Author: Gavin Giovannoni

Old but good news: children and adolescents get their first licensed DMT in Europe

I personally want to thank all those involved in getting fingolimod licensed as the first disease-modifying therapy for children and adolescents with MS. Getting this trial done was a ‘mission impossible’. Novartis, the steering committee, investigators and all study participants must be congratulated on getting past the finish line. History will judge this as an important milestone for MSers and the wider MS community.


However, I am very disappointed that the EMA (CHMP) only licensed this for highly-active or rapidly-evolving severe MS. Why the restrictive label? When will the EMA beging to trust neurologist, MSers and their families to do the right thing? The way the EMA treat us is insulting and does not put MSers’ interests first. 

Surely it is time to change fingolimod’s label? We need fingolimod to be first-line. Why can’t we be trusted to use fingolimod wisely in the interests of our patients with active MS? Surely it is safer than alemtuzumab? Possibly safer than ocrelizumab? Can someone explain the thinking and logic behind the latest pair of EMA handcuffs?

The following is verbatim from the EMA’s website:

On 20 September 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for the medicinal product Gilenya. The marketing authorisation holder for this medicinal product is Novartis Europharm Limited.

The CHMP adopted an extension to the existing indication as follows:

“Gilenya is indicated as single disease modifying therapy in highly active relapsing remitting multiple sclerosis for the following groups of adult patients and paediatric patients aged 10 years and older:


Patients with highly active disease despite a full and adequate course of treatment with at least one disease-modifying therapy (for exceptions and information about washout periods see sections 4.4 and 5.1).

or


Patients with rapidly evolving severe relapsing-remitting multiple sclerosis defined by 2 or more disabling relapses in one year, and with 1 or more Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI.”

Detailed recommendations for the use of this product will be described in the updated summary of product characteristics (SmPC), which will be published in the revised European public assessment report (EPAR), and will be available in all official European Union languages after a decision on this change to the marketing authorisation has been granted by the European Commission.


The timing of this is fortuitous as the study has recently been published in the NEJM:

Chitnis et al. Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis. N Engl J Med. 2018 Sep 13;379(11):1017-1027.


BACKGROUND: Treatment of patients younger than 18 years of age with multiple sclerosis has not been adequately examined in randomized trials. We compared fingolimod with interferon beta-1a in this population.

METHODS: In this phase 3 trial, we randomly assigned patients 10 to 17 years of age with relapsing multiple sclerosis in a 1:1 ratio to receive oral fingolimod at a dose of 0.5 mg per day (0.25 mg per day for patients with a body weight of ≤40 kg) or intramuscular interferon beta-1a at a dose of 30 μg per week for up to 2 years. The primary end point was the annualized relapse rate.

RESULTS: Of a total of 215 patients, 107 were assigned to fingolimod and 108 to interferon beta-1a. The mean age of the patients was 15.3 years. Among all patients, there was a mean of 2.4 relapses during the preceding 2 years. The adjusted annualized relapse rate was 0.12 with fingolimod and 0.67 with interferon beta-1a (absolute difference, 0.55 relapses; relative difference, 82%; P<0.001). The key secondary end point of the annualized rate of new or newly enlarged lesions on T2-weighted magnetic resonance imaging (MRI) was 4.39 with fingolimod and 9.27 with interferon beta-1a (absolute difference, 4.88 lesions; relative difference, 53%; P<0.001). Adverse events, excluding relapses of multiple sclerosis, occurred in 88.8% of patients who received fingolimod and 95.3% of those who received interferon beta-1a. Serious adverse events occurred in 18 patients (16.8%) in the fingolimod group and included seizures (in 4 patients), infection (in 4 patients), and leukopenia (in 2 patients). Serious adverse events occurred in 7 patients (6.5%) in the interferon beta-1a group and included infection (in 2 patients) and supraventricular tachycardia (in 1 patient).

CONCLUSIONS: Among pediatric patients with relapsing multiple sclerosis, fingolimod was associated with a lower rate of relapse and less accumulation of lesions on MRI over a 2-year period than interferon beta-1a but was associated with a higher rate of serious adverse events. Longer studies are required to determine the durability and safety of fingolimod in pediatric multiple sclerosis. (Funded by Novartis Pharma; PARADIGMS ClinicalTrials.gov number, NCT01892722 .).

Comment in: Therapy in Multiple Sclerosis – Coming of Age. [N Engl J Med. 2018].


CoI: Multiple; in addition Prof G is a member of the PARADIGMS trial steering committee

A quick summary of Prof G’s Twitter activity (17-23 Sept 2018)

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Shame on Barts Health NHS Trust

 

In our patch of East London if you have MS and live in Newham you get a very poor service; for example, you are 3-4 times more likely to require an emergency or non-elective hospital admission compared to if you live in Tower Hamlets or Hackney (our local London boroughs).

Why? 

We think the main reason is that there are no community-based MS clinical nurse specialists in Newham. We have been trying to progress a business case for a nurse post at Newham. The business case was due to be primed by the MS Trust and partly covered by the Newham CCG (clinical commissioning group), but as Barts Health is essentially bankrupt they won’t sign off on their part of the deal, i.e. to continue to fund our contribution to the post after two years. 
 
Our Trust is in special measures which mean external bean counters (consultants) come in and block all non-essential services or spend. This is all part of our CIPs (cost improvement plans) to make our NHS Trust financially viable. They don’t really care about MSers living in Newham who will continue to need admission for UTIs, falls, fractures, faecal impaction, pneumonia, pressure sores, etc. The MS Trust has data that shows that within the first year of specialist nurse appointment unplanned or emergency MS-related hospital admission fall by over 40%. In other words, MS clinical nurse specialists pay for themselves and at the same time improve the quality of life of their patients and families. Barts Health NHS don’t care. It is shameful that we such local variation in MS services.


Variations like these in local and regional MS services is one of the reasons why we are holding a meeting on ‘MS Service Provision in the UK; the Way Forward‘ in Birmingham on the 1st and 2nd of November. We will hopefully tackle thorny issues such as the above. Another issue is why do MSers in socioeconomic groups 4 & 5 not get the same services compared to MSers in socioeconomic groups 1, 2 & 3? Why can’t MSers who are referred into specialist services from DGHs (district general hospitals) get a more prompt service? Why are they worse off than MSers who are managed directly by the specialist centre? Why do MSers with relapsing-MS get a better deal than those with more advanced or progressive MS? These are just a few of the questions we will attempt to answer at this meeting. 

 
The good news is that the response to our meeting has been overwhelming with representatives from all over the UK. I sincerely hope we can come up with some common sense solutions to the issues raised. At the end of the day, we simply want to get rid of post-code prescribing and inequity in MS service provision across the UK. 
 
UK Centres signed-up to attend the variation in MS Services Meeting
 
We plan to record the talks and some of the discussions from the meeting and put them online. We will let you know when this happens as well as the outcome of the meeting. 
 
We need a wider debate about how we want the NHS to evolve and how MS services are delivered. 
 
CoI: multiple
Rachel Horne interviews ProfG to ascertain why the Department of Health and NICE have said no to ocrelizumab for treating people with PPMS. 


“We don’t care a toss about PPMSers, all we are worried about is rationing high-cost drugs and making sure we keep the system simple”, said a DoH spokesperson. “We cannot change the NHS accounting system to have two prices for the same drug”, he added

“Why?”, asked Prof G.

“Don’t you understand, how the NHS works?”, he replied. 




“I am too conflicted to take on this challenge. People without conflicts of interests will need to take the fight to the DoH and Government”, concludes ProfG. 


CoI: multiple

News: Prof G is fuming, why?

I am considering giving up working for the NHS. How can I face my patients with active PPMS and tell them we can’t treat their disease because the Department of Health/NHS won’t come to the table with a deal that involves differential pricing of ocrelizumab?


NICE has just said no to ocrelizumab for treating active PPMS on the NHS. Why? The problem is that the price of ocrelizumab has been set for RRMS and this is too expensive for the NHS; i.e. it is not cost-effective for the treatment of PPMS based on its efficacy in PPMS and the fact that ocrelizumab has to be compared to best supportive care (no treatment) for PPMS. In comparison, in RRMS ocrelizumab was compared to all the other DMTs. To address these issues I have been told that Roche agreed to lower the price for ocrelizumab for the PPMS indication so that it would be cost-effective. This would mean that ocrelizumab would need two prices on the NHS books; a more expensive price to treat RRMS and a cheaper price for PPMS. Apparently, the Department of Health is not prepared to go there. Why not? In short, they don’t give a toss about PPMSers. For the DoH and the NHS, this is just another can of worms they want to be kicked into the long grass. 

This decision creates inequity; those PPMSer lucky enough to be wealthy and have money will get ocrelizumab privately, those lucky enough to have been in clinical trials will get it from Roche as part of the extension study and those lucky enough to live in another EU country will be on it via their healthcare system. There is a chance the Scottish NHS may say yes, then we would end up with the situation that Scotthish PPMSers will have access to ocrelizumab, but not English PPMSers.  

What can we do about it? I think we need to launch a protest campaign that includes the following:
  1. An open petition; we will need 100,000 signatories to trigger a debate in the house of commons.
  2. A passive email/letter campaign; each and every one of you who cares about the treatment of PPMS needs to write to your MP to ask for an explanation.
  3. Street protests; we need to organise a protest and march on the DoH. Do you think they will respond to a 1,000s of MSers, their families and friends outside the DoH’s HQ in Whitehall? We could block Whitehall with wheelchair users. 
  4. We need to media behind the campaign; article after article and TV programmes about the issues raised by this perverse decision. We need the broader public to know about the issues. The implications of the ocrelizumab rejection go far beyond the treatment of a small group of PPMSers. 
If any of you want to help please contact me. I need ideas as well. 


If this decision was about breast cancer or HIV there would be national protests. The pink and red ribbon brigades would be out in force. Let’s make it an orange ribbon day. 


CoI: multiple; I sat on the steering committee for the ORATORIO (ocrelizumab in PPMS) trial and I am the principal investigator of the ORATORIO-HAND trial (ocrelizumab in advanced PPMS). I am conflicted up to my eyeballs, but I am also an advocate for my patients. They need me to stick my head above the parapet and fight for them, which is what I am going to do. 

Has your neurologist discussed HPV vaccination with you?

What to advise MSers about the HPV vaccine?



You may be aware that for almost a decade young girls living in the UK have been offered the HPV vaccine at ~12-14 years of age. The HPV vaccine is to prevent infection with the sexually transmitted human papillomavirus (HPV) that is known to cause cervical cancer and several other cancers. The current issue is that innovation never stands still, technology moves on and society changes its behaviour. All of these are coming together to create a perfect storm that has major implications for MSers. 



The innovation: The current NHS funded vaccine (Gardasil) covers only 4 strains of HPV and reduces the risk of cervical cancer by ~67%. The newer more advanced HPV vaccine covers 9 HPV strains and reduces the risk of cervical cancer by over 90%. The problem is the Department of Health are not yet prepared to pay for the more expensive vaccine that covers 9 strains. It is important to realise that the newer vaccine also covers more strains of HPV that cause warts, in particular, genital warts. Is this important? Yes, it is. If you decide to go onto an immunosuppressive therapy, in particular, an immune reconstitution therapy or IRT, then suppression of your immune system allows the virus to escape and to start replicating. I am aware of two cases at other centres who have had alemtuzumab only to see their genital warts become a major problem. I am also aware of a patient who developed a problem when her common old garden variety of cutaneous warts spread post-alemtuzumab. These anecdotal cases are very important and I now view warts, be they genital or cutaneous, as a relative contraindication to IRTs, particularly the non-selective IRTs such as alemtuzumab and HSCT. 


Social changes: There are public health issues that are as relevant to MSers as the general population. HPV is not only a problem for women. HPV is a well-established cause of penile and anal cancer and causes a small proportion of throat and oesophageal cancers. Therefore it makes sense for males to be vaccinated against HPV as well. In the UK boys who have sex with boys and are prepared to admit it can have the HPV vaccine. But what about men? The rationale for targeting the general population is to reduce the pool of susceptible people and thereby reduce the spread of the virus. Epidemiologists call the latter herd immunity. For herd immunity to be effective you typically need over 90% of the population to vaccinated.


The epidemiology of HPV infection is also changing. People are becoming infected later in life and are spreading the virus. Social media and dating apps have revolutionised the dating world and many older people are becoming promiscuous in older age and are having unsafe sex. As a result of this, there has been a large increase in the incidence of sexually transmitted diseases in older people, including HPV infections. This has prompted some commentators to suggest that public health officials extend the HPV vaccine to all women and possibly all men. Why wouldn’t you want to reduce your risk of getting cervical cancer? Isn’t prevention better than having to treat HPV infection and its downstream effects, i.e. premalignant cervical lesions or cervical cancer?


As a result of these trends, an increasing number of MSers are asking about the HPV vaccine. Similarly, when I go to meetings neurologists are asking me for advice or what to do about vaccines, in particular, the HPV vaccine There are several questions that HPV vaccination raises that are directly relevant to MSers.


Question 1: If I have been vaccinated with the older quadrivalent vaccine could I receive the new vaccine to cover the other strains of the virus?


Yes, there is data that shows that the previous vaccination against HPV doesn’t stop your immune system from responding to the components cover the new strains.


Question 2: As I am on a DMT can I have the HPV vaccine?


This all depends on the DMT you are on. For the non-immunosuppressive immunomodulators such as interferon-beta and glatiramer acetate vaccination is not a problem. These agents do not blunt immune responses to vaccines. For the other DMTs to story is not that clear. Fingolimod and ocrelizumab are known to blunt vaccine responses. Vaccine responses to component vaccines on dimethyl fumarate have been studied and were normal. However, I am not aware of any specific studies looking at the HPV vaccine. I would, however, think it would be fine to receive the HPV vaccine if you are on DMF. Teriflunomide is similarly unlikely to blunt the immune response to HPV, but we don’t have specific data on the HPV vaccine and teriflunomide Natalizumab mode of action is unique and is unlikely to affect peripheral immune responses. For the IRTs (alemtuzumab, cladribine, mitoxantrone and HSCT) vaccination should be delayed until after immune system reconstitution.


Question 3: I need to start a DMT, but I want to have the HPV vaccine or extend my cover with the new polyvalent vaccine, how long will I need to wait before I can start treatment?


The polyvalent vaccine at the moment requires 2 or 3 doses with the last dose given at 5 or 6 months. Ideally, to give your immune system a chance to respond to the vaccine you will need to wait until 4 weeks after the final booster, i.e. 6 or 7 months.


Question 4: Should I delay starting DMTs to have the vaccine?


There is no simple answer to this question. You have to balance the risks and benefits of having the vaccine against the risks of untreated MS. In relation to the IRTs, I would suggest going ahead and starting the IRT and delaying the vaccine until you have reconstituted your immune system. Delaying starting an IRT to have the vaccine does not make immunological sense in that the memory responses you have just made to the vaccine could potentially get depleted and depending on the intensity of the immunodepletion may not recover. For maintenance DMTs, in particular, fingolimod, dimethyl fumarate and ocrelizumab, you should probably delay starting treatment to have the vaccine.


Question 5: If I want the new polyvalent vaccine will the NHS cover it?


At present, the answer is no. Public Health England cover the quadrivalent vaccine under the national vaccine programme. If you want to be vaccinated against HPV you will have to cover the costs of the vaccine yourself. This is not too dissimilar to what happens with travel vaccines.



As you can see HPV vaccination is one of those factors that have to be put in the mix when deciding which is the correct DMT for you. It is not a major factor but is an important factor nevertheless. At the moment I don’t routinely advise my patients on this topic, but it is something that has future health implications, be they sexual, so maybe we need to do this routinely. What is your view on this? Do you think healthcare professionals should be obliged to discuss issue around vaccination before the start of a DMT?

CoI: multiple

Should Prof G do less blogging and more walking the talk?

Did you know that approximately 25% of people diagnosed with a radiologically-isolated syndrome (RIS), or asymptomatic MS, already cognitive impairment and smaller brains? This indicates that even before MS has been diagnosed the disease processes are already causing subclinical damage to brains of people destined to develop full-blown MS in the future. The reason you are not aware of this is that the brain has spare capacity, reserve or some redundancy to allows you to compensate for this early damage.


What about hand function (#ThinkHand)?

The study below takes these observations one step further and show that RISers also have deficits in hand function that they are not aware of. Using a super intelligent glove with sensors these researchers showed that finger-to-thumb opposition at maximum speed and paced two-handed movements were abnormal when compared to control or normal subjects. These abnormalities of hand function were related to the number of lesions on MRI or MS disease pathology. In all likelihood, these RISers would not be aware of these abnormalities, unless they were using their hands at a very high level, for example, professional musicians. Or then again they may simply ignore them as something else. Isn’t this disease scary?



What are the implications of this research for the MS community? Firstly, it argues for us changing the diagnostic criteria to allow us to diagnose MS earlier, in the RIS phase, so that we can offer these patients treatment. Some of the naysayers will say that by allowing MS to be diagnosed earlier we will misdiagnose too many people with MS who don’t have the disease. I am not sure if this is correct. If we developed new diagnostic criteria for asymptomatic MS and tested them properly in a prospective group of RISers and compared them to the gold standard, i.e. pathological diagnosed MS, we could assess the sensitivity and specificity of the criteria and their positive and negative predictive value to address this criticism.

Did you know that the various renditions of the current MS diagnostic criteria have never been validated against a pathological gold-standard? We can make some assumptions that they do okay based on the findings of one or two post-mortem studies, but we can’t be confident about their performance outside areas of high MS prevalence. Secondly, this study supports using hand function as an outcome measure in clinical trials, it seems that if we use sensitive tests of hand function we may be able to use these measures to assess DMTs that delay worsening or even improve hand function.



Two things that I could potentially do as a result of this paper. The first is to walk the talk and write a proposal for a new set of MS diagnostic criteria, which will include asymptomatic MS. The proposal will need to include a study to validate the new criteria against a pathological gold-standard and to test the criteria in high, intermediate and low prevalence areas. A pathological (biopsy or post-mortem) gold standard is required because none of the previous MS diagnostic criteria has ever been validated in this way. The reason for studying the performance of the new criteria in different MS prevalence areas is that the positive and negative predictive values of diagnostic criteria, i.e. their ability for them get the diagnose right depends on how common or rare MS is and how common or rare MS mimics are in the particular area. Against me walking the talk is that I am not sure if I have it in me to take on the MS community in terms of redefining MS.



The other action point that I will take away from this research is that we should try and include this glove as part of our ORATORIO-HAND and CHARIOT-MS studies. We could do small add-on studies to test the utility of the glove and compare it to the 9HPT and the ABILHAND PROM. Another proposal would be to use the glove to assess the impact that neuro-rehabilitation has on hand function. Because the glove has a much lower floor effect, i.e. it even detects abnormalities in asymptomatic MSers, it could potentially be a much better outcome measure in disease improvement trials.



Lot’s to do and not enough time to do it all. Maybe less talking (less blogging) and more walking 😉





BACKGROUND: An engineered glove measuring finger motor performance previously showed ability to discriminate early-stage multiple sclerosis (MS) patients from healthy controls (HC). Radiologically isolated syndrome (RIS) classifies asymptomatic subjects with brain MRI abnormalities suggestive of multiple sclerosis.



METHODS: We assessed 17 asymptomatic subjects with radiologically isolated syndrome (RIS) and 17 HC. They performed finger-to-thumb opposition sequences at their maximal velocity, metronome-paced bimanual movements and conventional and diffusion tensor MRI.



RESULTS: Subjects with RIS showed lower (p=0.005) maximal velocity and higher (p=0.006) bimanual coordination impairment than HC. In RIS, bimanual coordination correlated with T2-lesion volume, fractional anisotropy and radial diffusivity in the white matter.



CONCLUSIONS: These findings point out the relevance of fine hand measures as a robust marker of subclinical disability.



By: Gavin Giovannoni


CoI: none in relation to this post

How soon would you like your MS diagnosed?

 

The MS prodrome; how real is it? 


Multiple sclerosis has a preclinical phase during which irreversible damage occurs. This phase is typically associated with subtle symptoms and signs that aren’t enough to warrant a diagnosis of MS and we, therefore refer to this as the MS prodrome. Identifying a prodrome is important as it may allow you to diagnose MS earlier. With the emergence of disease-modifying therapies identifying patients in the preclinical phase of the disease provides the potential to improve disease outcomes; the earlier you modify the course of MS the greater will be the impact on the long-term trajectory. In addition, preservation of brain reserve should reduce the inevitable impact that ‘normal ageing’ has on MS outcome over your life.


Helen Tremlett’s group in British Columbia have cleverly used health administrative and clinical databases in Canada, show increased healthcare utilization prior to the development of a first demyelinating event, compatible with MS. The so-called rate ratios increased steadily between five years and one year before the first demyelinating disease claim, which is an indicator that the increase healthcare utilization was due to the MS prodrome. The study findings support other published observations describing an MS prodrome.


It should not be a surprise that physician or neurologist generated codes that were associated with MS included disorders of the central and peripheral nervous system, disorders of the eye and cerebrovascular disease. Hospital and prescription data were poor predictors, however, hospitalizations related to the urinary system or spinal cord diseases, or prescriptions for urinary antispasmodics or anti-vertigo preparations, were associated with 2 to 3-fold higher odds of developing MS in the future.


MS in common with other neurodegenerative diseases also has a latent, or pre-disease, state prior to the preclinical and clinical phases. The latency phase refers to the so-called ‘at risk’ period prior to the onset of focal inflammatory lesions that defines MS pathologically. Migration studies, between areas of high and low prevalence, indicate that from exposure to the putative environmental risk factors and the onset of the disease is somewhere between 10 and 20 years. Similarly, pathological studies indicate that the preclinical phase of MS could potentially be decades. A large Danish series found that approximately a quarter of cases with pathological evidence of MS at post-mortem were never diagnosed with MS in life. Either these subjects had asymptomatic MS or their symptoms were put down to some other ailment.


In general, MS begins before the first clinical attack; the majority of patients presenting with a clinically isolated syndrome (CIS) have older, inactive, lesions on their MRI that does not account for the CIS. Familial studies demonstrate that some siblings, including unidentical and identical twins, have lesions on MRI compatible with demyelination and/or the presence of oligoclonal IgG bands in their CSF; this is despite the majority of these siblings never going onto to develop MS. The MS endophenotype is the term that we use to capture the ‘at risk’, ‘asymptomatic’, ‘prodromal’ and ‘clinical’ phases of MS.


Redefining MS to capture the different phases of the disease should allow us to study the impact of DMTs on both the asymptomatic (radiologically isolated syndrome – RIS) or prodromal phases. Recent studies have demonstrated that even at these earlier stages of MS there is evidence of end-organ or brain damage.


There is an ongoing debate whether, or not, we should extend the diagnosis of MS into this asymptomatic, and now the prodromal, phases of the disease and to offer these people DMTs. I have little doubt about this and hope the next rendition of the McDonald MS diagnostic criteria will extend the diagnosis of MS into the asymptomatic phase of the disease. Redefining when MS begins will allow us to test whether very early intervention in the disease course improves long-term outcome rather than waiting for the disease to become symptomatic.

 
 

Högg et al. Mining healthcare data for markers of the multiple sclerosis prodrome. Mult Scler Relat Disord. 2018 Aug 8;25:232-240.


BACKGROUND: Previous studies suggest the existence of a prodromal period in multiple sclerosis, but little is known about the phenotypic characteristics. This study aims to characterize the multiple sclerosis (MS) prodrome using data mining analytics in the healthcare setting.



METHODS: We identified people with MS and matched general population controls using health administrative data in two Canadian provinces (British Columbia and Saskatchewan). Using a training dataset (66.6% of British Columbia’s cohort), L1 penalized logistic regression models were fitted to predict MS from physician and hospital encounters (via International Classification of Diseases [ICD] codes) and prescriptions filled (as drug classes) during the five years before the MS case’s first demyelinating event. Internal and external validation of identified predictors was performed using logistic regression on the remaining British Columbia (33.4%) and Saskatchewan data. Adjusted odds ratios (aORs) and Area under the Curve (AUC) metrics for the models’ predictive performance were reported.


RESULTS: We identified 8,669 MS cases and 40,867 controls. Good predictive performance was observed for physician data (internal/external validation AUC = 0.81/0.79). Physician-generated ICD codes that were associated with MS and validated in both provinces included disorders of the central and peripheral nervous system, disorders of the eye, and cerebrovascular disease (aOR = 1.3-7.0). Overall, hospital and prescription data showed very poor and poor predictive performance (internal/external validation AUCs = 0.54/0.55 and 0.66/0.61, respectively). However, hospitalizations related to the urinary system or spinal cord diseases, or prescriptions for urinary antispasmodics or anti-vertigo preparations, were associated with 2 to 3-fold higher odds of MS (aOR = 2.3-3.3).


CONCLUSIONS: Findings provide insight into the clinical characteristics of the MS prodrome. Diagnostic codes from physician encounters were capable of differentiating between MS cases and controls.


CoI: none in relation to this post

Walking, or Running, the Talk – ProfG does it

Regular exercise is good for you. Two week’s ago I did a post on setting up a national challenge on using the parkrun platform to raise awareness about exercise and to get the MS community behind exercise. The following are the results of the survey you completed.



 The results are self-evident; we need to make this happen. 



I am smitten by #Run4MS as the proposed name for the initiative. It is catchy, it says exactly what it is for and the hashtag makes it ideal of using it on social media. 

 You may have noticed that I am walking, or more correctly running, the talk; I completed my first parkrun on Saturday. I have already had some informal discussions with some of my team at Barts-MS and we will almost certainly be putting a team together a team to enter the challenge. 

 I have now handed the ball over to the MS Trust and Parkrun to make this happen. I am not sure of the exact format, but the initiative is likely to take the form of a national challenge to get the MS community walking and running. We will use the Parkrun platform, simply because it exists and the MS ambassadors of Parkrun contacted us to do something with them.

 Parkruns are 5km runs that are held each Saturday in a local park near you and allow you to complete 5km and log an official time. The challenge will be to get every MS team in the UK, and possibly the world, to sign-up for the challenge and collect 5km runs. The team with the most Parkruns after a certain period of time, say a 6- or 12-month period, will win the challenge. The challenge has to be over a prolonged period of time to get people exercising consistently. The is not a one-off thing; the real objective is to get people exercising regularly and to stay exercising longterm. 

Some of you will be saying, but I can’t run. I know there are some of you who can’t run but then there will be others who are simply unfit. For you, I would suggest starting the ‘couch to 5K’ programme that is designed to get you off the couch and running 5km in just nine weeks. The plan involves three runs a week with a rest day in between and a different running schedule each week. The NHS is promoting this using an app developed by the BBC, the programme or app builds you up gradually with a mix of running and walking.


 The good thing about making this initiative into a challenge is that it will build teams (people are competitive) and it will increase your participation. 
Let’s do it! 

Thank you. 

 CoI: I am a runner, albeit one with a failing right hip

DIY SlideShare site

Dear Blog Reader


I must apologise; my SlideShare site has been disabled by LinkedIn. I have been told that many of my slides include copyrighted material. Strictly speaking, this is correct. However, LinkedIn doesn’t understand that academics often use each other’s materials for teaching/academic purposes without getting specific agreements in place to address copyright issues. I have therefore been forced to move off the SlideShare platform and to improvise. I have had to set-up my own site (Prof G’s Slides) to allow you access to my slides after my talks. I hope my DIY tech solution works. 



The following is my first presentation that has been uploaded on the site: Copenhagen 23-Aug-2018


Thanks

Prof G

P.S. The great tragedy is that all the blog posts that are dependent on embedded material from SlideShare will be spoilt. If there is one lesson to learn from this experience is that you shouldn’t rely on one technology platform.