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

BACKGROUND AIMS: Nitric oxide, a major inhibitory nonadrenergic, noncholinergic neurotransmitter that relaxes smooth muscle, may be implicated in the pathophysiology of visceral hypersensitivity in irritable bowel syndrome (IBS). Impaired bioavailability of the nitric oxide precursor molecule L-arginine and higher concentrations of methylarginines (endogenous inhibitors of nitric oxide synthesis) are known to impair nitric oxide synthesis in numerous gastrointestinal cell types. We therefore examined serum concentrations of L-arginine and the methylarginines in a nested case-control study, to assess whether these factors are associated with adult IBS.Data on clinical characteristics, methylarginines, and L-arginine (measured using LC-MS/MS) were collected from a random population-based cohort of Australian adults (median age = 64 years; IQR = 60-70). Cases of IBS, defined according to Rome III criteria (N = 156), and controls (N = 332) were identified from within the cohort at the 5-year follow-up.In adjusted logistic regression analyses, L-arginine, asymmetric dimethylarginine, symmetric dimethylarginine, L-arginine/asymmetric dimethylarginine ratio, and Kessler-10 psychological distress scores were significantly associated with IBS (p 0.05). [Correction added on 18 September 2021, after first online publication: In the preceding sentence, the value (p 0.05) has been changed to (p 0.05)]. Similar results were found for IBS subtypes. Higher serum L-arginine concentration had the strongest association with IBS diagnosis, with an odds ratio of 9.03 for those with serum L-arginine at the 75th (84 μmol/L) versus 25th (46 μmol/L) percentile (95% CI: 5.99-13.62). L-arginine had the best discriminative ability with a bias-adjusted area under the receiver operator characteristic curve of 0.859.Higher serum concentrations of L-arginine and endogenous methylarginines are strongly associated with IBS in adults.

OBJECTIVE: Irritable bowel syndrome (IBS) is a chronic disorder associated with an abnormal gastrointestinal microbiome. Microbiome-host interactions are known to influence organ function including in the central nervous system; thus, we sought to identify whether IBS may be a risk factor for the development of glaucoma.DESIGN: Two prospective cohort studies.SUBJECTS: The 1958 United Kingdom Birth Cohort (UKBC; 9091 individuals) and the Danish National Registry of Patients (DNRP; 62,541 individuals with IBS and 625,410 matched general population cohort members).METHODS: In the UKBC, participants were surveyed throughout life (including at ages 42 and 50). The DNRP contains records of hospital-based contacts and prescription data from the national prescription database.MAIN OUTCOME MEASURE: The main outcome measure was incidence of glaucoma. In the UKBC, incident glaucoma at age 50 (n = 48) was determined through comparison of survey responses at ages 42 and 50 years. In the DNRP, glaucoma was assessed by hospital diagnosis (n = 1510), glaucoma surgery (n = 582) and initiation of glaucoma medications (n = 1674).RESULTS: In the UKBC, the odds ratio (OR) of developing glaucoma between ages 42 and 50 in persons with a chronic IBS diagnosis was increased [OR: 5.84, 95% confidence interval (CI): 2.26-15.13]. People with an IBS diagnosis in the DNRP had a hazard ratio (HR) of 1.35 for developing physician-diagnosed glaucoma (95% CI: 1.16-1.56), an HR of 1.35 for undergoing glaucoma surgery (95% CI: 1.06-1.70) and an HR of 1.19 for initiating glaucoma medication (95% CI: 1.03-1.38).CONCLUSIONS: In two large European cohort studies, IBS is a risk factor for glaucoma.

Background Research in lifestyle interventions focusing on nutrition and physical activity in people living with psychotic illness, highlights anthropometric and metabolic benefits of these interventions. However, little is known about potential factors to consider during implementation into real-world contexts. Community-managed organisations (CMOs) that provide services for people with mental illness, offer an ideal implementation context for lifestyle interventions. Successful translation of lifestyle interventions into CMOs may be achieved though considering the factors associated with program access and delivery in these settings. This study primarily aimed to identify the factors that affect program access in a local CMO from the perspective of consumers and staff. The secondary aim was to describe the elements that impact on program delivery from the perspective of staff. Methods Thirteen semi-structured interviews were conducted with 6 consumers and 7 staff in a CMO in regional Australia. Topics explored in interviews were based on implementation concepts identified in the “Integrated Promoting Action on Research Implementation in Health Systems” (i-PARIHS) knowledge translation framework. Thematic data analysis was conducted using Nvivo software. Results Emergent themes on issues that influenced program access were (1) consumer financial status, domestic responsibilities, and health; (2) the design and delivery of programs; (3) structure and practices of the organisation; (4) attitude, skills and effort of staff involved in program delivery; and (5) social connections and stigma experienced by consumers during program access. Moreover, staff perceptions on elements that impacted program delivery highlighted themes on consumer attendance and interest in prospective programs, availability and restrictions to the use of funding, as well as the organisational structure and practices. Conclusions The factors affecting program access and delivery can generally be managed or planned for during the design of lifestyle interventions and subsequent translation into the CMO context. However, resolution of issues related to consumer financial status and health requires the collaboration of various government sectors for system-wide solutions.

Objectives Supporting healthy ageing is a key priority worldwide. Physical activity, diet quality and sleep are all associated with health outcomes, but few studies have explored their independent associations with all-cause mortality in an older population in the same model. The study aim was to examine associations between step-count, self-reported diet quality, restless sleep, and all-cause mortality in adults aged 55–85 years. Design A prospective cohort study of adults in Newcastle, New South Wales, Australia. Method Data were from 1697 participants (49.3% women; baseline mean age 65.4 ± 7.1 years). Daily steps (measured by pedometer), diet quality (from a modified Australian Recommended Food Score), and frequency of restless sleep (by self-report) were assessed in relation to all-cause mortality using Cox proportional hazard regression with adjustment for sex, age, household income and smoking. Baseline data were collected between January 2005 and April 2008, and last follow-up was in March 2017 (median follow-up 9.6 years). Results Higher step count (HR: 0.93, 95%CI: 0.88–0.98 per 1000-step increment) and higher diet quality (HR: 0.86, 95%CI: 0.74–0.99 per 8-point increment in diet quality score) were associated with reduced mortality risk. Restless sleep for ≥3 nights/week was not associated with mortality risk (HR: 1.03, 95%CI: 0.78–1.39). Sensitivity analyses, adjusting for chronic disease and excluding deaths Conclusions Increased daily steps and consumption of a greater variety of nutrient-dense foods every week would result in substantial health benefits for older people. Future research should include a greater variety of sleep measures.

OBJECTIVES: Previous research has investigated whether the apolipoprotein E (APOE) e4 allele, which is associated with an increased risk of cognitive decline, is also associated with hearing loss in older people. Results of the very limited research to date are conflicting, and sample sizes for all but one study were small. The present study aimed to investigate whether there is an association between the APOE e4 allele and hearing loss in a large, population-based sample of community-dwelling older adults. DESIGN: Cross-sectional audiometric data on hearing levels and APOE genotypes for 2006 participants (aged 55 to 85 years) of the Hunter Community Study were analyzed using multiple linear regression to examine the association between APOE e4 carrier status and the 4-frequency pure-tone average (0.5 to 4 kHz) in the better hearing ear, and also across individual frequencies in the better ear. RESULTS: Observed and expected APOE allele frequency distributions did not differ significantly overall from established general population allele frequency distributions. Unadjusted modeling using better ear pure-tone average showed a statistically significant association between APOE e4 allele status (0, 1, 2 copies) and reduced hearing loss, but when the model was adjusted for age, this was no longer statistically significant. Across individual hearing frequencies, unadjusted regression modeling showed APOE e4 status was significantly associated with a reduction in mean hearing thresholds at 1 and 2 kHz, but again this effect was no longer statistically significant after adjusting for age. CONCLUSIONS: The results of this study did not provide any evidence of a statistically significant association between APOE e4 allele status and hearing loss for older adults. Further investigation of the effect of homozygous carrier status on hearing thresholds is required.

Background The efficacy of antibiotics in appendicitis remains controversial, and physicians are not confident in prescribing antibiotics as the first line treatment. This network meta-analysis was conducted to assess the efficacy and safety of individual antibiotics in uncomplicated appendicitis. Methods Randomized controlled trials (RCTs) were identified from MEDLINE and SCOPUS databases since inception to July 2017. Studies. Network meta-analysis was applied to estimate treatment effects and safety. Probability of being the best treatment was estimated using surface under the cumulative ranking curve (SUCRA). Results Among 9 RCTs meeting our inclusion criteria. A network meta-analysis indicated that those receiving antibiotics had about 12–32% lower chance of treatment success and lower risk of complication about 23–86%, especially Beta-lactamase than appendectomy. The overall appendicitis recurrence rate in the antibiotic group was about 18.2%. The SUCRA indicated that appendectomy was ranked first for treatment success and least complications, followed by Beta-lactamase. Conclusions Appendectomy is still the most effective treatment in uncomplicated appendicitis but it carries complications. Beta-lactamase, might be an alternative treatment if there are any contraindications for operation.

© 2019 AMPCo Pty Ltd 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.

The consumption of nitrate-rich vegetables can acutely lower blood pressure and improve mediators shown to optimise vascular health. However, we do not yet understand the impact of long-term habitual dietary nitrate intake and its association with CVD. Therefore, the aim of this investigation was to examine the relationship between habitual dietary nitrate intakes and risk of CHD in women from the Nurses’ Health Study. We prospectively followed 62 535 women who were free from diabetes, CVD and cancer at baseline in 1986. Information on diet was updated every 4 years with validated FFQ. The main outcome was CHD defined by the occurrence of non-fatal myocardial infarction or fatal CHD. Cox proportional hazard regression models were used to estimate the relative risks (RR) and 95 % CI. During 26 years of follow-up, 2257 cases of CHD were identified. When comparing the highest quintile of nitrate intake with the lowest quintile, in aged-adjusted analysis there was a protective association for CHD (RR=0·77, 95 % CI 0·68, 0·97; P=0·0002) which dissipated after further adjustment for smoking, physical activity, BMI and race (RR=0·91; 95 % CI 0·80, 1·04; P=0·27). This magnitude of association was further attenuated once we adjusted for the Alternative Healthy Eating Index excluding vegetable and fruit consumption (RR=1·04, 95 % CI 0·91, 1·20; P=0·34). Dietary nitrate intake was not related to the risk of CHD after adjustment for other lifestyle and non-vegetable dietary factors in a large group of US women.

Measures of lung function are heritable, and thus, we sought to utilise genetics to propose drug-repurposing candidates that could improve respiratory outcomes. Lung function measures were found to be genetically correlated with seven druggable biochemical traits, with further evidence of a causal relationship between increased fasting glucose and diminished lung function. Moreover, we developed polygenic scores for lung function specifically within pathways with known drug targets and investigated their relationship with pulmonary phenotypes and gene expression in independent cohorts to prioritise individuals who may benefit from particular drug-repurposing opportunities. A transcriptome-wide association study (TWAS) of lung function was then performed which identified several drug–gene interactions with predicted lung function increasing modes of action. Drugs that regulate blood glucose were uncovered through both polygenic scoring and TWAS methodologies. In summary, we provided genetic justification for a number of novel drug-repurposing opportunities that could improve lung function., eLife digest Chronic respiratory disorders like asthma affect around 600 million people worldwide. Although these illnesses are widespread, they can have several different underlying causes, making them difficult to treat. Drugs that work well on one type of respiratory disorder may be completely ineffective on another. Understanding the biological and environmental factors that cause these illnesses will allow them to be treated more effectively by tailoring therapies to each patient. Reduced lung function is a factor in respiratory disorders and it can have many genetic causes. Studying the genes of patients with reduced lung function can reveal the genes involved, some of which may already be targets of existing drugs for other illnesses. So, could a patient’s genetics be used to repurpose existing drugs to treat their respiratory disorders? Reay et al. combined three methods to link genetics and biological processes to the causes of reduced lung function. The results reveal several factors that could lead to new treatments. In one example, reduced lung function showed a link to genes associated with high blood sugar. As such, treatments used in diabetes might help improve lung function in some patients. Reay et al. also developed a scoring system that could predict the efficacy of a treatment based on a patient’s genetics. The study suggests that COVID-19 infection could be affected by blood sugar levels too. Chronic respiratory disorders are a critical issue worldwide and have proven difficult to treat, but these results suggest a way to identify new therapies and target them to the right patients. The findings also support a connection between lung function and blood sugar levels. This implies that perhaps existing diabetes treatments – including diet and lifestyle changes aimed at reducing or limiting blood sugar – could be repurposed to treat respiratory disorders in some patients. The next step will be to perform clinical trials to test whether these therapies are in fact effective.

There is a lack of evidence to determine if diet quality is associated with cognitive performance in older adults. Therefore, the aim of this study was to examine whether diet quality is associated with cognitive performance among older adults. A cross-sectional, secondary analysis of baseline data from the Hunter Community Study (HCS), comparing diet quality, measured using the Australian Recommended Food Score (ARFS), along with validated cognitive performance instruments the Audio Recorded Cognitive Screen (ARCS) and the Mini-Mental State Examination (MMSE) were undertaken in adults aged 55–85 years, living in Newcastle, NSW, Australia. Adjusted linear regression analyses showed that, compared with the lowest ARFS quintile, those in the highest quintile had an ARCS score 5.883 units greater (p &lt, 0.001, R2 = 0.0098). Furthermore, when quintiles of ARFS score were tested against each ARCS sub-scale score, statistically significant associations were observed with the greatest effect for the Memory (β = 4.055, p = 0.001, R2 = 0.0065) and Attention (β = 4.136, p = 0.002, R2 = 0.0047) domains. No statistically significant associations were observed between quintiles of ARFS and MMSE score in the adjusted linear regression analyses. In conclusion, a positive association was observed between diet quality and cognitive performance within this sample of older Australian adults. Further investigation of the above association over time, when follow-up data becomes available, in longitudinal analysis is recommended.

Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two-sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels (P

This review examined the risk of cardiovascular disease in adults with metabolically healthy overweight/obesity. A systematic review and meta-analysis using data from Medline, EMBASE, SCOPUS and Cochrane Library searched from inception up to 31st October 2019. We included prospective cohort studies of adults who are metabolically healthy or unhealthy. Outcomes were fatal and nonfatal cardiovascular events, all-cause mortality. Pooled relative risk was calculated for each outcome in populations with metabolically healthy overweight and metabolically healthy obesity using metabolically healthy normal weight as reference. A random-effects model was used for meta-analysis, and risk of bias assessment tool for nonrandomized studies assessed risk of bias within each study. Twenty-three prospective cohort studies with 4,492,723 participants were included. Cardiovascular disease risk was increased in metabolically healthy groups with overweight (RR = 1.34, CI: 1.23-1.46, n = 20, I2 = 90.3%) and obesity (RR = 1.58, CI: 1.34-1.85, n = 21, I2 = 92.2) compared with a reference group with metabolically healthy normal weight. Cardiovascular disease risk was similar irrespective of the number of risk factors used to define metabolically healthy and the risk remained in the group with no metabolic risk factors. Cardiovascular disease risk is increased in populations with overweight and obesity classified as metabolically healthy even when there were no metabolic risk factors.

Background Laparoscopic appendectomy (LA) has been popular for decades because of shorter hospitalization and return to routine activity. However, complications (e.g., surgical site infection [SSI] and intra-abdominal abscess [IAA]) relative to open appendectomy (OA) are still debated. We therefore conducted an umbrella review to systematically appraise meta-analyses (MAs) comparing SSI and IAA between LA and OA. Methods Meta-analyses that included only randomized controlled trials were identified from MEDLINE and Scopus databases from inception until July 2018. Their findings were described, the number of overlapping studies was assessed using corrected covered area, and excess significant tests were also assessed. Finally, effect sizes of SSI and IAA were repooled. Results Ten MAs were eligible; SSI was reported in all MAs and IAA in 8 MAs. Surgical site infection rate was 48% to 70% lower in LA than OA, but conversely, IAA rate was 1.34 to 2.20 higher in LA than OA. Overlapping included studies for SSI and IAA were 61% and 54%, respectively, indicating that less information was added across MAs. However, there was no evidence of bias from excess significant tests when pooling SSI or IAA estimates. The risk ratios (95% confidence interval) comparing LA versus OA were repooled in adults and children yielding risk ratios of 0.56 (0.47-0.67) and 0.40 (0.25-0.65) for SSI, and 1.20 (0.88-1.63) and 1.05 (0.61-1.80) for IAA. Conclusion Evidence from this umbrella review indicates that LA carries a significantly lower risk of SSI but likely a higher risk of IAA than OA. Level of evidence Systematic review/meta-analysis, level I.

Impaired lung function is associated with significant morbidity and mortality. Restrictive and obstructive lung disorders are a large contributor to decreased lung function, as well as the acute impact of infection. Measures of pulmonary function are heritable, and thus, we sought to utilise genomics to propose novel drug repurposing candidates which could improve respiratory outcomes. Lung function measures were found to be genetically correlated with metabolic and hormone traits which could be pharmacologically modulated, with a causal effect of increased fasting glucose on diminished lung function supported by latent causal variable models and Mendelian randomisation. We developed polygenic scores for lung function specifically within pathways with known drug targets to prioritise individuals who may benefit from particular drug repurposing opportunities, accompanied by transcriptome-wide association studies to identify drug-gene interactions with potential lung function increasing modes of action. These drug repurposing candidates were further considered relative to the host-viral interactome of three viruses with associated respiratory pathology (SARS-CoV2, influenza, and human adenovirus). We uncovered an enrichment amongst glycaemic pathways of human proteins which putatively interact with virally expressed SARS-CoV2 proteins, suggesting that antihyperglycaemic agents may have a positive effect both on lung function and SARS-CoV2 progression.

BackgroundBody mass index (BMI), uric acid (UA) diabetes mellitus (DM) and hypertension (HT) are known risk factors of declined kidney function, and are associated with fetuin-A. However, the causal pathways of these associations are unclear. We therefore used cohort data to explore possible causal pathways of fetuin-A and kidney function. MethodologyWe used data of the Electricity Generating Authority of Thailand cohort 2009 (n= 2305). A causal pathway was constructed, which considered fetuin-A as study factor, BMI, UA, DM, and HT as mediators, and eGFR as the outcome. A generalized-structural equation model (GSEM) with 1000-replication bootstrapping was applied to assess the causal effects adjusting for covariates. ResultsThe fetuin-A → eGFR pathway showed a direct association of fetuin-A on eGFR with the coefficient of -0.0072 (95% CI: -0.0119, -0.0025). In addition, the indirect effects of fetuin-A→ BMI → eGFR was also significant with the coefficient of 0.00086 (0.00025, 0.0016; implying that every one unit of BMI increased, resulting from increasing fetuin-A, would significantly increase eGFR 0.00086 (0.00025, 0.0016) mL/min/1.73m2. There was a negative effect of fetuin-A on eGFR through BMI and UA pathway (Fetuin-A→BMI→UA→eGFR ) as well as the HT pathway (Fetuin-A→BMI→HT→eGFR ) with average casual mediation effects (ACME) of -0.00132 (-0.00177, -0.00092) and -0.00139 (-0.00237, -0.00069). Fetuin-AàDMàHTàeGFR was also statistically significant with the ACME of -0.00223 (-0.00535, -0.00066).ConclusionOur study has shed some light on the possible role of fetuin-A in the etiology of declining renal function through the mediatory roles of BMI, UA, DM and HT in the various complex causal pathways leading to declining kidney function in our study cohort. Further studies are however recommended to examine the pathomechanisms involved in the mediational processes of these studied risk factors in the etiology of declining kidney function.

BackgroundPeanut allergy affects 3% of Australian children and has a higher risk of anaphylaxis than most food allergies. Predicting who is likely to develop anaphylaxis is still an inexact science. The fraction of exhaled nitric oxide (FeNO) shows promise as a biomarker involved in peanut allergy, as nitric oxide plays a role in inhibiting mast cell degranulation which is relevant in anaphylaxis, where mast cell degranulation plays a mediator role. The aim of this study was to assess the change in FeNO in children during peanut challenge.MethodsThirty-six children aged from 5 to 17 years were recruited for open-labelled peanut challenge. Participants had skin prick test to peanut performed, and serum collected for Ara h2 specific IgE and peanut specific IgE. FeNO was measured by portable device (NIOX VERO) prior to and throughout the peanut challenge.ResultsWhen grouped according to reaction type at peanut challenge (anaphylaxis, clinical allergy not anaphylaxis and tolerant), there were significant differences in the mean change in FeNO measurement between the anaphylaxis group and the clinical allergy, not anaphylaxis group (p = 0.005), and between the anaphylaxis group and tolerant group (p ConclusionsFeNO decreased more significantly in those who subsequently developed anaphylaxis than in those with clinical allergy, not anaphylaxis or negative peanut challenge (tolerance). As a bedside test that can be used in children, it has potential for further research into mechanisms of anaphylaxis in food allergy and potentially assists in predicting an imminent anaphylactic reaction in some patients.Trial registrationClinicalTrials.gov: PEAnut Anaphylaxis Predictors (PEAAP) NCT02424136.

Objective. This systematic review aimed to measure the association between neutrophil lymphocyte ratio (NLR) and cardiovascular disease (CVD) risk. Methods. Relevant studies were identified from Medline and Scopus databases. Observational studies with NLR as a study factor were eligible for review. The outcomes of interest were any type of CVD including acute coronary syndrome, coronary artery disease, stroke, or a composite of these cardiovascular events. Mean differences in NLR between CVD and non-CVD patients were pooled using unstandardized mean difference (USMD). Odds ratios of CVD between high and low NLR groups were pooled using a random effects model. Results. Thirty-eight studies (n=76,002) were included. High NLR was significantly associated with the risks of CAD, ACS, stroke, and composite cardiovascular events with pooled ORs of 1.62 (95% CI: 1.38-1.91), 1.64 (95% CI: 1.30, 2.05), 2.36 (95% CI: 1.44, 2.89), and 3.86 (95% CI: 1.73, 8.64), respectively. In addition, mean NLRs in CAD, ACS, and stroke patients were significantly higher than in control groups. Conclusion. High NLR was associated with CAD, ACS, stroke, and composite cardiovascular events. Therefore, NLR may be a useful CVD biomarker.

Background People with psychosis die on average 25 years earlier than those in the general population, with cardiovascular disease (CVD) contributing to much of the excess mortality. This cross-sectional study aimed to identify the relationship between lifestyle risk factors for CVD – poor nutrition, smoking and low physical activity levels – and dyslipidaemia, hypertension and hyperglycaemia while controlling for potential confounders in 1825 people from the Survey of High Impact Psychosis (SHIP) in Australia. We also aimed to identify clustering patterns of lifestyle risk factors and associated demographic variables. Methods Three logistic regressions were used to predict the effect of nutrition, smoking and physical activity on dyslipidaemia, hypertension and hyperglycaemia while controlling for clozapine use, sex and age. Clustering patterns of nutrition, smoking and physical activity were examined using the two-step cluster method which is based on hierarchical cluster analysis. Demographic variables associated with different clusters were identified using measures of association. Results Smoking status had a positive association with dyslipidaemia (adjusted odds ratio = 0.50; 95% confidence interval = 0.32–0.78; p = 0.002). Other cardiovascular disease lifestyle risk factors did not have a significant relationship with dyslipidaemia, hypertension and hyperglycaemia. Clustering patterns of lifestyle risk factors showed that younger men, with low education levels, and relying on a government pension, were most likely to display the poorest lifestyle risk behaviours. The largest cluster (42%) of participants was characterised by a mixed demographic profile and were most likely to display poor nutrition and low physical activity levels but less likely to smoke. Conclusions Only smoking status had a significant positive association with dyslipidaemia which could indicate that there are additional factors affecting the relationship between other cardiovascular lifestyle risk factors and dyslipidaemia, hypertension and hyperglycaemia in people with psychosis. Unknown confounders and traditional lifestyle risk factors may explain the high rates of CVD in this group. Clustering of lifestyle risk factors and their demographic profiles could help the design of intervention programs in people with psychosis.

Objective Age-related hearing loss is associated with endothelial dysfunction and increased cardiovascular risk, suggesting a vascular etiology. Methylarginines are endogenous nitric oxide synthase inhibitors that cause endothelial dysfunction and increase cardiovascular disease risk. This study is the first to examine the hypothesis that higher serum concentrations of methylarginines are associated with greater hearing loss prevalence. Study design/patients Cross-sectional audiometric data on hearing levels, and serum methylarginines were collected from a population-based sample of 630 older community-dwelling adults. Results Linear regression analysis showed a statistically significant association between higher serum concentrations of asymmetric dimethylarginine (ADMA) and L-arginine and greater degrees of hearing loss for males, particularly over 75 years. Higher body mass index and previous history of stroke were also associated with hearing loss. For females, ADMA concentration was not associated with hearing loss, but higher serum L-arginine concentrations were associated with reduced hearing loss prevalence in older females. Antihypertensive medication use was also associated with reduced hearing loss prevalence. LDL cholesterol and previous myocardial infarction were associated with greater hearing loss. Conclusion This study showed a significant association between serum concentrations of ADMA and hearing loss for males, consistent with the association between endothelial dysfunction and hearing loss. The opposite effect of L-arginine on hearing loss in males versus females might reflect a different role of this precursor toward nitric oxide versus methylated arginines synthesis. These findings are potentially clinically significant if the association between ADMA and hearing loss is causal, as serum methylarginine levels are modifiable through pharmacotherapeutic/lifestyle interventions.

Context Depleted nitric oxide levels in the human body play a major role in cardiovascular disease pathogenesis. Inorganic nitrate/nitrite (rich dietary sources include beetroot and spinach) can act as a nitric oxide donor because nitrate/nitrite can be metabolized to produce nitric oxide. Objective This review and meta-analysis sought to investigate the role of inorganic nitrate/nitrite in preventing or treating cardiovascular disease risk factors in humans. Data Sources Electronic databases, including Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane, and Scopus, were searched. Data Extraction Experimental trials examining the effect of oral inorganic nitrate/nitrite intake on cardiovascular disease risk factors were included for systematic analysis. Results Thirty-four studies were included for qualitative synthesis, 23 of which were eligible for meta-analysis. Included studies measured the following outcomes: blood pressure, endothelial function, arterial stiffness, platelet aggregation, and/or blood lipids. Inorganic nitrate intake was found to significantly reduce resting blood pressure (systolic blood pressure: -4.80 mmHg, P

IntroductionThe COVID-19 pandemic is creating immense psychosocial disturbance. While global, broad-based research is being conducted, little is known about the effects of the COVID-19 pandemic on health and well-being or how protective and resilience factors influence the human response in Australian rural and regional communities. Rural and regional communities often have less resources to deal with such public health emergencies and face additional environmental adversity. Healthcare workers, including those in rural and regional areas, have felt the immediate impacts of COVID-19 in a multitude of ways and these impacts will continue for years to come. Therefore, this study aims to describe and understand the impacts of the COVID-19 pandemic on the rural and regional healthcare workforce within the Loddon Mallee region, Victoria, Australia.Methods and analysisThis prospective cohort of rural and regional healthcare workers will be recruited and followed over 3 years to examine the effects of the COVID-19 pandemic on their health and well-being. Self-administered online questionnaires will be administered every 6 months for a 36-month period. Multiple outcomes will be assessed; however, the primary outcomes are emotional health and well-being and psychological resilience. Emotional health and well-being will be measured using validated instruments that will assess multiple domains of the emotional health and well-being continuum.Linear and logistic regression and latent growth curve modelling will be used to examine the association between baseline and follow-up participant emotional health, well-being and resilience while adjusting for potentially time-varying confounding variables. Participant characteristics measured at baseline will also be tested for association with incident health, morbidity, mortality and health service utilisation outcomes at follow-up.Ethics and disseminationEthical approval has been obtained through the Bendigo Health Human Research Ethics Committee. The study findings will be disseminated through international conferences, international peer-reviewed journals and social media.Trial registration numberACTRN12620001269921.

The last two decades have marked a growing understanding of the interaction occurring between bone and immune cells. The chronic inflammation and immune system dysfunction commonly observed to occur during the ageing process and as part of a range of other pathological conditions, commonly associated with osteoporosis has led to the recognition of these processes as important determinants of bone disease. This is further supported by the recognition that the immune and bone systems in fact share regulatory mechanisms and progenitor molecules. Research into this complex synergy has provided a better understanding of the immunopathogenesis underlying bone diseases such as osteoporosis. However, existing research has largely focussed on delineating the role played by inflammation in pathogenic bone destruction, despite increasing evidence implicating autoantibodies as important drivers of osteoporosis. This review shall attempt to provide a comprehensive overview of existing research examining the role played by autoantibodies in osteoporosis in order to determine the potential for further research in this area. Autoantibodies represent promising targets for the improved treatment and diagnosis of inflammatory bone loss., Highlights • Immune and bone systems recognised to share regulatory mechanisms and progenitor molecules. • Osteoclasts and osteoblasts are continuously controlled by a variety of cells of the immune system. • Altered bone composition often observed to occur alongside diseases characterised by immune dysfunction. • Immune disturbance linked to pathogenic bone loss through the action of inflammatory markers and autoantibodies.

Background and aims Despite worldwide reductions in active smoking, non-smokers continue to be exposed to environmental tobacco smoke, especially at home or workplace. There is a well-recognised association between active smoking and peripheral arterial disease, however, a relationship to environmental tobacco smoke exposure is less substantiated. The aims of this paper are to review the literature regarding the association between environmental tobacco smoke and peripheral arterial disease and identify the public health implications of the findings. Methods Selected electronic databases (Medline, EMBASE, CINAHL, PsychINFO and Scopus) were searched for studies published up to August 2017. Key words and inclusion/exclusion criteria applied. A manual search of reference lists of studies selected for review was also performed. Results Of the initial 150 studies identified, 12 met inclusion criteria for review. Three studies showed a positive association between environmental tobacco smoke exposure and definitive diagnosis of peripheral arterial disease, 6 studies demonstrated a positive association with features of vascular injury, and 3 studies found no significant positive or negative association. Conclusions An association between exposure to environmental tobacco smoke and development of peripheral arterial disease or clinically significant arterial injury in non-smokers is supported by moderate quality evidence in the literature. Larger, longitudinal observational studies addressing current limitations, including sources of bias, inconsistency and imprecision, are needed to provide more robust and consistent evidence. Regardless, evidence of potential detrimental impacts supports ongoing restrictions on freedom to smoke in public areas, including the workplace, and has implications for those exposed in the home environment.

An increased risk of cardiovascular disease (CVD) has long been recognized amongst people with autoimmune disease. It has been unclear whether this is due mainly to the ensuing treatment, particularly steroids, or whether some of this risk is due to the autoimmune process itself with subsequent inflammation. Indeed, a large body of evidence supports a role for chronic inflammation in atherogenesis, and autoantibodies have been identified as mediators in this complex inflammatory environment. Our aim is to carry out a systematic review of existing literature in order to formally establish the strength of the association between autoantibodies and atherosclerosis, amongst individuals without clinical autoimmune disease. An electronic search of five databases to June 2016 was performed by two independent reviewers. Inclusion criteria were analytical studies of adults, with at least two studies per autoantibody. Quality analysis was carried out using the Newcastle-Ottawa scale and the Cochrane Risk of Bias Quality Assessment Tool where appropriate. Where possible, studies were pooled using random effects models. Raised levels of anti-cardiolipin (odds ratio [OR] = 1.30; 95% CI: 1.15-1.49) and anti-oxidized low-density lipoprotein Immunoglobulin (Ig) G (OR = 1.25; 95% CI: 1.11-1.41), unspecified anti-cyclic citrullinated protein (OR = 3.09; 95% CI: 1.49-6.41) and anti-human heat shock protein 60 IgA (OR = 1.57; 95% CI: 1.15-2.16) were observed to increase the risk of cardiovascular outcomes. Alternatively, Anti-phosphorylcholine IgM (OR = 1.31; 95% CI: 1.14-1.50) conferred protection against CVD. Our results support an important role for autoantibodies in mediating cardiovascular events, independent of therapeutic treatments. Future research may focus on the presence of autoantibodies as markers of immune dysregulation and CVD risk.

Background First‐generation cephalosporins (such as cefazolin) are recommended as antibiotic prophylaxis in groin hernia repair, but other broad‐spectrum antibiotics have also been prescribed in clinical practice. This was a systematic review and network meta‐analysis to compare the efficacy of different antibiotic classes for prevention of surgical‐site infection (SSI) after hernia repair. Methods RCTs were identified that compared efficacy of antibiotic prophylaxis on SSI after inguinal or femoral hernia repair from PubMed and Scopus databases up to March 2016. Data were extracted independently by two reviewers. Network meta‐analysis was applied to assess treatment efficacy. The probability of being the best antibiotic prophylaxis was estimated using surface under the cumulative ranking curve (SUCRA) analysis. Results Fifteen RCTs (5159 patients) met the inclusion criteria. Interventions were first‐generation (7 RCTs, 1237 patients) and second‐generation (2 RCTs, 532) cephalosporins, β‐lactam/β‐lactamase inhibitors (6 RCTs, 619) and fluoroquinolones (2 RCTs, 581), with placebo as the most common comparator (14 RCTs, 2190). A network meta‐analysis showed that β‐lactam/β‐lactamase inhibitors and first‐generation cephalosporins were significantly superior to placebo, with a pooled risk ratio of 0·44 (95 per cent c.i. 0·25 to 0·75) and 0·62 (0·42 to 0·92) respectively. However, none of the antibiotic classes was significantly different from the others. SUCRA results indicated that β‐lactam/β‐lactamase inhibitors and first‐generation cephalosporins were ranked first and second respectively for best prophylaxis. Conclusion β‐Lactam/β‐lactamase inhibitors followed by first‐generation cephalosporins ranked as the most effective SSI prophylaxis for adult patients undergoing groin hernia repair., Best antibiotic for hernia repair

Context Long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFAs) are widely considered as nootropic agents that may be beneficial in reversing cognitive impairment. Objective The present systematic review of randomized controlled trials was conducted to determine the changes in cognitive function after intervention with LCn-3PUFA supplementation in non-demented adults, including those with mild cognitive impairment. Data Sources Five databases (MEDLINE, CINAHL, Scopus, EMBASE, and the Cochrane Library) were searched systematically along with reference lists of selected articles. Study Selection Studies were eligible for inclusion if they measured the effect of LCn-3PUFA supplementation on cognition in non-demented adults. Data Extraction A total of 787 records were screened, of which 25 studies were eligible for inclusion. Treatment effects were summarized as global cognitive function for primary outcome and measured using the Mini-Mental State Examination and individual cognitive domains for secondary outcome. The pooled effect sizes were estimated using Hedge’s g and random-effects modeling. Data Analysis Results from randomized controlled trials indicate that LCn-3PUFAs have no effect on global cognitive function (Hedge’s g = 0.02; 95% confidence interval, −0.12 to 0.154), and among the specific cognitive domains, only memory function showed a mild benefit (Hedge’s g = 0.31; P = 0.003; z = 2.945). Conclusion The existing literature suggests that LCn-3PUFA supplementation could provide a mild benefit in improving memory function in non-demented older adults. Systematic Review Registration PROSPERO registration no. CRD42017078664.

ObjectivesTo conduct a systematic review and meta-analysis and to pool the incremental net benefits (INBs) of glucagon-like peptide 1 (GLP1) compared with other therapies in type 2 diabetes mellitus (T2DM) after metformin monotherapy failure.Research design and methodsThe study design is a systematic review and meta-analysis. We searched MEDLINE (via PubMed), Scopus and Tufts Registry for eligible cost–utility studies up to June 2018, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We conducted a systematic review and pooled the INBs of GLP1s compared with other therapies in T2DM after metformin monotherapy failure. Various monetary units were converted to purchasing power parity, adjusted to 2017 US$. The INBs were calculated and then pooled across studies, stratified by level of country income; a random-effects model was used if heterogeneity was present, and a fixed-effects model if it was absent. Heterogeneity was assessed using Q test and I2statistic.ResultsA total of 56 studies were eligible, mainly from high-income countries (HICs). The pooled INBs of GLP1s compared with dipeptidyl peptidase-4 inhibitor (DPP4i) (n=10), sulfonylureas (n=6), thiazolidinedione (TZD) (n=3), and insulin (n=23) from HICs were US$4012.21 (95% CI US$−571.43 to US$8595.84, I2=0%), US$3857.34 (95% CI US$−7293.93 to US$15 008.61, I2=45.9%), US$37 577.74 (95% CI US$−649.02 to US$75 804.50, I2=92.4%) and US$14 062.42 (95% CI US$8168.69 to US$19 956.15, I2=86.4%), respectively. GLP1s were statistically significantly cost-effective compared with insulins, but not compared with DPP4i, sulfonylureas, and TZDs. Among GLP1s, liraglutide was more cost-effective compared with lixisenatide, but not compared with exenatide, with corresponding pooled INBs of US$4555.09 (95% CI US$3992.60 to US$5117.59, I2=0) and US$728.46 (95% CI US$−1436.14 to US$2893.07, I2=0), respectively.ConclusionGLP1 agonists are a cost-effective choice compared with insulins, but not compared with DPP4i, sulfonylureas and TZDs.PROSPERO registration numberCRD42018105193.

Objective:To explore if better diet quality scores as a measure of adherence to the Australian Dietary Guidelines (ADG) and the Mediterranean diet (MedDiet) are associated with a lower incidence of hypertension and non-fatal CVD.Design:Prospective analysis of the 1946–1951 cohort of the Australian Longitudinal Study on Women’s Health (ALSWH). The Australian Recommended Foods Score (ARFS) was calculated as an indicator of adherence to the ADG; the Mediterranean Diet Score (MDS) measured adherence to the MedDiet. Outcomes included hypertension and non-fatal CVD. Generalised estimating equations estimated OR and 95 % CI across quartiles of diet quality scores.Setting:Australia, 2001–2016.Participants:1946–1951 cohort of the ALSWH (n 5324), without CVD, hypertension and diabetes at baseline (2001), with complete FFQ data.Results:There were 1342 new cases of hypertension and 629 new cases of non-fatal CVD over 15 years of follow-up. Multivariate analysis indicated that women reporting better adherence to the ARFS (≥38/74) had 15 % (95 % CI 1, 28 %; P = 0·05) lower odds of hypertension and 46 % (95 % CI 6, 66 %; P = 0·1) lower odds of non-fatal CVD. Women reporting better adherence to the MDS (≥8/17) had 27 % (95 % CI 15, 47 %; P = 0·0006) lower odds of hypertension and 30 % (95 % CI 2, 50 %; P = 0·03) lower odds of non-fatal CVD.Conclusions:Better adherence to diet quality scores is associated with lower risk of hypertension and non-fatal CVD. These results support the need for updated evidenced based on the ADG as well as public health nutrition policies in Australia.

The objective of this review was to pool and rank the efficacy of lifestyle intervention strategies targeting weight, body mass index, waist circumference and waist-to-hip ratio in people with psychosis by comparing the effect size of these weight outcomes. Secondary to this, the objective was to stratify the lifestyle interventions according to their inclusion of dietary information that adheres to Australian Dietary Guidelines.People living with psychosis have a significantly increased risk of all-cause mortality, with cardiovascular disease a considerable contributor to this risk. Controlling lifestyle risk factors, which include smoking, poor diet and inadequate physical activity, leads to significant weight reduction and decreases cardiovascular disease risk. Previous reviews on this topic have not clearly identified essential components of lifestyle interventions in people with psychosis, mainly due to statistical limitations of analyses. This review employed a network meta-analysis, which compares more than two groups of interventions and ranks them according to efficacy, thus providing a global estimate of effect. Additionally, available reviews have not assessed compliance of dietary information offered in lifestyle interventions to established guidelines.This review considered randomized controlled trials that delivered lifestyle interventions to community-dwelling adults with psychotic disorders. Outcomes of interest included weight, body mass index, waist circumference and waist-to-hip ratio.The Cochrane Library, MEDLINE/PreMEDLINE, Embase, CINAHL, Scopus and PsycINFO were searched for studies published in English from 1985 to June 2018. Data were qualitatively summarized, during which lifestyle intervention subgroups were created (based on key similarities) and then compared in direct meta-analyses and network meta-analyses. Assessment of study adherence to Australian Dietary Guidelines was conducted in a narrative format.Thirty-two randomized controlled trials were included, and the overall quality of these studies ranged from what appeared to be low to moderate. Lifestyle intervention studies contained both a dietary and physical activity component, with the exception of two studies that focused solely on physical activity. Delivery of dietary and physical activity information was mainly through education; however, some studies provided additional structure to the intervention by offering tailored advice or helping participants to set goals, and providing regular review of progress for diet, physical activity or both. Results from network-meta-analyses showed that only studies with a structured approach for both diet and physical activity demonstrated significant decreases in weight (effect size = -4.12, 95% confidence interval = -7.772 to -2.760, P = 0.000) and body mass index (effect size = -2.94, 95% confidence interval = -1.78 to -0.357, P = 0.003). Waist circumference subgroup comparisons mainly comprised single studies; therefore, findings were inconclusive. Dietary information provided in studies generally complied with Australian Dietary Guidelines; however, none of the studies complied with all guidelines.Lifestyle interventions incorporating both dietary and physical activity components led to the greatest decreases in weight (4.1 kg) and body mass index (2.9 points) among people with psychosis. Important intervention strategies for both components are the personalization of education through tailored advice or goal setting, and a corresponding progress review. Dietary information in the included studies appeared to comply with the Australian Dietary Guidelines. However, these findings were weakened by an increased risk of bias, complex and multicomponent study designs, and lack of clarity in reporting of study methodology.

Background Diabetes is increasing in incidence, morbidity and treatment costs globally, hence prevention strategies need to be explored. Animal studies and some human data have shown that zinc can improve glycaemic control, but the impact of this effect in a pre-diabetic population remains uncertain. This study is designed to investigate whether zinc gluconate and lifestyle coaching can improve glucose handling and ultimately reduce diabetes incidence in an at-risk pre-diabetic population in Australia. Methods/design The study will be a randomised, placebo-controlled, double-blind clinical trial. The study will be conducted at the Hunter New England Local Health District New South Wales (NSW), Australia. Pre-diabetic (haemoglobin A1c [HbA1c] 5.7–6.4) male and female participants (n = 410) aged 40–70 years will be recruited through the Diabetes Alliance Network, a collaboration of diabetes specialists and general practitioner practices. All participants will be given routine care to encourage healthy lifestyle changes using a telephone coaching service (Get Healthy Information and Coaching Service, NSW Health) and then randomised to receive a supplement, either zinc gluconate (equivalent to 30 mg of elemental zinc) or placebo of identical appearance for 12 months. The identity of the supplements will be blinded to both research personnel and the participants. Participants will be asked to complete medical, lifestyle and dietary surveys and will have baseline and final visits at their general practitioner practice. Primary outcomes will be HbA1c and insulin sensitivity collected at baseline and at 1, 6 and 12 months; secondary outcomes will include fasting blood glucose, fasting cholesterol, blood pressure and body mass index. The primary efficacy endpoint will be judged at 6 months. Discussion This study will generate new evidence about the potential for health coaching, with or without zinc supplementation, to improve glucose handling and ultimately to reduce progression from pre-diabetes to diabetes. Trial registration Australian and New Zealand Clinical Trials Registry, ACTRN12618001120268. Registered on 6 July 2018. Electronic supplementary material The online version of this article (10.1186/s13063-019-3317-4) contains supplementary material, which is available to authorized users.

The elucidation of the metabolic pathways of the amino acid arginine and their role in health and disease have been an intensive focus of basic and clinical research for over a century. The recent advent of robust analytical techniques for biomarker assessment in large population cohorts has allowed the investigation of the pathophysiological role of specific arginine metabolites in key chronic disease states in old age, particularly those characterised by a reduced synthesis of endothelial nitric oxide, with consequent vascular disease and atherosclerosis. Two arginine metabolites have been increasingly studied in regard to their potential role in risk stratification and in the identification of novel therapeutic targets: the methylated arginine asymmetric dimethylarginine (ADMA) and the arginine analogue homoarginine. Higher circulating concentrations of ADMA, a potent inhibitor of nitric oxide synthesis, have been shown to predict adverse cardiovascular outcomes. By contrast, there is emerging evidence that homoarginine might exert cardioprotective effects. This review highlights recent advances in the biological and clinical role of ADMA and homoarginine in cardiovascular disease and other emerging fields, particularly chronic obstructive pulmonary disease, dementia, and depression. It also discusses opportunities for future research directions with the ultimate goal of translating knowledge of arginine metabolism, and its role in health and disease, into the clinical care of older adults.

Summary Persistent immune thrombocytopenia (ITP) patients require second‐line treatments, for which information on clinical outcomes are lacking. A systematic review and network meta‐analysis (NMA) were conducted. Only randomised controlled trials (RCT) of second‐line drugs in adult persistent ITP patients with platelet response, platelet count, any bleeding or serious adverse events (SAE) outcome were eligible. Twelve RCTs (n = 1313) were included in NMA. For platelet response outcome, eltrombopag and romiplostin were the best relative to placebo; the former had a non‐significant advantage [risk ratio (RR) = 1·10 (95% confidence interval: 0·46, 2·67)]. Both treatments were superior to rituximab and recombinant human thrombopoietin (rhTPO)+rituximab, with corresponding RRs of 4·56 (1·89, 10·96) and 4·18 (1·21, 14·49) for eltrombopag; 4·13 (1·56, 10·94) and 3·79 (1·02, 14·09) for romiplostim. For platelet count, romiplostim ranked highest, followed by eltrombopag, rhTPO+rituximab, and rituximab. For bleeding, rituximab had lowest risk, followed by eltrombopag and romiplostim. For SAEs, rhTPO+rituximab had highest risk, followed by rituximab, eltrombopag and romiplostim. From clustered ranking, romiplostim had the best balance between short‐term efficacy and SAEs, followed by eltrombopag. In conclusion, romiplostim and eltrombopag may yield high efficacy and safety. Rituximab may not be beneficial due to lower efficacy and higher complications compared with the thrombopoietin receptor agonists. RCTs with long‐term clinical outcomes are required.

To pool prevalence of nonconvulsive seizure, nonconvulsive status epilepticus, and epileptiform activity detected by different electroencephalography types in critically ills and to compare detection rates among them.MEDLINE (via PubMed) and SCOPUS (via Scopus) STUDY SELECTION:: Any type of study was eligible if studies were done in adult critically ill, applied any type of electroencephalography, and reported seizure rates. Case reports and case series were excluded.Data were extracted independently by two investigators. Separated pooling of prevalence of nonconvulsive seizure/nonconvulsive status epilepticus/epileptiform activity and odds ratio of detecting outcomes among different types of electroencephalography was performed using random-effect models. This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and also adhered to the Meta-analyses Of Observational Studies in Epidemiology guidelines. Quality of evidence was assessed with the Newcastle-Ottawa Quality Assessment Scale for observational studies and Cochrane methods for randomized controlled trial studies.A total of 78 (16,707 patients) and eight studies (4,894 patients) were eligible for pooling prevalence and odds ratios. For patients with mixed cause of admission, the pooled prevalence of nonconvulsive seizure, nonconvulsive status epilepticus, either nonconvulsive seizure or nonconvulsive status epilepticus detected by routine electroencephalography was 3.1%, 6.2%, and 6.3%, respectively. The corresponding prevalence detected by continuous electroencephalography monitoring was 17.9%, 9.1%, and 15.6%, respectively. In addition, the corresponding prevalence was high in post convulsive status epilepticus (33.5%, 20.2%, and 32.9%), CNS infection (23.9%, 18.1%, and 23.9%), and post cardiac arrest (20.0%, 17.3%, and 22.6%). The pooled conditional log odds ratios of nonconvulsive seizure/nonconvulsive status epilepticus detected by continuous electroencephalography versus routine electroencephalography from studies with paired data 2.57 (95% CI, 1.11-5.96) and pooled odds ratios from studies with independent data was 1.57 (95% CI, 1.00-2.47).Prevalence of seizures detected by continuous electroencephalography was significantly higher than with routine electroencephalography. Prevalence was particularly high in post convulsive status epilepticus, CNS infection, and post cardiac arrest.

Neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, is associated with cardiovascular events (CVEs), but its causal pathway is unknown. We aimed to explore the extent to which NLR is directly associated with CVEs or mediated through diabetes mellitus (DM), hypertension (HT) and creatinine (Cr). The study used data on 2,501 subjects from the Electricity Generating Authority of Thailand cohort 2002–2012. Two causal pathways A: NLR→(DM→Cr→HT)→CVEs and B: NLR→(DM → HT→Cr)→CVEs were constructed. A generalized structural equation model and 1,000-replication bootstrapping were applied. The incidence rate of CVE was 8.8/1000/year. Prevalence rates of HT, DM, and chronic kidney disease were 45.1%, 23.6%, and 16.5%, respectively. The total effect of NLR on CVEs was explained partly (44%) by a direct effect and partly (56%) by an indirect effect through DM, HT and Cr. For pathway A, the direct OR of NLR on CVE was 1.25 (95% CI: 1.13, 1.39); the ORs for the indirect effects of NLR on CVEs mediated through DM, Cr, and poor-controlled HT were 1.06 (95% CI: 1.01, 1.11), 1.01 (95% CI: 1.00, 1.02), and 1.07 (95% CI: 1.01, 1.14) respectively. Results were similar for pathway B. Our findings demonstrate that roughly half of the relationship between NLR and CVEs may be mediated through DM, HT and Cr.

Convincing evidence exists for the positive effect of an improvement in diet quality on age-related cognitive decline, in part due to dietary fatty acid intake. A cross-sectional analysis of data from the Hunter Community Study (HCS) (n = 2750) was conducted comparing dietary data from a validated Food Frequency Questionnaire (FFQ) with validated cognitive performance measures, Audio Recorded Cognitive Screen (ARCS) and Mini Mental State Examination (MMSE). Adjusted linear regression analysis found statistically significant associations between dietary intake of total n-6 fatty acids (FA), but no other FAs, and better cognitive performance as measured by the ARCS (RC = 0.0043, p = 0.0004, R2 = 0.0084). Multivariate regression analyses of n-6 FA intakes in quartiles showed that, compared with the lowest quartile (179.8&ndash, 1150.3 mg), those in the highest quartile (2315.0&ndash, 7449.4 mg) had a total ARCS score 2.1 units greater (RC = 10.60466, p = 0.006, R2 = 0.0081). Furthermore, when n-6 FA intake was tested against each of the ARCS domains, statistically significant associations were observed for the Fluency (RC = 0.0011432, p = 0.007, R2 = 0.0057), Visual (RC = 0.0009889, p = 0.034, R2 = 0.0050), Language (RC = 0.0010651, p = 0.047, R2 = 0.0068) and Attention (RC = 0.0011605, p = 0.017, R2 = 0.0099) domains, yet there was no association with Memory (RC = &minus, 0.000064, p = 0.889, R2 = 0.0083). No statistically significant associations were observed between FA intakes and MMSE. A higher intake of total n-6 FA, but not other types of FA, was associated with better cognitive performance among a representative sample of older aged Australian adults.

Nitric oxide (NO) facilitates anti-atherosclerotic effects. Vegetables are a major source of dietary nitrate. Experimental data indicates that dietary nitrate can significantly reduce major risk factors for atherosclerosis and subsequent cardiovascular disease (CVD), as nitrate can be metabolized to produce NO via the nitrate-nitrite-NO pathway. The purpose of this study was to prospectively investigate the association between habitual dietary nitrate intakes and the incidence of self-reported CVD-related complications within a representative sample of middle-aged Australian women (1946–1951 cohort of the Australian Longitudinal Study on Women’s Health). Women free from disease at baseline who had completed the food frequency questionnaire data were included. Generalized estimating equations were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) across quartiles for nitrate intakes. Of the 5324 women included for analysis, there were 1951 new cases of CVD-related complications over 15-years of follow-up. Women reporting higher total dietary nitrate intakes (Q4 &gt, 78.2 mg/day) and vegetable nitrate intakes (Q4 &gt, 64.4 mg/day) were 25% and 27% reduced risk of developing CVD-related complications respectively, compared with women reporting low total (Q1 &lt, 45.5 mg/day) and vegetable nitrate intakes (Q1 &lt, 34.8 mg/day). Our findings were consistent with other observational data indicating that dietary nitrate may explain some of the cardiovascular benefits of vegetable consumption.

Purpose Tooth loss or periodontal disease is associated with systemic endothelial dysfunction, which has been implicated in primary open-angle glaucoma (POAG). The relationship between oral health and POAG has received limited attention. Thus, we evaluated the association between oral health history and risk of POAG and POAG subtypes. Design Prospective cohort study. Participants Health Professionals Follow-up Study participants (40 536 men) followed biennially from 1986 to 2012. At each 2-year risk period, eligible participants were aged 40+ years, were free of POAG, and reported eye examinations. Methods By using validated questions, we updated participants' status on number of natural teeth, teeth lost, periodontal disease with bone loss, and root canal treatments. Main Outcome Measures During follow-up, 485 incident cases of POAG were confirmed with medical records and classified into subtypes defined by intraocular pressure (IOP; ≥ or Results Number of natural teeth, periodontal disease, and root canal treatment were not associated with POAG. However, compared with no report of tooth loss, a report of losing teeth within the past 2 years was associated with a 1.45-fold increased risk of POAG (95% CI, 1.06–1.97); in particular, a report within the past 2 years of both losing teeth and having a prevalent diagnosis of periodontal disease was associated with a 1.85-fold increased risk of POAG (95% CI, 1.07–3.18). The associations with recent tooth loss were not significantly different for the POAG subtypes ( P for heterogeneity ≥0.36), although associations were strongest in relation to the POAG subtypes with IOP Conclusions Although the number of natural teeth was not associated with risk of POAG, recent tooth loss was associated with an increased risk of POAG. Because these findings may be due to chance, they need confirmation in larger studies.

Background We conducted a systematic review and meta-analysis of interferon regulatory factor 6 and 8q24 polymorphisms with nonsyndromic cleft lip with/without cleft palate (NSCL/P). Methods Data extraction was independently performed by two reviewers. Genotypic effects of four polymorphisms from 31 studies were pooled separately by ethnicity using a mixed-effect logit model with accounting for heterogeneity. Results For rs2235371, AA and GA carried, respectively, 51% (95% confidence interval [CI], 37%–61%) and 42% (95% CI, 32%–50%) lower risks of NSCL/P than GG genotypes in Asians, but these genotypes were not significant in Caucasians. For rs2013162, only AA was significant, that is, carried 0.65 (95% CI, 0.52–0.82) times lower odds than CC in Caucasians but not for Asians. For rs642961, AA and GA genotypes, respectively, carried 2.47 (95% CI, 1.41–4.35) and 1.40 (95% CI, 1.12–1.75) times higher odds in Asian, and 2.03 (95% CI, 1.52–2.71) and 1.58 (95% CI, 1.37–1.82) times higher odds in Caucasians compare with GG genotypes. For rs987525, AA and CA genotypes carried 2.27 (95% CI, 1.43–3.60) and 1.34 (95% CI, 1.02–1.77) times higher odds in Asian, and 5.25 (95% CI, 3.98–6.91) and 2.13 (95% CI–1.82, 2.49) times higher odds in Caucasians, and 1.42 (95% CI, 1.10–1.82) and 1.28 (95% CI, 1.09–1.50) times higher odds in mixed ethnicities compared with CC genotypes. These variant effects remained significant based on applying Bonferroni corrected-thresholds, except in the mixed ethnicity. Conclusion We show robust variant effects in NSCL/P. Considering them with other genes and risk factors might be useful to improve prediction of NSCL/P occurrence. Birth Defects Research (Part A), 2016. © 2016 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc.

Background Research has shown that vaccination with Streptococcus pneumoniae reduced the extent of atherosclerosis in experimental animal models. It is thought that phosphorylcholine lipid antigens in the S. pneumoniae cell wall induce the production of antibodies that cross-react with oxidized low-density lipoprotein, a component of atherosclerotic plaques. These antibodies may bind to and facilitate the regression of the plaques. Available data provide evidence that similar mechanisms also occur in humans, leading to the possibility that pneumococcal vaccination protects against atherosclerosis. A systematic review and meta-analysis, including 8 observational human studies, of adult pneumococcal polysaccharide vaccination for preventing cardiovascular disease in people older than 65 years, showed a 17% reduction in the odds (odds ratio 0.83, 95% CI 0.71-0.97) of having an acute coronary syndrome event. Methods/Design The AUSPICE is a multicenter, randomized, placebo-controlled, double-blind, clinical trial to formally test whether vaccination with the pneumococcal polysaccharide vaccine protects against cardiovascular events (fatal and nonfatal acute coronary syndromes and ischemic strokes). Cardiovascular outcomes will be obtained during 4 to 5 years of follow-up, through health record linkage with state and national administrative data sets. Conclusion This is the first registered randomized controlled trial (on US, World Health Organization, Australia and New Zealand trial registries) to be conducted to test whether vaccination with the pneumococcal polysaccharide vaccine will reduce cardiovascular events. If successful, vaccination can be readily extended to at-risk groups to reduce the risk of cardiovascular diseases.

Background: Statins are proposed as a chemoprevention agent for breast cancer due to their anti-inflammatory effect. The effects of lipophilic and hydrophilic statins on breast cancer risk might be different due to their different pharmacologic properties. Therefore, this study aimed to assess a casual-effect of lipophilic and hydrophilic statins on breast cancer risk using a counterfactual framework approach. Methods: A cross-sectional study of 15,718 women who were screened for breast cancer at Mammographic center, Ramathibodi Hospital, Bangkok, Thailand, was conducted during September 2011 to 2012. A counterfactual framework approach was applied to assess causal effects of treatments (i.e., lipophilic and hydrophilic statins) on outcome (i.e. breast cancer). Multi-logit and logistic regression models were used for treatment and outcome models, respectively. An inverse probability weight regression analysis (IPWRA) was then applied to estimate potential outcome mean (POM) and average treatment effect (ATE) by combining the outcome and treatment models. Results: Breast cancer risks were 0.0072 (95% CI: 0.0055, 0.0089), 0.0051 (95% CI: 0.0008, 0.0095), and 0.0038 (95% CI: 0.002, 0.0056) for non-statin users, hydrophilic, and lipophilic statin users, respectively. The estimated risk differences were -0.0021 (95% CI: -0.0067, 0.0026) and -0.0034 (95% CI: -0.0059, -0.0009) for hydrophilic and lipophilic statins respectively. The number needed to treat for hydrophilic and lipophilic statins were 2.1 (95% CI: -2.6, 6.7) and 3.4 (95% CI: 1.0, 5.9) per 1000 subjected, respectively. Conclusions: Our results suggested that using lipophilic statin could significantly reduce risk of breast cancer in Thai women.

People with Type 1 diabetes (T1D) have been shown to be an at-risk group for the development of disordered eating behaviours, however, the validity of tools used to assess disordered eating behaviours in T1D is unclear. This review aimed to identify tools used to screen or identify disordered eating behaviours and eating disorders in people with T1D, and evaluate the validity and reliability of these tools. A systematic search strategy was conducted to October 2019 according to the PRISMA guidelines. The search strategy retrieved 2714 articles, with 100 articles describing 90 studies included in the review. Studies were predominantly conducted in adolescent females in clinical settings. Forty-eight individual tools were used across retrieved studies. Overall, the quality of tools reported in included articles was poor, with high risk of bias due to the use of non-validated tools (n = 44 articles) and few studies comparing to the reference standard (n = 10 articles) of a diagnostic interview. This review shows that a variety of tools have been used to screen and identify disordered eating behaviours and eating disorders in people with T1D. Future research including comparison to a gold standard diagnostic interview is warranted to further evaluate the validity and reliability of available tools.

Background To develop and validate a risk stratification model of severe injury (SI) and death to identify and prioritize road traffic injury (RTI) patients for transportation to an appropriate trauma center (TC). Methods A 2-phase multicenter-cross-sectional study with prospective data collection was collaboratively conducted using 9 dispatch centers (DC) across Thailand. Among the 9 included DC, 7 and 2 DCs were used for development and validation, respectively. RTI patients who were treated and transported to hospitals by advanced life support (ALS) response units were enrolled. Multiple logistic regression was used to derive risk prediction score of death in 48 h and SI (new injury severity score ≥ 16). Calibration/discrimination performances were explored. Results A total of 5359 and 2097 RTIs were used for development and external validation, respectively. Seven and 9 predictors among demographic data, mechanism of injury, physic data, EMS operation, and prehospital managements were significant predictors of death and SI, respectively. Risk prediction models fitted well with the developed data (O/E ratios of 1.00 (IQR: 0.69, 1.01) and 0.99 (IQR: 0.95, 1.05) for death and SI, respectively); and the C statistics of 0.966 (0.961, 0.972) and 0.913 (0.905, 0.922). The risk scores were further stratified as low, moderate and high risk. The derive models did not fit well with external data but they were improved after recalibrating the intercepts. However, the model was externally good/excellent discriminated with C statistics from 0.896 (0.871, 0.922) to 0.981 (0.971, 0.991). Conclusion Risk prediction models of death and SI were developed with good calibration and excellent discrimination. The model should be useful for ALS response units in proper allocation of patients.

ISSUE ADDRESSED Lifestyle interventions use nutrition and physical activity behaviour modification techniques to decrease obesity and cardio-metabolic risk in people with psychosis. Evidence on the specific behaviour modification strategies applied to decrease obesity is weakened by inadequate methodology reporting of lifestyle interventions. A systematic review that we conducted earlier highlighted a possible deficiency in reporting; hence we aim to critically appraise lifestyle intervention studies that target weight outcomes for people with psychosis against the methods component of the CONSORT statement for randomised trials of nonpharmacologic treatments. METHODS COMPONENT We considered randomised controlled studies which delivered lifestyle interventions to community-dwelling adults with psychotic disorders, and included those with the following outcomes of interest: weight, body mass index, waist circumference and waist-to-hip ratio. The Cochrane Library, MEDLINE/PREMEDLINE, EMBASE, CINAHL, Scopus and PsycINFO were searched for English publications between 1985 and 2018. Methodology and reporting of studies were evaluated using the CONSORT statement for randomised trials of nonpharmacologic treatments. RESULTS Thirty-two studies met the inclusion criteria. Critical appraisals revealed that reporting of lifestyle intervention studies was generally incomplete. Fewer than 50% provided the recommended information on trial design, participant characteristics, detail of interventions, outcomes, sample size, randomisation, blinding and statistical methods. CONCLUSIONS Application of guidelines, like the CONSORT statement, in future publications of lifestyle interventions for people with psychosis will improve accuracy of reporting. SO WHAT?: Enhanced reporting in lifestyle intervention studies for people with psychosis will promote guideline creation and translation of research, which is likely to positively impact physical health outcomes.

Summary Background & aims Chronic inflammation drives the development of insulin resistance and type 2 diabetes. Long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) eicosapentaenoic acid (EPA, c20:5n-3) and docosahexaenoic acid (DHA, c22:6n-3) may protect against type 2 diabetes development. The aim of this current study is to determine whether LCn-3PUFA status is associated with type 2 diabetes in the Hunter Community Study. Methods Men and women aged 55–85 years were randomly selected from the electoral roll and invited to participate. Participants were included in the current study if they had plasma phospholipid fatty acid composition data available and diabetes status could be determined. LCn-3PUFA status was determined by fatty acid composition of plasma phospholipids (EPA + DHA, %,w/w). Diabetes was determined according to World Health Organisation criteria. Insulin was measured in n = 251 participants and HOMA-IR calculated. Results In total, n = 2092 (diabetes: n = 249) participants were included. After adjusting for confounders of diabetes, LCn-3PUFA status was inversely associated with diabetes in overweight/obese females (OR [95%CI]: 0.90 [0.80, 1.00], p = 0.045) but not males (p-interactionsex = 0.041). Overweight/obese females with diabetes had significantly lower levels of DHA than those without diabetes (mean difference [95%CI]: −0.53 [−0.87, −0.20], p = 0.002), with no difference in EPA. LCn-3PUFA was inversely associated with HOMA-IR (r = −0.175, p = 0.005). Conclusions This study provides further evidence of a sex-dependent association between LCn-3PUFA and type 2 diabetes. Causal pathways between LCn-3PUFA and type 2 diabetes merits delineation.

Previously thought to be mainly a disorder of childhood and early adult life, coeliac disease (CeD) is increasingly diagnosed in older adults. This may be important given the association between CeD and osteoporosis. The primary aim of this study was to determine the seroprevalence of undiagnosed CeD (&lsquo, at-risk serology&rsquo, ) in an older Australian community and relate this to a diagnosis of osteoporosis and fractures during a follow-up period of 12 years. We included participants from the Hunter Community Study (2004&ndash, 2007) aged 55&ndash, 85, who had anti-tissue transglutaminase (tTG) titres, human leukocyte antigen (HLA) genotypes, and bone mineral density measurements at baseline. Follow-up data included subsequent diagnosis of CeD and fractures using hospital information. &lsquo, At-risk&rsquo, serology was defined as both tTG and HLA positivity. Complete results were obtained from 2122 patients. The prevalence of &lsquo, at-risk&rsquo, serology was 5%. At baseline, 3.4% fulfilled criteria for a diagnosis of osteoporosis. During a mean of 9.7 years of follow-up, 7.4% of the cohort suffered at least one fracture and 0.7% were subsequently diagnosed with CeD. At-risk serology was significantly associated with osteoporosis in a multivariate model (odds ratio 2.83, 95% confidence interval 1.29&ndash, 6.22), there was insufficient power to look at the outcome of fractures. The results of this study demonstrate that at-risk CeD serology was significantly associated with concurrent osteoporosis but not future fractures. Most individuals with a serological diagnosis of CeD were not diagnosed with CeD during the follow-up period according to medical records. Coeliac disease likely remains under-diagnosed.

Laparoscopic totally extra-peritoneal inguinal hernia repair is the standard option for inguinal hernia treatment. However, there are various types of mesh fixation and their relative uses are still controversial. This network meta-analysis was conducted to compare and rank the different fixations available for TEP. Medline and Scopus databases were search until February 1, 2017 and using randomized controlled trials comparing outcomes between different mesh fixation techniques were included. The results demonstrated that fifteen RCTs (n = 1783) were eligible for pooling. Five types of mesh fixation were used; metallic tack, no-fixation, absorbable tack, suture, and glue. Network meta-analysis that use metallic tack as the reference, indicated that suture and glue both carried a lower risk of recurrence with pooled risk ratios (RR) of 0.29 (95% CI 0.00, 18.81) and 0.29 (0.07, 1.30), respectively. For overall complications, absorbable tack had lower risk (0.63, 95% CI: 0.02, 16.13). However, none of these estimates reached statistical significance. So, this network meta-analysis suggests that glue and absorbable tack might be best in lowering recurrence risk and complications. However, a large scale RCT is still needed to confirm these results.

Bone loss is characteristic of the ageing process and a common complication of many autoimmune diseases. Research has highlighted a potential role of autoantibodies in pathologic bone loss. The confounding effects of immunomodulatory drugs make it difficult to establish the contribution of autoantibodies amongst autoimmune disease sufferers. We attempted to examine the relationship between autoantibodies and bone mass in a population of 2812 elderly participants without clinical autoimmune disease. Serum samples were assayed for a panel of autoantibodies (anti-nuclear, extractable nuclear antigen, anti-neutrophil cytoplasmic, thyroid peroxidase, tissue transglutaminase, anti-cardiolipin, rheumatoid factor, and cyclic citrullinated peptide). Bone mass was measured using quantitative ultrasound (QUS) of the calcaneus. The relationship between each autoantibody and bone mass was determined using linear regression models. Anti-nuclear autoantibodies were the most prevalent, positive in approximately 11%, and borderline in roughly 23% of our sample. They were also the only autoantibody observed to be significantly associated with QUS index in the univariate analysis (n=1628; r=−0.20; 95% CI: −0.40–0.00; p=0.046). However, statistical significance was lost after adjustment for various other potential confounders. None of the other autoantibodies was associated with QUS index in either univariate or multivariate analysis. We are limited by the cross-sectional nature of the study and the low prevalence of autoantibodies in our nonclinical sample.

This study investigated whether inflammation may explain the relationship between depression and incident cardiovascular hospitalisations. Participants (55-85 years) completed baseline depression and physical assessment. Those without self-reported cardiovascular events were followed prospectively for hospital admissions for angina, myocardial infarction and cerebral infarction (median 937 days). Across 5140 person-years of risk (N = 1692), there were 47 incident cardiovascular hospitalisations (2.8 %). Controlling for age and gender, interleukin (IL)-6, C-reactive protein (CRP), body mass index (BMI) and waist-to-hip ratio were associated with future cardiovascular events. Mediation analysis showed that CRP accounted for 8.1 % and IL-6 10.9 % of the effect of depression on cardiovascular events, and including the indirect effect in the model substantially reduced the direct relationship between depression and cardiovascular hospitalisations. BMI and waist-to-hip ratio accounted for indirect effects of 7.7 and 10.4 %, respectively. Inflammatory markers partly explain the association between depression and cardiovascular events, although other shared factors also likely contribute.