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Introduction: About 44% of Aboriginal and/or Torres Strait Islander women smoke during pregnancy compared to 12% of their general population counterparts. Evidence-based quit smoking advice received from health care professionals (HCPs) can increase smoking cessation rates. However, HCPs lack culturally appropriate smoking cessation training, which is a major barrier to provision of smoking cessation care for this population., Methods and Analysis: iSISTAQUIT is a multicentre, single arm study aiming to implement and evaluate the evidence-based, culturally competent iSISTAQUIT smoking cessation training among health practitioners who provide support and assistance to pregnant, Aboriginal and Torres Strait Islander women in Australia. This project will implement the iSISTAQUIT intervention in Aboriginal Medical Services and Mainstream Health Services. The proposed sample size is 10 of each of these services (total N = 20), however if the demand is higher, we will aim to accommodate up to 30 services for the training. Participating sites and their HCPs will have the option to choose one of the two iSISTAQUIT packages available: a) Evaluation- research package b) Training package (with or without continued professional development points). Training will be provided via an online eLearning platform that includes videos, text, interactive elements and a treatment manual. A social media campaign will be conducted from December 2021 to September 2022 to raise brand and issue awareness about smoking cessation for Aboriginal and Torres Strait Islander women in pregnancy. This national campaign will consist of systematic advertising and promotion of iSISTAQUIT and video messages through various social media platforms., Analysis: We will use the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation and Maintenance) to plan, evaluate and report the intervention impact of iSISTAQUIT. Effectiveness of social media campaign will be assessed via social media metrics, cross-sectional surveys, and interviews., Discussion: This innovative research, using a multi-component intervention, aims to practically apply and integrate a highly translatable smoking cessation intervention in real-world primary care settings in Aboriginal Medical Services and Mainstream services. The research benefits Aboriginal women, babies and their family and community members through improved support for smoking cessation during pregnancy. The intervention is based on accepted Australian and international smoking cessation guidelines, developed and delivered in a culturally appropriate approach for Aboriginal communities., Competing Interests: All authors declare that they have no conflicts of interest., (Copyright: © 2022 Gould (Judean) et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aims to describe the prevalence of depression and anxiety among a population sample of people at high risk for type 2 diabetes in Kerala, India, and examine the relationship between depressive symptoms, anxiety, and incident Type 2 Diabetes Mellitus (T2DM) over a two-year period. We used data from the Kerala Diabetes Prevention Program, a cluster-randomized controlled trial for diabetes prevention among 1007 high-risk individuals. The prevalence of depression and anxiety were estimated using the 9-item Patient Health Questionnaire and the Generalized Anxiety Disorder 7-item scale, respectively. We calculated proportions for depression and anxiety and performed generalized estimating equations (GEE) to examine the relationship between baseline mental health status and incident T2DM. The prevalence of depression and anxiety at baseline were 7.5% and 5.5%, respectively. Compared with those reporting none/low symptoms, the odds ratio for incident diabetes was 1.07 (95% CI 0.54-2.12) for participants with moderate to severe depression and 0.73 (95% CI 0.23-2.28) for participants with moderate to severe anxiety, after adjusting for potential confounders. Our findings suggest that the prevalence of depression and anxiety were higher than those previously reported in the general population in India. However, among this sample of community-based adults at high risk of developing T2DM, the presence of moderate to severe depression and/or anxiety symptoms was not significantly associated with the risk of developing T2DM. Trial registration: Australia and New Zealand Clinical Trials Registry ACTRN12611000262909. Registered 10 March 2011., Competing Interests: The authors have declared that no competing interests exist.

Cardiovascular diseases (CVDs) are major contributors to morbidity and mortality in lower-middle-income countries (LMICs). Features of the natural environment, such as greenness, are a potential, modifiable determinant of CVD, yet there is a lack of evidence, particularly in LMICs. Our study investigated associations between residential greenness, measured using the Normalized Difference Vegetation Index (NDVI), and self-reported heart disease in 5268 Sri Lankan men aged 34 to 55 years. Multivariable logistic regression models were fitted to examine associations between mean NDVI within 100 m, 400 m, 800 m, 1600 m, and 2000 m of the residential address, adjusting for age, marital status, income, education, alcohol consumption, smoking and road length. Fully adjusted models showed that a 0.1 increase in mean NDVI was associated with lower odds of heart disease when using the 400 m (OR: 0.80; 95% CI: 0.64, 1.00), 800 m (OR: 0.85; 95% CI: 0.63, 1.14), and 2000 m (OR: 0.74; 95% CI: 0.48, 1.13) buffers. Further research in different contexts, and with improved outcome measures, is needed to confirm relationships between residential greenness and heart disease in rural areas and in LMICs., Competing Interests: The authors have declared that no competing interests exist.

Background: Cardiometabolic disorders are frequently observed among those who have obesity as measured by body mass index (BMI). However, there is limited data available on the cardiometabolic profile of those who are non-obese by BMI but with a high body fat percentage (BFP), a phenotype frequently observed in the Indian population. We examined the prevalence of individuals with normal weight obesity (NWO) and the cardiometabolic profile of NWO individuals at high risk for type 2 diabetes(T2D) in a south Asian population., Material and Methods: In the Kerala Diabetes Prevention Program, individuals aged between 30 to 60 years were screened using the Indian Diabetes Risk Score(IDRS) in 60 rural communities in the Indian state of Kerala. We used data from the baseline survey of this trial for this analysis which included 1147 eligible high diabetes risk individuals(IDRS >60). NWO was defined as BMI within the normal range and a high BFP (as per Asia-pacific ethnicity based cut-off); Non-obese (NO) as normal BMI and BFP and overtly obese (OB) as BMI ≥25 kg/m2 irrespective of the BFP. Data on demographic, clinical and biochemical characteristics were collected using standardized questionnaires and protocols. Body fat percentage was assessed using TANITA body composition analyser (model SC330), based on bioelectrical impedance., Results: The mean age of participants was 47.3 ± 7.5 years and 46% were women. The proportion with NWO was 32% (n = 364; 95% CI: 29.1 to 34.5%), NO was 17% (n = 200) and OB was 51% (n = 583). Among those with NWO, 19.7% had T2D, compared to 18.7% of those who were OB (p value = 0.45) and 8% with NO (p value = 0.003). Among those with NWO, mean systolic and diastolic blood pressure were 129 ± 20; 78 ± 12 mmHg, compared to 127 ± 17; 78±11 mmHg among those with OB (p value = 0.12;0.94) and 120 ± 16; 71±10 mmHg among with NO (p value<0.001; 0.001), respectively. A similar pattern of association was observed for LDL cholesterol and triglycerides. After adjusting for other risk factors, the odds of having diabetes (OR:2.72[95% CI:1.46-5.08]) and dyslipidemia (2.37[1.55-3.64]) was significantly more in individuals with NWO as compared to non-obese individuals., Conclusions: Almost one-third of this South Asian population, at high risk for T2D, had normal weight obesity. The significantly higher cardiometabolic risk associated with increased adiposity even in lower BMI individuals has important implications for recognition in clinical practice., Competing Interests: The authors have declared that no competing interests exist.

Background: Multimorbidity, the presence of 2 or more non-communicable diseases (NCDs), is a major contributor to inequalities of health in Australia and Japan. We use nationally representative data to examine (i) the relationships between multimorbidity with healthcare utilisation and productivity loss and (ii) whether these relationships differed by socioeconomic groups., Methods: Cross-sectional analyses using the Household, Income, and Labour Dynamics in Australia (HILDA) and the Japanese Study of Aging and Retirement (JSTAR) surveys. We examined 6,382 (HILDA) and 3,503 (JSTAR) adults aged ≥50 years. We applied multivariable regression, logistic and negative binomial models., Results: Prevalence of multimorbidity was overall 38.6% (46.0%, 36.1%, 28.9% amongst those in the lowest, middle and highest education group, respectively) in Australia, and 28.4% (33.9%, 24.6%, 16.6% amongst those in the lowest, middle and highest education group, respectively) in Japan. In Australia and Japan, more NCDs was associated with greater healthcare utilisation. In Australia and Japan, more NCDs was associated with higher mean number of sick leave days amongst the employed and lower odds of being employed despite being in the labour force. The association between multimorbidity and lower retirement age was found in Australia only., Conclusion: Having more NCDs pose significant economic burden to the health system and wider society in Australia and Japan. Targeted policies are critical to improve financial protection, especially for lower income groups who are more likely to have multiple NCDs. These individuals incur both high direct and indirect costs, which lead to a greater risk of impoverishment., Competing Interests: The authors have declared that no competing interests exist.

Background: Risk factors for cardiovascular disease (CVD) are negatively correlated with socio-economic status (SES) in high-income countries (HIC) but there has been little research on their distribution by household SES within low-and middle-income countries (LMICs). Considering the limited data from LMICs, this paper examines the association between behavioural and cardiovascular risk factors and household SES in Papua New Guinea (PNG)., Methods: Reported here are results of 671 participants from the 900 randomly selected adults aged 15-65 years. These adults were recruited from three socioeconomically and geographically diverse surveillance sites (peri-urban community, rural Highland and an Island community) in PNG in 2013-2014. We measured their CVD risk factors (behavioural and metabolic) using a modified WHO STEPS risk factor survey and analysis of blood samples. We assessed SES by education, occupation and creating a household wealth index based on household assets. We calculated risk ratios (RR) and their 95% confidence intervals (CI) using a generalized linear model to assess the associations between risks and SES., Findings: Elevated CVD risk factors were common in all SES groups but the CVD metabolic risk factors were most prevalent among homemakers, peri-urban and rural highlands, and the highest (4th and 5th) wealth quintile population. Adults in the highest wealth quintile had high risks of obesity, elevated HbA1c and metabolic syndrome (MetS) that were greater than those in the lowest quintile although those in the highest wealth quintiles were less likely to smoke tobacco. Compared to people from the Island community, peri-urban residents had increased risks of increased waist circumference (WC) (RR: 1.67, 95%CI: 1.21-2.31), hypertension (RR: 2∙29, 95%CI: 1∙89-4.56), high cholesterol (RR: 2∙22, 95%CI: 1∙20-4∙10), high triglycerides (RR: 1∙49, 95%CI: 1∙17-1∙91), elevated HbA1c (RR: 5∙54, 95%CI: 1∙36-21∙56), and Metabolic syndrome (MetS) (RR: 2∙04, 95%CI: 1∙25-3∙32). Similarly, Rural Highland residents had increased risk of obesity (Waist Circumference RR: 1∙70, 95%CI: 1∙21-3∙38, Waist-Hip-Ratio RR:1∙48, 95%CI: 1∙28-1∙70), hypertension (RR: 2∙60, 95%CI: 1∙71-3∙95), high triglycerides (RR: 1∙34, 95%CI: 1∙06-1∙70) and MetS (RR: 1∙88, 95%CI: 1∙12-3∙16) compared to those in the rural Island site., Interpretation: CVD risk factors are common in PNG adults but their association with SES varies markedly and by location. Our findings show that all community members are at risk of CVD weather they are part of high or low SES groups. These results support the notion that the association between CVD risk factors and SES differ greatly accordingly to the type of SES measure used, risk factors and the population studied. In addition, our findings contribute further to the limited literature in LMIC. Longitudinal studies are needed to monitor changes in rapidly changing societies such as PNG to inform public health policy for control and prevention of NCDs in the country., Competing Interests: The commercial funding PNG ExxonMobil Partnerships for this study does not alter our adherence to PLOS ONE Editorial policies on sharing data and materials.

This study examined how classroom peer relations can be described in terms of the network of help relations among students, and the positions students take up in this help network, and whether the structure of adolescent classroom help networks and individual network positions were associated with academic achievement. Help networks were based on the peer nomination question "Who helps you with problems?" Building on previous studies on classroom climate and individual network position, higher academic achievement was expected in classrooms with: a dense help network; no or a few network isolates (referring to students that did not give or receive help at all); less segmentation in help relations; equally distributed help nominations. In addition, higher achievement was expected for individuals with more helpers and a more central position in the help network. Using the Dutch SNARE data (54 classrooms; 1,144 students), the multilevel models suggested that lower achievement was related to an unequal distribution of help relations in a classroom. Moreover, the centrality of individuals in the help network was linked to higher achievement. Classrooms varied strongly on network dimensions, and networks that would theoretically be expected to be most beneficial for achievement (with high density, a few isolates, low segmentation, and high equality) turned out to be highly uncommon. The findings demonstrated that subtle network processes were relevant for academic success, and that classroom network characteristics are associated with classroom-level variation in academic achievement. Descriptive results underlined the complexity of the social context of classrooms, and the absence of 'beneficial' classrooms suggests that researchers should adjust their notion of what is a beneficial or detrimental classroom environment for adolescents., Competing Interests: The authors have declared that no competing interests exist.

Previous studies investigating to what extent students in elementary schools defend their victimized classmates typically treated defending as an individual characteristic. Defending should, however, be seen as a directed dyadic relationship between a victim and a defender, who are embedded multiple positive and negative relationships with each other and their classmates. Accordingly, in the present study defending was investigated using social network analysis. More specifically, it was investigated to what extent defending relationships co-occurred with friendship and dislike relationships involving not only the victim and the defender but also other classmates. Bivariate Exponential Random Graph Models (ERGMs) were used to analyze the defending-friendship and defending-dislike relationships in seven grade-three classrooms. As hypothesized, the results indicated that victimized students were likely to be defended by students who they perceive as friends or who perceive them as friends. Moreover, defending was likely to occur when the victim and (potential) defender had the same friends. Victimized students were unlikely to be defended by classmates whom they disliked or who had indicated to dislike them. Finally, defending was likely to occur between students who disliked the same classmates., Competing Interests: The authors have declared that no competing interests exist.

Aim: To examine the characteristics of community health workers (CHWs) involved in diabetes prevention programmes (DPPs) and their contributions to expected outcomes., Methods: Electronic databases including PubMed-MEDLINE, EBSCOHost, and SCOPUS/EMBASE were searched for studies published between January 2000 and March 2016. All studies that used CHWs to implement DPP in ≥18-year-old participants without diabetes but at high risk for developing the condition, irrespective of the study design, setting or outcomes measured, were included. Results were synthesized narratively., Results: Forty papers of 30 studies were identified. Studies were mainly community-based and conducted in minority populations in USA. Sample sizes ranged from 20 participants in a single community to 2369 participants in 46 communities. Although CHWs were generally from the local community, their qualifications, work experience and training received differed across studies. Overall the training was culturally sensitive and/or appropriate, covering topics such as the importance of good nutrition and the benefits of increased physical activity, communication and leadership. CHWs delivered a variety of interventions and also screened or recruited participants. The shared culture and language between CHWs and participants likely contributed to better programme implementation and successful outcomes., Conclusions: The complexity of DPPs and the diverse CHW roles preclude attributing specific outcomes to CHW involvement. Nevertheless, documenting potential CHW roles and the relevant training required may optimise CHW contributions and facilitate their involvement in DPPs in the future.

Genome-wide association studies have revealed several common genetic risk variants for ulcerative colitis (UC). However, little is known about the contribution of rare, large effect genetic variants to UC susceptibility. In this study, we performed a deep targeted re-sequencing of 122 genes in Dutch UC patients in order to investigate the contribution of rare variants to the genetic susceptibility to UC. The selection of genes consists of 111 established human UC susceptibility genes and 11 genes that lead to spontaneous colitis when knocked-out in mice. In addition, we sequenced the promoter regions of 45 genes where known variants exert cis-eQTL-effects. Targeted pooled re-sequencing was performed on DNA of 790 Dutch UC cases. The Genome of the Netherlands project provided sequence data of 500 healthy controls. After quality control and prioritization based on allele frequency and pathogenicity probability, follow-up genotyping of 171 rare variants was performed on 1021 Dutch UC cases and 1166 Dutch controls. Single-variant association and gene-based analyses identified an association of rare variants in the MUC2 gene with UC. The associated variants in the Dutch population could not be replicated in a German replication cohort (1026 UC cases, 3532 controls). In conclusion, this study has identified a putative role for MUC2 on UC susceptibility in the Dutch population and suggests a population-specific contribution of rare variants to UC.

Background: With the increasing use of anti-TNF therapy in inflammatory bowel disease (IBD), a shift of costs has been observed with medication costs replacing hospitalization and surgery as major cost driver. We aimed to explore the evolution of IBD-related costs over two years of follow-up., Methods and Findings: In total 1,307 Crohn's disease (CD) patients and 915 ulcerative colitis (UC) patients were prospectively followed for two years by three-monthly web-based questionnaires. Changes of healthcare costs, productivity costs and out-of-pocket costs over time were assessed using mixed model analysis. Multivariable logistic regression analysis was used to identify costs drivers. In total 737 CD patients and 566 UC were included. Total costs were stable over two years of follow-up, with annual total costs of €7,835 in CD and €3,600 in UC. However, within healthcare costs, the proportion of anti-TNF therapy-related costs increased from 64% to 72% in CD (p<0.01) and from 31% to 39% in UC (p < 0.01). In contrast, the proportion of hospitalization costs decreased from 19% to 13% in CD (p<0.01), and 22% to 15% in UC (p < 0.01). Penetrating disease course predicted an increase of healthcare costs (adjusted odds ratio (adj. OR) 1.95 (95% CI 1.02-3.37) in CD and age <40 years in UC (adj. OR 4.72 (95% CI 1.61-13.86))., Conclusions: BD-related costs remained stable over two years. However, the proportion of anti-TNF-related healthcare costs increased, while hospitalization costs decreased. Factors associated with increased costs were penetrating disease course in CD and age <40 in UC.

Objective: Working through a depressive illness can improve mental health but also carries risks and costs from reduced concentration, fatigue, and poor on-the-job performance. However, evidence-based recommendations for managing work attendance decisions, which benefit individuals and employers, are lacking. Therefore, this study has compared the costs and health outcomes of short-term absenteeism versus working while ill ("presenteeism") amongst employed Australians reporting lifetime major depression., Methods: Cohort simulation using state-transition Markov models simulated movement of a hypothetical cohort of workers, reporting lifetime major depression, between health states over one- and five-years according to probabilities derived from a quality epidemiological data source and existing clinical literature. Model outcomes were health service and employment-related costs, and quality-adjusted-life-years (QALYs), captured for absenteeism relative to presenteeism, and stratified by occupation (blue versus white-collar)., Results: Per employee with depression, absenteeism produced higher mean costs than presenteeism over one- and five-years ($42,573/5-years for absenteeism, $37,791/5-years for presenteeism). However, overlapping confidence intervals rendered differences non-significant. Employment-related costs (lost productive time, job turnover), and antidepressant medication and service use costs of absenteeism and presenteeism were significantly higher for white-collar workers. Health outcomes differed for absenteeism versus presenteeism amongst white-collar workers only., Conclusions: Costs and health outcomes for absenteeism and presenteeism were not significantly different; service use costs excepted. Significant variation by occupation type was identified. These findings provide the first occupation-specific cost evidence which can be used by clinicians, employees, and employers to review their management of depression-related work attendance, and may suggest encouraging employees to continue working is warranted.

Background: The bile acid-activated nuclear receptor Farnesoid X Receptor (FXR) is critical in maintaining intestinal barrier integrity and preventing bacterial overgrowth. Patients with Crohn's colitis (CC) exhibit reduced ileal FXR target gene expression. FXR agonists have been shown to ameliorate inflammation in murine colitis models. We here explore the feasibility of pharmacological FXR activation in CC., Methods: Nine patients with quiescent CC and 12 disease controls were treated with the FXR ligand chenodeoxycholic acid (CDCA; 15 mg/kg/day) for 8 days. Ileal FXR activation was assessed in the fasting state during 6 hrs after the first CDCA dose and on day 8, by quantification of serum levels of fibroblast growth factor (FGF) 19. Since FGF19 induces gallbladder (GB) refilling in murine models, we also determined concurrent GB volumes by ultrasound. On day 8 ileal and cecal biopsies were obtained and FXR target gene expression was determined., Results: At baseline, FGF19 levels were not different between CC and disease controls. After the first CDCA dose, there were progressive increases of FGF19 levels and GB volumes during the next 6 hours in CC patients and disease controls (FGF19: 576 resp. 537% of basal; GB volumes: 190 resp. 178% of basal) without differences between both groups, and a further increase at day 8. In comparison with a separate untreated control group, CDCA affected FXR target gene expression in both CC and disease controls, without differences between both groups., Conclusions: Pharmacological activation of FXR is feasible in patients with CC. These data provide a rationale to explore the anti-inflammatory properties of pharmacological activation of FXR in these patients., Trial Registration: TrialRegister.nl NTR2009.

Background: We previously showed that activation of the bile salt nuclear receptor Farnesoid X Receptor (FXR) protects against intestinal inflammation in mice. Reciprocally, these inflammatory mediators may decrease FXR activation. We investigated whether FXR activation is repressed in the ileum and colon of inflammatory bowel disease (IBD) patients in remission. Additionally, we evaluated whether genetic variation in FXR is associated with IBD., Methods: mRNA expression of FXR and FXR target gene SHP was determined in ileal and colonic biopsies of patients with Crohn's colitis (n = 15) and ulcerative colitis (UC; n = 12), all in clinical remission, and healthy controls (n = 17). Seven common tagging SNPs and two functional SNPs in FXR were genotyped in 2355 Dutch IBD patients (1162 Crohn's disease (CD) and 1193 UC) and in 853 healthy controls., Results: mRNA expression of SHP in the ileum is reduced in patients with Crohn's colitis but not in patients with UC compared to controls. mRNA expression of villus marker Villin was correlated with FXR and SHP in healthy controls, a correlation that was weaker in UC patients and absent in CD patients. None of the SNPs was associated with IBD, UC or CD, nor with clinical subgroups of CD., Conclusions: FXR activation in the ileum is decreased in patients with Crohn's colitis. This may be secondary to altered enterohepatic circulation of bile salts or transrepression by inflammatory signals but does not seem to be caused by the studied SNPs in FXR. Increasing FXR activity by synthetic FXR agonists may have benefit in CD patients.