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INTRODUCTION: Low back pain (LBP) is commonly treated with opioid analgesics despite evidence that these medicines provide minimal or no benefit for LBP and have an established profile of harms. International guidelines discourage or urge caution with the use of opioids for back pain; however, doctors and patients lack practical strategies to help them implement the guidelines. This trial will evaluate a multifaceted intervention to support general practitioners (GPs) and their patients with LBP implement the recommendations in the latest opioid prescribing guidelines. METHODS AND ANALYSIS: This is a cluster randomised controlled trial that will evaluate the effect of educational outreach visits to GPs promoting opioid stewardship alongside non-pharmacological interventions including heat wrap and patient education about the possible harms and benefits of opioids, on GP prescribing of opioids medicines dispensed. At least 40 general practices will be randomised in a 1:1 ratio to either the intervention or control (no outreach visits; GP provides usual care). A total of 410 patient-participants (205 in each arm) who have been prescribed an opioid for LBP will be enrolled via participating general practices. Follow-up of patient-participants will occur over a 1-year period. The primary outcome will be the cumulative dose of opioid dispensed that was prescribed by study GPs over 1 year from the enrolment visit (in morphine milligram equivalent dose). Secondary outcomes include prescription of opioid medicines, benzodiazepines, gabapentinoids, non-steroidal anti-inflammatory drugs by study GPs or any GP, health services utilisation and patient-reported outcomes such as pain, quality of life and adverse events. Analysis will be by intention to treat, with a health economics analysis also planned. ETHICS AND DISSEMINATION: The trial received ethics approval from The University of Sydney Human Research Ethics Committee (2022/511). The results will be disseminated via publi

BACKGROUND: E-health, defined as the use of information and communication technologies to improve healthcare delivery and health outcomes, has been promoted as a cost-effective strategy to treat adolescent overweight and obesity. However, evidence supporting this claim is lacking. OBJECTIVES: Assess the potential cost-effectiveness of a hypothetical e-health intervention for adolescents with overweight and obesity. METHODS: The costs and effect size (BMI reduction) of the hypothetical intervention were sourced from recent systematic reviews. Using a micro-simulation model with a lifetime time horizon, we conducted a modelled cost-utility analysis of the intervention compared to a 'do-nothing' approach. To explore uncertainty, we conducted bootstrapping on individual-level costs and quality-adjusted life years (QALYs) and performed multiple one-way sensitivity analyses. RESULTS: The incremental cost-effectiveness ratio (ICER) for the e-health intervention was dominant (cheaper and more effective), with a 96% probability of being cost-effective at a willingness-to-pay (WTP) of $50 000/QALY. The ICER remained dominant in all sensitivity analyses except when using the lower bounds of the hypothetical intervention effect size, which reduced the probability of cost-effectiveness at a WTP of $50 000/QALY to 51%. CONCLUSION: E-health interventions for treatment of adolescent overweight and obesity demonstrate very good cost-effectiveness potential and should be considered by healthcare decision makers. However, further research on the efficacy of such interventions is warranted to strengthen the case for investment.

INTRODUCTION: Emergency department (ED) overcrowding is a global problem and a threat to the quality and safety of emergency care. Providing timely and safe emergency care therein is challenging. To address this in New South Wales (NSW), Australia, the Emergency nurse Protocol Initiating Care-Sydney Triage to Admission Risk Tool (EPIC-START) was developed. EPIC-START is a model of care incorporating EPIC protocols, the START patient admission prediction tool, and a clinical deterioration tool to support ED flow, timely care, and patient safety. The aim of this study is to evaluate the impact of EPIC-START implementation across 30 EDs on patient, implementation, and health service outcomes. METHODS AND ANALYSIS: This study protocol adopts an effectiveness-implementation hybrid design (Med Care 50: 217-226, 2012) and uses a stepped-wedge cluster randomised control trial of EPIC-START, including uptake and sustainability, within 30 EDs across four NSW local health districts spanning rural, regional, and metropolitan settings. Each cluster will be randomised independently of the research team to 1 of 4 dates until all EDs have been exposed to the intervention. Quantitative and qualitative evaluations will be conducted on data from medical records and routinely collected data, and patient, nursing, and medical staff pre- and post-surveys. ETHICS AND DISSEMINATION: Ethical approval for the research was received from the Sydney Local Health District Research Ethics Committee (Reference Number 2022/ETH01940) on 14 December 2022. TRIAL REGISTRATION: Australian and New Zealand Clinical trial, ACTRN12622001480774p. Registered on 27 October 2022.

Aims: To explore whether there is a different strength of association between self-rated health and all-cause mortality in people with type 2 diabetes across three country groupings: nine countries grouped together as 'established market economies'; Asia; and Eastern Europe. Methods: The ADVANCE trial and its post-trial follow-up were used in this study, which included 11 140 people with type 2 diabetes from 20 countries, with a median follow-up of 9.9 years. Self-rated health was reported on a 0–100 visual analogue scale. Cox proportional hazard models were fitted to estimate the relationship between the visual analogue scale score and all-cause mortality, controlling for a range of demographic and clinical risk factors. Interaction terms were used to assess whether the association between the visual analogue scale score and mortality varied across country groupings. Results: The visual analogue scale score had different strengths of association with mortality in the three country groupings. A 10-point increase in visual analogue scale score was associated with a 15% (95% CI 12–18) lower mortality hazard in the established market economies, a 25% (95% CI 21–28) lower hazard in Asia, and an 8% (95% CI 3–13) lower hazard in Eastern Europe. Conclusions: Self-rated health appears to predict 10-year all-cause mortality for people with type 2 diabetes worldwide, but this relationship varies across groups of countries.

Abstract Background There is a crisis of non-communicable diseases (NCDs) in the Pacific Islands, and poor diets are a major contributor. The COVID-19 pandemic and resulting economic crisis will likely further exacerbate the burden on food systems. Pacific Island leaders have adopted a range of food policies and regulations to improve diets. This includes taxes and regulations on compositional standards for salt and sugar in foods or school food policies. Despite increasing evidence for the effectiveness of such policies globally, there is a lack of local context-specific evidence about how to implement them effectively in the Pacific. Methods Our 5-year collaborative project will test the feasibility and effectiveness of policy interventions to reduce salt and sugar consumption in Fiji and Samoa, and examine factors that support sustained implementation. We will engage government agencies and civil society in Fiji and Samoa, to support the design, implementation and monitoring of evidence-informed interventions. Specific objectives are to: (1) conduct policy landscape analysis to understand potential opportunities and challenges to strengthen policies for prevention of diet-related NCDs in Fiji and Samoa; (2) conduct repeat cross sectional surveys to measure dietary intake, food sources and diet-related biomarkers; (3) use Systems Thinking in Community Knowledge Exchange (STICKE) to strengthen implementation of policies to reduce salt and sugar consumption; (4) evaluate the impact, process and cost effectiveness of implementing these policies. Quantitative and qualitative data on outcomes and process will be analysed to assess impact and support scale-up of future interventions. Discussion The project will provide new evidence to support policy making, as well as developin

Background Function after acute stroke using the modified Rankin Scale (mRS) is usually assessed at a point in time. The analytical implications of serial mRS measurements to evaluate functional recovery over time is not completely understood. We compare repeated-measures and single-measure analyses of the mRS from a randomized clinical trial. Methods and Results Serial mRS data from AFFINITY (Assessment of Fluoxetine in Stroke Recovery), a double-blind placebo randomized clinical trial of fluoxetine following stroke (n=1280) were analyzed to identify demographic and clinical associations with functional recovery (reduction in mRS) over 12 months. Associations were identified using single-measure (day 365) and repeated-measures (days 28, 90, 180, and 365) partial proportional odds logistic regression. Ninety-five percent of participants experienced a reduction in mRS after 12 months. Functional recovery was associated with age at stroke <70 years; no prestroke history of diabetes, coronary heart disease, or ischemic stroke; prestroke history of depression, a relationship partner, living with others, independence, or paid employment; no fluoxetine intervention; ischemic stroke (compared with hemorrhagic); stroke treatment in Vietnam (compared with Australia or New Zealand); longer time since current stroke; and lower baseline National Institutes of Health Stroke Scale & Patient Health Questionnaire-9 scores. Direction of associations was largely concordant between single-measure and repeated-measures models. Association strength and variance was generally smaller in the repeated-measures model compared with the single-measure model. Conclusions Repeated-measures may improve trial precision in identifying trial associations and effects. Further repeated-measures stroke analyses are required to prove methodological value. Registration URL: http://www.anzctr.org.au; Unique identifier: ACTRN12611000774921.

BACKGROUND AND AIM: To determine risk factors for incident chronic kidney disease (CKD) in a large population-based cohort. METHODS: This prospective opt-in population-based cohort study is based on the 45 and Up Study, where New South Wales residents aged ≥45 years were randomly sampled from the Services Australia database and agreed to complete the 45 and Up Study baseline questionnaire and have their responses linked to their health data in routinely collected databases. The primary outcome was the development of incident CKD, defined as eGFR < 60 mL/min/1.73 m2 . CKD incidence was calculated using Poisson regression. Risk factors for incident CKD were assessed using Cox regression in multivariable models. RESULTS: In 39 574 participants who did not have CKD at enrolment, independent factors associated with developing CKD included: older age, regional residence (HR 1.38 (1.27-1.50) for outer regional vs major city), smoking (1.13 (1.00-1.27) for current smoker vs non-smoker), obesity (1.25 (1.16-1.35) for obese vs normal body mass index), diabetes mellitus (1.41 (1.33-1.50)), hypertension (1.53 (1.44-1.62)), coronary heart disease (1.13 (1.07-1.20)), depression/anxiety (1.16 (1.09-1.24)) and cancer (1.29 (1.20-1.39)). Migrants were less likely to develop CKD compared with people born in Australia (0.88 (0.83-0.94)). Gender, partner status and socioeconomic factors were not independently associated with developing CKD. CONCLUSIONS: This large population-based study found multiple modifiable and non-modifiable factors were independently associated with developing CKD. In the Australian setting, the risk of CKD was higher with regional residence. Differences according to socioeconomic status were predominantly explained by age, comorbidities and harmful health-related behaviours.

Objective: To investigate long-term adherence to guideline-recommended cardioprotective medications following hospitalization for an acute myocardial infarction (AMI), and identify characteristics associated with adherence. Methods: An Australian population-based cohort study was used to identify participants who had their first AMI between 2006 and 2014 and were alive after 12 months. Linked routinely collected hospital, and prescription medication claims data was used to study adherence over time. Predictors and rates of adherence to both lipid-lowering medication and renin-angiotensin system blockade at 12 months post-AMI was assessed. Results: 14,200 people (mean age 69.9 years, 38.7% female) were included in our analysis. At 12 months post-AMI, 29.5% (95% CI: 28.8-30.3%) of people were adherent to both classes of medication. Individuals receiving treatment with both lipid-lowering medication and renin-angiotensin system blockade during the 6 months prior to their AMI were over 9 times more likely to be adherent to both medications at 12 months post-AMI (66.2% 95% CI: 64.8-67.5%) compared to those with no prior medication use (treatment naïve) (7.1%, 95% CI: 6.4-7.9%). Prior cardiovascular treatment was the strongest predictor of long-term adherence even after adjusting for age, sex, education and income. Conclusions: Despite efforts to improve long-term medication adherence in patients who have experienced an acute coronary event, considerable gaps remain. Of particular concern are people who are commencing guideline-recommended cardioprotective medication at the time of their AMI. The relationship between prior cardiovascular treatments and post AMI adherence offers insight into the support needs for the patient. Health care intervention strategies, strengthened by enabling policies, are needed to provide support to patients through the initial months following their AMI.

Background and Purpose: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76-1.14]; P=0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P=0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P=0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P=0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P=0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effec

Introduction Cardiovascular diseases (CVDs) are the leading causes of death and disability worldwide. Reducing dietary salt consumption is a potentially cost-effective way to reduce blood pressure and the burden of CVD. To date, economic evidence has focused on sodium reduction in food industry or processed food with blood pressure as the primary outcome. This study protocol describes the planned within-trial economic evaluation of a low-sodium salt substitute intervention designed to reduce the risk of stroke in China. Methods and analyses The economic evaluation will be conducted alongside the Salt Substitute and Stroke Study: a 5-year large scale, cluster randomised controlled trial. The outcomes of interest are quality of life measured using the EuroQol-5-Dimensions and major adverse cardiovascular events. Costs will be estimated from a healthcare system perspective and will be sought from the routinely collected data available within the New Rural Cooperative Medical Scheme. Cost-effectiveness and cost-utility analyses will be conducted, resulting in the incremental cost-effectiveness ratio expressed as cost per cardiovascular event averted and cost per quality-adjusted life year gained, respectively. Ethics and dissemination The trial received ethics approval from the University of Sydney Ethics Committee (2013/888) and Peking University Institutional Review Board (IRB00001052-13069). Informed consent was obtained from each study participant. Findings of the economic evaluation will be published in a peer-reviewed journal and presented at international conferences. Trial registration number ClinicalTrials.gov Registry (NCT02092090).

Introduction Falls have a multifactorial aetiology, which may limit the effectiveness of the common approach of exercise as the sole intervention strategy. Multifactorial interventions could be more effective in people at high risk of falling; however, the focus of such interventions has traditionally been quite narrow. This paper describes the design of a randomised controlled trial that will evaluate the effectiveness of an eHealth programme, which addresses cumulative effects of key fall-risk factors across the triad of physical, affective and cognitive functions on falls in older people. Methods and analysis 518 older people aged 65 years and over with high fall risk, defined as having a history of falls in the past 6 months, self-reported fear of falling or being aged 80 years or over, will be recruited via local advertisements, newsletters and presentations, and randomised to an intervention or health education control group. The intervention comprises balance exercise, cognitive-motor exercise and cognitive-behavioural therapy, with their dosage based on participant's baseline balance, executive function and mood. The primary outcome is the rate of falls in the 12 months after randomisation. Secondary outcomes at 6 and 12 months comprise programme adherence, healthcare use, physical activity, balance and mobility, cognitive function, psychological well-being, quality of life, health literacy and user experience and attitudes towards the programme. Data will be analysed following intention to treat to gauge real-world effectiveness. We will further determine complier averaged causal effects to correct for varying adherence and conduct economic analyses to gain insight into cost-effectiveness and cost-utility. Ethics and dissemination Ethical approval was obtained from the University of New South Wales (UNSW) Human Research Ethics Committee in December 2017. Outcomes will be disseminated via peer-reviewed articles, conference presentations, community events and

Cardiovascular diseases (CVD) are the leading cause of death in Indonesia, and there are large disparities in access to recommended preventative treatments across the country, particularly in rural areas. Technology-enabled screening and management led by community health workers have been shown to be effective in better managing those at high risk of CVD in a rural Indonesian population; however, the economic impacts of implementing such an intervention are unknown. We conducted a modelled cost-effectiveness analysis of the SMARThealth intervention in rural villages of Malang district, Indonesia from the payer perspective over a 10-year period. A Markov model was designed and populated with epidemiological and cost data collected in a recent quasi-randomized trial, with nine health states representing a differing risk for experiencing a major CVD event. Disability-Adjusted Life Years (DALYs) were estimated for the intervention and usual care using disability weights from the literature for major CVD events. Annual treatment costs for CVD treatment and prevention were $US83 under current care and $US144 for those receiving the intervention. The intervention had an incremental cost-effectiveness ratio of $4288 per DALY averted and $3681 per major CVD event avoided relative to usual care. One-way and probabilistic sensitivity analyses demonstrated that the results were robust to plausible variations in model parameters and that the intervention is highly likely to be considered cost-effective by decision-makers across a range of potentially acceptable willingness to pay levels. Relative to current care, the intervention was a cost-effective means to improve the management of CVD in this rural Indonesian population. Further scale-up of the intervention offers the prospect of significant gains in population health and sustainable progress toward universal health coverage for the Indonesian population.

INTRODUCTION: One in three people aged 65 years and over fall each year. The health, economic and personal impact of falls will grow substantially in the coming years due to population ageing. Developing and implementing cost-effective strategies to prevent falls and mobility problems among older people is therefore an urgent public health challenge. StandingTall is a low-cost, unsupervised, home-based balance exercise programme delivered through a computer or tablet. StandingTall has a simple user-interface that incorporates physical and behavioural elements designed to promote compliance. A large randomised controlled trial in 503 community-dwelling older people has shown that StandingTall is safe, has high adherence rates and is effective in improving balance and reducing falls. The current project targets a major need for older people and will address the final steps needed to scale this innovative technology for widespread use by older people across Australia and internationally. METHODS AND ANALYSIS: This project will endeavour to recruit 300 participants across three sites in Australia and 100 participants in the UK. The aim of the study is to evaluate the implementation of StandingTall into the community and health service settings in Australia and the UK. The nested process evaluation will use both quantitative and qualitative methods to explore uptake and acceptability of the StandingTall programme and associated resources. The primary outcome is participant adherence to the StandingTall programme over 6 months. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the South East Sydney Local Health District Human Research Ethics Committee (HREC reference 18/288) in Australia and the North West- Greater Manchester South Research Ethics Committee (IRAS ID: 268954) in the UK. Dissemination will be via publications, conferences, newsletter articles, social media, talks to clinicians and consumers and meetings with health departments/managers. TRIA

During infection, enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC) directly manipulate various aspects of host cell function through the translocation of type III secretion system (T3SS) effector proteins directly into the host cell. Many T3SS effector proteins are enzymes that mediate post-translational modifications of host proteins, such as the glycosyltransferase NleB1, which transfers a single N-acetylglucosamine (GlcNAc) to arginine residues, creating an Arg-GlcNAc linkage. NleB1 glycosylates death-domain containing proteins including FADD, TRADD and RIPK1 to block host cell death. The NleB1 paralogue, NleB2, is found in many EPEC and EHEC strains but to date its enzymatic activity has not been described. Using in vitro glycosylation assays combined with mass spectrometry, we found that NleB2 can utilize multiple sugar donors including UDP-glucose, UDP-GlcNAc and UDP-galactose during glycosylation of the death domain protein, RIPK1. Sugar donor competition assays demonstrated that UDP-glucose was the preferred substrate of NleB2 and peptide sequencing identified the glycosylation site within RIPK1 as Arg603, indicating that NleB2 catalyses arginine glucosylation. We also confirmed that NleB2 catalysed arginine-hexose modification of Flag-RIPK1 during infection of HEK293T cells with EPEC E2348/69. Using site-directed mutagenesis and in vitro glycosylation assays, we identified that residue Ser252 in NleB2 contributes to the specificity of this distinct catalytic activity. Substitution of Ser252 in NleB2 to Gly, or substitution of the corresponding Gly255 in NleB1 to Ser switches sugar donor preference between UDP-GlcNAc and UDP-glucose. However, this switch did not affect the ability of the NleB variants to inhibit inflammatory or cell death signalling during HeLa cell transfection or EPEC infection. NleB2 is thus the first identified bacterial Arg-glucose transferase that, similar to the NleB1 Arg-GlcNAc transferase, inhibits host

Background: Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods: AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings: Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, p

Aims: To use linked routinely-collected health data to estimate diabetes prevalence and incidence in an Australian cohort of adults aged ≥45 years, and examine risk factors associated with incident disease. Research design and methods: The EXamining ouTcomEs in chroNic Disease in the 45 and Up Study (EXTEND45) Study is a linked data study that combines baseline questionnaire responses from the population-based 45 and Up Study (2006–2009, n = 267,153) with multiple routinely-collected health databases up to December 2014. Among participants with ≥1 linked result for any laboratory test, diabetes status was determined from multiple data sources according to standard biochemical criteria, use of glucose-lowering medication or self-report, and the prevalence and incidence rate calculated. Independent risk factors of incident diabetes were examined using multivariable Cox regression. Results: Among 152,169 45 and Up Study participants with ≥1 linked laboratory result in the EXTEND45 database (mean age 63.0 years; 54.9% female), diabetes prevalence was 10.8% (95% confidence interval [CI] 10.6%–10.9%). Incident disease in those without diabetes at baseline (n = 135,810; mean age 62.5 years; 56.1% female) was 10.0 per 1,000 person-years (95% CI 9.8–10.2). In all age groups, diabetes incidence was lower in women compared to men, an association that persisted in the fully adjusted analyses. Other independent risk factors of diabetes were older age, being born outside of Australia (with the highest rate of 19.2 per 1,000 person-years observed in people born in South and Central Asia), lower education status, lower annual household income, residence in a major city, family history of diabetes, personal history of cardiovascular disease or hypertension, higher body mass index, smoking and long sleeping hours. Conclusions: Our study represents an efficient approach to assessing diabetes frequency and its risk factors in the community. The infrastructure provided by the EXTEND45 S

Objective: To assess the cost-effectiveness of a computer-guided quality improvement intervention for primary health care management of cardiovascular disease (CVD) in people at high risk. Design: Modelled cost-effectiveness analysis of the HealthTracker intervention and usual care for people with high CVD risk, based on TORPEDO trial data on prescribing patterns, changes in intermediate risk factors (low-density lipoprotein cholesterol, systolic blood pressure), and Framingham risk scores. Participants: Hypothetical population of people with high CVD risk attending primary health care services in a New South Wales primary health network (PHN) of mean size. Intervention: HealthTracker, integrated into health care provider electronic health record systems, provides real time decision support, risk communication, a clinical audit tool, and a web portal for performance feedback. Main outcome measures: Incremental cost-effectiveness ratios (ICERs): difference in costs of the intervention and usual care divided by number of CVD events averted with HealthTracker. Results: The estimated numbers of major CVD events over five years per 1000 patients at high CVD risk were lower in PHNs using HealthTracker, both for patients with prior CVD events (secondary prevention; 259 v 267 with usual care) and for those without prior events (primary prevention; 168 v 176). Medication costs were higher and hospitalisation costs lower with HealthTracker than with usual care for both primary and secondary prevention. The estimated ICER for one averted CVD event was $7406 for primary prevention and $17 988 for secondary prevention. Conclusion: Modelled cost-effectiveness analyses provide information that can assist decisions about investing in health care quality improvement interventions. We estimate that HealthTracker could prevent major CVD events for less than $20 000 per event averted. Trial registration (TORPEDO): Australian New Zealand Clinical Trials Registry, ACTRN 12611000478910.

During infection, Salmonella species inject multiple type III secretion system (T3SS) effector proteins into host cells that mediate invasion and subsequent intracellular replication. At early stages of infection, Salmonella exploits key regulators of host intracellular vesicle transport, including the small GTPases Rab5 and Rab7, to subvert host endocytic vesicle trafficking and establish the Salmonella-containing vacuole (SCV). At later stages of intracellular replication, interactions of the SCV with Rab GTPases are less well defined. Here we report that Rab1, Rab5, and Rab11 are modified at later stages of Salmonella infection by SseK3, an arginine N-acetylglucosamine (GlcNAc) transferase effector translocated via the Salmonella pathogenicity island 2 (SPI-2) type III secretion system. SseK3 modified arginines at positions 74, 82, and 111 within Rab1 and this modification occurred independently of Rab1 nucleotide binding. SseK3 exhibited Golgi localization that was independent of its glycosyltransferase activity but Arg-GlcNAc transferase activity was required for inhibition of alkaline phosphatase secretion in transfected cells. While SseK3 had a modest effect on SEAP secretion during infection of HeLa229 cells, inhibition of IL-1 and GM-CSF cytokine secretion was only observed upon over-expression of SseK3 during infection of RAW264.7 cells. Our results suggest that, in addition to targeting death receptor signaling, SseK3 may contribute to Salmonella infection by interfering with the activity of key Rab GTPases.

INTRODUCTION: Prior studies have revealed the increasing prevalence of obesity and its associated health effects among ageing adults in resource poor countries. However, no study has examined the long-term and economic impact of overweight and obesity in sub-Saharan Africa. Therefore, we quantified the long-term impact of overweight and obesity on life expectancy (LE), quality-adjusted life years (QALYs) and total direct healthcare costs. METHODS: A Markov simulation model projected health and economic outcomes associated with three categories of body mass index (BMI): healthy weight (18.5≤BMI <25.0); overweight (25.0≤BMI < 30.0) and obese (BMI ≥30.0 kg/m2) in simulated adult cohorts over a 50-year time horizon from age fifty. Costs were estimated from government and patient perspectives, discounted 3% annually and reported in 2017 US$. Mortality rates from Ghanaian lifetables were adjusted by BMI-specific all-cause mortality HRs. Published input data were used from the 2014/2015 Ghana WHO Study on global AGEing and adult health data. Internal and external validity were assessed. RESULTS: From age 50 years, average (95% CI) remaining LE for females were 25.6 (95% CI: 25.4 to 25.8), 23.5 (95% CI: 23.3 to 23.7) and 21.3 (95% CI: 19.6 to 21.8) for healthy weight, overweight and obesity, respectively. In males, remaining LE were healthy weight (23.0; 95% CI: 22.8 to 23.2), overweight (20.7; 95% CI: 20.5 to 20.9) and obesity (17.6; 95% CI: 17.5 to 17.8). In females, QALYs for healthy weight were 23.0 (95% CI: 22.8 to 23.2), overweight, 21.0 (95% CI: 20.8 to 21.2) and obesity, 19.0 (95% CI: 18.8 to 19.7). The discounted total costs per female were US$619 (95% CI: 616 to 622), US$1298 (95% CI: 1290 to 1306) and US$2057 (95% CI: 2043 to 2071) for healthy weight, overweight and obesity, respectively. QALYs and costs were lower in males. CONCLUSION: Overweight and obesity have substantial health and economic impacts, hence the urgent need for cost-effective preventive strateg

Children that are unrestrained while travelling in a motor vehicle are more vulnerable to serious injury and death. The greatest levels of crash protection are achieved when children use the most age or size appropriate form of restraint. In this study, we aimed to examine the effectiveness of the introduction of age-appropriate child restraint legislation on serious and fatal injury in five Australian states and territories. For this interrupted time series analysis, we used a segmented regression method to assess the association between the implementation of child-restraint legislation and motor-vehicle related serious injuries and fatalities using data obtained from transport authorities in each jurisdiction. We estimated the change in annual rates after the implementation of legislation with the number of motor-vehicle accidents resulting in fatalities or serious injuries as the outcome, and the total number of injuries (minor, serious and fatal) as an offset in the model. We identified 10882 motor-vehicle related crashes resulting in fatalities (n = 188), serious injuries (n = 1730) and minor injuries (n = 8964). In NSW and VIC, the rate ratio was statistically significant and positive, indicating an increase in the rate of serious injuries and fatalities in the period post-legislation compared to the period prior to legislation. In all other states and territories, we did not find a statistically significant effect of legislation Road safety programs incorporating interventions targeted at increasing awareness of optimal restraint practices, strengthened enforcement and measures to improve the affordability of restraints are needed to support legislation.

Background: Elevated blood pressure incurs a major health and economic burden, particularly in low-income and middle-income countries. The Triple Pill versus Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) trial showed a greater reduction in blood pressure in patients using fixed-combination, low-dose, triple-pill antihypertensive therapy (consisting of amlodipine, telmisartan, and chlorthalidone) than in those receiving usual care in Sri Lanka. We aimed to assess the cost-effectiveness of the triple-pill strategy. Methods: We did a within-trial (6-month) and modelled (10-year) economic evaluation of the TRIUMPH trial, using the health system perspective. Health-care costs, reported in 2017 US dollars, were determined from trial records and published literature. A discrete-time simulation model was developed, extrapolating trial findings of reduced systolic blood pressure to 10-year health-care costs, cardiovascular disease events, and mortality. The primary outcomes were the proportion of people reaching blood pressure targets (at 6 months from baseline) and disability-adjusted life-years (DALYs) averted (at 10 years from baseline). Incremental cost-effectiveness ratios were calculated to estimate the cost per additional participant achieving target blood pressure at 6 months and cost per DALY averted over 10 years. Findings: The triple-pill strategy, compared with usual care, cost an additional US$9·63 (95% CI 5·29 to 13·97) per person in the within-trial analysis and $347·75 (285·55 to 412·54) per person in the modelled analysis. Incremental cost-effectiveness ratios were estimated at $7·93 (95% CI 6·59 to 11·84) per participant reaching blood pressure targets at 6 months and $2842·79 (−28·67 to 5714·24) per DALY averted over a 10-year period. Interpretation: Compared with usual care, the triple-pill strategy is cost-effective for patients with mild-to-moderate hypertension. Scaled up investment in the triple pill for hypertension

Objectives: To develop a model to predict future socioeconomic inequalities in body mass index (BMI) and obesity. Design: Microsimulation modelling using BMI data from adult participants of Australian Health Surveys, and published data on the relative risk of mortality in relation to BMI and socioeconomic position (SEP), based on education. Setting: Australia. Participants: 74 329 adults, aged 20 and over from Australian Health Surveys, 1995-2015. Primary and secondary outcome measures: The primary outcomes were BMI trajectories and obesity prevalence by SEP for four birth cohorts, born 10 years apart, centred on 1940, 1950, 1960 and 1970. Results: Simulations projected persistent or widening socioeconomic inequality in BMI and obesity over the adult life course, for all birth cohorts. Recent birth cohorts were predicted to have greater socioeconomic inequality by middle age, compared with earlier cohorts. For example, among men, there was no inequality in obesity prevalence at age 60 for the 1940 birth cohort (low SEP 25% (95% CI 17% to 34%); high SEP 26% (95% CI 19% to 34%)), yet for the 1970 birth cohort, obesity prevalence was projected to be 51% (95% CI 43% to 58%) and 41% (95% CI 36% to 46%) for the low and high SEP groups, respectively. Notably, for more recent birth cohorts, the model predicted the greatest socioeconomic inequality in severe obesity (BMI >35 kg/m 2) at age 60. Conclusions: Lower SEP groups and more recent birth cohorts are at higher risk of obesity and severe obesity, and its consequences in middle age. Prevention efforts should focus on these vulnerable population groups in order to avoid future disparities in health outcomes. The model provides a framework for further research to investigate which interventions will be most effective in narrowing the gap in socioeconomic disparities in obesity in adulthood.

BACKGROUND AND OBJECTIVES: This study investigated the effect of management - including home medicines reviews and chronic disease management plans funded through the Medicare Benefits Schedule - on self-reported medication non-adherence. METHOD: An observational cohort study including 244 individuals with an exacerbation of chronic illness enrolled into the Care Navigation randomised controlled trial of integrated care. Non-adherence was measured using the Morisky-Greene-Levine self-reported adherence tool. RESULTS: The cohort comprised an equal number of older men and women with, on average, three chronic diseases, receiving between five and 10 unique medications each month and visiting a general practitioner (GP) more than 50 times in the year prior to completing the questionnaire. Forty per cent reported non-adherence, which was greater in males (relative risk [RR]: 1.73; 95% confidence interval [CI]: 1.25, 2.54) and in patients reporting a recent fall (RR 1.40; 95% CI: 1.02, 1.89). GP-initiated chronic disease management programs did not influence adherence. DISCUSSION: Despite almost weekly contact with GPs, two in five patients were non-adherent. Better methods of encouraging adherence are needed.