Terence Dwyer

Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study

Abstract Objective To examine whether past high sun exposure is associated with a reduced risk of multiple sclerosis. Design Population based case-control study. Setting Tasmania, latitudes 41-3°S. Participants 136 cases with multiple sclerosis and 272 controls randomly drawn from the community and matched on sex and year of birth. Main outcome measure Multiple sclerosis defined by both clinical and magnetic resonance imaging criteria. Results Higher sun exposure when aged 6-15 years (average 2-3 hours or more a day in summer during weekends and holidays) was associated with a decreased risk of multiple sclerosis (adjusted odds ratio 0.31, 95% confidence interval 0.16 to 0.59). Higher exposure in winter seemed more important than higher exposure in summer. Greater actinic damage was also independently associated with a decreased risk of multiple sclerosis (0.32, 0.11 to 0.88 for grades 4-6 disease). A dose-response relation was observed between multiple sclerosis and decreasing sun exposure when aged 6-15 years and with actinic damage. Conclusion Higher sun exposure during childhood and early adolescence is associated with a reduced risk of multiple sclerosis. Insufficient ultraviolet radiation may therefore influence the development of multiple sclerosis.

Higher 25-hydroxyvitamin D Is Associated with Lower Relapse Risk in Multiple Sclerosis

A protective association between higher vitamin D levels and the onset of multiple sclerosis (MS) has been demonstrated; however, its role in modulating MS clinical course has been little studied. We investigated whether higher levels of serum 25‐hydroxyvitamin D (25‐OH‐D) were associated with a lower risk of relapses in people with MS.

Factors Potentiating the Risk of Sudden Infant Death Syndrome Associated with the Prone Position

BACKGROUND In several studies the sudden infant death syndrome (SIDS) has been significantly associated with sleeping in the prone position. It is not known how the prone position increases the risk of SIDS. METHODS We analyzed data from a case-control study (58 infants with SIDS and 120 control infants) and a prospective cohort study (22 infants with SIDS and 213 control infants) in Tasmania. Interactions were examined in matched analyses with a multiplicative model of interaction. RESULTS In the case-control study, SIDS was significantly associated with sleeping in the prone position, as compared with other positions (unadjusted odds ratio, 4.5; 95 percent confidence interval, 2.1 to 9.6). The strength of this association was increased among infants who slept on natural-fiber mattresses (P = 0.05), infants who were swaddled (P = 0.09), infants who slept in heated rooms (P = 0.006), and infants who had had a recent illness (P = 0.02). These variables had no significant effect on infants who did not sleep in the prone position. A history of recent illness was significantly associated with SIDS among infants who slept prone (odds ratio, 5.7; 95 percent confidence interval, 1.8 to 19) but not among infants who slept in other positions (odds ratio, 0.83). In the cohort study, the risk of SIDS was greater among infants who slept prone on natural-fiber mattresses (odds ratio, 6.6; 95 percent confidence interval, 1.3 to 33) than among infants who slept prone on other types of mattresses (odds ratio, 1.8). CONCLUSIONS When infants sleep prone, the elevated risk of SIDS is increased by each of four factors: the use of natural-fiber mattresses, swaddling, recent illness, and the use of heating in bedrooms.

Prospective cohort study of prone sleeping position and sudden infant death syndrome

Studies of the link between prone sleeping position and sudden infant death syndrome have been criticised on grounds of recall bias and for not taking into account possible confounding effects. To avoid recall bias and to allow measurement of important biological factors a prospective cohort study of the cause of sudden infant death syndrome (SIDS) is being conducted. The infants included are those at high risk of the syndrome as assessed by a perinatal score. Of the 3110 members of the cohort born between January, 1988, and end of March, 1990, 23 infants later died of SIDS. Sleep position information was available for 15 of these. Matched analysis to control for the confounding effects of infant birthweight and maternal age indicated that prone sleeping position was associated with an increased risk of SIDS (OR 4.47 95% Cl [1.30-15.43]). The findings are strengthened by the results of a concurrent retrospective case-control study of 42 SIDS cases in which the prone position was also associated with an increased risk of SIDS (unadjusted OR 3.45 [1.59-7.49]).

Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, Australia

BackgroundAdequate 25(OH)D levels are required to prevent adverse effects on bone health. Population-based data on factors associated with 25(OH)D levels of people with MS have been lacking. Objectives To examine the prevalence and determinants of vitamin D insufficiency in a population-based sample of MS cases and controls, and to compare 25(OH)D status between MS cases and controls, taking into account case disability.MethodsWe conducted a population based case-control study in Tasmania, Australia (latitude 41-3°S) on 136 prevalent cases with MS confirmed by magnetic resonance imaging and 272 community controls, matched on sex and year of birth. Measurements included serum 25(OH)D, sun exposure, skin type, dietary vitamin D intake and disability including EDSS.ResultsA high prevalence of vitamin D insufficiency was found in MS cases and controls. Among MS cases, increasing disability was strongly associated with lower levels of 25(OH)D and with reduced sun exposure. Cases with higher disability (EDSS > 3) were more likely to have vitamin D insufficiency than controls (OR = 3.07 (1.37, 6.90) for 25(OH)D >40 nmol/l), but cases with low disability were not (OR = 0.87 (0.41, 1.86)).ConclusionThe strong associations between disability, sun exposure and vitamin D status indicate that reduced exposure to the sun, related to higher disability, may contribute to the high prevalence of vitamin D insufficiency found in this population-based MS case sample. Active detection of vitamin D insufficiency among people with MS and intervention to restore vitamin D status to adequate levels should be considered as part of the clinical management of MS.

Influence of Age on Associations Between Childhood Risk Factors and Carotid Intima-Media Thickness in Adulthood The Cardiovascular Risk in Young Finns Study, the Childhood Determinants of Adult Health Study, the Bogalusa Heart Study, and the Muscatine Study for the International Childhood Cardiovascular Cohort (i3C) Consortium

Background— Atherosclerosis has its roots in childhood. Therefore, defining the age when childhood risk exposure begins to relate to adult atherosclerosis may have implications for pediatric cardiovascular disease prevention and provide insights about the early determinants of atherosclerosis development. The aim of this study was to investigate the influence of age on the associations between childhood risk factors and carotid artery intima-media thickness, a marker of subclinical atherosclerosis. Methods and Results— We used data for 4380 members of 4 prospective cohorts—Cardiovascular Risk in Young Finns Study (Finland), Childhood Determinants of Adult Health study (Australia), Bogalusa Heart Study (United States), and Muscatine Study (United States)—that have collected cardiovascular risk factor data from childhood (age 3 to 18 years) and performed intima-media thickness measurements in adulthood (age 20 to 45 years). The number of childhood risk factors (high [highest quintile] total cholesterol, triglycerides, blood pressure, and body mass index) was predictive of elevated intima-media thickness (highest decile) on the basis of risk factors measured at age 9 years (odds ratio [95% confidence interval] 1.37 [1.16 to 1.61], P =0.0003), 12 years (1.48 [1.28 to 1.72], P <0.0001), 15 years (1.56 [1.36 to 1.78], P <0.0001), and 18 years (1.57 [1.31 to 1.87], P <0.0001). The associations with risk factors measured at age 3 years (1.17 [0.80 to 1.71], P =0.42) and 6 years (1.20 [0.96 to 1.51], P =0.13) were weaker and nonsignificant. Conclusions— Our analyses from 4 longitudinal cohorts showed that the strength of the associations between childhood risk factors and carotid intima-media thickness is dependent on childhood age. On the basis of these data, risk factor measurements obtained at or after 9 years of age are predictive of subclinical atherosclerosis in adulthood. # Clinical Perspective {#article-title-31}

Skipping breakfast: longitudinal associations with cardiometabolic risk factors in the Childhood Determinants of Adult Health Study

BACKGROUND The long-term effects of skipping breakfast on cardiometabolic health are not well understood. OBJECTIVE The objective was to examine longitudinal associations of breakfast skipping in childhood and adulthood with cardiometabolic risk factors in adulthood. DESIGN In 1985, a national sample of 9-15-y-old Australian children reported whether they usually ate breakfast before school. During follow-up in 2004-2006, 2184 participants (26-36 y of age) completed a meal-frequency chart for the previous day. Skipping breakfast was defined as not eating between 0600 and 0900. Participants were classified into 4 groups: skipped breakfast in neither childhood nor adulthood (n = 1359), skipped breakfast only in childhood (n = 224), skipped breakfast only in adulthood (n = 515), and skipped breakfast in both childhood and adulthood (n = 86). Diet quality was assessed, waist circumference was measured, and blood samples were taken after a 12-h fast (n = 1730). Differences in mean waist circumference and blood glucose, insulin, and lipid concentrations were calculated by linear regression. RESULTS After adjustment for age, sex, and sociodemographic and lifestyle factors, participants who skipped breakfast in both childhood and adulthood had a larger waist circumference (mean difference: 4.63 cm; 95% CI: 1.72, 7.53 cm) and higher fasting insulin (mean difference: 2.02 mU/L; 95% CI: 0.75, 3.29 mU/L), total cholesterol (mean difference: 0.40 mmol/L; 95% CI: 0.13, 0.68 mmol/L), and LDL cholesterol (mean difference: 0.40 mmol/L; 95% CI: 0.16, 0.64 mmol/L) concentrations than did those who ate breakfast at both time points. Additional adjustments for diet quality and waist circumference attenuated the associations with cardiometabolic variables, but the differences remained significant. CONCLUSIONS Skipping breakfast over a long period may have detrimental effects on cardiometabolic health. Promoting the benefits of eating breakfast could be a simple and important public health message.

Prospects for Epigenetic Epidemiology

Epigenetic modification can mediate environmental influences on gene expression and can modulate the disease risk associated with genetic variation. Epigenetic analysis therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. The spatial and temporal variance in epigenetic profile is of particular relevance for developmental epidemiology and the study of aging, including the variable age at onset for many common diseases. This review serves as a general introduction to the topic by describing epigenetic mechanisms, with a focus on DNA methylation; genetic and environmental factors that influence DNA methylation; epigenetic influences on development, aging, and disease; and current methodology for measuring epigenetic profile. Methodological considerations for epidemiologic studies that seek to include epigenetic analysis are also discussed.

The High Prevalence of Vitamin D Insufficiency across Australian Populations Is Only Partly Explained by Season and Latitude

Background Inadequate sun exposure and dietary vitamin D intake can result in vitamin D insufficiency. However, limited data are available on actual vitamin D status and predictors in healthy individuals in different regions and by season. Methods We compared vitamin D status [25-hydroxyvitamin D; 25(OH)D] in people < 60 years of age using data from cross-sectional studies of three regions across Australia: southeast Queensland (27°S; 167 females and 211 males), Geelong region (38°S; 561 females), and Tasmania (43°S; 432 females and 298 males). Results The prevalence of vitamin D insufficiency (≤ 50 nmol/L) in women in winter/spring was 40.5% in southeast Queensland, 37.4% in the Geelong region, and 67.3% in Tasmania. Season, simulated maximum daily duration of vitamin D synthesis, and vitamin D effective daily dose each explained around 14% of the variation in 25(OH)D. Although latitude explained only 3.9% of the variation, a decrease in average 25(OH)D of 1.0 (95% confidence interval, 0.7–1.3) nmol/L for every degree increase in latitude may be clinically relevant. In some months, we found a high insufficiency or even deficiency when sun exposure protection would be recommended on the basis of the simulated ultraviolet index. Conclusion Vitamin D insufficiency is common over a wide latitude range in Australia. Season appears to be more important than latitude, but both accounted for less than one-fifth of the variation in serum 25(OH)D levels, highlighting the importance of behavioral factors. Current sun exposure guidelines do not seem to fully prevent vitamin D insufficiency, and consideration should be given to their modification or to pursuing other means to achieve vitamin D adequacy.

Regional Variation in Multiple Sclerosis Prevalence in Australia and Its Association with Ambient Ultraviolet Radiation

The aim of this study was to conduct an ecological analysis of the extent to which ultraviolet radiation (UVR) levels might explain the regional variation of multiple sclerosis (MS) in Australia. MS prevalence data for six Australian regions were compared with UVR levels of the largest city in each region, with some other climatic variables and with the melanoma incidence in the same regions. A close association was found between the theoretical MS prevalence predicted from UVR levels and the actual prevalence. Furthermore, the negative correlation between UVR and MS prevalence (r = –0.91, p = 0.01) was higher than the positive correlation observed for UVR and malignant melanoma incidence (r = 0.75, p = 0.15 for males and r = 0.80, p = 0.10 for females). This study demonstrated that the regional variation in MS prevalence in the continent of Australia could be closely predicted by regional UVR levels. It is consistent with the hypothesis that UVR exposure may reduce the risk of MS possibly via T-lymphocyte-mediated immunosuppression. Analytical epidemiology studies are required to investigate this specific hypothesis.