Patient-orientated longitudinal study of multiple sclerosis in south west England (The South West Impact of Multiple Sclerosis Project, SWIMS) 1: protocol and baseline characteristics of cohort

<p>Abstract</p> <p>Background</p> <p>There is a need for greater understanding of the impact of multiple sclerosis (MS) from the perspective of individuals with the condition. The South West Impact of MS Project (SWIMS) has been designed to improve understanding of disease impact using a patient-centred approach. The purpose is to (1) develop improved measurement instruments for clinical trials, (2) evaluate longitudinal performance of a variety of patient-reported outcome measures, (3) develop prognostic predictors for use in individualising drug treatment for patients, particularly early on in the disease course.</p> <p>Methods</p> <p>This is a patient-centred, prospective, longitudinal study of multiple sclerosis and clinically isolated syndrome (CIS) in south west England. The study area comprises two counties with a population of approximately 1.7 million and an estimated 1,800 cases of MS. Self-completion questionnaires are administered to participants every six months (for people with MS) or 12 months (CIS). Here we present descriptive statistics of the baseline data provided by 967 participants with MS.</p> <p>Results</p> <p>Seventy-five percent of those approached consented to participate. The male:female ratio was 1.00:3.01 (n = 967). Average (standard deviation) age at time of entry to SWIMS was 51.6 (11.5) years (n = 961) and median (interquartile range) time since first symptom was 13.3 (6.8 to 24.5) years (n = 934). Fatigue was the most commonly reported symptom, with 80% of participants experiencing fatigue at baseline. Although medication use for symptom control was common, there was little evidence of effectiveness, particularly for fatigue. Nineteen percent of participants were unable to classify their subtype of MS. When patient-reported subtype was compared to neurologist assessment for a sample of participants (n = 396), agreement in disease sub-type was achieved in 63% of cases. There were 836 relapses, reported by 931 participants, in the twelve months prior to baseline. Twenty-three percent of the relapsing-remitting group and 12% of the total sample were receiving disease-modifying therapy at baseline.</p> <p>Conclusions</p> <p>Demographics of this sample were similar to published data for the UK. Overall, the results broadly reflect clinical experience in confirming high symptom prevalence, with relatively little complete symptom relief. Participants often had difficulty in defining MS relapses and their own MS type.</p

Patient Uncertainty Questionnaire-Rheumatology (PUQ-R): development and validation of a new patient-reported outcome instrument for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a mixed methods study

Background An in-depth qualitative exploration of uncertainty in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) led to the development of a five-domain conceptual framework of patient uncertainty in these two conditions. The purpose of this study was to develop and evaluate a new patient-reported outcome (PRO) instrument for patient uncertainty in SLE and RA on the basis of this empirically developed conceptual framework. Methods Cognitive debriefing interviews were conducted to pre-test the initial items generated on the basis of the preliminary qualitative exploration of patient uncertainty in SLE and RA. Two separate field tests were conducted in five hospital sites to evaluate the measurement properties of the new instrument; the first to identify and form scales, and the second to assess measurement properties of the final version in an independent sample. Psychometric evaluation was conducted in line with the Rasch Measurement Theory (RMT), examining the extent to which sample to scale targeting was satisfactory, measurement scales were constructed effectively and the sample was measured successfully. Traditional psychometric techniques were also used to provide complementary analyses best understood by clinicians. Results Pre-testing supported the relevance, acceptability and comprehensibility of the initial items. Findings indicated that the Patient Uncertainty Questionnaire for Rheumatology PUQ-R instrument fulfilled the expectations of RMT to a large extent (including person separation index 0.73 – 0.91). The PUQ-R comprises 49 items across five scales; symptoms and flares (14 items), medication (11 items), trust in doctor (8 items), self-management (6 items) and impact (10 items) which further displayed excellent measurement properties as assessed against the traditional psychometric criteria (including Cronbach’s alpha 0.82 – 0.93). Conclusion The PUQ-R has been developed and evaluated specifically for patients with SLE and RA. By quantifying uncertainty, the PUQ-R has the potential to support evidence-based management programmes and research

Clinical correlates of grey matter pathology in multiple sclerosis

Traditionally, multiple sclerosis has been viewed as a disease predominantly affecting white matter. However, this view has lately been subject to numerous changes, as new evidence of anatomical and histological changes as well as of molecular targets within the grey matter has arisen. This advance was driven mainly by novel imaging techniques, however, these have not yet been implemented in routine clinical practice. The changes in the grey matter are related to physical and cognitive disability seen in individuals with multiple sclerosis. Furthermore, damage to several grey matter structures can be associated with impairment of specific functions. Therefore, we conclude that grey matter damage - global and regional - has the potential to become a marker of disease activity, complementary to the currently used magnetic resonance markers (global brain atrophy and T2 hyperintense lesions). Furthermore, it may improve the prediction of the future disease course and response to therapy in individual patients and may also become a reliable additional surrogate marker of treatment effect

Internet-based self-help treatment for depression in multiple sclerosis: study protocol of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Depression in MS patients is frequent but often not treated adequately. An important underlying factor may be physical limitations that preclude face-to-face contact. Internet-based treatment showed to be effective for depressive symptoms in general and could thus be a promising tool for treatment in MS.</p> <p>Methods/design</p> <p>Here, we present a study protocol to investigate the effectiveness of a 5 week Internet-based self-help problem solving treatment (PST) for depressive symptoms in MS patients in a randomized controlled trial. We aim to include 166 MS patients with moderate to severe depressive symptoms who will be randomly assigned to an Internet-based intervention (with or without supportive text-messages) or waiting list control group. The primary outcome is the change in depressive symptoms defined by a change in the sum score on the Beck Depression Inventory (BDI-II). Secondary outcomes will include measures of anxiety, fatigue, cognitive functioning, physical and psychological impact of MS, quality of life, problem solving skills, social support, mastery, satisfaction and compliance rate. Assessments will take place at baseline (T0), within a week after the intervention (T1), at four months (T2) and at ten months follow-up (T3: only the intervention group). The control group will be measured at the same moments in time. Analysis will be based on the intention-to-treat principle.</p> <p>Discussion</p> <p>If shown to be effective, Internet-based PST will offer new possibilities to reach and treat MS patients with depressive symptoms and to improve the quality of care.</p> <p>Trial Registration</p> <p>The Dutch Cochrane Center, NTR2772</p

Biochemistry and physiology of gastrointestinal somatostatin

Somatostatin, a tetradecapeptide initially isolated from the ovine hypothalamus, is widely distributed throughout the gastrointestinal tract where it may act as a hormone, local chemical messenger, or neurotransmitter to elicit many physiological actions. Release of somatostatin from D cells in the gut is regulated by mechanisms that are both dependent on and independent of cAMP. In most cases somatostatin acts to inhibit the function of its target cells. It performs this action in part via pertussis-toxin-sensitive inhibitory guanine nucleotide-binding proteins that regulate adenylate cyclase activity. Other mechanisms may involve sites of action distal to intracellular second messenger systems .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44411/1/10620_2005_Article_BF01536041.pd