Leigh Blizzard

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.

Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis

Background There is a striking latitudinal gradient in multiple sclerosis (MS) prevalence, but exceptions in Mediterranean Europe and northern Scandinavia, and some systematic reviews, have suggested that the gradient may be an artefact. The authors sought to evaluate the association between MS prevalence and latitude by meta-regression. Methods and findings Studies were sourced from online databases, reference mining and author referral. Prevalence estimates were age-standardised to the 2009 European population. Analyses were carried out by means of random-effects meta-regression, weighted with the inverse of within-study variance. The authors included 650 prevalence estimates from 321 peer-reviewed studies; 239 were age-standardised, and 159 provided sex-specific data. The authors found a significant positive association (change in prevalence per degree-latitude) between age-standardised prevalence (1.04, p<0.001) and latitude that diminished at high latitudes. Adjustment for prevalence year strengthened the association with latitude (2.60, p<0.001). An inverse gradient in the Italian region reversed on adjustment for MS-associated HLA-DRB1 allele distributions. Adjustment for HLA-DRB1 allele frequencies did not appreciably alter the gradient in Europe. Adjustment for some potential sources of bias did not affect the observed associations. Conclusion This, the most comprehensive review of MS prevalence to date, has confirmed a statistically significant positive association between MS prevalence and latitude globally. Exceptions to the gradient in the Italian region and northern Scandinavia are likely a result of genetic and behavioural–cultural variations. The persistence of a positive gradient in Europe after adjustment for HLA-DRB1 allele frequencies strongly supports a role for environmental factors which vary with latitude, the most prominent candidates being ultraviolet radiation (UVR)/vitamin D.

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.

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.

Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial

Objectives To compare standard high flow oxygen treatment with titrated oxygen treatment for patients with an acute exacerbation of chronic obstructive pulmonary disease in the prehospital setting. Design Cluster randomised controlled parallel group trial. Setting Ambulance service in Hobart, Tasmania, Australia. Participants 405 patients with a presumed acute exacerbation of chronic obstructive pulmonary disease who were treated by paramedics, transported, and admitted to the Royal Hobart Hospital during the trial period; 214 had a diagnosis of chronic obstructive pulmonary disease confirmed by lung function tests in the previous five years. Interventions High flow oxygen treatment compared with titrated oxygen treatment in the prehospital (ambulance/paramedic) setting. Main outcome measure Prehospital or in-hospital mortality. Results In an intention to treat analysis, the risk of death was significantly lower in the titrated oxygen arm compared with the high flow oxygen arm for all patients (high flow oxygen n=226; titrated oxygen n=179) and for the subgroup of patients with confirmed chronic obstructive pulmonary disease (high flow n=117; titrated n=97). Overall mortality was 9% (21 deaths) in the high flow oxygen arm compared with 4% (7 deaths) in the titrated oxygen arm; mortality in the subgroup with confirmed chronic obstructive pulmonary disease was 9% (11 deaths) in the high flow arm compared with 2% (2 deaths) in the titrated oxygen arm. Titrated oxygen treatment reduced mortality compared with high flow oxygen by 58% for all patients (relative risk 0.42, 95% confidence interval 0.20 to 0.89; P=0.02) and by 78% for the patients with confirmed chronic obstructive pulmonary disease (0.22, 0.05 to 0.91; P=0.04). Patients with chronic obstructive pulmonary disease who received titrated oxygen according to the protocol were significantly less likely to have respiratory acidosis (mean difference in pH 0.12 (SE 0.05); P=0.01; n=28) or hypercapnia (mean difference in arterial carbon dioxide pressure −33.6 (16.3) mm Hg; P=0.02; n=29) than were patients who received high flow oxygen. Conclusions Titrated oxygen treatment significantly reduced mortality, hypercapnia, and respiratory acidosis compared with high flow oxygen in acute exacerbations of chronic obstructive pulmonary disease. These results provide strong evidence to recommend the routine use of titrated oxygen treatment in patients with breathlessness and a history or clinical likelihood of chronic obstructive pulmonary disease in the prehospital setting. Trial registration Australian New Zealand Clinical Trials Register ACTRN12609000236291.

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.

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.

Brain Atrophy in Type 2 Diabetes Regional distribution and influence on cognition

OBJECTIVE Type 2 diabetes (T2DM) is associated with brain atrophy and cerebrovascular disease. We aimed to define the regional distribution of brain atrophy in T2DM and to examine whether atrophy or cerebrovascular lesions are feasible links between T2DM and cognitive function. RESEARCH DESIGN AND METHODS This cross-sectional study used magnetic resonance imaging (MRI) scans and cognitive tests in 350 participants with T2DM and 363 participants without T2DM. With voxel-based morphometry, we studied the regional distribution of atrophy in T2DM. We measured cerebrovascular lesions (infarcts, microbleeds, and white matter hyperintensity [WMH] volume) and atrophy (gray matter, white matter, and hippocampal volumes) while blinded to T2DM status. With use of multivariable regression, we examined for mediation or effect modification of the association between T2DM and cognitive measures by MRI measures. RESULTS T2DM was associated with more cerebral infarcts and lower total gray, white, and hippocampal volumes (all P < 0.05) but not with microbleeds or WMH. T2DM-related gray matter loss was distributed mainly in medial temporal, anterior cingulate, and medial frontal lobes, and white matter loss was distributed in frontal and temporal regions. T2DM was associated with poorer visuospatial construction, planning, visual memory, and speed (P ≤ 0.05) independent of age, sex, education, and vascular risk factors. The strength of these associations was attenuated by almost one-half when adjusted for hippocampal and total gray volumes but was unchanged by adjustment for cerebrovascular lesions or white matter volume. CONCLUSIONS Cortical atrophy in T2DM resembles patterns seen in preclinical Alzheimer disease. Neurodegeneration rather than cerebrovascular lesions may play a key role in T2DM-related cognitive impairment.

Ageing and gait variability—a population-based study of older people

BACKGROUND gait variability may be an important predictor of falls risk, but its characteristics are poorly understood. OBJECTIVE to examine the relationship between age and gait variability in a population-based sample of older people. DESIGN cross-sectional study. METHODS in people aged 60-86 years (n = 412), temporal and spatial gait variability measures were recorded with a GAITRite walkway. Regression analysis was used to model the relationship between age and gait variability adjusting for height, weight and self-reported chronic disease. Further adjustment was made for gait speed to examine its influence on the associations. RESULTS older age was associated with greater variability (P < 0.05) in all gait measures. All relationships were linear, except that between age and step time variability, which was curvilinear in women. Adjusting for gait speed changed the magnitude of the age coefficient by 62-86% for temporal variability measures, 25% for step length variability and 5-12% for step width variability. CONCLUSION age is linearly associated with greater intra-individual gait variability for most gait measures, except for step time variability in women. Gait speed may mediate the association between age and temporal variability measures. Further study is needed to understand the factors responsible for the greater gait variability with ageing.