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.

Antiseptic Skin Preparation Agents to Prevent Surgical Site Infection in Colorectal Surgery: A 3-Armed Randomized Controlled Trial.

BACKGROUND: There is much debate surrounding the ideal antiseptic skin preparation agent to reduce postoperative surgical site infection. International guidelines suggest that chlorhexidine- and alcohol-containing compounds have superior efficacy. However, there are minimal clinical trials specifically looking at skin preparation agents for colorectal surgery. OBJECTIVE: The aim of this study was to compare the efficacy of chlorhexidine in alcohol versus povidone-iodine in alcohol versus povidone-iodine in aqueous solution for the prevention of surgical site infection in colorectal surgery. DESIGN: This is a prospective, 3-armed, randomized controlled trial. SETTING: This study was conducted at the 800-bed John Hunter Hospital and Newcastle Private Hospital, with all subspecialty services in New South Wales, Australia. PATIENTS: All eligible, consenting adults undergoing colorectal surgery between July 2015 and December 2018 were included. INTERVENTIONS: Patients were andomized to receive preincision skin preparation with one of the following: chlorhexidine in 70% alcohol, povidone-iodine in 70% alcohol, or povidone-iodine in aqueous solution. MAIN OUTCOME MEASURE: The primary measure was surgical site infection within 30 days. RESULTS: A total of 482 patients were randomized to chlorhexidine in alcohol, povidone-iodine in alcohol, or aqueous povidone-iodine. The overall surgical site infection rate was 22% (107/482). There was no difference in rates of surgical site infection: 20.6% (29/141), 22.8% (44/193), and 23.0% (34/148), respectively ( p = 0.5267). There was no difference in complication rates: 54.6% (77/141), 46.1% (89/193), and 49.3% (73/148), respectively ( p = 0.1762). The median length of stay was 6 days in all 3 groups. LIMITATIONS: This is a subset analysis of a larger clinical trial for all forms of incisional surgery (the NewSKIN Prep trial), and noninferiority cannot be assessed. Changes in government regulations resulted in a change from 0.5% chlorhexidine in 70% ethanol to 2% chlorhexidine in 70% ethanol during the trial. CONCLUSION: This large, prospective, randomized clinical trial appears to indicate that there is no difference in surgical site infection, complications, or length of stay among the 3 commonest forms of skin preparation in colorectal surgery. See Video Abstract at http://links.lww.com/DCR/B875 .New Zealand Clinical Trials registry: ACTRN12615000021572Agentes antisépticos para la preparación de la piel para prevenir la infección del sitio quirúrgico en la cirugía colorrectal: un ensayo clínico aleatorizado de tres grupos. ANTECEDENTES: Existe un gran debate en torno al agente de preparación de la piel antiséptico ideal para reducir la infección posoperatoria del sitio quirúrgico. Las pautas internacionales sugieren que los compuestos que contienen clorhexidina y alcohol tienen una eficacia. Sin embargo, existen ensayos clínicos mínimos que analizan específicamente los agentes de preparación de la piel para la cirugía colorrectal. OBJETIVO: Comparar la eficacia de la clorhexidina en alcohol versus povidona yodada en alcohol versus povidona yodada en solución acuosa para la prevención de la infección del sitio quirúrgico en cirugía colorrectal. DISEO: Este es un ensayo controlado aleatorio prospectivo de tres brazos. AJUSTE: Este estudio se realizó en el Hospital John Hunter de 800 camas y el Hospital Privado de Newcastle con todos los servicios de subespecialidad en Nueva Gales del Sur, Australia. PACIENTES: Se incluyeron todos los adultos elegibles que dieron su consentimiento para someterse a una cirugía colorrectal entre julio de 2015 y diciembre de 2018. INTERVENCIONES: Aleatorizados para recibir una preparación para la piel previa a la incisión con uno de: clorhexidina en alcohol al 70%, povidona yodada en alcohol al 70% o povidona yodada en solución acuosa. MEDIDA DE RESULTADO PRINCIPAL: La medida principal fue la infección del sitio quirúrgico dentro de los 30 días. RESULTADOS: Un total de 482 pacientes fueron aleatorizados para recibir clorhexidina en alcohol, povidona yodada en alcohol o povidona yodada acuosa. La tasa global de infección del sitio quirúrgico fue del 22% (107/482). No hubo diferencias en las tasas de infección del sitio quirúrgico; 20,6% (29/141), 22,8% (44/193) y 23,0% (34/148) respectivamente; p = 0,5267. No hubo diferencia en las tasas de complicaciones; 54,6% (77/141), 46,1% (89/193) y 49,3% (73/148) respectivamente; p = 0,1762. La duración media de la estancia hospitalaria fue de 6,0 días en los tres grupos. LIMITACIONES: Este es un análisis de subconjunto de un ensayo clínico más grande para todas las formas de cirugía incisional (el ensayo NewSKIN Prep) y no se puede evaluar la no inferioridad. Los cambios en las regulaciones gubernamentales dieron como resultado un cambio de clorhexidina al 0,5% en etanol al 70% a clorhexidina al 2% en etanol al 70% durante la prueba. CONCLUSINES: Este gran ensayo clínico prospectivo y aleatorizado parece indicar que no hay diferencia en la infección del sitio quirúrgico, las complicaciones o la duración de la estancia entre las 3 formas más comunes de preparación de la piel en la cirugía colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B875 . (Traducción-Dr. Gonzalo Hagerman )Este ensayo se registró de forma prospectiva en el registro de ensayos clínicos de Australia Nueva Zelanda el 15/01/2015: ACTRN12615000021572.

Secondary Prevention of Stroke: Study Protocol for a Telehealth-Delivered Physical Activity and Diet Pilot Randomized Trial (ENAbLE-Pilot).

BACKGROUND: Increasing physical activity (PA) and improving diet quality are opportunities to improve secondary stroke prevention, but access to appropriate services is limited. Interventions co-designed with stroke survivors and delivered by telehealth are a potential solution. AIM: The aim of this study is to test the feasibility, safety, and potential efficacy of a 6-month, telehealth-delivered PA and/or dietary (DIET) intervention. METHODS: Pilot randomized trial. 80 adults with previous stroke who are living at home with Internet access and able to exercise will be randomized in a 2 × 2 factorial (4-arm) pilot randomized, open-label, blinded outcome assessment trial to receive PA, DIET, PA + DIET, or control interventions via telehealth. The PA intervention aims to support participants to meet the minimum recommended levels of PA (150 min/week moderate exercise), and the DIET intervention aims to support participants to follow the AusMed (Mediterranean-style) diet. The control group receives usual care plus education about PA and healthy eating. The co-primary outcomes are feasibility (proportion and characteristics of eligible participants enrolled and proportion of scheduled intervention sessions attended) and safety (adverse events) at 6 months. The secondary outcomes include recurrent stroke risk factors (blood pressure, physical activity levels, and diet quality), fatigue, mood, and quality of life. Outcomes are measured at 3, 6, and 12 months. CONCLUSION: This trial will produce evidence for the feasibility, safety, and potential effect of telehealth-delivered PA and DIET interventions for people with stroke. Results will inform development of an appropriately powered trial to test effectiveness to reduce major risk factors for recurrent stroke. TRIAL REGISTRATION: ACTRN12620000189921.

Thrombolysis implementation intervention and clinical outcome: a secondary analysis of a cluster randomized trial.

BACKGROUND: Multiple studies have attempted to increase the rate of intravenous thrombolysis for ischemic stroke using interventions to promote adherence to guidelines. Still, many of them did not measure individual-level impact. This study aimed to make a posthoc comparison of the clinical outcomes of patients in the "Thrombolysis ImPlementation in Stroke (TIPS)" study, which aimed to improve rates of intravenous thrombolysis in Australia. METHODS: A posthoc analysis was conducted using individual-level patient data. Excellent (Three-month post treatment modified Rankin Score 0-2) and poor clinical outcome (Three-month post treatment modified Rankin Score 5-6) and post treatment parenchymal haematoma were the three main outcomes, and a mixed logistic regression model was used to assess the difference between the intervention and control groups. RESULTS: There was a non-significant higher odds of having an excellent clinical outcome of 57% (odds ratio: 1.57; 95% CI: 0.73-3.39) and 33% (odds ratio: 1.33; 95% CI: 0.73-2.44) during the active-and post-intervention period respectively, for the intervention compared to the control group. A non-significant lower odds of having a poor clinical outcome was also found in the intervention, relative to control group of 4% (odds ratio: 0.96; 95% CI: 0.56-2.07) and higher odds of having poor outcome of 44% (odds ratio: 1.44 95% CI: 0.61-3.41) during both active and post-intervention period respectively. Similarly, a non-significant lower odds of parenchymal haematoma was also found for the intervention group during the both active- (odds ratio: 0.53; 95% CI: 0.21-1.32) and post-intervention period (odds ratio: 0.96; 95% CI: 0.36-2.52). CONCLUSION: The TIPS multi-component implementation approach was not effective in reducing the odds of post-treatment severe disability at 90 days, or post-thrombolysis hemorrhage. TRIAL REGISTRATION: Clinical Trial Registration-URL: http://www.anzctr.org.au/ Unique Identifier: ACTRN12613000939796 .

Evaluating recruitment strategies for AUSPICE, a large Australian community-based randomised controlled trial.

OBJECTIVES: To examine the effectiveness of different strategies for recruiting participants for a large Australian randomised controlled trial (RCT), the Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE). DESIGN, SETTING, PARTICIPANTS: Men and women aged 55-60 years with at least two cardiovascular risk factors (hypertension, hypercholesterolaemia, overweight/obesity) were recruited for a multicentre placebo-controlled RCT assessing the effectiveness of 23-valent pneumococcal polysaccharide vaccine (23vPPV) for preventing cardiovascular events. METHODS: Invitations were mailed by the Australian Department of Human Services to people in the Medicare database aged 55-60 years; reminders were sent 2 weeks later. Invitees could respond in hard copy or electronically. Direct recruitment was supplemented by asking invitees to extend the invitation to friends and family (snowball sampling) and by Facebook advertising. MAIN OUTCOME: Proportions of invitees completing screening questionnaire and recruited for participation in the RCT. RESULTS: 21 526 of 154 992 invited people (14%) responded by completing the screening questionnaire, of whom 4725 people were eligible and recruited for the study. Despite the minimal study burden (one questionnaire, one clinic visit), the overall participation rate was 3%, or an estimated 10% of eligible persons. Only 16% of eventual participants had responded within 2 weeks of the initial invitation letter (early responders); early and late responders did not differ in their demographic or medical characteristics. Socio-economic disadvantage did not markedly influence response rates. Facebook advertising and snowball sampling did not increase recruitment. CONCLUSIONS: Trial participation rates are low, and multiple concurrent methods are needed to maximise recruitment. Social media strategies may not be successful in older age groups. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12615000536561.

A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration.

Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.

National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: Australian clinical guidelines for the diagnosis and management of atrial fibrillation 2018.

INTRODUCTION: Atrial fibrillation (AF) is increasing in prevalence and is associated with significant morbidity and mortality. The optimal diagnostic and treatment strategies for AF are continually evolving and care for patients requires confidence in integrating these new developments into practice. These clinical practice guidelines will assist Australian practitioners in the diagnosis and management of adult patients with AF. Main recommendations: These guidelines provide advice on the standardised assessment and management of patients with atrial fibrillation regarding: screening, prevention and diagnostic work-up; acute and chronic arrhythmia management with antiarrhythmic therapy and percutaneous and surgical ablative therapies; stroke prevention and optimal use of anticoagulants; and integrated multidisciplinary care. Changes in management as a result of the guideline: Opportunistic screening in the clinic or community is recommended for patients over 65 years of age. The importance of deciding between a rate and rhythm control strategy at the time of diagnosis and periodically thereafter is highlighted. ß-Blockers or non-dihydropyridine calcium channel antagonists remain the first line choice for acute and chronic rate control. Cardioversion remains first line choice for acute rhythm control when clinically indicated. Flecainide is preferable to amiodarone for acute and chronic rhythm control. Failure of rate or rhythm control should prompt consideration of percutaneous or surgical ablation. The sexless CHA2DS2-VA score is recommended to assess stroke risk, which standardises thresholds across men and women; anticoagulation is not recommended for a score of 0, and is recommended for a score of ≥ 2. If anticoagulation is indicated, non-vitamin K oral anticoagulants are recommended in preference to warfarin. An integrated care approach should be adopted, delivered by multidisciplinary teams, including patient education and the use of eHealth tools and resources where available. Regular monitoring and feedback of risk factor control, treatment adherence and persistence should occur.

Developing a multi-component immune model for evaluating the risk of respiratory illness in athletes.

Clinical and laboratory identification of the underlying risk of respiratory illness in athletes has proved problematic. The aim of this study was to determine whether clinical data, combined with immune responses to standardised exercise protocols and genetic cytokine polymorphism status, could identify the risk of respiratory illness (symptoms) in a cohort of highly-trained athletes. Male endurance athletes (n=16; VO2max 66.5 ± 5.1 mL.kg-1.min-1) underwent a clinical evaluation of known risk factors by a physician and comprehensive laboratory analysis of immune responses both at rest and after two cycling ergometer tests: 60 min at 65% VO2max (LONG); and 6 x 3 min intervals at 90% VO2max (INTENSE). Blood tests were performed to determine Epstein Barr virus (EBV) status and DNA was genotyped for a panel of cytokine gene polymorphisms. Saliva was collected for measurement of IgA and detection of EBV DNA. Athletes were then followed for 9 months for self-reported episodes of respiratory illness, with confirmation of the underlying cause by a sports physician. There were no associations with risk of respiratory illness identified for any parameter assessed in the clinical evaluations. The laboratory parameters associated with an increased risk of respiratory illnesses in highly-trained athletes were cytokine gene polymorphisms for the high expression of IL-6 and IFN-É£; expression of EBV-DNA in saliva; and low levels of salivary IgA concentration. A genetic risk score was developed for the cumulative number of minor alleles for the cytokines evaluated. Athletes prone to recurrent respiratory illness were more likely to have immune disturbances that allow viral reactivation, and a genetic predisposition to pro-inflammatory cytokine responses to intense exercise.

Daily step count and the need for hospital care in subsequent years in a community-based sample of older Australians.

OBJECTIVES: To determine the extent to which physical activity reduces the number of hospital bed-days for Australians over 55, using an objective measure of activity. DESIGN, SETTING AND PARTICIPANTS: 9784 Newcastle residents aged 55 years or more were invited to participate. 3253 responders were eligible and wore pedometers for one week during 2005-2007; their hospital data from recruitment to 31 March 2015 were analysed (mean follow-up time: 8.2 years). Complete data for 2110 people were available for analysis. MAIN OUTCOME MEASURES: Mean annual hospital bed-days, according to individual step count. RESULTS: There was a statistically significant reduction in the number of hospital bed-days associated with higher step counts; the incidence rate ratio per extra 1000 steps per day at baseline was 0.91 (95% CI, 0.90-0.94). The disease-specific reductions were significant for admissions for cancer and diabetes, but not for cardiovascular disease. The difference between 4500 and 8800 steps per day (the upper and lower quartile boundaries for step count) was 0.36 bed-days per person per year, after adjusting for age, sex, number of medications, number of comorbidities, smoking and alcohol status, and education. When analysis was restricted to hospital admissions after the first 2 years of follow-up, the difference was 0.29 bed-days per person per year. CONCLUSIONS: More active people require less hospital care, and an achievable extra 4300 steps per day would result in an average of one less day in hospital for each 3 years of life.

A novel MMP12 locus is associated with large artery atherosclerotic stroke using a genome-wide age-at-onset informed approach.

Genome-wide association studies (GWAS) have begun to identify the common genetic component to ischaemic stroke (IS). However, IS has considerable phenotypic heterogeneity. Where clinical covariates explain a large fraction of disease risk, covariate informed designs can increase power to detect associations. As prevalence rates in IS are markedly affected by age, and younger onset cases may have higher genetic predisposition, we investigated whether an age-at-onset informed approach could detect novel associations with IS and its subtypes; cardioembolic (CE), large artery atherosclerosis (LAA) and small vessel disease (SVD) in 6,778 cases of European ancestry and 12,095 ancestry-matched controls. Regression analysis to identify SNP associations was performed on posterior liabilities after conditioning on age-at-onset and affection status. We sought further evidence of an association with LAA in 1,881 cases and 50,817 controls, and examined mRNA expression levels of the nearby genes in atherosclerotic carotid artery plaques. Secondly, we performed permutation analyses to evaluate the extent to which age-at-onset informed analysis improves significance for novel loci. We identified a novel association with an MMP12 locus in LAA (rs660599; p = 2.5×10⁻7), with independent replication in a second population (p = 0.0048, OR(95% CI) = 1.18(1.05-1.32); meta-analysis p = 2.6×10⁻8). The nearby gene, MMP12, was significantly overexpressed in carotid plaques compared to atherosclerosis-free control arteries (p = 1.2×10⁻¹5; fold change = 335.6). Permutation analyses demonstrated improved significance for associations when accounting for age-at-onset in all four stroke phenotypes (p<0.001). Our results show that a covariate-informed design, by adjusting for age-at-onset of stroke, can detect variants not identified by conventional GWAS.

Seasonal Variation in Spontaneous Cervical Artery Dissection: Comparing between UK and Australian Sites.

BACKGROUND: Cervical artery dissection (CAD) is a leading cause of stroke among middle-aged adults, but the etiology is unclear. Some reports of seasonal variation in CAD incidence have been suggested but may reflect extreme climatic conditions. Seasonal variation may implicate more transient seasonal causes such as proinflammatory or hypercoagulable states. This study aimed to assess whether CAD incidence varied with season between UK and Australian sites. Also, this study aimed to determine whether there was a different pattern of seasonal variation between arteries (carotid and vertebral) and any association between CAD incidence and clinical factors. METHODS: This was a retrospective observational study of patients older than 18 years with radiological diagnosis of internal carotid or vertebral arterial dissection, from sites in Australia and the UK. Clinical variables were compared between autumn-winter and spring-summer and site of dissection. RESULTS: A total of 133 CAD cases were documented in Australia and 242 in the UK. There was a seasonal pattern to CAD incidence in countries in both the northern and the southern hemispheres, with a trend for dissection to occur more commonly in autumn, winter, and spring than in summer (incidence rate ratios [IRR] 1.4-1.5, P < .05). CAD counts were also slightly higher in internal carotid than in vertebral artery (IRRs 1.168, 1.43, and 1.127, respectively). Neither systolic blood pressure nor pulse pressure was significantly associated with CAD counts. CONCLUSIONS: CAD occurs more commonly in cooler months regardless of geographical location, suggesting transient seasonal causes may be important in the pathophysiology. This effect was slightly higher in internal carotid than in vertebral artery, suggesting differing trigger mechanisms between dissection sites.

Investigation of a Suicide Ideation Risk Profile in People With Co-occurring Depression and Substance Use Disorder.

Disengagement from services is common before suicide, hence identifying factors at treatment presentation that predict future suicidality is important. This article explores risk profiles for suicidal ideation among treatment seekers with depression and substance misuse. Participants completed assessments at baseline and 6 months. Baseline demographics, psychiatric history, and current symptoms were entered into a decision tree to predict suicidal ideation at follow-up. Sixty-three percent of participants at baseline and 43.5% at follow-up reported suicidal ideation. Baseline ideation most salient when psychiatric illness began before adulthood, increasing the rate of follow-up ideation by 16%. Among those without baseline ideation, dysfunctional attitudes were the most important risk factor, increasing rates of suicidal ideation by 35%. These findings provide evidence of factors beyond initial diagnoses that increase the likelihood of suicidal ideation and are worthy of clinical attention. In particular, providing suicide prevention resources to those with high dysfunctional attitudes may be beneficial.

Immersion of Bovine Eyeballs After 1 Hour in Seawater Does Not Result in Elevation of Postmortem Vitreous Humor Sodium and Chloride Levels.

BACKGROUND: Elevations in postmortem vitreous sodium chloride (PMVSC) levels may help in differentiating saltwater/seawater drowning (SWD) deaths from immersion deaths not related to drowning (DNRD). It is unclear whether the elevation is related to blood/plasma electrolyte changes after inhalation of seawater as hypothesized in SWDs or possibly caused by electrolyte diffusion and/or osmosis across the outer coats of the eyeball during immersion. AIM: To investigate the changes in bovine PMVSC levels at different time points while immersed in seawater. METHODS: Bovine eyeballs were obtained from an abattoir and randomized into 2 groups: a) submerged in seawater ("wet" group) or b) placed in an impermeable plastic bag that was immersed in seawater ("dry" group). The PMVSC levels from 6 eyeballs were measured from each group (without replacement) at 30 minutes, 1 hour, 6 hours, and 12 hours. RESULTS: There was no significant difference in mean PMVSC levels between the 2 groups at 30-minute and 1-hour intervals. A significant difference was noted from 6 hours onward. DISCUSSION: There is no statistically significant elevation in bovine PMVSC levels when immersed in seawater for up to 1 hour. Assuming similar physical properties in humans, any elevations in PMVSC levels in bodies immersed in seawater for less than 1 hour should not be caused by immersion.

Study protocol: a stepped wedge cluster randomised controlled trial of a healthy lifestyle intervention for people attending residential substance abuse treatment.

BACKGROUND: Cardiovascular disease and cancer are leading causes of mortality for people with a history of alcohol or other substance use disorders. These chronic diseases share the same four primary behavioural risk factors i.e. excessive alcohol use, smoking, low intake of fruit and vegetables and physical inactivity. In addition to addressing problematic alcohol use, there is the potential for substance abuse treatment services to also address these other behaviours. Healthy Recovery is an 8-session group-based intervention that targets these multiple behavioural health risk factors and was developed specifically for people attending substance abuse treatment. This protocol describes a Cancer Institute NSW funded study that assesses the effectiveness of delivering Healthy Recovery for people who are attending residential alcohol and other substance abuse treatment. METHODS/DESIGN: The study uses a stepped wedge randomised controlled design, where randomisation occurs at the service level. Participants will be recruited from residential rehabilitation programs provided by The Australian Salvation Army. All participants who (1) currently smoke tobacco and (2) are expected to be in the residential program for the duration of the 5-week intervention will be asked to participate in the study. Those participants residing at the facilities assigned to the treatment condition will complete Healthy Recovery. The intervention is manual guided and will be delivered over a 5-week period, with participants attending 8 group sessions. All participants will continue to complete The Salvation Army residential program, a predominantly 12-step based, modified therapeutic community. Participants in the control condition will complete treatment as usual. Research staff blind to treatment allocation will complete the primary and secondary outcome assessments at baseline and then at weeks 8, 20 and 32 weeks post intervention. DISCUSSION: This study will provide comprehensive data on the effect of delivering a healthy lifestyle intervention (i.e. Healthy Recovery) within a residential substance abuse setting. If shown to be effective, this intervention can be disseminated within other residential substance abuse programs. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Register (ANZCTR): ACTRN12615000165583. Registered 19(th) February 2015.

Predictors of suicidal ideation in older people: a decision tree analysis.

OBJECTIVES: Suicide among older adults is a major public health issue worldwide. Although studies have identified psychological, physical, and social contributors to suicidal thoughts in older adults, few have explored the specific interactions between these factors. This article used a novel statistical approach to explore predictors of suicidal ideation in a community-based sample of older adults. DESIGN: Prospective cohort study. PARTICIPANTS AND SETTING: Participants aged 55-85 years were randomly selected from the Hunter Region, a large regional center in New South Wales, Australia. MEASUREMENTS: Baseline psychological, physical, and social factors, including psychological distress, physical functioning, and social support, were used to predict suicidal ideation at the 5-year follow-up. Classification and regression tree modeling was used to determine specific risk profiles for participants depending on their individual well-being in each of these key areas. RESULTS: Psychological distress was the strongest predictor, with 25% of people with high distress reporting suicidal ideation. Within high psychological distress, lower physical functioning significantly increased the likelihood of suicidal ideation, with high distress and low functioning being associated with ideation in 50% of cases. A substantial subgroup reported suicidal ideation in the absence of psychological distress; dissatisfaction with social support was the most important predictor among this group. The performance of the model was high (area under the curve: 0.81). CONCLUSIONS: Decision tree modeling enabled individualized "risk" profiles for suicidal ideation to be determined. Although psychological factors are important for predicting suicidal ideation, both physical and social factors significantly improved the predictive ability of the model. Assessing these factors may enhance identification of older people at risk of suicidal ideation.

Self-reported contacts for mental health problems by rural residents: predicted service needs, facilitators and barriers.

BACKGROUND: Rural and remote Australians face a range of barriers to mental health care, potentially limiting the extent to which current services and support networks may provide assistance. This paper examines self-reported mental health problems and contacts during the last 12 months, and explores cross-sectional associations between potential facilitators/barriers and professional and non-professional help-seeking, while taking into account expected associations with socio-demographic and health-related factors. METHODS: During the 3-year follow-up of the Australian Rural Mental Health Study (ARMHS) a self-report survey was completed by adult rural residents (N = 1,231; 61% female; 77% married; 22% remote location; mean age = 59 years), which examined socio-demographic characteristics, current health status factors, predicted service needs, self-reported professional and non-professional contacts for mental health problems in the last 12 months, other aspects of help-seeking, and perceived barriers. RESULTS: Professional contacts for mental health problems were reported by 18% of the sample (including 14% reporting General Practitioner contacts), while non-professional contacts were reported by 16% (including 14% reporting discussions with family/friends). Perceived barriers to health care fell under the domains of structural (e.g., costs, distance), attitudinal (e.g., stigma concerns, confidentiality), and time commitments. Participants with 12-month mental health problems who reported their needs as met had the highest levels of service use. Hierarchical logistic regressions revealed a dose-response relationship between the level of predicted need and the likelihood of reporting professional and non-professional contacts, together with associations with socio-demographic characteristics (e.g., gender, relationships, and financial circumstances), suicidal ideation, and attitudinal factors, but not geographical remoteness. CONCLUSIONS: Rates of self-reported mental health problems were consistent with baseline findings, including higher rural contact rates with General Practitioners. Structural barriers displayed mixed associations with help-seeking, while attitudinal barriers were consistently associated with lower service contacts. Developing appropriate interventions that address perceptions of mental illness and attitudes towards help-seeking is likely to be vital in optimising treatment access and mental health outcomes in rural areas.

Feasibility of internet-delivered mental health treatments for rural populations.

PURPOSE: Rural populations face numerous barriers to mental health care. Although internet-delivered mental health treatments may offer an accessible and cost-effective answer to these barriers, there has been little evaluation of the feasibility of this approach among rural communities. METHODS: Data were obtained from a random rural community sample through the third wave of the Australian Rural Mental Health Study. Attitudes towards internet-delivered mental health treatments and availability of internet access were explored. Data were analysed to identify sub-groups in whom internet-delivered treatments may be usefully targeted. RESULTS: Twelve hundred and forty-six participants completed the survey (mean age 59 years, 61% females, 22% from remote areas). Overall, 75% had internet access and 20% would consider using internet-based interventions, with 18% meeting both of these feasibility criteria. Logistic regression revealed feasibility for internet-delivered mental health treatment was associated with younger age, male gender, being a carer, and a 12-month mental health problem. Participants who had used internet-delivered services in the past were significantly more likely to endorse these treatments as acceptable. CONCLUSIONS: There is considerable potential for internet-delivered treatments to increase service accessibility to some sub-groups, particularly among people with mental health problems who are not currently seeking help. Resistance to internet treatments appears to be largely attitudinal, suggesting that enhancing community education and familiarity with such programs may be effective in improving perceptions and ultimately access.

Development of a diagnostic support tool for predicting cervical arterial dissection in primary care.

OBJECTIVES: Cervical arterial dissection (CAD) is an important cause of stroke in young people which may be missed because early features may mimic migraine or a musculoskeletal presentation. The study aimed to develop a diagnostic support tool for early identification of CAD. DESIGN: Retrospective observational study. SETTING: Tertiary hospital. PARTICIPANTS: Radiologically confirmed CAD cases (n = 37), non-CAD stroke cases (n = 20), and healthy controls (n = 100). MAIN OUTCOME MEASURES: The presence of CAD is confirmed with imaging. Predictive variables included risk factors and clinical characteristics of CAD. Variables with a p-value <0.2 included in a multivariable model. Predictive utility of the model is assessed by calculating area underthe ROC curve (AUC). RESULTS: The model including four variables: age 40-55 years (vs < 40), trauma, recent onset headache, and > 2 neurological features, demonstrated excellent discrimination: AUC of 0.953 (95% CI: 0.916, 0.987). A predictive scoring system (total score/7) identified an optimal threshold of ≥ 3 points, with a sensitivity of 87% and specificity of 79%. CONCLUSIONS: The study identified a diagnostic support tool with four variables to predict increased risk of CAD. Validation in a clinical sample is needed to confirm variables and refine descriptors to enable clinicians to efficiently apply the tool.Optimum cutoff scores of ≥ 3/7 points will help identify those in whom CAD should be considered and further investigation instigated. The potential impact of the tool is to improve early recognition of CAD in those with acute headache or neck pain, thereby facilitating more timely medical intervention, preventing inappropriate treatment, and improving patient outcomes.Wordcount: 3195.

Exploring a Potential Interaction Between the Effect of Specific Maternal Smoking Patterns and Comorbid Antenatal Depression in Causing Postpartum Depression.

Purpose: To explore a potential interaction between the effect of specific maternal smoking patterns and the presence of antenatal depression, as independent exposures, in causing postpartum depression (PPD). Methods: This case-control study of participants with singleton term births (N = 51220) was based on data from the 2017-2018 Pregnancy Risk Assessment Monitoring System. Multivariable log-binomial regression models examined the main effects of smoking patterns and self-reported symptoms of antenatal depression on the risk of PPD on the adjusted risk ratio (aRR) scale and tested a two-way interaction adjusting for covariates selected in a directed acyclic graph (DAG). The interaction effects were measured on the additive scale using relative excess risk due to interaction (RERI), the attributable proportion of interaction (AP), and the synergy index (SI). Causal effects were defined in a counterfactual framework. The E-value quantified the potential impact of unobserved/unknown covariates, conditional on observed covariates. Results: Among 6841 women in the sample who self-reported PPD, 35.7% also reported symptoms of antenatal depression. Out of 3921 (7.7%) women who reported smoking during pregnancy, 32.6% smoked at high intensity (≥10 cigarettes/day) in all three trimesters and 36.6% had symptoms of antenatal depression. The main effect of PPD was the strongest for women who smoked at high intensity throughout pregnancy (aRR 1.65; 95% CI: 1.63, 1.68). A synergistic interaction was detected, and the effect of all maternal smoking patterns was augmented, particularly in late pregnancy for Increasers and Reducers. Conclusion: Strong associations and interaction effects between maternal smoking patterns and co-occurring antenatal depression support smoking prevention and cessation interventions during pregnancy to lower the likelihood of PPD.

Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits.

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10-8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10-126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10-44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10-34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.