Helen Ford

Disease-specific quality of life in multiple sclerosis: the effect of disease modifying treatment

Disease specific quality of life was measured in the Leeds Multiple Sclerosis (MS) Treatment Programme (n-/210) using the self-report Leeds MS Quality of Life (LMSQoL) scale. The results showed a significant and sustained increase in quality of life associated with ‘disease modifying’ treatment. This contrasts with the Expanded Disability Status Scores (EDSS), which showed no measurable improvement. An increase in the LMSQoL score did not correlate with baseline age, disease duration, disability or number of prior relapses. There was no significant difference in treatment effect between relapsing-remitting and secondary progressive MS patients, or between patients receiving different products. However, patients with a poor quality of life at baseline showed the most benefit from treatment. Those who had their treatment stopped due to progression, side-effects or lack of effect had significantly lower LMSQoL scores on treatment. In this study, the LMSQoL scale was responsive to change and was easy to administer in a clinical setting.

Screening for the risk of job loss in multiple sclerosis (MS): development of an MS-specific Work Instability Scale (MS-WIS).

Background: Multiple Sclerosis (MS) mainly presents amongst those of working age. Depending upon the type of MS, many people embark upon a long period of managing their day-to-day work-related needs in the face of intermittent and sometimes persistent disabling symptoms. The objective of this study was to explore the concept of work instability (WI) following the onset of MS and develop a Work Instability Scale (WIS) specific to this population. Method: WI amongst those with MS in work was explored through qualitative interviews which were then used to generate items for a WIS. Rasch analysis was used to refine the scaling properties of the MS-WIS, which was then validated against expert vocational assessment by occupational health physiotherapists and ergonomists. Results: The resulting measure is a 22-item, self-administered scale which can be scored in three bands indicating low, medium and high risk of WI (job retention) problems. The scale meets modern psychometric requirements for measurement, indicated by adequate fit to the Rasch model with absence of local dependency and differential item functioning (DIF) by age, gender and hours worked. Conclusions: The scale presents an opportunity in routine clinical practice to take positive action to reduce sickness absence and prevent job loss.

Bacterial meningitis in developing countries.

Hemophilus influenza, Streptococcus pneumoniae, and Neisseria meningitidis account for over 75% of all cases of bacterial meningitis. S. pneumoniae is the commonest causative organism in many developing countries, particularly in Africa. In developing countries overall case fatality rates of 33-44% have been reported, rising to over 60% in adult groups. S. pneumoniae accounts for the highest mortality worldwide. Sequela rates of 22-26% of survivors have been found in African studies, mostly of a neurological nature. There have been few reports of AIDS-related bacterial meningitis in the USA, and a recent study from Uganda found no association between HIV infection and meningococcal meningitis. Stronger associations have been found between opportunistic infections, both viral (cytomegalovirus, herpes virus) and non-viral (TB, Toxoplasma gondii, Cryptococcus neoformans). A lumbar puncture and analysis of the cerebrospinal fluid should be performed on suspected cases unless there is suspicion of impending coning (decreasing consciousness or focal neurological signs). The intramuscular administration of chloramphenicol alone is comparable with intravenous use, and can be given as a shorter course of therapy (2 or 3 days) followed by an oral course. The use of adjunct therapy with corticosteroids in children is now commonplace in the USA and Europe. It appears reasonable to use dexamethasone, given early and in high dosage (0.15 mg/kg 6 hourly for 4 days), in those patients who are severely ill. Rifampicin is effective for chemoprophylaxis (10 mg/kg twice daily for 2 days for meningococcal contacts, 20 mg/kg once daily for 4 days for hemophilus contacts, maximum 600 mg per dose). The recent development and introduction of conjugate vaccines for H. influenza (HIB) has led to rapid reductions in the incidence of hemophilus meningitis in many European countries. An important step in improving prognosis is to increase awareness in both health workers and the public, to encourage early hospital referral, and early antibiotic therapy.

Bacterial meningitis in Swaziland: an 18 month prospective study of its impact.

STUDY OBJECTIVE--To describe the epidemiology, clinical features, and outcome of bacterial meningitis in Swaziland. DESIGN--Prospective study of patients diagnosed as having meningitis of nonviral aetiology during an 18 month period from February 1991 to July 1992. SETTING--Four regional hospitals covering the population of the four districts in Swaziland. SUBJECTS--All patients with non-viral meningitis admitted to hospital within the study period. MAIN RESULTS--Altogether 85 patients were reported to have bacterial meningitis: 48.3% were aged under 1 year. Causative organisms were identified in 60% of cases, and Streptococcus pneumoniae was found to be the commonest (49% of cases). Overall, case fatality was 38.8% for all age groups, and 62.5% (15 of 25) for adults. Neurological sequelae occurred in 22.4%. Three of the adult cases were HIV seropositive. Seizures, but not duration of symptoms before admission, were associated with a poor prognosis. There was a significant rise in incidence related to a period of drought. Fifteen patients were reported with tuberculous meningitis, of whom five were known to be HIV seropositive; the case fatality was 73.3%. CONCLUSIONS--The aetiology and age distribution of cases of meningitis differs greatly from that in developed countries. Rising HIV infection may have an important impact on the future incidence of meningitis. The high case mortality found should encourage efforts towards earlier diagnosis and treatment, and strengthens the need to develop appropriate vaccines.

Research into practice: 10 years of international public health partnership between the UK and Swaziland

BACKGROUND There is increasing interest in global health partnerships. However, evidence of benefit remains weak. We report on the impact of a 10-year public health partnership between the UK and Swaziland. Swaziland has the highest rates of TB and HIV in the world. Health services are being overwhelmed and patients suffer the cost and inconvenience of centralized services. Our international health partnership was set up to promote the translation of public health research into practice. METHODS The partnership is based on six principles: sustainability; robust measurement; evidence-based practice; patient-centred improvement; systems approach and researchers as implementers. Based on rigorous health needs assessments and informed by international evidence, we have achieved a number of successful changes. RESULTS The partnership has been successful in the development of a community TB service; a chronic disease programme for epilepsy; implementation of guidelines; implementation of ART programmes; nurse-led community ART clinics; innovations to improve follow-up and expert patients. CONCLUSION Global inequalities are increasing rapidly and international partnership has an important role in tackling this threat. Partnerships should be based on sustainable, long-term links with a strong foundation of trust and mutual support. Effective leadership, good communication, clinical engagement and interagency collaboration are pre-requisites for the successful implementation of success.

Myocarditis and diffuse skeletal muscle oedema: new features of neuromyelitis optica spectrum disorder? A case report.

We present a case report of newly diagnosed neuromyelitis optica spectrum disorder (NMOSD) with associated myocarditis and diffuse oedema of the pelvic and anterior compartment thigh muscles on magnetic resonance imaging. Aquaporin 4 antibodies are expressed in skeletal myofibres but involvement of skeletal muscle is rarely reported in NMOSD and myocarditis has not previously been described in this context. This case highlights the need for further research into the involvement of cardiac and skeletal muscle in NMOSD.

The effect of consent guidelines on a multiple sclerosis register.

Background The 1998 Data Protection Act and guidelines from the General Medical Council on informed consent have caused concern for medical researchers and particularly those involved in the management of disease registers. Objective The aim of this study was to determine rates of consent for a multiple sclerosis (MS) community-based register and to investigate authorization bias by examining the characteristics of those refusing consent. Methods A consent letter was developed with the advice and support of an advisory group which included people with MS. All people with MS on the prevalent register (n=820) were informed about the register and its purposes and asked to indicate whether they would like their details to be removed from the register. Results Thirty-four (4.1%) people with MS asked for their details to be removed from the register. There was a significant difference in disease course in this group with more patients with benign relapsing-remitting disease compared to the prevalent population. There was no significant difference in age or sex distribution. The proportion of people not giving consent was similar to a local stroke register. Prospectively all new patients have given written informed consent. Conclusion Patients refusing consent may have different disease characteristics than those who consent. The potential for response bias needs to be considered in the development of a UK MS register.

Lesson of the month 2: Transient reversible amnesia in multiple sclerosis

ABSTRACT Transient amnestic syndromes are fascinating clinical entities and there are several subtypes. Transient global amnesia (TGA) is characterised by sudden onset of anterograde amnesia with repetitive questioning, lasting less than 24 hours. The pathophysiology of TGA involves the medial temporal lobes and hippocampi. Episodes of TGA are thought to involve venous congestion with Valsalva-like activities, vascular or migrainous mechanisms. In contrast, transient epileptic amnesia manifests as brief and frequent episodes of amnesia due to seizure activity in the temporal lobes. Transient memory disturbances can also be caused by transient ischaemic attack. We describe the first reported case of transient reversible amnesia directly attributable to acute demyelination. This case reminds us that multiple sclerosis relapses may present with acute cognitive impairment rather than the more classical physical symptoms. This is an important learning point in terms of appropriate management and eligibility for disease-modifying drugs.

A Systematic Review of Discrete-Choice Experiments and Conjoint Analysis Studies in People with Multiple Sclerosis

BackgroundMultiple sclerosis (MS) is a chronic disabling, inflammatory, and degenerative disease of the central nervous system that, in most cases, requires long-term disease-modifying treatment (DMT). The drugs used vary in efficacy and adverse effect profiles. Several studies have used attribute-based stated-preference methods, primarily to investigate patient preferences for initiating or escalating DMT.ObjectivesTo conduct a systematic review of attribute-based stated-preference studies in people with MS to identify common methods employed and to assess study quality, with reference to the specific challenges of this disease area.MethodsWe conducted a systematic search for studies related to attribute-based stated-preference and MS in multiple databases, including Cochrane and MEDLINE. Studies were included if they were published in a peer-reviewed journal, were on the topic of MS, and used a survey methodology that measured stated preferences for attributes of a whole. Analysis was conducted using narrative synthesis and summary statistics. Study quality was judged against the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) conjoint analysis checklist.ResultsWe identified 16 relevant articles reporting 17 separate studies, all but one focusing on DMTs. Most studies were discrete-choice experiments. Study quality was generally high, but we recommend the following: (1) that consideration of sample sizes be improved, (2) that survey design choices be justified and documented, (3) that qualitative approaches for attribute and level selection be incorporated to better involve patients, and (4) that reporting of experimental practice be improved. The effects of DMTs on reproduction and the impact of how risk and uncertainty are presented were identified as neglected research topics. The ISPOR conjoint analysis checklist was found to be unsuitable for the assessment of study quality.ConclusionAttribute-based stated preference is a useful method with which to examine the preferences of people with MS in their choice of DMT. However, further research embracing the methodological recommendations identified, particularly greater use of qualitative methods in attribute development, is needed.

Psychological determinants of job retention in multiple sclerosis

Background: Maintaining paid work is a key issue for people with multiple sclerosis (PwMS). Different factors, including psychological attributes, can influence job retention. Understanding their role should inform potential interventions to help PwMS retain employment. Objectives: The aim of this study was to identify the key factors which improve job retention in an employed cohort of PwMS. Methods: This three-year longitudinal study used validated self-completed measures of physical and psychological factors at four time points over 28 months. Results: Of 208 employed PwMS, just over 1 in 10 was no longer working at the end of the study. Three variables were predictive of continuing employment; low ‘work instability’ at baseline increased the odds of job retention by a factor of 12.76; high levels of self-efficacy by a factor of 4.66 and being less than 50 years of age increased the odds of job retention by a factor of 3.90. Path analysis demonstrated the mediating role of self-efficacy between the physical impact of MS and the level of work instability at exit. Conclusion: Screening for work instability and self-efficacy in a clinical setting followed by appropriate interventions to increase self-efficacy and reduce work instability could aid job retention in MS.