To determine whether body mass index (BMI) or vitamin D status is associated with MRI measures of neurodegeneration in a cohort of individuals with relapsing-remitting multiple sclerosis (RRMS) or ...clinically isolated syndrome (CIS).
Expression, Proteomics, Imaging, Clinical (EPIC) is a longitudinal multiple sclerosis (MS) cohort study at the University of California, San Francisco. Participants had clinical evaluations, brain MRI, and blood draws annually. We evaluated patients with CIS or RRMS at baseline. In multivariate repeated-measures analyses adjusted for age, sex, ethnicity, smoking status, and use of MS treatments, annual 25-hydroxyvitamin D levels and BMI were evaluated for their association with subsequent brain volumes (normalized gray matter nGMV, brain parenchymal nBPV, and white matter volumes, as determined by Structural Image Evaluation using Normalization of Atrophy-X).
Among 469 participants, each 1-kg/m
higher BMI was independently associated with reduced nGMV in multivariate models (-1.1 mL, 95% confidence interval CI -1.8 to -0.5,
= 0.001). BMI was likewise independently associated with nBPV (nBPV per 1-kg/m
greater BMI: -1.1 mL, 95% CI -2.1 to -0.05,
= 0.039). Vitamin D levels did not appear to be meaningfully associated with brain volumes.
Higher BMI appears to be associated with greater reductions in nGMV and nBPV, which is relevant because, in particular, nGMV loss portends greater longer-term disability. Because obesity is modifiable, further studies should explore these relationships in detail, and evaluating the effect of reducing BMI on imaging and clinical outcomes in MS may be warranted.
Climate change and marine litter are inextricably linked, and their interaction manifests differently depending on the specific environmental and biological characteristics, and other human ...activities taking place. The negative impacts resulting from those synergistic interactions are threatening coastal and marine ecosystems and the many goods and services they provide. This is particularly pervasive in the coastal zone of the Indian subcontinent. India is already experiencing severe climate change impacts, which are projected to worsen in the future. At the same time, the country is gripped by a litter crisis that is overwhelming authorities and communities and hindering the country's sustainable development goals. The coastal environment and communities of the southern states of Kerala and Tamil Nadu are particularly vulnerable to the impacts of climate change. While these state governments and authorities are stepping up efforts to improve the management of their coastal zones, the scale and severity of these issues are mounting. Here we review the combined effects of climate change and marine litter pollution in Southern India, focusing on the Gulf of Mannar Reserve in Tamil Nadu and the Malabar Coast in Kerala. Finally, we discuss effective management options that could help improve resilience and sustainability.
Objective:
We sought to determine whether vitamin D status is associated with developing new T2 lesions or contrast‐enhancing lesions on brain magnetic resonance imaging (MRI) in relapsing multiple ...sclerosis (MS).
Methods:
EPIC is a 5‐year longitudinal MS cohort study at the University of California at San Francisco. Participants had clinical evaluations, brain MRI, and blood draws annually. From the overall cohort, we evaluated patients with clinically isolated syndrome or relapsing–remitting MS at baseline. In univariate and multivariate (adjusted for age, sex, ethnicity, smoking, and MS treatments) repeated measures analyses, annual 25‐hydroxyvitamin D levels were evaluated for their association with subsequent new T2‐weighted and gadolinium‐enhancing T1‐weighted lesions on brain MRI, clinical relapses, and disability (Expanded Disability Status Scale EDSS).
Results:
A total of 2,362 3T brain MRI scans were acquired from 469 subjects. In multivariate analyses, each 10ng/ml higher 25‐hydroxyvitamin D level was associated with a 15% lower risk of a new T2 lesion (incidence rate ratio IRR, 0.85; 95% confidence interval CI, 0.76–0.95; p = 0.004) and a 32% lower risk of a gadolinium‐enhancing lesion (IRR, 0.68; 95% CI, 0.53–0.87; p = 0.002). Each 10ng/ml higher vitamin D level was associated with lower subsequent disability (−0.047; 95% CI, −0.091 to −0.003; p = 0.037). Higher vitamin D levels were associated with lower, but not statistically significant, relapse risk. Except for the EDSS model, all associations were stronger when the within‐person change in vitamin D level was the predictor.
Interpretation:
Vitamin D levels are inversely associated with MS activity on brain MRI. These results provide further support for a randomized trial of vitamin D supplementation. ANN NEUROL 2012;72:234–240.
The role of sex as an important biological determinant of vulnerability to sustaining injury and gender as a social determinate of access to resources, referral for medical care and perceived ...disability remains conflicted in injured workers. The purpose of this study was to examine sex and gender disparity following a compensable work-related shoulder injury.
This study involved cross-sectional analyses of data of two independent samples of workers with shoulder injury. Measures of disability and pain were the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) and Numerical Pain Rating Scale (NPRS) for patients seen at an Early Shoulder Physician Assessment (ESPA) program and the American Shoulder and Elbow Surgeons (ASES) assessment form and Visual Analogue Scale (VAS) for the sample who underwent surgery.
The files of 1000 (443 females, 557 men) consecutive patients seen at an ESPA program and 150 (44 females, and 106 men) consecutive patients who underwent rotator cuff surgery (repair or decompression) were reviewed. Significant gender disparity was observed in the referral pattern of injured workers seen at the ESPA program who were referred for surgical consultation (22 vs. 78 % for females and males respectively, p < 0.0001). The independent rotator cuff surgical group had a similar gender discrepancy (29 % vs. 71 %, p < 0.0001). The timeframe from injury to surgery was longer in women in the surgical group (p = 0.01). As well, women waited longer from the date of consent to date of surgery (p = 0.04). Women had higher incidence of repetitive injuries (p = 0.01) with men reporting higher incidence of falls (p = 0.01). Women seen at the ESPA program were more disabled than men (p = 0.02). Women in both samples had a higher rate of medication consumption than men (p = 0.01 to <0.0001). Men seen at the ESPA program had a higher prevalence of full thickness rotator cuff tears (p < 0.0001) and labral pathology (p = 0.01). However, these pathologies did not explain gender disparity in the subsample of ESPA who were referred for surgical consultation or those who had surgery.
Sex and gender disparity exists in workers with shoulder injuries and is evident in the mechanism of injury, perceived disability, medication consumption, referral pattern, and wait time for surgery.
Multiple sclerosis is a common disease with proven heritability, but, despite large-scale attempts, no underlying risk genes have been identified. Traditional linkage scans have so far identified ...only one risk haplotype for multiple sclerosis (at HLA on chromosome 6), which explains only a fraction of the increased risk to siblings. Association scans such as admixture mapping have much more power, in principle, to find the weak factors that must explain most of the disease risk. We describe here the first high-powered admixture scan, focusing on 605 African American cases and 1,043 African American controls, and report a locus on chromosome 1 that is significantly associated with multiple sclerosis.
An underlying complex genetic susceptibility exists in multiple sclerosis (MS), and an association with the
HLA-DRB1*1501-DQB1*0602 haplotype has been repeatedly demonstrated in high-risk (northern ...European) populations. It is unknown whether the effect is explained by the
HLA-DRB1 or the
HLA-DQB1 gene within the susceptibility haplotype, which are in strong linkage disequilibrium (LD). African populations are characterized by greater haplotypic diversity and distinct patterns of LD compared with northern Europeans. To better localize the HLA gene responsible for MS susceptibility, case-control and family-based association studies were performed for
DRB1 and
DQB1 loci in a large and well-characterized African American data set. A selective association with
HLA-DRB1*15 was revealed, indicating a primary role for the
DRB1 locus in MS independent of
DQB1*0602. This finding is unlikely to be solely explained by admixture, since a substantial proportion of the susceptibility chromosomes from African American patients with MS displayed haplotypes consistent with an African origin.
Background Expediting rotator cuff surgery is expected to facilitate recovery and return to work in injured workers. This case-control study examined the effect of expedited rotator cuff surgery on ...recovery and work status in injured workers. Materials and methods Injured workers who had undergone an expedited rotator cuff surgery funded by parallel-pay insurance (study group) were compared with workers who had used the public health insurance (control group) while adjusting for sex, age, severity of pathology, and follow-up period. Disability was measured by the American Shoulder and Elbow Surgeons (ASES) Standardized Assessment Form score. The percentage of patients who exceeded the minimal clinically important difference of 17 points in the ASES was calculated. Results The study group waited less time to have surgery than the control group ( P < .0001), reported less disability after surgery, and had a higher number of patients whose improvement exceeded the minimal clinically important difference (119 vs. 65, P < .0001). The study group was more likely to be working at the time of the final follow-up ( P < .0001). The final multivariable regressions, which adjusted for unmatched variables, such as dominant side involvement, mechanism of injury, and associated operations that were different between groups, were consistent with univariable analyses indicating superior results in the study group. Conclusions Injured workers who underwent expedited rotator cuff surgery reported less disability and had a more successful return to work after surgery than injured workers who waited longer for specialist assessment and surgery within the public health system.
Variation in major histocompatibility complex genes on chromosome 6p21.3, specifically the human leukocyte antigen HLA-DR2 or DRB1*1501-DQB1*0602 extended haplotype, confers risk for multiple ...sclerosis (MS). Previous studies of DRB1 variation and both MS susceptibility and phenotypic expression have lacked statistical power to detect modest genotypic influences, and have demonstrated conflicting results. Results derived from analyses of 1339 MS families indicate DRB1 variation influences MS susceptibility in a complex manner. DRB1*15 was strongly associated in families (P=7.8×10−31), and a dominant DRB1*15 dose effect was confirmed (OR=7.5, 95% CI=4.4–13.0, P<0.0001). A modest dose effect was also detected for DRB1*03; however, in contrast to DRB1*15, this risk was recessive (OR=1.8, 95% CI=1.1–2.9, P=0.03). Strong evidence for under-transmission of DRB1*14 (P=5.7×10−6) even after accounting for DRB1*15 (P=0.03) was present, confirming a protective effect. In addition, a high risk DRB1*15 genotype bearing DRB1*08 was identified (OR=7.7, 95% CI=4.1–14.4, P<0.0001), providing additional evidence for trans DRB1 allelic interactions in MS. Further, a significant DRB1*15 association observed in primary progressive MS families (P=0.0004), similar to relapsing-remitting MS families, suggests that DRB1-related mechanisms are contributing to both phenotypes. In contrast, results obtained from 2201 MS cases argue convincingly that DRB1*15 genotypes do not modulate age of onset, or significantly influence disease severity measured using expanded disease disability score and disease duration. These results contribute substantially to our understanding of the DRB1 locus and MS, and underscore the importance of using large sample sizes to detect modest genetic effects, particularly in studies of genotype–phenotype relationships.
Autoimmune mechanisms are thought to have a major role in the pathogenesis of multiple sclerosis. We aimed to identify coexisting autoimmune phenotypes in patients with multiple sclerosis from ...families with several members with the disease and in their first-degree relatives.
A total of 176 families (386 individuals and 1107 first-degree relatives) were characterised for a history of other autoimmune disorders. Family-based or case–control analyses were done to assess the association of cytotoxic T-lymphocyte-antigen 4 (
CTLA4) and protein tyrosine phosphatase (
PTPN22) variants with susceptibility to multiple sclerosis.
46 (26%) index cases reported at least one coexisting autoimmune disorder. The most common were Hashimoto thyroiditis (10%), psoriasis (6%), inflammatory bowel disease (3%), and rheumatoid arthritis (2%). 112 (64%) families with a history of multiple sclerosis reported autoimmune disorders (excluding multiple sclerosis) in one or more first-degree relatives, whereas 64 (36%) families reported no history of autoimmunity. Similar to index cases, Hashimoto thyroiditis, psoriasis, and inflammatory bowel disease were also the most common disorders occurring in family members. A common variant within
CTLA4 was strongly associated with multiple sclerosis in families who had other autoimmune diseases (p=0·009) but not in families without a history of other autoimmune disorders (p=0·90).
The presence of various immune disorders in families with several members with multiple sclerosis suggests that the disease might arise on a background of a generalised susceptibility to autoimmunity. This distinct multiple-sclerosis phenotype, defined by its association with other autoimmune diseases, segregates with specific genotypes that could underlie the common susceptibility.
There is minimal research on demographics, type of injury and diagnosis of injured workers with shoulder problems. The purposes of this study were: 1) to document the demographics of patients with ...shoulder complaints referred to an Early Shoulder Physician Assessment (ESPA) Program and to describe the recommended management, and 2) to examine the relationship between patient characteristics and their subjective complaints of pain and functional difficulty.
This study involved a retrospective review of electronic files of injured workers mostly seen within the first 16 weeks of injury or recurrence. Measures of functional difficulty and pain were the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) and Numeric Pain Scale (NPS).
Files of 550 consecutive patients, 260 females (47%), 290 men (53%) were examined. The average age was 49 (SD = 11, range 22-77), with 28 (5%) patients being 65 years of age or older. Patients who were not working were the most disabled group based on Quick DASH (F = 49.93, p < 0.0001) and NPS (F = 10.24, p = 0.002). Patients who were working full time performing regular duties were the least disabled according to both measures, the QuickDASH (F = 10.24, p = 0.002) and NPS (F = 7.57, p = 0.006). Patients waiting more than 16 weeks were slightly older (53 years of age vs. 49, p = 0.045) than those who met the criteria for early assessment with similar levels of pain and functional difficulty. Biceps pathology had the highest prevalence (37%). Full thickness tear had a prevalence of 14%. Instability, labral lesions and osteoarthritis of glenohumeral joint were uncommon conditions (3, 2 and 1% respectively). Fifty-five patients (10%) were surgical candidates and had higher scores on QuickDASH (F = 7.16, p = 0.008) and NPS (F = 4.24, p = 0.04) compared to those who did not require surgery.
This study provides information on characteristics and prevalence of important variables in injured workers with shoulder problems and highlights the impact of these characteristics on pain and disability.
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