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Abstract Background Many Australian adults are not receiving timely or effective diabetes management to prevent or delay the onset of diabetes related complications. Integrated care, a worldwide trend in healthcare reform, aims to reduce the fragmented delivery of health services and improve outcomes. This study aimed to test whether a specialist-led integrated model of care provided to a small subset of patients in general practices leads to spillover clinical improvements in all patients of the practice with type 2 diabetes. Methods Seventy-two general practice sites (clusters) in New South Wales, Australia received the Diabetes Alliance intervention, creating a non-randomised open cohort stepped wedge trial. The intervention comprised of case conferencing, delivered directly to a small proportion of adults with type 2 diabetes (n = 1,072) of the general practice sites; as well as practice feedback, education and training. Spillover clinical improvements were assessed on all adults with type 2 diabetes within the general practice sites (n = 22,706), using practice level data recorded in the MedicineInsight electronic database, compared before and after the intervention. Outcome measures included frequency of diabetes screening tests in line with the Annual Cycle of Care, and clinical results for weight, blood pressure, HbA1c, lipids, and kidney function. Results Compared to before Diabetes Alliance, the odds of all practice patients receiving screening tests at or above the recommended intervals were significantly higher for all recommended tests after Diabetes Alliance (odds ratio range 1.41–4.45, p

Abstract Background The effectiveness of the NSW Health “Get Healthy Information and Coaching Service® ”(Get Healthy) to facilitate weight loss on a population scale has been documented, but this was based on self-reported measures. Our study aims to test the effectiveness of the Get Healthy Service on objectively measured weight, BMI, waist circumference, and changes in other health behaviours, including nutrition, physical activity and alcohol intake. Methods Men and women aged 40–70 years (n = 154) with pre-diabetes (5.7% < HbA1c

Background: In this paper we outline the protocol for an implementation-effectiveness trial of ecofit, a multi-component mHealth intervention aimed at increasing participation in resistance and aerobic physical activity using the outdoor built environment (i.e., outdoor gyms) and social support. We have previously demonstrated the efficacy and effectiveness of the ecofit program in insufficiently active people with (or at risk of) type 2 diabetes and community-dwelling adults, respectively. The objective of this trial is to compare the effects of two implementation support models (i.e., ‘Low’ versus ‘Moderate’) on the reach (primary outcome), uptake, dose received, impact and fidelity of the ecofit program. Research design and methods: This hybrid type III implementation-effectiveness study will be evaluated using a two-arm randomized controlled trial, including 16 outdoor gym locations in two large regional municipalities in New South Wales, Australia. Outdoor gym locations will be pair-matched, based on an established socio-economic status consensus-based index (high versus low), and randomized to the ‘Low’ (i.e., ecofit app only) or ‘Moderate’ (i.e., ecofit app, face-to-face workout sessions and QR codes) implementation support group. The primary outcome of ‘reach’ will be measured using a modified version of the ‘System for Observing Play and Recreation in Communities’, capturing outdoor gym use amongst community members. Conclusion: This implementation-effectiveness trial will evaluate the effects of different levels of implementation support on participation in resistance-focused physical activity using mHealth and outdoor gyms across the broader community. This may guide widespread dissemination for councils (municipalities) nation-wide wanting to promote outdoor gym usage. Trial registry: This trial was preregistered with the Australian and New Zealand Clinical Trial Registry (ACTRN12624000261516).

Abstract 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.

Abstract 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.

Abstract Research Impact Assessment (RIA) represents one of a suite of policies intended to improve the impact generated from investment in health and medical research (HMR). Positivist indicator-based approaches to RIA are widely implemented but increasingly criticised as theoretically problematic, unfair, and burdensome. This commentary proposes there are useful outcomes that emerge from the process of applying an indicator-based RIA framework, separate from those encapsulated in the metrics themselves. The aim for this commentary is to demonstrate how the act of conducting an indicator-based approach to RIA can serve to optimise the productive gains from the investment in HMR. Prior research found that the issues regarding RIA are less about the choice of indicators/metrics, and more about the discussions prompted and activities incentivised by the process. This insight provides an opportunity to utilise indicator-based methods to purposely optimise the research impact. An indicator-based RIA framework specifically designed to optimise research impacts should: focus on researchers and the research process, rather than institution-level measures; utilise a project level unit of analysis that provides control to researchers and supports collaboration and accountability; provide for prospective implementation of RIA and the prospective orientation of research; establish a line of sight to the ultimate anticipated beneficiaries and impacts; Include process metrics/indicators to acknowledge interim steps on the pathway to final impacts; integrate ‘next’ users and prioritise the utilisation of research outputs as a critical measure; Integrate and align the incentives for researchers/research projects arising from RIA, with those existing within the prevailing research system; integrate with existing peer-review processes; and, adopt a system-wide approach where incremental improvements in the probability of translation from individual research projects, yields higher impact across the whole funding portfolio. Optimisation of the impacts from HMR investment represents the primary purpose of Research Impact policy. The process of conducting an indicator-based approach to RIA, which engages the researcher during the inception and planning phase, can directly contribute to this goal through improvements in the probability that an individual project will generate interim impacts. The research project funding process represents a promising forum to integrate this approach within the existing research system.

Abstract Background Improving the coordination and integration of health services is recognised nationally and internationally as a key strategy for improving the quality of diabetes care. The Australian Diabetes Alliance Program (DAP) is an integrated care model implemented in the Hunter New England Local Health District (HNELHD), New South Wales (NSW), in which endocrinologists and diabetes educators collaborate with primary care teams via case-conferencing, practice performance review, and education sessions. The objective of this study was to report on general practitioners’ (GPs) perspectives on DAP and whether the program impacts on their skills, knowledge, and approach in delivering care to adult patients with type 2 diabetes. Methods Four primary care practices with high rates of monitoring haemoglobin A1c (HbA1c) levels (> 90% of patients annually) and five practices with low rates of monitoring HbA1c levels (

Introduction Migraine headache is a significant health problem affecting patients’ psychological well-being and quality of life. Several network meta-analyses (NMAs) have compared the efficacy of migraine prophylaxis medications. However, some have focused exclusively on oral medications, while others were limited to injectable medications. Moreover, none of these NMAs conducted a stratified analysis between treatment-naïve patients and those with prior treatment failure. Therefore, this systematic review and NMA will compare the efficacy among all treatments for migraine prophylaxis, stratified by the treatment status of patients (ie, treatment-naïve and previous treatment failure).Methods and analysis Randomised-controlled trials that included patients with chronic or episodic migraine, assessed the efficacy of oral or injectable treatments for migraine prophylaxis and measured the outcomes as monthly migraine day, monthly headache day, migraine-related disability, health-related quality of life or adverse drug events will be eligible for inclusion in this review. Relevant studies will be searched from Medline, Scopus, the US National Institutes of Health Register, and the World Health Organization International Clinical Trials Registry Platform (WHO-ICTRP) databases since inception through 15 August 2023. Risk of bias assessment will be performed using a revised tool for assessing the risk of bias in randomised trials. Two-stage NMA will be applied to compare relative treatment effects among all treatments of migraine prophylaxis. Surface under the cumulative ranking curve will be applied to estimate and rank the probability to be the best treatment. Consistency assumption will be assessed using a design-by-treatment interaction model. Publication bias will be assessed by comparison-adjusted funnel plot. All analyses will be stratified according to patients’ status (ie, treatment-naïve and prior treatment failure).Ethics and dissemination This study is a systematic review protocol collecting data from published literature and does not require approval from an institutional review board. Results from this systematic review will be published in a peer-reviewed journal.PROSPERO registration number CRD42020171843.

Introduction Venous thromboembolism (VTE) is a recognised postsurgical risk. Current prevention methods involve low molecular weight heparin (LMWH), graduated compression stockings (GCS), and intermittent pneumatic compression devices (IPCDs). Australian guidelines, commonly adopted by surgeons, recommend LMWH with GCS and/or IPCDs. IPCDs pose clinical risks, increase care burden, are poorly tolerated, and are costly single-use plastic items. Utilising only LMWH and GCS, without IPCDs, could be more practical, patient-friendly, and cost-effective, with added environmental benefits.Methods This is a multicentre, prospective, two-arm randomised controlled non-inferiority trial at five New South Wales (NSW) hospitals, in Australia. We propose to randomise 4130 participants in a 1:1 ratio between arm A: LMWH+GCS+IPCDs (n=2065) or arm B: LMWH+GCS (n=2065). The primary outcome of interest is symptomatic VTE (deep vein thrombosis/pulmonary embolism) identified at the day 30 phone follow-up (FU), confirmed by ultrasound or imaging. Radiologists interpreting the lower-extremity ultrasonography will be blinded to intervention allocation. Secondary outcomes are quality of life at baseline, days 30 and 90 FU using the 5-level European Quality of Life Score, compliance and adverse events with IPCDs, GCS, and LMWH, as well as healthcare costs (from the perspective of the patient and the hospital), and all-cause mortality. The trial has 90% power to detect a 2% non-inferiority margin to detect a reduction rate of VTE from 4% to 2%.Ethics and dissemination This study has been approved by the Hunter New England Human Research Ethics Committee (2022/ETH02276) protocol V.10, 13 July 2023. Study findings will be presented at local and national conferences and in scientific research journals.Trial registration number ANZCTR12622001527752

Malnutrition rates in Advanced Liver Disease (ALD) are significantly higher than those in well-compensated liver disease. In addition to its physiological impact, malnutrition is detrimental for quality of life and social, emotional, and psychological well-being. Studies within oncology and renal supportive care have identified the influence of non-physiological factors on malnutrition risk. Integrating similar factors into malnutrition screening for ALD could improve identification of at-risk patients to optimize treatment planning. This qualitative study aimed to understand the holistic factors influencing nutritional status in the ALD population. Semi-structured interviews with 21 patients, carers, and clinicians explored the experiences of malnutrition in ALD. Thematic analysis revealed five key themes: (i) appropriateness of healthcare delivery; (ii) health- and food-related factors; (iii) high symptom burden, (iv) social support impacting well-being, and (v) physical and structural supports. Current screening methods do not adequately capture all potential drivers of malnutrition in the ALD population. Adopting a more supportive approach including both physiological and non-physiological factors in ALD malnutrition screening may promote more timely and comprehensive nutritional interventions that address the complex and holistic needs of patients living with ALD.

Abstract Background Obstructive sleep apnea (OSA) during pregnancy is a risk factor for preeclampsia possibly through a link to placental physiology. This study evaluates the efficacy of continuous positive airway pressure (CPAP) on the modulation of blood pressure and the reduction in preeclampsia in women with high-risk pregnancy and OSA. Methods A multicenter open-label, randomized controlled trial comparing CPAP treatment versus usual antenatal care was conducted in three academic hospitals in Bangkok, Thailand. Participants included singleton pregnant women aged older than 18 years with any high-risk condition (i.e., chronic hypertension, obesity, history of preeclampsia or gestational diabetes in the previous pregnancy, or diabetes), and OSA (respiratory disturbance index 5–29.99 events/hour by polysomnography), who presented either in the first trimester (gestational age, GA 0–16 weeks) or subsequently developed OSA during the 2nd trimester (GA 24–28 weeks). The primary endpoint was blood pressure during antenatal care. Secondary endpoints included the incidence of preeclampsia. An intention-to-treat analysis was performed with additional per-protocol and counterfactual analyses for handling of nonadherence. Results Of 340 participants, 96.5% were recruited during the first trimester. Thirty participants were later excluded leaving 153 and 157 participants in the CPAP and usual-care groups for the modified-intention-to-treat analysis. CPAP adherence rate was 32.7% with average use of 2.5 h/night. Overall, CPAP treatment significantly lowered diastolic blood pressure (DBP) by − 2.2 mmHg [95% CI (− 3.9, − 0.4), p = 0.014], representing approximately − 0.5 mmHg per hour of CPAP use [95%CI (− 0.89, − 0.10), p = 0.013]. CPAP treatment also altered the blood pressure trajectory by continuously lowering DBP throughout pregnancy with mean differences (95% CI) of − 3.09 (− 5.34, − 0.93), − 3.49 (− 5.67, − 1.31) and − 3.03 (− 5.20, − 0.85) mmHg at GA 18–20, 24–28, and 32–34 weeks, respectively compared to 0–16 weeks. Preeclampsia rate was 13.1% (20/153 participants) in the CPAP and 22.3% (35/157 participants) in the usual-care group with a risk difference (95% CI) of − 9% (− 18%, − 1%, p-value = 0.032) and a number-needed-to-treat (95% CI) of 11 (1, 21). Conclusions CPAP treatment in women with even mild-to-moderate OSA and high-risk pregnancy demonstrated reductions in both DBP and the incidence of preeclampsia. CPAP treatment also demonstrated a sustained reduction in DBP throughout gestation. Trial registration ClinicalTrial.GovNCT03356106, retrospectively registered November 29, 2017.

Abstract Background Few randomised controlled trials specifically focus on prevention in rural populations. Cardiovascular disease (CVD) contributes to approximately one quarter of deaths in Australia. Nutrition is a key component affecting many risk factors associated with CVD, including hypercholesterolaemia. However, access to medical nutrition therapy (MNT) is limited for people living in rural areas, potentially exacerbating inequities related to health outcomes. Telehealth services present an opportunity to improve MNT access and address healthcare disparities for rural populations. The present study aims to evaluate feasibility, acceptability, and cost-effectiveness of a telehealth MNT CVD intervention program in lowering CVD risk over 12-months in regional and rural primary health care settings. Methods/design A cluster randomised controlled trial set in rural and regional general practices in NSW, Australia, and their consenting patients (n = 300 participants). Practices will be randomised to either control (usual care from their General Practitioner (GP) + low level individualised dietetic feedback) or intervention groups (usual care from their GP + low level individualised dietetic feedback + telehealth MNT intervention). Telehealth consultations will be delivered by an Accredited Practising Dietitian (APD), with each intervention participant scheduled to receive five consultations over a 6-month period. System-generated generic personalised nutrition feedback reports are provided based on completion of the Australian Eating Survey – Heart version (AES-Heart), a food frequency questionnaire. Eligible participants must be assessed by their GP as at moderate (≥ 10%) to high (> 15%) risk of a CVD event within the next five years using the CVD Check calculator and reside in a regional or rural area within the Hunter New England Central Coast Primary Health Network (HNECC PHN) to be eligible for inclusion. Outcome measures are assessed at baseline, 3, 6 and 12 months. The primary outcome is reduction in total serum cholesterol. Evaluation of the intervention feasibility, acceptability and cost-effective will incorporate quantitative, economic and qualitative methodologies. Discussion Research outcomes will provide knowledge on effectiveness of MNT provision in reducing serum cholesterol, and feasibility, acceptability, and cost-effectiveness of delivering MNT via telehealth to address CVD risk in rural regions. Results will inform translation to health policy and practice for improving access to clinical care in rural Australia. Trial registration This trial is registered at anzctr.org.au under the acronym HealthyRHearts (Healthy Rural Hearts), registration number ACTRN12621001495819.

Abstract Objective: Web-based dietary interventions could support healthy eating. The Advice, Ideas and Motivation for My Eating (Aim4Me) trial investigated the impact of three levels of personalised web-based dietary feedback on diet quality in young adults. Secondary aims were to investigate participant retention, engagement and satisfaction. Design: Randomised controlled trial. Setting: Web-based intervention for young adults living in Australia. Participants: 18–24-year-olds recruited across Australia were randomised to Group 1 (control: brief diet quality feedback), Group 2 (comprehensive feedback on nutritional adequacy + website nutrition resources) or Group 3 (30-min dietitian consultation + Group 2 elements). Australian Recommended Food Score (ARFS) was the primary outcome. The ARFS subscales and percentage energy from nutrient-rich foods (secondary outcomes) were analysed at 3, 6 and 12 months using generalised linear mixed models. Engagement was measured with usage statistics and satisfaction with a process evaluation questionnaire. Results: Participants (n 1005, 85 % female, mean age 21·7 ± 2·0 years) were randomised to Group 1 (n 343), Group 2 (n 325) and Group 3 (n 337). Overall, 32 (3 %), 88 (9 %) and 141 (14 %) participants were retained at 3, 6 and 12 months, respectively. Only fifty-two participants (15 % of Group 3) completed the dietitian consultation. No significant group-by-time interactions were observed (P > 0·05). The proportion of participants who visited the thirteen website pages ranged from 0·6 % to 75 %. Half (Group 2 = 53 %, Group 3 = 52 %) of participants who completed the process evaluation (Group 2, n 111; Group 3, n 90) were satisfied with the programme. Conclusion: Recruiting and retaining young adults in web-based dietary interventions are challenging. Future research should consider ways to optimise these interventions, including co-design methods.

BackgroundIn patients with type 2 diabetes (T2D) and a history of heart failure (HF), sodium–glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated cardiovascular (CV) benefits. However, the comparative efficacy of individual SGLT2is remains uncertain. This network meta-analysis (NMA) compared the efficacy and safety of five SGLT2is (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and sotagliflozin) on CV outcomes in these patients.Materials and methodsPubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched up to September 23, 2022, to identify all randomized controlled trials (RCTs) comparing SGLT2is to placebo in T2D patients with HF. The main outcomes included composite CV death/heart failure hospitalization (HFH), HFH, CV death, all-cause mortality, and adverse events. Pairwise and NMA approaches were applied.ResultsOur analysis included 11 RCTs with a total of 20,438 patients with T2D and HF. All SGLT2is significantly reduced HFH compared to standard of care (SoC) alone. “Add-on” SGLT2is, except ertugliflozin, significantly reduced composite CV death/HFH relative to SoC alone. Moreover, canagliflozin had lower composite CV death/HFH compared to dapagliflozin. Based on the surface under the cumulative ranking curve (SUCRA), the top-ranked SGLT2is for reducing HFH were canagliflozin (95.5%), sotagliflozin (66.0%), and empagliflozin (57.2%). Head-to-head comparisons found no significant differences between individual SGLT2is in reducing CV death. “Add-on” SGLT2is reduced all-cause mortality compared with SoC alone, although only dapagliflozin was statistically significant. No SGLT2is were significantly associated with serious adverse events. A sensitivity analysis focusing on HF-specific trials found that dapagliflozin, empagliflozin, and sotagliflozin significantly reduced composite CV death/HFH, consistent with the main analysis. However, no significant differences were identified from their head-to-head comparisons in the NMA. The SUCRA indicated that sotagliflozin had the highest probability of reducing composite CV death/HFH (97.6%), followed by empagliflozin (58.4%) and dapagliflozin (44.0%).ConclusionSGLT2is significantly reduce the composite CV death/HFH outcome. Among them, canagliflozin may be considered the preferred treatment for patients with diabetes and a history of heart failure, but it may also be associated with an increased risk of any adverse events compared to other SGLT2is. However, a sensitivity analysis focusing on HF-specific trials identified sotagliflozin as the most likely agent to reduce CV death/HFH, followed by empagliflozin and dapagliflozin.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022353754.

BackgroundSevere periodontitis affects 26% of Thai adults and 11.2% of adults globally and is characterized by the loss of alveolar bone height. Full-mouth examination by periodontal probing is the gold standard for diagnosis but is time- and resource-intensive. A screening model to identify those at high risk of severe periodontitis would offer a targeted approach and aid in reducing the workload for dentists. While statistical modelling by a logistic regression is commonly applied, optimal performance depends on feature selections and engineering. Machine learning has been recently gaining favor given its potential discriminatory power and ability to deal with multiway interactions without the requirements of linear assumptions. ObjectiveWe aim to compare the performance of screening models developed using statistical and machine learning approaches for the risk prediction of severe periodontitis. MethodsThis study used data from the prospective Electricity Generating Authority of Thailand cohort. Dental examinations were performed for the 2008 and 2013 surveys. Oral examinations (ie, number of teeth and oral hygiene index and plaque scores), periodontal pocket depth, and gingival recession were performed by dentists. The outcome of interest was severe periodontitis diagnosed by the Centre for Disease Control–American Academy of Periodontology, defined as 2 or more interproximal sites with a clinical attachment level ≥6 mm (on different teeth) and 1 or more interproximal sites with a periodontal pocket depth ≥5 mm. Risk prediction models were developed using mixed-effects logistic regression (MELR), recurrent neural network, mixed-effects support vector machine, and mixed-effects decision tree models. A total of 21 features were considered as predictive features, including 4 demographic characteristics, 2 physical examinations, 4 underlying diseases, 1 medication, 2 risk behaviors, 2 oral features, and 6 laboratory features. ResultsA total of 3883 observations from 2086 participants were split into development (n=3112, 80.1%) and validation (n=771, 19.9%) sets with prevalences of periodontitis of 34.4% (n=1070) and 34.1% (n=263), respectively. The final MELR model contained 6 features (gender, education, smoking, diabetes mellitus, number of teeth, and plaque score) with an area under the curve (AUC) of 0.983 (95% CI 0.977-0.989) and positive likelihood ratio (LR+) of 11.9 (95% CI 8.8-16.3). Machine learning yielded lower performance than the MELR model, with AUC (95% CI) and LR+ (95% CI) values of 0.712 (0.669-0.754) and 2.1 (1.8-2.6), respectively, for the recurrent neural network model; 0.698 (0.681-0.734) and 2.1 (1.7-2.6), respectively, for the mixed-effects support vector machine model; and 0.662 (0.621-0.702) and 2.4 (1.9-3.0), respectively, for the mixed-effects decision tree model. ConclusionsThe MELR model might be more useful than machine learning for large-scale screening to identify those at high risk of severe periodontitis for periodontal evaluation. External validation using data from other centers is required to evaluate the generalizability of the model.

Objectives There is little evidence to suggest the best model of palliative and end-of-life care (PEOLC) in an acute care hospital. We introduced a bundle of care to drive improvements in PEOLC; this bundle included three full-time nursing positions providing a palliative care clinical consult service with physician backup, as well as educating staff, using the NSW Resuscitation Plan and the Last-Days-of-Life Toolkit.Methods Two audits were performed at John Hunter Hospital, a tertiary hospital in Newcastle, Australia, each sampling from all deaths in a 12-month period, one prior to and one after the bundle of care was introduced. Sampling was stratified into deaths that occurred within 4–48 hours of admission and after 48 hours. Key outcomes/data points were recorded and compared across the two time periods.Results Statistically significant improvements noted included: lower mortality on the wards after 48 hours of admission, better recognition of the dying patient, increased referral to palliative care nurses and physicians, reduction in the number of medical emergency team calls and increase in the use of comfort care and resuscitation plans. Currently, 73% of patients have their end-of-life wishes observed as per their advance care directive.Conclusion A bundle of care involving dedicated nurses with physician backup providing a consult service and education is an effective method for driving improvements in PEOLC.

Abstract Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common cause of chronic liver disease and can progress to nonalcoholic steatohepatitis and cirrhosis. This study aims to summarize the evidence for the effects of curcumin on MAFLD progression. Studies were identified from Medline and Scopus databases until April 2022. Systematic reviews and meta-analyses (SRMA) and randomized controlled trials (RCT) were selected based on pre-specified criteria. Three reviewers independently extracted data and assessed quality of included studies. Of the 427 identified records, 6 SRMAs and 16 RCTs were included in the analysis. Very high overlap was observed among SRMAs with corrected covered area of 21.9%. From an updated meta-analysis, curcumin demonstrated significant improvement in aspartate and alanine aminotransferase with pooled mean difference [95% confidence interval (CI)] of −3.90 (−5.97, −1.82) and −5.61 (−9.37, −1.85) units/L, respectively. Resolution and improvement of hepatic steatosis was higher in curcumin than control group with pooled relative risk (95% CI) of 3.53 (2.01, 6.22) and 3.41 (1.36, 8.56), respectively. Curcumin supplementation also led to lower fasting blood sugar, body mass index, and total cholesterol. Further trials should be conducted to assess the effect of curcumin on liver histology, especially regarding non-invasive hepatic fibrosis and steatosis.

Abstract Background Multikinase inhibitors (MKIs) represent the main treatment options for advanced hepatocellular carcinoma (aHCC). However, accessibility in developing countries is limited. A chemotherapy, Fluorouracil and Oxaliplatin (FOLFOX), offers a less expensive treatment. Therefore, this study sought to compare the clinical effectiveness of FOLFOX with Sorafenib as a first‐line treatment for aHCC in real‐life practice. Methods A retrospective aHCC cohort from four Thai hospitals was investigated for patients who received FOLFOX or Sorafenib between 2013–2019. Multiple imputation by chained equations addressed missing covariate data in a treatment effect model using Weight‐adjusted‐censoring inverse‐probability‐weighted regression adjustment; overall survival (OS) and progression‐free survival (PFS) were estimated. Results A total of 504 patients were included, (Sorafenib [n = 382] and FOLFOX [n = 122]). The treatment effect model estimated a median OS for Sorafenib and FOLFOX of 11.38 and 8.22 months, representing a significantly shorter OS (95% confidence interval) of −3.16 (−6.21, −0.11) months for FOLFOX, p = 0.042. A significant shorter median PFS of FOLFOX to Sorafenib of −2.13 (−3.03, −1.24) months, p

Background: The relationship between overweight or obesity and depressive symptoms in individuals with or without cardio-metabolic abnormalities is unclear. In a cross-sectional study we examined the odds of experiencing depressive symptoms in overweight or obese older adults with or without metabolic abnormalities. Methods: The participants included 3318 older adults from the Hunter Community Study Cohort with a Body Mass Index (BMI) ≥ 18.5 kgm2, stratified by BMI and metabolic health risk. Obesity was defined as BMI ≥ 30 kgm2 and metabolically healthy as the absence of metabolic risk factors, according to International Diabetic Federation criteria for metabolic syndromes. Moderate to severe depressive symptoms were defined as a Centre for Epidemiological Studies Depression Scale (CES-D) score ≥ 16. Results: Compared to the metabolically healthy normal weight (MHNW) group, the odds of experiencing moderate/severe depressive symptoms were higher in those classified as a metabolically unhealthy normal weight (MUNW) (odds ratio (OR) = 1.25, 95% Confidence Interval (CI): 0.76–2.06) or metabolically unhealthy obesity (MUO) (OR = 1.48, 95% CI: 1.00–2.19), but not in those classified as metabolically unhealthy overweight (MUOW) (OR = 0.96, 95% CI: 0.63–1.45), metabolically healthy overweight (MHOW) (OR = 0.80, 95% CI: 0.51–1.26), and metabolically healthy obesity (MHO) (OR = 1.03, 95% CI: 0.65–1.64). Compared with MHNW males, the odds of moderate/severe depressive symptoms were increased in all other BMI category–metabolic health groups for males and females. Limitations: Our relatively small sample size and cross-sectional design did not allow us to robustly establish causality. Conclusion: The odds of experiencing moderate/severe depressive symptoms were increased in metabolically unhealthy older adults regardless of normal weight or obesity, with the odds of having moderate/severe depressive symptoms being higher in females than in males.

IntroductionMost pregnant women with substance use problems smoke, and few will quit during their pregnancy. Tobacco treatment is often overlooked, with the focus usually placed on other substance use. Additionally, few targeted effective treatments for this group exist. To address this, the feasibility of an intensive tobacco treatment incorporating contingency management (CM) that featured non–face-to-face delivery was examined.MethodsA single-arm pre-post design feasibility trial was conducted in three antenatal services that support women who use substances in metropolitan Australia. Participants were over the age of 15, had 5 considered favorable).DiscussionThis study demonstrated the feasibility and acceptability of a consumer-informed, non–face-to-face intensive tobacco treatment, highlighting the potential of remotely delivered technology-based CM to reduce the health impact of tobacco smoking in high-priority populations. The intervention demonstrates scale-up potential. Future studies should extend treatment into the postpartum period, utilizing new technologies to enhance CM delivery and improve counseling provision and partner support.Clinical trial registrationhttps://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374196, ACTRN1261800056224.

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

Abstract Background The reno-protective effect of second-line treatments in type 2 diabetes has been assessed by clinical trials but generalizability to routine clinical practice is still uncertain. We aimed to assess the effectiveness of these treatments, when added to metformin, on the risk of chronic kidney disease (CKD). Methods A real-world, hospital-based, type 2 diabetes cohort was retrospectively assembled at Ramathibodi Hospital from 2010 to 2019. Patients who received sulfonylureas (SU), thiazolidinediones (TZD), dipeptidyl peptidase-4 inhibitors (DPP4i), or sodium-glucose cotransporter-2 inhibitors (SGLT2i), as second-line antihyperglycemic treatment were included. Treatment effect models with inverse probability weighting and regression adjustment were used to estimate CKD risk according to treatment. Results CKD was identified in 4,132 of the 24,777 patients with type 2 diabetes (16.7%). The CKD incidence (95% CI) was 4.1% (2.2%, 6.9%), 13.5% (12.5%, 14.6%), 14.8% (13.5%, 16.1%), and 18.0% (17.4%, 18.5%) for patients receiving SGLT2i, DPP4i, TZD, and SU treatment, respectively. The average treatment effects (i.e., the difference in CKD risk) for SGLT2i, DPP4i, and TZD compared to SU were − 0.142 (− 0.167, − 0.116), − 0.046 (− 0.059, − 0.034), and − 0.004 (− 0.023, 0.014), respectively, indicating a significant reduction in CKD risk of 14.2% and 4.6% in the SGLT2i and DPP4i groups, respectively, compared to the SU group. Furthermore, SGLT2i significantly reduced CKD risk by 13.7% (10.6%, 16.8%) and 9.5% (6.8%, 12.2%) when compared to TZD and DPP4i, respectively. Conclusions Our study identified 14.2%, 13.7%, and 9.5% reduced CKD risk in Thai patients with type 2 diabetes who were treated with SGLT2i compared to those treated with SU, TZD, and DPP4i, respectively, in real-world clinical data. Previous evidence of a reno-protective effect of SGLT2i reported in other populations is consistent with our observations in this Southeast Asian cohort.

Abstract Opioid addiction (OA) is moderately heritable, yet only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data together with published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (rg > 0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p = 2.56 × 10–9). Gene-based analyses identified novel genome-wide significant associations with PPP6C and FURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.

Introduction: Various pharmacological treatments are available for preterm infants with patent ductus arteriosus (PDA), but their risks and benefits are controversial. This study aimed to identify the best treatment for PDA using network meta-analysis (NMA) and risk-benefit assessment (RBA). Methods: Relevant randomized controlled trials (RCTs) were identified from MEDLINE, Scopus, and the Cochrane Library. RCTs were eligible if they were studied for preterm or low birth weight infants with presymptomatic PDA and hemodynamically significant PDA (hsPDA). The outcomes were PDA closure for a benefit and the composite risk outcome of adverse effects (AEs) for risk. An NMA was used to estimate the treatment effects of benefit and risk. The RBA helped to incorporate the risk and benefits of multiple treatments. Then, an incremental risk-benefit ratio was calculated by dividing the incremental risk by benefit using data from NMA, and they were jointly simulated using Monte Carlo methods. Finally, net clinical benefit (NCB) probability curves were constructed at varying acceptability thresholds. Results: Seventy RCTs with hsPDA were eligible considering 13 different interventions, but data on presymptomatic PDA were not enough for pooling. The clustered ranking plot from NMA indicated that 3 interventions (i.e., high-dose oral ibuprofen, standard-dose oral acetaminophen, and standard-dose oral ibuprofen) yielded high PDA closure and low AE. These three treatments and additional commonly used indomethacin were considered in the RBA. Given an acceptable threshold of 25% or having one AE out of four PDA closures, high-dose oral ibuprofen had a 36% chance of having the highest NCB, followed by standard-dose oral acetaminophen (27%), and oral ibuprofen (23.7%). Subgroup analysis indicated that the chances of having the highest NCB of GA ≥28 weeks were similar to that of all available studies. The best for GA

Abstract Purpose This study reports economic evaluation of mesh fixation in open and laparoscopic hernia repair from a prospective real-world cohort study, using cost-effectiveness analysis (CEA) and cost-utility analysis (CUA). Methods A prospective real-world cohort study was conducted in two university-based hospitals in Thailand from November 2018 to 2019. Patient data on hernia features, operative approaches, clinical outcomes, associated cost data, and quality of life were collected. Models were used to determine each group’s treatment effect, potential outcome means, and average treatment effects. An incremental cost-effectiveness ratio was used to evaluate the incremental risk of hernia recurrences. Results The 261 patients in this study were divided into six groups: laparoscopic with tack (LT, n = 47), glue (LG, n = 26), and self-gripping mesh (LSG, n = 30), and open with suture (OS, n = 117), glue (OG, n = 18), and self-gripping mesh (OSG, n = 23). Hernia recurrence was most common in LSG. The mean utility score was highest in OG and OSG (both 0.99). Treatment costs were generally higher for laparoscopic than open procedures. The cost-effectiveness plane for utility and hernia recurrence identified LSG as least cost effective. Cost-effectiveness acceptability curves identified OG as having the highest probability of being cost effective at willingness to pay levels between $0 and $3,300, followed by OSG. Conclusion Given the similarity of hernia recurrence among all major procedures, the cost of surgery may impact the decision. According to our findings, open hernia repair with adhesive or self-gripping mesh appears most cost-effective.

Abstract Background The aim of this study was to examine the effect of a practice change intervention to support the implementation of guideline-recommended care for addressing alcohol use in pregnancy on self-reported alcohol use during pregnancy. Methods A randomized, stepped-wedge controlled trial in three clusters (sectors) within the Hunter New England Local Health District (NSW, Australia). We evaluated a practice change intervention that supported the introduction of a new model of care for reducing alcohol use in pregnancy, consistent with local and international guidelines, and implemented in random order across the sectors. Each week throughout the study period, pregnant women who attended any public antenatal services within the previous week, for a 27–28 or 35–36 week gestation visit, were randomly sampled and invited to participate in the survey. The intended intervention for all women was Brief advice (to abstain from alcohol and information about potential risks). Women identified as medium-risk alcohol consumers using the Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) were to be offered referral to a phone coaching service, and women identified as high-risk were to be offered referral to a Drug and Alcohol Service. Rates of self-reported alcohol use (AUDIT-C risk level and special occasion drinking) were summarized and compared in groups of women pre-intervention and post-intervention using multivariable logistic regression. Results Surveys were completed by 1309 women at pre-intervention and 2540 at post-intervention. The majority of women did not drink during pregnancy (pre-intervention: 89.68%; post-intervention: 90.74%). There was no change in the proportion of women classified as No risk from drinking (AUDIT-C score = 0) or Some risk from drinking (AUDIT-C score ≥ 1) pre- or post-intervention (p = 0.08). However, a significant reduction in special occasion drinking was observed (pre-intervention: 11.59%; post-intervention: 8.43%; p

BackgroundStroke has multiple modifiable and nonmodifiable risk factors and represents a leading cause of death globally. Understanding the complex interplay of stroke risk factors is thus not only a scientific necessity but a critical step toward improving global health outcomes. ObjectiveWe aim to assess the performance of explainable machine learning models in predicting stroke risk factors using real-world cohort data by comparing explainable machine learning models with conventional statistical methods. MethodsThis retrospective cohort included high-risk patients from Ramathibodi Hospital in Thailand between January 2010 and December 2020. We compared the performance and explainability of logistic regression (LR), Cox proportional hazard, Bayesian network (BN), tree-augmented Naïve Bayes (TAN), extreme gradient boosting (XGBoost), and explainable boosting machine (EBM) models. We used multiple imputation by chained equations for missing data and discretized continuous variables as needed. Models were evaluated using C-statistics and F1-scores. ResultsOut of 275,247 high-risk patients, 9659 (3.5%) experienced a stroke. XGBoost demonstrated the highest performance with a C-statistic of 0.89 and an F1-score of 0.80 followed by EBM and TAN with C-statistics of 0.87 and 0.83, respectively; LR and BN had similar C-statistics of 0.80. Significant factors associated with stroke included atrial fibrillation (AF), hypertension (HT), antiplatelets, HDL, and age. AF, HT, and antihypertensive medication were common significant factors across most models, with AF being the strongest factor in LR, XGBoost, BN, and TAN models. ConclusionsOur study developed stroke prediction models to identify crucial predictive factors such as AF, HT, or systolic blood pressure or antihypertensive medication, anticoagulant medication, HDL, age, and statin use in high-risk patients. The explainable XGBoost was the best model in predicting stroke risk, followed by EBM.

Introduction Multiple cohort studies have been established to investigate the impact of early life factors on development and health outcomes. In Australia the majority of these studies were established more than 20 years ago and, although longitudinal in nature, are inherently susceptible to socioeconomic, environmental and cultural influences which change over time. Additionally, rapid leaps in technology have increased our understanding of the complex role of gene–environment interactions in life course health, highlighting the need for new cohort studies with repeated biological sampling and in-depth phenotype data across the first 1000 days of life from conception.Methods and analysis The Newcastle 1000 (NEW1000) Study, based in the regional city of Newcastle, New South Wales, was developed after an extensive consultation process involving 3 years of discussion with key stakeholders and healthcare consumer organisations and seven healthcare consumer workshops. This prospective population-based pregnancy cohort study will recruit 500 families per year for 5 years, providing detailed, longitudinal, multisystem phenotyping, repeated ultrasound measures and serial sample collection to investigate healthcare consumer identified health outcomes of priority. Stage 1 will involve recruitment of pregnant participants and their partners at 14 weeks gestation, with dense phenotype data and biological samples collected at 14, 20, 28 and 36 weeks gestation and serial ultrasound measures at 20, 28, 36 and 40 weeks, with postpartum follow-up at 6 weeks and 6 months. Biological samples will be used for biomarker discovery and sequencing of the genome, transcriptome, epigenome, microbiome and metabolome.Ethics and dissemination Ethics approval was obtained from Hunter New England Local Health District Ethics Committee (2020/ETH02881). Outcomes will be published in peer-reviewed journals, disseminated to participants through the NEW1000 website, presented at scientific conferences, and written reports to local, state and national government bodies and key stakeholders in the healthcare system to inform policy and evidence-based practice.

Introduction The Australian population presenting with surgical pathology is becoming older, frailer and more comorbid. Shared decision-making is rapidly becoming the gold standard of care for patients considering high-risk surgery to ensure that appropriate, value-based healthcare decisions are made. Positive benefits around patient perception of decision-making in the immediacy of the decision are described in the literature. However, short-term and long-term holistic patient-centred outcomes and cost implications for the health service require further examination to better understand the full impact of shared decision-making in this population.Methods We propose a novel multidisciplinary shared decision-making model of care in the perioperative period for patients considering high-risk surgery in the fields of general, vascular and head and neck surgery. We assess it in a two arm prospective randomised controlled trial. Patients are randomised to either ‘standard’ perioperative care, or to a multidisciplinary (surgeon, anaesthetist and end-of-life care nurse practitioner or social worker) shared decision-making consultation. The primary outcome is decisional conflict prior to any surgical procedure occurring. Secondary outcomes include the patient’s treatment choice, how decisional conflict changes longitudinally over the subsequent year, patient-centred outcomes including life impact and quality of life metrics, as well as morbidity and mortality. Additionally, we will report on healthcare resource use including subsequent admissions or representations to a healthcare facility up to 1 year.Ethics and dissemination This study has been approved by the Hunter New England Human Research Ethics Committee (2019/ETH13349). Study findings will be presented at local and national conferences and within scientific research journals.Trial registration number ACTRN12619001543178.

ObjectivesThis network meta-analysis aims to compare the efficacy and safety of new anti-diabetic medications for the treatment of non-alcoholic fatty liver disease (NAFLD).Materials and methodsPubMed and Scopus were searched from inception to 27th March 2022 to identify all randomized controlled trials (RCTs) in NAFLD patients. Outcomes included reductions in intrahepatic steatosis (IHS) and liver enzyme levels. The efficacy and safety of DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors, and other therapies were indirectly compared using a NMA approach. Unstandardized mean difference (USMD) with 95% confidence intervals (CI) were calculated.Results2,252 patients from 31 RCTs were included. “Add-on” GLP-1 agonists with standard of care (SoC) treatment showed significantly reduced IHS compared to SoC alone [USMD (95%CI) -3.93% (-6.54%, -1.33%)]. Surface under the cumulative ranking curve (SUCRA) identified GLP-1 receptor agonists with the highest probability to reduce IHS (SUCRA 88.5%), followed by DPP-4 inhibitors (SUCRA 69.6%) and pioglitazone (SUCRA 62.2%). “Add-on” GLP-1 receptor agonists were also the most effective treatment for reducing liver enzyme levels; AST [USMD of -5.04 (-8.46, -1.62)], ALT [USMD of -9.84 (-16.84, -2.85)] and GGT [USMD of -15.53 (-22.09, -8.97)] compared to SoC alone. However, GLP-1 agonists were most likely to be associated with an adverse event compared to other interventions.ConclusionGLP-1 agonists may represent the most promising anti-diabetic treatment to reduce hepatic steatosis and liver enzyme activity in T2DM and NAFLD patients. Nevertheless, longer-term studies are required to determine whether this delays progression of liver cirrhosis in patients with NAFLD and T2DM.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021259336.1.

ObjectiveSystemic arterial hypertension (HT) is a major modifiable risk factor for cardiovascular disease (CVDs), associated with all-cause death (ACD). Understanding its progression from the early state to late complications should lead to more timely intensification of treatment. This study aimed to construct a real-world cohort profile of HT and to estimate transition probabilities from the uncomplicated state to any of these long-term complications; chronic kidney disease (CKD), coronary artery disease (CAD), stroke, and ACD.MethodsThis real-world cohort study used routine clinical practice data for all adult patients diagnosed with HT in the Ramathibodi Hospital, Thailand from 2010 to 2022. A multi-state model was developed based on the following: state 1-uncomplicated HT, 2-CKD, 3-CAD, 4-stroke, and 5-ACD. Transition probabilities were estimated using Kaplan-Meier method.ResultsA total of 144,149 patients were initially classified as having uncomplicated HT. The transition probabilities (95% CI) from the initial state to CKD, CAD, stroke, and ACD at 10-years were 19.6% (19.3%, 20.0%), 18.2% (17.9%, 18.6%), 7.4% (7.1%, 7.6%), and 1.7% (1.5%, 1.8%), respectively. Once in the intermediate-states of CKD, CAD, and stroke, 10-year transition probabilities to death were 7.5% (6.8%, 8.4%), 9.0% (8.2%, 9.9%), and 10.8% (9.3%, 12.5%).ConclusionsIn this 13-year cohort, CKD was observed as the most common complication, followed by CAD and stroke. Among these, stroke carried the highest risk of ACD, followed by CAD and CKD. These findings provide improved understanding of disease progression to guide appropriate prevention measures. Further investigations of prognostic factors and treatment effectiveness are warranted.

Abstract Background Asymptomatic hyperuricemia was found to be associated with increased cardiovascular disease risk but the potential benefits of urate-lowering therapy (ULT) remain controversial. We conducted a systematic review and network meta-analysis (NMA) with frequentist model to estimate the efficacy and safety of ULT in asymptomatic hyperuricemia. Methods MEDLINE, Embase, and Scopus were searched without language restrictions. Randomized controlled trials (RCT) of adults with asymptomatic hyperuricemia were eligible if they compared any pair of ULTs (i.e., allopurinol, febuxostat, probenecid, benzbromarone, sulfinpyrazone, rasburicase, lesinurad, and topiroxostat) and placebo or no ULT, and had outcomes of interest, including composite renal events, major adverse cardiovascular events, serum urate levels, estimated glomerular filtration rate (eGFR), systolic blood pressure, and adverse events. Results NMA with frequentist approach was applied to estimate relative treatment effects, i.e., risk ratio (RR) and mean difference (MD). A total of 23 RCTs were eligible. NMA identified beneficial effects of ULT on composite renal events and eGFR but not for other outcomes. Allopurinol and febuxostat had significantly lower composite renal events than placebo (RR 0.39, 95% confidence interval [CI] 0.23 to 0.66, and RR 0.68, 95% CI 0.46 to 0.99, respectively). Both treatments also resulted in significantly higher eGFR than placebo (MD 3.69 ml/min/1.73 m2, 95% CI 1.31 to 6.08, and MD 2.89 ml/min/1.73 m2, 95% CI 0.69 to 5.09, respectively). No evidence of inconsistency was identified. Conclusions Evidence suggests that allopurinol and febuxostat are the ULTs of choice in reducing composite renal events and improving renal function. Trial registration. This study was registered with PROSPERO: CRD42019145908. The date of the first registration was 12th November 2019.

IntroductionNeuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory CNS demyelinating disease. Two groups of monoclonal antibodies (mAbs) are used to prevent disease relapse, i.e., Food and Drug Administration (FDA)-approved mAbs (e.g., eculizumab satralizumab, inebilizumab), and off-label mAb drugs (e.g., rituximab and tocilizumab). The FDA-approved mAbs have high efficacy but more expensive compared to the off-labels, and thus are less accessible. This systematic review and network meta-analysis (NMA) was to assess the efficacy and safety of both classes of mAbs compared to the current standard treatments.MethodsSystematically searches were conducted in MEDLINE and SCOPUS from inception until July 2021. Randomized-controlled trials (RCTs) were eligible if they compared any pair of treatments (mAbs, immunosuppressive drugs, or placebo) in adult patients with NMOSD. Studies with AQP4-IgG positive or negative were used in the analysis. Probability of relapse and time to event were extracted from the Kaplan-Meier curves using Digitizer. These data were then converted into individual patient time-to-event data. A one-stage mixed-effect survival model was applied to estimate the median time to relapse and relative treatment effects using hazard ratios (HR). Two-stage NMA was used to determine post-treatment annualized relapse rate (ARR), expanded disability status score (EDSS) change, and serious adverse events (SAE). Risk of bias was assessed using the revised cochrane risk of bias tool.ResultsA total of 7 RCTs with 776 patients were eligible in the NMA. Five of the seven studies were rated low risk of bias. Both FDA-approved and off-label mAbs showed significantly lower risk of relapse than standard treatments, with HR (95% CI) of 0.13 (0.07, 0.24) and 0.16 (0.07, 0.37) respectively. In addition, the FDA-approved mAbs had 20% lower risk of relapse than the off-label mAbs, but this did not reach statistical significance. The ARRs were also lower in FDA-approved and off-label mAbs than the standard treatments with the mean-difference of−0.27 (-0.37,−0.16) and−0.31(-0.46,−0.16), respectively.ConclusionThe off-label mAbs may be used as the first-line treatment for improving clinical outcomes including disease relapse, ARR, and SAEs for NMOSD in countries where resources and accessibility of the FDA-approved mAbs are limited.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=283424, identifier: CRD42021283424.

Abstract Background Clinical guideline recommendations for addressing alcohol consumption during pregnancy are sub-optimally implemented and limited evidence exists to inform practice improvements. The aim of this study was to estimate the effectiveness of a practice change intervention in improving the provision of antenatal care addressing alcohol consumption during pregnancy in public maternity services. Methods A randomised stepped-wedge controlled trial was undertaken with all public maternity services in three sectors (one urban, two regional/rural) of a single local health district in New South Wales, Australia. All antenatal care providers were subject to a seven-month multi-strategy intervention to support the introduction of a recommended model of care. For 35 months (July 2017 – May 2020) outcome data were collected from randomly selected women post an initial, 27–28 weeks and 35–36 weeks gestation antenatal visit. Logistic regression models assessed intervention effectiveness. Results Five thousand six hundred ninety-four interviews/online questionnaires were completed by pregnant women. The intervention was effective in increasing women’s reported receipt of: assessment of alcohol consumption (OR: 2.63; 95% CI: 2.26–3.05; p

Abstract Objective: To identify the optimal AUSDRISK threshold score to screen for pre‐diabetes and diabetes. Methods: A total of 406 adult patients not diagnosed with diabetes were screened in General Practices (GP) between May and October 2019. All patients received a point of care (POC) HbA1c test. HbA1c test results were categorised into diabetes (≥6.5% or ≥48 mmol/mol), pre‐diabetes (5.7–6.4% or 39–47 mmol/mol), or normal (

Abstract Background In the context of ever-growing health expenditure and limited resources, economic evaluations aid in making evidence-informed policy decisions. Cost-utility analysis (CUA) is often used, and CUA data synthesis is also desirable, but methodological issues are challenged. Hence, we aim to provide a step-by-step process to prepare the CUA data for meta-analysis. Methods Data harmonisation methods were constructed specifically considering CUA methodology, including inconsistent reports, economic parameters, heterogeneity (i.e., country’s income, time horizon, perspective, modelling approaches, currency, willingness to pay). An incremental net benefit (INB) and its variance were estimated and pooled across studies using a basic meta-analysis by COMER. Results Five scenarios show how to obtain INB and variance with various reported data: Study reports the mean and variance (Scenario 1) or 95% confidence interval (Scenario 2) of ΔC, ΔE, and ICER for INB/variance calculations. Scenario 3: ΔC, ΔE, and variances are available, but not for the ICER; a Monte Carlo was used to simulate ΔC and ΔE data, variance and covariance can be then estimated leading INB calculation. Scenario-4: Only the CE plane was available, ΔC and ΔE data can be extracted; means of ΔC, ΔE, and variance/covariance can be estimated accordingly, leading to INB/variance estimates. Scenario-5: Only mean cost/outcomes and ICER are available but not for variance and the CE-plane. A variance INB can be borrowed from other studies which are similar characteristics, including country income, ICERs, intervention-comparator, time period, country region, and model type and inputs (i.e., discounting, time horizon). Conclusion Out data harmonisation and meta-analytic methods should be useful for researchers for the synthesis of economic evidence to aid policymakers in decision making.

People with dementia (PWD) are at risk for medication-related harm due to their impaired cognition and frequently being prescribed many medications. This study evaluated a medication safety intervention (including pharmacist medication reconciliation and review) for PWD during an unplanned admission to hospital. This article reports the effect of the intervention on polypharmacy, potentially inappropriate medications (PIMs), and anticholinergic burden scores for PWD. A pre-post design using an intervention site and a control site was conducted in 2017–2019, in a regional area in New South Wales, Australia. Polypharmacy, PIMs, and anticholinergic burden were measured at admission, discharge, and three months after discharge. There were 628 participants including 289 at the control site and 339 at the intervention site. Polypharmacy was 95% at admission and 90% at discharge. PIMs at admission were 95–98% across timepoints and decreased significantly at discharge. The mean anticholinergic score decreased significantly between admission (2.40–3.15) and discharge (2.01–2.57). Reduced PIMs at discharge were correlated with reduced anticholinergic burden (rho = 0.48–0.55, p < 0.001). No significant differences were identified between the study and control sites for Polypharmacy, PIMs, and anticholinergic burden rates and scores. High rates of polypharmacy and PIMs in this study indicate a study population with multiple comorbidities. This intervention was feasible to implement but was limited due to difficulty recruiting participants and deaths during the study. Future multisite studies should be designed to recruit larger study samples to evaluate interventions for improving medication safety for PWD and improve outcomes for these vulnerable people.

This randomized controlled trial is aimed at assessing the efficacy of combining time-restricted eating (TRE) with behavioral economic (BE) interventions and comparing it to TRE alone and to the usual care for reducing fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and other cardiometabolic risk factors among patients with impaired fasting glucose (IFG). Seventy-two IFG patients aged 18–65 years were randomly allocated for TRE with BE interventions (26 patients), TRE alone (24 patients), or usual care (22 patients). Mean FPG, HbA1c, and other cardiometabolic risk factors among the three groups were compared using a mixed-effect linear regression analysis. Mean body weight, FPG, HbA1c, fasting insulin, and lipid profiles did not significantly differ among the three groups. When considering only patients who were able to comply with the TRE protocol, the TRE group showed significantly lower mean FPG, HbA1c, and fasting insulin levels compared to the usual care group. Our results did not show significant differences in body weight, blood sugar, fasting insulin, or lipid profiles between TRE plus BE interventions, TRE alone, and usual care groups. However, TRE might be an effective intervention in lowering blood sugar levels for IFG patients who were able to adhere to the TRE protocol.

Abstract Background Older people living in Residential Aged Care (RAC) are at high risk of clinical deterioration. Telehealth has the potential to provide timely, patient-centred care where transfer to hospital can be a burden and avoided. The extent to which video telehealth is superior to other forms of telecommunication and its impact on management of acutely unwell residents in aged care facilities has not been explored previously. Methods In this study, video-telehealth consultation was added to an existing program, the Aged Care Emergency (ACE) program, aiming at further reducing Emergency Department (ED) visits and hospital admissions. This controlled pre-post study introduced video-telehealth consultation as an additional component to the ACE program for acutely unwell residents in RACs. Usual practice is for RACs and ACE to liaise via telephone. During the study, when the intervention RACs called the ED advanced practice nurse, video-telehealth supported clinical assessment and management. Five intervention RACs were compared with eight control RACs, all of whom refer to one community hospital in regional New South Wales, Australia. Fourteen months pre-video-telehealth was compared with 14 months post-video-telehealth using generalized linear mixed models for hospital admissions after an ED visit and ED visits. One thousand two hundred seventy-one ED visits occurred over the 28-month study period with 739 subsequent hospital admissions. Results There were no significant differences in hospital admission or ED visits after the introduction of video-telehealth; adjusted incident rate ratios (IRR) were 0.98 (confidence interval (CI) 0.55 to 1.77) and 0.89 (95% CI 0.53 to 1.47) respectively. Conclusions Video-telehealth did not show any incremental benefit when added to a structured hospital avoidance program with nursing telephone support. Trial registration The larger Aged Care Emergency evaluation is registered with ANZ Clinical Trials Registry, ACTRN12616000588493.

This systematic review was conducted to explore natural language processing (NLP) focusing on text representation techniques and algorithms used previously to identify recurrent cancer diagnoses from electronic medical records (EMR), and an assessment of their detection performance. Relevant studies were identified from PubMed, Scopus, ACM Digital Library, and IEEE databases since inception to August 18, 2022. Data, including text representation methods, model algorithms and performance, and type of clinical notes, were extracted from individual studies by two independent reviewers. Study risk of bias was assessed using the prediction model risk of bias assessment tool. Of the 412 studies identified, 17 were eligible for inclusion, with 15 representing models that were not externally validated. Three text representations were used: statistical, context-free, and contextual representations (bidirectional encoder representations from transformers (BERT) and its variants), from 12, 6, and 3 studies, respectively. The corresponding median harmonic precision and recall means (F1 scores) for these representations were 0.43, 0.87, and 0.72, respectively. The algorithms applied included rule-based, machine learning, and deep learning approaches with median F1 scores of 0.71, 0.43, and 0.76, respectively. In conclusion, this systematic review suggests that deep learning models that use PubMedBERT as a text representation perform best. These findings are clinically informative for the selection of appropriate approaches for the detection of recurrent cancer from electronic medical records.

Background: Diabetic retinopathy (DR) is one of the most common complications in type 2 diabetes (T2D) with an estimated prevalence of 22%. Predictive modelling has largely been dependent on Cox proportional hazards (CPH) with assumptions of linearity and constant hazards. Machine learning (ML) approaches may prove advantageous in more adequately capturing non-linear effects. Objective: To construct and compare DR prediction models using CPH and ML models with time-varying covariates. Design: Real-world, retrospective cohort study. Setting: A tertiary care hospital in Thailand. Participants: Data on 48,622 T2D patients from electronic health records between 1st January 2010 and 31st December 2019. Methods: Time-to-event time-varying models that included 13 variables were trained in diabetic retinopathy prediction. The CPH and ML models were compared using left-truncated right censoring relative risk forest (LTRC-RRF) and left-truncated right censoring conditional inference forest (LTRC-CIF) algorithms. Results: The CPH model outperformed both ML approaches with a Harrell's C-index (c-index) of 0.70 compared to c-indices of 0.51–0.57 for the ML models in the test dataset. Both CPH and ML models showed insulin use and the presence of chronic kidney disease increased DR risk. Sodium glucose transporter 2 inhibitors and dyslipidemia were associated with reduced DR risk. Conclusion: CPH provided better predictive power for DR risk than ML modelling using real world data. The presence of comorbidities and the use of antidiabetic medications were associated with the greatest drivers of DR risk.

Objectives: To develop an automated international classification of diseases (ICD) coding tool using natural language processing (NLP) and discharge summary texts from Thailand. Materials and methods: The development phase included 15,329 discharge summaries from Ramathibodi Hospital from January 2015 to December 2020. The external validation phase included Medical Information Mart for Intensive Care III (MIMIC-III) data. Three algorithms were developed: naïve Bayes with term frequency-inverse document frequency (NB-TF-IDF), convolutional neural network with neural word embedding (CNN-NWE), and CNN with PubMedBERT (CNN-PubMedBERT). In addition, two state-of-the-art models were also considered; convolutional attention for multi-label classification (CAML) and pretrained language models for automatic ICD coding (PLM-ICD). Results: The CNN-PubMedBERT model provided average micro- and macro-area under precision-recall curve (AUPRC) of 0.6605 and 0.5538, which outperformed CNN-NWE (0.6528 and 0.5564), NB-TF-IDF (0.4441 and 0.3562), and CAML (0.6257 and 0.4964), with corresponding differences of (0.0077 and −0.0026), (0.2164 and 0.1976), and (0.0348 and 0.0574), respectively. However, CNN-PubMedBERT performed less well relative to PLM-ICD, with corresponding AUPRCs of 0.7202 and 0.5865. The CNN-PubMedBERT model was externally validated using two subsets of MIMIC-III; MIMIC-ICD-10, and MIMIC-ICD-9 datasets, which contained 40,923 and 31,196 discharge summaries. The average micro-AUPRCs were 0.3745, 0.6878, and 0.6699, corresponding to directly predictive MIMIC-ICD-10, MIMIC-ICD-10 fine-tuning, and MIMIC-ICD-9 fine-tuning approaches; the average macro-AUPRCs for the corresponding models were 0.2819, 0.4219 and 0.5377, respectively. Discussion: CNN-PubMedBERT performed second-best to PLM-ICD, with considerable variation observed between average micro- and macro-AUPRC, especially for external validation, generally indicating good overall prediction but limited predictive value for small sample sizes. External validation in a US cohort demonstrated a higher level of model prediction performance. Conclusion: Both PLM-ICD and CNN-PubMedBERT models may provide useful tools for automated ICD-10 coding. Nevertheless, further evaluation and validation within Thai and Asian healthcare systems may prove more informative for clinical application.

IntroductionThe cardiovascular benefits of multiple antihyperglycemic drugs as add-on therapies to metformin in the real-practice are unclear. This study aimed to directly compare major adverse cardiovascular events (CVE) associated with these multiple drugs.MethodsAn emulation of a target trial was conducted using a retrospective-cohort data of type 2 diabetes mellitus (T2DM) prescribed with second-line drugs on top of metformin, including sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i), thiazolidinediones (TZD) and sulfonylureas (SUs). We applied inverse probability weighting and regression adjustment using intention-to-treat (ITT), per-protocol analysis (PPA) and modified ITT. Average treatment effects (ATE) were estimated using SUs as the reference.Results and DiscussionAmong 25,498 patients with T2DM, 17,586 (69.0%), 3,261 (12.8%), 4,399 (17.3%), and 252 (1.0%) received SUs, TZD, DPP4i, and SGLT2i. Median follow-up time was 3.56 (1.36-7.00) years. CVE was identified in 963 patients. The ITT and modified ITT approaches showed similar results; the ATE (i.e., the difference of CVE risks) for SGLT2i, TZD, and DPP4i compared to SUs were -0.020(-0.040, -0.0002), -0.010(-0.017, -0.003), and -0.004(-0.010, 0.002), respectively, indicating 2% and 1% significant absolute risk reduction in CVE in SGLT2i and TZD compared to SUs. These corresponding effects were also significant in the PPA with ATEs of -0.045(-0.060, -0.031), -0.015(-0.026, -0.004), and -0.012(-0.020, -0.004). In addition, SGLT2i had 3.3% significant absolute risk reduction in CVE relative to DPP4i. Our study demonstrated benefits of SGLT2i and TZD in reducing CVE in T2DM patients compared to SUs when added to metformin.

Abstract Background Weight gain during pregnancy that is outside of recommended levels is associated with a range of adverse outcomes for the mother and child, including gestational diabetes, pre-eclampsia, preterm birth, and obesity. Internationally, 60–80% of pregnant women report gaining weight outside of recommended levels. While guideline recommendations and RCT evidence support the provision of antenatal care that supports healthy gestational weight gain, less than 10% of health professionals routinely weigh pregnant women; discuss weight gain, diet, and physical activity; and provide a referral for additional support. This study aims to determine the effectiveness of an implementation intervention in increasing the provision of recommended gestational weight gain care by maternity services. Methods A stepped-wedge controlled trial, with a staggered implementation intervention, will be conducted across maternity services in three health sectors in New South Wales, Australia. The implementation intervention will consist of evidence-based, locally-tailored strategies including guidelines and procedures, reminders and prompts, leadership support, champions, training, and monitoring and feedback. Primary outcome measures will be the proportion of women who report receiving (i) assessment of gestational weight gain; (ii) advice on gestational weight gain, dietary intake, and physical activity; and (iii) offer of referral to a telephone coaching service or local dietetics service. Measurement of outcomes will occur via telephone interviews with a random sample of women who attend antenatal appointments each week. Economic analyses will be undertaken to assess the cost, cost-consequence, cost-effectiveness, and budget impact of the implementation intervention. Receipt of all care elements, acceptance of referral, weight gain during pregnancy, diet quality, and physical activity will be measured as secondary outcomes. Process measures including acceptability, adoption, fidelity, and reach will be reported. Discussion This will be the first controlled trial to evaluate the effectiveness of a implementation intervention in improving antenatal care that addresses gestational weight gain. The findings will inform decision-making by maternity services and policy agencies and, if the intervention is demonstrated to be effective, could be applied at scale to benefit the health of women and children across Australia and internationally. Trial registration Australian and New Zealand Clinical Trials Registry, ACTRN12621000054819 . Registered on 22 January 2021

Abstract The specific prevalence and outcome of pulmonary hypertension after mitral valve replacement (MVR) is not well documented. The aim of the study was to determine the prevalence and prognostic impact of pulmonary hypertension after MVR. In addition, we sought to determine the threshold of mortality risk according to echocardiography derived pulmonary pressures and those echocardiographic characteristics that are associated with increased mortality. Using the National Echocardiography Database of Australia, patients who had undergone MVR were identified with estimated right ventricular systolic pressure (eRVSP) assessed and linked to patient mortality during mean follow up of 1917 days. Classification and regression tree analysis was used to identify the most powerful predictors of mortality. A total of 10,994 patients who had undergone echocardiography following MVR (mean age 65.2 ± 16, 44.8% women) were studied (mean follow‐up 1917 days). The prevalence of PH (defined as eRSVP ≥40 mmHg) was 64.1% (7042/10,994). Severe PH (eRVSP ≥60 mmHg) was seen in 42.3% (4671/10,994). Mortality in individuals with PH was greater than amongst individuals without PH (41.1% vs. 26.3%). Age, tricuspid regurgitation and left ventricular dysfunction were also associated with mortality. There is a high prevalence of PH after MVR which confers an adverse prognosis. Improved therapeutic approaches to mitral valve disease and the subsequent development of PH are essential.

IntroductionPeople experiencing severe mental illness (SMI) smoke at much higher rates than the general population and require additional support. Engagement with existing evidence-based interventions such as quitlines and nicotine replacement therapy (NRT) may be improved by mental health peer worker involvement and tailored support. This paper reports on a qualitative study nested within a peer researcher-facilitated tobacco treatment trial that included brief advice plus, for those in the intervention group, tailored quitline callback counseling and combination NRT. It contextualizes participant life experience and reflection on trial participation and offers insights for future interventions.MethodsQualitative semi-structured interviews were conducted with 29 participants in a randomized controlled trial (intervention group n = 15, control group n = 14) following their 2-month (post-recruitment) follow-up assessments, which marked the end of the “Quitlink” intervention for those in the intervention group. Interviews explored the experience of getting help to address smoking (before and during the trial), perceptions of main trial components including assistance from peer researchers and tailored quitline counseling, the role of NRT, and other support received. A general inductive approach to analysis was applied.ResultsWe identified four main themes: (1) the long and complex journey of quitting smoking in the context of disrupted lives; (2) factors affecting quitting (desire to quit, psychological and social barriers, and facilitators and reasons for quitting); (3) the perceived benefits of a tailored approach for people with mental ill-health including the invitation to quit and practical resources; and (4) the importance of compassionate delivery of support, beginning with the peer researchers and extended by quitline counselors for intervention participants. Subthemes were identified within each of these overarching main themes.DiscussionThe findings underscore the enormity of the challenges that our targeted population face and the considerations needed for providing tobacco treatment to people who experience SMI. The data suggest that a tailored tobacco treatment intervention has the potential to assist people on a journey to quitting, and that compassionate support encapsulating a recovery-oriented approach is highly valued.Clinical trial registrationThe Quitlink trial was registered with ANZCTR (www.anzctr.org.au): ACTRN12619000244101 prior to the accrual of the first participant and updated regularly as per registry guidelines.

Background purposeA substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort.Materials and methodsAnalyses relied upon imaging and clinical data from the international MRI-GENIE study. Imaging data comprised both Fluid-attenuated inversion recovery (FLAIR) for white matter hyperintensity (WMH) burden estimation and diffusion-weighted imaging (DWI) sequences for the assessment of acute stroke lesions. The initial step featured the systematic evaluation of occurrences of MAL within one and several vascular supply territories. Associations between MAL and important imaging and clinical characteristics were subsequently determined. The interaction effect between single and multiple lesion status and lesion volume was estimated by means of Bayesian hierarchical regression modeling for both stroke severity and functional outcome.ResultsWe analyzed 2,466 patients (age = 63.4 ± 14.8, 39% women), 49.7% of which presented with a single lesion. Another 37.4% experienced MAL in a single vascular territory, while 12.9% featured lesions in multiple vascular territories. Within most territories, MAL occurred as frequently as single lesions (ratio ∼1:1). Only the brainstem region comprised fewer patients with MAL (ratio 1:4). Patients with MAL presented with a significantly higher lesion volume and acute NIHSS (7.7 vs. 1.7 ml and 4 vs. 3, pFDR < 0.001). In contrast, patients with a single lesion were characterized by a significantly higher WMH burden (6.1 vs. 5.3 ml, pFDR = 0.048). Functional outcome did not differ significantly between patients with single versus multiple lesions. Bayesian analyses suggested that the association between lesion volume and stroke severity between single and multiple lesions was the same in case of anterior circulation stroke. In case of posterior circulation stroke, lesion volume was linked to a higher NIHSS only among those with MAL.ConclusionMultiple lesions, especially those within one vascular territory, occurred more frequently than previously reported. Overall, multiple lesions were distinctly linked to a higher acute stroke severity, a higher total DWI lesion volume and a lower WMH lesion volume. In posterior circulation stroke, lesion volume was linked to a higher stroke severity in multiple lesions only.

Acute ischemic stroke impacts men and women differently. Here, the authors show how different lesion patterns in men and women are linked to the extent of stroke severity.

Abstract Background The aim of the current study is to assess the natural history and prognostic value of elevated left ventricular end-diastolic pressure (LVEDP) in patients with ST-segment elevation myocardial infarction (STEMI) after reperfusion with thrombolysis; we utilize data from the Thrombolysis in Myocardial Infarction (TIMI) II study. Methods A total of 3339 patients were randomized to either an invasive (n = 1681) or a conservative (n = 1658) strategy in the TIMI II study following thrombolysis. To make the current cohort as relevant as possible to modern pharmaco-invasively managed cohorts, patients in the invasive arm with TIMI flow grade ≥ 2 (N = 1201) at initial catheterization are included in the analysis. Of these, 259 patients had a second catheterization prior to hospital discharge, and these were used to define the natural history of LVEDP in reperfused STEMI. Results The median LVEDP for the whole cohort was 18 mmHg (IQR: 12–23). Patients were divided into quartiles by LVEDP measured during the first cardiac catheterization. During a median follow up of 3 (IQR: 2.1–3.2) years, quartile 4 (highest LVEDP) had the highest incidence of mortality and heart failure admissions. In the cohort with paired catheterization data, the LVEDP dropped slightly from 18 mmHg (1QR: 12–22) to 15 mmHg (IQR: 10–20) (p = 0.01) from the first to the pre-hospital discharge catheterization. Conclusions LVEDP remains largely stable during hospitalisation post-STEMI. Elevated LVEDP is a predictor of death and heart failure hospitalization in STEMI patients undergoing successful thrombolysis. Graphic abstract