-
[show abstract]
[hide abstract]
ABSTRACT: Clinical diagnosis of amyotrophic lateral sclerosis (ALS) in patients presenting with cramps and fasciculations may not be evident at the first consultation. Sequential reviews, clinical and neurophysiological, form an important part of clinical practice in such cases. Recent attempts to delineate a more benign group with cramps and fasciculations have lacked information on the long term profile, both clinical and neurophysiological. Four patients who were initially diagnosed as suffering from benign cramps and fasciculations, but who subsequently progressed to ALS, are described. We propose that a diagnosis of benign cramps and fasciculations should not be considered secure without a minimum follow up of 4-5 years.
Journal of Neurology 10/2010; 258(4):573-8. · 3.47 Impact Factor
-
Mike Boggild
[show abstract]
[hide abstract]
ABSTRACT: The recent emergence of 'higher efficacy/higher risk' therapies in relapsing remitting multiple sclerosis (RRMS) asks questions of current treatment paradigms in this disorder. For those patients who present with very aggressive relapsing disease or early treatment failure on an interferon, a number of treatment options need to be considered. One such strategy is that of induction treatment regimens combining a short-course of an immunosuppressive drug to enable prompt control of inflammatory disease activity, followed by maintenance therapy with an immunomodulatory treatment. Immunosuppressants in general cannot be given over extended periods because of toxicity associated with cumulative exposure. However, in the short term, the risks associated with their use are probably less than those risks associated with inadequate control of relapse activity in aggressive onset disease. In particular, several groups have investigated the potential use of mitoxantrone induction followed by maintenance therapy with glatiramer acetate (GA). The evidence emerging from such studies suggests that brief immunosuppression with mitoxantrone followed by maintenance therapy with GA may provide a synergistic effect on control of disease activity and can be administered with an acceptable risk. The effectiveness of such induction regimens should encourage physicians to reconsider thresholds to define treatment failure on 'first-line' therapies, the criteria for acceptable disease control, as well as the relative place of induction and escalation treatment strategies in the management of RRMS.
Journal of the Neurological Sciences 03/2009; 277 Suppl 1:S50-4. · 2.35 Impact Factor
-
Mark Pickin,
Cindy L Cooper,
Timothy Chater,
Anthony O'Hagan,
Keith R Abrams,
Nicola J Cooper, Mike Boggild,
Jackie Palace,
George Ebers,
James B Chilcott,
Paul Tappenden,
Jon Nicholl
[show abstract]
[hide abstract]
ABSTRACT: Risk sharing schemes represent an innovative and important approach to the problems of rationing and achieving cost-effectiveness in high cost or controversial health interventions. This study aimed to assess the feasibility of risk sharing schemes, looking at long term clinical outcomes, to determine the price at which high cost treatments would be acceptable to the NHS.
This case study of the first NHS risk sharing scheme, a long term prospective cohort study of beta interferon and glatiramer acetate in multiple sclerosis (MS) patients in 71 specialist MS centres in UK NHS hospitals, recruited adults with relapsing forms of MS, meeting Association of British Neurologists (ABN) criteria for disease modifying therapy. Outcome measures were: success of recruitment and follow up over the first three years, analysis of baseline and initial follow up data and the prospect of estimating the long term cost-effectiveness of these treatments.
Centres consented 5560 patients. Of the 4240 patients who had been in the study for a least one year, annual review data were available for 3730 (88.0%). Of the patients who had been in the study for at least two years and three years, subsequent annual review data were available for 2055 (78.5%) and 265 (71.8%) patients respectively. Baseline characteristics and a small but statistically significant progression of disease were similar to those reported in previous pivotal studies.
Successful recruitment, follow up and early data analysis suggest that risk sharing schemes should be able to deliver their objectives. However, important issues of analysis, and political and commercial conflicts of interest still need to be addressed.
BMC Neurology 02/2009; 9:1. · 2.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To generate evidence on the longer term cost effectiveness of disease modifying treatments in patients with relapsing-remitting multiple sclerosis.
Prospective cohort study with historical comparator.
Specialist multiple sclerosis clinics in 70 centres in the United Kingdom.
Patients with relapsing-remitting multiple sclerosis who started treatment from May 2002 to April 2005 under the UK risk sharing scheme.
Treatment with interferon beta or glatiramer acetate in accordance with guidelines of the UK Association of British Neurologists.
Observed utility weighted progression in disability at two years' follow-up assessed on the expanded disability status scale (EDSS) compared with that expected by applying the progression rates in a comparator dataset, modified for patients receiving treatment by multiplying by the hazard ratio derived separately for each disease modifying treatment from the randomised trials.
In the primary per protocol analysis, progression in disability was worse than that predicted and worse than that in the untreated comparator dataset ("deviation score" of 113%; excess in mean disability status scale 0.28). In sensitivity analyses, however, the deviation score varied from -72% (using raw baseline disability status scale scores, rather than applying a "no improvement" algorithm) to 156% (imputing missing data for year two from progression rates for year one).
It is too early to reach any conclusion about the cost effectiveness of disease modifying treatments from this first interim analysis. Important methodological issues, including the need for additional comparator datasets, the potential bias from missing data, and the impact of the "no improvement" rule, will need to be addressed and long term follow-up of all patients is essential to secure meaningful results. Future analyses of the cohort are likely to be more informative, not least because they will be less sensitive to short term fluctuations in disability.
BMJ (Clinical research ed.). 01/2009; 339:b4677.
-
Clinical evidence 01/2005;
