Associations between vitamin D metabolites, antiretroviral therapy and bone mineral density in people with HIV.

RATIONALE: To see if vitamin D and antiretroviral therapy are associated with bone mineral density (BMD) in people with HIV. RESULT: Lower hip BMD was associated with tenofovir (an antiretroviral medicine) in those with 25(OH)D ≥50 nmol/L. SIGNIFICANCE: The relationship between antiretroviral therapy and hip BMD differs depending on vitamin D status. INTRODUCTION: People with HIV have an increased risk of low BMD and fractures. Antiretroviral therapy contributes to this increased risk. The aim of this study was to evaluate associations between vitamin D metabolites and antiretroviral therapy on BMD. METHODS: The simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-lamivudine trial (STEAL) was an open-label, prospective randomised non-inferiority study that compared simplification of current nucleoside reverse transcriptase inhibitors (NRTIs) to fixed-dose combination tenofovir-emtricitabine (TDF-FTC) or abacavir-lamivudine. Serum 25(OH)D and 1,25(OH)2D were measured in 160 individuals (90 receiving TDF-FTC, 70 receiving other NRTIs) at baseline from this study. Multivariable linear regression models were constructed to evaluate the covariates of 1,25(OH)2D and BMD. RESULTS: Protease inhibitor use (p = 0.02) and higher body mass index (BMI) (p = 0.002) were associated with lower 1,25(OH)2D levels in those with 25(OH)D <50 nmol/L. However, TDF-FTC use (p = 0.01) was associated with higher 1,25(OH)2D levels, but only in those with 25(OH)D ≥50 nmol/L. White ethnicity (p = 0.02) and lower BMI (p < 0.001) in those with 25(OH)D <50 nmol/L and with TDF-FTC use (p = 0.008) in those with 25(OH)D ≥50 nmol/L were associated with lower hip BMD. TDF-FTC use, higher serum calcium and serum ßCTX, winter, and lower bone-specific alkaline phosphatase (BALP) and BMI were associated with lower lumbar spine BMD. CONCLUSION: TDF-FTC use (versus non-TDF-FTC use) was associated with lower hip BMD, and this difference was more pronounced in those with 25(OH)D ≥50 nmol/L. Serum 25(OH)D <50 nmol/L was associated with lower hip BMD in all participants. Therefore, the associations between antiretroviral therapy and hip BMD differ depending on vitamin D status.

Incidence trends of keratinocytic skin cancers and melanoma in Israel 2006-11.

BACKGROUND: The incidence of melanoma and keratinocyte cancers (KCs) is rising worldwide. Squamous cell carcinomas (SCCs) and basal cell carcinoma (BCCs) are the most common of all cancers. OBJECTIVES: To determine trends in the incidence of melanoma, BCC and SCC among 1·7 million members of Maccabi Healthcare Services (MHS) from 2006 to 2011. METHODS: Data on patients newly diagnosed with melanoma, SCC and BCC were collected from the MHS Cancer Registry and based on histology reports from the centralized pathology laboratory. Age-specific and overall age-adjusted European standardized rates were computed. Trends were estimated by calculating average annual percentage change (AAPC). RESULTS: During the 6-year study period, 16,079 patients were diagnosed with at least one BCC, 4767 with SCC and 1264 with invasive melanoma. Age-standardized incidence rates were 188, 58 and 17 per 100,000 person years for BCC, SCC and melanoma, respectively. All lesions were more common among men and primarily affected the elderly. BCC rates were stable throughout the study period [AAPC -0·7%, 95% confidence interval (CI) -4·5 to 3·2], while the incidence of SCC increased significantly (AAPC 15·5%, 95% CI 2·6-30·0). In contrast, melanoma rates continuously decreased (AAPC -3·0%, 95%CI -4·5 to -0·1). CONCLUSIONS: The incidence of KC in Israel is high. The disparities in incidence trends between SCC, BCC and melanoma allude to their different aetiologies. These findings underscore the importance of continuous monitoring, education and prevention programmes in a growing high-risk population.

The relationship between ambient ultraviolet radiation (UVR) and objectively measured personal UVR exposure dose is modified by season and latitude.

Despite the widespread use of ambient ultraviolet radiation (UVR) as a proxy measure of personal exposure to UVR, the relationship between the two is not well-defined. This paper examines the effects of season and latitude on the relationship between ambient UVR and personal UVR exposure. We used data from the AusD Study, a multi-centre cross-sectional study among Australian adults (18-75 years), where personal UVR exposure was objectively measured using polysulphone dosimeters. Data were analysed for 991 participants from 4 Australian cities of different latitude: Townsville (19.3°S), Brisbane (27.5°S), Canberra (35.3°S) and Hobart (42.8°S). Daily personal UVR exposure varied from 0.01 to 21 Standard Erythemal Doses (median = 1.1, IQR: 0.5-2.1), on average accounting for 5% of the total available ambient dose. There was an overall positive correlation between ambient UVR and personal UVR exposure (r = 0.23, p < 0.001). However, the correlations varied according to season and study location: from strong correlations in winter (r = 0.50) and at high latitudes (Hobart, r = 0.50; Canberra, r = 0.39), to null or even slightly negative correlations, in summer (r = 0.01) and at low latitudes (Townsville, r = -0.06; Brisbane, r = -0.16). Multiple regression models showed significant effect modification by season and location. Personal exposure fraction of total available ambient dose was highest in winter (7%) and amongst Hobart participants (7%) and lowest in summer (1%) and in Townsville (4%). These results suggest season and latitude modify the relationship between ambient UVR and personal UVR exposure. Ambient UVR may not be a good indicator for personal exposure dose under some circumstances.

The AusD Study: a population-based study of the determinants of serum 25-hydroxyvitamin D concentration across a broad latitude range.

Observational studies suggest that people with a high serum 25-hydroxyvitamin D (25(OH)D) concentration may have reduced risk of chronic diseases such as osteoporosis, multiple sclerosis, type 1 diabetes, cardiovascular disease, and some cancers. The AusD Study (A Quantitative Assessment of Solar UV Exposure for Vitamin D Synthesis in Australian Adults) was conducted to clarify the relationships between ultraviolet (UV) radiation exposure, dietary intake of vitamin D, and serum 25(OH)D concentration among Australian adults residing in Townsville (19.3°S), Brisbane (27.5°S), Canberra (35.3°S), and Hobart (42.8°S). Participants aged 18-75 years were recruited from the Australian Electoral Roll between 2009 and 2010. Measurements were made of height, weight, waist:hip ratio, skin, hair, and eye color, blood pressure, and grip strength. Participants completed a questionnaire on sun exposure and vitamin D intake, together with 10 days of personal UV dosimetry and an associated sun-exposure and physical-activity diary that was temporally linked to a blood test for measurement of 25(OH)D concentration. Ambient solar UV radiation was also monitored at all study sites. We collected comprehensive, high-quality data from 1,002 participants (459 males, 543 females) assessed simultaneously across a range of latitudes and through all seasons. Here we describe the scientific and methodological issues considered in designing the AusD Study.

Influence of solar UVA on erythemal irradiances.

Many materials in everyday use such as window glass in homes and offices, glass in sunrooms and greenhouses, vehicle glass and some brands of sunscreens act as a barrier to the shorter UVB wavelengths while transmitting some of the longer UVA wavelengths. This paper reports on the erythemal exposures due to the UVA waveband encountered over a 12-month period for a solar zenith angle (SZA) range of 4 degrees to 80 degrees and the resulting times required for an erythemal exposure of one standard erythemal dose (SED) due to the erythemal exposures to the UVA wavelengths. The minimum time for an exposure of one SED due to the UVA wavelengths in winter is approximately double that what it is in summer. The time period of 40 to 60 min was the most frequent length of time for an exposure of one SED with 60 to 80 min the next frequent length of time required for a one SED exposure.

The D-Health Trial: A randomized trial of vitamin D for prevention of mortality and cancer.

BACKGROUND: Vitamin D, specifically serum 25(OH)D has been associated with mortality, cancer and multiple other health endpoints in observational studies, but there is a paucity of clinical trial evidence sufficient to determine the safety and effectiveness of population-wide supplementation. We have therefore launched the D-Health Trial, a randomized trial of vitamin D supplementation for prevention of mortality and cancer. Here we report the methods and describe the trial cohort. METHODS: The D-Health Trial is a randomized placebo-controlled trial, with planned intervention for 5years and a further 5years of passive follow-up through linkage with health and death registers. Participants aged 65-84years were recruited from the general population of Australia. The intervention is monthly oral doses of 60,000IU of cholecalciferol or matching placebo. The primary outcome is all-cause mortality. Secondary outcomes are total cancer incidence and colorectal cancer incidence. RESULTS: We recruited 21,315 participants to the trial between February 2014 and May 2015. The participants in the two arms of the trial were well-balanced at baseline. Comparison with Australian population statistics shows that the trial participants were less likely to report being in fair or poor health, to be current smokers or to have diabetes than the Australian population. However, the proportion overweight or with health conditions such as arthritis and angina was similar. CONCLUSIONS: Observational data cannot be considered sufficient to support interventions delivered at a population level. Large-scale randomized trials such as the D-Health Trial are needed to inform public health policy and practice.

Vitamin D effective ultraviolet wavelengths due to scattering in shade.

Solar UVB radiation (280-320 nm) is an initiator of Vitamin D3 production in the human skin. While numerous studies have been conducted in relation to the biological impact of UV exposure in full sun, less research has investigated the irradiances in shade. The purpose of this study was to determine the levels of UV radiation in relation to Vitamin D3 induction with six commonly encountered shade environments for the larger solar zenith angles observed during autumn and winter. Spectral UV irradiance measurements were made under relatively clear sky conditions at a sub-tropical Southern Hemisphere site for six specific shade environments and solar zenith angle between 35 degrees and 60 degrees to investigate the biologically effective UV irradiances for pre-Vitamin D3 production. Data from this research indicates that pre-Vitamin D3 effective UV wavelengths in the shade were most significant for tree shade and a shade umbrella. Compared to that in full sun, pre-Vitamin D3 effective UV wavelengths were at levels of approximately 52 and 55%, respectively, beneath the shade umbrella and in tree shade. UVB irradiance levels in the shade of a northern facing covered veranda and in a car with windows closed were significantly less than those beneath the shade umbrella, with levels of approximately 11 and 0%, respectively, of those in full sun. Shade is important as a UV minimisation strategy; however, it may also play an important role in providing the human body with adequate levels of UVB radiation for pre-Vitamin D3 production without experiencing the relatively higher levels of UVA irradiances present in full sun.

An internet based approach to improve general practitioners' knowledge and practices: the development and pilot testing of the "ABC's of vitamin D" program.

BACKGROUND: Online continuing medical education (CME) offers a number of advantages for physicians including flexibility with regards to location and timing of use. In order to effect physician practices and improve patient outcomes, it is important that the development of online CME is theory and evidence-based. OBJECTIVES: This paper aims to describe the development of an online CME program for practising general practitioners (GPs) on vitamin D and sun health called "The ABC's of Vitamin D for GPs" using elements of design principles for physician-education web sites as a framework. The paper will also report the program's usability and acceptability pilot test results. METHODS: The ABC's of Vitamin D program was developed following nine principles: needs assessment; evidence-based content development; multimodal program and modularisation; clinical cases; tailoring and interactivity; audit and feedback; credibility of the web site host; patient education materials; ease of use and navigation. Among the 20 GPs invited, acceptability and useability was tested with 12 GPs (60%) who agreed to participate and were interviewed following use of the program. The study was conducted between 2011 and 2013. RESULTS: An online CME program consisting of eight modules was constructed. Of the 12 participating GPs, most (n=11) reported that the program was clear and easy to understand, logical, easy to navigate, and took a reasonable amount of time (estimated between 1 and 3h) to complete. Eleven of 12 participants said they would use the program as an accredited CME activity and all participants indicated that the program was 'very or somewhat' likely to lead to changes in the advice patients are given. CONCLUSION: This study found that a theory and evidence based approach for the development of an online CME program for GPs was acceptable to users. Further research is needed to examine whether the online CME program is effective at changing GP practices and improving patient outcomes.

Diffuse solar UV radiation and implications for preventing human eye damage.

Ocular UV exposure is a function of both the direct and diffuse components of solar radiation. Broadband global and diffuse UV measurements were made in the morning, noon and afternoon. Thirty sets of measurements were made in summer and 50 in each of the other seasons at each of the periods in full sun. Corresponding sets were made in the shade of Australian evergreen trees: 42 trees in summer and 50 in each of the other seasons. The percentage diffuse UV was higher for the shorter 320-400 nm range (UVB) than for 280-320 nm (UVA). The percentage diffuse UVB ranged from 23 to 59%, whereas the percentage diffuse UVA ranged from 17 to 31%. The percentage diffuse UV was lower at noon than in the morning and afternoon with the difference more pronounced for the UVB. The average percentage diffuse UVB over all the measurements in the tree shade for the morning, noon and afternoon was 62, 58 and 71%, respectively, and the average percentage diffuse UVA was 52, 51 and 59%, respectively.

Ultraviolet radiation penetrating vehicle glass: a field based comparative study.

The solar UV transmitted through automobile glass was measured in the field in two cars using a spectroradiometer. The two cars were identical except that one of the cars had all of the windows (except the windshield) tinted. The measured spectral erythemal UV on a horizontal plane with the windows fully closed was reduced in the tinted car by a factor of 42 when compared with the erythemal UV measured in the untinted car. The ambient UVA irradiances at various locations within four different makes of car and a tractor were also measured with a broad band UVA handheld meter. The average normalized daily UVA exposure (measured with a broad band UVA meter) was 1.3 times higher in a large family sedan when compared with that in a small hatchback and the UVA exposure in a car with tinted windows was 3.8 times less than in a similar untinted car.

Comparison of the spectral biologically effective solar ultraviolet in adjacent tree shade and sun.

The solar spectral UVR irradiances in tree shade and sunlight have been measured in a sub-tropical southern hemisphere summer. The spectral data allowed the UVB and UVA irradiances and the biologically effective irradiances to be calculated for different harmful biological processes to human skin and eyes. The average of the ratio of the UVA to UVB irradiances was lower by 26% in the shade compared with the same ratio in the sun. The spectral shade ratio calculated as the ratio of the spectral biologically effective irradiances in the shade to those in the adjacent sun decreased with increasing wavelength for all of the trees. The decrease in the shade ratio was approximately 42% at 400 nm compared with the shade ratio at 300 nm. Despite the UVR protection provided by tree shade, the erythemal UVR exposure received in 1 h in the tree shade exceeded the occupational limit for UVR exposure.

Comparison of biologically damaging spectral solar ultraviolet radiation at a southern hemisphere sub-tropical site.

The first dataset of a complete year of biologically damaging spectral UV at a sub-tropical latitude in the southern hemisphere has been presented. The new data provides a baseline dataset against which comparisons can be made in the future to establish if there have been any long term trends in the biologically damaging UV. The general shape of the variation of the daily biologically damaging exposures through the year depends on the relative response of the various action spectra at the different wavelengths. The ratio of the daily erythemal to actinic exposures drops by approximately 20 to 25% from winter to summer. The ratio of the erythemal to DNA exposures drops by approximately 50% over the same period. In contrast, the ratio of the erythemal to plant damage exposures is higher in summer compared to winter. This is due to the changes in the relative proportion of UVA to UVB wavebands and relative responses of the different action spectra. The relative changes for the different action spectra show that the erythemal action spectrum cannot be used as a proxy for other biologically damaging responses.

Optical properties of poly(2,6-dimethyl-1,4-phenylene oxide) film and its potential for a long-term solar ultraviolet dosimeter.

The optical properties of poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) film have been characterized in order to develop an alternative method for UV dosimetry with a focus on long-term human exposure measurements. The dynamic range of PPO film was found to extend to 2 MJ m(-2) of broadband UV exposure independently of film thickness, providing an exposure range of roughly four summer days at subtropical latitudes. The sensitivity of the film to UV exposure was positively related to film thickness in the 20-40 microm range. Films of 40 microm thickness proved to be the most suitable for long-term human UV exposure measurements. The temperature independence of the response of 40 microm PPO film was established from 1.5 degrees C to 50 degrees C within a dosimeter response uncertainty of 6.5%. Dose-rate independence was also demonstrated within 8% of the mean dosimeter response. The spectral response approximates the CIE erythemal action spectrum between 300 and 340 nm, with a peak response at 305 nm. A large deviation from this action spectrum was observed at shorter wavelengths. Investigation of the angular response in both the azimuth and altitude planes showed a cosine error of less than 6.2% between 0 degrees and 40 degrees, and did not exceed 13.3% at any angle greater than 40 degrees. These results indicate that PPO film satisfies the requirements for use as a UV dosimeter, and may be employed in long-term human exposure measurements.

Personal exposure distribution of solar erythemal ultraviolet radiation in tree shade over summer.

The personal radiant exposure distribution of solar erythemal UV in tree shade for an upright posture was measured, with measurements over the whole summer for a total of 17 trees. For each tree, the personal radiant exposure distribution was measured for both the morning and afternoon periods. The exposure ratios averaged over all the trees and over the morning and afternoon periods ranged from 0.16 to 0.49 for the different anatomical sites. A numerical model was employed to estimate the UV radiant exposure to humans in tree shade over the entire summer. The body sites with the higher exposure ratios in the tree shade were the vertex of the head, shoulders and forearms with radiant exposures over the summer of 1300 MED to the vertex of the head and 1100 MED to the shoulders and forearms. These radiant exposures in the shade are substantially higher than the ambient erythemal UV measured in full sun on a horizontal plane over a full summer at a more temperate northern hemisphere latitude. The average radiant exposures per day to each anatomical site for a complete day in the tree shade ranged from 4.6 to 14.6 MED. This research has provided new data that is essential to quantify human UV exposure during outdoor activities.

The facial distribution of erythemal ultraviolet exposure in south-east Queensland.

This paper presents a method for the evaluation of the distribution of the facial erythemal UV exposure and the erythemal UV exposure per unit area of the face using only eight dosimeters located on the vertex of the head, forehead, nose, chin, left and right ears and left and right cheeks. An overall picture of the parts of the face receiving high UV exposures is provided. The distribution of the erythemal UV exposure to the human face at a subtropical latitude was shown to change with time of year and with cloud cover. On two days with similar solar zenith angles, the ratio of the erythemal UV exposure to the nose compared with that on a horizontal plane changed from 0.47 to 0.84 with increased cloud cover. At the same time, the total erythemal exposure per unit area of the face dropped from 122 to 56 ml cm-2. Although the absolute exposures decreased, the nose received a relatively high exposure.

Evaluation of differences in ultraviolet exposure during weekend and weekday activities.

The weekday UV exposures to anatomical sites were evaluated for outdoor workers, home workers, adolescents, indoor workers, school staff and students in south-east Queensland, Australia. Additionally, the UV exposures at weekends of school staff, school students, indoor workers and outdoor workers were evaluated. The weekday exposures per day ranged from 1.0 to 11.0 SED for winter to summer respectively. During spring, the ratios of the personal exposures divided by the ambient exposures at the weekend to the personal exposures divided by the ambient exposures on the weekdays to the neck, hand and left arm were at least 3.4, 2.0 and 0.67 for the indoor workers, school staff and students and outdoor workers respectively. The same ratios for the erythemal UV exposures over the year, estimated from the exposures on four days in each of the four seasons, were at least 2.3 for the school staff and at least 1.3 for the 13 to 19 year old school students. These results reinforce the importance of targeting prevention programmes to both weekend and weekday exposures.

Horizontal and sun-normal spectral biologically effective ultraviolet irradiances.

The dependence of the spectral biologically effective solar UV irradiance on the orientation of the receiver with respect to the sun has been determined for relatively cloud-free days at a sub-tropical Southern Hemisphere latitude for the solar zenith angle range 35-64 degrees. For the UV and biologically effective irradiances, the sun-normal to horizontal ratio for the total UV ranges from 1.18 +/- 0.05 to 1.27 +/- 0.06. The sun-normal to horizontal ratio for biologically effective irradiance is dependent on the relative effectiveness of the relevant action spectrum in the UV-A waveband. In contrast to the total UV, the diffuse UV and diffuse biologically effective irradiances are reduced in a sun-normal compared with a horizontal orientation by a factor ranging from 0.70 +/- 0.05 to 0.76 +/- 0.03.

Spectral shade ratios on horizontal and sun normal surfaces for single trees and relatively cloud free sky.

Spectral shade ratios, defined as the ratios of the spectral irradiances on horizontal and sun normal planes in the tree shade to those on a horizontal plane in sunlight, were calculated. These planes were in the shade of an isolated medium canopy density tree and a sparse canopy density tree at the tree shade sites of the centre, edge and trunk. The sun normal plane was employed as there are some activities that have exposures to parts of the body that are orientated in a sun normal plane. The horizontal plane shade ratios for the medium density canopy dropped by 47-56% from the ratios in the range 301 to 310 nm to the ratios in the range 391 to 400 nm. In absolute terms, the largest change in the shade ratio of 0.28 was for the centre and edge sites compared to 0.07 for the trunk. Similarly, for the sun normal plane, the ratio dropped by 40-49% with an absolute reduction of 0.19 for the edge and 0.04 for the trunk. For the sparse density canopy, the decrease in the shade ratios over the same wavelength range was a drop by 37-42% on a horizontal plane or, in absolute terms, a reduction by 0.22 for the edge and 0.13 for the trunk. Similarly, the decrease was 34-39% on the sun normal plane or, in absolute terms, a reduction by 0.19 for the edge and 0.12 for the trunk.

Lower body anatomical distribution of solar ultraviolet radiation on the human form in standing and sitting postures.

Humans undertake their daily activities in a number of different postures. This paper aims to compare the anatomical distribution of the solar erythemal UV to human legs for standing and sitting postures. The exposure ratios to the legs (ratio of the UV exposure to a particular anatomical site compared to the ambient) have been measured with UV dosimeters for standing and sitting postures of a manikin. The exposure ratios for the legs ranged from 0 to 0.75 for the different anatomical sites for the sitting posture in summer (December through February) compared to 0.14 to 0.39 for the standing posture. In winter (June through August) the exposure ratios ranged from 0.01 to 0.91 for sitting to 0.17 to 0.81 for standing. For the anterior thigh and shin, the erythemal UV exposures increased by a factor of approximately 3 for sitting compared to standing postures. The exposure ratios to specific anatomical sites have been multiplied by the ambient erythemal UV exposures for each day to calculate the annual exposures. The annual erythemal exposures to the anterior thigh and ankle were predicted to be higher than 800 MED for humans sitting outdoors each day between noon and 13:00 h Australian Eastern Standard Time (EST). For humans standing outdoors during this time, the annual erythemal UV exposure averaged over each leg site was 436 MED, whereas, the averaged annual erythemal UV exposure was 512 MED for the sitting posture. Similarly, the annual erythemal UV exposure averaged over each of the sites was 173 MED for humans standing outdoors between 09:00 h EST and noon each Saturday morning and 205 MED for humans sitting outdoors during this time. These results show that there is increased risk of non-melanoma skin cancer and malignant melanoma to the lower body if no UV preventative strategies are employed while in a sitting posture compared to a standing posture.

Diffuse component of solar ultraviolet radiation in tree shade.

The first set of quantitative data of diffuse erythemal UV and UV-A radiation in tree shade at a sub-tropical Southern Hemisphere latitude is presented. Over the summer, approximately 60% of the erythemal UV radiation in tree shade is due to the diffuse component. Similarly, approximately 56% of the UV-A radiation in tree shade is due to the diffuse component. In tree shade these diffuse UV percentages are relatively constant from the morning to noon to afternoon periods. In comparison, in full sun, there is a decrease in the percentage of diffuse UV from morning to noon to afternoon. The exposures to diffuse UV on a horizontal plane in tree shade between 9:00 EST and 15:00 EST are of the order of 4 MED (minimum erythemal dose) and 14 J cm(-2) for erythemal UV and UV-A, respectively. The high diffuse UV component in the shade may result in high UV exposures not only to unprotected parts of the body on a horizontal plane, but also in equally high UV irradiances to parts of the body, including the eyes and face, that are not UV protected.