Using Genetics to Inform Interventions Related to Sodium and Potassium in Hypertension.

BACKGROUND: Hypertension is a key risk factor for major adverse cardiovascular events but remains difficult to treat in many individuals. Dietary interventions are an effective approach to lower blood pressure (BP) but are not equally effective across all individuals. BP is heritable, and genetics may be a useful tool to overcome treatment response heterogeneity. We investigated whether the genetics of BP could be used to identify individuals with hypertension who may receive a particular benefit from lowering sodium intake and boosting potassium levels. METHODS: In this observational genetic study, we leveraged cross-sectional data from up to 296 475 genotyped individuals drawn from the UK Biobank cohort for whom BP and urinary electrolytes (sodium and potassium), biomarkers of sodium and potassium intake, were measured. Biologically directed genetic scores for BP were constructed specifically among pathways related to sodium and potassium biology (pharmagenic enrichment scores), as well as unannotated genome-wide scores (conventional polygenic scores). We then tested whether there was a gene-by-environment interaction between urinary electrolytes and these genetic scores on BP. RESULTS: Genetic risk and urinary electrolytes both independently correlated with BP. However, urinary sodium was associated with a larger BP increase among individuals with higher genetic risk in sodium- and potassium-related pathways than in those with comparatively lower genetic risk. For example, each SD in urinary sodium was associated with a 1.47-mm Hg increase in systolic BP for those in the top 10% of the distribution of genetic risk in sodium and potassium transport pathways versus a 0.97-mm Hg systolic BP increase in the lowest 10% (P=1.95×10-3). This interaction with urinary sodium remained when considering estimated glomerular filtration rate and indexing sodium to urinary creatinine. There was no strong evidence of an interaction between urinary sodium and a standard genome-wide polygenic score of BP. CONCLUSIONS: The data suggest that genetic risk in sodium and potassium pathways could be used in a precision medicine model to direct interventions more specifically in the management of hypertension. Intervention studies are warranted.

Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

What care do people with dementia receive at the end of life? Lessons from a retrospective clinical audit of deaths in hospital and other settings.

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.

'Quitlink': Outcomes of a randomised controlled trial of peer researcher facilitated referral to a tailored quitline tobacco treatment for people receiving mental health services.

OBJECTIVE: The aim of this study was to test the effectiveness of a tailored quitline tobacco treatment ('Quitlink') among people receiving support for mental health conditions. METHODS: We employed a prospective, cluster-randomised, open, blinded endpoint design to compare a control condition to our 'Quitlink' intervention. Both conditions received a brief intervention delivered by a peer researcher. Control participants received no further intervention. Quitlink participants were referred to a tailored 8-week quitline intervention delivered by dedicated Quitline counsellors plus combination nicotine replacement therapy. The primary outcome was self-reported 6 months continuous abstinence from end of treatment (8 months from baseline). Secondary outcomes included additional smoking outcomes, mental health symptoms, substance use and quality of life. A within-trial economic evaluation was conducted. RESULTS: In total, 110 participants were recruited over 26 months and 91 had confirmed outcomes at 8 months post baseline. There was a difference in self-reported prolonged abstinence at 8-month follow-up between Quitlink (16%, n = 6) and control (2%, n = 1) conditions, which was not statistically significant (OR = 8.33 [0.52, 132.09] p = 0.131 available case). There was a significant difference in favour of the Quitlink condition on 7-day point prevalence at 2 months (OR = 8.06 [1.27, 51.00] p = 0.027 available case). Quitlink costs AU$9231 per additional quit achieved. CONCLUSION: The Quitlink intervention did not result in significantly higher rates of prolonged abstinence at 8 months post baseline. However, engagement rates and satisfaction with the 'Quitlink' intervention were high. While underpowered, the Quitlink intervention shows promise. A powered trial to determine its effectiveness for improving long-term cessation is warranted.

Improving end-of-life care for people with dementia: a mixed-methods study.

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.

Sex-specific effects of birth weight on longitudinal behavioural outcomes in children and adolescents: findings from the raine study.

Previous cross-sectional studies suggest that birth weight (BW) is associated with aggression-, social- and attention problems differently in boys and girls. We sought to test if these differences could be confirmed in a longitudinal study. The 1989 Raine Study provided prospectively collected data on perinatal variables and repeated child behaviour checklist assessments from ages 5 to 17. Linear mixed effects models provided crude and adjusted relationships between BW and childhood behaviour at a conservative significance threshold using prenatal maternal covariables in adjusted models. Sensitivity analyses included an age10 teacher assessment. Data on behaviour, BW and sex, was available in 2269 participants. Male sex was associated with increased aggression problems at lower BW compared to females in the crude model (Interaction B: -0.436, 98.3%CI: [-0.844, -0.0253]), but not the adjusted model (Interaction B: -0.310, 98.3%CI: [-0.742, 0.140]). Male sex was associated with increased attention problems at lower BW compared to females in both the crude model (Interaction B: -0.334, 98.3%CI: [-0.530, -0.137]) and the adjusted model (Interaction B: -0.274, 98.3%CI: [-0.507, -0.0432]). Male sex was associated with increased social problems at lower BW compared to females in both the crude model (Interaction B: -0.164, 98.3%CI: [-0.283, -0.0441]) and the adjusted model (Interaction B: -0.148, 98.3%CI: [-0.285, -0.00734]). Using repeated measures from ages 5-17 we were able to show a crude and adjusted male vulnerability to lower BW in the development of attention problems and social problems. We did not find a BW x sex interaction for the development of aggressive behaviour.

External validation and revision of Penn incisional hernia prediction model: A large-scale retrospective cohort of abdominal operations.

BACKGROUND: Incisional hernia (IH) manifests in 10%-15% of abdominal surgeries and patients at elevated risk of this complication should be identified for prophylactic intervention. This study aimed to externally validate the Penn hernia risk calculator. METHODS: The Ramathibodi abdominal surgery cohort was constructed by linking relevant hospital databases from 2010 to 2021. Penn hernia risk scores were calculated according to the original model which was externally validated using a seven-step approach. An updated model which included four additional predictor variables (i.e., age, immunosuppressive medication, ostomy reversal, and transfusion) added to those of the three original predictors (i.e., body mass index, chronic liver disease, and open surgery) was also evaluated. The area under the receiver operating characteristic curve (AUC) was estimated, and calibration performance was compared using the Hosmer-Lemeshow goodness-of-fit method for the observed/expected (O/E) ratio. RESULTS: A total of 12,155 abdominal operations were assessed. The original Penn model yielded fair discrimination with an AUC (95% confidence interval (CI)) of 0.645 (0.607, 0.683). The updated model that included the additional predictor variables achieved an acceptable AUC (95% CI) of 0.733 (0.698, 0.768) with the O/E ratio of 0.968 (0.848, 1.088). CONCLUSION: The updated model achieved improved discrimination and calibration performance, and should be considered for the identification of high-risk patients for further hernia prevention strategy.

The relevance of rich club regions for functional outcome post-stroke is enhanced in women.

This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI-GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas-defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non-rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long-term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.

Overweight or obesity increases the risk of cardiovascular disease among older Australian adults, even in the absence of cardiometabolic risk factors: a Bayesian survival analysis from the Hunter Community Study.

OBJECTIVE: To estimate the risk of cardiovascular disease (CVD) in older adults with overweight or obesity without metabolic risk factors using a Bayesian survival analysis. DESIGN: Prospective cohort study with median follow-up of 9.7 years. SETTING: Newcastle, New South Wales, Australia. PARTICIPANTS: A total of 2313 community-dwelling older men and women. INTERVENTION/EXPOSURE: Participants without known CVD and with a body mass index (BMI) ≥ 18.5 kg m2 were stratified by BMI and metabolic risk to create six BMI-metabolic health categories. Metabolic risk was defined according to the International Diabetes Federation criteria for metabolic syndrome. 'Metabolically healthy' was defined as absence of metabolic risk factors. Bayesian survival analysis, incorporating prior information from a previously published meta-analysis was used to assess the effect of BMI-metabolic health categories on time from recruitment to CVD. MAIN OUTCOME: Incident physician-diagnosed CVD, defined as fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, angina, or coronary revascularisation procedure, was determined by linkage to hospital admissions records and Medicare Australia data. Secondary outcomes were cardiovascular mortality and all-cause mortality. RESULTS: From 2313 adults with complete metabolic health data over a median follow-up of 9.7 years, 283 incident CVD events, 58 CVD related deaths and 277 deaths from any cause occurred. In an adjusted Bayesian survival model of complete cases with informative prior and metabolically healthy normal weight as the reference group, the risk of CVD was increased in metabolically healthy overweight (HR = 1.52, 95% credible interval 0.96-2.36), and in metabolically healthy obesity (HR = 1.86, 95% credible interval 1.14-3.08). Imputation of missing metabolic health and confounding data did not change the results. CONCLUSION: There was increased risk of CVD in older adults with overweight or obesity, even in the absence of any metabolic abnormality. This argues against the notion of 'metabolically healthy' overweight or obesity.

Treatment of obstructive sleep apnea in high risk pregnancy: a multicenter randomized controlled trial.

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.

Evaluation of the Effectiveness of Behavioral Economic Incentive Programs for Goal Achievement on Healthy Diet, Weight Control and Physical Activity: A Systematic Review and Network Meta-analysis.

BACKGROUND: Healthy diet, weight control and physical activity to reduce obesity can be motivated by financial incentives (FI). Behavioral-economic approaches may improve the incentivization effectiveness. This study compares and ranks the effectiveness of standard and behavioral incentivization for healthy diet, weight control, and physical activity promotion. PURPOSE: To investigate whether behavioral-economic insights improve incentivization effectiveness. METHODS: A systematic search of Medline and Scopus was performed from database inception to December 2020. Study characteristics, program designs, and risk ratio (RR) were extracted. A two-stage network meta-analysis pooled and ranked intervention effects. RESULTS: There were 35 eligible RCTs. For diet-weight control, standard FI, deposit contract (deposit), lottery-based incentive (lottery), and standard-FI + lottery increased goal achievement compared to no-FI but only deposit was statistically significant with pooled RRs and 95% confidence intervals (CI) of 1.21 (0.94, 1.56), 1.79 (1.04, 3.05), 1.45 (0.99, 2.13), and 1.73 (0.83, 3.63). For physical activity, standard-FI, deposit, and lottery significantly increased goal achievement compared to no-FI, with pooled RRs of 1.38 (1.13, 1.68), 1.63 (1.24, 2.14) and 1.43 (1.14, 1.80), respectively. In a follow-up period for physical activity, only deposit significantly increased goal achievement compared to no-FI, with pooled RRs of 1.39 (1.11, 1.73). CONCLUSION: Deposit, followed by lottery, were best for motivating healthy diet, weight control and physical activity at program end. Post-intervention, deposit then standard-FI were best for motivating physical activity. Behavioral insights can improve incentivization effectiveness, although lottery-based approaches may offer only short-term benefit regarding physical activity. However, the imprecise intervention effects were major concerns.

Healthy diet, weight control and physical activity to reduce obesity can be motivated by financial incentives (FI). Behavioral-economic approaches may improve the effectiveness of FI programs. This study aims to investigate whether behavioral-economic insights improve incentivization effectiveness for healthy diet, weight control, and physical activity promotion. We conducted a systematic review of published randomized controlled trials (RCTs), then pooled the interested results, compared and ranked the effectiveness of standard and behavioral incentivization programs by a two-stage network meta-analysis. There were 35 eligible RCTs. For diet-weight control, standard FI, deposit contract (deposit), lottery-based incentive (lottery), and standard-FI + lottery increased goal achievement compared to no-FI but only deposit was statistically significant. For physical activity, standard-FI, deposit, and lottery significantly increased goal achievement compared to no-FI. In a follow-up period for physical activity, only deposit significantly increased goal achievement compared to no-FI. In conclusion, deposit, followed by lottery, were best for motivating healthy diet, weight control and physical activity at program end. Post-intervention, deposit then standard-FI were best for motivating physical activity. This shows that behavioral insights can improve incentivization effectiveness, although lottery-based approaches may offer only short-term benefit regarding physical activity.

HealthyRHearts - reducing cholesterol in rural adults via telehealth-based medical nutrition therapy: protocol for a cluster randomised controlled trial.

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.

Optimizing the Yield of Abnormal Preoperative Chest Radiographs in Elective Non-cardiothoracic Surgery: Development of a Risk Prediction Score and External Validation.

BACKGROUND: Guideline recommendations for preoperative chest radiographs vary to the extent that individual patient benefit is unclear. We developed and validated a prediction score for abnormal preoperative chest radiographs in adult patients undergoing elective non-cardiothoracic surgery. METHODS: Our prospective observational study recruited 703 adult patients who underwent elective non-cardiothoracic surgery at Ramathibodi Hospital. We developed a risk prediction score for abnormal preoperative chest radiographs with external validation using data from 411 patients recruited from Thammasat University Hospital. The discriminative performance was assessed by receiver operating curve analysis. In addition, we assessed the contribution of abnormal chest radiographs to perioperative management. RESULTS: Abnormal preoperative chest radiographs were found in 19.5% of the 703 patients. Age, pulmonary disease, cardiac disease, and diabetes were significant factors. The model showed good performance with a C-statistics of 0.739 (95% CI, 0.691-0.786). We classified patients into four groups based on risk scores. The posttest probabilities in the intermediate-, intermediate-high-, and high-risk groups were 33.2%, 59.8%, and 75.7%, respectively. The model fitted well with the external validation data with a C statistic of 0.731 (95% CI, 0.674-0.789). One (0.4%) abnormal chest radiograph from the low-risk group and three (2.4%) abnormal chest radiographs from the intermediate-to-high-risk group had a major impact on perioperative management. CONCLUSIONS: Four predictors including age, pulmonary disease, cardiac disease, and diabetes were associated with abnormal preoperative chest radiographs. Our risk score demonstrated good performance and may help identify patients at higher risk of chest abnormalities.

Efficacy of technology-based personalised feedback on diet quality in young Australian adults: results for the advice, ideas and motivation for my eating (Aim4Me) randomised controlled trial.

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.

Prevalence and clinical risk prediction of hypertriglyceridaemia in a community cohort.

BACKGROUND: Hypertriglyceridaemia (HTG; defined as ≥1.7 mmol/L) has a prevalence of 18-33% with significant inter-regional variation. Despite meta-analysis demonstrating its association with increased risk of cardiovascular disease, only 40% of HTG is identified in the community resulting in underutilisation of lipid-lowering therapy and specialist clinics. An increase in awareness of its clinical risk factors is needed to improve the identification and management of HTG to prevent cardiovascular risk. AIMS: To evaluate the prevalence, distribution and clinical predictors of HTG ≥1.7 mmol/L in a representative community group. METHODS: Data were obtained from the Hunter Community Study (HCS), a longitudinal cohort of community-dwelling men and women aged 55-85 years residing in Newcastle, New South Wales. Fasting triglycerides were identified based on the availability of fasting blood glucose level and categorised according to normal (<1.7 mmol/L), mild (1.7 to <2.3 mmol/L) and moderate-severe HTG (≥2.3 mmol/L). Clinical predictors of HTG were assessed using linear and logistic regression models. RESULTS: Of 2536 triglyceride levels, 2216 (87%) were in a fasting state and included in the study. Three hundred and two (13.6%) participants had mild HTG and 221 (10.0%) participants had moderate-severe HTG. Significant clinical predictors of HTG included male gender, increasing body mass index, current smoking, decreasing daily step counts, increasing fasting glucose and higher thyroid-stimulating hormone. Alcohol intake and blood pressure were not significant in either adjusted regression model. CONCLUSIONS: HTG ≥1.7 mmol/L is common, affecting 24% of the HCS. Clinical predictors identify modifiable risk factors for cardiovascular risk management. Clinician education to promote awareness is required to improve patient outcomes.

Australian general practitioners' perspectives on integrating specialist diabetes care with primary care: qualitative study.

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 (< 80% of patients annually) from HNELHD, NSW provided the sampling frame. A total of nine GPs were interviewed. The transcripts from the interviews were reviewed and analysed to identify emergent patterns and themes. RESULTS: Overall, GPs were supportive of DAP. They considered that DAP resulted in significant changes in their knowledge, skills, and approach and improved the quality of diabetes care. Taking a more holistic approach to care, including assessing patients with diabetes for co-morbidities and risk factors that may impact on their future health was also noted. DAP was noted to increase the confidence levels of GPs, which enabled active involvement in the provision of diabetes care rather than referring patients for tertiary specialist care. However, some indicated the program could be time consuming and greater flexibility was needed. CONCLUSIONS: GPs reported DAP to benefit their knowledge, skills and approach for managing diabetes. Future research will need to investigate how to improve the intensity and flexibility of the program based on the workload of GPs to ensure long-term acceptability of the program.

Prioritising and incentivising productivity within indicator-based approaches to Research Impact Assessment: a commentary.

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.

Persistence of Detectable Anti-Pneumococcal Antibodies 4 Years After Pneumococcal Polysaccharide Vaccination in a Randomised Controlled Trial: The Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE).

AIM: Mouse models have indicated that the pneumococcal polysaccharide vaccine (PPV) can reduce atherosclerosis. This is probably through a process of molecular mimicry, where phosphorylcholine in the capsular polysaccharide of the vaccine elicits antibodies that cross-react with oxidised low-density lipoprotein and reduce plaque. We investigated whether a similar mechanism occurs in humans. METHODS: A large national blinded, randomised, placebo-controlled trial of the PPV (Australian Study for the Prevention through Immunisation of Cardiovascular Events [AUSPICE]) is underway with fatal and nonfatal cardiovascular disease (CVD) events as the primary outcome. Participants at one centre agreed to a substudy measuring a number of biomarkers and surrogates of CVD over 4 years, including anti-pneumococcal antibodies (immunoglobulin G and immunoglobulin M), C-reactive protein, carotid intima-media thickness, pulse wave velocity, insulin, fasting blood glucose, glycated haemoglobin, and hepatorenal index. RESULTS: Antipneumococcal immunoglobulin G and immunoglobulin M were both present and statistically significantly increased in the treated group compared to control at 4 years. However, there were no differences in any of the surrogate measures of CVD or metabolic markers at 4 years. CONCLUSIONS: While there were prolonged differences in anti-pneumococcal antibody titres following PPV vaccination, these did not appear to provide any cardioprotective effect, as measured by a range of markers. Final results using the fatal and nonfatal CVD events await the completion of national health record linkage next year. TRIAL REGISTRATION: ACTRN12615000536561.

Antiseptic Skin Agents to Prevent Surgical Site Infection After Incisional Surgery: A Randomized, Three-armed Combined Non-inferiority and Superiority Clinical Trial (NEWSkin Prep Study).

OBJECTIVE: To compare SSI rates between the skin preparation agents: PI-Aq, povidone-iodine with alcohol (PI-Alc), and chlorhexidine with alcohol (C-Alc). BACKGROUND: Guidelines suggest that alcohol-containing chlorhexidine solutions are the gold standard for skin preparation before surgery. It remains difficult to determine whether it is the chlorhexidine component or the addition of alcohol that confers the most benefit. METHODS: We conducted a multicenter, prospective, combined non-inferiority (PI-Alc vs C-Alc) and superiority (PI-Alc vs PI-Aq) randomized clinical trial. Participants were randomized 1:1:1 to receive either C-Alc, PI-Alc, or PI-Aq. The primary outcome was SSI rate as defined by the Centers for Disease Control. Secondary outcomes were complication rates, length of hospital stay, readmissions, and skin reactions. RESULTS: Between January 2015 and December 2018, 3213 patients were randomized (C-Alc: 1076, PI-Alc: 1075, and PI-Aq: 1062). Mean age of participants was 57% and 55% were female. SSI rates were: C-Alc 11.09%, PI-Alc 10.88%, and PI-Aq 12.56%. PI-Alc was found to be non-inferior to C-Alc (mean difference, -0.21%; 95% confidence interval, -2.85 to 2.44; P = 0.0009 non-inferiority), whereas PI-Alc was not superior to PI-Aq (mean difference, -1.68%; 95% confidence interval, -4.40 to 1.05; P = 0.2302). There were no differences seen in secondary outcomes between groups and no treatment related adverse events or deaths occurred. CONCLUSIONS: PI-Alc is non-inferior to C-Alc and not superior to PI-Aq. This is at odds with current guidelines that suggest alcohol-based chlorhexidine solutions should routinely be used for surgical skin preparation. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry: ANZCTRN12615000021571. www.anzctr.org.au.

Effect of asthma management with exhaled nitric oxide versus usual care on perinatal outcomes.

INTRODUCTION: Asthma exacerbations in pregnancy are associated with adverse perinatal outcomes. We aimed to determine whether fractional exhaled nitric oxide (F ENO)-based asthma management improves perinatal outcomes compared to usual care. METHODS: The Breathing for Life Trial was a multicentre, parallel-group, randomised controlled trial conducted in six hospital antenatal clinics, which compared asthma management guided by F ENO (adjustment of asthma treatment according to exhaled nitric oxide and symptoms each 6-12 weeks) to usual care (no treatment adjustment as part of the trial). The primary outcome was a composite of adverse perinatal events (preterm birth, small for gestational age (SGA), perinatal mortality or neonatal hospitalisation) assessed using hospital records. Secondary outcomes included maternal asthma exacerbations. Concealed random allocation, stratified by study site and self-reported smoking status was used, with blinded outcome assessment and statistical analysis (intention to treat). RESULTS: Pregnant women with current asthma were recruited; 599 to the control group (608 infants) and 601 to the intervention (615 infants). There were no significant group differences for the primary composite perinatal outcome (152 (25.6%) out of 594 control, 177 (29.4%) out of 603 intervention; OR 1.21, 95% CI 0.94-1.56; p=0.15), preterm birth (OR 1.14, 95% CI 0.78-1.68), SGA (OR 1.06, 95% CI 0.78-1.68), perinatal mortality (OR 3.62, 95% CI 0.80-16.5), neonatal hospitalisation (OR 1.24, 95% CI 0.89-1.72) or maternal asthma exacerbations requiring hospital admission or emergency department presentation (OR 1.19, 95% CI 0.69-2.05). CONCLUSION: F ENO-guided asthma pharmacotherapy delivered by a nurse or midwife in the antenatal clinic setting did not improve perinatal outcomes.