Solar ultraviolet radiation exposure, and incidence of childhood acute lymphocytic leukaemia and non-Hodgkin lymphoma in a US population-based dataset.

BACKGROUND: Acute lymphocytic leukaemia (ALL) and non-Hodgkin lymphoma (NHL) are among the commonest types of childhood cancer. Some previous studies suggested that elevated ultraviolet radiation (UVR) exposures increase ALL risk; many more indicate NHL risk is reduced. METHODS: We assessed age<20 ALL/NHL incidence in Surveillance, Epidemiology and End Results data using AVGLO-derived UVR irradiance/cumulative radiant exposure measures, using quasi-likelihood models accounting for underdispersion, adjusted for age, sex, racial/ethnic group and other county-level socioeconomic variables. RESULTS: There were 30,349 cases of ALL and 8062 of NHL, with significant increasing trends of ALL with UVR irradiance (relative risk (RR) = 1.200/mW/cm2 (95% CI 1.060, 1.359, p = 0.0040)), but significant decreasing trends for NHL (RR = 0.646/mW/cm2 (95% CI 0.512, 0.816, p = 0.0002)). There was a borderline-significant increasing trend of ALL with UVR cumulative radiant exposure (RR = 1.444/MJ/cm2 (95% CI 0.949, 2.197, p = 0.0865)), and significant decreasing trends for NHL (RR = 0.284/MJ/cm2 (95% CI 0.166, 0.485, p < 0.0001)). ALL and NHL trend RR is substantially increased among those aged 0-3. All-age trend RRs are most extreme (increasing for ALL, decreasing for NHL) for Hispanics for both UVR measures. CONCLUSIONS: Our more novel finding, of excess UVR-related ALL risk, is consistent with some previous studies, but is not clear-cut, and in need of replication.

Cutaneous melanoma, prostate-specific antigen testing and the subsequent risk of prostate cancer diagnosis: a prospective analysis of the 45 and Up Study.

BACKGROUND: The association between cutaneous melanoma and subsequent risk of prostate cancer (PC) was examined in a large population-based cohort study. METHODS: Male participants in the Sax Institute's 45 and Up Study (Australia) were recruited between 2006 and 2009. Questionnaire data and linked administrative health data from the Centre for Health Record Linkage and Services Australia identified melanomas diagnosed between 1/1/1994 and 12 months before Study recruitment (i.e., between 2005 and 2008), incident PCs, primary healthcare utilisation and prostate-specific antigen (PSA) tests. Men were excluded from the current analyses if they had a recorded PC or other cancer diagnosis other than melanoma and non-melanoma skin cancer prior to recruitment. Multivariable Cox regression was used to estimate hazard ratios (HRs) adjusting for PSA-testing frequency before PC diagnosis. RESULTS: Of 96,548 eligible men, 1899 were diagnosed with melanoma during the melanoma diagnosis period and 3677 incident PC diagnosed during follow-up (latest date 31/12/2013). Men with melanoma diagnosis had increased risk of a subsequent PC diagnoses (vs. no melanoma; fully adjusted HR = 1.32; 95% CI: 1.09-1.60). There was weak evidence of higher risks of a subsequent PC diagnosis for men diagnosed with more than one melanoma compared to men diagnosed with only one melanoma (p = 0.077), and if first melanoma diagnosis was 10 to 15 years before Study recruitment (fully adjusted HR = 2.05; 95% CI [1.35, 3.12]). CONCLUSION: Melanoma diagnosis was associated with increased risk of subsequent PC diagnosis, after adjusting for PSA testing and primary healthcare utilisation. While our ability to adjust for PC screening reduced risk of detection bias, we acknowledge that residual confounding from increased medical surveillance after melanoma diagnoses cannot be entirely ruled out.

The effect of vitamin D supplementation on pain: an analysis of data from the D-Health randomised controlled trial.

Observational studies suggest that 25-hydroxy vitamin D (25(OH)D) concentration is inversely associated with pain. However, findings from intervention trials are inconsistent. We assessed the effect of vitamin D supplementation on pain using data from a large, double-blind, population-based, placebo-controlled trial (the D-Health Trial). 21 315 participants (aged 60-84 years) were randomly assigned to a monthly dose of 60 000 IU vitamin D3 or matching placebo. Pain was measured using the six-item Pain Impact Questionnaire (PIQ-6), administered 1, 2 and 5 years after enrolment. We used regression models (linear for continuous PIQ-6 score and log-binomial for binary categorisations of the score, namely 'some or more pain impact' and 'presence of any bodily pain') to estimate the effect of vitamin D on pain. We included 20 423 participants who completed ≥1 PIQ-6. In blood samples collected from 3943 randomly selected participants (∼800 per year), the mean (sd) 25(OH)D concentrations were 77 (sd 25) and 115 (sd 30) nmol/l in the placebo and vitamin D groups, respectively. Most (76 %) participants were predicted to have 25(OH)D concentration >50 nmol/l at baseline. The mean PIQ-6 was similar in all surveys (∼50·4). The adjusted mean difference in PIQ-6 score (vitamin D cf placebo) was 0·02 (95 % CI (-0·20, 0·25)). The proportion of participants with some or more pain impact and with the presence of bodily pain was also similar between groups (both prevalence ratios 1·01, 95 % CI (0·99, 1·03)). In conclusion, supplementation with 60 000 IU of vitamin D3/month had negligible effect on bodily pain.

Vitamin D Supplementation and Antibiotic Use in Older Australian Adults: An Analysis of Data From the D-Health Trial.

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/.

Impact of personal genomic risk information on melanoma prevention behaviors and psychological outcomes: a randomized controlled trial.

PURPOSE: We evaluated the impact of personal melanoma genomic risk information on sun-related behaviors and psychological outcomes. METHODS: In this parallel group, open, randomized controlled trial, 1,025 Australians of European ancestry without melanoma and aged 18-69 years were recruited via the Medicare database (3% consent). Participants were randomized to the intervention (n = 513; saliva sample for genetic testing, personalized melanoma risk booklet based on a 40-variant polygenic risk score, telephone-based genetic counseling, educational booklet) or control (n = 512; educational booklet). Wrist-worn ultraviolet (UV) radiation dosimeters (10-day wear) and questionnaires were administered at baseline, 1 month postintervention, and 12 months postbaseline. RESULTS: At 12 months, 948 (92%) participants completed dosimetry and 973 (95%) the questionnaire. For the primary outcome, there was no effect of the genomic risk intervention on objectively measured UV exposure at 12 months, irrespective of traditional risk factors. For secondary outcomes at 12 months, the intervention reduced sunburns (risk ratio: 0.72, 95% confidence interval: 0.54-0.96), and increased skin examinations among women. Melanoma-related worry was reduced. There was no overall impact on general psychological distress. CONCLUSION: Personalized genomic risk information did not influence sun exposure patterns but did improve some skin cancer prevention and early detection behaviors, suggesting it may be useful for precision prevention. There was no evidence of psychological harm.

Cumulative solar ultraviolet radiation exposure and basal cell carcinoma of the skin in a nationwide US cohort using satellite and ground-based measures.

BACKGROUND: Basal cell carcinoma of the skin (BCC) is the most common cancer in populations of European ancestry. Although consistently linked with basal cell carcinoma of the skin in case-control studies, few prospective cohort studies have evaluated the shape of the exposure-response of basal cell carcinoma associated with cumulative radiant solar ultraviolet exposure (UVR). METHODS: We followed 63,912 white cancer-free US radiologic technologists from entry (1983-1998) to exit (2003-2005) with known ultraviolet irradiance at up to 5 residential locations. Using generalized-additive and relative risk models we analyzed the exposure-response of basal cell carcinomas associated with ambient cumulative ultraviolet radiant exposure using ground-based National Solar Radiation database Average Daily Total Global data and satellite-based National Aeronautics and Space Administration Total Ozone Mapping Spectrometer data. RESULTS: There were 2151 technologists with an incident primary basal cell carcinoma. Risk of basal cell carcinoma rose with increasing cumulative ultraviolet radiation exposure using both measures, such that 1 MJ cm- 2 increased basal cell carcinoma risk by 8.48 (95% CI 5.22, 11.09, p < 0.001) and by 10.15 (95% CI 6.67, 13.10, p < 0.001) per 10,000 persons per year using the Average Daily Total Global and Total Ozone Mapping Spectrometer ultraviolet data, respectively; relative risk was likewise elevated. There was some evidence of upward curvature in the cumulative ultraviolet exposure response using both exposure measures with a greater increase in risk of basal cell carcinoma at higher levels of ultraviolet radiation exposure, but less evidence for curvature in relative risk. There are indications of substantial variation of relative risk with time after exposure and age at exposure, so that risk is highest for the period 10-14 years after ultraviolet radiation exposure and for those exposed under the age of 25. CONCLUSIONS: We observed increases in risk of basal cell carcinoma and a similar exposure-response for ground-based and satellite ultraviolet radiation measures. Our observations suggest that interventions should concentrate on persons with higher levels of ultraviolet radiation exposure.

Personal ultraviolet Radiation exposure in a cohort of Chinese mother and child pairs: the Chinese families and children study.

BACKGROUND: Few studies in China have examined personal ultraviolet radiation (UVR) exposure using polysulfone dosimetry. METHODS: In this study, 93 mother and adolescent child pairs (N = 186) from two locations in China, one rural (higher latitude) and one urban (lower latitude), completed 3 days of personal UVR dosimetry and a sun/clothing diary, as part of a larger pilot study. RESULTS: The average daily ambient UVR in each location as measured by dosimetry was 20.24 Minimal Erythemal Doses (MED) in the rural location and 20.53 MED in the urban location. Rural mothers had more average daily time outdoors than urban mothers (5.5 h, compared with 1.5 h, in urban mothers) and a much higher daily average personal UVR exposure (4.50 MED, compared with 0.78 MED in urban mothers). Amongst adolescents, rural males had the highest average daily personal UVR exposure, followed by rural females, urban females and urban males (average 2.16, 1.05, 0.81, and 0.48 MED, respectively). CONCLUSIONS: Although based on small numbers, our findings show the importance of geographic location, age, work/school responsibilities, and sex of the adolescents in determining personal UVR exposure in China. These results suggest that latitude of residence may not be a good proxy for personal UVR exposure in all circumstances.

Effect of solar ultraviolet radiation exposure on serum 25(OH)D concentration: a pilot randomised controlled trial.

Sunlight generates vitamin D, but there are scant human data from randomised trials on which to base health policy advice about how much sun exposure is necessary to change 25(OH)D concentrations. The purpose of the study was to evaluate the feasibility of using solar ultraviolet (UV) radiation exposure to generate a change in 25(OH)D concentration in a randomised controlled trial (RCT). The intervention tested in this RCT was supervised exposure to one standard erythemal dose (SED; 100 J m-2) of solar UV radiation three days per week for three weeks with approximately 35% of the body surface area not covered by clothing. Thirty-six fair-skinned (skin type II and III) indoor workers from Brisbane, Australia were randomised into either the intervention group (n = 16) or the control group (n = 20); the latter did not receive any supervised sun exposure. We asked both groups to use sunscreen and to minimise time outdoors during the study period. We collected blood samples at baseline, once per week during the three week intervention period, and four weeks after the intervention finished. The cumulative UV radiation exposure over the intervention period measured using polysulphone badges was higher in the intervention group than in the control group (median 8 vs. 4 SEDs, p = 0.14). After three weeks, the mean serum 25(OH)D concentration increased from 60 to 65 nmol l-1 in the intervention group and from 55 to 57 nmol l-1 in the control group. After adjustment for baseline 25(OH)D, the mean change per week during the intervention phase was non-significantly higher in the intervention than in the control group (0.7 vs. 0.3; p = 0.35). This difference was not sustained during the follow-up period. Large field trials are needed to inform policy about how much natural sun exposure is required to raise 25(OH)D concentrations. This pilot identified key issues that need to be considered in the design of such a trial.

Google as a cancer control tool in Queensland.

BACKGROUND: Recent advances in methodologies utilizing "big data" have allowed researchers to investigate the use of common internet search engines as a real time tool to track disease. Little is known about its utility with tracking cancer incidence. This study aims to investigate the potential correlates of monthly internet search volume indexes (SVIs) and observed monthly age standardised incidence rates (ASRs) for breast cancer, colorectal cancer, melanoma and prostate cancer. METHODS: The monthly ASRs for the four cancers in Queensland were calculated using data from the Queensland Cancer Registry between January 2006 and December 2012. The monthly SVIs of the respective cancer search terms in Queensland were accessed from Google Trends for the same period. A time series seasonal decomposition method was performed to detect the seasonal patterns of SVIs and ASRs. Pearson's correlation coefficient and time series cross-correlation analysis were used to assess the associations between SVIs and ASRs. Linear regression models were used to examine the power of SVIs to predict monthly in ASRs. RESULTS: Increases in the monthly ASRs of the four cancers were significantly correlated with increases in the monthly SVIs of the respective cancers except for colorectal cancer. The predictive power of the SVIs to explain variances in the corresponding ASRs varied by cancer type, with the percent explained ranging from 5.6% for breast cancer to 17.9% for skin cancer (SVI) with melanoma (ASR). Some improvement in the variation explained was obtained by including more search terms or lagged SVIs for the respective cancers in the linear regression models. The seasonal analysis indicated that the SVIs peaked periodically at around their respective cancer awareness months. CONCLUSIONS: Using SVIs from a popular internet search engine was only able to explain a small portion of changes in the respective ASRs. While an expanded regression model explained a higher proportion of variability, the interpretation of this was difficult. Further development and refinement of this approach will be needed before search-based cancer surveillance can provide useful information regarding resource deployment to guide cancer control and track the impact of cancer awareness and education programmes.

Temporal changes in loss of life expectancy due to cancer in Australia: a flexible parametric approach.

PURPOSE: To evaluate changes in cancer mortality burden over time by assessing temporal trends in life expectation for Australian residents diagnosed with cancer. METHODS: The study cohort consisted of all people diagnosed with cancer in the period 1990-2000 and aged 15-89 years (n = 1,275,978), with mortality follow-up to 31 December 2010. Flexible parametric survival models incorporating background age-sex-year-specific population mortality rates were applied to generate the observed survival curves for all cancers combined and selected major cancer types. Predicted values of loss of life expectancy (LOLE) in years were generated and then averaged across calendar year and age group (15-49, 50-69 and 70-89 years) or spread of disease (localized, regional, distant, unknown). RESULTS: The greatest LOLE burden was for lung cancer (14.3 years per diagnosis) and lowest for melanoma (2.5 years). There was a significant decrease in LOLE over time (-0.13 LOLE per year) for all cancers combined. Decreases were also observed for female breast cancer (-0.21), prostate cancer (-0.17), colorectal cancer (-0.08), melanoma (-0.07) and stomach cancer (-0.02), with slight increases for lung cancer (+0.04). When restricted to the sub-cohort from New South Wales with spread of disease information, these decreases in LOLE were primarily among cancers categorized as localized or regional spread at diagnosis. CONCLUSIONS: In Australia, persons diagnosed with cancer have a steadily improving outlook that exceeds that expected by general improvement in population life expectancy. The overall improvement is observed in persons with localized or regional cancers but not in those with advanced cancers, findings which encourage earlier diagnosis.

Investigating the patterns and determinants of seasonal variation in vitamin D status in Australian adults: the Seasonal D Cohort Study.

BACKGROUND: Vitamin D status generally varies seasonally with changing solar UVB radiation, time in the sun, amount of skin exposed, and, possibly, diet. The Seasonal D Study was designed to quantify the amplitude and phase of seasonal variation in the serum concentration of 25-hydroxyvitamin D, (25OH)D)) and identify the determinants of the amplitude and phase and those of inter-individual variability in seasonal pattern. METHODS: The Seasonal D Study collected data 2-monthly for 12 months, including demographics, personal sun exposure using a diary and polysulphone dosimeters over 7 days, and blood for serum 25(OH)D concentration. The study recruited 333 adults aged 18-79 years living in Canberra (35°S, n = 168) and Brisbane (27°South, n = 165), Australia. DISCUSSION: We report the study design and cohort description for the Seasonal D Study. The study has collected a wealth of data to examine inter- and intra-individual seasonal variation in vitamin D status and serum 25(OH)D levels in Australian adults.

Diagnosis of an additional in situ melanoma does not influence survival for patients with a single invasive melanoma: A registry-based follow-up study.

Using a large (N= 25 493) population-based cohort from Queensland, Australia, we compared melanoma survival among cases with a single invasive melanoma only against those who also had a diagnosis of a single in situ melanoma. After adjustment for sex, age, body site, clinicopathological subtype, thickness and ulceration, it was found that there was no difference (P = 0.99) in 10-year melanoma-specific mortality following a diagnosis of an invasive lesion, whether or not an in situ melanoma was also present. We conclude that in situ melanomas do not alter the prognosis of an invasive melanoma.

Insulin-like growth factor-I and UVB photoprotection in human keratinocytes.

Ultraviolet radiation (UVR), in particular the UVB spectrum, is a risk factor for skin cancer development. The generation and accumulation of UVB-induced genetic mutations are fundamental premalignant events. Keratinocyte interactions between other cutaneous cell populations and the surrounding microenvironment determine cell fate and acute photoresponses. In this study, the importance of the insulin-like growth factor (IGF) system, in particular the insulin-like growth factor-I (IGF-I), on influencing key processes in the keratinocyte acute photoresponse was investigated. Exogenous IGF-I and other growth factors present in dermal fibroblast-conditioned media (CM) were found to significantly enhance keratinocyte survival following UVB irradiation in vitro. This pretreatment was also shown to cause a shift in the expression levels of various DNA damage response proteins. Consequently, this was associated with accelerated rates of UVB-induced cyclobutane pyrimidine dimer removal in these samples. Finally, activation of the IGF system influenced cell cycle progression in UVB-irradiated keratinocytes. Taken together, these results highlight the importance of the IGF signalling network in initiating the repair of potentially mutagenic DNA damage in human keratinocytes. The dysregulation of these processes may therefore have significant implications in the aetiology of skin cancers and other cutaneous diseases.

Basal cell carcinomas on sun-protected vs. sun-exposed body sites: a comparison of phenotypic and environmental risk factors.

BACKGROUND: Basal cell carcinoma (BCC) is the most commonly diagnosed cancer in White populations. There are indications that risk factors for BCC may differ according to the anatomic site of the tumour but this is not well understood. PURPOSE: To compare phenotypic and environmental risk factors for BCCs arising on sun-protected sites with that of those on sun-exposed sites. METHODS: We conducted a case-case study in which people who had been diagnosed with incident BCC were recruited between February 2012 and September 2013 in Brisbane, Australia. RESULTS: Fair skin (OR: 4.50; 95% CI: 1.22, 16.59), having more than 15 lesions frozen/burnt off compared to less than 5 (OR: 5.68; 95% CI: 1.78, 18.08) and severe acne (OR: 5.25; 95% CI: 1.34, 20.56) were associated with increased risk of BCC on sun-protected sites. The presence of more than 5 nevi on the body was associated with decreased risk (OR: 0.28; 95% CI: 0.11, 0.71). CONCLUSIONS: BCCs on sun-protected sites arise as a result of excessive sun exposure, most likely combined with phenotypic susceptibility. The strong negative association with nevi also suggests that there are constitutional factors that underlie the propensity for BCCs to arise on these body sites.

The contributions of solar ultraviolet radiation exposure and other determinants to serum 25-hydroxyvitamin D concentrations in Australian adults: the AusD Study.

The Quantitative Assessment of Solar UV [ultraviolet] Exposure for Vitamin D Synthesis in Australian Adults (AusD) Study aimed to better define the relationship between sun exposure and serum 25-hydroxyvitamin D (25(OH)D) concentration. Cross-sectional data were collected between May 2009 and December 2010 from 1,002 participants aged 18-75 years in 4 Australian sites spanning 24° of latitude. Participants completed the following: 1) questionnaires on sun exposure, dietary vitamin D intake, and vitamin D supplementation; 2) 10 days of personal ultraviolet radiation dosimetry; 3) a sun exposure and physical activity diary; and 4) clinical measurements and blood collection for 25(OH)D determination. Our multiple regression model described 40% of the variance in 25(OH)D concentration; modifiable behavioral factors contributed 52% of the explained variance, and environmental and demographic or constitutional variables contributed 38% and 10%, respectively. The amount of skin exposed was the single strongest contributor to the explained variance (27%), followed by location (20%), season (17%), personal ultraviolet radiation exposure (8%), vitamin D supplementation (7%), body mass index (weight (kg)/height (m)(2)) (4%), and physical activity (4%). Modifiable behavioral factors strongly influence serum 25(OH)D concentrations in Australian adults. In addition, latitude was a strong determinant of the relative contribution of different behavioral factors.

Sunlight and other determinants of circulating 25-hydroxyvitamin D levels in black and white participants in a nationwide U.S. study.

Circulating 25-hydroxyvitamin D (25(OH)D), a marker for vitamin D status, is associated with bone health and possibly cancers and other diseases; yet, the determinants of 25(OH)D status, particularly ultraviolet radiation (UVR) exposure, are poorly understood. Determinants of 25(OH)D were analyzed in a subcohort of 1,500 participants of the US Radiologic Technologists (USRT) Study that included whites (n = 842), blacks (n = 646), and people of other races/ethnicities (n = 12). Participants were recruited monthly (2008-2009) across age, sex, race, and ambient UVR level groups. Questionnaires addressing UVR and other exposures were generally completed within 9 days of blood collection. The relation between potential determinants and 25(OH)D levels was examined through regression analysis in a random two-thirds sample and validated in the remaining one third. In the regression model for the full study population, age, race, body mass index, some seasons, hours outdoors being physically active, and vitamin D supplement use were associated with 25(OH)D levels. In whites, generally, the same factors were explanatory. In blacks, only age and vitamin D supplement use predicted 25(OH)D concentrations. In the full population, determinants accounted for 25% of circulating 25(OH)D variability, with similar correlations for subgroups. Despite detailed data on UVR and other factors near the time of blood collection, the ability to explain 25(OH)D was modest.

Predicting vitamin D deficiency in older Australian adults.

OBJECTIVE: There has been a dramatic increase in vitamin D testing in Australia in recent years, prompting calls for targeted testing. We sought to develop a model to identify people most at risk of vitamin D deficiency. DESIGN AND PARTICIPANTS: This is a cross-sectional study of 644 60- to 84-year-old participants, 95% of whom were Caucasian, who took part in a pilot randomized controlled trial of vitamin D supplementation. MEASUREMENTS: Baseline 25(OH)D was measured using the Diasorin Liaison platform. Vitamin D insufficiency and deficiency were defined using 50 and 25 nmol/l as cut-points, respectively. A questionnaire was used to obtain information on demographic characteristics and lifestyle factors. We used multivariate logistic regression to predict low vitamin D and calculated the net benefit of using the model compared with 'test-all' and 'test-none' strategies. RESULTS: The mean serum 25(OH)D was 42 (SD 14) nmol/1. Seventy-five per cent of participants were vitamin D insufficient and 10% deficient. Serum 25(OH)D was positively correlated with time outdoors, physical activity, vitamin D intake and ambient UVR, and inversely correlated with age, BMI and poor self-reported health status. These predictors explained approximately 21% of the variance in serum 25(OH)D. The area under the ROC curve predicting vitamin D deficiency was 0·82. Net benefit for the prediction model was higher than that for the 'test-all' strategy at all probability thresholds and higher than the 'test-none' strategy for probabilities up to 60%. CONCLUSION: Our model could predict vitamin D deficiency with reasonable accuracy, but it needs to be validated in other populations before being implemented.

Building healthy bones throughout life: an evidence-informed strategy to prevent osteoporosis in Australia.

Osteoporosis imposes a tremendous burden on Australia: 1.2 million Australians have osteoporosis and 6.3 million have osteopenia. In the 2007­08 financial year, 82 000 Australians suffered fragility fractures, of which > 17 000 were hip fractures. In the 2000­01 financial year, direct costs were estimated at $1.9 billion per year and an additional $5.6 billion on indirect costs. Osteoporosis was designated a National Health Priority Area in 2002; however, implementation of national plans has not yet matched the rhetoric in terms of urgency. Building healthy bones throughout life, the Osteoporosis Australia strategy to prevent osteoporosis throughout the life cycle, presents an evidence-informed set of recommendations for consumers, health care professionals and policymakers. The strategy was adopted by consensus at the Osteoporosis Australia Summit in Sydney, 20 October 2011. Primary objectives throughout the life cycle are: to maximise peak bone mass during childhood and adolescence to prevent premature bone loss and improve or maintain muscle mass, strength and functional capacity in healthy adults to prevent and treat osteoporosis in order to minimise the risk of suffering fragility fractures, and reduce falls risk, in older people. The recommendations focus on three affordable and important interventions ­ to ensure people have adequate calcium intake, vitamin D levels and appropriate physical activity throughout their lives. Recommendations relevant to all stages of life include: daily dietary calcium intakes should be consistent with Australian and New Zealand guidelines serum levels of vitamin D in the general population should be above 50nmol/L in winter or early spring for optimal bone health regular weight-bearing physical activity, muscle strengthening exercises and challenging balance/mobility activities should be conducted in a safe environment.

Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial.

OBJECTIVE: To investigate whether supplementing older adults with monthly doses of vitamin D alters the incidence of major cardiovascular events. DESIGN: Randomised, double blind, placebo controlled trial of monthly vitamin D (the D-Health Trial). Computer generated permuted block randomisation was used to allocate treatments. SETTING: Australia from 2014 to 2020. PARTICIPANTS: 21 315 participants aged 60-84 years at enrolment. Exclusion criteria were self-reported hypercalcaemia, hyperparathyroidism, kidney stones, osteomalacia, sarcoidosis, taking >500 IU/day supplemental vitamin D, or unable to give consent because of language or cognitive impairment. INTERVENTION: 60 000 IU/month vitamin D3 (n=10 662) or placebo (n=10 653) taken orally for up to five years. 16 882 participants completed the intervention period: placebo 8270 (77.6%); vitamin D 8552 (80.2%). MAIN OUTCOME MEASURES: The main outcome for this analysis was the occurrence of a major cardiovascular event, including myocardial infarction, stroke, and coronary revascularisation, determined through linkage with administrative datasets. Each event was analysed separately as secondary outcomes. Flexible parametric survival models were used to estimate hazard ratios and 95% confidence intervals. RESULTS: 21 302 people were included in the analysis. The median intervention period was five years. 1336 participants experienced a major cardiovascular event (placebo 699 (6.6%); vitamin D 637 (6.0%)). The rate of major cardiovascular events was lower in the vitamin D group than in the placebo group (hazard ratio 0.91, 95% confidence interval 0.81 to 1.01), especially among those who were taking cardiovascular drugs at baseline (0.84, 0.74 to 0.97; P for interaction=0.12), although the P value for interaction was not significant (<0.05). Overall, the difference in standardised cause specific cumulative incidence at five years was -5.8 events per 1000 participants (95% confidence interval -12.2 to 0.5 per 1000 participants), resulting in a number needed to treat to avoid one major cardiovascular event of 172. The rate of myocardial infarction (hazard ratio 0.81, 95% confidence interval 0.67 to 0.98) and coronary revascularisation (0.89, 0.78 to 1.01) was lower in the vitamin D group, but there was no difference in the rate of stroke (0.99, 0.80 to 1.23). CONCLUSIONS: Vitamin D supplementation might reduce the incidence of major cardiovascular events, although the absolute risk difference was small and the confidence interval was consistent with a null finding. These findings could prompt further evaluation of the role of vitamin D supplementation, particularly in people taking drugs for prevention or treatment of cardiovascular disease. TRIAL REGISTRATION: ACTRN12613000743763.

Vitamin D supplementation and cognition-Results from analyses of the D-Health trial.

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.