Yesterday I was told to “Keep on Rockin” so today a musical post before ProfG gets back
You would argue there is a big difference, but when you hear the drummer jokes, maybe there is not a lot of difference. Is there?
How many neurologists (Drummers) does it take to change a lightbulb?
Five: One to screw the bulb in, and four to talk about how much better
Gavin Giovannoni (Neil Peart) could’ve done it.
What do you do if you accidentally run over a neurologist (Drummer)?
Sadly its this
What’s the difference between a Neurologist (Drummer) and a artifical Intelligence Neurologist (Drum) Machine?
You only have to punch the information into the machine once!
We are in 2020 and we are still having this debate about whether we should treat early and effectively or not. Do we learn from past errors?
The people who have most to gain from effective disease control are children with MS. They repair the best, so get MS under control ASAP to reap maximum rewards. Whilst I appreciate that parents are worried about their children, is the “softly-softly” approach in their best interest, when we know what happens in adults?
Indeed, I was rather horrified that “At the limits” conference debate where the neurologists voted overwhelmingly for putting Children on inferior products in trials. I guess it should not surprise me, because Neurologists must be like drummers and they have thought that it is OK to put adults on inferior products, to help with the marketing, even when the data smacks them in the face that it is not OK.
A trial is planned of escalation verses highly effective treatments. What will it show in a few years?, I wonder?
Long term effect of delayed treatment on disability in patients with paediatric onset multiple sclerosis: A prospective Danish cohort study. Kopp TI, Blinkenberg M, Petersen T, Sorensen PS, Magyari M. Mult Scler Relat Disord. 2020 Jan 17;40:101956.
BACKGROUND: A consensus of early treatment with disease-modifying therapies (DMT) in multiple sclerosis (MS) has been reached based on several observational and experimental studies in adults. However, paediatric onset (PO)MS appears phenotypically different from adult onset MS, characterized by increased relapse rate and pronounced radiological activity on MRI. The objective of this study was to investigate the long-term consequences of delayed treatment start in POMS on disability in a real-world, population-based setting.
METHODS: Based on prospectively collected data from The Danish Multiple Sclerosis Registry, we defined a cohort of MS patients with onset before the age of 18 years, who were born in 1980 or later, and started treatment with a DMT between 1998 and 2018. The POMS cohort was stratified according to treatment start within 2 years of onset (N = 140) or later (N = 151). Annualised relapse rate in each study group was compared using a negative binomial regression; and Cox proportional hazard model was used to estimate hazard ratios (HR) of time to sustained Expanded Disability Status Scale (EDSS) score 4, 6-month confirmed EDSS worsening and 6-month confirmed EDSS improvement, respectively, according to disease duration.
RESULTS: The POMS cohort had a total median follow-up time of 7.7 years (interquartile range 4.6-11.6). There was no association between risk of relapses in patients with delayed treatment start compared to earlier treatment start. Patients starting on a DMT later than 2 years after onset had a 2.52-fold increased risk of reaching sustained EDSS 4 compared to those starting within 2 years of onset (HR=2.52, 95% confidence interval (CI)=1.01-6.34). For every year increment from onset to start of first DMT, the risk of reaching sustained EDSS 4 increased by 17% (HR=1.17, 95% CI=1.05-1.30). In line with this, the risk of reaching confirmed EDSS worsening was increased by 44% compared to those starting earlier, although not statistically significant (HR=1.44, 95% CI=0.95-2.19). Starting on a DMT later was associated with 61% decreased chance of confirmed EDSS improvement compared to those starting earlier (HR=0.39, 95% CI=0.26-0.59). For every year increment from onset to starting DMT, the risk of confirmed EDSS improvement decreased by 10% (HR=0.90, 95% CI=0.84-0.96).
CONCLUSIONS: Delayed treatment start in this POMS cohort was associated with shorter time to reach sustained EDSS 4 and confirmed EDSS worsening, and decreased chance of reaching confirmed EDSS improvement, and thus support early treatment start in POMS patients.
This was a perspective study meaning that they followed people up with those being treated early and those getting later treatment.
Next up. How does fingolimod work?
Reading this next paper…the focus is T cells and T cells subsets. Whilst B cells are depleted that’s as far as it goes and so the memory and other B cell subsets get ignored. So the message is not filtering through in this instance and oppertunities are being missed by ignoring the B cells. T regs are depleted, in fact virtually every thing is deleted. A point is made that effector memory cells are less affected, but this is the dominant T cell subset that enters the CNS in MS, so if they were not affected you would not expect fingolimod to work. This would argue against the importance of T cells,. However there is a peripheral depletion even in the effector memory T cell subset.
Hjorth M, Dandu N, Mellergård J (2020) Treatment effects of fingolimod in multiple sclerosis: Selective changes in peripheral blood lymphocyte subsets. PLoS ONE 15(2): e0228380. https://doi.org/10.1371/journal.pone.0228380
BACKGROUND:Treatment with fingolimod reduces inflammation in multiple sclerosis (MS) by inhibiting lymphocyte egress from lymph nodes. We aimed to map, in detail, the alterations in peripheral blood lymphocyte subpopulations in relation to clinical outcome in MS patients treated with fingolimod
METHODS:Paired blood samples from relapsing-remitting MS patients (n = 19) were collected before and after one year of treatment with fingolimod (0.5 mg/day). Absolute counts and relative proportions of a broad set of T- B- and NK-cell subsets were analyzed by flow cytometry. Blood samples from 18 healthy controls were used for baseline comparisons.
RESULTS:Treatment with fingolimod markedly decreased the absolute numbers of all major lymphocyte subsets, except for NK cells. The reduction was most pronounced within the T helper (Th) and B cell populations (p<0.001). By phenotyping differentiation status of T cells, dramatic reductions within the naïve and central memory (CM) cell populations were found (p<0.001), while a less pronounced reduction was observed among effector memory (EM) cells (p<0.001). The numbers of regulatory T cells (Tregs) were also decreased (p<0.001), but to a lesser extent than other T cell populations, resulting in a relative preservation of Tregs with a memory phenotype (p = 0.002).
CONCLUSIONS:Our results confirm that fingolimod therapy markedly reduces lymphocyte counts in peripheral blood of MS patients. Subgroup analysis of T cells showed that naïve and CM Th cells were the most profoundly affected and that memory Tregs were relatively preserved.
So really, is there a difference between neurologists and drummers, sometimes it worries me. How many times do they need to be told?
OK I won’t do myself any favours with this post….but I don’t write the academic literature, I just comment on it
However it is important that we get MS under control as soon as possible
Personal and societal costs of multiple sclerosis in the UK: A population-based MS Registry study.Nicholas RS, Heaven ML, Middleton RM, Chevli M, Pulikottil-Jacob R, Jones KH, Ford DV. Mult Scler J Exp Transl Clin. 2020 Jan 22;6(1):2055217320901727.
OBJECTIVES:To investigate through survey and data linkage, healthcare resource use and costs (except drugs), including who bears the cost, of multiple sclerosis in the United Kingdom by disease severity and type.
METHODS:The United Kingdom Multiple Sclerosis Register deployed a cost of illness survey, completed by people with multiple sclerosis and linked this with data within the United Kingdom Multiple Sclerosis Register and from their hospital records. Resource consumption was categorised as being medical or non-medical and costed by National Health Service and social services estimates for 2018.
RESULTS:We calculated £509,003 in non-medical costs over a year and £435,488 in medical costs generated over 3 months. People with multiple sclerosis reported self-funding 75% of non-medical costs with non-medical interventions having long-term potential benefits. Costs increased with disability as measured by patient-reported Expanded Disability Status Score and Multiple Sclerosis Impact Scale, with Multiple Sclerosis Impact Scale physical being a more powerful predictor of costs than the patient-reported Expanded Disability Status Score. Two distinct groups were identified: medical and non-medical interventions (n = 138); and medical interventions only (n = 399). The medical and non-medical group reported increased disease severity and reduced employment but incurred 80% more medical costs per person than the medical-only group.
CONCLUSIONS:The importance of disability in driving costs is illustrated with balance between medical and non-medical costs consistent with the United Kingdom health environment. People with multiple sclerosis and their families fund a considerable proportion of non-medical costs but non-medical interventions with longer term impact could affect future medical costs.
Have a read its open access and if you live in the UK consider signing up to the MS Register.