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No randomized controlled trial has evaluated the effect of long-term alcohol interventions on mortality. Results reported in existing observational studies may be subject to selection bias and time-varying confounding. Using data from the Australian Longitudinal Study on Women's Health 1946–1951 birth cohort, collected regularly from 1996–2016, we estimated all-cause and cancer mortality had women been assigned various alcohol interventions (in categories ranging from 0 to >30 g/day ethanol, or reduced to ≤20 g/day if higher) at baseline, and had they maintained these levels of consumption. The cumulative risks for all-cause and cancer mortality were 5.6% (10,118 women followed for 20 years) and 2.9% (18 years), respectively. For all-cause and cancer mortality, baseline ethanol up to 30 g/day showed lower risk and >30 g/day showed higher risk relative to abstention. Had women sustainedly followed the interventions, a similar relationship was observed for all-cause mortality. However, the negative association observed for intakes ≤30 g/day and positive association for intakes >30 g/day was not evident for cancer mortality. Our findings suggest that all-cause mortality could have been lower than observed if this cohort of women had consumed some alcohol (no more than 30 g/day) rather than no consumption, but cancer mortality might not. [ABSTRACT FROM AUTHOR]

Background: Quantifying the benefits and harms of breast cancer screening accurately is important for planning and evaluating screening programs and for enabling women to make informed decisions about participation. However, few cohort studies have attempted to estimate benefit and harm simultaneously. Aims: We aimed to quantify the impact of mammographic screening on breast cancer mortality and overdiagnosis using a cohort of women invited to attend Australia's national screening program, BreastScreen. Methods: In a cohort of 41,330 women without prior breast cancer diagnosis, screening, or diagnostic procedures invited to attend BreastScreen Western Australia in 1994‐1995, we estimated the cumulative risk of breast cancer mortality and breast cancer incidence (invasive and ductal carcinoma in situ) from age 50 to 85 years for attenders and non‐attenders. Data were obtained by linking population‐based state and national health registries. Breast cancer mortality risks were estimated from a survival analysis that accounted for competing risk of death from other causes. Breast cancer risk for unscreened women was estimated by survival analysis, while accounting for competing causes of death. For screened women, breast cancer risk was the sum of risk of being diagnosed at first screen, estimated using logistic regression, and risk of diagnosis following a negative first screen estimated from a survival analysis. Results: For every 1,000 women 50 years old at first invitation to attend BreastScreen, there were 20 (95% CI 12‐30) fewer breast cancer deaths and 25 (95% CI 15‐35) more breast cancers diagnosed for women who attended than for non‐attendees by age 85. Of the breast cancers diagnosed in screened women, 21% (95% CI 13%‐27%) could be attributed to screening. Discussion: The estimated ratio of benefit to harm was consistent with, but slightly less favourable to screening than most other estimates from cohort studies. Conclusion: Women who participate in organised screening for breast cancer in Australia have substantially lower breast cancer mortality, while some screen‐detected cancers may be overdiagnosed. [ABSTRACT FROM AUTHOR]

Background: Observational studies have consistently found a link between low serum 25‐hydroxyvitamin D concentration and higher risk of cognitive impairment. Results from randomized controlled trials have been mixed, and few have been conducted in the general population. Methods: We recruited 21,315 community‐dwelling Australians aged between 60 and 84 years to participate in the D‐Health Trial, a randomized, double‐blind, placebo‐controlled trial. The intervention was monthly oral doses of 60,000 international units of vitamin D or placebo for 5 years. We assessed cognitive function in a randomly sampled group of participants aged ≥70 years using the Telephone Interview for Cognitive Status (TICS) at 2 and 5 years after randomization. The primary outcome for this analysis was TICS score; the secondary outcome was the proportion of people who had cognitive impairment (defined as TICS score ≤25). We analyzed data using mixed models (linear and logistic). Results: We interviewed 3887 participants at year 2 and 3614 participants at year 5. The mean TICS score at these time points was 32.3 and 32.2, respectively. Vitamin D supplementation did not affect cognitive function as measured by TICS score (mean difference between vitamin D and placebo groups 0.04; 95% CI −0.14 to 0.23), or alter risk of cognitive impairment (odds ratio 1.00; 95% CI 0.75 to 1.33). Conclusions: Monthly bolus doses of vitamin D supplementation neither enhanced nor hindered cognitive function among older adults. Population‐wide vitamin D supplementation of older adults that are largely vitamin D replete is unlikely to substantially benefit cognition. [ABSTRACT FROM AUTHOR]

Background: Vitamin D supplementation may reduce the risk or severity of infection, but this has been investigated in few large population-based trials. We analyzed data from the D-Health Trial, using prescription of antibiotics as a surrogate for infection.Methods: The D-Health Trial is a randomized, double-blind, placebo-controlled trial in which 21 315 Australians aged 60-84 years were randomized to 60 000 IU of supplementary vitamin D3 or placebo monthly for 5 years. For this analysis, the primary outcome was the number of antibiotic prescription episodes; secondary outcomes were total number of prescriptions, repeat prescription episodes, and antibiotics for urinary tract infection. We estimated incidence rate ratios (IRRs) using negative binomial regression, and odds ratios using logistic regression.Results: Vitamin D supplementation slightly reduced the number of prescription episodes (IRR, 0.98; 95% confidence interval [CI], .95-1.01), total prescriptions (IRR, 0.97; 95% CI, .93-1.00), and repeat prescription episodes (IRR, 0.96; 95% CI, .93-1.00). There was stronger evidence of benefit in people predicted to have insufficient vitamin D at baseline (prescription episodes IRR, 0.93; 95% CI, .87-.99).Conclusions: Vitamin D may reduce the number of antibiotic prescriptions, particularly in people with low vitamin D status. This supports the hypothesis that vitamin D has a clinically relevant effect on the immune system.Clinical Trials Registration: Australian New Zealand Clinical Trials Registry: ACTRN12613000743763. https://www.anzctr.org.au/. [ABSTRACT FROM AUTHOR]

Objectives: Previously, based on 6 months of follow-up, we showed that HPV self-sampling improved participation in cervical screening compared to a reminder letter for Pap testing for never- and under-screened women. Here, we report follow-up and related screening outcomes for women who participated in the initial self-sampling over two screening rounds. Setting: The randomised controlled trial was conducted in Australia. Methods: Never- and under-screened women were randomly allocated to the HPV self-sampling or the reminder for Pap test arm and followed at 6 and 36 months since the kits were first mailed. Results: The first round of HPV self-sampling kits were mailed from May–July 2014 to 12 572 women. After 36 months, 19% of never-screened and 9% of under-screened women returned a kit for HPV testing; 2.7% were HPV 16/18 and 5.8% non-16/18 HPV positive. Compliance with first round follow-up was 84% (95% CI: 77.1–89.5%). Non-compliant and cytology triage negative women were mailed another kit at 12 months. Compliance at 12-month follow-up was 59.3% (49.4 to 68.6%). Of 37 women with a 12-month repeat HPV, 70% were positive. Of women who tested negative for HPV in the first round (n = 1573), 25% attended regular screening in the next round and none had CIN2 + detected. The overall prevalence of CIN2 + was 8.5 per 1000 screened (4.8 to 13.9 per 1000). Conclusion: While self-sampling can successfully engage women, compliance with repeat testing may require monitoring. The clinician-supported self-collection pathway now in use in Australia will likely improve women's engagement with follow-up. [ABSTRACT FROM AUTHOR]

We examined demographic and lifestyle risk factors for incidence of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) in an Australian cohort of 20,975 participants aged 40–63 at recruitment (1990–1994). Information on GERD and BE was collected between 2007 and 2010. GERD symptoms were defined as self-reported heartburn or acid regurgitation. BE was defined as endoscopically confirmed columnar-lined esophagus. Risk factors for developing GERD symptoms, BE diagnosis, age at symptom onset, and age at BE diagnosis were quantified using regression. During a mean follow-up of 15.8 years, risk of GERD symptoms was 7.5% (n  = 1,318) for daily, 7.5% (n  = 1,333) for 2–6 days/week, and 4.3% (n  = 751) for 1 day/week. There were 210 (1.0%) endoscopically diagnosed BE cases, of whom 141 had histologically confirmed esophageal intestinal metaplasia. Female sex, younger age, lower socioeconomic position (SEP) and educational attainment, and former smoking were associated with higher GERD risk. Male sex and smoking were associated with earlier GERD symptom onset. Men, older participants, those with higher SEP, and former smokers were at higher BE risk. There was some evidence higher SEP was associated with earlier BE diagnosis. GERD and BE had different demographic risk factors but shared similar lifestyle factors. Earlier GERD symptom onset for men and smokers might have contributed to higher BE risk. The SEP patterns observed for GERD and BE suggest potential inequity in access to care. These findings would be important in the development of clinical risk prediction models for early detection of BE. [ABSTRACT FROM AUTHOR]

Background: Falls cause considerable morbidity and mortality in older people. It is unclear how vitamin D supplementation affects falls risk, particularly when taken at high doses. We sought to determine whether monthly high‐dose vitamin D supplementation reduces risk and incidence of falls. Methods: We used data from the randomized, double‐blind, placebo‐controlled D‐Health Trial conducted in Australia. Between February 2014 and May 2015, 21 315 participants aged 60–84 years were randomized (1:1) to monthly doses of either 60 000 IU of colecalciferol or placebo for a maximum of 5 years. People who reported a history of osteomalacia, sarcoidosis, hyperparathyroidism, hypercalcaemia or kidney stones or who were taking >500 IU/day supplementary vitamin D were ineligible. Each year, we collected blood samples from ~450 randomly sampled participants from each trial arm and measured 25‐hydroxyvitamin D [25(OH)D]. Falls, a prespecified tertiary outcome, were ascertained using annual surveys and, for a subset of participants, 3‐month falls diaries. The primary outcome for this analysis was any fall in the month before completing an annual survey. As part of our process to maintain blinding, we used random samples of participants (surveys, n = 16 000; diaries, n = 2400), with equal numbers per group. Participants with no outcome data were excluded. Following an intention‐to‐treat approach, we analysed outcomes using logistic, ordinal and negative binomial regression. Registration: Australian New Zealand Clinical Trials Registry (ACTRN12613000743763); registered 4 July 2013. Results: Mean treatment duration was 4.3 years (standard deviation [SD] = 1.4 years). Mean serum 25(OH)D concentrations during the trial were 114.8 (SD 30.3) nmol/L and 77.5 (SD 25.2) nmol/L in the vitamin D and placebo groups, respectively. Survey and diary analytic sets included 15 416 and 2200 participants, respectively; approximately half were randomized to vitamin D (surveys: 50.1%; diaries: 50.4%). Vitamin D had no effect on falling in the past month (odds ratio [OR] 1.02, 95% confidence interval [CI] 0.95–1.10). There was an interaction with body mass index (BMI) (P‐interaction = 0.001); vitamin D increased risk in participants with BMI < 25 kg/m2 (OR 1.25, 95% CI 1.09–1.43), but there was no effect in those with BMI ≥ 25 kg/m2 (OR 0.95, 95% CI 0.87–1.04). Analyses of diary data were consistent with these findings. The incidence of hypercalcaemia and kidney stones did not differ between groups. Conclusions: Monthly high‐dose vitamin D supplementation did not reduce risk of falling. A possible increased risk of falling with vitamin D supplementation in people with normal BMI warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Self-reported physical activity is inaccurate, yet few investigators attempt to adjust for measurement error when estimating risks for health outcomes. We estimated what the association between self-reported physical activity and colorectal cancer risk would be if physical activity had been assessed using accelerometry instead.Methods: We conducted a validation study in which 235 Australian adults completed a telephone-administered International Physical Activity Questionnaire (IPAQ), and wore an accelerometer (Actigraph GT3X+) for 7 days. Using accelerometer-assessed physical activity as the criterion measure, we calculated validity coefficients and attenuation factors using a structural equation model adjusted for age, sex, education and body mass index. We then used a regression calibration approach to apply the attenuation factors to data from the Melbourne Collaborative Cohort Study (MCCS) to compute bias-adjusted hazard ratios (HR) and 95% confidence intervals (CI).Results: Average daily minutes of physical activity from the short form of the International Physical Activity Questionnaire (IPAQ-short) were substantially higher than accelerometer-measured duration (55 versus 32 min). The validity coefficient (0.32; 95% CI: 0.20, 0.43) and attenuation factor (0.20; 95% CI: 0.12, 0.28) were low. The HRs for colorectal cancer risk for high (75th percentile; 411 min/week) versus low (25th percentile; 62 min/week) levels of self-reported physical activity were 0.95 (95% CI: 0.87, 1.05) before and 0.78 (95% CI: 0.47, 1.28) after bias adjustment.Conclusions: Over-estimation of physical activity by the IPAQ-short substantially attenuates the association between physical activity and colorectal cancer risk, suggesting that the protective effect of physical activity has been previously underestimated. [ABSTRACT FROM AUTHOR]

Investigators in large-scale population health studies face increasing difficulties in recruiting representative samples of participants. Nonparticipation, item nonresponse, and attrition, when follow-up is involved, often result in highly selected samples even in well-designed studies. We aimed to assess the potential value of multilevel regression and poststratification, a method previously used to successfully forecast US presidential election results, for addressing biases due to nonparticipation in the estimation of population descriptive quantities in large cohort studies. The investigation was performed as an extensive case study using baseline data (2013–2014) from a large national health survey of Australian males (Ten to Men: The Australian Longitudinal Study on Male Health). Analyses were performed in the open-source Bayesian computational package RStan. Results showed greater consistency and precision across population subsets of varying sizes when compared with estimates obtained using conventional survey sampling weights. Estimates for smaller population subsets exhibited a greater degree of shrinkage towards the national estimate. Multilevel regression and poststratification provides a promising analytical approach to addressing potential participation bias in the estimation of population descriptive quantities from large-scale health surveys and cohort studies. [ABSTRACT FROM AUTHOR]

Background: In a previous paper, we had assumed that the risk of screen-detected breast cancer mostly reflects inherent risk, and the risk of whether a breast cancer is interval versus screen-detected mostly reflects risk of masking. We found that inherent risk was predicted by body mass index (BMI) and dense area (DA) or percent dense area (PDA), but not by non-dense area (NDA). Masking, however, was best predicted by PDA but not BMI. In this study, we aimed to investigate if these associations vary by tumor characteristics and mode of detection.Methods: We conducted a case-control study nested within the Melbourne Collaborative Cohort Study of 244 screen-detected cases matched to 700 controls and 148 interval cases matched to 446 controls. DA, NDA and PDA were measured using the Cumulus software. Tumor characteristics included size, grade, lymph node involvement, and ER, PR, and HER2 status. Conditional and unconditional logistic regression were applied as appropriate to estimate the Odds per Adjusted Standard Deviation (OPERA) adjusted for age and BMI, allowing the association with BMI to be a function of age at diagnosis.Results: For screen-detected cancer, both DA and PDA were associated to an increased risk of tumors of large size (OPERA ~ 1.6) and positive lymph node involvement (OPERA ~ 1.8); no association was observed for BMI and NDA. For risk of interval versus screen-detected breast cancer, the association with risk for any of the three mammographic measures did not vary by tumor characteristics; an association was observed for BMI for positive lymph nodes (OPERA ~ 0.6). No associations were observed for tumor grade and ER, PR and HER2 status of tumor.Conclusions: Both DA and PDA were predictors of inherent risk of larger breast tumors and positive nodal status, whereas for each of the three mammographic density measures the association with risk of masking did not vary by tumor characteristics. This might raise the hypothesis that the risk of breast tumours with poorer prognosis, such as larger and node positive tumours, is intrinsically associated with increased mammographic density and not through delay of diagnosis due to masking. [ABSTRACT FROM AUTHOR]

Objectives. To test whether shade sails will increase the use of passive recreation areas (PRAs). Methods. We conducted a stratified randomized pretest–posttest controlled design study in Melbourne, Australia, and Denver, Colorado, in 2010 to 2014. We randomized a sample of 144 public parks with 2 PRAs in full sun in a 1:3 ratio to treatment or control. Shade sails were built at 1 PRA per treatment park. The outcome was any use of the study PRA (n = 576 pretest and n = 576 posttest observations; 100% follow-up). Results. Compared with control PRAs (adjusted probability of use: pretest = 0.14, posttest = 0.17), use of treatment PRAs (pretest = 0.10, posttest = 0.32) was higher at posttest (odds ratio [OR] = 3.91; 95% confidence interval [CI] = 1.71, 8.94). Shade increased use of PRAs in Denver (control: pretest = 0.18, posttest = 0.19; treatment: pretest = 0.16, posttest = 0.47) more than Melbourne (control: pretest = 0.11, posttest = 0.14; shaded: pretest = 0.06, posttest = 0.19; OR = 2.98; 95% CI = 1.09, 8.14). Conclusions. Public investment in shade is warranted for skin cancer prevention and may be especially useful in the United States. [ABSTRACT FROM AUTHOR]

Objective: To investigate relationships between mortality and circulating 25-hydroxyvitamin D (25(OH)D), 25-hydroxycholecalciferol (25(OH)D3) and 25-hydroxyergocalciferol (25(OH)D2).Design: Case-cohort study within the Melbourne Collaborative Cohort Study (MCCS). We measured 25(OH)D2 and 25(OH)D3 in archived dried blood spots by LC-MS/MS. Cox regression was used to estimate mortality hazard ratios (HR), with adjustment for confounders.Setting: General community.Subjects: The MCCS included 29 206 participants, who at recruitment in 1990-1994 were aged 40-69 years, had dried blood spots collected and no history of cancer. For the present study we selected participants who died by 31 December 2007 (n 2410) and a random sample (sub-cohort, n 2996).Results: The HR per 25 nmol/l increment in concentration of 25(OH)D and 25(OH)D3 were 0·86 (95 % CI 0·78, 0·96; P=0·007) and 0·85 (95 % CI 0·77, 0·95; P=0·003), respectively. Of 5108 participants, sixty-three (1·2 %) had detectable 25(OH)D2; their mean 25(OH)D concentration was 11·9 (95 % CI 7·3, 16·6) nmol/l higher (P<0·001). The HR for detectable 25(OH)D2 was 1·80 (95 % CI 1·09, 2·97; P=0·023); for those with detectable 25(OH)D2, the HR per 25 nmol/l increment in 25(OH)D was 1·06 (95 % CI 0·87, 1·29; P interaction=0·02). HR were similar for participants who reported being in good, very good or excellent health four years after recruitment.Conclusions: Total 25(OH)D and 25(OH)D3 concentrations were inversely associated with mortality. The finding that the inverse association for 25(OH)D was restricted to those with no detectable 25(OH)D2 requires confirmation in populations with higher exposure to ergocalciferol. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnoea is a common disorder with under-rated clinical impact, which is increasingly being recognised as having a major bearing on global disease burden. Men are especially vulnerable and become a priority group for preventative interventions. However, there is limited information on prevalence of the condition in Australia, its co-morbidities, and potential risk factors.Methods: We used data from 13,423 adult men included in the baseline wave of Ten to Men, an Australian national study of the health of males, assembled using stratified cluster sampling with oversampling from rural and regional areas. Those aged 18-55 years self-completed a paper-based questionnaire that included a question regarding health professional-diagnosed sleep apnoea, physical and mental health status, and health-related behaviours. Sampling weights were used to account for the sampling design when reporting the prevalence estimates. Odds ratios were used to describe the association between health professional-diagnosed sleep apnoea and potential correlates while adjusting for age, country of birth, and body-mass index (BMI).Results: Prevalence of self-reported health professional-diagnosed sleep apnoea increased from 2.2 % in age 18-25 years to 7.8 % in the age 45-55 years. Compared with those without sleep apnoea, those with sleep apnoea had significantly poorer physical, mental, and self-rated health as well as lower subjective wellbeing and poorer concentration/remembering (p < 0.001 for all). Sleep apnoea was significantly associated with older age (p < 0.001), unemployment (p < 0.001), asthma (p = 0.011), chronic obstructive pulmonary disease/chronic bronchitis (p = 0.002), diabetes (p < 0.001), hypercholesterolemia (p < 0.001), hypertension (p < 0.001), heart attack (p < 0.001), heart failure (p < 0.001), angina (p < 0.001), depression (p < 0.001), post-traumatic stress disorder (p < 0.001), other anxiety disorders (p < 0.001), schizophrenia (p = 0.002), overweight/obesity (p < 0.001), insufficient physical activity (p = 0.006), smoking (p = 0.005), and high alcohol consumption (p < 0.001).Conclusion: Health professional-diagnosed sleep apnoea is relatively common, particularly in older males. Associations between sleep apnoea and cardiovascular, metabolic, respiratory, and psychiatric disorders have important clinical and public health implications. As men are especially vulnerable to sleep apnoea as well as some of its chronic co-morbidities, they are potentially a priority group for health interventions. Modifiable lifestyle related factors such as smoking, alcohol consumption, level of physical activity and BMI are possible key foci for interventions. [ABSTRACT FROM AUTHOR]

Background: Diabetes is a global public health issue. It is associated with significant disability, morbidity and mortality risks and substantial healthcare costs. Of great concern is the fact that its prevalence is rising, particularly amongst the young, while epidemiological data regarding the incidence, prevalence and complications of early-onset type 2 diabetes is noted to be sparse.Methods: We used data from the baseline wave of Ten to Men, a national cohort study of Australian males, to investigate the social and health-related correlates of Australian males aged 18-49 years reporting being diagnosed with diabetes.Results: The estimated prevalence of a self-reported diabetes diagnosis amongst Australian males aged 18-49 years was 2.95 % (95 % CI: 2.54-3.43 %). Within this age group, approximately 75 % of those diagnosed with diabetes are expected to be living with a known diagnosis of type 2 diabetes; the remainder are expected to be living with type 1 diabetes. Of the 20 social and health-related factors considered, we found evidence to support the association of eighteen factors after adjusting for age and body mass index. The strongest correlates of reporting a diabetes diagnosis, associated with a ≥2-fold increase in the odds of reporting diabetes were being aged 35-49 years, being unemployed, being obese, seeing a doctor for a check-up more frequently, reporting comorbid high blood pressure or physical or mental health comorbidities and worse self-rated and physical health status.Conclusion: Australian males aged 18-49 years who are living with a known diagnosis of diabetes are more likely to be socio-economically disadvantaged and suffer substantially worse health status than Australian males aged 18-49 years living without a diabetes diagnosis. Based on the associations detected in this study, older, single males living in regional areas who are socioeconomically disadvantaged, obese and/or who have other comorbidities may be an important subgroup to target for diabetes screening, disease management and prevention efforts. [ABSTRACT FROM AUTHOR]

We are very pleased to introduce Ten to Men, the Australian Longitudinal Study on Male Health. Ten to Men is, to our knowledge, the largest national all-male cohort study in the world. It involves 15,988 males who were aged between 10 and 55 years when we recruited them in 2013/14. Together, the articles in this collection provide an overview of the study's methods, examples of some of the key questions it can answer, and guidance for researchers wishing to use it. Perhaps most importantly, the articles demonstrate the enormous potential Ten to Men has to make a real difference to our understanding of male health and the factors that influence it. [ABSTRACT FROM AUTHOR]

Background: The Australian Longitudinal Study on Male Health (Ten to Men) was established in 2011 to build the evidence base on male health to inform policy and program development.Methods: Ten to Men is a national longitudinal study with a stratified multi-stage cluster random sample design and oversampling in rural and regional areas. Household recruitment was conducted from October 2013 to July 2014. Males who were aged 10 to 55 years residing in private dwellings were eligible to participate. Data were collected via self-completion paper questionnaires (participants aged 15 to 55) and by computer-assisted personal interview (boys aged 10 to 14). Household and proxy health data for boys were collected from a parent via a self-completion paper-based questionnaire. Questions covered socio-demographics, health status, mental health and wellbeing, health behaviours, social determinants, and health knowledge and service use.Results: A cohort of 15,988 males aged between 10 and 55 years was recruited representing a response fraction of 35 %.Conclusion: Ten to Men is a unique resource for investigating male health and wellbeing. Wave 1 data are available for approved research projects. [ABSTRACT FROM AUTHOR]

Background: Reported associations between protein intake from different sources and type 2 diabetes (T2D) have been inconsistent. Objective: We prospectively examined the relations of total, animal, and plant protein intakes with incident T2D. Design: We followed 21,523 participants (women: 61.7%) between 1990 and 2007 from the Melbourne Collaborative Cohort Study who were free of diabetes, cardiovascular disease, cancer, and kidney stones at baseline. We also conducted a meta-analysis that included the results from our cohort and from 10 previous prospective studies. Results: A total of 929 new cases (4.3%) of T2D were documented during a mean of 11.7 y of follow-up. Multivariate-adjusted ORs for incident T2D in the highest compared with lowest quintiles of total and animal protein intakes as percentages of energy were 1.23 (95% CI: 0.96, 1.56; P-trend = 0.029) and 1.29 (95% CI: 0.99, 1.67; P-trend = 0.014), respectively. These associations appeared to be greater in men and in participants with normal baseline plasma glucose, body mass index, or blood pressure. Plant protein intake was inversely associated with incident T2D in women only (OR; 0.60; 95% CI: 0.37, 0.99). In the meta-analysis of 11 prospective cohort studies with 505,624 participants and 37,918 T2D cases (follow-up range: 5-24 y), pooled RRs for the comparison of the highest with lowest categories of total, animal, and plant protein intakes were 1.09 (95% CI: 1.06, 1.13), 1.19 (95% CI: 1.11, 1.28), and 0.95 (95% CI: 0.89, 1.02), respectively. Associations between animal protein intake and T2D were similar across sex, geographic region, length of follow-up, study quality, and method of expressing protein intake. An inverse association between plant protein intake and T2D was observed in women (RR: 0.93; 95% CI: 0.85, 1.00) and in US populations (RR: 0.91; 95% CI: 0.84, 0.97). Conclusion: Higher intakes of total and animal protein were both associated with increased risks of T2D, whereas higher plant protein intake tended to be associated with lower risk of T2D. [ABSTRACT FROM AUTHOR]

Age-related loss of skeletal muscle is associated with increased risk of functional limitation and cardiovascular (CV) mortality. In the elderly abdominal aortic calcification (AAC) can increase CV risk by altering aortic properties which may raise blood pressure and increase cardiac workload. This study investigated the association between low muscle mass and AAC in community-dwelling older Australians. Data for this cross-sectional analysis were drawn from a 2010 sub-study of the Melbourne Collaborative Cohort Study in the setting of community-dwelling older adults. Three hundred and twenty-seven participants [mean age = 71 ± 6 years; mean BMI = 28 ± 5 kg/m(2); females n = 199 (62 %)] had body composition determined by dual-energy x-ray absorptiometry (DXA) and AAC determined by radiography. Participants were stratified into tertiles of sex-specific BMI-normalised appendicular lean mass (ALM). Those in the lowest tertile were considered to have low relative muscle mass. Aortic calcification score (ACS) was determined visually as the extent of calcification on the aortic walls between L1 and L4 vertebrae (range: 0-24). Severe AAC was defined as ACS ≥ 6. Prevalence of any AAC was highest in participants with low relative muscle mass (74 %) compared to the middle (65 %) and upper (53 %) tertiles (p trend = 0.006). The lower ALM/BMI tertile had increased odds (Odds ratio = 2.3; 95 % confidence interval: 1.1-4.6; p = 0.021) of having any AAC; and having more severe AAC (2.2; 1.2-4.0; p = 0.009) independent of CV risk factors, serum calcium and physical activity. AAC is more prevalent and severe in community-dwelling older adults with low relative muscle mass. Maintaining muscle mass could form part of a broader primary prevention strategy in reducing AAC. [ABSTRACT FROM AUTHOR]

The importance of addressing health disparities experienced by boys and men reached tangible prominence in Australia with adoption of the 2010 National Male Health Policy and the establishment of a national longitudinal study on male health—Ten to Men. Ten to Men is based on a holistic model of health with a strong focus on social determinants and health and well-being over the life course. Given the life course focus, we set out to assess if health-related characteristics and the correlates of self-rated health differ across the life course among four sociologically defined generations of Australian males. While some differences in the correlates of good or excellent health were observed across generations, addressing obesity and depression appear to be important for improving the health of Australian males of all ages. [ABSTRACT FROM AUTHOR]

Background: Studies reporting the association between change in weight or body mass index during midlife and risk of colorectal cancer have found inconsistent results, and only one study to date has reported the association between change in waist circumference (a measure of central adiposity) and risk of colorectal cancer.Methods: We investigated the association between risk of colorectal cancer and changes in directly measured waist circumference and weight from baseline (1990-1994) to wave 2 (2003-2007). Cox regression, with age as the time metric and follow-up starting at wave 2, adjusted for covariates selected from a causal model, was used to estimate the Hazard Ratios (HRs) and 95 % Confidence Intervals (CIs) for the change in waist circumference and weight in relation to risk of colorectal cancer.Results: A total of 373 cases of colorectal cancer were diagnosed during an average 9 years of follow-up of 20,605 participants. Increases in waist circumference and weight were not associated with the risk of colorectal cancer (HR per 5 cm increase in waist circumference = 1.02; 95 % CI: 0.95, 1.10; HR per 5 kg increase in weight = 0.93; 0.85, 1.02). For individuals with a waist circumference at baseline that was less than the sex-specific mean value there was a slight increased risk of colorectal cancer associated with a 5 cm increase in waist circumference at wave 2 (HR = 1.08; 0.97, 1.21).Conclusion: Increases in waist circumference and weight during midlife do not appear to be associated with the risk of colorectal cancer. [ABSTRACT FROM AUTHOR]

Background Conventionally, cohort studies have assessed the association between alcohol and all-cause mortality by using alcohol intake at enrolment. Methods In the Melbourne Collaborative Cohort Study, participants were asked about usual frequency and quantity of beverage-specific alcohol intake for 10-year periods starting at age 20 from which current, past and lifetime intakes were calculated. We used Cox regression to estimate hazard ratios for mortality for 39 577 participants of the Melbourne Collaborative Cohort Study aged 40-69 at baseline. Results After a mean follow-up of 15 years/person, we identified 4639 deaths. Associations between all-cause mortality and lifetime, current (baseline) and past intake were J shaped, with lower mortality at low intake (e.g. <40 g/dayfor men and 10 g/day for women using lifetime intake) and elevated mortality at higher intake. For men, consistent light-to-moderate drinking (>0-39/>0-39 g/day) from age 20 to baseline age was associated with a 16% lower mortality, while heavy drinking at both ages (≥80/≥40 and ≥40/0 g/day) was associated with higher mortality compared with stable abstinence. Conclusions Our findings support a reduced mortality risk associated with low-dose drinking but also highlight a higher mortality risk for consistent heavy drinking from a young age. [ABSTRACT FROM AUTHOR]

Observational studies have suggested that 25-hydroxyvitamin D (25(OH)D) levels are associated with inflammatory markers. Most trials reporting significant associations between vitamin D intake and inflammatory markers used specific patient groups. Thus, we aimed to determine the effect of supplementary vitamin D using secondary data from a population-based, randomised, placebo-controlled, double-blind trial (Pilot D-Health trial 2010/0423). Participants were 60- to 84-year-old residents of one of the four eastern states of Australia. They were randomly selected from the electoral roll and were randomised to one of three trial arms: placebo (n 214), 750 μg (n 215) or 1500 μg (n 215) vitamin D3, each taken once per month for 12 months. Post-intervention blood samples for the analysis of C-reactive protein (CRP), IL-6, IL-10, leptin and adiponectin levels were available for 613 participants. Associations between intervention group and biomarker levels were evaluated using quantile regression. There were no statistically significant differences in distributions of CRP, leptin, adiponectin, leptin:adiponectin ratio or IL-10 levels between the placebo group and either supplemented group. The 75th percentile IL-6 level was 2·8 pg/ml higher (95 % CI 0·4, 5·8 pg/ml) in the 1500 μg group than in the placebo group (75th percentiles:11·0 v. 8·2 pg/ml), with a somewhat smaller, non-significant difference in 75th percentiles between the 750 μg and placebo groups. Despite large differences in serum 25(OH)D levels between the three groups after 12 months of supplementation, we found little evidence of an effect of vitamin D supplementation on cytokine or adipokine levels, with the possible exception of IL-6. [ABSTRACT FROM PUBLISHER]

Unlabelled: Background The study evaluated acceptability, invitation letters and the test kit for a trial of human papillomavirus (HPV) self-sampling among never- and under-screened women in Australia.Methods: Victorian women, 30-69 years, who had never had a Pap test or were overdue for one, participated. Four focus groups including eight to nine participants segmented by age (30-49 and 50-69 years) and screening history (never- and under-screened) were conducted in August 2013. Discussions were recorded and transcribed verbatim and data analysed using thematic content analysis.Results: The response to the concept of HPV self-sampling was positive. Decision-making was largely influenced by the content of a pre-invitation letter. Appealing features of self-sampling were cost (free), convenience (home-based) and anticipated less discomfort (with a swab) than a Pap test. Small kits that fit in mailboxes were preferred over post office parcel collection. The perceived barriers include concerns about test accuracy and lack of confidence that a home-based test would give the same results as a physician administered test. Women wanted information on the timing of receipt of the results and information about the organisation providing the test.Conclusion: HPV self-sampling is a possible alternative for Australian women who are reluctant to have a Pap test and may increase the likelihood of participation in cervical cancer screening if women's concerns about it can be addressed. The findings of this study are relevant for researchers, policymakers and practitioners implementing self-sampling for under-screened women as part of cervical screening programs. [ABSTRACT FROM AUTHOR]

Purpose: To determine and compare the prevalence of age-related macular degeneration (AMD) in older Australians of Anglo-Celtic and Southern European origin. Methods: A total of 21,132 participants of the Melbourne Collaborative Cohort Study, aged 47-86 years, were assessed for AMD in 2003-2007 with non-mydriatic fundus photography. Of these, 14% were born in Southern Europe (Greece, Italy or Malta), with the remaining 86% of Anglo-Celtic origin, born in Australia, the United Kingdom or New Zealand. Results: Overall, 2694 participants (12.7%) had early stages of AMD, defined as either one or more drusen ≥125 μm (with or without pigmentary abnormalities) or one or more drusen 63-124 μm with pigmentary abnormalities in a 6000-μm diameter grading grid, in the absence of late AMD in either eye. A total of 122 participants (0.6%) had late AMD, defined as either geographic atrophy or neovascular AMD. In logistic regression analysis, adjusted for age, sex, smoking, education and physical activity, Southern Europeans compared to Anglo-Celts had a higher prevalence of the early stages of AMD (odds ratio, OR, 1.15, 95% confidence interval, CI, 1.00-1.34), and lower prevalence of late AMD (OR 0.36, 95% CI 0.17-0.78). Conclusions: Australians of Southern European origin have a higher prevalence of the early stages of AMD and lower prevalence of late AMD compared to those of Anglo-Celtic origin. Although AMD prevalence in the older age group(s) of Southern Europeans could be underestimated due to disparity in participation rates, it is likely that both lifestyle and genetic factors play their parts in differential AMD prevalence in these ethnic groups. [ABSTRACT FROM AUTHOR]

Background: Organized screening based on Pap tests has substantially reduced deaths from cervical cancer in many countries, including Australia. However, the impact of the program depends upon the degree to which women participate. A new method of screening, testing for human papillomavirus (HPV) DNA to detect the virus that causes cervical cancer, has recently become available. Because women can collect their own samples for this test at home, it has the potential to overcome some of the barriers to Pap tests. The iPap trial will evaluate whether mailing an HPV self-sampling kit increases participation by never- and under-screened women within a cervical screening program. Methods/Design: The iPap trial is a parallel randomized controlled, open label, trial. Participants will be Victorian women age 30-69 years, for whom there is either no record on the Victorian Cervical Cytology Registry (VCCR) of a Pap test (never-screened) or the last recorded Pap test was between five to fifteen years ago (under-screened). Enrolment information from the Victorian Electoral Commission will be linked to the VCCR to determine the never-screened women. Variables that will be used for record linkage include full name, address and date of birth. Never- and under-screened women will be randomly allocated to either receive an invitation letter with an HPV self-sampling kit or a reminder letter to attend for a Pap test, which is standard practice for women overdue for a test in Victoria. All resources have been focus group tested. The primary outcome will be the proportion of women who participate, by returning an HPV self-sampling kit for women in the self-sampling arm, and notification of a Pap test result to the Registry for women in the Pap test arm at 3 and 6 months after mailout. The most important secondary outcome is the proportion of test-positive women who undergo further investigations at 6 and 12 months after mailout of results. Discussion: The iPap trial will provide strong evidence about whether HPV self-sampling could be used in Australia to improve participation in cervical screening for never-and under-screened women. [ABSTRACT FROM AUTHOR]

Despite a vast improvement in the survival of people living with HIV (PLHIV) since the introduction of combination antiretroviral treatment (cART), little change in the self-rated health of PLHIV has been observed since the introduction of cART in Australia. Difficulties with attaining employment or achieving financial security have been noted as some of the key challenges still facing PLHIV in the post-cART era. As a result, we investigated the independent association of a number of key social determinants of health with self-rated health among HIV-positive gay and bisexual men in Australia. Data from two recent national, cross-sectional surveys of PLHIV (the HIV Futures 5 and 6 surveys) were used. Logistic regression was used to assess the independent association of ethnicity, region of residence, education level, employment status, after-tax income, experience of HIV-related discrimination, level of social support, relationship status and recent sexual activity with reporting good–excellent self-rated health, after adjusting for clinical factors and other social determinants of health. Multiple imputation was used to estimate missing data for variables with >5% missing data. Of the 1713 HIV-positive gay/bisexual men who responded to the HIV Futures 5 and 6 surveys, information on self-rated health was available for 99.3%. Close to three-quarters of these respondents (72.1%) reported their self-rated health as good or excellent; the remainder (27.9%) reported their self-rated health as poor or fair. In multivariable analysis involving 89.3% of respondents, being employed, reporting recent sexual activity, a greater number of sources of social support and a higher weekly after-tax income were found to be independently associated with reporting good–excellent self-rated health. Despite the inability of this study to detect causal associations, addressing barriers to employment and sexual activity, and mechanisms to increase social support, is likely to have positive health effects for PLHIV in Australia. [ABSTRACT FROM AUTHOR]

Background: Observational data suggested that supplementation with vitamin D could reduce risk of infection, but trial data are inconsistent. Objective: We aimed to examine the effect of oral vitamin D supplementation on antibiotic use. Design: We conducted a post hoc analysis of data from pilot D-Health, which is a randomized trial carried out in a general community setting between October 2010 and February 2012. A total of 644 Australian residents aged 60-84 y were randomly assigned to receive monthly doses of a placebo (n = 214) or 30,000 (n = 215) or 60,000 (n = 215) IU oral cholecalciferol for ⩽12 mo. Antibiotics prescribed during the intervention period were ascertained by linkage with pharmacy records through the national health insurance scheme (Medicare Australia). Results: People who were randomly assigned 60,000 IU cholecalciferol had nonsignificant 28% lower risk of having antibiotics prescribed at least once than did people in the placebo group (RR: 0.72; 95% CI: 0.48, 1.07). In analyses stratified by age, in subjects aged ⩾70 y, there was a significant reduction in antibiotic use in the highdose vitamin D compared with placebo groups (RR: 0.53; 95% CI: 0.32, 0.90), whereas there was no effect in participants aged <70 y (RR: 1.07; 95% CI: 0.58, 1.97) (P-interaction = 0.1). Conclusion: Although this study was a post hoc analysis and statistically nonsignificant, this trial lends some support to the hypothesis that supplementation with 60,000 IU vitamin D/mo is associated with lower risk of infection, particularly in older adults. The trial was registered at the Australian New Zealand Clinical Trials Registry (anzctr.org.au) as ACTRN12609001063202 [ABSTRACT FROM AUTHOR]

This article reports on a research that aims to report the burden and cost of non-melanoma skin cancer treatments (NMSC) in Australia and project estimates of numbers and costs to 2015. The study used data obtained from Medicare Australia for NMSC by excision, curettage, among others, between the period January 1997-December 31, 2010. The research found that the total number of NMSC treatments rose from 412,493 in 1997 to 767,347 in 2010. The article also discusses the study's conclusion.

BACKGROUND: Questionnaire-based studies investigating blood donation history rely on the accurate recall of information from participants for results to be valid. This study aimed to retrieve electronic records from a national blood donation service and link them to self-reported history of donation to assess agreement between the two sources. STUDY DESIGN AND METHODS: Between 2004 and 2006, a sample of participants of northern European descent was selected from the Melbourne Collaborative Cohort Study (n = 31,192) to participate in the 'HealthIron' study (n = 1438). A total of 1052 participants completed questionnaires that included questions about blood donation history. In 2009, consenting participants' records were linked to the Australian Red Cross Blood Service (ARCBS) to provide information on blood donations made between 1980 and follow-up (2004-2006). Those who commenced blood donation before 1980 were excluded. RESULTS: A total of 718 participants were available for analysis. Of these, 394 (55%) provided signed consent, including 182 (82%) of the 227 participants who self-reported ever donating blood. The two data sources were concordant for 331 (87%) of participants, with a κ statistic of 0.74 (SE, 0.05) indicating a high level of agreement. Participants tended to overstate by a factor of 2.0 (95% confidence interval, 1.7-2.2) the number of donations they had made when compared with ARCBS records. CONCLUSION: Participants in studies assessing self-reported blood donation history are likely to correctly indicate whether or not they have ever donated blood. Quantitative estimates are potentially inaccurate and could benefit from validating a sample of records to quantify the bias. [ABSTRACT FROM AUTHOR]

The article discusses a study that assessed the relationship between dietary sodium intake and blood pressure in older adults in Australia. It details the measurement of urinary excretion of sodium and potassium, urinary sodium-to-potassium ratio, and clinic blood pressure. It provides evidence of a positive relationship between sodium intake and blood pressure. The effectiveness of a population-wide reduction in sodium intake to reduce blood pressure in Australian adults is suggested.

The Kidskin Study is a 5-year intervention study (1995–1999) involving 1,776 5- and 6-year-old children attending 33 primary schools in Perth, Western Australia. The aim of the study is to design, implement, and evaluate an intervention to reduce sun exposure in young children. There are three study groups: a control group, a “moderate intervention” group, and a “high intervention” group. The control schools receive the standard Western Australian health education curriculum, while the moderate and high intervention schools receive a specially designed curricular intervention. In addition, children in the high intervention group receive program materials over the summer holidays, when exposure is likely to be highest, and are offered sun-protective swimwear at low cost. The main outcome measure is the number of nevi on the back. Other outcomes include nevi on the chest (boys only), face, and arms, levels of suntanning, degree of freckling, and sun-related behaviors. At baseline, the three groups were similar with respect to nevi and freckling after adjustment for observer and month of observation. Sun exposure was slightly higher in the high intervention group. The groups were also similar with respect to most potential confounders, although they differed with respect to Southern European ethnicity and parental education. Am J Epidemiol 1999;150:164–73. [ABSTRACT FROM PUBLISHER]

A number of studies have suggested that environmental contamination with organochlorine pesticides may be related to risk of breast cancer. To investigate this association in a rural part of Australia, organochlorine contamination data from a breast milk organochlorine study conducted in the state of Victoria in 1993 were used. The state was divided into 11 statistical divisions. Standardized incidence ratios (SIRs) for the 11 regions were calculated using breast cancer incidence data from 1983 to 2002. During that time, 47,250 breast cancer cases occurred in Victoria, which had an average population of 2,147,409 women. The Ovens-Murray region, which was the region most contaminated with organochlorine pesticides, showed an elevated SIR of 1.10 (95%CI, 1.03–1.17), although two other regions with lower organochlorine contamination levels also had elevated SIRs. The rural part of the Ovens-Murray region, where the main pesticide use occurred, had the highest SIR, 1.15 (95%CI, 1.07–1.23). We did not find any significant correlation between organochlorine contamination and the age-standardized rate of breast cancer across all regions. But a positive dose-response relationship using an adjusted negative binomial model was detected for heptachlor epoxide. Our study may provide limited support for the role of environmental contamination with organochlorine pesticides in the development of breast cancer. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effect of dietary folate intake on the relation between alcohol consumption and breast cancer risk. Design Prospective cohort study. Setting Melbourne, Australia. Participants 17 447 Anglo-Australian women resident in Melbourne, aged 40-69 years at recruitment in 1990-4, and followed up until 31 December 2003. Main outcome measure Invasive breast cancers diagnosed during follow-up and ascertained through the Victorian cancer registry. Results 537 invasive breast cancers were diagnosed. Compared with lifetime abstainers, the hazard ratio for breast cancer in women who consumed an average of 40 g or more of alcohol daily at baseline was 1.41 (95% confidence interval 0.90 to 2.23). No direct association was found between dietary folate intake and risk of breast cancer, but a high folate intake mitigated the excess risk associated with alcohol. The estimated hazard ratio of an alcohol consumption of 40 g/day or more was 2.00 (1.14 to 3.49) for women with intakes of 200 µg/day of folate and 0.77 (0.33 to 1.80) for 400 µg/day of folate (P = 0.04 for interaction between alcohol and folate). Conclusions An adequate dietary intake of folate might protect against the increased risk of breast cancer associated with alcohol consumption. [ABSTRACT FROM AUTHOR]

Objective: The aims of the study were to determine whether Greek or Italian migrants to Australia have an elevated incidence of type 2 diabetes compared with Australian-born individuals and to what extent any differences can be explained by known risk factors.Research Design and Methods: This was a prospective study of 34,097 men and women aged 40-69 years born in Greece, Italy, Australia, or New Zealand who were free from diabetes at baseline. For all self-reported cases of diabetes at the 4-year follow-up, a confirmation of diagnosis was sought from medical practitioners. Of these, anyone for whom there was no evidence against a diagnosis of type 2 diabetes was considered a case subject.Results: Follow-up was completed by 29,331 (86%) participants, and 334 case subjects were identified. The cumulative incidence of type 2 diabetes among Greek (2.6%) and Italian (2.4%) migrants was more than three times that in Australian-born (0.7%) individuals. After adjusting for age only, the odds ratios (ORs) for being of Greek and Italian origin compared with Australian origin were 3.8 (95% CI 2.9-5.0) and 3.3 (2.6-4.3), respectively. The only known risk factor for type 2 diabetes that materially affected these ORs was BMI. After adjusting for BMI and age, the ORs for being of Greek and Italian origin, respectively, were 2.4 (1.8-3.2) and 2.0 (1.5-2.6).Conclusions: Greek and Italian migrants to Australia have a more than three times greater incidence of type 2 diabetes than Australian-born individuals, and this is only partly explained by BMI. Although weight control will remain important for these high-risk groups, identification of other risk factors is required. [ABSTRACT FROM AUTHOR]

Abstract Objectives: To determine whether an aid to the diagnosis of pigmented skin lesions reduces the ratio of benign lesions to melanomas excised in general practice. Design: Controlled trial randomised by practice. Setting: General practices in Perth, Western Australia. Participants: 468 general practitioners in 223 practices. Interventions: Intervention practices were given an algorithm and instant camera to assist with the diagnosis of pigmented skin lesions. All practices were given national guidelines on managing melanoma. Main outcome measures: Ratio of benign pigmented lesions to melanomas excised. Analyses conducted with and without inclusion of seborrhoeic keratoses. Results: At baseline the ratios of benign to malignant lesions were lower in the intervention group than in the control group. During the trial period the ratios were higher in the intervention group (19:1 v 17:1 without seborrhoeic keratoses and 29:1 v 26:1 with seborrhoeic keratoses). After adjustment for patients' age, sex, and socioeconomic status, the ratio was 1.02 times higher (95% confidence interval 0.68 to 1.51, P = 0.94) in the intervention group when seborrhoeic keratoses were not included and 1.03 times higher (0.71 to 1.50, P = 0.88) when seborrhoeic keratoses were included. General practitioners in the intervention group were less likely than those in the control group to excise the most recent pigmented skin lesion they managed (22% v 48%, P < 0.001) and to refer the patient to a specialist (16% v 27%, P= 0.06). Conclusions: Provision of the algorithm and camera did not decrease the ratio of benign pigmented skin lesions to melanomas excised by general practitioners. [ABSTRACT FROM AUTHOR]

Objectives: Depression is a significant public health issue for men, however men are less likely to use mental health services. Alternative interventions, such as physical activity, may be of value for this population. This study sought to determine what levels and intensity of physical activity are associated with lower depression prevalence in Australian men.Methods: Using baseline data from 13,884 participants in the Australian Longitudinal Study on Male Health we compared current depression in men who completed the recommended 150 min of physical activity in the past week with men who did not. Duration of activity was examined using logistic regression with restricted cubic splines. Intensity of physical activity was examined by isotemporal substitution of hours of moderate activity with hours of vigorous activity.Results: Men who completed at least 150 min/week of activity had lower odds of moderate/severe depression symptoms. Duration of activity was inversely associated with moderate/severe depression symptoms. Among physically active men, each additional hour of moderate activity replaced with vigorous activity was associated with lower odds of depression.Limitations: This is a cross-sectional study and so cannot determine causal direction in the relationship between physical activity and depression symptoms observed. Self-report measures of physical activity are widely used but are not as accurate as biometric measurement.Conclusions: In adult men, meeting minimum recommendations is associated with lower current depression. Increased duration and greater intensity of activity were both associated with further reduction in prevalence. Promoting higher levels of physical activity is potentially an intervention for improving men's mental wellbeing. [ABSTRACT FROM AUTHOR]

Aims: Inverse associations between vitamin D status and risk of type 2 diabetes observed in epidemiological studies could be biased by confounding and reverse causality. We investigated the prospective association between vitamin D status and type 2 diabetes and the possible role of reverse causality.Methods: We conducted a case-cohort study within the Melbourne Collaborative Cohort Study (MCCS), including a random sample of 628 participants who developed diabetes and a sex-stratified random sample of the cohort (n = 1884). Concentration of 25-hydroxyvitamin D (25(OH)D) was measured using liquid chromatography-tandem mass spectrometry in samples collected at recruitment. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of type 2 diabetes for quartiles of 25(OH)D relative to the lowest quartile and per 25 nmol/L increase in 25(OH)D, adjusting for confounding variables.Results: The ORs for the highest versus lowest 25(OH)D quartile and per 25 nmol/L increase in 25(OH)D were 0.60 (95% CI: 0.44, 0.81) and 0.76 (95% CI: 0.63, 0.92; p = 0.004), respectively. In participants who reported being in good/very good/excellent health approximately four years after recruitment, ORs for the highest versus lowest 25(OH)D quartile and per 25 nmol/L increase in 25(OH)D were 0.46 (95% CI: 0.29, 0.72) and 0.71 (95% CI: 0.56, 0.89; p = 0.003), respectively.Conclusions: In this sample of middle-aged Australians, vitamin D status was inversely associated with the risk of type 2 diabetes, and this association did not appear to be explained by reverse causality. [ABSTRACT FROM AUTHOR]

Background & Aims: Erectile dysfunction is common among older men and has been associated with low serum 25-hydroxy vitamin D concentration. However, this association may be due to uncontrolled confounding, and there is a paucity of evidence from interventional studies. We aimed to examine the effect of vitamin D supplementation on the prevalence of erectile dysfunction, in an exploratory analysis using data from a large randomized controlled trial., Methods: The D-Health Trial recruited Australians aged 60-84 years between January 2014 and May 2015 and randomly assigned them to supplementation with 60,000 IU of vitamin D or placebo per month for up to 5 years. Blood samples were collected annually from randomly selected participants (total N = 3943). We assessed erectile dysfunction at the end of the third year of follow-up. We used log-binomial regression to examine the effect of vitamin D on the prevalence of erectile dysfunction overall, and within sub-groups., Results: Of the 11,530 men enrolled, 8920 (77.4 %) completed the erectile dysfunction question and were included in the analysis. After three years of supplementation, the mean serum 25-hydroxy vitamin D concentration was 76 nmol/L (standard deviation (SD) 24.94) in the placebo group and 106 nmol/L (SD 26.76) in the vitamin D group (p < 0.0001). The prevalence of erectile dysfunction was 58.8 % and 59.0 % in the vitamin D and placebo groups, respectively (prevalence ratio 1.00, 95 % CI 0.97, 1.03); there was no evidence of an effect of vitamin D in any subgroup analyses., Conclusion: Supplementing older men with vitamin D is unlikely to prevent or improve erectile dysfunction., Clinical Trials Registry: (ACTRN12613000743763)., Competing Interests: Declaration of competing interest PW has funding from Astra Zeneca for an unrelated study of ovarian cancer. PE reports grants and other from Amgen and Alexion, grants from Sanofi, and other from Pfizer, ASBMR, IOF, and APCO Healthy Bones Australia. DW reports speaker payment from Pierre Fabre Australia. MR reports consulting fees from BXTAccelyon and other with Bayer. All other authors declare no competing interests., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Introduction: Electronic cigarette (e-cigarette) use in Australia has rapidly increased since the 2017 National Health and Medical Research Council (NHMRC) Chief Executive Officer (CEO) statement on e-cigarettes. The type of products available and the demographic characteristics of people using these products have changed. New evidence has been published and there is growing concern among public health professionals about the increased use, particularly among young people who do not currently smoke combustible cigarettes. The combination of these issues led NHMRC to review the current evidence and provide an updated statement on e-cigarettes. In this article, we describe the comprehensive process used to review the evidence and develop the 2022 NHMRC CEO statement on electronic cigarettes., Main Recommendations: E-cigarettes can be harmful; all e-cigarette users are exposed to chemicals and toxins that have the potential to cause adverse health effects. There are no health benefits of using e-cigarettes if you do not currently smoke tobacco cigarettes. Adolescents are more likely to try e-cigarettes if they are exposed to e-cigarettes on social media. Short term e-cigarette use may help some smokers to quit who have been previously unsuccessful with other smoking cessation aids. There are other proven safe and effective options available to help smokers to quit., Changes in Management as a Result of This Statement: The evidence base for the harms of e-cigarette use has strengthened since the previous NHMRC statement. Significant gaps in the evidence base remain, especially about the longer term health harms of using e-cigarettes and the toxicity of many chemicals in e-cigarettes inhaled as an aerosol., (© 2023 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Background: Hypothyroidism is common, and in iodine-sufficient areas, it is primarily caused by autoimmune destruction of the thyroid gland. Observational studies have consistently shown an inverse association between serum 25-hydroxyvitamin D concentration and autoimmune diseases; however, there is a lack of evidence from randomized controlled trials to support a benefit of vitamin D supplementation, particularly for autoimmune thyroid diseases. We, therefore, aimed to assess the effect of vitamin D supplementation on the incidence of hypothyroidism. Methods: We analyzed data from the D-Health Trial ( n  = 21,315), a randomized double-blind placebo-controlled trial of 60,000 international units per month of supplemental vitamin D 3 among Australians aged 60 years and over. Hypothyroidism, a tertiary outcome of the D-Health Trial, was defined by treatment with levothyroxine, ascertained through linkage with the Australian Pharmaceutical Benefits Scheme. The outcome was time to first prescription of levothyroxine. We began follow-up at 12 months after randomization; people who had died or who had been dispensed levothyroxine during the first year were excluded. Flexible parametric survival models were used to assess the effect of vitamin D supplementation on hypothyroidism, overall and within strata defined by age, sex, body mass index, and predicted baseline vitamin D status. Results: We included 17,851 participants in the main analysis (vitamin D  = 8939; placebo = 8912). During a median follow-up of 4.1 years (interquartile range 4.1-4.1), 293 participants developed hypothyroidism (vitamin D  = 138 [1.5%]; placebo = 155 [1.7%]). Vitamin D supplementation did not significantly reduce the incidence of hypothyroidism (overall hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.71-1.12). There was some suggestion of an effect in females (overall HR 0.78; CI 0.58-1.06) but not in males (overall HR 1.06; CI 0.74-1.50; p interaction 0.20). Conclusions: Vitamin D supplementation did not reduce the incidence of hypothyroidism overall; however, the possible beneficial effect observed in females warrants further investigation. Clinical Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12613000743763.

Background: While remaining incurable, median overall survival for MM now exceeds 5 years. Yet few studies have investigated how modifiable lifestyle factors influence survival. We investigate whether adiposity, diet, alcohol, or smoking are associated with MM-related fatality., Research Design and Methods: We recruited 760 incident cases of MM via cancer registries in two Australian states during 2010-2016. Participants returned questionnaires on health and lifestyle. Follow-up ended in 2020. Flexible parametric survival models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for lifestyle exposures and risk of all-cause and MM-specific fatality., Results: Higher pre-diagnosis Alternative Healthy Eating Index (AHEI) scores were associated with reduced MM-specific fatality (per 10-unit score, HR = 0.84, 95%CI = 0.70-0.99). Pre-diagnosis alcohol consumption was inversely associated with MM-specific fatality, compared with nondrinkers (0.1-20 g per day, HR = 0.59, 95%CI = 0.39-0.90; >20 g per day, HR = 0.67, 95%CI = 0.40-1.13). Tobacco smoking was associated with increased all-cause fatality compared with never smoking (former smokers: HR = 1.44, 95%CI = 1.10-1.88; current smokers: HR = 1.30, 95%CI = 0.80-2.10). There was no association between pre-enrollment body mass index (BMI) and MM-specific or all-cause fatality., Conclusions: Our findings support established recommendations for healthy diets and against smoking. Higher quality diet, as measured by the AHEI, may improve survival post diagnosis with MM.

Background: Evidence suggests that vitamin D influences the immune system. Recent studies indicate that vitamin D supplementation may reduce the severity of infections, but this has not been confirmed., Objectives: The objective of this study was to assess the effect of vitamin D supplementation on hospitalization for infection., Methods: The D-Health Trial was a randomized, double-blind, placebo-controlled trial of monthly 60,000 international units of vitamin D 3 for 5 y among 21,315 Australians aged 60-84 y. Hospitalization for infection, ascertained through linkage with hospital admitted patient data, is a tertiary outcome of the trial. The primary outcome for this post-hoc analysis was hospitalization for any infection. Secondary outcomes were extended hospitalization for infection (length of stay >3 d and >6 d) and hospitalization for respiratory tract, skin, and gastrointestinal infections. We used negative binomial regression to estimate the effect of vitamin D supplementation on outcomes., Results: Participants (46% women, mean age: 69 y), were followed up for a median of 5 y. Vitamin D supplementation had little or no effect on the incidence of hospitalization for any infection [incidence rate ratio (IRR): 0.95; 95% CI: 0.86, 1.05], respiratory tract (IRR: 0.93; 95% CI: 0.81, 1.08), skin (IRR: 0.95; 95% CI: 0.76, 1.20), gastrointestinal infections (IRR: 1.03; 95% CI: 0.84, 1.26), or hospitalizations lasting >3 d (IRR: 0.94; 95% CI: 0.81, 1.09), with all CIs consistent with a null finding. People supplemented with vitamin D had fewer hospitalizations lasting >6 d (IRR: 0.80; 95% CI: 0.65, 0.99)., Conclusions: We did not find a protective effect of vitamin D on hospitalization for infection, but it reduced the number of extended hospitalizations. In populations where few people are vitamin D deficient, the effect of population-wide supplementation is likely to be small, but these findings support previous studies suggesting that vitamin D plays a role in infectious disease. The D-Health Trial is registered at the Australian New Zealand Clinical Trials Registry as ACTRN12613000743763., (Copyright © 2022 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Observational studies suggest a link between vitamin D and the composition of the gut microbiome, but there is little evidence from randomized controlled trials of vitamin D supplementation. We analyzed data from the D-Health Trial, a randomized, double-blind, placebo-controlled trial. We recruited 21,315 Australians aged 60-84 y and randomized them to 60,000 IU of vitamin D 3 or placebo monthly for 5 y. Stool samples were collected from a sample of 835 participants (417 in the placebo and 418 in the vitamin D group) approximately 5 y after randomization. We characterized the gut microbiome using 16S rRNA gene sequencing. We used linear regression to compare alpha diversity indices (i.e. Shannon index (primary outcome), richness, inverse Simpson index), and the ratio of Firmicutes to Bacteroidetes between the two groups. We analyzed between-sample (beta) diversity (i.e. Bray Curtis distance and UniFrac index) using principal coordinate analysis and used PERMANOVA to test for significant clustering according to randomization group. We also assessed the difference in the abundance of the 20 most abundant genera between the two groups using negative binomial regression model with adjustment for multiple testing. Approximately half the participants included in this analysis were women (mean age 69.4 y). Vitamin D supplementation did not alter the Shannon diversity index (mean 3.51 versus 3.52 in the placebo and vitamin D groups, respectively, p  = 0.50). Similarly, there was little difference between the groups for other alpha diversity indices, the abundance of different genera, and the Firmicutes-to-Bacteroidetes ratio. We did not observe clustering of bacterial communities according to randomization group. In conlusion, monthly doses of 60,000 IU of vitamin D supplementation for 5 y did not alter the composition of the gut microbiome in older Australians.

Objectives: To investigate whether vitamin D supplementation reduces depressive symptoms and incidence of antidepressant use., Methods: We used data from the D-Health Trial (N = 21,315), a randomized double-blind placebo-controlled trial of monthly vitamin D 3 for the prevention of all-cause mortality. Participants were Australians aged 60-84 years. Participants completed the Patient Health Questionnaire (PHQ-9) at 1, 2 and 5 years after randomization to measure depressive symptoms; national prescribing records were used to capture antidepressant use. We used mixed models and survival models., Results: Analyses of PHQ-9 scores included 20,487 participants (mean age 69·3 years, 46% women); the mean difference (MD) in PHQ-9 score (vitamin D vs. placebo) was 0·02 (95% CI -0·06, 0·11). There was negligible difference in the prevalence of clinically relevant depression (PHQ-9 score ≥10) (odds ratio 0·99; 95% CI 0·90, 1·08). We included 16,670 participants in the analyses of incident antidepressant use (mean age 69·4 years, 43% women). Incidence of antidepressant use was similar between the groups (hazard ratio [HR] 1·04; 95% CI 0·96, 1·12). In subgroup analyses, vitamin D improved PHQ-9 scores in those taking antidepressants at baseline (MD -0·25; 95% CI -0·49, -0·01; p-interaction = 0·02). It decreased risk of antidepressant use in participants with predicted 25(OH)D concentration <50 nmol/L (HR 0·88; 95% CI 0·75, 1·02; p-interaction = 0·01) and increased risk in those with predicted 25(OH)D ≥ 50 nmol/L (HR 1·10; 95% CI 1·01, 1·20)., Conclusion: Monthly supplementation with high-dose vitamin D 3 was not of benefit for measures of depression overall, but there was some evidence of benefit in subgroup analyses., Clinical Trial Registration: The trial is registered on the Australian New Zealand Clinical Trials Registry: ACTRN12613000743763. https://www.anzctr.org.au/., (© 2022 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Background: Vitamin D may play a role in prevention of keratinocyte cancer (KC), but observational studies examining the association between serum 25-hydroxy vitamin D concentration and KC are largely uninformative because sun exposure causes both KC and vitamin D production. There is scant evidence from clinical trials of supplementary vitamin D., Objectives: To examine the effect of vitamin D supplementation on the risk of developing KC., Methods: We used data from the D-Health Trial, a randomized placebo-controlled trial of vitamin D supplementation (60 000 international units monthly for 5 years) among Australians aged ≥60 years. KC outcomes were captured through linkage to a national administrative dataset for those who consented (N = 20 334; 95%). We used negative binomial regression to analyse the incidence of KC excisions and the incidence of actinic lesions treated using cryotherapy or serial curettage, and flexible parametric survival models for analysis of time to first KC excision., Results: Randomization to vitamin D supplementation did not reduce the incidence of KC lesions treated by excision [incidence rate ratio (IRR) 1·04; 95% confidence interval (CI) 0·98-1·11], the incidence of actinic lesions treated using other methods (IRR 1·01; 95% CI 0·95-1·08) or time to first histologically confirmed KC excision (hazard ratio 1·02; 95% CI 0·97-1·08). However, in subgroup analysis vitamin D increased the incidence of KC excisions in adults aged ≥ 70 years (IRR 1·13, 95% CI 1·04-1·23; P-value for interaction = 0·01)., Conclusions: Vitamin D supplementation did not reduce the incidence of KC or other actinic lesions. What is already known about this topic? Laboratory studies have suggested possible protective effects of vitamin D on skin cancer. Observational studies investigating the association between vitamin D and risk of keratinocyte cancer are largely uninformative as ultraviolet radiation both causes skin cancer and is the primary source of vitamin D. The evidence from randomized controlled trials of vitamin D is limited and inconclusive. What does this study add? This population-based, randomized controlled trial suggests that supplementing older adults with a high monthly dose of vitamin D for 5 years does not affect the incidence of keratinocyte cancer., (© 2022 British Association of Dermatologists.)

Background: The effect of supplementing unscreened adults with vitamin D 3 on mortality is unclear. We aimed to determine whether monthly doses of vitamin D 3 influenced mortality in older Australians., Methods: We did a randomised, double-blind, placebo-controlled trial of oral vitamin D 3 supplementation (60 000 IU per month) in Australians 60 years or older who were recruited across the country via the Commonwealth electoral roll. Participants were randomly assigned (1:1), using automated computer-generated permuted block randomisation, to receive one oral gel capsule of either 60 000 IU vitamin D 3 or placebo once a month for 5 years. Participants, staff, and investigators were blinded to study group allocation. The primary endpoint was all-cause mortality assessed in all participants who were randomly assigned. We also analysed mortality from cancer, cardiovascular disease, and other causes. Hazard ratios (HRs) and 95% CIs were generated using flexible parametric survival models. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000743763., Findings: Between Feb 14, 2014, and June 17, 2015, we randomly assigned 21 315 participants, including 10 662 to the vitamin D group and 10 653 to the placebo group. In 4441 blood samples collected from randomly sampled participants (N=3943) during follow-up, mean serum 25-hydroxy-vitamin D concentrations were 77 (SD 25) in the placebo group and 115 (SD 30) nmol/L in the vitamin D group. Following 5 years of intervention (median follow-up 5·7 years [IQR 5·4-6·7]), 1100 deaths were recorded (placebo 538 [5·1%]; vitamin D 562 [5·3%]). 10 661 participants in the vitamin D group and 10 649 participants in the placebo group were included in the primary analysis. Five participants (one in the vitamin D group and four in the placebo group) were not included as they requested to be withdrawn and their data to be destroyed. The HR of vitamin D 3 effect on all-cause mortality was 1.04 [95% CI 0·93 to 1·18]; p=0·47)and the HR of vitamin D 3 effect on cardiovascular disease mortality was 0·96 (95% CI 0·72 to 1·28; p=0·77). The HR for cancer mortality was 1·15 (95% CI 0·96 to 1·39; p=0·13) and for mortality from other causes it was 0·83 (95% CI 0·65 to 1·07; p=0·15). The odds ratio for the per-protocol analysis was OR 1·18 (95% CI 1·00 to 1·40; p=0·06). In exploratory analyses excluding the first 2 years of follow-up, those randomly assigned to receive vitamin D had a numerically higher hazard of cancer mortality than those in the placebo group (HR 1·24 [95% CI 1·01-1·54]; p=0·05)., Interpretation: Administering vitamin D 3 monthly to unscreened older people did not reduce all-cause mortality. Point estimates and exploratory analyses excluding the early follow-up period were consistent with an increased risk of death from cancer. Pending further evidence, the precautionary principle would suggest that this dosing regimen might not be appropriate in people who are vitamin D-replete., Funding: The D-Health Trial is funded by National Health and Medical Research Council., Competing Interests: Declaration of interests PMW has funding from AstraZeneca for an unrelated study of ovarian cancer. PRE reports grants and honoraria from Amgen, honoraria from Sanofi, grants from Novartis, grants from Eli-Lilly, and grants from Alexion. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: To examine the association between circulating 25(OH)D concentrations and incidence of total hip replacement for osteoarthritis in a prospective cohort study., Methods: This study examined a random sample of 2651 participants in the Melbourne Collaborative Cohort Study who had 25(OH)D concentrations measured from dried blood spots collected in 1990-1994. Participants who underwent total hip replacement for osteoarthritis between January 2001 and December 2018 were identified by linking the cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of total hip replacement for osteoarthritis in relation to 25(OH)D concentrations, adjusted for confounders., Results: Eighty-six men and eighty-seven women had a total hip replacement for osteoarthritis. Compared with men in the lowest (1st) quartile of 25(OH)D concentration, the HR for total hip replacement was 2.32 (95% CI 1.05, 5.13) for those in the 2nd quartile, 2.77 (95% CI 1.28, 6.00) for those in the 3rd quartile, and 1.73 (95% CI 0.75, 4.02) for those in the highest quartile of 25(OH)D concentrations (p for trend 0.02). There was little evidence of an association in women., Conclusions: Higher circulating 25(OH)D concentrations were associated with an increased risk of total hip replacement for osteoarthritis in men but not in women. Although the underlying mechanism warrants further investigation, our findings highlight the need to determine the optimal levels of circulating 25(OH)D to reduce the risk of hip osteoarthritis., (© 2021. The Author(s).)

Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (P homogeneity = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences., (© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Observational studies have linked vitamin D deficiency with acute respiratory tract infection, but results from randomised controlled trials are heterogeneous. We analysed data from the D-Health Trial to determine whether supplementing older Australian adults, recruited from the general population, with monthly doses of vitamin D reduced the risk, duration, and severity of acute respiratory tract infections., Methods: We used data from the D-Health Trial, a randomised, double-blind, placebo-controlled trial of monthly vitamin D supplementation, for which acute respiratory infection was a pre-specified trial outcome. Participants were supplemented and followed for up to 5 years. The trial was set within the Australian general population, using the Commonwealth Electoral Roll as the sampling frame, but also allowing some volunteers to participate. Participants were men and women aged 60 to 79 years (with volunteers up to age 84 years). Participants were randomly assigned to receive either vitamin D or placebo (1:1) using computer-generated permuted block randomisation, which was stratified by age, sex, and state. This was an automated process and the assignment list was not visible to study staff or investigators. Active and placebo gel capsules, identical in appearance to ensure masking, were labelled A and B and the code was not available to study staff or investigators. Participants were asked to report occurrence of acute respiratory symptoms over the previous month via annual surveys, and a subset of participants completed 8-week respiratory symptom diaries in winter. As part of our process to maintain blinding, a random sample of participants was selected for analysis of survey data and a separate sample selected for analysis of diary data. Blood samples were obtained from a random sample of participants (about 450 per group per year) and serum 25-hydroxy vitamin D (25[OH]D) concentrations were measured to monitor adherence. We used regression models to estimate odds ratios (OR), rate ratios, and rate differences. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000743763., Findings: Between Jan 13, 2014, and May 26, 2015, 421 207 invitations were sent, 40 824 people were interested in participating, and 21 315 participants were recruited and randomised. Of the 16 000 participants selected for potential analysis of survey data, 15 373 were included in the analysis; 295 in the vitamin D group and 332 in the placebo group who were missing data for all five annual surveys were excluded from the analysis. Of the 3800 selected for potential analysis of diary data, 3070 were invited to complete the diaries because 730 had already withdrawn. 2598 people were included in the analysis; 218 people in the vitamin D group and 254 in the placebo group were missing data and were therefore excluded from the analysis. In blood samples collected from randomly sampled participants throughout the trial, the mean serum 25(OH)D concentration was 114·8 (SD 30·3) nmol/L in the vitamin D group and 77·5 (25·2) nmol/L in the placebo group. Vitamin D supplementation did not reduce the risk of acute respiratory tract infection (survey OR 0·98, 95% CI 0·93 to 1·02; diary OR 0·98, 0·83 to 1·15). Analyses of diary data showed reductions in the overall duration of symptoms and of severe symptoms, but these were small and unlikely to be clinically significant., Interpretation: Monthly bolus doses of 60 000 IU of vitamin D did not reduce the overall risk of acute respiratory tract infection, but could slightly reduce the duration of symptoms in the general population. These findings suggest that routine vitamin D supplementation of a population that is largely vitamin D replete is unlikely to have a clinically relevant effect on acute respiratory tract infection., Funding: National Health and Medical Research Council., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Long-term effects of physical activity and television (TV) viewing on mortality have been inferred from observational studies. The associations observed do not allow for inferences about the effects of population interventions and could be subject to bias due to time-varying confounding., Methods: Using data from the Australian Diabetes, Obesity and Lifestyle Study, collected in 1999-2000 (T0), 2004-2005 (T1), and 2011-2012 (T2), we applied the parametric g-formula to estimate cumulative risks of death under hypothetical interventions on physical activity and/or TV viewing determined from self-report while adjusting for time-varying confounding., Results: In the 6377 participants followed up for 13 yr from 2004 to 2005 to death or censoring in 2017, 781 participants died. The observed cumulative risk of death was 12.2%. The most effective hypothetical intervention was to increase weekly physical activity to >300 min (risk ratio (RR), 0.66 (0.46-0.86) compared with a "worst-case" scenario; RR, 0.83 (0.73-0.94) compared with no intervention). Reducing daily TV viewing to <2 h in addition to physical activity interventions did not show added survival benefits. Reducing TV viewing alone was least effective in reducing mortality (RR, 0.85 (0.60-1.10) compared with the worst-case scenario; RR, 1.06 (0.93-1.20) compared with no intervention)., Conclusions: Our findings suggested that sustained interventions to increase physical activity could lower all-cause mortality over a 13-yr period, and there might be limited gain from intervening to reduce TV viewing time in a relatively healthy population., (Copyright © 2020 by the American College of Sports Medicine.)