Sunday, 26 March 2017

#ClinicSpeak & NeuroSpeak: MS drugs and your mouth

How common are oral side effect in pwMS on medication? #ClinicSpeak #NeuroSpeak #MSBlog

Most pwMS are on poly-pharmacy (multiple prescribed medications) both DMTs and symptomatic treatments. The review article below highlights the problem. It identified 18 oral side effects with dryness of the mouth (xerostomia) being the most common, followed by abnormal taste (dysgeusia), difficulty swallowing (dysphagia), mouth ulceration and sinusitis. The anti-cholinergic drugs were the commonest cause of dry mouth, whilst immunosuppressants resulted in more infection related side-effects.

How common is the problem? In my experience, apart from dry mouth, this is not a major problem. As I don't routinely ask about mouth problems I maybe missing this issue. I you are a medication and have a side effect involving the mouth can you please let us know and we can then set-up a survey to see how common it is? Thank you. 

Cockburn et al. Managing the oral side effects of medications used to treat multiple sclerosis. Aust Dent J. 2017 Mar 9. doi: 10.1111/adj.12510.

BACKGROUND: Many medications used to manage multiple sclerosis (MS) affect oral health. This review aimed to identify the oral side effects of the current drugs recommended in Australia to treat MS and make dental practitioners aware of the range of symptoms.

METHODS: The Australian Therapeutic Guidelines and the Australian Medicines Handbook were searched for medications used to treat MS. For each medication, the generic name, class, route of administration, dosage and drug company reported side-effects were extracted from the online Monthly Index of Medical Specialties (MIMs) database. Meyler's Side Effect of Drugs Encyclopaedia was used to identify any additional oral adverse reactions to medications used to treat MS.

RESULTS: Fourteen drugs were identified for the treatment of MS progression and 13 drugs for the treatment of MS symptoms. For these medications, 18 oral side effects were documented: xerostomia was the most common, followed by dysgeusia, dysphagia, mouth ulceration and sinusitis. Anticholinergic drugs caused xerostomia while immunosuppressants resulted in more infection related side-effects.

CONCLUSIONS: Dental practitioners should be aware of the range of symptoms likely to be reported by this population. Clinicians are encouraged to continue providing dental care for their patients who develop MS and refer complex cases to specialists.

The New Publication Paradigm..Money down the toilet

Historically we would publish our papers in scientific journals. We would donate our work for free and sometimes even pay a page charge to do this.

We would assign copyright to the publishers. They may give you 50-100 reprints for free to give away.

Librabries would take a subscription to the journals and academics could get access to the journals via their library.

The Internet occurred and people have instant access and they don't go to libraries anymore.

However, the People who have the ears of Government and the Research Councils said that work paid for by the Public should be accessible to the Public so they generated the concept of "open access" 

The journals laughed not only could they get you to pay publication fees, get libraries to pay for subscriptions but now they could also charge and open access fee. This can be $1,500-$5,000 per article to get this "Gold open access" so they become accessible right away.

This cost is often only a fraction of the actual cost to do the work

The research councils (NIH equivalent) would pay the open access fee, but now the research councils give a set amount to the universities to pay for this. They give less than the actual cost, so universities loose money or they stop funding this and make you do "Green Open access" where the article is embargoed for some time before a copy of the accepted paper (not the published type set version) is available.

Charities said yes do this but won't pay the fees.

Journals had another laugh, because what they did was set up new open access journals. 

They are common in cases of high impact journals where people send their best work to. The top journal turns the paper down but says that you can submit to their open access journal  for quick reviewing and then pay the open access fee "ker ching".

Importantly it allowed for a load of chancers to set up loads of rubbish open-access journals. You submit a paper to them and then pay for the pleasure of publishing. Ten papers could be $20,000 and all you have to do is house the pdf document on a server as there is no printed version and the work can be typeset in the middle or far East using computer software to increase your profit margin. 
Ker-ching, Ker-ching. They don't even pay to put the work on "Pubmed" so no one is aware of paper. 

They invite you submit (we get loads of these each day) and them charge you. Like mugs some people do this. They are desperate to fill their pages and publish any old c**p. 

They also think of loads of titles to make new journal sound like existing good ones so the "Journal of Immunology" could become a new Immunology Journal or International Journal of Immunology.

Today, I got a request to submit to the "Annals of multiple sclerosis and related disorder". 

Wonder what the editors of "Anals of Neurology" and "Multiple Sclerosis and related Disorders think about i?

What next "Multiple Sclerosis and related Disorders journal"

Is this a waste of money?

Saturday, 25 March 2017

#CarerSpeak & #ClinicSpeak: child carers

Austerity Britain and the army of child carers. What should we do? #ClinicSpeak #MSBlog #CarerSpeak

#CarerSpeak is the new label or #tag for posts of direct relevance to MS carers

"Dear Professor Giovannoni, Can you help? I am 14 and I care for my Mum. Her multiple sclerosis is getting worse and I now have to spend most of my time looking after her. I have to prepare her tablets for her each day and remind her to take them. I have started to send her text reminders from school otherwise she forgets to take her lunchtime tablets. When I get home from school I often have to clean-up the mess she has made. My father left us when I was 9 and my aunts and uncles live near Liverpool. My mother does not want help and wants us to cope. Mum is unable to walk down the stairs and has taken to hopping down the stairs on her bum. The other day she slipped and slid down the stairs on her back. She got a carpet burn and now has a row of sores over her spine. I worry about leaving her at home when I go to school."

The scenario above is just one of many I have encountered over the years as a MS expert. There is literally an army of child carers out there looking after disabled parents with chronic diseases. As austerity bites, and social care budgets get squeezed, the number of children in this position will increase. The study below highlights the issue; compared with children of ‘healthy’ parents, children of a parent with MS report all of the issues raised in the case above; they have lower life satisfaction and are less likely to be happy (positive affect). As predicted, better adjustment in children of a parent with MS was related to higher levels of social support, lower stress, greater reliance on approach coping strategies (problem solving, seeking support and acceptance) and less reliance on avoidant coping (wishful thinking and denial). 

JLS met up with young carers who look after relatives suffering from multiple sclerosis.

We realise there is a massive unmet need out there to help adolescents of pwMS and are in the discussion phase of designing a course specifically targeting teenagers of pwMS. If you have been engaged with a course like this before we would be interested to hear from you; what was good and bad? Any suggestions are welcome. If you have MS and teenage children would you enrol them on a course to learn more about MS and more importantly would they attend? 

Pakenham & Bursnall. Relations between social support, appraisal and coping and both positive and negative outcomes for children of a parent with multiple sclerosis and comparisons with children of healthy parents. Clinical Rehabilitation  2006 Vol 20, Issue 8, pp. 709 - 723.

Objective: To examine adjustment in children of a parent with multiple sclerosis within a stress and coping framework and compare them with those who have ‘healthy’ parents.

Subjects: A total of 193 participants between 10 and 25 years completed questionnaires; 48 youngsters who had a parent with multiple sclerosis and 145 youngsters who reported that they did not have a parent with an illness or disability.

Method: A questionnaire survey methodology was used. Variable sets included caregiving context (e.g. additional parental illness, family responsibilities, parental functional impairment, choice in helping), social support (network size, satisfaction), stress appraisal, coping (problem solving, seeking support, acceptance, wishful thinking, denial), and positive (life satisfaction, positive affect, benefits) and negative (distress, health) adjustment outcomes.

Results: Caregiving context variables significantly correlated with poorer adjustment in children of a parent with multiple sclerosis included additional parental illness, higher family responsibilities, parental functional impairment and unpredictability of the parent's multiple sclerosis, and less choice in helping. As predicted, better adjustment in children of a parent with multiple sclerosis was related to higher levels of social support, lower stress appraisals, greater reliance on approach coping strategies (problem solving, seeking support and acceptance) and less reliance on avoidant coping (wishful thinking and denial). Compared with children of ‘healthy’ parents, children of a parent with multiple sclerosis reported greater family responsibilities, less reliance on problem solving and seeking social support coping, higher somatization and lower life satisfaction and positive affect.

Conclusions: Findings delineate the key impacts of young caregiving and support a stress and coping model of adjustment in children of a parent with multiple sclerosis.

MS lymphocytes making new myelin

El Behi M, Sanson C, Bachelin C, Guillot-Noël L, Fransson J, Stankoff B, Maillart E, Sarrazin N, Guillemot V, Abdi H, Cournu-Rebeix I, Fontaine B, Zujovic V.
Brain. 2017. doi: 10.1093/brain/awx008. [Epub ahead of print]

One major challenge in multiple sclerosis is to understand the cellular and molecular mechanisms leading to disease severity progression. The recently demonstrated correlation between disease severity and remyelination emphasizes the importance of identifying factors leading to a favourable outcome. Why remyelination fails or succeeds in multiple sclerosis patients remains largely unknown, mainly because remyelination has never been studied within a humanized pathological context that would recapitulate major events in plaque formation such as infiltration of inflammatory cells. 

Therefore, we developed a new paradigm by grafting healthy donor or multiple sclerosis patient lymphocytes in the demyelinated lesion of nude mice spinal cord. We show that lymphocytes play a major role in remyelination whose efficacy is significantly decreased in mice grafted with multiple sclerosis lymphocytes compared to those grafted with healthy donors lymphocytes. 

Mechanistically, we demonstrated in vitro that lymphocyte-derived mediators influenced differentiation of oligodendrocyte precursor cells through a crosstalk with microglial cells. Among mice grafted with lymphocytes from different patients, we observed diverse remyelination patterns reproducing for the first time the heterogeneity observed in multiple sclerosis patients. 

Comparing lymphocyte secretory profile from patients exhibiting high and low remyelination ability, we identified novel molecules involved in oligodendrocyte precursor cell differentiation and validated CCL19 as a target to improve remyelination. 

Specifically, exogenous CCL19 abolished oligodendrocyte precursor cell differentiation observed in patients with high remyelination pattern. Multiple sclerosis lymphocytes exhibit intrinsic capacities to coordinate myelin repair and further investigation on patients with high remyelination capacities will provide new pro-regenerative strategies.

Last week we had the story that Treg cells produced a molecule that promoted remyelination and this week we have something similar but they take human cells and inject them into a nude mouse.

A nude mouse is a mutant mouse that does not make hair, but they also do not make T cells and so they can't reject human cells that are transplanted into the mouse. They injected a toxin to make demyelinated lesion as the toxin kills oligodendrocytes.

They then inject human cells, which they have activated,into the mice and find that they promote repair. As the mice were not genetically engineered e.g. to be MHC compatible, the T cells would not be able to talk to the lymphocytes. They go a test bleed from the eye by putting a needle into the retro-orbital sinus, which was banned (as their are alternatives) in the UK about 25 years ago, to check the cells are still present. They find there is variability in the repair potential, They found that MS blood cells demonstrate that multiple sclerosis lymphocytes did not interfere with OPC recruitment, but impeded OPC differentiation. This had an effect of via microglial cells and when they looked at 72 secreted molecule they found differences in three IL-7 and IL-20 which are immune growth factors and CCL-19 which is a protein that attracts cells called a chemokine. The latter was lower from people with MS. 
Taking advantage of our innovative in vivo model to study the role of human lymphocytes in remyelination, we demonstrated a strong implication of adaptive immune cells in this repair process. In particular, multiple sclerosis patient lymphocytes induce detrimental environment for the repair process notably by directing MIGs toward a pro-inflammatory M1 phenotype. Strikingly, the molecular cues needed for a successful remyelination were different when considering multiple sclerosis patient and healthy donor lymphocytes

Friday, 24 March 2017

#PoliticalSpeak: impact or lack of impact

Why has academia become so bureaucratic? #PoliticalSpeak #MSBlog

Life as an academic is becoming increasingly complicated and frustrating; I spend an extraordinary amount of time doing administration. We have been asked to start preparing for the next REF, which is likely to be in 2020, and need your help. 

In the UK academic institutions are assessed every 6-7 years as part of the Research Excellence Framework exercise or REF. As part of this assessment we have to provide 'impact case studies' demonstrating the impact of our research on wider society. Impact is defined as ‘an effect on, change or benefit to the economy, society, culture, public policy or services, health, the environment or quality of life, beyond academia’.

We had an informal discussion yesterday about what academic activities we are engaged in have impact and how can we show impact. If we have to submit an impact statement next REF we will need to be able to demonstrate how we are having impact with the relevant metrics, etc. As you are quite close to our activities you could help us prioritise our efforts so that we can focus on the academic activities that are most likely to succeed. This exercise will also help focus our minds as a group. Thank you. 

CoI: multiple