Barts-MS rose-tinted-odometer: ★★★★★ (seeing purple; a Sunday morning purple)
Could you imagine if we made the treatment target in MS a cure? This is a very contentious issue; however, based on the current dogma that MS is an autoimmune disease driven by rogue autoreactive cells we should have the ability to either purge these cells from the body or imprison them via tolerance mechanisms indefinitely. Do you agree?
After being taken to task on using the C-word (see blog post 19-May-21) I am relieved that you readers condone the use of the word. This means we can now hopefully refine the definition of an MS cure, look to see if any pwMS treated with immune reconstitution therapies (IRTs) fulfil the definition of an MS cure. Please be aware that an MS cure doesn’t mean the restoration of lost neurological function; you can be cured of further autoimmune attacks on the nervous system, but the damage that is already done won’t necessarily be repaired as part of the cure. This is why we need to at least offer IRTs as early as possible in the course of the disease, which is why we need to have the option of using IRTs first-line. I hope this makes sense.
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.
Survey Disclaimer: No personal identifiers will be collected as part of these surveys unless otherwise stated. By completing these surveys you are consenting to the data you provide being analysed by Professor Giovannoni and his collaborators. Results of these surveys will be presented on this blog and maybe submitted for publication.
Thank you for completing yesterday’s poll. It is quite clear that you, our blog readers, want us to prioritise the following changes to the way we prescribe DMTs in the NHS. The most important priority is for pwMS to access immune reconstitution therapies (alemtuzumab, cladribine and HSCT) early as 1st-line therapies for active MS. Please note if you have rapidly evolving severe MS (RES) you can be treated with alemtuzumab and cladribine first-line, but outside of this very small group of patients, we can’t prescribe IRTs first-line. For more information on RES vs. active MS classification system and its implications for some pwMS, I would recommend you read ‘Watchful Waiting 2‘.
The next priority is access to natalizumab, a very high efficacy therapy, as 1st-line therapy for active MS. At the moment the only agent that covers this broad bracket is ocrelizumab. My reading into this is that if you don’t have RES but just active MS, you would like more choice and not simply have one high-efficacy option first-line.
The third priority relates to treating advanced or progressive MS, i.e. getting rid of the stopping criteria when people with MS reach EDSS 7.0 (wheelchair) and liberalise the prescribing of ocrelizumab and siponimod for primary progressive and secondary progressive MS, respectively. My interpretation of the latter is that you want to challenge the active vs. inactive progressive MS dichotomy.
Finally, treating asymptomatic MS and liberalising the use of platform therapies and fingolimod is not a priority. This worries me because as we move into an area of testing and exploring the induction-maintenance paradigm we need to be able to use platform therapies 2nd- and 3rd-line. I have made the point before that pwMS are not going to be able to remain on anti-CD20 therapies indefinitely because of the potential risks; for example, as your immunoglobulin levels drop and serious infections increase the benefit-risk balance changes. Therefore, we are going to need to test de-escalation approaches to derisk anti-CD20 and other chronic immunosuppressive treatments. This is the rationale of the iTeri study that I have proposed doing; i.e. induction with ocrelizumab or rituximab followed by maintenance with teriflunomide.
I would be interested to know if you are surprised by the poll’s findings?
I wonder if the Australian neurologists chuckle when they read this sort of blog post? They have no restrictions on how they treat MS and can use any DMT, including AHSCT, as they and their patients see fit. If only the NHS would allow us to practice in this way 🙁
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.
Barts-MS rose-tinted-odometer: ★★★★★ (seeing green; the green shoots of spring)
I was asked yesterday if I could have a wish and change three things in relation to the prescribing of MS DMTs in the NHS, which ones would I prioritise? Can you help? The idea is to make changes based on how we would want to manage MS proactively as possible and to give pwMS choice. The idea of this exercise is to get an idea of what is most important to the MS community given our current restrictions. Please note you can add your own priority at the bottom of the survey if you don’t feel satisfied with the limited selection provided.
The poll will take 3 seconds to complete and you are welcome to complete it if you live outside of the UK and/or are not someone with MS.
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.
After my blog post on potentially curing MS, I have been criticised by several people in the MS community for using the C-word. Do you agree? Have I raised false hopes?
I am of the opinion that unless we define what an MS cure looks like and then look for it we will never find it; i.e. the holy grail will always elude us. Another factor is that if we are really curing some people with MS with IRTs (immune reconstitution therapies) shouldn’t the MS community know about it? Wouldn’t that shift the risk:benefit ratio in favour of the benefits? Just maybe more people will choose to be treated with AHSCT, alemtuzumab or cladribine if there was a small chance of a cure. One commentator has suggested I use the term long-term remission rather than cure. The problem with long-term remission is that it doesn’t quite have the same emotional impact as a cure.
One of my patients with both MS and breast cancer was bowled over by her breast cancer consultant who said to her, “we have an 80% chance of curing you of your breast cancer”. Saying “we have an 80% chance of putting your breast cancer into long-term remission”, just doesn’t quite cut the mustard.
If you have the time can you please respond to this three-question survey, which will take you literally 15 seconds to complete? Thank you.
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.
If you don’t measure it you can’t change it. The fact that the UK was performing so poorly relative to other EU countries on the EMSP’s MS barometer was one of the reasons why I got into MS politics and helped put together the ‘Brain Health: Time Matters’ policy document.
In 2015, despite being the second wealthiest nation in Europe, the UK was in the bottom three of the EU league table in terms of prescribing DMTs, particularly high efficacy DMTs. Fortunately, things have improved slightly and we are now mid-table, but way below average (see figure below). Is this good enough? NO! The under-treatment of MS in the UK will obviously be linked to poorer outcomes, i.e. more disabled, more unemployed, more demented and smaller-brained people living with MS in the UK compared to comparator countries above us in the league table.
I am often asked if I had MS what country would I want to live in to have my MS treated. I rarely hesitate, it has to be either Sweden or Australia. Why? Because these two countries have universal healthcare policies and they both allow their MSologists to manage MS how they see fit. This is why both Sweden and Australia have about 70% of their patients on high efficacy DMTs. There are also no Swedish or Australian DMT police standing over their consultants saying you can only use drug X or refer this patient for HSCT if they fulfil these criteria. Yes, the Swedish and Australian healthcare systems trust their consultants to get on with the job they have been trained to do, i.e. to treat MS with very little central interference.
Some conservative neurologists argue that both Sweden and Australia are over-treating MS and by doing so they are exposing people who will eventually turn out to have benign MS to unnecessary risks associated with high-efficacy DMTs. Please remember that only a small minority of people with MS turn out to have benign MS. Therefore the non-Swedish-Australian or conservative approach to treating MS puts the majority of pwMS at risk of under-treating their disease to protect the minority. This could be referred to as the anti-vaxxer approach to treating MS; let’s not treat MS aggressively so that we harm nobody.
In comparison, the Swedes and Australians will be exposing a small proportion of their benign MS patients to unnecessary risks to offer the majority the protection their brains need from under-treated MS. This is like the public health approach to vaccines; let’s treat MS aggressively to improve the outcome of the majority and by doing this we are prepared to accept some collateral damage in terms of adverse events.
Another argument that is often used against the active-treatment approach of the Swedes and Australians is that if everyone ends up on high efficacy therapy what do you do next? I counter this argument by saying these patients are probably on high-efficacy treatment because they need to be on high-efficacy treatment.
The other issue that needs discussion is the variation within countries and even within MS centres. When I first saw the DMT prescribing data from Blueteq, the NHS high-cost drug database, I was appalled. There is such wide variation between UK centres in terms of DMT prescribing behaviour that even NHS England are concerned. It can’t be right that some MS centres have 80% of their patients on high-efficacy DMTs and other centres have less than 20% of their patients on these treatments.
Some UK centres don’t prescribe some classes of DMT. In fact, the latter may be illegal. There is in fact an act of parliament stating that NHS centres have to offer NICE approved therapies. Therefore refusing to offer and treat someone who is eligible for say alemtuzumab could be legally challenged. As a result of this variation, we started the Raising-the-Bar initiative to address variation in MS service provision across the UK. A national audit is the keystone of this initiative and all MS centres will be able to see how they are performing relative to the national average and other regional centres. Hopefully, this national audit data will act as the catalyst to stop the scourge of undertreated MS in the UK.
The audit data will be so granular that it has the potential to expose outliers at the individual consultant level. For example, if one consultant has no patients treated with alemtuzumab, cladribine or HSCT and his/her colleagues in the same centre has substantial patients on these treatments it may trigger a review of that consultant’s fitness to practice as an MSologist. I am sure many neurologists will be appalled by this suggestion, but this type of individual performance review is widely used in surgical specialities and will arrive in neurology soon. In fact, it already has in some countries. If you are an epilepsy expert and are not referring a certain proportion of your patients for epilepsy surgery every year then you will have your fitness to practice as an epilepsy expert questioned. Epileptologists have agreed that a small number of patients with drug-resistant epilepsy will benefit from surgery and if one of their colleagues is not identifying and referring these patients for surgery then they are not practising according to international standards.
My dream is that every MS centre in the UK will not only have access to their audit data for quality and performance review but patients will be able to access this data on a publically available website so that that can ascertain how conservative or active their MS centre is at treating MS. My vision is to have an MS-Advisor app modelled on TripAdvisor that will allow patients to review and provide feedback on their MS service. There is nothing like a bad review to change behaviour.
So if you have MS and think your disease is being under-treated you should ask your HCP for their audit figures, i.e. how many of their patients are on DMTs, how many are on high efficacy DMTs and how do their figures compare to their colleagues and to the national average. If they are not prepared to provide you with this data you can always put in a freedom of information request.
Yes, the Raising-the-Bar national audit is going to make it hard for participating centres to not participate in the audit and to ignore their own audit data. The objectives of the RtB initiative is to raise the standard of MS services for pwMS, to reduce the under-treatment of MS and to ultimately improve MS outcomes and the quality of life of our NHS patients.
So when I ask has your neurologist flipped; I mean has your neurologist adopted a more active approach to treating MS. Are they flipping the pyramid?
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.
This week I was asked by two patients independently of each other who had delayed access to treatment if this could explain why they now have secondary progressive MS. In parallel, I had a meeting with a friend yesterday, who was the primary driver of the 21-year interferon-beta follow-up survival study (see below), who said that to him this was the most convincing data to support the early treatment paradigm in MS.
In summary, trial subjects in the pivotal original interferon-beta-1b study who had delayed access to interferon-beta-1b because they were randomised to receive placebo were 50% less likely to be alive at 21 years compared to study subjects with early access to treatment. Was this due to the impact of interferon-beta on MS or some other confounding factor? In the 69 pwMS for whom information on the relationship of death to MS was available 78% were judged to have died from MS-related complications. This tells us that IFN-beta increases your life expectancy by reducing MS-related complications that can cause death in the future. The latter include swallowing problems that are associated with aspiration pneumonia, urinary dysfunction that lead to urinary tract infections and septicaemia, immobility and pressure sores, falls and fractures, to name the most common causes of premature death in pwMS.
You need to remember that this was a placebo-controlled study and the subjects on placebo were switched to active treatment after 3 years, with some subjects having to wait up to 5 years (trial recruitment was from June 1988 to May 1990; with placebo-treated subjects given free commercial supply as of October 1993). What this study shows is that delaying access to treatment by just 3-5 years has a major impact on long-term outcomes.
Please note that apart from suicide most pwMS get to EDSS 10 or death as a result of MS by passing through EDSS stages 2, 4, 6 (stick), 8 (wheelchair/bed). So my answer to these patients was yes your delayed access to DMTs in the early 2000s is almost certainly the reason why you now have secondary progressive MS and are disabled.
Please note this there is now overwhelming evidence from other controlled trials and real-life data to support the interferon-beta 21-year mortality data. In fact, the debate about early treatment and MS outcomes is so widely accepted that it has now has shifted from early access to DMTs to early access to highly effective DMTs, i.e. flipping the pyramid. It is clear that pwMS who are treated with more effective DMTs first-line do so much better than those who are asked to wait (watchful waiting) or are escalated gradually up the DMT ladder (slow escalation). This is why, despite us designing the early treat-2-target NEDA trial, our centre couldn’t participate in the trial comparing maintenance-escalation vs. flipping the pyramid. We simply don’t have equipoise; in other words, we don’t think it is ethical to randomise patients to a treatment arm that is less effective and hence will result in poorer long-term outcomes and probably poorer long-term survival. This is why it is our current clinical practice to offer pwMS who have active disease and are eligible under the NHSE algorithm for treatment access to highly effective treatment first-line.
We are so convinced about the early treatment that we are doing the ATTACK-MS trial, which will explore if access to the highly effective treatment natalizumab, 2 months earlier than what happens in routine practice, improves outcomes. Yes, we will be randomising patients before they have finished the MS diagnostic pathway to treatment vs. delayed access, i.e. only 2 months later when they have a definitive diagnosis of MS. We anticipate that the ATTACK-MS study will activate the MS community to treat the MS brain as we treat the brain in stroke. Forget about years, every day, week or month for the untreated MS brain is like every second, minute or hour in the non-perfused brain of a person having a stroke.
Yes, in MS time really is brain and by delaying access to DMTs and potentially highly effective DMTs is unacceptable in the modern era of treating MS. The data below not only supports the maxim “Time is Brain” but “Time is Life“, why would anyone wait to treat someone with active MS knowing this?
Objective: To examine the effects of interferon beta (IFNβ)-1b on all-cause mortality over 21 years in the cohort of 372 patients who participated in the pivotal randomized clinical trial (RCT), retaining (in the analysis) the original randomized treatment-assignments.
Methods: For this randomized long-term cohort study, the primary outcome, defined before data collection, was the comparison of all-cause mortality between the IFNβ-1b 250 μg and placebo groups from the time of randomization through the entire 21-year follow-up interval (intention-to-treat, log-rank test for Kaplan-Meier survival curves). All other survival outcomes were secondary.
Results: After a median of 21.1 years from RCT enrollment, 98.4%(366 of 372) of patients were identified, and, of these, 81 deaths were recorded (22.1% [81 of 366]). Patients originally randomly assigned to IFNβ-1b 250 μg showed a significant reduction in all-cause mortality over the 21-year period compared with placebo (p = 0.0173), with a hazard ratio of 0.532 (95% confidence interval 0.314-0.902). The hazard rate of death at long-term follow-up by Kaplan-Meier estimates was reduced by 46.8% among IFNβ-1b 250 μg-treated patients (46.0% among IFNβ-1b 50 μg-treated patients) compared with placebo. Baseline variables did not influence the observed treatment effect.
Conclusions: There was a significant survival advantage in this cohort of patients receiving early IFNβ-1b treatment at either dose compared with placebo. Near-complete ascertainment, together with confirmatory findings from both active treatment groups, strengthens the evidence for an IFNβ-1b benefit on all-cause mortality.
Classification of evidence: This study provides Class III evidence that early treatment with IFNβ-1b is associated with prolonged survival in initially treatment-naive patients with relapsing-remitting multiple sclerosis.
Objectives: Compared with controls, multiple sclerosis (MS) patients die, on average, 7–14 years prematurely. Previously, we reported that, 21 years after their participation in the pivotal randomised, controlled trial (RCT) of interferon β-1b, mortality was reduced by 46–47% in the two groups who received active therapy during the RCT. To determine whether the excessive deaths observed in placebo-treated patients was due to MS-related causes, we analysed the causes-of-death (CODs) in these three, randomised, patient cohorts.
Design: Long-term follow-up (LTF) of the pivotal RCT of interferon β-1b.
Setting: Eleven North American MS-centres participated.
Participants: In the original RCT, 372 patients participated, of whom 366 (98.4%) were identified after a median of 21.1 years from RCT enrolment.
Interventions: Using multiple information sources, we attempted to establish COD and its relationship to MS in deceased patients.
Primary outcome: An independent adjudication committee, masked to treatment assignment and using prespecified criteria, determined the likely CODs and their MS relationships.
Results: Among the 366 MS patients included in this LTF study, 81 deaths were recorded. Mean age-at-death was 51.7 (±8.7) years. COD, MS relationship, or both were determined for 88% of deaths (71/81). Patients were assigned to one of nine COD categories: cardiovascular disease/stroke; cancer; pulmonary infections; sepsis; accidents; suicide; death due to MS; other known CODs; and unknown COD. Of the 69 patients for whom information on the relationship of death to MS was available, 78.3% (54/69) were adjudicated to be MS related. Patients randomised to receive placebo during the RCT (compared with patients receiving active treatment) experienced an excessive number of MS-related deaths.
Conclusions: In this long-term, randomised, cohort study, MS patients receiving placebo during the RCT experienced greater all-cause mortality compared to those on active treatment. The excessive mortality in the original placebo group was largely from MS-related causes, especially, MS-related pulmonary infections.
If you are interested you can watch my presentation from last year’s ACTRIMS-ECTRIMS meeting during which I make the case for flipping the pyramid. Please note the ATTACK-MS study paradigm takes this concept of time is brain even further. Do you agree with this approach?
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.
Someone asked yesterday why did I give George Jelinek’s book ‘Overcoming MS’ a positive review and yet we don’t promote it openly on the blog? Very simple our policy is not to advertise commercial products on this blog and if we promoted OMS then what about the other MS-related lifestyle and wellness programmes? I am still pissed off with myself for not making it clear that I don’t support the OMS diet. Yes, I support the principles of OMS in terms of lifestyle interventions, but I simply can’t support the OMS diet. The diet is simply not evidence-based. In fact, there is no ‘MS diet’ that is evidence-based so anyone who claims their diet needs to be followed to treat MS can’t be doing this from any position of authority.
So why did I give OMS a positive review?
The principles that underpin OMS are scientifically sound, but a lot of them are not evidence-based, i.e. they are not supported by randomised controlled trials. Some of the lifestyle recommendations in OMS are also quite extreme and hence are very difficult to follow. I view George Jelinek as the lifestyle-wellness equivalent of the ‘ultra-distance marathon runner’. You don’t need to run ultra-distance marathons to derive the benefits from running, some people do just fine on subscribing to and running regular 5km park runs. It is horses for courses. I think the important messages in OMS and other lifestyle-wellness programmes are:
Lifestyle-wellness interventions are not alternative medicine, but complementary; i.e. you need to do them in addition to taking for example DMTs.
Lifestyle-wellness interventions need to be personalised. In particular, they need to be affordable, compatible with your culture, your worldview and your belief systems.
Lifestyle-wellness interventions fall on a continuum they are not all or nothing phenomenon. You can engage with some aspects of a programme and not others. In other words, doing something is better than doing nothing.
You need to be self-motivated to stick to a healthy lifestyle and wellness programme. I think herein lies the secret of the success of the programmes. Setting goals and sticking to them is self-rewarding. The rewards centres in the brain make you feel good about yourself and motivate you further. The downside is that when you slip you have a sense of self-loathing and guilt. These emotions are part of the package; they are the regulatory or negative emotional feedback loop. My personal opinion is that slipping occasionally is fine, but you need to earn the off-days.
Lifestyle wellness programmes take a holistic view of the management of the disease. Saying this is easy, but it is very difficult to set up a lifestyle-wellness service in the NHS. What is the evidence and how do we show that the programme will be cost-saving to justify the investment? In addition, adherence rates to lifestyle-wellness interventions are very poor. This is a conundrum that challenges HCPs and behavioural psychologists but is not an insurmountable obstacle. There are examples that when politicians, HCPs and the general public get behind a national lifestyle and wellness programme it can work. A good example of this is what Finland has done at a population level over the last 20 years.
Lifestyle-wellness interventions should be adopted by everyone regardless of whether, or not, you have MS. This is why we set up the Barts-MS Brain Health challenge and why I started the Think Brain Health initiative. Getting HCPs to personally engage with their own Brain Health would make them think about their patients’ health. In addition, patients are more likely to take the advice seriously from a Brain Healthy HCP than from an HCP who is unhealthy. If you smoke, are unfit, overweight and eat badly how can you tell your patients to stop smoking, to start exercising, change their diet and lose weight? Unless you walk the talk you are not credible.
Most lifestyle-wellness interventions are common sense with an evidence base from outside the field of MS. However, like any other field, the lifestyle-wellness space is full of quacks and charlatans so be careful to accept anything at face value. Do your research and ask questions. For example, what is the evidence that you need to follow a gluten-free diet? Plant-based diet? Etc? Unless you have documented gluten sensitivity there is no evidence. Similarly, the war on fats, and saturated fats, is built on a very poor evidence base. It is clear that fats, and saturated fats, are not bad for you if eaten in moderation. I am sure more evidence will emerge around this issue in the next few years. It is clear that at present processed and ultra-processed foods are in the dog house and justifiably so. I am adamant that what you eat needs to be compatible with your culture which is why I wrote a piece on Medium about Diet as a Philosophy.
Please let common sense rule the day and if you find you like, and enjoy, walking or running 1 km or 5 km, who knows you may gradually extend your walks and runs to 10 km, half-marathons, marathons and possibly ultra-marathons. The intensity and distance are not that important it is getting started and staying committed that is important.
So I yes I have gone lukewarm on OMS because it is not the be-all and end-all of MS management. I have also heard from many independent sources that George Jelinek promotes it openly as an alternative option for the management of MS. I have seen many tragic examples of patients under my care who are now very disabled as a result of using lifestyle and wellness programmes as an alternative option to DMTs to manage their MS. OMS should only ever be used as a complementary MS management tool.
Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the position of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.
I did a post a few weeks ago about the secondary malignancy risk associated with longterm continuous immunosuppression and included a survey. The following are the results of the survey, which are quite disturbing. It is clear that a significant number of readers of this blog, although aware of the secondary cancer risk, are not been given standardised information about cancer risk and cancer screening. This is another piece of work that needs to be done and done well. Some of the comments are quite telling as well, including some personal critcism.
Who is interested in working on an evidence-based calculator of secondary malignancy risk in relation to MS DMTs? It will at least need to include the following variables:
Gender
Ethnicity
Age
Family history
Environmental risk factors, e.g. sun exposure, HPV vaccination status
Type of immunosuppression, i.e. continuous (anti-CD20, S1P modulators) vs. short-term (alemtuzumab, cladribine)
Intensity of immunosuppression
Duration of immunosuppression
Prior treatment history
Prior cancer history
I suspect many health and life insurance companies have actuarial data on this already and could potentially create a risk calculator using real-life data.
Are you lonely? Have you lost a loved on during COVID-19? Have you lost your job or had to reduce your income because of COVID-19? Can you make ends meet at the end of the month? Are you worried about your future? How is your relationship with your partner? Are you depressed? Anxious? Are you sleeping well? Are you drinking too much alcohol? Are you feeling guilty? Self-loathing? Failed ambitions? …..
These sorts of questions rarely come up in a standard MSology consultation because most classically trained HCPs working in a secondary or tertiary care environment haven’t been trained to deal with what we refer to as the Social Determinants of Health (SDoH). However, it is clear the SDoH have an outsized impact on health outcomes, which is likely to include MS outcomes. This is why we launched our #ThinkSocial campaign several years ago and have started several activities to see if there is anything we can do to help tackle the SDoH.
A story: Recently one of my patients chastised me for telling her off for her poor diet, which consisted mainly of bread. She lives alone, which may explain why she eats so poorly. She has marmite or jam on toast for breakfast, a sandwich for lunch and if she feels hungry another piece of toast for dinner…..
What should Prof G do to manage this patient?….. find out.
I can clearly see the cynics saying ‘focus on what you are trained to do and leave the SDoH to general practice, social care and the charitable sector’. Yes and no. Yes, it is easy to say this is not my responsibility, but when you are trying to do your best medically to improve MS outcomes only to get trumped by the SDoH it makes it look like your service is failing. Our patient population in the east end of London is one of the most deprived populations in England. When we recently analysed deprivation data from HES (hospital episode statistics) the only area worse off than us in England was Liverpool. On the other end of the scale were Cambridge and Oxford. So if we compared outcomes of the MS patient populations in Liverpool and east London and note they are doing worse than pwMS living in Oxford and Cambridge it may not have anything to do with our MS and other services, but simply represent levels of deprivation and its associated poorer outcomes.
How SDoH result in poor outcomes is likely to be due to the effects of chronic stress on the brain. Stress is a well-defined biological or physiological response of the body. Stress results in high levels of so-called stress hormones. These stress hormones have a direct and negative effect on the brain and other organ systems, which causes them to age prematurely and malfunction. Ask anyone who is stressed and they will tell they don’t feel well. Stressed people and stressed populations are more forgetful, more tired, have poorer sleep and tend to engage in unhealthy behaviours (smoking, alcohol, poor diet, sedentary) and have much higher mental health problems (depression, anxiety, addiction, suicide). In general, pwMS are more stressed and the reasons for this are not only obvious but potentially modifiable.
The main stress hormone is cortisol. Cortisol works via glucocorticoid receptors, which are found all over the body including the hippocampus, amygdala and frontal cortex, three brain regions involved in memory and emotions. Chronic stress is associated with reduced volume and malfunction of these areas. In pwMS, these areas may already be damaged from MS lesions, which increases the MS brain’s vulnerability to chronic stress. So if you want to improve MS outcomes you can’t ignore the SDoH and chronic stress. Do you agree?
This is why I have been promoting the marginal gains philosophy to the management of MS, which is based on Sir David Brailsford approach to competitive cycling and is the reason why the British cycling teams has been so dominant in the last two decades.
“The whole principle came from the idea that if you broke down everything you could think of that goes into riding a bike, and then improved it by 1%, you will get a significant increase when you put them all together.”
Sir David Brailsford
“If we break down everything we can think of that goes into improving MS outcomes, and then improving each one by 1%, we will get a significant increase when we put them all together.”
Prof. Gavin Giovannoni
So when we launched our ‘no patient left behind’ motto at the first MS Academy ‘Raising-the-Bar’ meeting to address variation and inequalities in access to MS healthcare in the UK we included a workstream to tackle the SDoH. How we do this is currently being defined, but we have an ambitious programme of work. Whatever happens, we will need to involve the whole MS community, which includes readers of this blog. So if you have any ideas to tackle the SDoH please share them with us.
For the last five decades, science has managed to delineate the mechanisms by which stress hormones can impact on the human brain. Receptors for glucocorticoids are found in the hippocampus, amygdala and frontal cortex, three brain regions involved in memory processing and emotional regulation. Studies have shown that chronic exposure to stress is associated with reduced volume of the hippocampus and that chronic stress can modulate volumes of both the amygdala and frontal cortex, suggesting neurotoxic effects of stress hormones on the brain. Yet, other studies report that exposure to early adversity and/or familial/social stressors can increase vulnerability to stress in adulthood. Models have been recently developed to describe the roles that neurotoxic and vulnerability effects can have on the developing brain. These models suggest that developing early stress interventions could potentially counteract the effects of chronic stress on the brain and results going along with this hypothesis are summarized.
Did you know that as of September 2020, only 54.1% of the public in the UK and 42.5% in the USA would ‘definitely’ accept a COVID-19 vaccine to protect themselves?
I sincerely hope these figures are wrong and have changed substantially since September 2020. Why? These vaccine acceptance rates are lower than the proportion of vaccinated people required to achieve the anticipated herd immunity levels for SARS-CoV-2. Interestingly, in the study that produced these disturbing figures (see below), a higher proportion of individuals in both the UK and the USA would ‘definitely’ vaccinate to protect family, friends and at-risk groups, suggesting that effective altruistic messaging may be required to boost vaccine uptake. This is why I have always taken the line that vaccination is not necessarily about you, but society and in the case of COVID-19 vulnerable people.
It is clear that misinformation/disinformation campaigns on social media have a remarkable effect on individual behaviour and lead to vaccine hesitancy. It is clear from recent political events across the globe that we need to move beyond the ‘post-truth era’ and reclaim the moral high ground and to start trusting our experts again. We have put in place institutions, such as our drug regulatory agencies, to protect the public. The fact that they have the necessary ‘deep expertise’ and have vetted and licensed several COVID-19 vaccines makes them safe to use at a population level. So my message is simple if you are offered a chance to be vaccinated with one of the COVID-19 vaccines take up the offer ASAP. The vaccine will not only protect you but your fellow citizens as well. In fact, you will be saving lives.
The more unvaccinated people there are. particularly unvaccinated immunosuppressed individuals, the more opportunity the virus has to mutate and develop immune escape variants, i.e. new virus strains that are resistant to immunity from the current vaccines. These new strains will extend the pandemic, killed more people and make the economic impact of the pandemic worse. Based on this alone several commentators make the point that we all have a duty to be vaccinated.
What this study also shows that there is more to simply fighting the virus to end this pandemic; we have a propaganda war on our hands fighting both misinformation and disinformation about the safety and efficacy of COVID-19 vaccinations. I think we all have a responsibility to join this battle. Everyone needs to say something like ‘I am a vaccinee and proud of it’ or ‘I have done my duty and have had the vaccine’. I am not a marketeer or advertising creative, but if you could come up with some catchy slogans we could then all push them out on social media and start a campaign. What do you think?
The widespread acceptance of a vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will be the next major step in fighting the coronavirus disease 2019 (COVID-19) pandemic, but achieving high uptake will be a challenge and maybe impeded by online misinformation. To inform successful vaccination campaigns, we conducted a randomized controlled trial in the UK and the USA to quantify how exposure to online misinformation around COVID-19 vaccines affects the intent to vaccinate to protect oneself or others. Here we show that in both countries—as of September 2020—fewer people would ‘definitely’ take a vaccine than is likely required for herd immunity, and that, relative to factual information, recent misinformation induced a decline in the intent of 6.2 percentage points (95th percentile interval 3.9 to 8.5) in the UK and 6.4 percentage points (95th percentile interval 4.0 to 8.8) in the USA among those who stated that they would definitely accept a vaccine. We also find that some sociodemographic groups are differentially impacted by exposure to misinformation. Finally, we show that scientific-sounding misinformation is more strongly associated with declines in vaccination intent.
