of reported approaches to tapering conducted across rural and non-rural contexts showed that tapering opioids is complex and challenging, and identified several barriers and enablers. Successful outcomes in rural areas appear likely through therapeutic relationships, coordination and support, by using modalities and models of care that are appropriate in rural settings and by paying attention to harm minimisation., Conclusion: Rural primary care providers do not have access to resources available in metropolitan centres for dealing with patients who have chronic non-cancer pain and are taking opioid medications. They often operate alone or in small group practices, without peer support and access to multidisciplinary and specialist teams. Opioid tapering approaches described in the literature include regulation, multimodal and multidisciplinary approaches, primary care provider support, guidelines, and patient-centred strategies. There is little research to inform tapering in rural contexts. Our review provides a synthesis of the current evidence in the form of a conceptual model. This preliminary model could inform the development of a model of care for use in implementation research, which could test a variety of mechanisms for supporting decision making, reducing primary care providers' concerns about potential harms arising from opioid tapering, and improving patient outcomes., (© 2020 AMPCo Pty Ltd.)

Background: Undernutrition is strongly associated with poverty - levels of undernutrition are higher in poor countries than in better-off countries. Social protection especially cash transfer is increasingly recognized as an important strategy to accelerate progress in improving maternal and child nutrition. A critical method to improve nutrition knowledge and influence feeding practices is through behaviour change communication intervention. The Shonjibon Cash and Counselling study aims to assess the effectiveness of unconditional cash transfers combined with a mobile application on nutrition counselling and direct counselling through mobile phone in reducing the prevalence of stunting in children at 18 months., Method: The study is a longitudinal cluster randomised controlled trial, with two parallel groups, and cluster assignment by groups of villages. The cohort of mother-child dyads will be followed-up over the intervention period of approximately 24 months, starting from recruitment to 18 months of the child's age. The study will take place in north-central Bangladesh. The primary trial outcome will be the percentage of stunted children at 18 m as measured in follow up assessments starting from birth. The secondary trial outcomes will include differences between treatment arms in (1) Mean birthweight, percentage with low birthweight and small for gestational age (2) Mean child length-for age, weight for age and weight-for-length Z scores (3) Prevalence of child wasting (4) Percentage of women exclusively breastfeeding and mean duration of exclusive breastfeeding (5) Percentage of children consuming > 4 food groups (6) Mean child intake of energy, protein, carbohydrate, fat and micronutrients (7) Percentage of women at risk of inadequate nutrient intakes in all three trimesters (8) Maternal weight gain (9) Household food security (10) Number of events for child suffering from diarrhoea, acute respiratory illness and fever (11) Average costs of mobile phone BCC and cash transfer, and benefit-cost ratio for primary and secondary outcomes., Discussion: The proposed trial will provide high-level evidence of the efficacy and cost-effectiveness of mobile phone nutrition behavior change communication, combined with unconditional cash transfers in reducing child undernutrition in rural Bangladesh., Trial Registration: The study has been registered in the Australian New Zealand Clinical Trials Registry ( ACTRN12618001975280 ).

Introduction: Although person-centredness is a key principle of integrated care, successfully embedding and improving person-centred care for older people remains a challenge. In the context of a cross-European project on integrated care for older people living at home, the objective of this paper is to provide insight at an overarching level, into activities aimed at improving person-centredness within the participating integrated care sites. The paper describes experiences with these activities from the service providers' and service users' perspectives., Methods: A multiple embedded case study design was conducted that included thirteen integrated care sites for older people living at home., Results: Service providers were positive about the activities that aimed to promote person-centred care and thought that most activities (e.g. comprehensive needs assessment) positively influenced person-centredness. Experiences of service users were mixed. For some activities (e.g. enablement services), discrepancies were identified between the views of service providers and those of service users., Discussion and Conclusion: Evaluating activities aimed at promoting person-centredness from both the service providers' and service users' perspectives showed that not all efforts were successful or had the intended consequences for older people. Involvement of older people in designing improvement activities could ensure that care and support reflect their needs and preferences, and build positive experiences of care and support., Competing Interests: Nick Goodwin and Mirella Minkman are affiliated with the International Foundation for Integrated Care, which supports the journal publishing this paper., (Copyright: © 2020 The Author(s).)

Targeted delivery of chemotherapeutics aims to increase efficacy and lower toxicity by concentrating drugs at the site-of-action, a method embodied by the seven current FDA-approved antibody-drug conjugates (ADC). However, a variety of pharmacokinetic challenges result in relatively narrow therapeutic windows for these agents, hampering the development of new drugs. Here, we use a series of prostate-specific membrane antigen-binding single-domain (Humabody) ADC constructs to demonstrate that tissue penetration of protein-drug conjugates plays a major role in therapeutic efficacy. Counterintuitively, a construct with lower in vitro potency resulted in higher in vivo efficacy than other protein-drug conjugates. Biodistribution data, tumor histology images, spheroid experiments, in vivo single-cell measurements, and computational results demonstrate that a smaller size and slower internalization rate enabled higher tissue penetration and more cell killing. The results also illustrate the benefits of linking an albumin-binding domain to the single-domain ADCs. A construct lacking an albumin-binding domain was rapidly cleared, leading to lower tumor uptake (%ID/g) and decreased in vivo efficacy. In conclusion, these results provide evidence that reaching the maximum number of cells with a lethal payload dose correlates more strongly with in vivo efficacy than total tumor uptake or in vitro potency alone for these protein-drug conjugates. Computational modeling and protein engineering can be used to custom design an optimal framework for controlling internalization, clearance, and tissue penetration to maximize cell killing. SIGNIFICANCE: A mechanistic study of protein-drug conjugates demonstrates that a lower potency compound is more effective in vivo than other agents with equal tumor uptake due to improved tissue penetration and cellular distribution., (©2020 American Association for Cancer Research.)

Introduction: Integrated care implies sustained change in complex systems and progress is not always linear or easy to assess. The Central Coast integrated Care Program (CCICP) was planned as a ten-year place-based system change. This paper reports the first formative evaluation to provide a detailed description of the implementation of the CCICP, after two years of activity, and the current progress towards integrated care., Theory and Methods: Progress towards integrated care achieved by the CCICP was evaluated using the Project INTEGRATE Framework data in a mixed methods approach included semi-structured interviews (n = 23) and Project INTEGRATE Framework based surveys (n = 27). All data collected involved key stakeholders, with close involvement in the program, self-reporting., Results: Progress has been mixed. Gains had most clearly been made in the areas of clinical and professional integration; specifically, relationship building and improved collaboration and cooperation between service providers. The areas of systemic and functional integration were least improved with funding uncertainty being an ongoing significant problem. The evaluation also showed that the Project INTEGRATE framework provided a consistent language for CCICP partners and for evaluators and consistent indicators of progress. The framework also helped to identify key facilitators and barriers., Discussion and Conclusion: The findings highlight the willingness and commitment of key staff but also the importance of leadership, good communication, relationship building, and cultural transformation., Competing Interests: The authors have no competing interests to declare.

Background: Allograft failure is common in lung-transplant recipients and leads to poor outcomes including early death. No reliable clinical tools exist to identify patients at high risk for allograft failure. This study tested the use of donor-derived cell-free DNA (%ddcfDNA) as a sensitive marker of early graft injury to predict impending allograft failure., Methods: This multicenter, prospective cohort study enrolled 106 subjects who underwent lung transplantation and monitored them after transplantation for the development of allograft failure (defined as severe chronic lung allograft dysfunction [CLAD], retransplantation, and/or death from respiratory failure). Plasma samples were collected serially in the first three months following transplantation and assayed for %ddcfDNA by shotgun sequencing. We computed the average levels of ddcfDNA over three months for each patient (avddDNA) and determined its relationship to allograft failure using Cox-regression analysis., Findings: avddDNA was highly variable among subjects: median values were 3·6%, 1·6% and 0·7% for the upper, middle, and low tertiles, respectively (range 0·1%-9·9%). Compared to subjects in the low and middle tertiles, those with avddDNA in the upper tertile had a 6·6-fold higher risk of developing allograft failure (95% confidence interval 1·6-19·9, p = 0·007), lower peak FEV1 values, and more frequent %ddcfDNA elevations that were not clinically detectable., Interpretation: Lung transplant patients with early unresolving allograft injury measured via %ddcfDNA are at risk of subsequent allograft injury, which is often clinically silent, and progresses to allograft failure. FUND: National Institutes of Health., (Published by Elsevier B.V.)

The use of early-stage zebrafish for biomedical research spans early organogenesis to free-swimming larva. A key benefit of this model organism is that repeated assessments spanning several days can be performed of individual larvae within a single experiment, often in conjunction with administered drugs. However, the initiation of feeding, typically at 5 days postfertilization (dpf), can make serial assessments challenging. Therefore, delayed feeding would increase the utility of the model. To ask whether feeding could be delayed without adversely affecting larval growth and development up to 39 dpf, we systematically raised zebrafish and introduced feeding at 5 dpf or delayed initial feeding up to 9 dpf. We assessed survival into the juvenile stage (39 dpf) and anterior-posterior length at this age as proxies for growth and development. Delaying feeding initiation up to 8 dpf did not decrease baseline survival of greater than 90%; survival decreased to 66% only when delayed to 9 dpf. Larval length was no different under any of these conditions. Our findings define 9 dpf as the critical age before which larval zebrafish must be fed when raising to 39 dpf. The option to delay feeding to 8 dpf will broaden experimental applications for the zebrafish larval model.

Objective: As part of the EU-funded Project INTEGRATE, the research sought to develop an evidence-based understanding of the key dimensions and items of integrated care associated with successful implementation across varying country contexts and relevant to different chronic and/or long-term conditions. This paper identifies the core dimensions of integrated care based on a review of previous literature on the topic., Methodology: The research reviewed literature evidence from the peer-reviewed and grey literature. It focused on reviewing research articles that had specifically developed frameworks on integrated care and/or set out key elements for successful implementation. The search initially focused on three main scientific journals and was limited to the period from 2006 to 2016. Then, the research snowballed the references from the selected published studies and engaged leading experts in the field to supplement the identification of relevant literature. Two investigators independently reviewed the selected articles using a standard data collection tool to gather the key elements analyzed in each article., Results: A total of 710 articles were screened by title and abstract. Finally, 18 scientific contributions were selected, including studies from grey literature and experts' suggestions. The analysis identified 175 items grouped in 12 categories., Conclusions: Most of the key factors reported in the literature derive from studies that developed their frameworks in specific contexts and/or for specific types of conditions. The identification and classification of the elements from this literature review provide a basis to develop a comprehensive framework enabling standardized descriptions and benchmarking of integrated care initiatives carried out in different contexts.

People with eating disorders (EDs) have an elevated risk for both nonsuicidal self-injury (NSSI) and suicide compared to the general population. This study tests two theoretically derived models examining interoceptive deficits as a risk factor for NSSI, and examining interoceptive deficits, NSSI, fearlessness about death, and pain tolerance as risk factors for suicide. Ninety-six adult, treatment-seeking women with EDs completed self-report questionnaires at a single time point. Interoceptive deficits were significantly associated with NSSI, and NSSI was in turn associated with both pain tolerance and fearlessness about death. Further, pain tolerance was in turn associated with past suicide attempts, although fearlessness about death was not associated with suicide attempts. Interoceptive deficits had a direct association with fearlessness about death but not pain tolerance. Results regarding the relation between interoceptive deficits and suicide attempts were mixed, yet overall suggest that interoceptive deficits are related to suicide attempts largely indirectly, through the effects of mediating variables such as NSSI, fearlessness about death, and pain tolerance. Results suggest that interoceptive deficits and pain tolerance merit further investigation as potential risk factors for fatal and nonfatal self-harm among individuals with EDs., (© 2017 The American Association of Suicidology.)

Background: Antibody-mediated rejection (AMR) often progresses to poor health outcomes in lung transplant recipients (LTRs). This, combined with the relatively insensitive clinical tools used for its diagnosis (spirometry, histopathology) led us to determine whether clinical AMR is diagnosed significantly later than its pathologic onset. In this study, we leveraged the high sensitivity of donor-derived cell-free DNA (ddcfDNA), a novel genomic tool, to detect early graft injury after lung transplantation., Methods: We adjudicated AMR and acute cellular rejection (ACR) in 157 LTRs using the consensus criteria of the International Society for Heart and Lung Transplantation (ISHLT). We assessed the kinetics of allograft injury in relation to ACR or AMR using both clinical criteria (decline in spirometry from baseline) and molecular criteria (ddcfDNA); percent ddcfDNA was quantitated via shotgun sequencing. We used a mixed-linear model to assess the relationship between and ddcfDNA levels and donor-specific antibodies (DSA) in AMR + LTRs., Results: Compared with ACR, AMR episodes (n = 42) were associated with significantly greater allograft injury when assessed by both spirometric (0.1 liter vs -0.6 liter, p < 0.01) and molecular (ddcfDNA) analysis (1.1% vs 5.4%, p < 0.001). Allograft injury detected by ddcfDNA preceded clinical AMR diagnosis by a median of 2.8 months. Within the same interval, spirometry or histopathology did not reveal findings of allograft injury or dysfunction. Elevated levels of ddcfDNA before clinical diagnosis of AMR were associated with a concurrent rise in DSA levels., Conclusion: Diagnosis of clinical AMR in LTRs lags behind DSA-associated molecular allograft injury as assessed by ddcfDNA., (Copyright © 2018. Published by Elsevier Inc.)