Enterococcus faecalis-derived adenine enhances enterohaemorrhagic Escherichia coli Type 3 Secretion System-dependent virulence.

Interactions between microbiota and enteric pathogens can promote colonization resistance or enhance pathogenesis. The pathobiont Enterococcus faecalis increases enterohaemorrhagic E. coli (EHEC) virulence by upregulating Type 3 Secretion System (T3SS) expression, effector translocation, and attaching and effacing (AE) lesion formation on enterocytes, but the mechanisms underlying this remain unknown. Using co-infection of organoids, metabolomics, supplementation experiments and bacterial genetics, here we show that co-culture of EHEC with E. faecalis increases the xanthine-hypoxanthine pathway activity and adenine biosynthesis. Adenine or E. faecalis promoted T3SS gene expression, while transcriptomics showed upregulation of adeP expression, which encodes an adenine importer. Mechanistically, adenine relieved High hemolysin activity (Hha)-dependent repression of T3SS gene expression in EHEC and promoted AE lesion formation in an AdeP-dependent manner. Microbiota-derived purines, such as adenine, support multiple beneficial host responses; however, our data show that this metabolite also increases EHEC virulence, highlighting the complexity of pathogen-microbiota-host interactions in the gut.

Consumer Preferences for a Healthcare Appointment Reminder in Australia: A Discrete Choice Experiment.

BACKGROUND: It is essential to consider the evidence of consumer preferences and their specific needs when determining which strategies to use to improve patient attendance at scheduled healthcare appointments. OBJECTIVES: This study aimed to identify key attributes and elicit healthcare consumer preferences for a healthcare appointment reminder system. METHODS: A discrete choice experiment was conducted in a general Australian population sample. The respondents were asked to choose between three options: their preferred reminder (A or B) or a 'neither' option. Attributes were developed through a literature review and an expert panel discussion. Reminder options were defined by four attributes: modality, timing, content and interactivity. Multinomial logit and mixed multinomial logit models were estimated to approximate individual preferences for these attributes. A scenario analysis was performed to estimate the likelihood of choosing different reminder systems. RESULTS: Respondents (n = 361) indicated a significant preference for an appointment reminder to be delivered via a text message (ß = 2.42, p < 0.001) less than 3 days before the appointment (ß = 0.99, p < 0.001), with basic details including the appointment cost (ß = 0.13, p < 0.10), and where there is the ability to cancel or modify the appointment (ß = 1.36, p < 0.001). A scenario analysis showed that the likelihood of choosing an appointment reminder system with these characteristics would be 97%. CONCLUSIONS: Our findings provide evidence on how healthcare consumers trade-off between different characteristics of reminder systems, which may be valuable to inform current or future systems. Future studies may focus on exploring the effectiveness of using patient-preferred reminders alongside other mitigation strategies used by providers.

Estimating the cost of sports injuries: A scoping review.

OBJECTIVES: Provide an overview of the methods used to estimate the cost of sports-related injury published to date, and to highlight considerations and opportunities for future research. DESIGN: Scoping review. METHODS: Scopus, MEDLINE and CINHAL were searched from 1st January 2000 to 1st January 2023. Studies were screened by two independent reviewers and were eligible if they reported on a cost analysis or cost estimation of sports related injury. RESULTS: Thirty-one studies fulfilled the inclusion criteria. Twenty-seven studies (87 %) were published since 2014. The type of costs included direct healthcare costs (12 studies), indirect costs (10 studies) and a combination of both (9 studies). Twenty-one studies (68 %) used a bottom-up costing approach to measure costs of sports injury and estimated direct costs from the service rates or fee schedules of health systems, hospital, insurance companies or national insurance boards. A top-down approach was used in seven studies (23 %) to estimate the indirect salary cost of time-loss injuries using data from publicly available resources. Ten studies were from the cost perspective of a sporting organisation (32 %). There was a lack of explicit reporting of the costing method used and the perspective of those bearing the costs. CONCLUSIONS: Estimating the cost of sports injuries is an emerging area of research, with publications increasing in recent years. However, there remains a lack of methodological guidance to inform or appraise these studies. The expansion of established cost of illness checklists with sport injury explanations to guide future cost of sports injury studies is recommended.

Process evaluation of a tailored nudge intervention to promote appropriate care and treatment of older patients at the end-of-life.

BACKGROUND: Non-beneficial treatment affects a considerable proportion of older people in hospital, and some will choose to decline invasive treatments when they are approaching the end of their life. The Intervention for Appropriate Care and Treatment (InterACT) intervention was a 12-month stepped wedge randomised controlled trial with an embedded process evaluation in three hospitals in Brisbane, Australia. The aim was to increase appropriate care and treatment decisions for older people at the end-of-life, through implementing a nudge intervention in the form of a prospective feedback loop. However, the trial results indicated that the expected practice change did not occur. The process evaluation aimed to assess implementation using the Consolidated Framework for Implementation Research, identify barriers and enablers to implementation and provide insights into the lack of effect of the InterACT intervention. METHODS: Qualitative data collection involved 38 semi-structured interviews with participating clinicians, members of the executive advisory groups overseeing the intervention at a site level, clinical auditors, and project leads. Online interviews were conducted at two times: implementation onset and completion. Data were coded to the Consolidated Framework for Implementation Research and deductively analysed. RESULTS: Overall, clinicians felt the premise and clinical reasoning behind InterACT were strong and could improve patient management. However, several prominent barriers affected implementation. These related to the potency of the nudge intervention and its integration into routine clinical practice, clinician beliefs and perceived self-efficacy, and wider contextual factors at the health system level. CONCLUSIONS: An intervention designed to change clinical practice for patients at or near to end-of-life did not have the intended effect. Future interventions targeting this area of care should consider using multi-component strategies that address the identified barriers to implementation and clinician change of practice. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry (ANZCTR), ACTRN12619000675123p (approved 06/05/2019).

Stakeholders' preferences for the design and delivery of virtual care services: A systematic review of discrete choice experiments.

This systematic review aimed to synthesise evidence from discrete choice experiments (DCEs) eliciting preferences for virtual models of care, as well as to assess the quality of those DCEs and compare the relative preferences for different stakeholder groups. Articles were included if published between January 2010 and December 2022. Data were synthesised narratively, and attributes were assessed for frequency, significance, and relative importance using a semi-quantitative approach. Overall, 21 studies were included encompassing a wide range of virtual care modalities, with the most common setting being virtual consultations for outpatient management of chronic conditions. A total of 135 attributes were identified and thematically classified into six categories: service delivery, service quality, technical aspects, monetary aspects, health provider characteristics and health consumer characteristics. Attributes related to service delivery were most frequently reported but less highly ranked. Service costs were consistently significant across all studies where they appeared, indicating their importance to the respondents. All studies examining health providers' preferences reported either system performance or professional endorsement attributes to be the most important. Substantial heterogeneity in attribute selection and preference outcomes were observed across studies reporting on health consumers' preferences, suggesting that the consideration of local context is important in the design and delivery of person-centred virtual care services. In general, the experimental design and analysis methods of included studies were clearly reported and justified. An improvement was observed in the quality of DCE design and analysis in recent years, particularly in the attribute development process. Given the continued growth in the use of DCEs within healthcare settings, further research is needed to develop a standardised approach for quantitatively synthesising DCE findings. There is also a need for further research on preferences for virtual care in post-pandemic contexts, where emerging evidence suggests that preferences may differ to those observed in pre-pandemic times.

From pilot to a multi-site trial: refining the Early Detection of Deterioration in Elderly Residents (EDDIE +) intervention.

BACKGROUND: Early Detection of Deterioration in Elderly Residents (EDDIE +) is a multi-modal intervention focused on empowering nursing and personal care workers to identify and proactively manage deterioration of residents living in residential aged care (RAC) homes. Building on successful pilot trials conducted between 2014 and 2017, the intervention was refined for implementation in a stepped-wedge cluster randomised trial in 12 RAC homes from March 2021 to May 2022. We report the process used to transition from a small-scale pilot intervention to a multi-site intervention, detailing the intervention to enable future replication. METHODS: The EDDIE + intervention used the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to guide the intervention development and refinement process. We conducted an environmental scan; multi-level context assessments; convened an intervention working group (IWG) to develop the program logic, conducted a sustainability assessment and deconstructed the intervention components into fixed and adaptable elements; and subsequently refined the intervention for trial. RESULTS: The original EDDIE pilot intervention included four components: nurse and personal care worker education; decision support tools; diagnostic equipment; and facilitation and clinical support. Deconstructing the intervention into core components and what could be flexibly tailored to context was essential for refining the intervention and informing future implementation across multiple sites. Intervention elements considered unsustainable were updated and refined to enable their scalability. Refinements included: an enhanced educational component with a greater focus on personal care workers and interactive learning; decision support tools that were based on updated evidence; equipment that aligned with recipient needs and available organisational support; and updated facilitation model with local and external facilitation. CONCLUSION: By using the i-PARIHS framework in the scale-up process, the EDDIE + intervention was tailored to fit the needs of intended recipients and contexts, enabling flexibility for local adaptation. The process of transitioning from a pilot to larger scale implementation in practice is vastly underreported yet vital for better development and implementation of multi-component interventions across multiple sites. We provide an example using an implementation framework and show it can be advantageous to researchers and health practitioners from pilot stage to refinement, through to larger scale implementation. TRIAL REGISTRATION: The trial was prospectively registered with the Australia New Zealand Clinical Trial Registry (ACTRN12620000507987, registered 23/04/2020).

Preferences for Palliative and End-of-Life Care: A Systematic Review of Discrete Choice Experiments.

OBJECTIVES: Understanding what matters most to patients and their caregivers is fundamental to delivering high-quality care. This systematic review aimed to characterize and appraise the evidence from discrete choice experiments eliciting preferences for palliative care. METHODS: A systematic literature search was undertaken for publications up until August 2022. Data were synthesized narratively. Thematic analysis was applied to categorize attributes into groups. Attribute development, frequency, and relative importance were analyzed. Subgroup analyses were conducted to compare outcomes between patient and proxy respondents. RESULTS: Seventeen studies spanning 11 countries were included; 59% of studies solely considered preferences for patients with cancer. A range of respondent groups were represented including patients (76%) and proxies (caregivers [35%], health providers [12%], and the public [18%]). A total of 117 individual attributes were extracted and thematically grouped into 8 broad categories and 21 subcategories. Clinical outcomes including quality of life, length of life, and pain control were the most frequently reported attributes, whereas attributes relating to psychosocial components were largely absent. Both patients and proxy respondents prioritized pain control over additional survival time. Nevertheless, there were differences between respondent cohorts in the emphasis on other attributes such as access to care, timely information, and low risk of adverse effects (prioritized by patients), as opposed to cost, quality, and delivery of care (prioritized by proxies). CONCLUSIONS: Our review underscores the vital role of pain control in palliative care; in addition, it shed light on the complexity and relative strength of preferences for various aspects of care from multiple perspectives, which is useful in developing personalized, patient-centered models of care for individuals nearing the end of life.

Alternative Reimbursement Models for Health Providers in High-Performance Sport: Stakeholder Experiences and Perceptions.

BACKGROUND: Value-based healthcare provider reimbursement models have been proposed as an alternative to traditional fee-for-service arrangements that can align financial reimbursement more closely to the outcomes of value to patients and society. This study aimed to investigate stakeholder perceptions and experiences of different reimbursement systems for healthcare providers in high-performance sport, with a focus on fee-for-service versus salaried provider models. METHODS: Three in-depth semi-structured focus group discussions and one individual interview were conducted with key stakeholders across the Australian high-performance sport system. Participants included healthcare providers, health managers, sports managers and executive personnel. An interview guide was developed using the Exploration, Preparation, Implementation, Sustainment framework, with key themes deductively mapped to the innovation, inner context and outer context domains. A total of 16 stakeholders participated in a focus group discussion or interview. RESULTS: Participants identified several key advantages of salaried provider models over fee-for-service arrangements, including: the potential for more proactive and preventive models of care; enhanced inter-disciplinary collaboration; and the ability for providers to have a deeper understanding of context and how their role aligns with a broader set of priorities for an athlete and the organisation. Noted challenges of salaried provider models included the potential for providers to revert to reactive care delivery when not afforded adequate capacity to provide services, and difficulties for providers in demonstrating and quantifying the value of their work. CONCLUSIONS: Our findings suggest that high-performance sporting organisations seeking to improve primary prevention and multidisciplinary care should consider salaried provider arrangements. Further research to confirm these findings using prospective, experimental study designs remains a priority.

Economic evaluation of an integrated virtual care programme for people with chronic illness who are frequent users of health services in Australia.

OBJECTIVE: The MeCare programme is a tailored virtual care initiative targeted at frequent users of health services who have at least one chronic condition including cardiovascular disease, chronic respiratory disease, diabetes or chronic kidney disease. The programme aims to prevent unnecessary hospitalisations by helping patients to self-manage, improve their health literacy and engage in positive health behaviours. This study investigates the impact of the MeCare programme on healthcare resource use, costs and patient-reported outcomes. METHODS AND ANALYSIS: A retrospective pre-post study design was adopted. Data on emergency department presentations, hospital admissions, outpatient appointments and their associated costs were obtained from administrative databases. Probabilistic sensitivity analysis using Monte Carlo simulation was used to model changes in resource use and costs prior to, and following, participant enrolment on the MeCare programme. Generalised linear models were used to investigate the observed changes in patient-reported outcomes. RESULTS: The MeCare programme cost $A624 per participant month to deliver. Median monthly rates of ED presentations, hospital admissions and average length of stay post-MeCare reduced by 76%, 50% and 12%, respectively. This translated to a median net cost saving of $A982 per participant month (IQR: -1936; -152). A significant, positive trend in patient experience based on responses to the Patient Assessment of Care for Chronic Conditions Questionnaire was observed over the duration of programme enrolment. DISCUSSION: The MeCare programme is likely to result in substantial cost savings to the health system, while maintaining or improving patient-reported outcomes. Further research in multisite randomised studies is needed to confirm the generalisability of these results.

Evaluating the costs and consequences of computerized clinical decision support systems in hospitals: a scoping review and recommendations for future practice.

OBJECTIVE: Sustainable investment in computerized decision support systems (CDSS) requires robust evaluation of their economic impacts compared with current clinical workflows. We reviewed current approaches used to evaluate the costs and consequences of CDSS in hospital settings and presented recommendations to improve the generalizability of future evaluations. MATERIALS AND METHODS: A scoping review of peer-reviewed research articles published since 2010. Searches were completed in the PubMed, Ovid Medline, Embase, and Scopus databases (last searched February 14, 2023). All studies reported the costs and consequences of a CDSS-based intervention compared with current hospital workflows. Findings were summarized using narrative synthesis. Individual studies were further appraised against the Consolidated Health Economic Evaluation and Reporting (CHEERS) 2022 checklist. RESULTS: Twenty-nine studies published since 2010 were included. Studies evaluated CDSS for adverse event surveillance (5 studies), antimicrobial stewardship (4 studies), blood product management (8 studies), laboratory testing (7 studies), and medication safety (5 studies). All studies evaluated costs from a hospital perspective but varied based on the valuation of resources affected by CDSS implementation, and the measurement of consequences. We recommend future studies follow guidance from the CHEERS checklist; use study designs that adjust for confounders; consider both the costs of CDSS implementation and adherence; evaluate consequences that are directly or indirectly affected by CDSS-initiated behavior change; examine the impacts of uncertainty and differences in outcomes across patient subgroups. DISCUSSION AND CONCLUSION: Improving consistency in the conduct and reporting of evaluations will enable detailed comparisons between promising initiatives, and their subsequent uptake by decision-makers.

Role of the Water-Metal Ion Bridge in Quinolone Interactions with Escherichia coli Gyrase.

Fluoroquinolones are an important class of antibacterials, and rising levels of resistance threaten their clinical efficacy. Gaining a more full understanding of their mechanism of action against their target enzymes-the bacterial type II topoisomerases gyrase and topoisomerase IV-may allow us to rationally design quinolone-based drugs that overcome resistance. As a step toward this goal, we investigated whether the water-metal ion bridge that has been found to mediate the major point of interaction between Escherichia coli topoisomerase IV and Bacillus anthracis topoisomerase IV and gyrase, as well as Mycobacterium tuberculosis gyrase, exists in E. coli gyrase. This is the first investigation of the water-metal ion bridge and its function in a Gram-negative gyrase. Evidence suggests that the water-metal ion bridge does exist in quinolone interactions with this enzyme and, unlike the Gram-positive B. anthracis gyrase, does use both conserved residues (serine and acidic) as bridge anchors. Furthermore, this interaction appears to play a positioning role. These findings raise the possibility that the water-metal ion bridge is a universal point of interaction between quinolones and type II topoisomerases and that it functions primarily as a binding contact in Gram-positive species and primarily as a positioning interaction in Gram-negative species. Future studies will explore this possibility.

Protocol for a process evaluation of a stepped wedge randomised controlled trial to reduce unnecessary hospitalisations of older people from residential aged care: the EDDIE+ study.

INTRODUCTION: The Early Detection of Deterioration in Elderly residents (EDDIE+) programme is a theory-informed, multi-component intervention aimed at upskilling and empowering nursing and personal care staff to identify and manage early signs of deterioration in residents of aged care facilities. The intervention aims to reduce unnecessary hospital admissions from residential aged care (RAC) homes. Alongside a stepped wedge randomised controlled trial, an embedded process evaluation will be conducted to assess the fidelity, acceptability, mechanisms of action and contextual barriers and enablers of the EDDIE+ intervention. METHODS AND ANALYSIS: Twelve RAC homes in Queensland, Australia are participating in the study. A comprehensive mixed-methods process evaluation, informed by the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework, will assess intervention fidelity, contextual barriers and enablers, mechanisms of action, and the acceptability of the programme from various stakeholder perspectives. Quantitative data will be collected prospectively from project documentation, including baseline context mapping of participating sites, activity tracking and regular check-in communication sheets. Qualitative data will be collected postintervention via semi-structured interviews with a range of stakeholder groups. The i-PARIHS constructs of innovation, recipients, context and facilitation will be applied to frame the analysis of quantitative and qualitative data. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the Bolton Clarke Human Research Ethics Committee (approval number: 170031) with administrative ethical approval granted by the Queensland University of Technology University Human Research Ethics Committee (2000000618). Full ethical approval includes a waiver of consent for access to residents' demographic, clinical and health services de-identified data. A separate health services data linkage based on RAC home addresses will be sought through a Public Health Act application. Study findings will be disseminated through multiple channels, including journal publications, conference presentations and interactive webinars with a stakeholder network. TRIAL REGISTRATION NUMBER: Australia New Zealand Clinical Trial Registry (ACTRN12620000507987).

Implementation costs of hospital-based computerised decision support systems: a systematic review.

BACKGROUND: The importance of accurately costing implementation strategies is increasingly recognised within the field of implementation science. However, there is a lack of methodological guidance for costing implementation, particularly within digital health settings. This study reports on a systematic review of costing analyses conducted alongside implementation of hospital-based computerised decision support systems. METHODS: PubMed, Embase, Scopus and CINAHL databases were searched between January 2010 and August 2021. Two reviewers independently screened and selected original research studies that were conducted in a hospital setting, examined the implementation of a computerised decision support systems and reported implementation costs. The Expert Recommendations for Implementing Change Framework was used to identify and categorise implementation strategies into clusters. A previously published costing framework was applied to describe the methods used to measure and value implementation costs. The reporting quality of included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards checklist. RESULTS: Titles and abstracts of 1836 articles were screened, with nine articles eligible for inclusion in the review. Implementation costs were most frequently reported under the 'evaluative and iterative strategies' cluster, followed by 'provide interactive assistance'. Labour was the largest implementation-related cost in the included papers, irrespective of implementation strategy. Other reported costs included consumables, durable assets and physical space, which was mostly associated with stakeholder training. The methods used to cost implementation were often unclear. There was variation across studies in the overall quality of reporting. CONCLUSIONS: A relatively small number of papers have described computerised decision support systems implementation costs, and the methods used to measure and value these costs were not well reported. Priorities for future research should include establishing consistent terminology and appropriate methods for estimating and reporting on implementation costs. TRIAL REGISTRATION: The review protocol is registered with PROSPERO (ID: CRD42021272948).

Child Maltreatment and Long-Term Physical and Mental Health Outcomes: An Exploration of Biopsychosocial Determinants and Implications for Prevention.

Child maltreatment rates remain unacceptably high and rates are likely to escalate as COVID-related economic problems continue. A comprehensive and evidence-building approach is needed to prevent, detect and intervene where child maltreatment occurs. This review identifies key challenges in definitions, overviews the latest data on prevalence rates, reviews risk and protective factors, and examines common long-term mental health outcomes for children who experience maltreatment. The review takes a systems approach to child maltreatment outcomes through its focus on the overall burden of disease, gene-environment interactions, neurobiological mechanisms and social ecologies linking maltreatment to mental ill-health. Five recommendations relating to the accurate measurement of trends, research on brain structures and processes, improving the reach and impact of teleservices for detecting, preventing and treating child maladjustment, community-based approaches, and building population-focused multidisciplinary alliances and think tanks are presented.

The social predictors of paternal antenatal mental health and their associations with maternal mental health in the Queensland Family Cohort prospective study.

Antenatal depression (AND) affects 1 in 10 fathers, potentially negatively impacting maternal mental health and well-being during and after the transition to parenthood. However, few studies have assessed the social predictors of paternal AND or their possible associations with maternal mental health. We analysed data from 180 couples participating in the Queensland Family Cohort longitudinal study. Both parents completed surveys measuring mental health, relationship quality, social support, and sleep quality at 24 weeks of pregnancy. Mothers also completed the same surveys 6 weeks' postpartum. Antenatal depression, stress, and anxiety were highest among fathers reporting lower social support and higher sleep impairment. Maternal AND, stress, and anxiety were higher among mothers reporting higher physical pain and poor sleep quality. Postnatally, mothers reporting lower social support also reported higher depression, anxiety, stress, and psycho-social well-being. While there were no significant associations between AND among fathers and maternal antenatal or postnatal depression, an exploratory analysis revealed that mothers whose partners reported lower antenatal social support also reported lower postnatal social support and higher postnatal depression. Our findings highlight the importance of including data among fathers to achieve a whole family approach to well-being during the transition to parenthood.

Cost-effectiveness of guideline-based care provision for patients with diabetes-related foot ulcers: A modelled analysis using discrete event simulation.

AIMS: The provision of guideline-based care for patients with diabetes-related foot ulcers (DFU) in clinical practice is suboptimal. We estimated the cost-effectiveness of higher rates of guideline-based care, compared with current practice. METHODS: The costs and quality-adjusted life-years (QALYs) associated with current practice (30% of patients receiving guideline-based care) were compared with seven hypothetical scenarios with increasing proportion of guideline-based care (40%, 50%, 60%, 70%, 80%, 90% and 100%). Comparisons were made using discrete event simulations reflecting the natural history of DFU over a 3-year time horizon from the Australian healthcare perspective. Incremental cost-effectiveness ratios were calculated for each scenario and compared to a willingness-to-pay of AUD 28,000 per QALY. Probabilistic sensitivity analyses were conducted to incorporate joint parameter uncertainty. RESULTS: All seven scenarios with higher rates of guideline-based care were likely cheaper and more effective than current practice. Increased proportions compared with current practice resulted in between AUD 0.28 and 1.84 million in cost savings and 11-56 additional QALYs per 1000 patients. Probabilistic sensitivity analyses indicated that the finding is robust to parameter uncertainty. CONCLUSIONS: Higher proportions of patients receiving guideline-based care are less costly and improve patient outcomes. Strategies to increase the proportion of patients receiving guideline-based care are warranted.

Impact of a prospective feedback loop on care review activities in older patients at the end of life. A stepped-wedge randomised trial.

BACKGROUND: Hospitalisation rates for older people are increasing, with end-of-life care becoming a more medicalised experience. Innovative approaches are warranted to support early identification of the end-of-life phase, communicate prognosis, provide care consistent with people's preferences, and improve the use of healthcare resources. The Intervention for Appropriate Care and Treatment (InterACT) trial aimed to increase appropriate care and treatment decisions for older people at the end of life, through implementation of a prospective feedback loop. This paper reports on the care review outcomes. METHODS: A stepped-wedge randomised controlled trial was conducted in three large acute hospitals in Queensland, Australia between May 2020 and June 2021. The trial identified older people nearing the end of life using two validated tools for detecting deterioration and short-term death. Admitting clinical teams were provided with details of patients identified as at-risk with the goal of increasing awareness that end of life was approaching to facilitate appropriate patient centred care and avoid non-beneficial treatment. We examined the time between when the patient was identified as 'at-risk' and three outcomes: clinician-led care review discussions, review of care directive measures and palliative care referrals. These were considered useful indicators of appropriate care at the end of life. RESULTS: In two hospitals there was a reduction in the review of care directive measures during the intervention compared with usual care at 21 days (reduced probability of - 0.08; 95% CI: - 0.12 to - 0.04 and - 0.14; 95% CI: - 0.21 to - 0.06). In one hospital there was a large reduction in clinician-led care review discussions at 21 days during the intervention (reduced probability of - 0.20; 95% CI: - 0.28 to - 0.13). There was little change in palliative care referrals in any hospital, with average probability differences at 21 days of - 0.01, 0.02 and 0.04. DISCUSSION: The results are disappointing as an intervention designed to improve care of hospitalised older people appeared to have the opposite effect on care review outcomes. The reasons for this may be a combination of the intervention design and health system challenges due to the pandemic that highlight the complexity of providing more appropriate care at the end of life. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry, ACTRN12619000675123 (registered 6 May 2019).

Cost-Effectiveness of Care Coordination for Children With Chronic Noncomplex Medical Conditions: Results From a Multicenter Randomized Clinical Trial.

OBJECTIVES: To assess the cost-effectiveness of care coordination, compared with standard care, for children with chronic noncomplex medical conditions. METHODS: A total of 81 children aged between 2 and 15 years newly diagnosed with a noncomplex chronic condition were randomized to either care coordination or standard care as part of a multicenter randomized controlled trial. Families receiving care coordination were provided access to an Allied Health Liaison Officer, who facilitated family-centered healthcare access across hospital, education, primary care, and community sectors. Costs were estimated over a 12-month period from the perspective of the Australian health system. Health outcomes were valued as quality-adjusted life-years (QALYs). Caregiver productivity costs were included in an alternative base-case analysis, and key assumptions were tested in a series of one-way sensitivity analyses. A probabilistic sensitivity analysis was conducted to investigate the overall impact of uncertainty in the data. RESULTS: Children in the intervention arm incurred an average of $17 in additional health system costs (95% confidence interval -3861 to 1558) and gained an additional 0.031 QALYs (95% confidence interval -0.29 to 0.092) over 12 months, producing an incremental cost-effectiveness ratio of $548 per QALY. When uncertainty was considered, there was a 73% likelihood that care coordination was cost-effective from a health system perspective, assuming a willingness to pay of $50 000 per QALY. This increased to 78% when caregiver productivity costs were included. CONCLUSIONS: Care coordination is likely to be a cost-effective intervention for children with chronic noncomplex medical conditions in the Australian healthcare setting.

Associations between COVID-19 lockdown and post-lockdown on the mental health of pregnant women, postpartum women and their partners from the Queensland family cohort prospective study.

BACKGROUND: There are very few developed countries where physical isolation and low community transmission has been reported for COVID-19 but this has been the experience of Australia. The impact of physical isolation combined with low disease transmission on the mental health of pregnant women is currently unknown and there have been no studies examining the psychological experience for partners of pregnant women during lockdown. The aim of the current study was to examine the impact of the first COVID-19 lockdown in March 2020 and post lockdown from August 2020 on the mental health of pregnant women or postpartum women and their partners. METHODS: Pregnant women and their partners were prospectively recruited to the study before 24 weeks gestation and completed various questionnaires related to mental health and general wellbeing at 24 weeks gestation and then again at 6 weeks postpartum. The Depression, Anxiety and Stress Scale (DASS-21) and the Edinburgh Postnatal Depression Scale (EPDS) were used as outcome measures for the assessment of mental health in women and DASS-21 was administered to their partners. This analysis encompasses 3 time points where families were recruited; before the pandemic (Aug 2018-Feb 2020), during lockdown (Mar-Aug 2020) and after the first lockdown was over (Sept-Dec 2020). RESULTS: There was no significant effect of COVID-19 lockdown and post lockdown on depression or postnatal depression in women when compared to a pre-COVID-19 subgroup. The odds of pregnant women or postpartum women experiencing severe anxiety was more than halved in women during lockdown relative to women in the pre-COVID-19 period (OR = 0.47; 95%CI: 0.27-0.81; P = 0.006). Following lockdown severe anxiety was comparable to the pre-COVID-19 women. Lockdown did not have any substantial effects on stress scores for pregnant and postpartum women. However, a substantial decrease of over 70% in the odds of severe stress was observed post-lockdown relative to pre-COVID-19 levels. Partner's depression, anxiety and stress did not change significantly with lockdown or post lockdown. CONCLUSION: A reproductive age population appear to be able to manage the impact of lockdown and the pandemic with some benefits related to reduced anxiety.

Interactions between Enterohemorrhagic Escherichia coli (EHEC) and Gut Commensals at the Interface of Human Colonoids.

The interactions between the gut microbiota and pathogens are complex and can determine the outcome of an infection. Enterohemorrhagic Escherichia coli (EHEC) is a major human enteric pathogen that colonizes the colon through attaching and effacing (AE) lesions and uses microbiota-derived molecules as cues to control its virulence. Different gut commensals can modulate EHEC virulence. However, the lack of an animal model that recapitulates the human pathophysiology of EHEC infection makes it challenging to investigate how variations in microbiota composition could affect host susceptibility to this pathogen. Here, we addressed these interactions building from simple to more complex in vitro systems, culminating with the use of the physiological relevant human colonoids as a model to study the interactions between EHEC and different gut commensals. We demonstrated that Bacteroides thetaiotaomicron and Enterococcus faecalis enhance virulence expression and AE lesion formation in cultured epithelial cells, as well as on the colonic epithelium, while commensal E. coli did not affect these phenotypes. Importantly, in the presence of these three commensals together, virulence and AE lesion are enhanced. Moreover, we identified specific changes in the metabolic landscape promoted by different members of the gut microbiota and showed that soluble factors released by E. faecalis can increase EHEC virulence gene expression. Our study highlights the importance of interspecies bacterial interactions and chemical exchange in the modulation of EHEC virulence. IMPORTANCE Enterohemorrhagic E. coli (EHEC) is a natural human pathogen that poorly colonizes mice. Hence, the use of murine models to understand features of EHEC infection is a challenge. In this study, we use human colonoids as a physiologically relevant model to study interactions between EHEC and gut commensals. We demonstrate that the ability of EHEC to form AE lesions on the intestinal epithelium is enhanced by the presence of certain gut commensals, such as B. thetaiotaomicron and E. faecalis, while it is not affected by commensal E. coli. Furthermore, we show that commensal bacteria differently impact the metabolic landscape. These data suggest that microbiota compositions can differentially modulate EHEC-mediated disease.