Author: Rachael Hansford

ECTRIMS 2016

Conference details: 14-17 September, 2016; London, UK
News source: ECTRIMS congress organisers, and company press releases
First published online: 13/10/16


ECTRIMS and EAN join forces to formulate the first European MS treatment guidelines 

The Clinical Guideline on the pharmacological management of people with Multiple Sclerosis was developed jointly by ECTRIMS and European Academy of Neurology (EAN).

This is the largest European collaboration to consider therapeutic guidelines for MS and have been developed following the GRADE methodology that implies a sequential assessment of the quality of evidence, followed by judgment about the balance between desirable and undesirable effects, and subsequent decision about the strength of a recommendation. The main recommendations presented by Susana Otero (Multiple Sclerosis Center of Catalonia, Barcelona, Spain) are based on the latest evidence available worldwide and have been agreed by a large working group of key MS experts across Europe, as well as patient representatives from MS advocacy groups, such as EMSP and MSIF.

New guidelines for patients with clinically isolated syndrome

One of the key consensus statements which came out of the recent ECTRIMS/EAN meeting concerns patients with clinically isolated syndrome. These are patients that have had only one neurological incident and do not fulfil current diagnostic criteria for MS.

Based on the available evidence and mindful that MS is a progressive disease and delay in starting disease modifying treatments can have long-term consequences, the steering committee has recommended that CIS patients with visible abnormalities on MRI scans should receive disease modifying drugs (DMD) prior to diagnosis.

Consensus on treating patients with established MS

Research advances in recent decades mean that clinicians now have a large choice of effective drugs for the treatment of patient with confirmed MS. However, few of those drugs have been compared directly and the trial populations are too heterogeneous to draw direct comparisons.

The ECTRIMS/EAN steering group have therefore recommended that choosing the right drug for an individual patients with established MS should remain in the hands of the treating neurologist taking into account the patient’s history, their age, their level of disease activity, their comorbidities and, very importantly, their personal preferences.  Drug choices may also depend on availability within different healthcare systems and different licencing regulations across Europe.

The experts within the committee hope that on-going and future trials may provide further clarity and recommendations will be made as time goes on, when the evidence on which to base them becomes available.

Guidelines on monitoring the effectiveness of MS treatments

The steering group did agree that regardless of the drug chosen, regular monitoring should take place to investigate whether that treatment is having an impact on the disease.

The timing of monitoring will depend on many factors and will differ between countries but the ideal is for patients to have an MRI scan about 12 months after starting a drug treatment. If there is a poor treatment response, then the treatment strategy should be to move on to a more aggressive drug

Susana Otero, Multiple Sclerosis Center of Catalonia, Barcelona, Spain

Guidelines for treating patients with Primary Progressive MS (PPMS)

PPMS is diagnosed in around 10-15% of MS patients and currently has no disease modifying pharmacological treatment. Ocrelizumab, a potential treatment for PPMS, has recently be tested in a phase 3 clinical trial and results have been very encouraging, but the drug is currently still under review by the European Medicines Agency.

The ECTRIMS/EAN steering group has recommended that PPMS patients should receive Ocrelizumab and this consensus statement will be included in the published guideline – but only if the drug is licenced before the publication date, explains Otero.


ECF Satellite Symposium at ECTRIMS attended by 1600 MS professionals

The European Charcot Foundation welcomed more than 1600 MS professionals at its Satellite Symposium held during the congress.

The symposium “the role of B-cells in MS pathogenesis” chaired by Prof. Giancarlo Comi, addressed the following topics:

1.Why antibody therapy in MS (Prof. H.P. Hartung – Germany)

2.Update of the role of b-cells follicles in MS (Prof. R. Reynolds – UK)

3.Anti b-cells therapy in MS and related disorders (Prof. G. Comi – Italy)

Find out more about the European Charcot Foundation annual meeting in November at http://www.charcot-ms.org/en/24rd-annual-meeting-1/


Global research is focusing on better therapies for all stages of multiple sclerosis

The final late-breaking session session at ECTRIMS included news on the progress that is being made in determining the most effective drug treatments for the relapsing remitting stage of MS and in developing much-needed novel therapies for the secondary, progressive stage.

Alemtuzumab: using real world clinical data to find out how it compares to other MS drugs

One of the key presentations reported important results comparing alemtuzumab with beta interferon, fingolimod and natalizumab. All four drugs are licensed for the treatment of patients in the relapsing-remitting stage of MS, in which episodes of new neurological symptoms are followed by at least partial recovery.

Research over the last two decades has revolutionised therapy for MS patients and disease-modifying drugs are now often used as soon as a diagnosis is made in order to slow disease progression and delay the onset of disability.

New drugs have been developed regularly and individual treatments have been licensed when they have proved effective compared with placebo or one established treatment. A new drug does not need to be tested against all available treatments for MS, so the efficacy of already licensed drugs is difficult to compare. A comparison over different clinical trials is compromised by the fact that individual trials may differ significantly in their design and may be undertaken in very different groups of people.

The answer to this problem is to gather data on how all these drugs perform after they are approved for use in the clinic. MSBase (https://www.msbase.org) is a registry that aims to collect clinical outcome data from people with MS in real-world clinical practice. By collecting sufficiently large amounts of such data, it is possible to statistically match the different patient populations and allows comparing the efficacy of different treatments in routine clinical practice.

Tomas Kalincik (University of Melbourne, Australia), on behalf of the MSBase collaboration, presented results from a study comparing the efficacy of alemtuzumab against three other treatments (fingolimod, beta interferon and natalizumab), all of which have been shown previously to reduce the frequency of MS relapses.

The real world data confirmed trial results and showed that alemtuzumab was better at suppressing relapses compared to beta interferon and fingolimod, and was similarly effective compared to natalizumab. Although patients treated with natalizumab showed slightly more clinical improvement than those treated with alemtuzumab, the rates of disability progression did not appear to differ significantly between the two drugs.

These findings demonstrate that real-world data obtained as part of clinical practice can be used to answer questions about the relative efficacy of treatments that would be difficult and prohibitively expensive to answer in dedicated treatment trials. This is important for people with MS, and the clinicians who advise them, to enable well-informed choices between treatments based on their relative efficacy and the risk of side effects.

More news about new treatments for secondary progressive MS

During the late break session, details were given about the EXPAND trial of the novel therapy siponimod (BAF312).

Many people with MS who have initially had relapses and remission eventually develop progressive disability that is not the result of relapses. This is known as secondary progressive MS (SPMS) and currently licensed treatments have only very moderate efficacy.

In the late breaking news session, Ludwig Kappos (University of Basel, Switzerland) reported the main results of EXPAND, which has included 1,651 patients with SPMS from 31 countries. SPMS patients, who were included only if they showed evidence of disability progression within the previous two years, were treated daily with either 2mg siponimod or a placebo (two patients were placed in the treatment group for every one patient in the placebo group).

The main outcome was confirmed MS progression over three months, measured using Expanded Disability Status Scale (EDSS) scores. When compared with placebo, siponimod reduced progression by 21% (HR 0.74), and this difference was statistically significant. At 6 months the reduction was 26%, and again this was statistically significant. Treatment effects were more noticeable in those who had had relapses, and treatment was associated with a reduction in the annualised relapse rate (which fell by about half compared with the placebo group).

The take home message from today is that EXPAND is the largest study to date to present data showing that a drug candidate for secondary progressive MS (siponimod) impacts on a clinical measure of disability progression. It is encouraging that we now have a potential treatment for SPMS that might be available for patients in the near future.

Prof. Xavier Montalban, President of the European Committee for Treatment and Research In Multiple Sclerosis


Refining the criteria used to diagnose MS at an early stage using MRI scan results

Presentation revealed the latest evidence-based thinking on how to use MRI scan results to diagnose MS with increasing accuracy.

Earlier this year, MAGNIMS, the European Collaborative Research Network that studies the use of MRI when diagnosing MS, published revised criteria for clinicians.

In his presentation at ECTRIMS, Paolo Preziosa (Vita-Salute San Raffaele University, Milan, Italy) a young investigator within MAGNIMS, outlined results showing that their most recent techniques do indeed make it possible to diagnose MS earlier and more accurately in patients with very few clinical signs of the disease.

Using MRI data in MS diagnosis requires continual reassessment

MRI scans have been used routinely to help diagnose MS since 2001. Over the last 15 years there have been huge advances in the technology and so the criteria used to diagnose MS in patients on the basis of their scans results have had to change too.

One of the key goals is to use MRI imaging to detect changes within the brain and spinal cord of someone who has Clinically Isolated Syndrome (CIS). This term is used to describe someone who has experienced a single episode of neurological symptoms. This episode may have lasted only a few days, leaving clinicians with very little to go on when attempting to determine the underlying cause.

One of the key factors that MRI data is used to look for is whether the symptoms are caused by lesions in the nervous system that are ‘disseminated in time and space’. Using MRI technology to judge whether abnormalities in the grey matter particularly are associated with a subtle spread and progression of the disease is at the heart of the recent criteria.

Defining the criteria for a diagnosis of MS

Preziosa explained that the new criteria for MS diagnosis in patients with CIS specify that at least two of the following signs are visible on a detailed MRI scan:

  1. At least one lesion in the spinal cord
  2. Three or more lesions in the periventricular white matter in the brain
  3. At least one lesion in the infratentorial region, which includes the cerebellum
  4. At least one lesion in the cortical or juxtacortical region of the brain – so in or near the grey matter
  5. At least one lesion in an optic nerve

Preziosa emphasised that scoring cortical lesions (the grey matter) and lesions involving the white matter next to the cortex (called juxtacortical lesions) when assessing ‘dissemination in space’ was a key change to the current criteria and one that required detailed investigation within a clinical study.

The MAGNIMS study to test out the new criteria

During their work on the recent consensus statements, the MAGNIMS group set up a study involving 72 patients with CIS who were recruited from five European centres and followed up for over 2 years. One of the objectives was to reveal better the lesions present in the grey matter and in the adjacent white matter.

Finding lesions in or near the grey matter can be particularly difficult: Preziosa explained that patients in the study had a double inversion recovery MRI (DIR MRI) scan at study entry as this increases grey matter lesion detection compared to standard MRI.

After two years, 90% of those recruited to the study had developed MS, while 10% were found to have a separate neurological condition.

Encouragingly, the use of DIR MRI to detect lesions in the grey matter led to more patients being correctly diagnosed with MS right at the start of the study.

The group concludes that the changes that they have proposed to the diagnostic criteria for MS do indeed make it possible to diagnose MS in someone with very early clinical symptoms much more accurately.

These refinements in criteria seem to be small steps, but for patients with early stage MS, they are very significant. Being able to give someone an accurate diagnosis of MS enables disease-modifying treatments to be given as early as possible. Equally, if someone does not have MS, their clinical team can then move forward to finding out what is the cause of their symptoms.

Professor David Miller, Vice President & Chair of Scientific Committee of ECTRIMS


How optic nerve imaging can help monitor therapeutic effects in MS

Presentations revealed how imaging the retina and optic nerves can provide key information on disease progression in MS, including how effective treatment strategies are at slowing down those changes.

A comprehensive series of reviews, data and original reports explored and defined how researchers can use the visual system to better understand the disease process responsible for MS – including, how imaging of the optic nerve and retina can offer an interventional trial platform for proof of concept studies.

The importance of OCT imaging

Peter Calabresi (Director of the MS Center at Johns Hopkins, Baltimore, MD, USA), began the session by outlining the use and importance of Optical Coherence Tomography (OCT) as a non-invasive technique that is able to display and quantify retinal pathology. This standard imaging technology is widely available and is reproducible across different centers. In fact, it has been validated as a reliable indicator of disease progression in both longitudinal and cross-sectional datasets.

Using OCT to monitor drug response in MS

Raju Kapoor (University College, London, UK) described several clinical trials that have assessed the neuroprotective potential of various drugs by studying their effect on patients with optic neuritis. Using visual system imaging to monitor the impact of treatments on optic nerves themselves is a significant advance. However, more encouraging, is the potential of monitoring the response within the visual system could also provide information about the impact of the drug on lesions elsewhere in the central nervous system.

Can OCT scans predict disease progression?

In his introduction, Calabresi touched on a recent meta-analysis showing how well OCT retinal scans can accurately predict clinical outcomes five years later, mentioning an update on new data on predictions at 10 years. Alissa Rothman, a researcher in Calabresi’s group went into the study in more detail.

A total of 89 participants were included, most of them female patients with relapsing remitting MS who had a baseline expanded disability status scale (EDSS) of 2.8. Status OCT scans were performed on each patient at entry and follow up took place over a 10-year period. After using various models and adjusting for confounding factors such as age, sex and a history of optic neuritis, the total macular volume measured by the original OCT scans was found to accurately predict the EDSS scores at the ten-year follow up point.

In particular, the changes within the eye over the first 2-3 years seem to have the greatest predictive value.

Finally, Justin McKee (University of Oxford, UK) presented the results of the Amiloride Acute Optic Neuritis trial (the ACTION trial). Amiloride, a repurposed diuretic, which targets and blocks acid sensing ion channel 1 (ASIC1), is over-expressed in mouse models of MS and is present in post-mortem tissue from MS patients.

Previously, McKee explained, a cohort study in progressive MS had suggested that Amiloride may have a neuroprotective effect in MS. He then reported his group’s current study in which 48 patients with acute optic neuritis (within 28 days of onset) were given 10mg of Amiloride or a placebo. Treatment was continued for 5 months, then stopped for a month before outcomes were measured at 6 months and then again at 12 months.

Disappointingly, thickness of the retinal nerve fibre layer in the Amiloride treatment group was not significantly less than in the placebo group. The study included a number of secondary outcome measures, but no differences were observed between the groups here either.

Discussions following the presentation explored reasons for this negative result and many experts present focused on the therapeutic window in acute optic neuritis, which is very likely to be as little as 7 days. The potential of earlier treatment with Amiloride cannot be dismissed completely.

Research in this area of MS is now focusing on ways to understand the way in which immunomodulatory therapies work – we know they do, but we don’t understand fully how. Another major focus is to find out more about the mechanisms that lead to neuronal loss in MS so that we can develop new therapies to target MS progression that occurs without discernable inflammatory lesions.

Peter Calabresi, Director of the MS Center at Johns Hopkins, Baltimore, MD, USA


Lipoic acid shows great potential as a disease modifying treatment for secondary progressive MS

One of the parallel sessions reported promising early results on the potential benefits of lipoic acid in secondary progressive MS.

Lipoic acid is produced naturally in our own bodies and is found in many foods, and previous laboratory work has suggested that taking supplements of lipoic acid may help reduce some of the disabling effects of MS. Now this drug candidate is being tested in early stage human trial and can be added to the small number of drugs in development for secondary progressive MS.

Why could lipoic acid be so important?

Most people with MS initially have episodes of neurological symptoms that come and go. This stage of the disease is described as relapsing remitting MS and can last or months or even years. Eventually, however, most people develop deficits that progress over time and their disease is then termed secondary progressive MS.

Much of the progressive disability that occurs in secondary progressive MS is thought to be due to the loss of nerve cells and fibres. Treatments that could prevent or slow this loss could have the potential to prevent or slow disability progression.

Unfortunately, although we now have a range of treatments available for relapsing remitting MS, there are no licensed treatments for secondary progressive MS. As lipoic acid is inexpensive and readily available, and it is tolerated at high doses by MS patients, it is an attractive drug candidate.

Details of the lipoic acid study

In their double-blinded pilot treatment trial of lipoic acid, Chataway et al. studied 51 people with confirmed secondary progressive MS for 96 weeks. Lipoic acid, at a dose of 1200mg per day, was given to 27 patients, with a further 24 receiving a placebo. Participants were monitored using MRI scans to measure whole brain atrophy, atrophy of brain substructures and the spinal cord, atrophy of the retina and macular region in the eye, and by clinical assessment and questionnaires to determine impact on symptoms and quality of life.

Promising results: lipoic acid prevents brain atrophy

At the end of the trial, MRI scans revealed a lower rate of whole brain atrophy in the lipoic acid treatment group compared to the placebo group. The rate of brain volume decline over time in those who took lipoic acid supplements was 0.22% per year and 0.65% per year in those who took the placebo. This is a 66% reduction, which is statically significant (p=0.004).

Lipoic acid treatments were well tolerated

The rate of serious adverse events was very similar between both groups. People in the lipoic acid group reported a higher rate of stomach upsets (an adverse effect) and a lower rate of falls (a benefit).

A very positive sign was also that more than 80% of the participants took the tablets regularly throughout the study period and only five participants withdrew during the course of the trial.

Taking lipoic acid forward in clinical trials

The study group recognises that this trial is a pilot. However, the strength of the response seen in patients with secondary progressive MS was sufficiently promising to warrant a larger trial to confirm the possible neuroprotective effects of lipoic acid and to further explore both the clinical benefits and the potential adverse effects.

The MS-STAT trial of high dose simvastatin has also shown a reduction in the rate of brain volume loss, and the EXPAND trial of siponimod, which will be presented at ECTRIMS tomorrow, has shown a beneficial effect on disability progression. Add in this study on lipoic acid and we are beginning to see several promising treatments emerge for secondary progressive MS.

Prof. Xavier Montalban, President of the European Committee for Treatment and Research In Multiple Sclerosis


Real world data from Biogen affirms efficacy of Tecfidera and 9 year safety profile

Further data show benefits of patient coaching in reducing discontinuation rates

Data presented from both real-world and clinical settings demonstrated that dimethyl fumarate delivered consistent1 and sustained efficacy2 among patients with relapsing-remitting multiple sclerosis (RRMS), and adds to its safety profile for up to nine years of treatment.3

Real world findings demonstrate efficacy of dimethyl fumarate versus other MS therapies

Retrospective results from the worldwide MSBase registry show that dimethyl fumarate reduced the risk of first relapse versus interferons by 26% (n=420 matched pairs; HR 0.74; 95% CI 0.57, 0.97; p=0.027), glatiramer acetate by 28% (n=382; 0.72; 0.54, 0.95; p=0.022) and teriflunomide by 34% (n=256; 0.66; 0.45, 0.99; p=0.042). In the primary analysis, no significant difference was found versus fingolimod-treated patients (n=415; 1.03; 0.73, 1.46; reference = FTY).1 Time to first relapse was measured using binomial propensity score matching.

The MSBase registry is one of the largest sources of real-world data and includes nearly 40,000 MS patients across 72 countries. Our analysis shows that dimethyl fumarate significantly reduced the risk of first relapse compared to platform therapies and teriflunomide, and had comparable efficacy to fingolimod

H. Butzkueven, Associate Professor in the Department of Medicine, University of Melbourne and one of the investigators for the study

As a secondary endpoint, the study also demonstrated similar and consistently lower annualised relapse rates (ARR) for dimethyl fumarate-treated patients versus those treated with interferons (0.23 [95% CI 0.19, 0.27] vs 0.26 [0.24, 0.29]), glatiramer acetate (0.24 [0.19, 0.28] vs 0.26 [0.23, 0.29]) and teriflunomide (0.17 [0.13, 0.22] vs 0.27 [0.22, 0.33]). ARR for dimethyl fumarate-treated patients was found to be similar but higher versus fingolimod-treated patients (0.22 [0.18, 0.27] vs 0.19 [0.17, 0.23]).1

Positive ARR findings were also reported in a second real-world study analysing data from over 3,500 dimethyl fumarate-treated patients from a US Commercial Claims Database. An average reduction in ARR of -0.11 (0.41 vs 0.30; p<0.05) was demonstrated in the year following initiation of dimethyl fumarate versus the year before initiation.4

The MSBase registry data also found that approximately twice as many dimethyl fumarate-treated patients discontinued treatment after six months of continuous therapy relative to fingolimod (HR 2.39; 95% CI 1.78, 3.20) and interferons (HR 1.40; 95% CI 1.07, 1.83).1 No difference was found versus glatiramer acetate (HR 1.18; 95% CI 0.89, 1.56) or teriflunomide (HR 0.95; 95% CI 0.66, 1.37).1

The use of patient coaching to reduce discontinuation rates was demonstrated in a retrospective real-world study. In patients treated with dimethyl fumarate, rates were reduced in coached patients by up to 48% versus controls (5.7%, 17.1% and 29.2% of coached patients [n=4750] stopped therapy after 3, 12 and 24 months, versus 10.4%, 25.2% and 56.4% of controls [n=3266], respectively).5

Reasons for therapy discontinuation differed between coached and control patients, with partly manageable side effects found to be the main reason for discontinuation for controls. These results could indicate the potential for patient coaching to play an essential role in overcoming such side effects for dimethyl fumarate patients.5

Additional real-world data presented by Biogen demonstrated that the safety profile of dimethyl fumarate remained consistent over nine years,3 and its overall benefit-risk remained favourable.6 These data also further substantiate current guidance for monitoring absolute lymphocyte counts (ALC) to mitigate the risk of moderate to severe prolonged lymphopenia during treatment with dimethyl fumarate.6

Data from ENDORSE further clarify benefits of dimethyl fumarate for newly-diagnosed patients

New 7-year data from the ENDORSE study, an extension to the DEFINE and CONFIRM clinical trials, demonstrated that ARR remained low at 7 years for both treatment groups (0.13 [95% CI 0.10–0.18] with dimethyl fumarate; 0.16 [95% CI 0.11–0.24] for patients switched from placebo). Switch patients experienced a 61% relative reduction in ARR following the switch to dimethyl fumarate after 2 years on placebo (ARR 0.26 [95% CI 0.18–0.37] vs 0.10 [0.07–0.15]; p<0.0001).2 These findings illustrate the potential of dimethyl fumarate to provide positive clinical outcomes over the long-term for people with relapsing remitting MS.

In addition, estimated 24-week confirmed disability progression (CDP) was 18.0% (95% CI 12.0–26.4) in the dimethyl fumarate group versus 26.4% (95% CI 17.4–38.7) in the switch group, representing a 41% risk reduction (95% CI 0.32–1.10, p=0.0979).2

References:

  1. Spelman T, et al.Comparative analysis of MS outcomes in dimethyl fumarate-treated patients relative to propensity matched fingolimod, interferon, glatiramer acetate, or teriflunomide. P1157. The 32ndCongress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016.
  2. Gold R, et al.Seven-year follow-up of the efficacy of delayed-release dimethyl fumarate in newly diagnosed patients with relapsing-remitting multiple sclerosis: integrated analysis of DEFINE, CONFIRM, and ENDORSE. P631. The 32ndCongress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016.
  3. Fox RJ, et al.Absolute lymphocyte count and lymphocyte subset profiles during long-term treatment with delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis. P716. The 32ndCongress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016.
  4. Boster A, et al.Annual relapse rates in multiple sclerosis patients treated with different disease-modify therapies – findings from a real world setting. EP1481. The 32ndCongress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016.
  5. Begus-Nahrmann Y, et al.The potential of individualized patient coaching to optimize treatment with delayed-release dimethyl fumarate: a retrospective analysis of patients with multiple sclerosis treated in a real-world setting. P1214. The 32ndCongress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016.
  6. Buckle G, et al.Effect of delayed-release dimethyl fumarate on lymphocyte subsets in patients with relapsing multiple sclerosis: a retrospective, multicentre, observational study (REALIZE). EP1495. The 32ndCongress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016.

Industry News

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A neurology news update

New data intelligence report analyses how people with neurological conditions in Wessex use hospital services and why

A new Neurology Intelligence Report provides insight into how people with various neurological conditions can be better supported to stay well. The report is the work of NHiS in partnership with Wessex Strategic Clinical Network and CLAHRC, and The National Institute for Health Research. It was launched at an event in Southampton on the 19 April 2016 and can be accessed at www.nhis.com/wessex-neurology-report?utm_
source=announcement&utm_medium=email-and-share&utm_campaign=
Wessex-Report-Launch


News from NICE

Suspecting Neurological Conditions – Recognition and Referral

The final scope and equality impact assessment for this NICE guideline have now been published, along with all the stakeholder comments that were received during consultation and NICE’s responses to these comments. See www.nice.org.uk/guidance/indevelopment/gid-cgwave0800/documents http://bit.ly/1WmcIGU


Stroke in Adults Quality Standard update released

The Stroke in adults quality standard has just been updated and is available from
 www.nice.org.uk/guidance/qs2/chapter/Update-information

Clinical News

Neurological care in England criticised by MPs report

The BBC recently reported that the Department of Health and the NHS are to be held to account in the months and years ahead with regard to provision of neurological care, following the publication of a Public Account Committee report. According to the BBC, the report recommends that NHS England find a way of tackling the problem of variation in services and explain how it will offer everyone with a long-term condition a personalised care plan. It also urges NHS England to make better use of the 650 neurologists in England, as well as other specialist nurses, to improve access to care for patients. Read the report at www.publications.parliament.uk/pa/cm201516/cmselect/cmpubacc/502/50202.htm


Parkinson’s Disease and sleep

According a new global study, sleep is the number one factor influencing well-being in people with Parkinson’s. Other factors highlighted were exercise, pain, stress and mood. You can read more about this study at http://parkinsonslife.eu/global-parkinsons-study-reveals-sleep-as-biggest-influence-on-wellbeing/

If you are interested in how you can help patients with sleep disorders, you may wish to read about the workshop with OT and sleep specialist, Andrew Green, taking place on the 4th of May. Details are available at www.communitytherapy.org.uk


Improving outcomes for people with neurological 
conditions

The Neurological Alliance is working with the NHS England Long Term Conditions Support Unit and the Strategic Clinical Network Neurology Collaborative to deliver a coordinated programme of work to improve care and outcomes for people living with neurological conditions. www.neural.org.uk/nhs-england-community-
project-for-neurology


Improving neurological function in MS

Recent research with the disease modifying MS drug, alemtuzumab, has shown it improves pre-existing disability in people with relapsing-remitting multiple sclerosis. This is according to the commonly used scale in MS, known as the Expanded Disability Status Scale (EDSS). The results lead the authors to conclude that ‘the findings may influence treatment decisions in patients with early, active relapsing-remitting MS displaying neurological deficits’. 
See www.jns-journal.com/article/S0022-510X(16)30090-9/abstract?rss=yes


Brighton and Sussex University Hospitals reduces general anaesthetic administration by a third

Royal Sussex County Hospital has helped to reduce the administration of general anaesthetic by a third in patients aged 4-17 by expanding its MR capability with the help of new technology from Siemens Healthcare. The MAGNETOM® Aera 1.5T is part of a threefold operation to provide enhanced MR access to paediatric patients, relocate the neurology department and ensure a better experience for inpatients, due to its wide bore and comfort-enhancing features.

“The new MAGNETOM Aera is adjacent to The Royal Alexandra Children’s Hospital which provides a safer and more comfortable transition for our paediatric patients,” states John Wilkinson, Imaging Services Manager at Royal Sussex County Hospital. “Since the installation, Royal Sussex has reduced the administration of general anaesthetic to paediatric patients by a third due to increased compliance and comfort. This is due to a combination of factors including the wide bore system, which makes the process less claustrophobic and an in-bore television, kindly donated by Rockinghorse Children’s Charity so paediatric patients can have a more enjoyable and relaxing experience.”

The system will also be used to ensure better throughput for neurology patients following Royal Sussex’s appointment as a regional centre for neurology.

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Ground-breaking treatment for TBI sufferers

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www.crcpress.com ISBN 9781482228243, priced at £25.99

Traumatic brain injury is the leading cause of death and disability around the world. Many years of productive life are lost and people suffer years of disability after brain injury. In addition it engenders great economic costs for individuals, families and society. Without effective treatment, many TBI victims lead lives of quiet desperation, isolation, and depression. The Lefaivre Rainbow Effect is ground-breaking treatment for TBI sufferers. Christine Lefaivre’s book and courses explore this transformative treatment, which focuses on the cognitive retraining of the brain based on pre-injury lifestyle as well as the organic damage.

“I have worked with Chris using this model, and have seen clients who initially had Glasgow Coma scores of 4-6 recover, over a period of years, to the point where they could live independently, hold employment, and have normal relationships.” Bill de Bosch Kemper, Neuropsychologist, Canada.

Traumatic Brain Injury Case Management online courses launched this April, and an examination series in conjunction with the University of British Columbia Continuing Studies will follow: http://rainboweffect.ca/

Christine’s textbook is available now in print and ebook formats: Traumatic Brain Injury Rehabilitation: The Lefaivre Rainbow Effect
Christine Lefaivre

www.crcpress.com ISBN 9781482228243, priced at £25.99.


Lumie lights to be used in Cambridge University research into Huntington’s Disease

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Cambridge-based light therapy specialist Lumie is to supply some of its lamps for use in a research study into Huntington’s Disease that is to be conducted by the School of Clinical Medicine’s Neurology Unit at Cambridge University.

24 of Lumie’s most powerful light boxes, Lumie Brazil, are being donated to the research project that will examine the efficacy and tolerability of two non-pharmaceutical interventions to improve the life and sleep quality of people who have Huntington’s disease. One of these interventions is bright light therapy, the other being sleep restriction therapy.

Huntington’s disease is caused by an inherited faulty gene that damages certain nerve cells in the brain. This brain damage gets progressively worse over time and can affect movement, cognition (perception, awareness, thinking, judgement) and behaviour. Early features can include personality changes, mood swings, fidgety movements, irritability and altered behaviour.

Cambridge-based Lumie is a light therapy specialist whose products promote a healthy sleep/wake cycle by regulating the body clock as well as helping patients to feel more energetic and productive throughout the day. Lumie Brazil offers a much higher light intensity than standard lighting, emitting 10,000 lux at 35cms. To put that in context, on a bright day but not in direct sunlight the level of brightness ranges from 10,000 to 25,000 lux while in direct sunlight that goes up from 32,000 to 100,000 lux. Bright light has been shown to have an immediate impact, increasing levels of alertness, boosting mood and improving performance.


New MR applications to provide greater efficiency in neurology departments

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Siemens Healthcare has launched a range of MR applications to help hospitals reduce the time needed for MR imaging within neurology. It is estimated that 20 to 25% of all MR examinations are neurological, with the number expected to grow in 2016. The applications have therefore been designed to help organisations increase patient throughput in order to maintain an efficient workflow.

One of the applications, Simultaneous Multi-Slice (SMS) EPI, employs an innovative technique to acquire imaging slices simultaneously rather than sequentially, reducing 2D acquisition times with acceleration factors up to eight. Simultaneous Multi-Slice (SMS) EPI can bring DTI and BOLD into clinical routine. This can particularly benefit surgical neurology cases through surgical mapping, potentially helping to reduce post-surgical deficits, and ultimately leading to improved efficiency in the utilisation of operating room resources.

A further application, GOBrain, enables clinically validated brain examinations in just five minutes. This can improve patient throughput, and costs per scan can potentially be reduced. Shorter scan times can also be better tolerated by patients, and can help reduce the need of sedations and rescans.

In addition to speed and quality, standardisation across systems is also an important element for hospitals. Siemens Healthcare has introduced the syngo® MR E11 software platform, a uniform application platform for the MAGNETOM® family and the Biograph mMR MR-Pet system. The focus, in addition to expanding the application offering, is achieving consistency across the entire fleet of systems and managing these effectively.

www.siemens.co.uk/healthcare


Xadago – a new treatment for PD

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The first new treatment for PD in 10 years will launch in the UK in May. Xadago has had marketing authorisation in Europe since February 2015, having been approved as an add-on to L-dopa alone or in combination with other PD medications in mid-late stage PD patients with motor fluctuations.

The active substance in Xadago, safinamide, is a monoamine oxidase-B (MAO-B) inhibitor. It blocks the enzyme monoamine oxidase type B (which breaks down dopamine), thereby helping to restore dopamine levels in the brain and improving the patient’s symptoms.

Xadago, as an add-on treatment to levodopa with or without other medicines for Parkinson’s disease, has been compared with placebo in two main studies involving 1,218 patients with late stage Parkinson’s Disease who experienced fluctuations. In both studies, 6 months treatment with Xadago increased the time during the day during which patients were ‘on’ and able to move by 30-60 minutes when compared with placebo. Another study showed maintenance of this effect for 24 months. Xadago is available as tablets (50 and 100 mg).

Find out more at a series of meetings organised by Profile Pharma. See advertisement on page 16 or call 01444 412772 for more details.


Danish design offers a lift for rehabilitation patients

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Patients in the UK are learning to walk again and being given new hope from a Danish invention. A new bodyweight-supported rehabilitation invention from Danish mobility company Ergolet offers earlier rehabilitation including gait-training, which improves motor function and strength after serious health problems such as an acquired brain injury.

The Ergo Trainer linear body relief system gives patients an equal body-weight support during training, removes the risk and fear of falls or strain, and props up user confidence along with their weight to let rehabilitation start earlier.

Developed in collaboration with Copenhagen University, its inventors say it offers increased mobility for people recovering from acquired brain injury caused by strokes, accidents and tumours, or learning to use prosthetic limbs.

“We can intensify physical training and show significantly faster, better recovery through an ergonomically designed device which makes the user feel safe and secure, and makes exercise fun and motivating”, said UK sales director David Lomas.

“Typically, products come with a built-in treadmill which is very limiting. Ergo Trainer is used with a variety of equipment or for various floor exercise. Clients can even kick a football around”.

It was developed in co-operation with the Centre for Rehabilitation of Brain Injury (CRBI), Copenhagen, and used in patient studies there with dramatic results. CRBI’s neurorehabilitation specialist Jørgen Jørgensen said stroke patients facing paralysis improved their walking speed by an average of 65% after a 12 week period.

Ergolet will run workshops at Neurological Rehabilitation Expo, on June 15-16 2016 with CRBI study results presented by Jørgen Jørgensen. Book free tickets at www.neurorehabexpo.co.uk

ACNR 2015;16(1): 34-35. Published online 14/6/16

Dementia Conference calls for “earlier and more accurate diagnosis” of growing disease

Professor Iain Lyburn, Medical Director and research lead at Cobalt Health, speaks to delegates at Cobalt’s inaugural annual Dementia Conference held in conjunction with Siemens Healthcare.

Medical charity Cobalt held its inaugural annual Dementia Conference in conjunction with Siemens Healthcare, attracting over 100 healthcare professionals including radiologists, neurologists, psychiatrists, and nursing staff. “Dementia is now being recognised for what it is – a sizeable concern that places a signifi­cant drain on resources, stated Professor Iain Lyburn, Medical Director and research lead at Cobalt Health. “While there continues to be no cure, heightening awareness is essential to early diagnosis.”

The annual Dementia Conference follows Cobalt’s recent unveiling of a new Biograph mCT Flow EdgeTM PET/CT system from Siemens Healthcare, installed at Cobalt Imaging Centre in Cheltenham. Anna Cartwright, UK Molecular Imaging Product Specialist at Siemens Healthcare said, “With the evolution of our PET/CT technology paving the way for enhanced dementia diagnosis through the elimination of stop-and-go imaging, Siemens is proud to have been able to support this inaugural event.”

For more information E. laura.bennett@siemens.com, www.siemens.co.uk

ACNR 2015;15(2):29.   Online 23/06/15

The United Kingdom Acquired Brain Injury Forum (Ukabif) 6th Annual Conference

Conference details: 27 November 2014, London, UK.

Over 250 delegates attended the 6th UKABIF Annual Conference which took place at the headquarters of the Royal College of General Practitioners in London’s Euston Square in November.

Over 250 delegates attended the United Kingdom Acquired Brain Injury Forum (UKABIF) 6th Annual Conference, which took place late November last year, at the London headquarters of the Royal College of General Practitioners. The morning presentations focused on commissioning rehabilitation services and were followed in the afternoon by discussions about the issues facing people with a brain injury from both service users and family perspectives.

Professor Michael Barnes, UKABIF Chair welcomes delegates.

The diverse audience included members of the interdisciplinary rehabilitation team, case managers, personal injury lawyers, social care workers, voluntary organisations, care providers and people who have had a brain injury.

Dr John Etherington, National Clinical Director for Rehabilitation and Recovery in the Community, NHS England opened the conference by saying that the National Health Service does not focus on rehabilitation, or even consider it to be an important part of healthcare services. However, rehabilitation is everyone’s business and all health professionals need to understand that it is important – but that remains a challenge. The vision is that in 10 years, rehabilitation will be a key part of every episode of care from acute all the way through to community services. However, the current commissioning structure is an obstacle to care – for example three months is not long enough for a rehabilitation programme, so why use that disease model to commission services? Dr Etherington emphasised that the right clinical and technical training is required to deliver rehabilitation services and that intensity and a significant duration of rehabilitation treatment is essential to produce outcomes for patients.

Neil Brownlee, Head of Service/Long-term Conditions Lead, Northumberland Head Injuries Service at the Northumberland, Tyne and Wear NHS Foundation Trust discussed their excellent model for commissioning Acquired Brain Injury services.

Dr Michael Dixon addressed delegates wearing several ‘hats’, including Chair of the NHS Alliance and the first President and Senior Adviser to the new organisation ‘NHS Clinical Commissioners’, which was created to represent Clinical Commissioning Groups (CCGs) bringing together the commissioning arms of the NHS Alliance, NHS Confederation and the National Association of Primary Care. He acknowledged that the rehabilitation of people with brain injuries has been haphazard. Dr Dixon acknowledged that rehabilitation commissioning needs to be sorted and in a timely fashion. However, Dr Dixon discussed some of the problems facing CCGs such as the increased cost of health services versus real income and a shrinking budget for patients. The reality, said Dr Dixon, is that ‘not everyone’s ambitions can be fulfilled’.

Dr John Etherington, National Clinical Director for Rehabilitation and Recovering in the Community, NHS England said: “By investing [in rehabilitation] we will save money”.

An excellent model for commissioning Acquired Brain Injury services was discussed by Neil Brownlee, Head of Service/Long-term Conditions Lead, Northumberland Head Injuries Service at the Northumberland, Tyne and Wear NHS Foundation Trust. This ‘one-stop shop’ is an integrated health and social care community service for people living in Northumberland who have had a traumatic brain injury. The service provides a holistic, interdisciplinary approach and clients are seen by specialist health and social care professionals. It is a timely and efficient model and has been demonstrating excellent outcomes since it was established 22 years ago. The persons’ needs are assessed and goals agreed to maximise the person’s independence and involvement in the community.   At any one time the service has between 100 and 150 service users with mild, moderate and severe traumatic brain injury.

Emma Gaudern, EMG Solicitors gave an interesting presentation on the issues and implications of the Mental Capacity Act. Emma currently acts as deputy for around 50 people and represents clients with a range of disabilities and many have significant communication problems. The Revd Dr Joanna Collicutt, Karl Jaspers Lecturer in Psychology and Spirituality, Ripon College, Oxford was thought provoking in her presentation on some of the ethical dilemmas posed by Acquired Brain Injury. Multiple impairments may be involved and they may relate to identity. What makes us who we are? How do we work out who we are? The person’s place in society may change after an Acquired Brain Injury or it can impact on memory which can be deconstructed or wiped out for large periods of time. The possibility for conflict is enormous and occurs with the past, present and future self as well as with the family, clinical team and carers.

James Piercy, science communicator and Maureen Le Marinel, past President of UNISON and current National Executive Council Member, both talked about the impact of brain injury on family members. James’s life changed dramatically in January 2011 when a serious road accident left him with a severe head injury. He was in hospital for nearly two months and whilst making a remarkable recovery, he still lives with the effects of his injury. James vividly described his recovery process in the context of him having to return to work and provide for his family. Maureen gave a moving talk about her niece, Katie who, at 12 years of age, was involved in a ‘hit and run’ accident which left her with a brain injury. Maureen outlined the need to involve the family in the rehabilitation programme and also highlighted the need for information. UNISON is currently distributing leaflets to promote the ‘Head and Brain Injury Information Signpost’, a UNISON and UKABIF joint collaboration. This web-based resource is for people with an Acquired Brain Injury, their families and all professionals involved in their care and support.

For further information, please contact: Chloë Hayward, UKABIF
T: 0845 6080788 • M: 07903 887655
E: info@ukabif.org.ukwww.ukabif.org.uk

ACNR 2014;15(1):36. Online 15/04/15

The European Association of Neuro-Oncology (EANO) Conference

Turin, Italy 9-12 October 2014

Nearly 1000 healthcare and allied professionals (including many “big names” from both sides of the Atlantic and beyond) attended the biennial EANO meeting which was held in the Lingotto Conference Centre in Turin, Italy, part of the converted former Fiat factory. This was constructed in the early 1900s, the design being unusual in that it had five floors, with raw materials going in at the ground floor, and cars built on a line that went up through the building. Finished cars emerged at rooftop level to go onto the test track (which featured in the film “The Italian Job” and is still there). However, the other thing for which this city is particularly famous, the Turin Shroud, was not available for viewing.

The conference opened with an Educational Day consisting of parallel clinical and laboratory science sessions, both having an emphasis on CNS metastasis. We mustn’t forget that whilst GBM (glioblastoma multiforme) is still a major challenge, approximately 40% of brain neoplasms are actually secondaries from other cancers eg lung, melanoma, breast etc, and these are an increasing problem as patients live longer due to treatments for the primaries becoming more effective. Although there are no exact data, one speaker cited brain “mets” as affecting 6% of the population. There were then another 21Ž2 days with up to four sessions running concurrently, including nursing and quality of life topics, evening satellite symposia sponsored by various companies, and poster viewings.

Read more…

Published online 23/01/15

Dr Chris Allen

Interview by GEMMA CUMMINS | Portrait by Paul Cash

A career highlight Realising, about 15 years after being appointed a Consultant Neurologist at Addenbrooke’s and five years after being appointed Clinical Dean in the University of Cambridge, that there was no place I would rather be in my career. I was a clinician working in a world class research centre, surrounded by the stimulation of young research students and clinical students and yet still spending much of my time in direct contact with patients.

Biggest regret That I probably never will write that novel, otherwise I refer readers to Edith Piaf.

Inspiring mentor Michael Harrison (at the Middlesex hospital), probably the best Neurologist of his generation and certainly the nicest, he inspired me in many ways personally and neurologically.

Most memorable patient There have been many, memorable for different reasons. One lasting impression was left by a patient with metastatic cancer I met as a clinical student. He said “I hope you’re not going to tell me I only have months to live, because some idiot of a doctor told me that 4 years ago!” This taught me never to specify any person’s lifespan…doctors are usually wrong when they try to guess how long someone has to live.

If I hadn’t been a neurologist When I was 10 years old, admiring my father, I wanted to be a fighter pilot. At school I was mainly interested in literature and art but good at biology, so medicine seemed to be a good practical choice. At various stages as an undergraduate I wanted to be a Psychiatrist, a Paediatrician and General Physician (internist) in that order (I never saw myself as a Surgeon). I only decided to commit to being a neurologist after nearly five years working post qualification in various medical specialties including two years as a general medical registrar. Already having an intellectual interest in the brain I realised that in neurology I would be able to practice the clinical method in its ultimately satisfying form, now aided by increasingly sophisticated neuroscience and imaging. Remember I started as a medical undergraduate the year levodopa was introduced as a treatment for Parkinson’s disease and qualified in the year CT imaging of the brain was introduced into clinical practice.

I now see that if I hadn’t become a neurologist I would have been very disappointed with my life (unless I had written that novel).

Hidden talent Having so few I prefer not to hide any talent I think I have!

Advice to budding Charcots (ie trainee neurologists) Never let someone else direct your career, believe in yourself but check your ambitions against reality. Try to end up doing something you are good at rather than something you wish you were good at. Disappointment in careers arises from a mismatch in a person’s ambition and his/her ability to achieve it. Take advice from multiple sources and then see what these different sources have in common. Always consider whether someone is advising you for their own benefit or yours. There is a lot of luck involved in the evolution of someone’s career but luck favours the prepared.

3 most important qualities in a neurologist He or she must be an empathetic physician. You must combine your knowledge of the science of disease and your clinical skills at identifying it with compassion for the individual, treating the patient and not the disease. Apply the scientific method to understand the disease and with this use human compassion to manage the patient’s illness. Try to be the neurologist you would like to consult.

Next frontier in neuroscience is… If I predict this I will be wrong. However I suspect it will be in the territory furthest from our understanding now, which is the frontier between the brain and the mind (and whether this is a discoverable border after all).

Guilty pleasure Eating too well. I don’t feel guilty about drinking too well and I’ve given up smoking long ago….as to other pleasures I feel no guilt.

Favourite tipple in favourite place A glass of American IPA anywhere with one or more of my grown up children, one a Neurologist, one a Clinical Psychologist and one on his way to becoming a Psychiatrist and all three, with their partners, my closest friends and the parents of my (soon to be) five grandchildren.

Favourite quote Voltaire is reported to have said “The effective physician is one who successfully entertains the patient whilst nature effects a cure”. When I told this to a neurosurgical colleague he said “I suppose you will be saying that the effective surgeon is one who successfully entertains himself whilst nature effects the cure”.

Most embarrassing moment When, on my first ward round as a clinical student at Guy’s Hospital, I realised that the zip on my trouser fly had totally failed.

Most cherished possession (apart from family) My Bamboo handled “Queen Square” style tendon hammer, a chimeric object derived from multiple sources over thirty years. It does more than obtain reflexes, it is my totem. Generations of registrars have been trained to retrieve it from lost regions of the hospital.

Fireside read Novels by the new generation of Indian and British Indian authors such as Amulya Malladi, Vikram Chandra and Amitav Ghosh.

Painting I would like on my wall A good one that I had painted, another unrealistic ambition, failing that “Sainte-Victoire Dagï” by Cezanne or David Hockney’s “Woldgate Woods”.

Desert island playlist I would take a collection which reminded me of various stages in my growing up:

  1. Harry Belafonte “The banana boat song (Day O).” My father would play this frequently whilst I was a child growing up in India, where he worked as a Tea Planter. My father was the greatest man I have ever known, my icon still.
  2. Cliff Richard “Livin’ lovin’ doll.” This came out when I was nearly 11 and my older brother played it endlessly in the school holidays.
  3. Charlie Parker “My old flame.” Charlie Parker was my musical obsession at 16 when I was wrestling with the choice of whether to do science A levels or English and History.
  4. Beatles “Love me do.” This peaked in the British charts at the same time as my last holiday visit to my parents in India; it marked the beginning of the crazy 1960’s as far as I was concerned.
  5. Rolling Stones “Get off of my cloud.” A reminder of my somewhat disorganised life as an undergraduate.
  6. Credence Clearwater Revival “Down on the Corner” Would remind me of more time in the “wasted” part of my youth.
  7. Cat Stevens “Morning has broken.” My long suffering wife was a Cat Stevens fan when we met and this was played at our wedding in 1973.
  8. Mozart Bassoon Concerto in B flat major, K. 191/186. I played Mozart cassettes nearly continuously in the car when travelling around East Anglia in anticipation of applying for my consultant post involving clinics in Cambridge, Peterborough and Kings Lynn.

ACNR 2015;14(6);16-17.  Online 23/01/15

Researchers develop 3D printed foot orthotics

Glasgow Caledonian University (GCU) researchers, in partnership with the University of Newcastle and Newcastle-based SME Peacocks Medical Group, have been awarded significant funding for the design and manufacture of innovative foot orthotics using 3D-printing technologies.

The project has been granted a £77,000 Small Business Research Initiative (SBRI) Healthcare development contract. SBRI Healthcare is an NHS England initiative, championed by the newly formed Academic Health Science Networks to develop innovative products and services that address unmet health needs.

The funding was awarded following a call to address challenges in improving diagnosis, self-management and prevention of musculoskeletal disorders.

Disabling foot and ankle conditions affect approximately 200 million European citizens. Over 300 million per annum is spent treating many of these people with orthoses and splints, often relying on hand-crafted manufacturing techniques which are slow, costly and difficult to reproduce.

With an increasingly ageing population and a growing health burden in long-term conditions, the global market for custom foot orthoses continues to grow.

The GCU team, led by Dr Gordon Hendry and Professor Jim Woodburn, will work with Peacocks Medical Group and researchers from Newcastle University on the ‘FootFEMan’ project, which will utilise a computational engineering tool called finite element analysis to improve the functional design of orthotic devices for individual patients.

The improved personalised design will then be printed layer by layer using 3D-printing techniques developed previously in the team’s award-winning EU-funded project, A-FOOTPRINT.

Dr Hendry said “We are confident that we can successfully 3D print new orthotic insole devices. This project will now enable us to improve each orthotic tailored to the individual patient according to whatever foot problem they have.

“We will test the new products in controlled clinical studies here at GCU to see if we can improve foot function during walking and further lessen disabling foot symptoms.”

Professor Woodburn added: “GCU’s collaborative partnership with Peacocks will enable them to maintain and grow their market position as the leading SME developing innovative and knowledge-based orthotic products.”

For more information, E. Fiona.ramsay@gcu.ac.uk

ACNR 2015;14(6);17.  Online 23/01/15