Thursday, 19 January 2017

#ClinicSpeak & #BrainHealth: online rating sites - good or bad?

Is your MS centre ready for open online reviews? #ClinicSpeak #BrainHealth

For the last year I have been promoting the concept of an msAdvisor for the field to help promote the 'Brain Health: Time Matters' policy document and to get adoption of the MS management principles we are promoting as part of the initiative. Therefore the following perspective piece in this week's NEJM is very timely. It is clear the US healthcare system is way ahead of the game with several online rating sites already established. The article describes some of the many issues linked to online rating sites. My personal opinion is that they need to offer disease-specific ratings. Why? Each disease has specific issues that are unique to that disease. In the case of MS this could for example refer to the use of MRI, or not, to monitor the disease, allowing pwMS access to their own results, etc. I don't want the msAdvisor to be used to 'name and shame' people and centres, but rather as a tool to nudge or encourage the adoption of 'best practice' as defined by peers. The app could also be used to educate and help pwMS self-manage their disease. The tool could also be used as an information resource. The app would have the ability to keep reviews anonymous and for a 'neutral moderator'.


What I would like to hear from you is the msAdvisor an app you would use? Do you think we should develop it? If, yes what content should we include in it?




Vivian Lee. Transparency and Trust — Online Patient Reviews of Physicians. N Engl J Med 2017; 376:197-199.

....... After years of academic debate over the role and value of patient-satisfaction scores and reviews of health care providers,1,2 Yelp, the online powerhouse of documenting customer satisfaction, is forcing the issue. With more than 102 million customer reviews to date, 6% of them in the health care arena, Yelp easily dwarfs longer-standing commercial physician-review sites such as Healthgrades and Vitals....

....... A recent analysis used natural language processing tools to evaluate 17,000 Yelp reviews of 1352 hospitals and showed that they revealed information similar to that covered by 7 of the 11 categories of patient satisfaction included in the Hospital Consumer Assessment of Healthcare Providers and Systems survey (HCAHPS), along with 12 categories not included in the HCAHPS, such as costs, billing, and scheduling......

....... I believe patient reviews and feedback can serve three main goals. First, like the peer-level perspectives on consumer products and services posted on Amazon, TripAdvisor, and Yelp, reviews of physicians or hospitals can help patients make more informed consumer decisions. Publicly available reviews can help address information asymmetry in the health care market and increase patients’ confidence in their own decisions. Collectively, by making clear their preference for higher-performing systems, patients can become a market force driving quality and value in health care.....

...... Second, patient reviews offer clinicians valuable performance feedback for learning and improving, both individually and across a system. Receptivity to performance feedback, which depends heavily on physicians’ acceptance of the data’s validity, facilitates a culture of continuous learning and patient-centeredness......

....... Third, health care systems and physicians who voluntarily share patient-review data visibly foster a spirit of trust with patients and the community. Patient reviews offer the opportunity to improve health care delivery while strengthening the provider–patient relationship......

Digesting Science in Bournemouth

I had the great pleasure of travelling to Bournemouth last weekend to help the Dorset MS Service deliver a Digesting Science event for their families.


The event was held in the incredibly well kitted out MS Society Osborne Centre in local West Parley. I was very impressed at the facilities in this centre and the programme of events that the branch runs to support people with and affected by MS. 

The families that took part enjoyed learning about how MS affects eye-sight, bladder function, walking, how we treat MS and how to prevent MS. The hands on activities were enjoyed by children aged between 5 and 12 years old and the feedback on the event was hugely positive. Thank you to everyone who came along to make the morning such a success.



Special thanks to Rod Slip for having us and Claire Williams and her colleagues from the Dorset MS Team based at Poole Hospital Michelle, Kirsty and Hannah for such great organisation ….and for the cake!

If you would like to host a Digesting Science event, please get in touch: booking (at) digestingscience.co.uk The kits can be sent to you free of charge and we can support you to deliver the event in your area.

The next London based Digesting Science event is in Whitechapel on Saturday the 25th March. More information here and how to book. 

Wednesday, 18 January 2017

#ClinicSpeak: DMF and abnormal liver function

Do you know what your last liver function test showed? If not you should. #ClinicSpeak #MSBlog

Do you know what your latest liver function tests showed? If you have MS and are on a DMT you are likely to be having regular blood tests and one of them are LFTs or liver function tests. The paper below highlights that a rare complication  (<1 in 1,000) of dimethyl fumarate (DMF) may be abnormal LFTs. These tend to occur early and be mild and transient and not associated with severe liver injury. 

I personally don't recall seeing this in any of my patients. I thing to point out is that we shouldn't always blame the DMT when we see abnormal LFTs; in my experience they are usually due to another factor, for example excess alcohol intake, concomitant medications or food supplements. In addition, it appears that pwMS can develop autoimmune hepatitis that is a second autoimmune disease. I have seen three such patients, one on interferon-beta, one on glatiramer acetate and another on natalizumab. I have also seen several patients with MS develop viral hepatitis. What we tend to do if we detect abnormal LFTs is to withdraw the drug to see if the results normalise and then rechallenge. If the rechallenge results in the LFTs becoming abnormal then we can be more confident that it is the cause of the problem. 


The message from this post is that you need to engage with your own monitoring; don't be shy to ask about your blood results. 

Muñoz et al. Liver injury associated with dimethyl fumarate in multiple sclerosis patients. Mult Scler. 2017 Jan 1:1352458516688351

BACKGROUND: In pre-approval trials, there was an increased incidence of mild, transient elevations of liver aminotransferases in study subjects treated with dimethyl fumarate (DMF).



OBJECTIVE/METHODS: To evaluate post-marketing cases of drug-induced liver injury associated with DMF.

RESULTS: We identified 14 post-marketing cases of clinically significant liver injury. Findings included newly elevated serum liver aminotransferase and bilirubin levels that developed as early as a few days after the first dose of DMF. The pattern of liver injury was primarily hepatocellular. No cases resulted in liver failure.

CONCLUSION: Health professionals should be alerted to possible serious liver injury in patients receiving DMF.

CoI: multiple

Out of the Frying Pan into the Fire?

Selmaj K, Barkhof F, Belova AN, Wolf C, van den Tweel ER, Oberyé JJ, Mulder R, Egging DF, Koper NP, Cohen JA; GATE study group. Switching from branded to generic glatiramer acetate: 15-month GATE trial extension results.Mult Scler. 2017 Jan 1:1352458516688956.

BACKGROUND:

Open-label 15-month follow-up of the double-blind, placebo-controlled Glatiramer Acetate clinical Trial to assess Equivalence with Copaxone® (GATE) trial.

OBJECTIVE:

To evaluate efficacy, safety, and tolerability of prolonged generic glatiramer acetate (GTR) treatment and to evaluate efficacy, safety, and tolerability of switching from brand glatiramer acetate (GA) to GTR treatment.

METHODS:

A total of 729 patients received GTR 20 mg/mL daily. Safety was assessed at months 12, 15, 18, 21, and 24 and Expanded Disability Status Scale and magnetic resonance imaging (MRI) scans at months 12, 18, and 24. The presence of glatiramer anti-drug antibodies (ADAs) was tested at baseline and months 1, 3, 6, 9, 12, 18, and 24.

RESULTS:

The mean number of gadolinium-enhancing lesions in the GTR/GTR and GA/GTR groups was similar at months 12, 18, and 24. The change in other MRI parameters was also similar in the GTR/GTR and GA/GTR groups. The annualized relapse rate (ARR) did not differ between the GTR/GTR and GA/GTR groups, 0.21 and 0.24, respectively. The incidence, spectrum, and severity of reported adverse events did not differ between the GTR/GTR and GA/GTR groups. Glatiramer ADA titers were similar in the GTR/GTR and GA/GTR groups.

CONCLUSION:

Efficacy and safety of GTR is maintained over 2 years. Additionally, switching from GA to GTR is safe and well tolerated.

Eventually the Patent Life of Glatiramer acetate has run out, its amazing that the lawyers have kept it going considering that the entity was created in the 1970s.
So whilst Teva has been busy convincing people to switch from once a day injection to thre times a week with abit more, the competitors have been making generic mixes to muscle in of the profits. This study looks at the turn coats that have turned their back on the branded version to go for the generic version because they don't like paying money for cardboard, which is the box it comes in, OK it may not come in carboard but  hope you get the point. That they are the same thing in differnt packaging. However the originals will have it that the genrics are not the same and have done the experiments to show cytokine X or Y responds differntly between the cheap stuff. Anyway proof is in the pudding and so what happens in real life?
In reality nothing happened it was a seamless switch and when you look at the annualised relapse rates of 0.2 (1 releapse every 5 years). I may have to eat some words and say it is not that different from that shown with alemtuzumab in the trials which was 0.18, is it great however when you look at how i think it works then it isn't in the same league as alemtuzumab.
So maybe not out of the pan into the fire but from the badda bing to the bosch-whallop. 

So will you swop?
I guess many will say if it ain't broken don't fix it and brand loyalty is what the companies hope for.

Alemtuzumab inhibits T regs again.

Pant AB, Wang Y, Mielcarz DW, Kasper EJ, Telesford KM, Mishra M, Haque A, Smith J, Kasper LH, Begum-Haque S. Alteration of CD39+Foxp3+ CD4 T cell and cytokine levels in EAE/MS following anti-CD52 treatment. J Neuroimmunol. 2016 Dec 21. pii: S0165-5728(16)30286-7.

While examining the therapeutic value of anti-CD52 antibody against EAE/MS, we identified a unique subset of CD39+ Tregs in repopulating GALT tissues, a major lymphoid reservoir, which was accompanied by amelioration of disease. Furthermore, anti-CD52 treatment leads to increased expression of BDNF, IL-10, and SMAD3 in the brains of EAE mice. This condition is associated with suppression of IL-17, a critical inflammatory factor in EAE/MS progression. Additionally, we found elevated levels of CD4+CD39+ Tregs in PBMCs of RRMS patients treated with humanized anti-CD52 mAb. Thus, anti-CD52 can affect multiple immune mediated pathways involved in the pathogenesis of EAE/MS.


This paper looked and found an increase in a Treg population that goes into the Gut Associated Lymphoid Tissue (GALT). This is reported to increase in MS, so is this a reason why MS goes away?

Time will tell...however are we being sold a curve ball?...

Does it tell us about why alemtuzumab works or does it tell us how alemtuzumab causes autoimmune side effects.