Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis (MS-STAT2): protocol for a multicentre, randomised controlled, double-blind, phase 3 clinical trial in the UK.

Introduction: There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS.

Methods And Analysis: MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.

Dyspnea (breathlessness) in amyotrophic lateral sclerosis/motor neuron disease: prevalence, progression, severity, and correlates.

Objective: Dyspnea, or breathlessness, is an important symptom in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). We examined the measurement properties of the Dyspnea-12.

Methods: Rasch analysis enabled conversion of raw Dyspnea-12 scores to interval level metric equivalents.

Correlates and trajectories of relapses in relapsing-remitting multiple sclerosis.

Background And Aims: In people with relapsing-remitting multiple sclerosis (pwRRMS), data from studies on non-pharmacological factors which may influence relapse risk, other than age, are inconsistent. There is a reduced risk of relapses with increasing age, but little is known about other trajectories in real-world MS care.

Methods: We studied longitudinal questionnaire data from 3885 pwRRMS, covering smoking, comorbidities, disease-modifying therapy (DMT), and patient-reported outcome measures, as well as relapses during the past year.

Quality assurance programs for vitamin A and E in serum: are we doing enough to assess laboratory performance?

Objectives: Monitoring serum vitamin A (retinol) and vitamin E (α-tocopherol) concentrations is common practice for assessing nutritional status. Measurement of these vitamins can be challenging due to several factors. Whilst the RCPAQAP Vitamins: Serum Program assists participating laboratories in harmonisation, the materials provided do not contain the analogues of retinol and α-tocopherol that may be present in real patient samples.

Measuring disability in multiple sclerosis: the WHODAS 2.0.

Introduction: Reliable measurement of disability in multiple sclerosis (MS) using a comprehensive, patient self-reported scale, such as the World Health Organization Disability Assessment Schedule (WHODAS) 2.0, would be of clinical and research benefit.

Methods: In the Trajectories of Outcome in Neurological Conditions-MS study, WHODAS 2.

Prevalence of depression in amyotrophic lateral sclerosis/motor neuron disease: multi-attribute ascertainment and trajectories over 30 months.

: Evidence is equivocal about the prevalence of depression in amyotrophic lateral sclerosis (ALS). This study uses a multi-attribute ascertainment of the prevalence of depression and examines this prevalence over time. : Patients with ALS were recruited into the Trajectories of Outcome in Neurological Conditions (TONiC-ALS) study.

Measuring coping in multiple sclerosis: The Coping Index-MS.

Background: Coping in multiple sclerosis (MS) refers to cognitive and behavioural efforts to manage stresses imposed by the illness. Existing generic and disease-specific coping scales do not meet modern guidelines for scale development and cannot produce interval-level metrics to allow for change scores.

Objective: The main aim of this study was to develop a brief patient-reported outcome measure for coping in MS, capable of interval-level measurement.

Measuring disability in amyotrophic lateral sclerosis/motor neuron disease: the WHODAS 2.0-36, WHODAS 2.0-32, and WHODAS 2.0-12.

To investigate whether the World Health Organization Disability Assessment Schedule 2.0 (WHODAS) can provide interval level measurement of disability in Amyotrophic Lateral Sclerosis (ALS), allowing parametric analyses. : Data on the WHODAS 12, 32, and 36-item versions, from 1120 patients studied at one or more time points, were fit to the Rasch model and comparisons made against ALSFRS-R, King's staging, and mortality.

The four self-efficacy trajectories among people with multiple sclerosis: Clinical associations and implications.

Background: Longitudinal studies among people with Multiple Sclerosis (pwMS) have shown that self-efficacy is linked to physical, cognitive and psychological functioning.

Objectives: To determine the distribution of self-efficacy in a large sample of pwMS, examining whether there are distinct groups which show different self-efficacy trajectories over time, and the health status characteristics of any groups identified.

Methods: Participants completed serial questionnaire packs, including Unidimensional Self-efficacy-MS (USE-MS) scale, for the Trajectories of Outcome in Neurological Conditions-MS (TONiC-MS) study over an average 46-month period.

The impact of smoking cessation on multiple sclerosis disease progression.

The negative impact of smoking in multiple sclerosis is well established; however, there is much less evidence as to whether smoking cessation is beneficial to progression in multiple sclerosis. Adults with multiple sclerosis registered on the United Kingdom Multiple Sclerosis Register (2011-20) formed this retrospective and prospective cohort study. Primary outcomes were changes in three patient-reported outcomes: normalized Multiple Sclerosis Physical Impact Scale (MSIS-29-Phys), normalized Multiple Sclerosis Walking Scale (MSWS-12) and the Hospital Anxiety and Depression Scale (HADS).

Quality of life in multiple sclerosis is dominated by fatigue, disability and self-efficacy.

Background And Objective: Quality of life in multiple sclerosis (MS) reflects complex relationships between symptoms (fatigue, spasticity pain, and bladder or vision dysfunction), disability, health perceptions, and self-efficacy.

Methods: In this cross-sectional study, a self-report questionnaire pack of patient reported outcome measures was collected from 5695 people with MS (pwMS) alongside clinical data from their neurologists. Each patient reported outcome measure was converted to interval-scaled estimates following fit to the Rasch model.

Measuring coping in people with amyotrophic lateral sclerosis using the Coping Index-ALS: A patient derived, Rasch compliant scale.

Objective: The progressively disabling and terminal nature of ALS/MND imposes major coping demands on patients. We wished to improve the psychometric properties of our previously published MND-Coping Scale, so that parametric analyses were valid, and to make it simpler for patients to complete and clinicians to score.

Methods: After a new qualitative analysis of 26 patients with ALS/MND, the draft Coping Index-ALS (CI-ALS) was administered to 465 additional patients, alongside COPE-60, General Perceived Self Efficacy scale, and WHOQOL-BREF.

Measuring quality of life in ALS/MND: validation of the WHOQOL-BREF.

The World Health Organization Quality of Life-BREF Scale (WHOQOL-BREF) is a generic QOL measure with four domains covering Physical, Psychological, Social and Environment. Providing the opportunity to contrast QoL with other conditions, or with population norms, the current study had three aims: 1) can the established domains of the WHOQOL-BREF be validated within a large ALS/MND population; 2) can a total score be validated and 3) can they provide interval level measurement? Data were obtained from the Trajectories of Outcomes in Neurological Conditions study. Internal construct validity was determined by fit of the data to the Rasch measurement model.

Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment.

Background: Anti-TNF exposure has been linked to demyelination events. We sought to describe the clinical features of demyelination events following anti-TNF treatment and to test whether affected patients were genetically predisposed to multiple sclerosis [MS].

Methods: We conducted a case-control study to describe the clinical features of demyelination events following anti-TNF exposure.

Health state utility values (QALY weights) for Huntington's disease: an analysis of data from the European Huntington's Disease Network (EHDN).

Background: Huntington's Disease (HD) is a hereditary neurodegenerative disorder which affects individuals' ability to walk, talk, think, and reason. Onset is usually in the forties, there are no therapies currently available that alter disease course, and life expectancy is 10-20 years from diagnosis. The gene causing HD is fully penetrant, with a 50% probability of passing the disease to offspring.

Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2).

Background: Evidence is conflicting about a causal role of inflammation in psychosis and, specifically, regarding antibodies binding to neuronal membrane targets, especially N-methyl-D-aspartate receptors. NMDAR, LGI1 and GABA-A antibodies were found more prevalent in people with psychosis than in healthy controls. We aim to test whether these antibodies are pathogenic and may cause isolated psychosis.

The relationships between symptoms, disability, perceived health and quality of life in amyotrophic lateral sclerosis/motor neuron disease.

: Using the Wilson and Cleary model linking clinical variables to quality of life, we explored the associations between physical and psychological factors, disability, perceived health and quality of life in ALS/MND. : The ongoing UK study of Trajectories of Outcomes in Neurological Conditions (TONiC) recruited participants with ALS/MND to complete a questionnaire pack including demographic factors and several patient reported outcome measures (PROMs); a clinician provided data on disease onset type and duration since diagnosis. All PROMs were transformed from ordinal raw scores to interval-scaled latent estimates via the Rasch measurement model.

Outcome of cell suspension allografts in a patient with Huntington's disease.

For patients with incurable neurodegenerative disorders such as Huntington's (HD) and Parkinson's disease, cell transplantation has been explored as a potential treatment option. Here, we present the first clinicopathological study of a patient with HD in receipt of cell-suspension striatal allografts who took part in the NEST-UK multicenter clinical transplantation trial. Using various immunohistochemical techniques, we found a discrepancy in the survival of grafted projection neurons with respect to grafted interneurons as well as major ongoing inflammatory and immune responses to the grafted tissue with evidence of mutant huntingtin aggregates within the transplant area.

Validating the portal population of the United Kingdom Multiple Sclerosis Register.

The UK Multiple Sclerosis Register (UKMSR) is a large cohort study designed to capture 'real world' information about living with multiple sclerosis (MS) in the UK from diverse sources. The primary source of data is directly from people with Multiple Sclerosis (pwMS) captured by longitudinal questionnaires via an internet portal. This population's diagnosis of MS is self-reported and therefore unverified.

Development and validation of Spasticity Index-Amyotrophic Lateral Sclerosis.

Objectives: Spasticity is a common and disabling feature of amyotrophic lateral sclerosis (ALS). There are currently no validated ALS-specific measures of spasticity. The aim of this study was to develop and use a self-report outcome measure for spasticity in ALS.

Cost-effectiveness analysis of abobotulinumtoxinA for the treatment of cervical dystonia in the United Kingdom.

Background: Cervical dystonia (CD) involves painful involuntary contraction of the neck and shoulder muscles and abnormal posture in middle-aged adults. Botulinum neurotoxin type A (BoNT-A) is effective in treating CD but little is known about its associated cost-effectiveness.

Objective: To evaluate the cost-effectiveness of abobotulinumtoxinA for treating CD from the UK payer perspective.

A multicentre evaluation of oropharyngeal secretion management practices in amyotrophic lateral sclerosis.

Failure to clear oral secretions can be debilitating for patients with amyotrophic lateral sclerosis (ALS), but the treatment of this symptom is poorly defined and there is no consensus on best practice. The objective of this study was to identify the treatments that are commonly prescribed, and to describe how experienced clinicians manage a patient with treatment resistant symptoms. Twenty-three clinicians were approached, of which 19 from 16 centres across the UK provided case report forms for a total of 119 ALS patients identified as having problematic oral secretions.

AbobotulinumtoxinA in the management of cervical dystonia in the United Kingdom: a budget impact analysis.

Background: Cervical dystonia (CD) can be effectively managed by a combination of botulinum neurotoxin A (BoNT-A) and conventional therapy (skeletal muscle relaxants and rehabilitative therapy), but the costs of different interventions in the UK vary.

Methods: A budget impact model was developed from the UK payer perspective with a 5-year time horizon to evaluate the effects of changing market shares of abobotulinumtoxinA, onabotulinumtoxinA, and incobotulinumtoxinA, and best supportive care from the UK payer perspective. Epidemiological and resource use data were retrieved from the published literature and clinical expert opinion.

Laboratory medicine best practice guideline: vitamins a, e and the carotenoids in blood.

Despite apparent method similarities between laboratories there appear to be confounding factors inhibiting uniform reporting and standardisation of vitamin assays. The Australasian Association of Clinical Biochemists (AACB) Vitamins Working Party, in conjunction with The Royal College of Pathologists of Australasia Quality Assurance Programs, has formulated a guideline to improve performance, reproducibility and accuracy of fat-soluble vitamin results. The aim of the guideline is to identify critical pre-analytical, analytical and post-analytical components of the analysis of vitamins A, E and carotenoids in blood to promote best practice and harmonisation.