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Background: Several recent studies have found a higher risk of multiple sclerosis (MS) among people with a low level of education. This has been suggested to reflect an effect of smoking and lower vitamin D status in the social class associated with lower levels of education., Objective: The objective of this paper is to investigate the association between level of education and MS risk adjusting for the known risk factors smoking, infectious mononucleosis, indicators of vitamin D levels and body size., Methods: Within the case-control study on Environmental Factors In MS (EnvIMS), 953 MS patients and 1717 healthy controls from Norway reported educational level and history of exposure to putative environmental risk factors., Results: Higher level of education were associated with decreased MS risk (p trend = 0.001) with an OR of 0.53 (95% CI 0.41-0.68) when comparing those with the highest and lowest level of education. This association was only moderately reduced after adjusting for known risk factors (OR 0.61, 95% CI 0.44-0.83). The estimates remained similar when cases with disease onset before age 28 were excluded., Conclusion: These findings suggest that factors related to lower socioeconomic status other than established risk factors are associated with MS risk., (© The Author(s), 2015.)

Objective: We aimed to compare the incidence and prevalence of psychiatric comorbidity in the multiple sclerosis (MS) population and in controls matched for age, sex, and geographic area., Methods: Using population-based administrative health data from 4 Canadian provinces, we identified 2 cohorts: 44,452 persons with MS and 220,849 controls matched for age, sex, and geographic area. We applied validated case definitions to estimate the incidence and prevalence of depression, anxiety, bipolar disorder, and schizophrenia from 1995 to 2005. We pooled the results across provinces using meta-analyses., Results: Of the MS cases, 31,757 (71.3%) were women with a mean (SD) age at the index date of 43.8 (13.7) years. In 2005, the annual incidence of depression per 100,000 persons with MS was 979 while the incidence of anxiety was 638, of bipolar disorder was 328, and of schizophrenia was 60. The incidence and prevalence estimates of all conditions were higher in the MS population than in the matched population. Although the incidence of depression was higher among women than men in both populations, the disparity in the incidence rates between the sexes was lower in the MS population (incidence rate ratio 1.26; 95% confidence interval: 1.07-1.49) than in the matched population (incidence rate ratio 1.50; 95% confidence interval: 1.21-1.86). Incidence rates were stable over time while prevalence increased slightly., Conclusions: Psychiatric comorbidity is common in MS, and more frequently affected the MS population than a matched population, although the incidence was stable over time. Men with MS face a disproportionately greater relative burden of depression when they develop MS than women., (© 2015 American Academy of Neurology.)

Background: Low vitamin D levels have been associated with an increased risk of multiple sclerosis (MS), although it remains unknown whether this relationship varies by age., Objective: The objective of this paper is to investigate the association between vitamin D3 supplementation through cod liver oil at different postnatal ages and MS risk., Methods: In the Norwegian component of the multinational case-control study Environmental Factors In Multiple Sclerosis (EnvIMS), a total of 953 MS patients with maximum disease duration of 10 years and 1717 controls reported their cod liver oil use from childhood to adulthood., Results: Self-reported supplement use at ages 13-18 was associated with a reduced risk of MS (OR 0.67, 95% CI 0.52-0.86), whereas supplementation during childhood was not found to alter MS risk (OR 1.01, 95% CI 0.81-1.26), each compared to non-use during the respective period. An inverse association was found between MS risk and the dose of cod liver oil during adolescence, suggesting a dose-response relationship (p trend = 0.001) with the strongest effect for an estimated vitamin D3 intake of 600-800 IU/d (OR 0.46, 95% CI 0.31-0.70)., Conclusions: These findings not only support the hypothesis relating to low vitamin D as a risk factor for MS, but further point to adolescence as an important susceptibility period for adult-onset MS., (© The Author(s), 2015.)

In the course of investigating anti-DNA autoantibodies, we examined IgM and IgG antibodies to poly-G and other oligonucleotides in the sera of healthy persons and those diagnosed with systemic lupus erythematosus (SLE), scleroderma (SSc), or pemphigus vulgaris (PV); we used an antigen microarray and informatic analysis. We now report that all of the 135 humans studied, irrespective of health or autoimmune disease, manifested relatively high amounts of IgG antibodies binding to the 20-mer G oligonucleotide (G20); no participants entirely lacked this reactivity. IgG antibodies to homo-nucleotides A20, C20 or T20 were present only in the sera of SLE patients who were positive for antibodies to dsDNA. The prevalence of anti-G20 antibodies led us to survey human, mouse and Drosophila melanogaster (fruit fly) genomes for runs of T20 and G20 or more: runs of T20 appear > 170,000 times compared with only 93 runs of G20 or more in the human genome; of these runs, 40 were close to brain-associated genes. Mouse and fruit fly genomes showed significantly lower T20/G20 ratios than did human genomes. Moreover, sera from both healthy and SLE mice contained relatively little or no anti-G20 antibodies; so natural anti-G20 antibodies appear to be characteristic of humans. These unexpected observations invite investigation of the immune functions of anti-G20 antibodies in human health and disease and of runs of G20 in the human genome., (© 2015 John Wiley & Sons Ltd.)

Province-wide population-based administrative health data from British Columbia (BC), Canada (population: approximately 4.5 million) were used to estimate the incidence and prevalence of multiple sclerosis (MS) and examine potential trends over time. All BC residents meeting validated health administrative case definitions for MS were identified using hospital, physician, death, and health registration files. Estimates of annual prevalence (1991-2008), and incidence (1996-2008; allowing a 5-year disease-free run-in period) were age and sex standardized to the 2001 Canadian population. Changes over time in incidence, prevalence and sex ratios were examined using Poisson and log-binomial regression. The incidence rate was stable [average: 7.8/100,000 (95 % CI 7.6, 8.1)], while the female: male ratio decreased (p = 0.045) but remained at or above 2 for all years (average 2.8:1). From 1991-2008, MS prevalence increased by 4.7 % on average per year (p < 0.001) from 78.8/100,000 (95 % CI 75.7, 82.0) to 179.9/100,000 (95 % CI 176.0, 183.8), the sex prevalence ratio increased from 2.27 to 2.78 (p < 0.001) and the peak prevalence age range increased from 45-49 to 55-59 years. MS incidence and prevalence in BC are among the highest in the world. Neither the incidence nor the incidence sex ratio increased over time. However, the prevalence and prevalence sex ratio increased significantly during the 18-year period, which may be explained by the increased peak prevalence age of MS, longer survival with MS and the greater life expectancy of women compared to men.

Background: Comorbidities are common in multiple sclerosis (MS). The high prevalence of pain in MS is well-established but the influence of comorbidities on pain, specifically, pain-related interference in activity is not., Objective: To examine the relationship between comorbidity and pain in MS., Methods: We recruited 949 consecutive patients with definite MS from four Canadian centres. Participants completed the Health Utilities Index (HUI-Mark III) and a validated comorbidity questionnaire at 3 visits over 2 years. The HUI's pain scale was dichotomized into two groups: those with/without pain that disrupts normal activities. We used logistic regression to assess the association of pain with each comorbidity individually at baseline and over time., Results: The incidence of disruptive pain over two years was 31.1 per 100 persons. Fibromyalgia, rheumatoid arthritis, irritable bowel syndrome, migraine, chronic lung disease, depression, anxiety, hypertension, and hypercholesterolemia were associated with disruptive pain (p<0.006). Individual-level effects on the presence of worsening pain were seen for chronic obstructive pulmonary disease (odds ratio [OR]: 1.50 95% CI: 1.08-2.09), anxiety (OR: 1.49 95% CI: 1.07-2.08), and autoimmune thyroid disease (OR: 1.40 95% CI: 1.00-1.97)., Conclusion: Comorbidity is associated with pain in persons with MS. Closer examination of these associations may provide guidance for better management of this disabling symptom in MS., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Intravenous immunoglobulins (IVIGs) are beneficial and safe for various diseases other than primary immunodeficiencies. Over the years, IVIG has been given for autoimmune diseases as an off-label adjunct therapy. While other biologic agents are indicated for rheumatoid arthritis (RA), IVIG may have a role for specific subgroups of RA patients where anti-cytokine blockers or rituximab may be unwarranted. Such subgroups may include patients with vasculitis, overlap rhupus syndrome, severe infections with active disease, and pregnancy. In addition, IVIG may be considered for juvenile chronic arthritis (JCA) and adult Still's disease. We review the literature for IVIG treatment in RA patients and for these subgroups., (Copyright © 2015 Elsevier B.V. All rights reserved.)

High socioeconomic status (SES) is generally associated with better health outcomes, but some research has linked it with an increased risk of multiple sclerosis (MS). The evidence for this association is inconsistent and has not previously been systematically reviewed. A systematic review of cohort and case-control studies in any language was conducted looking at the association between MS and SES. MEDLINE and EMBASE were searched for articles in all languages published up until 23 August 2013. Twenty-one studies from 13 countries were included in the review. Heterogeneity of study settings precluded carrying out a meta-analysis, and a qualitative synthesis was performed instead. Five studies, all from more unequal countries, reported an association between high SES and MS. Thirteen studies reported no evidence of an association, and three studies reported an association with low SES. These 16 studies largely came from more egalitarian countries. The evidence for an association between high SES and increased MS risk is inconsistent but with some indication of a stronger effect in countries and time periods with higher inequality. Firm conclusions are hampered by the failure of most studies to control for other important risk factors for MS., (© 2014 EAN.)

Breastfeeding for at least 4 months has been found to be associated with a reduced risk of immune-mediated diseases including multiple sclerosis (MS). Using data from a large multinational case-control study (EnvIMS), the association between MS and breastfeeding was investigated in two distinct populations. A questionnaire (EnvIMS-Q) which included a section on feeding during the first year of life was administered to MS cases and to age and sex frequency-matched controls from Italy and Norway. Logistic regression was used to estimate the odds ratio (ORs) and 95% confidence intervals (95% CIs) as a measure of the association between MS and exposure to prolonged breastfeeding (4 months or more, used as the reference category), vs. no breastfeeding or breastfeeding for less than 4 months (reduced exposure). Education, smoking habits, smoking in mother's pregnancy, and other types of milk used in infant feeding were included as covariates. A total of 547 cases and 1039 controls in Italy, and 737 cases and 1335 controls in Norway were studied. The distribution of prolonged (reference) breastfeeding differed between the Norwegian (65.4%) and the Italian (48.9%) study participants. A significant association between MS and reduced/no exposure to breastfeeding was found overall for Italy (OR(adj) = 1.37; 95% CI 1.09, 1.73), but not for Norway (OR(adj) = 1.14; 95% CI 0.92, 1.40). However, only in men, significant associations were observed for both populations (OR(Italy) = 2.33; 95% CI 1.50, 3.65, OR(Norway) = 2.13; 95% CI 1.37, 3.30). Reduced exposure to breastfeeding in males was found to be associated with increased risk of MS in Italy and in Norway.

Background: Obesity may be a risk factor for developing multiple sclerosis (MS)., Objective: We examined if body size influences the risk of MS in a population-based, case control study., Methods: A total of 953 cases and 1717 controls from Norway and 707 cases and 1333 controls from Italy reported their body size by choosing a silhouette 1 to 9 (largest) every fifth year from age 5 to 30 and at time of study. The body size-related MS risk was defined by odds ratios (ORs) in logistic regression analyses adjusting for age, smoking and outdoor activity., Results: In Norway a large body size (silhouettes 6-9) compared to silhouette 3 increased the risk of MS, especially at age 25 (OR 2.21; 95% CI 1.09-4.46 for men and OR 1.43; 95% CI 0.90-2.27 for women). When comparing silhouette 9 to 1, we found a significant dose-response from age 10 until age 30 peaking at age 25 (sex-adjusted OR 2.83; 95% CI 1.68-4.78). The association was present for at least 15 years prior to disease onset. No significant associations were found in Italy., Conclusions: Obesity from childhood until young adulthood is a likely risk factor for MS with a seemingly stronger effect in Norway than in Italy., (© The Author(s), 2014.)

Objectives: To identify statistical methods for harmonization, the procedures aimed at achieving the comparability of previously collected data, which could be used in the context of summary data and individual participant data meta-analysis of cognitive measures., Study Design and Setting: Environmental scan methods were used to conduct two reviews to identify (1) studies that quantitatively combined data on cognition and (2) general literature on statistical methods for data harmonization. Search results were rapidly screened to identify articles of relevance., Results: All 33 meta-analyses combining cognition measures either restricted their analyses to a subset of studies using a common measure or combined standardized effect sizes across studies; none reported their harmonization steps before producing summary effects. In the second scan, three general classes of statistical harmonization models were identified (1) standardization methods, (2) latent variable models, and (3) multiple imputation models; few publications compared methods., Conclusion: Although it is an implicit part of conducting a meta-analysis or pooled analysis, the methods used to assess inferential equivalence of complex constructs are rarely reported or discussed. Progress in this area will be supported by guidelines for the conduct and reporting of the data harmonization and integration and by evaluating and developing statistical approaches to harmonization., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Multiple sclerosis (MS) is a chronic disease of the central nervous system, often resulting in significant neurological disability. The causes of MS are not known; however, the incidence of MS is increasing, thereby suggesting that changes in lifestyle and/or environmental factors may be responsible. On this background, the Environmental Risk Factors in MS Study or EnvIMS study was designed to further explore the etiology of MS. The design and methodology are described, providing details to enable investigators to (i) use our experiences to design their own studies; (ii) take advantage of, and build on the methodological work completed for, the EnvIMS study; (iii) become aware of this data source that is available for use by the research community., Methods: EnvIMS is a multinational case-control study, enrolling 2,800 cases with MS and 5,012 population-based controls in Canada, Italy, Norway, Serbia and Sweden. The study was designed to investigate the most commonly implicated risk factors for MS etiology using a self-report questionnaire., Results/conclusions: The use of a common methodology to study MS etiology across several countries enhances the comparability of results in different geographic regions and research settings, reduces the resources required for study design and enhances the opportunity for data harmonization., (© 2015 S. Karger AG, Basel.)

Background: Parkinson's disease is characterized by numerous non-motor symptoms, including sleep disorders. Sleep apnea has been reported in a substantial proportion of patients with Parkinson's disease, but it is unclear whether it has significant consequences for the quality of life of those affected or whether it is associated with other manifestations of the disease., Objective: To verify whether sleep apnea is associated with more severe motor and non-motor clinical features in Parkinson's disease., Methods: Parkinson's disease patients underwent polysomnography to diagnose the presence of sleep apnea (apnea-hypopnoea index >10). Participants also underwent an extensive assessment, blinded to sleep apnea status, to determine disease severity, quantitative motor indices, motor subtypes, treatment complications, and sleep, autonomic, psychiatric, and sensory dysfunctions. Cognitive status was also determined with a complete neuropsychological assessment. Results were assessed using regression analysis adjusted for age, sex, and disease duration., Results: Of 92 patients examined, 19 had sleep apnea (21%) and 73 did not. We found no significant differences in motor and non-motor symptoms or signs between apneic and non-apneic Parkinson's disease patients. The use of different apnea-hypopnoea index cut-offs (>5 and >15) produced similar results., Conclusions: Our results show that sleep apnea is not associated with more severe motor or non-motor manifestations in Parkinson's disease. More studies including control groups are needed to confirm the implications of those results.

Current theories of object recognition in human vision make different predictions about whether the recognition of complex, multipart objects should be influenced by shape information about surface depth orientation and curvature derived from stereo disparity. We examined this issue in five experiments using a recognition memory paradigm in which observers (N = 134) memorized and then discriminated sets of 3D novel objects at trained and untrained viewpoints under either mono or stereo viewing conditions. In order to explore the conditions under which stereo-defined shape information contributes to object recognition we systematically varied the difficulty of view generalization by increasing the angular disparity between trained and untrained views. In one series of experiments, objects were presented from either previously trained views or untrained views rotated (15°, 30°, or 60°) along the same plane. In separate experiments we examined whether view generalization effects interacted with the vertical or horizontal plane of object rotation across 40° viewpoint changes. The results showed robust viewpoint-dependent performance costs: Observers were more efficient in recognizing learned objects from trained than from untrained views, and recognition was worse for extrapolated than for interpolated untrained views. We also found that performance was enhanced by stereo viewing but only at larger angular disparities between trained and untrained views. These findings show that object recognition is not based solely on 2D image information but that it can be facilitated by shape information derived from stereo disparity.

GNE Myopathy (GNEM) is a neuromuscular disorder caused by mutations in the GNE gene. It is a slowly progressive distal and proximal muscle weakness sparing the quadriceps. In this study, we applied our model of mutated M743T GNE enzyme skeletal muscle-cultured myoblasts and paired healthy controls to depict the pattern of signaling proteins controlling survival and/or apoptosis of the PI3K/AKT, BCL2, ARTS/XIAP pathways, examined the effects of metabolic changes/stimuli on their expression and activation, and their potential role in GNEM. Immunoblot analysis of the GNEM myoblasts indicated a notable increased level of activated PTEN and PDK1 and a trend of relative differences in the expression and activation of the examined signaling molecules with variability among the cultures. ANOVA analysis showed a highly significant interaction between the level of PTEN and the patients groups. In parallel, the interaction between the level of BCL2, BAX and PTEN with the specific PI3K/AKT inhibitor-LY294002 was highly significant for BCL2 and nearly significant for PTEN and BAX. The pattern of the ARTS/XIAP signaling proteins of GNEM and the paired controls was variable, with no significant differences between the two cell types. The response of the GNEM cells to the metabolic changes/stimuli: serum depletion and insulin challenge, as indicated by expression of selected signaling proteins, was variable and similar to the control cells. Taken together, our observations provide a clearer insight into specific signaling molecules influencing growth and survival of GNEM muscle cells.

Objective: Accurate estimates of the incidence and prevalence of epilepsy allow us to better assess its societal impact. Prevalence and incidence studies often use unvalidated screening tools resulting in estimates of uncertain accuracy. We present the Canadian Longitudinal Study on Aging-Epilepsy Algorithm (CLSA-EA) as well as the results of our validation study designed to estimate the diagnostic accuracy of this epilepsy ascertainment algorithm., Methods: We administered English or French-language versions of the CLSA-EA questionnaire to a consecutive sample of participants from a population-based cohort of 50,000 individuals aged between 45 and 85 years at baseline, as well as a consecutive sample of individuals from an epilepsy-enriched general neurology clinic. Every participant was also assessed by a study neurologist who, blinded to the results of the CLSA-EA, determined whether the person had epilepsy or not., Results: We recruited 242 consecutive participants, 34 of whom were diagnosed with epilepsy by a study neurologist. The sensitivity and specificity of the CLSA-EA for a lifetime history of epilepsy were 97.1% and 98.1%, and for active epilepsy were 100% and 98.6%, when we defined a positive screening test result as a positive response to the antiepileptic drug question and either the single self-report diagnosis or any of the symptom-based questions., Significance: The CLSA-EA was found to have a high sensitivity and specificity for the identification of adults with a lifetime history of epilepsy and active epilepsy. Although validation in other settings and age groups is required, the future application of this algorithm to population-based studies such as the CLSA should help to ensure more accurate estimates of the prevalence and incidence of epilepsy in the general population when a physician assessment is impossible., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

Tolerogenic dendritic cells (tDCs) have the potential to control the outcome of autoimmunity by modulating the immune response. The aim of this study was to uncover the tolerance efficacy attributed to beta-2-glycoprotein-I (β2GPI) tDCs or β2GPI domain-I (D-I) and domain-V (D-V)-tDCs in mice with antiphospholipid syndrome (APS). tDCs were pulsed with β2GPI or D-I or D-V derivatives. Our results revealed that β2GPI related tDCs phenotype includes CD80(high), CD86(high) CD40(high) MHC class II(high). The miRNA profiling encompass miRNA 23b(high), miRNA 142-3p(low) and miRNA 221(low). In addition the β2GPI related tDCs showed reduced secretion of IL-1β, IL-12 and IL-23. D-I tDCs treatment was more efficient than β2GPI tDCs in inducing of tolerance in APS mice, manifested by lowered titers of anti- β2GPI antibodies (Abs) and reduced percentage of fetal loss. Tolerance induction was accompanied by poor T cell response to β2GPI, high numbers of CD4 + CD25 + FOXP3 + T-regulatory cells (Treg), reduced levels of IFNγ, IL-17 and increased expression of IL-10 and TGFβ. Tolerance was successfully transferred by Treg cells from the tolerized mice to β2GPI immunized mice. We conclude that predominantly D-I-tDCs and β2GPI tDCs have the potential to attenuate experimental APS by induction of Treg cells, reduction of anti- β2GPI Abs titers and increased expression of anti-inflammatory cytokines. We suggest that β2-GPI-D-I-tDCs may offer a novel approach for developing therapy for APS patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by widespread organ involvement. Given the scope of modern treatment, there has been a rise in life expectancy and quality with a mean estimated 5-year survival of 82%-90%. Hence, hospitalizations of SLE patients for non-SLE related causes have not been investigated. Our aim was to characterize the SLE patients admitted to the internal medicine wards, the main diagnosis at admission, and the course of hospitalization and to compare the outcome with the general population. We expected to find a significant difference between the SLE population and the general population regarding hospitalization parameters. However we found a good prognosis for hospitalized SLE patients with non-related disease compared to the non-SLE group. SLE was not a significant prognostic factor for outcome in patients hospitalized in the internal medicine ward for non-related causes. Men with SLE had a worse prognosis during hospitalization when compared to females. The SLEDAI score was not an appropriate prognostic method for the outcome of hospitalization., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To describe the diagnostic accuracy of screening questionnaires to identify epilepsy in adults, we performed a systematic review of diagnostic studies that assessed the sensitivity and specificity of such screening questionnaires as compared to a physician's clinical assessment., Methods: We searched Ovid MEDLINE (1946 to present) and Ovid EMBASE (1947 to present) for studies that estimated the sensitivity and specificity of nonphysician administered screening questionnaires for adults with epilepsy. Both telephone and in-person administered questionnaires were included, whether applied to population or hospital/clinic-based cohorts. The risk of bias was assessed using the Quality Assessment of Diagnostic Studies-2 (QUADAS-2) tool., Results: Our initial search strategy resulted in 917 records. We found nine studies eligible for inclusion. The estimated sensitivity and specificity of the questionnaires used to identify persons with a lifetime history of epilepsy ranged from 81.5% to 100% and 65.6% to 99.2%, respectively. The sensitivity and specificity of these questionnaires in identifying persons with active epilepsy ranged from 48.6% to 100% and 73.9% to 99.9%, respectively. Overall we found a high risk of bias in patient selection and study flow in the majority of studies., Significance: We identified nine validation studies of epilepsy screening questionnaires, summarized their study characteristics, presented their results, and performed a rigorous quality assessment. This review serves as a basis for future studies by providing a systematic review of existing work. Future research addressing previous limitations will ultimately allow us to more accurately estimate the burden and risk of epilepsy in the general population., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

Introduction: As the population ages and the prevalence of comorbid conditions increases, the need for feasible, validated methods of comorbidity surveillance in chronic diseases such as multiple sclerosis (MS) increases., Methods: Using kappa (k) statistics, we evaluated the performance of administrative case definitions for comorbidities commonly observed in MS by comparing agreement between Manitoba (MB) administrative data and self-report (n = 606) and Nova Scotia (NS) administrative data and self-report (n = 1923)., Results: Agreement between the administrative definitions and self-report was substantial for hypertension (k = 0.69 [NS], 0.76 [MB]) and diabetes (k = 0.70 [NS], 0.66 [MB]); moderate for hyperlipidemia (k = 0.53 [NS], 0.51 [MB]) and heart disease (k = 0.42 [NS], 0.51 [MB]) and fair for anxiety (k = 0.27 [NS], 0.26 [MB]). In NS, agreement was substantial for inflammatory bowel disease (k = 0.71) and moderate for epilepsy (k = 0.48)., Conclusion: Administrative definitions for commonly observed comorbidities in MS performed well in 2 distinct jurisdictions. This suggests that they could be used more broadly across Canada and in national studies.

Objectives: The objective of this paper is to estimate the association between multiple sclerosis (MS) and measures of sun exposure in specific age periods in Norway and Italy., Methods: A total of 1660 MS patients and 3050 controls from Italy and Norway who participated in a multinational case-control study (EnvIMS) reported sun habits during childhood and adolescence., Results: A significant association between infrequent summer outdoor activity and increased MS risk was found in Norway and in Italy. The association was strongest between the ages of 16 and 18 years in Norway (odds ratio (OR) 1.83, 95% confidence interval (CI) 1.30-2.59), and between birth and age 5 years in Italy (OR 1.56, 95% CI 1.16-2.10). In Italy a significant association was also found during winter (OR 1.42, 95% CI 1.03-1.97). Frequent sunscreen use between birth and the age of 6 years was associated with MS in Norway (OR 1.44, 95% CI 1.08-1.93) after adjusting for outdoor activity during the same period. Red hair (OR 1.67, 95% CI 1.06-2.63) and blonde hair (OR 1.36, 95% CI 1.09-1.70) were associated with MS after adjusting for outdoor activity and sunscreen use., Conclusion: Converging evidence from different measures underlines the beneficial effect of sun exposure on MS risk., (© The Author(s) 2014.)

Patients with idiopathic REM sleep behavior disorder (iRBD) are at very high risk of developing neurodegenerative synucleinopathies, which are disorders with prominent autonomic dysfunction. Several studies have documented autonomic dysfunction in iRBD, but large-scale assessment of autonomic symptoms has never been systematically performed. Patients with polysomnography-confirmed iRBD (318 cases) and controls (137 healthy volunteers and 181 sleep center controls with sleep diagnoses other than RBD) were recruited from 13 neurological centers in 10 countries from 2008 to 2011. A validated scale to study the disorders of the autonomic nervous system in Parkinson's disease (PD) patients, the SCOPA-AUT, was administered to all the patients and controls. The SCOPA-AUT consists of 25 items assessing the following domains: gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillomotor, and sexual dysfunction. Our results show that compared to control subjects with a similar overall age and sex distribution, patients with iRBD experience significantly more problems with gastrointestinal, urinary, and cardiovascular functioning. The most prominent differences in severity of autonomic symptoms between our iRBD patients and controls emerged in the gastrointestinal domain. Interestingly, it has been reported that an altered gastrointestinal motility can predate the motor phase of PD. The cardiovascular domain SCOPA-AUT score in our study in iRBD patients was intermediate with respect to the scores reported in PD patients by other authors. Our findings underline the importance of collecting data on autonomic symptoms in iRBD. These data may be used in prospective studies for evaluating the risk of developing neurodegenerative disorders.

Background: Seasonal fluctuations in solar radiation and vitamin D levels could modulate the immune response against Epstein-Barr virus (EBV) infection and influence the subsequent risk of multiple sclerosis (MS)., Methods: Altogether 1660 MS patients and 3050 controls from Norway and Italy participating in the multinational case-control study of Environmental Factors In Multiple Sclerosis (EnvIMS) reported season of past infectious mononucleosis (IM)., Results: IM was generally reported more frequently in Norway (p=0.002), but was associated with MS to a similar degree in Norway (odds ratio (OR) 2.12, 95% confidence interval (CI) 1.64-2.73) and Italy (OR 1.72, 95% CI 1.17-2.52). For all participants, there was a higher reported frequency of IM during spring compared to fall (p<0.0005). Stratified by season of IM, the ORs for MS were 1.58 in spring (95% CI 1.08-2.31), 2.26 in summer (95% CI 1.46-3.51), 2.86 in fall (95% CI 1.69-4.85) and 2.30 in winter (95% CI 1.45-3.66)., Conclusions: IM is associated with MS independently of season, and the association is not stronger for IM during spring, when vitamin D levels reach nadir. The distribution of IM may point towards a correlation with solar radiation or other factors with a similar latitudinal and seasonal variation.

Objective: This controlled study investigated associations between comorbidity and medication in patients with polysomnographically confirmed idiopathic REM sleep behavior disorder (iRBD), using a large multicenter clinic-based cohort., Methods: Data of a self-administered questionnaire on comorbidity and medication use of 318 patients with iRBD and 318 matched controls were analyzed. Comparisons between cases and controls were made using logistic regression analysis., Results: Patients with iRBD were more likely to report depression (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.3-2.9) and concomitant antidepressant use (OR 2.2, 95% CI 1.4-3.6). Subanalysis of antidepressant agents revealed that the increased use of antidepressants in iRBD was due to selective serotoninergic reuptake inhibitors (OR 3.6, 95% CI 1.8-7.0) and not due to other antidepressant classes. Patients with iRBD reported more lifetime antidepressant use than comorbid depression (antidepressant use: OR 1.9, 95% CI 1.1-3.3; depression: OR 1.6, 95% CI 1.0-2.5). Patients with iRBD reported more ischemic heart disease (OR 1.9, 95% CI 1.1-3.1). This association did not change substantially when adjusting for cardiovascular risk factors (OR 2.3, 95% CI 1.3-3.9). The use of inhaled glucocorticoids was higher in patients with iRBD compared to controls (OR 5.3, 95% CI 1.8-15.8), likely reflecting the higher smoking rate in iRBD (smoking: OR 15.3, 95% CI 2.0-118.8; nonsmoking: OR 2.4, 95% CI 0.4-13.2) and consequent pulmonary disease., Conclusions: This large study confirms the association between comorbid depression and antidepressant use in iRBD. In addition, there was an unexpected association of iRBD with ischemic heart disease that was not explained by cardiovascular risk factors.

Objectives: Studies of multiple sclerosis (MS) incidence and prevalence from Africa, Asia, Australia and New Zealand are relatively scarce. We systematically reviewed MS incidence and prevalence in these regions including a standardized evaluation of study quality., Methods: We searched MEDLINE and EMBASE databases for studies of MS prevalence or incidence in Africa, Asia, Australia and New Zealand published in English or French between January 1, 1985 and January 31, 2011. Study quality was assessed using a standardized tool. All steps of the review were performed in duplicate., Results: Of 3925 citations identified, 28 studies met inclusion criteria and 21 of these were from Asia. Quality scores ranged from 1/8 to 8/8; the lowest scores were observed in studies from Asia (median 4/8, IQR 3,6). Prevalence was lowest in South African Blacks (0.22/100,000) and highest amongst Australian-born individuals in Australia (125/100,000). Prevalence increased over time in many countries. MS prevalence increased with increasing latitude only in some regions, and prevalence varied significantly with ethnicity. Eight studies reported incidence, which ranged from 0.67/100,000/year in Taiwan to 3.67/100,00/year in Australia., Conclusions: This comprehensive study provides an update of MS epidemiology in Africa, Asia, Australia, and New Zealand. Incidence and prevalence were lowest in Africa and Asia and highest in Australia, but many Asian studies were of poor quality. Use of consistent case ascertainment methods, standardized data collection tools, and similar outcomes would all improve study quality and comparability. The underlying basis of observed ethnic differences is an important area for future study., (© 2013 Elsevier B.V. All rights reserved.)

Background: Little is known about the contribution of frailty in improving patient-level prediction beyond readily available clinical information. The objective of this study is to compare the predictive ability of 129 combinations of seven frailty markers (cognition, energy, mobility, mood, nutrition, physical activity, and strength) and quantify their contribution to predictive accuracy beyond age, sex, and number of chronic diseases., Methods: Two cohorts from the Established Populations for Epidemiologic Studies of the Elderly were used. The model with the best predictive fit in predicting 6-year incidence of disability was determined using the Akaike Information Criterion. Predictive accuracy was measured by the C statistic., Results: Incident disability was 23% in one cohort and 20% in the other cohort. The "best model" in each cohort was found to be a model including between five and seven frailty markers including cognition, mobility, nutrition, physical activity, and strength. Predictive accuracy of the 129 models ranged from 0.73 to 0.77 across both cohorts. Adding frailty markers to age, sex, and chronic disease increased predictive accuracy by up to 3% in both cohorts (p < .001). The contribution of frailty increased up to 9% in the oldest age group., Conclusions: Adding frailty markers provided a modest increase in patient-level prediction of disability. Such a modest increase may still be worthwhile because while age, sex, and the number of chronic diseases are not modifiable, frailty may be. Further studies examining the contribution of frailty in improving prediction are needed before adopting frailty as a prognostic tool.

Background: Estimates of incidence and prevalence are needed to determine disease risk and to plan for health service needs. Although the province of Nova Scotia, Canada is located in a region considered to have a high prevalence of multiple sclerosis (MS), epidemiologic data are limited., Objective: We aimed to validate an administrative case definition for MS and to use this to estimate the incidence and prevalence of MS in Nova Scotia., Methods: We used provincial administrative claims data to identify persons with MS. We validated administrative case definitions using the clinical database of the province's only MS Clinic; agreement between data sources was expressed using a kappa statistic. We then applied these definitions to estimate the incidence and prevalence of MS from 1990 to 2010., Results: We selected the case definition using ≥7 hospital or physician claims when >3 years of data were available, and ≥3 claims where less data were available. Agreement between data sources was moderate (kappa = 0.56), while the positive predictive value was high (89%). In 2010, the age-standardized prevalence of MS per 100,000 population was 266.9 (95% CI: 257.1- 277.1) and incidence was 5.17 (95% CI: 3.78-6.56) per 100,000 persons/year. From 1990-2010 the prevalence of MS rose steadily but incidence remained stable., Conclusions: Administrative data provide a valid and readily available means of estimating MS incidence and prevalence. MS prevalence in Nova Scotia is among the highest in the world, similar to recent prevalence estimates elsewhere in Canada., Incidence et prévalence de la sclérose en plaques en Nouvelle-Écosse, Canada.

The effect of an educational program on antipsychotic prescribing was assessed in two Canadian long-term care centers (LTCC). In each center (Center A residents, n = 258 and Center B residents, n = 191, with dementia at program inception), the rate of change in the odds of using antipsychotics in residents was estimated using mixed-effects logistic regression during a 6-month program period and a 4-month postprogram period, with baseline proportions of use estimated during the 6 months prior to the program. Preprogram proportions of antipsychotic use were 41.6% and 46.2%, respectively. Antipsychotic use decreased during the program in both centers: (odds ratio with 95% CI: 0.943 per week [0.921, 0.965] and 0.969 per week [0.944, 0.994], respectively). During the postprogram period, antipsychotic use increased in Center A (1.039 per week [1.007, 1.072]) but decreased progressively in Center B. The study results suggest the need to implement an ongoing educational program in LTCC.

Objectives: To determine the association between self-rated health (SRH) and functional status, comorbidity, toxicity of treatment and mortality in older patients with newly-diagnosed cancer., Materials and Methods: Patients aged 65 and over, newly diagnosed were recruited at the Jewish General Hospital, Montreal, Canada. SRH and functional status [instrumental activities of daily living (IADL), basic activities of daily living (ADL), Eastern Cooperative Oncology Group performance status (ECOG PS), frailty markers and number of comorbid conditions] were evaluated prior to the start of treatment, and at 3, 6 and 12 months (SRH only). Treatment toxicity and mortality data were abstracted from the chart. Logistic regression was also used to examine the relationship between functional status, comorbidity and SRH at baseline. Logistic and Cox regression were used to examine the association between baseline SRH and treatment toxicity/time to death., Results: There were 112 participants enrolled on this study (median age 74.1). At baseline, 74 patients (66.1%) had a good SRH and 38 patients (33.9%) had poor SRH. Only an increasing number of comorbid conditions was associated with poor SRH at baseline in both univariate and multivariable analysis. We found no association between SRH and toxicity or mortality., Conclusion: A substantial proportion had poor SRH prior to and during cancer treatment. An increasing number of comorbidities was associated with poor SRH at baseline. SRH did not predict toxicity or mortality. Attention to comorbid conditions in older patients with cancer is warranted considering their impact on SRH in this population., (© 2013.)

Background: Studies suggest an altered risk of ischemic heart disease (IHD) in multiple sclerosis (MS), but data are limited. We aimed to validate and apply administrative case definitions to estimate the incidence and prevalence of IHD in MS., Methods: Using administrative data we identified persons with incident MS (MSPOP) and a matched general population (GPOP) cohort. We developed case definitions for IHD using ICD-9/10 codes and prescription claims, compared them to medical records, then applied them to evaluate the incidence and prevalence of IHD., Results: Agreement between medical records and the administrative definition using ≥1 hospital or ≥2 physician claims over 5 years was moderate (kappa=0.66; 95% CI: 0.42-0.90). In 2005, the age-standardized prevalence of IHD was 6.77% (95% CI: 5.48-8.07%) in the MSPOP and 6.11% (95% CI: 5.56-6.66%) in the GPOP. The prevalence of IHD was higher in the MSPOP than the GPOP among persons aged 20-44 years (prevalence ratio 1.87; 95% CI: 1.65-2.12) and aged 45-59 years (prevalence ratio 1.21; 95% CI: 1.08-1.35). The incidence of IHD was also higher in the MSPOP (incidence rate ratio 1.24; 95% CI: 0.97-1.59)., Conclusions: More than 5% of the MSPOP has IHD. The incidence of IHD was higher than expected in persons aged <60 years. Further evaluation of this issue is warranted., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Multiple sclerosis (MS) is the most common cause of neurological disability in young adults worldwide and approximately half of those affected are in Europe. The assessment of differential incidence and prevalence across populations can reveal spatial, temporal and demographic patterns which are important for identifying genetic and environmental factors contributing to MS. However, study methodologies vary and the quality of the methods can influence the estimates. This study aimed to systematically review European studies of incidence and prevalence of MS and to provide a quantitative assessment of their methodological quality., Methods: A comprehensive literature search was performed to obtain all original population-based studies of MS incidence and prevalence in European populations conducted and published between January 1985 and January 2011. Only peer-reviewed full-text articles published in English or French were included. All abstracts were screened for eligibility and two trained reviewers abstracted the data and graded the quality of each study using a tool specifically designed for this study., Results: There were 123 studies that met the inclusion criteria. The study estimates were highly heterogeneous, even within regions or countries. Quality was generally higher in the more recent studies, which also tended to use current diagnostic criteria. Prevalence and incidence estimates tended to be higher in the more recent studies and were higher in the Nordic countries and in northern regions of the British Isles. With rare exceptions, prevalence and incidence estimates were higher in women with ratios as high as 3:1. Few studies examined ethnicity. Epidemiological data at the national level was uncommon and there were marked geographical disparities in available data, with large areas of Europe unrepresented and other regions well-represented in the literature. Only 37% of the studies provided standardized estimates., Conclusions: Despite the breadth of the literature on the epidemiology of MS in Europe, inter-study comparisons are hampered by the lack of standardization. Further research should focus on regions not yet studied and the evaluation of ethnic differences in MS prevalence and incidence. National-level studies using current diagnostic criteria, validated case definitions and similar age- and sex-standardization would allow better geographical comparisons.

We validated seven chronic disease ascertainment algorithms for use in the Canadian Longitudinal Study on Aging. The algorithms pertained to diabetes mellitus type 2, parkinsonism, chronic airflow obstruction (CAO), hand osteoarthritis (OA), hip OA, knee OA, and ischemic heart disease. Our target recruitment was 20 cases and controls per disease; some cases were controls for unrelated diseases. Participants completed interviewer-administered disease symptom and medication use questionnaires. Diabetes cases and controls underwent fasting glucose testing; CAO cases and controls underwent spirometry testing. For each disease, the appropriate algorithm was used to classify participants' disease status (positive or negative for disease). We also calculated sensitivity and specificity using physician diagnosis as the reference standard. The final sample involved 176 participants recruited in three Canadian cities between 2009 and 2011. Most estimated sensitivities and specificities were 80 per cent or more, indicating that the seven algorithms correctly identified individuals with the target disease.

Objective: To compare the frequency of proxy-reported REM sleep behavior disorder (RBD) among relatives of patients with polysomnogram-diagnosed idiopathic RBD (iRBD) in comparison to controls using a large multicenter clinic-based cohort., Methods: A total of 316 patients with polysomnography-confirmed iRBD were recruited from 12 RBD study group centers, along with 316 controls matched on sex and age group. All subjects completed a self-administered questionnaire that collected proxy-reported information on family history of tremor, gait trouble, balance trouble, Parkinson disease, memory loss, and Alzheimer disease. The questionnaire also included a single question that asked about possible symptoms of RBD among first-degree relatives (siblings, parents, and children)., Results: A positive family history of dream enactment was reported in 13.8% of iRBD cases compared to 4.8% of controls (odds ratio [OR] = 3.9, 95% confidence interval [CI] 2.0-7.7). ORs were increased for both siblings (OR = 6.1, 95% CI 2.1-18.1) and parents (OR = 3.2, 95% CI 1.4-7.8). We found no significant difference in sex, current age (65.3 ± 10.2 vs 66.9 ± 10.2 years), or age at self-reported RBD onset (55.2 ± 11.7 vs 56.6 ± 15.1 years) in possible familial vs sporadic iRBD. No differences were found in family history of tremor, walking and balance troubles, Parkinson disease, memory loss, or Alzheimer disease., Conclusion: We found increased odds of proxy-reported family history of presumed RBD among individuals with confirmed iRBD. This suggests the possibility of a genetic contribution to RBD.

Objective: To assess the adherence and persistence with allopurinol therapy among gout patients and to identify risk factors for therapy discontinuation., Methods: The study population included adults in Maccabi Healthcare Services, a 2-million member health maintenance organization in Israel, who were diagnosed with gout between 2002 and 2008. Adherence with allopurinol was retrospectively assessed by calculating the proportion of days covered of dispensed prescriptions. Persistence was assessed by calculating the mean proportion of follow-up days covered with allopurinol for every study participant., Results: A total of 7644 patients were identified. Among men, the incidence of gout was strongly associated with age, ranging from 0.5 per 1000 among adults younger than 45 years to more than 36 per 1000 among elderly men aged 85 or older). A total of 1331 gout patients (17% of the study population) were adherent to allopurinol therapy, 36% and 47% had partial and poor adherence, respectively. Persistence analysis indicated that the average duration until therapy was discontinued was similar among men (358 days) and women (379 days). Women aged 45-64 years, non-married individuals, those of low socioeconomic status and those with lower body weight were more likely to discontinue therapy. Logistic regression (n = 2471, 32% of the study sample) showed a 4.5 risk of non-compliance among 45- to 65-year-old women. Better compliance was achieved among those with comorbidities, particularly among patients with concomitant cardiovascular disease., Conclusion: Only one out of six gout patients is adherent with allopurinol. Intervention programmes to increase adherence with treatment should focus on high-risk populations.

Biologic therapies for rheumatologic diseases, which are targeted at molecules involved in the mechanisms of the immune system, provide an alternative to the existing treatment methods of disease-modifying anti-rheumatic drugs and other immunosuppressive medications. However, the current drawbacks of biologic therapies, including the inconvenience of intravenous administration, the high costs of these drugs, and the adverse events associated with them, prevent their wide use as first-line medications. This review provides an update of the recent literature on the new biologic therapies available. The review concentrates on nine drugs: tocilizumab, rituximab, ofatumumab, belimumab, epratuzumab, abatacept, golimumab, certolizumab, and sifalimumab, which are used as therapies for rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, systemic sclerosis, or vasculitis.

Purpose: Little is known about the incidence of falls in cancer patients receiving cancer treatment. The aims were to explore the number of falls older adults report in the 6 months after cancer diagnosis, and if those with a fall were more frail than those who did not fall., Methods: Secondary data analysis of a prospective pilot study that recruited patients aged 65 and older with a new cancer diagnosis. At each interview (baseline, 3- and 6-month follow-up), participants were asked if they had a fall in the previous 3 months. The frailty markers and functional status were obtained at baseline, 3- and 6-month follow-up. Chi-square and t tests were used to compare those who had a fall to those who had no fall. Univariate logistic regression analysis was conducted to explore the association between sociodemographic and health characteristics and reporting a fall., Results: Seventeen participants (18.7%) reported one or more falls in the first 6 months after cancer diagnosis. Fifteen participants reported one or more falls in the 3 months prior to the cancer diagnosis. Those who had a fall and those with no fall were not different in terms of health and functioning. None of the sociodemographic and health characteristics including the frailty markers were associated with a fall., Conclusion: A fall is common in cancer patients. More research is needed to examine the risk factors for a fall in older adults receiving cancer treatment.

Background: While mental comorbidity is considered common in multiple sclerosis (MS), its impact is poorly defined; methods are needed to support studies of mental comorbidity. We validated and applied administrative case definitions for any mental comorbidities in MS., Methods: Using administrative health data we identified persons with MS and a matched general population cohort. Administrative case definitions for any mental comorbidity, any mood disorder, depression, anxiety, bipolar disorder and schizophrenia were developed and validated against medical records using a a kappa statistic (k). Using these definitions we estimated the prevalence of these comorbidities in the study populations., Results: Compared to medical records, administrative definitions showed moderate agreement for any mental comorbidity, mood disorders and depression (all k ≥ 0.49), fair agreement for anxiety (k = 0.23) and bipolar disorder (k = 0.30), and near perfect agreement for schizophrenia (k = 1.0). The age-standardized prevalence of all mental comorbidities was higher in the MS than in the general populations: depression (31.7% vs. 20.5%), anxiety (35.6% vs. 29.6%), and bipolar disorder (5.83% vs. 3.45%), except for schizophrenia (0.93% vs. 0.93%)., Conclusions: Administrative data are a valid means of surveillance of mental comorbidity in MS. The prevalence of mental comorbidities, except schizophrenia, is increased in MS compared to the general population.

Ferritin may play a direct role on the immune system. We sought to determine if elevated levels of ferritin in lupus patients correlate with disease activity and organ involvement in a large cohort. Ferritin levels (gender and age adjusted) were assessed in 274 lupus serum samples utilizing the LIASON Ferritin automated immunoassay method. Significant disease activity was determined if European Consensus Lupus Activity Index (ECLAM)>2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)>4. Utilizing an EXCEL database, we compared elevated ferritin levels to manifestations grouped by organ involvement, serology, and previous therapy. The patients were predominantly female (89%), median age was 37 years old, and disease duration was 10.6 ± 7.7 years. Hyperferritinemia was found in 18.6% of SLE patients. Compared to subjects with normal ferritin levels, a significantly greater proportion of patients with hyperferritinemia had thrombocytopenia (15.4% vs. 33.3%, p=0.003) and lupus anticoagulant (11.3% vs. 29.0%, p=0.01). Additionally, compared to normoferritinemic subjects, hyperferritinemic subjects had significantly higher total aCL (99.7 ± 369 vs. 30.9 ± 17.3 GPI, p=0.02) and aCL IgM antibody levels (75.3 ± 357.4 vs. 9.3 ± 10.3 GPI, p=0.02), and marginally lower aCL IgG antibody levels (9.2 ± 4.9 vs. 9.7 ± 3.9 GPI, p = 0.096). While the ECLAM score significantly correlated with hyperferritinemia (p=0.04), the SLEDAI score was marginally associated with hyperferritinemia (p = 0.1). Serositis was marginally associated with hyperferritinemia, but not with other manifestations. An association with serologic APS was encountered. Hyperferritinemia was associated with thrombocytopenia, lupus anticoagulant, and anti-cardiolipin antibodies suggest that it may be an early marker for secondary antiphospholipid syndrome in SLE patients.

How individuals age is affected by life experiences. What we know today about aging has been largely shaped by a generation who experienced the special circumstances of wartime in their formative years. In this review, we investigate the research question, "What is known about the physical health of Canadian veterans?" In answering this question, we summarize the literature on Canadian Veterans but also include international literature on the physical health of American and Australian Veterans, along with some information from reports from Great Britain and other parts of Europe. Areas in which veterans perhaps fare worse than civilians of similar age include general health, hearing loss, musculoskeletal disorders, infections, cirrhosis, skin conditions, stomach conditions, neurologic conditions, and cardiovascular disease. The differing effects of combat on female veterans are also summarized. The healthy warrior effect is discussed along with its impact on research findings and the importance of choosing an appropriate control group., (© The Author 2012. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Models of dopaminergic function in restless legs focus on central dopaminergic neurons. Domperidone, a peripheral dopamine blocker that cannot cross the blood-brain barrier, is commonly used in Parkinson's disease. After encountering a case of restless legs syndrome that dramatically worsened with domperidone, we assessed whether Parkinson's patients may have exacerbation of restless legs with domperidone., Methods: From two Parkinson's disease cohorts, we assessed restless legs prevalence according to standard criteria, in patients taking vs. not taking domperidone. Regression analysis was performed, adjusting for age, sex, disease duration, UPDRS, dopaminergic medications and other medications., Results: One hundred eighty four patients were assessed, of whom 46 (25%) had restless legs. Thirteen out of twenty seven (48%) patients on domperidone had restless legs compared to 33/157 (21%) without (p = 0.010). Other medications were not associated with restless legs., Conclusion: This unexpected finding suggests that dopaminergic neurons outside of the blood-brain barrier may be important in restless legs syndrome pathophysiology., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Although comorbidity is important in multiple sclerosis (MS), few validated methods for its assessment exist. We validated and applied administrative case definitions for several comorbidities in MS., Methods: Using provincial administrative data we identified persons with MS and a matched general population cohort. Case definitions for chronic lung disease (CLD), epilepsy, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and migraine were developed using administrative data, and validated against medical records. We applied these definitions to estimate the age-standardized prevalence of these comorbidities in the MS and matched cohorts., Results: Versus medical records, administrative case definitions showed moderate agreement for CLD (ĸ = 0.41), migraine (ĸ = 0.51), and epilepsy (ĸ = 0.44), fair agreement for IBS (ĸ = 0.36) and could not be calculated for IBD (small sample size). The 2005 prevalence of CLD was similar in the MS (15.6%) and general populations (14.4%). The prevalence of the remaining comorbidities was higher in the MS than the general populations: epilepsy (4.12 vs. 1.12%), IBD (0.78 vs. 0.65%), IBS (12.2 vs. 6.80%) and migraine (23.0 vs. 16.5%)., Conclusions: Administrative data are valid for tracking CLD, epilepsy, and migraine in MS. The prevalence of epilepsy, IBD, IBS and migraine is increased in MS versus the general population., (Copyright © 2012 S. Karger AG, Basel.)

Background: The incidence and prevalence of multiple sclerosis (MS) varies considerably around the world. No previous study has performed a comprehensive review examining the incidence and prevalence of MS across the Americas. The purpose of this study was to systematically review and assess the quality of studies estimating the incidence and/or prevalence of MS in North, Central and South American regions., Methods: A comprehensive literature search was performed using MEDLINE and EMBASE from January 1985 to January 2011. Search terms included 'multiple sclerosis', 'incidence', 'prevalence' and 'epidemiology'. Only full-text articles published in English or French were included. Study quality was assessed using an assessment tool based on recognized guidelines and designed specifically for this study., Results: A total of 3,925 studies were initially identified, with 31 meeting the inclusion criteria. The majority of studies examined North American regions (n = 25). Heterogeneity was high among all studies, even when stratified by country. Only half of the studies reported standardized rates, making comparisons difficult. Quality scores ranged from 3/8 to 8/8., Conclusion: This review highlights the gaps that still exist in the epidemiological knowledge of MS in the Americas, and the inconsistencies in methodologies and quality among the published studies. There is a need for future studies of MS prevalence and incidence to include uniform case definitions, employ comparable methods of ascertainment, report standardized results, and be performed on a national level. Other factors such as sex distribution, ethnic make-up and population lifestyle habits should also be considered., (Copyright © 2013 S. Karger AG, Basel.)

To describe the current practice and views of neurologists on transitioning patients from pediatric to adult care, a cross-sectional study of all pediatric and adult neurologists in the province of Quebec, Canada, was conducted. The response rate was 73% for pediatric and 49% for adult neurologists. Most pediatric neurologists do not have a patient transition program or policy in place. Although a transfer summary is commonly provided, critical information is often lacking. Nearly half of neurologists believed that patients experience a gap in care during the transition process, and most agreed that the transition process is often poorly coordinated, highlighting patient, family, and health care factors. Current practice does not follow existing consensus statements for transition of care with respect to timing, communication, and preparation, and many pediatric neurologists experience difficulty in finding an appropriate adult health care provider for their patients. Neurologists reported many challenges in the current transition of care process.

Purpose: Physicians are encouraged to discuss physical activity with their older adult patients. Studies of physician-initiated counseling have yielded inconsistent results, perhaps because older adults' perceptions and concerns about such counseling have not been addressed. The objective of the present work was therefore to explore such perceptions and their implications., Design: Qualitative study, using a grounded theory approach. Data were collected using both focus groups and semistructured interviews., Setting: Data were collected in several settings, including a fitness center and physicians' offices., Subjects: In a first sample, 56 adults aged 65 and older participated in one of six focus group sessions examining physical activity and exercise. Subsequently, 16 older adults participated in one of two focus groups comprising a second, validation sample. Individual semistructured interviews were conducted with a sample of five physicians., Methods: Data collection and analysis took place concurrently. Transcripts were analyzed using the constant comparative method. Recruitment, data collection, and analysis were informed by grounded theory., Results: Inactive older adults experiencing a health problem were more receptive than their healthy counterparts to receiving physical activity counseling from their physicians. Those who were receptive appeared to find such an intervention useful in leading to behavior change., Conclusion: This study suggests that physicians' efforts in physical activity counseling may have the best impact when provided in the context of a health problem.

Background: There has been little research on the relative importance of frailty markers. The objective was to investigate the association among seven frailty domains (nutrition, physical activity, mobility, strength, energy, cognition, and mood) and their relative contribution in explaining differences among individuals in five samples of older persons., Methods: Data from five studies of aging were analyzed using multiple correspondence analysis. Aggregation of frailty markers was evaluated using graphical output. Decomposition of variability was used to assess the relative contribution of each marker in each sample. Results were combined across the samples to assess the average contribution., Results: Frailty markers were found to consistently aggregate in each sample, suggesting a possible underlying construct. Physical strength had the highest contribution on average in explaining differences among individuals. Mobility and energy also had large contributions. Nutrition and cognition had the smallest contributions., Conclusions: Our results provide further evidence supporting the notion that frailty domains may belong to a common construct. Physical strength may be the most important discriminating characteristic.

Objective: Fibromyalgia adversely affects quality of life, yet little is known of the epidemiology of this condition in MS. We aimed to validate and apply administrative case definitions for fibromyalgia in MS., Methods: Using administrative health data we identified persons with MS and an age-, sex- and geographically-matched general population (GP) cohort. Case definitions for fibromyalgia were developed using ICD-9/10 codes, validated against medical records, and applied to evaluate the incidence and prevalence of fibromyalgia., Results: The case definition for fibromyalgia with ≥5 hospital or physician claims in 3 years had a sensitivity of 60%, specificity of 98%, and agreed moderately with medical records (κ=0.48). In 2005, the age-standardized prevalence of fibromyalgia was 6.82% (95% CI: 5.91-7.72) in the MS population and 3.04% (95% CI: 2.77-3.32) in the GP. After adjustment for age, sex and year, the incidence of fibromyalgia was 44% higher in the MS than the GP (IRR 1.44; 95% CI: 1.01-2.07). The incidence of fibromyalgia increased slightly over time in both populations., Conclusion: The incidence and prevalence of fibromyalgia are higher in the MS population than the general population. Fibromyalgia should be considered in the management of pain in persons with MS., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Despite the importance of comorbidity in multiple sclerosis (MS), methods for comorbidity assessment in MS are poorly developed., Objective: We validated and applied administrative case definitions for diabetes, hypertension, and hyperlipidemia in MS., Methods: Using provincial administrative data we identified persons with MS and a matched general population cohort. Case definitions for diabetes, hypertension, and hyperlipidemia were derived using hospital, physician, and prescription claims, and validated in 430 persons with MS. We examined temporal trends in the age-adjusted prevalence of these conditions from 1984-2006., Results: Agreement between various case definitions and medical records ranged from kappa (κ) =0.51-0.69 for diabetes, κ =0.21-0.71 for hyperlipidemia, and κ =0.52-0.75 for hypertension. The 2005 age-adjusted prevalence of diabetes was similar in the MS (7.62%) and general populations (8.31%; prevalence ratio [PR] 0.91; 0.81-1.03). The age-adjusted prevalence did not differ for hypertension (MS: 20.8% versus general: 22.5% [PR 0.91; 0.78-1.06]), or hyperlipidemia (MS: 13.8% versus general: 15.2% [PR 0.90; 0.67-1.22]). The prevalence of all conditions rose in both populations over the study period., Conclusion: Administrative data are a valid means of tracking diabetes, hypertension, and hyperlipidemia in MS. The prevalence of these comorbidities is similar in the MS and general populations.

Objective: Idiopathic REM sleep behavior disorder is a parasomnia characterized by dream enactment and is commonly a prediagnostic sign of parkinsonism and dementia. Since risk factors have not been defined, we initiated a multicenter case-control study to assess environmental and lifestyle risk factors for REM sleep behavior disorder., Methods: Cases were patients with idiopathic REM sleep behavior disorder who were free of dementia and parkinsonism, recruited from 13 International REM Sleep Behavior Disorder Study Group centers. Controls were matched according to age and sex. Potential environmental and lifestyle risk factors were assessed via standardized questionnaire. Unconditional logistic regression adjusting for age, sex, and center was conducted to investigate the environmental factors., Results: A total of 694 participants (347 patients, 347 controls) were recruited. Among cases, mean age was 67.7 ± 9.6 years and 81.0% were male. Cases were more likely to smoke (ever smokers = 64.0% vs 55.5%, adjusted odds ratio [OR] = 1.43, p = 0.028). Caffeine and alcohol use were not different between cases and controls. Cases were more likely to report previous head injury (19.3% vs 12.7%, OR = 1.59, p = 0.037). Cases had fewer years of formal schooling (11.1 ± 4.4 years vs 12.7 ± 4.3, p < 0.001), and were more likely to report having worked as farmers (19.7% vs 12.5% OR = 1.67, p = 0.022) with borderline increase in welding (17.8% vs 12.1%, OR = 1.53, p = 0.063). Previous occupational pesticide exposure was more prevalent in cases than controls (11.8% vs 6.1%, OR = 2.16, p = 0.008)., Conclusions: Smoking, head injury, pesticide exposure, and farming are potential risk factors for idiopathic REM sleep behavior disorder.