Friday, 1 July 2016

New MS progressive Gene is Rubbish?

Recently we posted that a Canadian group had found a gene is a family that may be associated with progression

Now you can skuttle off and do some studies to replicate the work and then spend months getting papers published but which time the whole world thinks that there is a progressive MS gene or you can use social media of epublishing (seemingly not peer reviewed) to get it out that you think the work is rubbish.

Who would say that the data was rubbish...someone on twitter?

People were rushing to their data bases to look if they could find any support and so far the answer is they can't

There are some more doubting Thomas'es or should I say doubting Chris'es (CLICK here)

"Abstract: a recent study by Wang et al claims the low-frequency variant NR1H3 p.Arg415Gln is pathological for multiple sclerosis and determines a patient’s likelihood of primary progressive disease. We sought to replicate this finding in the International MS Genetics Consortium (IMSGC) patient collection, which is 13-fold larger than the collection of Wang et al, but we find no evidence that this variant is associated either with MS or disease subtype. Wang et al also report a common variant association in the region, which we show captures the association the IMSGC reported in 2013. Therefore, we conclude that the reported low-frequency association is a false positive, likely generated by insufficient sample size. The claim of NR1H3 mutations describing a Mendelian form of MS, of which no examples exist, can therefore not be substantiated by data".

or for more click here

So it may fall by the wayside as an MS gene unless there is something special about these rare families in Canada, such that they have many shared genes and that allow the  NR1H3 variant to code for something.

The academic gloves are off.

The progress is about replication

Pinch of Salt

Nourbakhsh B, Graves J, Casper TC, Lulu S, Waldman A, Belman A, Greenberg B, Weinstock-Guttman B, Aaen G, Tillema JM, Hart J, Ness J, Rubin J, Krupp L, Gorman M, Benson L, Rodriguez M, Chitnis T, Rose J, Barcellos L, Waubant E; Network of Pediatric Multiple Sclerosis Centers. Dietary salt intake and time to relapse in paediatric multiple sclerosis.J Neurol Neurosurg Psychiatry. 2016 Jun 24. pii: jnnp-2016-313410. doi: 10.1136/jnnp-2016-313410. [Epub ahead of print]

BACKGROUND:Salt intake was reported to be associated with increased clinical and MRI activity in adult patients with relapsing-remitting multiple sclerosis (MS).

OBJECTIVE: To determine if salt intake is associated with time to relapse in patients with paediatric-onset MS.

METHODS: Paediatric-onset MS and patients with clinically isolated syndrome (CIS) within 4 years of disease onset were recruited from 15 paediatric MS centres in the USA as part of a case-control study. Patients with available prospective relapse data subsequent to enrolment were included in this project. Dietary sodium intake was assessed by self-report questionnaire using the validated Block Kids Food Screener. Cox proportional-hazards regression models were employed to determine the association of sodium density, excess sodium intake and sodium density tertiles with time to relapse following study enrolment, adjusting for several confounders.

RESULTS: 174 relapsing-remitting MS/CIS patients were included in this analysis (mean age of 15.0 years, and 64.9% females). Median duration of follow-up was 1.8 years. In an unadjusted analysis, density of daily sodium intake was not associated with time to relapse, and patients with excess sodium intake had no decrease in time to relapse as compared with patients with non-excess sodium intake. A
nalysis demonstrated that patients in the high tertile (top third) of sodium density had a Hazard Ratio of 0.69 (95% CI 0.37 to 1.30, p=0.25) and 1.37 (95% CI 0.74 to 2.51, p=0.32) compared with patients in the lowest tertile (lowest third) , respectively.

CONCLUSIONS: Higher salt intake was not associated with decreased time to relapse in patients with paediatric-onset MS.

It was reported that an increase in salt intake increased autoimmunity in mice and these studies where in the top ten cited papers and was in part supported by a study in MS. MD2 pointed out that the mouse studies used the equivalent of taking 0.6kg salt a day, enough to make you vomit, if rodents could vomit..which they can't. This comment was removed two times by Nature and on the third time it was added it stayed after we complained to them. The mouse stuff was barely repeatable and in this study the paediatric study the salt intake had no influence.

It is best to watch your salt intake for general health

Thursday, 30 June 2016

NewsSpeak & MSLondon: London MS Specialist Network

What should we do with the London MS group? #NewsSpeak #MSLondon #MSBlog

"I am one of the founder members of the London MS Group (LMSG), a loose network of London-based MSologists. We started the group just over 10 years ago. The aim of the group was for neurology consultants with a specialist interest in MS to meet 3-4 times a year to discuss issues in relation to the management and treatment of MS. Invitations are sent out to a list of neurologists who see people with MS at 7 regional neuroscience centres in and around London (Imperial College, St Georges Hospital, Kings College, Queen Square, Barts-MS, Royal Free and Queen's Romford) and from the regional feeder hospitals. The turnout of for the LMSG meetings has been highly variable and has becoming increasingly poor. Why? I suspect there are many reasons for this, but increasing numbers of competing commitments and meeting fatigue are the main reasons."

"We had a meeting last night and only 6 neurologists turned up; on one occasion only 3 neurologists attended. We decided last night to rejuvenate the group, change its name, expand its remit and formalise it as a registered organisation. We all agreed that London MS centres are at the vanguard of MS service development, treatment, management and research in the UK and we need a voice and a platform to promote this. As this organisation will impact on the management of close to 25,000 people with MS living in and around London it would be useful if you could tell us what you would want from this organisation. Should we include non-neurologists and other stakeholders? What about people with MS? Should we use the organisation to publish guidelines and set standards? For example, should we include the London MS-AHSCT Collaborative Group under the umbrella?"

GameSpeak & ClinicSpeak: Can we gamify MS life skills?

Can healthcare be delivered via a game? #MSBlog #GameSpeak #ClinicSpeak #BrainHealth

"Engagement and adoption is the biggest problems facing healthcare innovators, or wannabe healthcare innovators like me. We can come up with an idea very 5 minutes, but unless we can implement them, get them adopted, show that they have an impact on outcomes and are cost effective we are wasting our time and your time. On the other side of the coin getting the target population to change their behaviour is remarkably difficult. The paper below describes turning the process into a game with the hope that this will change behaviour. The downside of this is that not everyone necessarily likes games. What do you think? Could we design a game to nudge MSers to improve their lifestyles with the hope that it will improve outcomes? If you have any ideas or examples, in particular around Brain Health, I would be very interested to know about them. Please remember the game may also involve healthcare professionals."

Giunti G. Gamified Design for Health Workshop. Stud Health Technol Inform. 2016;225:605-6.

Increasing lifespans for chronic disease sufferers means a population of young patients who require lifestyle intervention from an early age. For multiple sclerosis (MS) patients, social problems begin with the decline of cognitive skills and their quality of life is affected. In this workshop, organizers will propose participants to work on different gamification design approaches to solve MS patients' engagement problem. Participants will obtain skills that can be extrapolated to other conditions that require patients change to adopt a different behavior. At the end, participants will present their proposed gamification design and discuss and comment each solution, assessing potential unintended outcomes and advantages.

Gut Microbiota is different in MS

Chen J, Chia N, Kalari KR, Yao JZ, Novotna M, Soldan MM, Luckey DH, Marietta EV, Jeraldo PR, Chen X, Weinshenker BG, Rodriguez M, Kantarci OH, Nelson H, Murray JA, Mangalam AK. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls.Sci Rep. 2016 Jun 27;6:28484. doi: 10.1038/srep28484.

Multiple sclerosis (MS) is an immune-mediated disease, the etiology of which involves both genetic and environmental factors. The exact nature of the environmental factors responsible for predisposition to MS remains elusive; however, it is hypothesized that gastrointestinal microbiota might play an important role in pathogenesis of MS. Therefore, this study was designed to investigate whether gut microbiota are altered in MS by comparing the fae
cal microbiota in relapsing remitting MS (RRMS) (n = 31) patients to that of age- and gender-matched healthy controls (n = 36). Phylotype profiles of the gut microbial populations were generated. Detailed faecal microbiome analyses revealed that MS patients had distinct microbial community profile compared to healthy controls. We observed an increased abundance of Psuedomonas, Mycoplana, Haemophilus, Blautia, and Dorea genera in MS patients, whereas control group showed increased abundance of Parabacteroides, Adlercreutzia and Prevotella genera. Thus our study is consistent with the hypothesis that MS patients have gut microbial dysbiosis and further study is needed to better understand their role in the aetiopathogenesis of MS.

Gut bacteria is a hot topic in science as it may help shape the immune response and this study says it is diiferent in MS. This will need repeating. We will see if feacal transplants affect MS as people have this procedure done. But what happened in other studies

Tremlett H, Fadrosh DW, Faruqi AA, Zhu F, Hart J, Roalstad S, Graves J, Lynch S, Waubant E; US Network of Pediatric MS Centers. Eur J Neurol. 2016 May 13. doi: 10.1111/ene.13026. [Epub ahead of print]

"Relative to controls, MS cases had a significant enrichment in relative abundance for members of the Desulfovibrionaceae (Bilophila, Desulfovibrio and Christensenellaceae) and depletion in Lachnospiraceae and Ruminococcaceae" 

 or Bacteroidaceae, Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and other Clostridiales. Compared with the other groups, untreated patients with multiple sclerosis had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation.

So no consistency so it is hard to know what this really means