What is Next for the Genetics of Multiple Sclerosis?

We review here our current understanding of the genetic aetiology of the common complex neurological disease multiple sclerosis (MS). The strongest genetic risk factor for MS is the major histocompatibility complex which was identified in the 1970s. In 2011, after a number of genome-wide association studies have been completed and have identified approximately 20 new genes for MS, we ask the question—what is next for the genetics of MS

Correction: Meta-Analysis of the Relationship between Multiple Sclerosis and Migraine.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PMCID: PMC3613438PMCID: PMC3613438PMCID: PMC3613438PMCID: PMC3613438[This corrects the article on p. e45295 in vol. 7.]

Laparoscopic surgery for Crohn’s disease: a meta-analysis of perioperative complications and long term outcomes compared with open surgery

BACKGROUND: Previous meta-analyses have had conflicting conclusions regarding the differences between laparoscopic and open techniques in patients with Crohn’s Disease. The objective of this meta-analysis was to compare outcomes in patients with Crohn’s disease undergoing laparoscopic or open surgical resection. METHODS: A literature search of EMBASE, MEDLINE, The Cochrane Central Register of Controlled Trials and the US National Institute of Health’s Clinical Trials Registry was completed. Randomized clinical trials and non-randomized comparative studies were included if laparoscopic and open surgical resections were compared. Primary outcomes assessed included perioperative complications, recurrence requiring surgery, small bowel obstruction and incisional hernia. RESULTS: 34 studies were included in the analysis, and represented 2,519 patients. Pooled analysis showed reduced perioperative complications in patients undergoing laparoscopic resection vs. open resection (Risk Ratio 0.71, 95% CI 0.58 – 0.86, P = 0.001). There was no evidence of a difference in the rate of surgical recurrence (Rate Ratio 0.78, 95% CI 0.54 – 1.11, P = 0.17) or small bowel obstruction (Rate Ratio 0.63, 95% CI 0.28 – 1.45, P = 0.28) between techniques. There was evidence of a decrease in incisional hernia following laparoscopic surgery (Rate Ratio 0.24, 95% CI 0.07 – 0.82, P = 0.02). CONCLUSIONS: This is the largest review in this topic. The results of this analysis are based primarily on non-randomized studies and thus have significant limitations in regards to selection bias, confounding, lack of blinding and potential publication bias. Although we found evidence of decreased perioperative complications and incisional hernia in the laparoscopic group, further randomized controlled trials, with adequate follow up, are needed before strong recommendations can be made

Protein-Protein Interaction Analysis Highlights Additional Loci of Interest for Multiple Sclerosis

PMCID: PMC3475710This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Age-Associated Hyper-Methylated Regions in the Human Brain Overlap with Bivalent Chromatin Domains

PMCID: PMC3454416This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: record-linkage study

BACKGROUND: Venous thromboembolism (VTE) is a common complication during and after a hospital admission. Although it is mainly considered a complication of surgery, it often occurs in people who have not undergone surgery, with recent evidence suggesting that immune-mediated diseases may play a role in VTE risk. We, therefore, decided to study the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in people admitted to hospital with a range of immune-mediated diseases. METHODS: We analysed databases of linked statistical records of hospital admissions and death certificates for the Oxford Record Linkage Study area (ORLS1:1968 to 1998 and ORLS2:1999 to 2008) and the whole of England (1999 to 2008). Rate ratios for VTE were determined, comparing immune-mediated disease cohorts with comparison cohorts. RESULTS: Significantly elevated risks of VTE were found, in all three populations studied, in people with a hospital record of admission for autoimmune haemolytic anaemia, chronic active hepatitis, dermatomyositis/polymyositis, type 1 diabetes mellitus, multiple sclerosis, myasthenia gravis, myxoedema, pemphigus/pemphigoid, polyarteritis nodosa, psoriasis, rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus. Rate ratios were considerably higher for some of these diseases than others: for example, for systemic lupus erythematosus the rate ratios were 3.61 (2.36 to 5.31) in the ORLS1 population, 4.60 (3.19 to 6.43) in ORLS2 and 3.71 (3.43 to 4.02) in the England dataset. CONCLUSIONS: People admitted to hospital with immune-mediated diseases may be at an increased risk of subsequent VTE. Our findings need independent confirmation or refutation; but, if confirmed, there may be a role for thromboprophylaxis in some patients with these diseases

High reprint orders in medical journals and pharmaceutical industry funding: case-control study

Objectives To assess the extent to which funding and study design are associated with high reprint orders

Funding source and primary outcome changes in clinical trials registered on ClinicalTrials.gov are associated with the reporting of a statistically significant primary outcome: a cross-sectional study.

BACKGROUND: We and others have shown a significant proportion of interventional trials registered on ClinicalTrials.gov have their primary outcomes altered after the listed study start and completion dates. The objectives of this study were to investigate whether changes made to primary outcomes are associated with the likelihood of reporting a statistically significant primary outcome on ClinicalTrials.gov. METHODS: A cross-sectional analysis of all interventional clinical trials registered on ClinicalTrials.gov as of 20 November 2014 was performed. The main outcome was any change made to the initially listed primary outcome and the time of the change in relation to the trial start and end date. FINDINGS: 13,238 completed interventional trials were registered with ClinicalTrials.gov that also had study results posted on the website. 2555 (19.3%) had one or more statistically significant primary outcomes. Statistical analysis showed that registration year, funding source and primary outcome change after trial completion were associated with reporting a statistically significant primary outcome . CONCLUSIONS:  Funding source and primary outcome change after trial completion are associated with a statistically significant primary outcome report on clinicaltrials.gov

Geography of hospital admissions for multiple sclerosis in England and comparison with the geography of hospital admissions for infectious mononucleosis: a descriptive study

Objective It is well recognised that variation in the geographical distribution of multiple sclerosis (MS) exists. Early studies in England have shown the disease to have been more common in the North than the South. However, this could be an artefact of inaccurate diagnosis and ascertainment, and recent data on MS prevalence are lacking. In the present study, data were analysed to provide a more contemporary map of the distribution of MS in England and, as infectious mononucleosis (IM) has been shown to be associated with the risk of MS, the geographical distribution of IM with that of MS was compared.Methods Analysis of linked statistical abstracts of hospital data for England between 1999 and 2005.Results There were 56 681 MS patients. The admission rate for MS was higher in females (22/10(5); 95% CI 21.8 to 22.3) than males (10.4/10(5); 95% CI 10.2 to 10.5). The highest admission rate for MS was seen for residents of Cumbria and Lancashire (North of England) (20.1/10(5); 95% CI 19.3 to 20.8) and the lowest admission rate was for North West London residents (South of England) (12.4/10(5); 95% CI 11.8 to 13.1). The geographical distributions of IM and MS were significantly correlated (weighted regression coefficient (r (w))=0.70, p<0.0001). Admission rates for MS were lowest in the area quintile with the highest level of deprivation and they were also lowest in the area quintile with the highest percentage of population born outside the UK. A significant association between northernliness and MS remained after adjustment for deprivation and UK birthplace.Conclusions The results show the continued existence of a latitude gradient for MS in England and show a correlation with the distribution of IM. The data have implications for healthcare provision, because lifetime costs of MS exceed 1 pound million per case in the UK, as well as for studies of disease causality and prevention