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.

Fasting vs no fasting prior to catheterisation laboratory procedures: the SCOFF trial.

BACKGROUND AND AIMS: Current guidelines recommend 6 hours of solid food and 2 hours of clear liquid fasting for patients undergoing cardiac procedures with conscious sedation. There are no data to support this practice, and previous single centre studies support the safety of removing fasting requirements. The objective of this study was to determine the non-inferiority of a no fasting strategy to fasting prior to cardiac catheterisation procedures which require conscious sedation. METHODS: This is a multicentre, investigator-initiated, non-inferiority randomised trial conduced in Australia with a prospective open label blinded endpoint design. Patients referred for coronary angiography, percutaneous coronary intervention or cardiac implantable electronic device (CIED) related procedures were enrolled. Patients were randomised 1:1 to fasting as normal (6 hours solid food and 2 hours clear liquid) or no fasting requirements (encouraged to have regular meals but not mandated to do so). Recruitment occurred from 2022 to 2023. The primary outcome was a composite of aspiration pneumonia, hypotension, hyperglycaemia and hypoglycaemia assessed with a Bayesian approach. Secondary outcomes included patient satisfaction score, new ventilation requirement (non-invasive and invasive), new intensive care unit admission, 30-day readmission, 30-day mortality, 30-day pneumonia. RESULTS: 716 patients were randomised with 358 in each group. Those in the fasting arm had significantly longer solid food fasting (13.2 versus 3.0 hours, Bayes factor >100 indicating extreme evidence of difference) and clear liquid fasting times (7.0 versus 2.4 hours, Bayes factor >100). The primary composite outcome occurred in 19.1% of patients in the fasting arm and 12.0% of patients in the no fasting arm. The estimate of the mean posterior difference in proportions in the primary composite outcome was -5.2% (95% CI -9.6 to -0.9, ) favouring no fasting. This result confirms non-inferiority (posterior probability >99.5%) and superiority (posterior probability 99.1%) of no fasting for the primary composite outcome. The no fasting arm had improved patient satisfaction scores with a posterior mean difference of 4.02 points (95% CI 3.36 to 4.67, Bayes factor >100). Secondary outcome events were similar. CONCLUSIONS: In patients undergoing cardiac catheterisation and CIED related procedures, no fasting was non-inferior and superior to fasting for the primary composite outcome of aspiration pneumonia, hypotension, hyperglycaemia and hypoglycaemia. Patient satisfaction scores were significantly better with no fasting. This supports removing fasting requirements for patients undergoing cardiac catheterisation laboratory procedures that require conscious sedation.

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.

Individual treatment effects of sodium-glucose co-transporter-2 inhibitors on the risk of chronic kidney disease in patients with type 2 diabetes: A counterfactual prediction model based on real-world data.

AIM: To estimate individual treatment effects (ITEs) of sodium-glucose co-transporter-2 inhibitors (SGLT2is) on lowering the risk of developing chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) and to identify those most probable to benefit from treatment. METHODS: This study followed a T2D cohort from Ramathibodi Hospital, Thailand, from 2015 to 2022. A counterfactual model was constructed to predict factual and counterfactual risks of CKD if patients did/did not receive SGLT2is. ITEs were estimated by subtracting the factual risk from the counterfactual risk of CKD. RESULTS: There were 1619 and 15 879 patients included in the SGLT2i and non-SGLT2i groups, respectively. The estimated ITEs varied from -1.19% to -17.51% with a median of -4.49%, that is, 50% of patients had a 4.49% or greater lower CKD risk if they received an SGLT2i. Patients who gained the greatest benefit from SGLT2is were more probable to be male, aged at least 60 years, with a history of diabetes duration of at least 3 months, hypertension, peripheral arterial disease, diabetic retinopathy and low high-density lipoprotein cholesterol. CONCLUSIONS: Our prediction model provides individualized information that helps target T2D patients who may benefit more from SGLT2is. This could help clinical decision making and implementation of personalized medicine in clinical practice, especially in resource-limited settings.

The Effect of Temporal Persistence of Loneliness on Dementia: A Longitudinal Analysis From the Hunter Community Study.

OBJECTIVES: Loneliness is common and becoming a public health concern. Although there is the clear evidence of the variable effect of temporal differences in loneliness (transient/situational and persistent/chronic) on health, their effect on dementia risk is unclear. This study aims to assess the effect of transient/situational and persistent/chronic loneliness on dementia risk. METHOD: Participants aged 55 years and older from the Hunter Community Study were recruited. Loneliness was measured using a single item measure. Dementia was defined as per International Classification of Disease-10 (ICD 10) codes. The Fine-Gray subdistribution hazard model was performed to calculate dementia risk. RESULTS: Of 1968 total participants with mean age of 66 years, (3%) 57 developed dementia and (7%) 135 died over the mean follow up of 10 years. Both persistent/chronic and transient/situational loneliness significantly increased the risk of all cause dementia in adjusted models (HR 2.74, 95% CI 1.11-6.88, p 0.03 and HR 2.35, 95% CI 1.21-4.55, p 0.01 respectively) with mean time to event of 9.7 years. Feeling lonely below the age of 70 years elevated the risk of dementia in later life (HR 4.01, 95% CI 1.40-11.50, p 0.01). CONCLUSIONS: Loneliness (both persistent/chronic and transient/situational) was associated with increased risk of all cause dementia, especially if loneliness was experienced before the age of 70 years. These results suggest that promoting coping strategies for loneliness especially in persons 70 years and younger may play a role in preventing dementia.

Spillover effects from a type 2 diabetes integrated model of care in 22,706 Australians: an open cohort stepped wedge trial.

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 < 0.0001). Significant improvements in clinical outcomes were observed for weight (absolute mean difference: -1.38 kg), blood pressure (systolic - 1.12 mmHg, diastolic - 1.18 mmHg), HbA1c (-0.03% at the mean), total cholesterol (-0.11 mmol/L), and triglycerides (-0.02 mmol/L) (p < 0.05). There were small but significant declines in kidney function. CONCLUSIONS: Integrated care delivered to a small subset of patients with type 2 diabetes across a large geographic region has spillover benefits that improve the process measures and clinical outcomes for all practice patients with type 2 diabetes. TRIAL REGISTRATION: ACTRN12622001438741; 10th November 2022, retrospectively registered: https://www.anzctr.org.au/ACTRN12622001438741.aspx .

Outcomes associated with postoperative cognitive dysfunction: a systematic review and meta-analysis.

BACKGROUND: Postoperative cognitive dysfunction (POCD) manifests as a subtle decline in cognition, potentially leading to unfavourable postoperative outcomes. We explored the impact of POCD on physical function, length of hospital stay (LOS), dementia and mortality outcomes. METHODS: PubMed and Scopus were searched until May 2023. All studies of major surgical patients that assessed POCD and outcomes of interest were included. POCD effects were stratified by surgery type (cardiac and noncardiac) and time of POCD assessment (<30 and ≥30 days postsurgery). RESULTS: Of 2316 studies, 20 met the inclusion criteria. POCD was not associated with functional decline postsurgery. Patients who experienced POCD postcardiac surgery had an increased relative risk (RR) of death of 2.04 [(95% CI: 1.18, 3.50); I2 = 0.00%]. Sensitivity analyses showed associations with intermediate-term mortality among noncardiac surgical patients, with an RR of 1.84 [(95% CI: 1.26, 2.71); I2 = 0.00%]. Patients who developed POCD <30 days postcardiac and noncardiac surgeries experienced longer LOS than those who did not [mean difference (MD) = 1.37 days (95% CI: 0.35, 2.39); I2 = 92.38% and MD = 1.94 days (95% CI: 0.48, 3.40); I2 = 83.29%, respectively]. Postoperative delirium (POD) may contribute to the heterogeneity observed, but limited data were reported within the studies included. CONCLUSIONS: Patients undergoing cardiac and noncardiac surgeries who developed POCD <30 days postsurgery had poorer outcomes and an increased risk of premature death. Early recognition of perioperative neurocognitive disorders in at-risk patients may enable early intervention. However, POD may confound our findings, with further studies necessary to disentangle the effects of POD from POCD on clinical outcomes.

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.

Effectiveness of NSW health get healthy telephone coaching in adults screened from general practices.

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 < 6.5%) were referred from GP Practices to the Get Healthy Service, NSW Health. A subset (n = 98) participated in the "Zinc In Preventing the Progression of pre-Diabetes" (ZIPPeD) trial (ACTRN12618001120268). RESULTS: The self-reported outcomes showed a statistically significant improvement from baseline to 12 months in weight (mean 2.7 kg loss, p < 0.001), BMI (mean 1 unit reduction, p < 0.001), and waist circumference (mean 4.3 cm reduction, p < 0.001). However, in the objectively measured outcomes from ZIPPeD, the differences were more modest, with point estimates of 0.8 kg mean weight loss (p = 0.1), 0.4 unit reduction in BMI (p = 0.03), and 1.8 cm reduction in waist circumference (p = 0.04). Bland-Altman plots indicated that discrepancies were due to a small number of participants who dramatically underestimated their weight or BMI. There were minimal changes in nutrition, physical activity, and alcohol. CONCLUSIONS: The potential benefits of Get Healthy should be interpreted with caution as we have shown significant differences between self-reported and objectively measured values. More valid and objective evidence is needed to determine the program's effectiveness and cost-effectiveness.

'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.

Prediction models for identifying medication overuse or medication overuse headache in migraine patients: a systematic review.

BACKGROUND: Migraine is a debilitating neurological disorder that presents significant management challenges, resulting in underdiagnosis and inappropriate treatments, leaving patients at risk of medication overuse (MO). MO contributes to disease progression and the development of medication overuse headache (MOH). Predicting which migraine patients are at risk of MO/MOH is crucial for effective management. Thus, this systematic review aims to review and critique available prediction models for MO/MOH in migraine patients. METHODS: A systematic search was conducted using Embase, Scopus, Medline/PubMed, ACM Digital Library, and IEEE databases from inception to April 22, 2024. The risk of bias was assessed using the prediction model risk of bias assessment tool. RESULTS: Out of 1,579 articles, six studies with nine models met the inclusion criteria. Three studies developed new prediction models, while the remaining validated existing scores. Most studies utilized cross-sectional and prospective data collection in specific headache settings and migraine types. The models included up to 53 predictors, with sample sizes from 17 to 1,419 participants. Traditional statistical models (logistic regression and least absolute shrinkage and selection operator regression) were used in two studies, while one utilized a machine learning (ML) technique (support vector machines). Receiver operating characteristic analysis was employed to validate existing scores. The area under the receiver operating characteristic (AUROC) for the ML model (0.83) outperformed the traditional statistical model (0.62) in internal validation. The AUROCs ranged from 0.84 to 0.85 for the validation of existing scores. Common predictors included age and gender; genetic data and questionnaire evaluations were also included. All studies demonstrated a high risk of bias in model construction and high concerns regarding applicability to participants. CONCLUSION: This review identified promising results for MO/MOH prediction models in migraine patients, although the field remains limited. Future research should incorporate important risk factors, assess discrimination and calibration, and perform external validation. Further studies with robust designs, appropriate settings, high-quality and quantity data, and rigorous methodologies are necessary to advance this field.

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.