Tuesday, 1 December 2015

Barts MS Advisory group…reporting! #BartsSpeak

Welcome to the first Bart MS Advisory Group blog post! 

To introduce ourselves, we are a small team of MSers given the challenge of working with Barts MS Team to look at new and existing issues from the patients point of view, making sure that your voice is always understood and heard. To date we have been given challenges by the Team although looking ahead our aim is also to get feedback from yourselves on issues that we can take up on your behalf. 

At our most recent meeting, our fourth, there were 4 of us out of a possible 5 which is about average attendance. We are a mix of MSers, between us we have both RRMS and PPMS with all the problems and challenges that go with these conditions, and while we are good colleagues now, we only met each other at the first meeting just over 12 months ago. 

Like yourselves, we have ongoing commitments, either family or employment or both but we try to make time to attend the quarterly meetings. As you may expect we have quite strong opinions on a number of subjects and we are more than happy to add our two pennies worth, however we do of course allow each other time to make their points!

We have worked with Alison (our gallant chairperson...!) on a number of subjects, including for example redesigning the format of the annual Barts MS Research Day which hopefully many of you attend. Last year our suggestion to have a more relaxed format whereby the doctors and clinicians sat with attendees answering their questions on a more personal basis, was implemented and feedback received was that this approach was popular. Looking ahead, one of our current projects is reviewing how those with MS can better prepare for either their annual check up or importantly provide support for those newly diagnosed with this condition. This is an ongoing project and we are looking for our suggestions and recommendations to be finalised soon and put into practice in 2016.

You can find out more about some of the projects that we’ve been involved with in and what the scope of our work is in our information tab.

All of what we do is ensuring your voice is heard - please have a look at what we are doing and let us know if there are any other issues or challenges we can help with 


The Barts MS Advisory Group.

Unrelated blogger Comments December

Sometimes you want to ask something that is related to the threads this is the place for you.

Copaxone another mechanism

Cortical excitability changes over time in progressive multiple sclerosis.Ayache SS, Créange A, Farhat WH, Zouari HG, Lesage C, Palm U, Abdellaoui M, Lefaucheur JP. Funct Neurol. 2015  25:1-8. [Epub ahead of print]

OBJECTIVE:Glatiramer acetate (GA; Copaxone), a disease-modifying therapy for multiple sclerosis (MS), promotes development of anti-inflammatory (M2, type II) monocytes that can direct differentiation of regulatory T cells. We investigated the innate immune signaling pathways that participate in GA-mediated M2 monocyte polarization.
METHODS: Monocytes were isolated from myeloid differentiation primary response gene 88 (MyD88)-deficient, Toll-IL-1 receptor domain-containing adaptor inducing interferon (IFN)-β (TRIF)-deficient, IFN-α/β receptor subunit 1 (IFNAR1)-deficient, and wild-type (WT) mice and human peripheral blood. GA-treated monocytes were stimulated with Toll-like receptor ligands, then evaluated for activation of kinases and transcription factors involved in innate immunity, and secretion of proinflammatory cytokines. GA-treated mice were evaluated for cytokine secretion and susceptibility to experimental autoimmune encephalomyelitis.
RESULTS: GA-mediated inhibition of proinflammatory cytokine production by monocytes occurred independently of MyD88 and nuclear factor-κB, but was blocked by TRIF deficiency. Furthermore, GA did not provide clinical benefit in TRIF-deficient mice. GA inhibited activation of p38 mitogen-activated protein kinase, an upstream regulator of activating transcription factor (ATF)-2, and c-Jun N-terminal kinase 1, which regulates IFN regulatory factor 3 (IRF3). Consequently, nuclear translocation of ATF-2 and IRF3, components of the IFN-β enhanceosome, was impaired. Consistent with these observations, GA inhibited production of IFN-β in vivo in WT mice, but did not modulate proinflammatory cytokine production by monocytes from IFNAR1-deficient mice.
CONCLUSION: Our results demonstrate that GA inhibits the type I IFN pathway in M2 polarization of monocytes independently of MyD88, providing an important mechanism connecting innate and adaptive immune modulation in GA therapy and valuable insight regarding its potential use with other MS treatments.

We like to publish the mechanism of action of drugs and copaxone gets a new one month on month. This time it inhibits an interferon pathway of inhibitory macrophage pathway and inhibited pro-inflammatory proteins it also inhibited beta interferon production in mice...but would this not be anti-inflammatory if beta interferon works....so long peeps can't wait for the next one

PoliticalSpeak & BrainHealth: financial incentives to reduce specialist referrals

New incentives will increase the delay in being diagnosed with MS. #PoliticalSpeak #BrainHealth #MSBlog

"I read last week's BMJ and was horrified to read that GP practices are being given money to cut the number of referrals they make to specialists. A FOI investigation by the GP rag Pulse has uncovered that several clinical commissioning groups (CCGs) are offering GP practices large payments for keeping within targets for specialist outpatient referrals. Some of the incentive schemes are even counting 2-week cancer referrals as part of the target. Wow; imagine if you have symptoms suggestive of a cancer and your GP would rather claim the cash for their practice than refer you for investigations. This is simply outrageous!"

"What are the implications for MSers? As part of our 'Brain Health - Time Matter in MS' policy document we highlight the long referral delays from GPs to a neurologist for patients presenting with neurological symptoms compatible with MS. These incentive schemes will simply increase this delay. We really need to oppose these schemes. I can't see who benefits from asking GPs to reduce their specialist referral rates by paying them a cash incentives, but the central NHS bean counters. What is happening to the NHS?"

"The above incentive scheme is no different to our 70:30 high-cost drug rule. Our high-cost drug prescribing is being capped based on last year's prescribing. If we under prescribe we will be given a 30% of our underprescribing as cashback by NHS England. If we over prescribe NHS England will only cover 70% of the costs and our Trust, or Hospital, will have to find the money from their existing budgets to cover the 30% shortfall. Therefore there is a cash incentive at a Trust level to encourage us to under prescribe, and a stick to stop us starting new patients on treatment. We are very concerned about this policy as it penalises new patients and any new treatments coming online. Patients started on DMTs tend to stay on treatment therefore the costs increase over time, therefore any new patients started on treatment will add to the total and we will have to get our Trust to find money to pay for the 30% penalty. As our Trust is in deficit where are they going to find the money? May be NHS England are asking us to negotiate a 30% discount with the Pharma companies who are selling these products or they are asking us to innovate. Could we badge off-label prescribing as innovation and save the NHS money that way?"

"Austerity is really putting clinicians in a very difficult position. We are meant to treat our patients based on the best evidence available. These policies are asking us to make financial decisions about referring, or not referring, prescribing high-cost DMTs, or not prescribing high-cost DMTs, to save the NHS money. Who is my primary responsibility to; my patients or the NHS? I am beginning to buy into the neoliberal conspiracy theory; the Tories want to run the NHS into the ground with the hope that we the public demand a solution. They will then propose a private funding, or insurance, solution to fund healthcare for those who can afford it. Am I wrong? Or am I am just being paranoid?"

Alex Matthews-King. A moral dilemma: GP practices offered incentives to cut urgent referrals. Pulse 1 October 2015.


..... Such schemes are not new – in 2012 former GPC chair Dr Laurence Buckman reported PCTs’ schemes to the GMC, declaring: ‘Taking money from patient care and pocketing it for reducing something you do is wrong.’......

..... But CCGs are now also increasingly using them to cut costs, in the shadow of a £22bn black hole in NHS finances......

..... The GPC says many of these schemes are ‘ethically questionable’ and Pulse has learned that the GMC looked into at least one of them to see if it is contrary to the guidance set out in Good Medical Practice.....

..... However, it is the inclusion of urgent cancer referrals that has caused most controversy. NHS Lambeth CCG is offering payments for practices moving towards the average 2014/15 CCG referral rate per 1,000 patients......

...... But it is the public perception of these payments to reduce referrals that is of particular concern, in the wake of the furore over NHS England’s ‘cash for diagnoses’ drive last year, whereby practices were paid £55 for each newly diagnosed case of dementia......

Venous thromboembolism you don't say!

Multiple sclerosis increases the risk of venous thromboembolism: a nationwide cohort analysis

Wei-Sheng Chung, Cheng-Li Lin, Tzung-Chang Tsai, Wu-Huei Hsu and Chia-Hung Kao

European Journal of Clinical Investigation

Article first published online: 27 NOV 2015, DOI: 10.1111/eci.12502


The purpose of this study was to evaluate the effects of multiple sclerosis (MS) on the risk of venous thromboembolism (VTE) development.

We identified patients diagnosed with MS in Taiwan between 1998 and 2010 using the National Health Insurance Research Database and the Catastrophic Illness Patient Database (RCIPD). Each MS patient was frequency matched to 4 controls according to age, sex and the year of MS registration to the RCIPD. Patients with a history of VTE and incomplete information of age and sex were excluded. All patients were followed up from the index year until VTE diagnosis, loss to follow-up or the end of 2010. We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) of VTE in the MS and comparison cohorts using Cox proportional hazards regression models.

We followed up 1238 MS patients and 4952 comparison patients for approximately 6437 and 27 595 person-years, respectively. After adjusting for age, sex and comorbidities, the MS patients exhibited a 6·87-fold increased risk of VTE compared with the control patients. Women with MS were associated with an 11·1-fold increased risk of VTE development compared with the non-MS women (95% CI: 2·70–45·5). The MS patients aged < 50 years exhibited a 14·8-fold increased risk of developing VTE compared with age-matched patients in the comparison cohort (95% CI: 2·99–73·4). The risk of VTE development increased with the duration of hospitalization stay.

MS patients are associated with significantly greater risk of developing VTE compared with non-MS patients.

I recall a blogger asking about venous thomboembolism (VTE) risk in MS in the distant past, and they're in luck as today there is study published on exactly this topic; albeit in Taiwan. PwMS in Taiwan between 1998-2010 versus controls were 6.87 times more likely to have a VTE (with a further increase to 11.1 times more likely if you were female) even after adjusting for age, gender and co-morbidities (i.e. other co-existing illnesses such as heart disease or diabetes). 
A similar study performed in the UK found this figure to 2.14 higher in PwMS (although this study did not adjust for co-morbidities; Ramagopalan SV et al. Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: record-linkage study, BMC Med 2011;9:1), whilst a Danish study identified that there was a risk but the overall risk was low (Christensen S et al. Multiple Sclerosis and risk of venous thromboembolism: a population-based cohort study, Neuroepidemiology 2012;38:76-83).
Not surprisingly the risk of VTE increases with the length of hospital stay (associated with immobility) and reduced limb mobility, particularly in the legs resulting in venous stasis and increased risk of thrombosis. The figure below alludes to the contribution of disability to the risk of VTE.
Figure: Kaplan-Meier plot mapping the probability of being free of VTE for PwMS (dashed line) and without MS (solid line) over time.
Currently in the UK PwMS are not started on VTE prevention agents upon hospital admission for their MS alone. These lines of discussion also raise the question of what about at home? Moreover, anti-embolic stockings now are no longer routinely recommended, so this leaves conservative measures such as early and effective mobilisation, hydration and subject education before and during inpatient stay, and on discharge.