Rodden M Middleton

Swansea University | SWAN · Faculty of Medicine Health and Life-Sciences

Introduction: Prescribing guidance for disease-modifying treatment (DMT) in multiple sclerosis (MS) is centred on a clinical diagnosis of relapsing-remitting MS (RRMS). DMT prescription guidelines and monitoring vary across countries. Standardising the approach to diagnosis of disease course, for example, assigning RRMS or secondary progressive MS...

Registries have the potential to tackle some of the current limitations in determining the long-term impact of multiple sclerosis. Online assessments using patient-reported outcomes can streamline follow-up enabling large-scale, long-term, cost-effective, home-based, and patient-focused data collection. However, registry data are sparsely sampled a...

Understanding the associations and potential drivers of long-term disability in Multiple Sclerosis (MS) is of clinical and prognostic value. Previous data have suggested a link between depression and disability accrual in MS. We aimed to determine whether depression in early MS predicts subsequent accrual of disability. Using data from the UK MS Re...

Purpose Genetic studies of multiple sclerosis (MS) susceptibility and severity have focused on populations of European ancestry. Studying MS genetics in other ancestral groups is necessary to determine the generalisability of these findings. The genetic Association study in individuals from Diverse Ancestral backgrounds with Multiple Sclerosis (ADA...

Background To assign a course of secondary progressive multiple sclerosis (MS) (SPMS) may be difficult and the proportion of persons with SPMS varies between reports. An objective method for disease course classification may give a better estimation of the relative proportions of relapsing–remitting MS (RRMS) and SPMS and may identify situations wh...

Background: Multiple sclerosis (MS) is frequently diagnosed in people of reproductive age, many of whom will become pregnant following diagnosis. Although many women report an improvement in symptoms and relapses during pregnancy, symptoms such as fatigue and spasticity are commonly reported and can worsen. Prescribing medications during pregnancy...

Background: Vaccines offer people with multiple sclerosis (PwMS) an effective protection against severe COVID-19 disease courses. However, representative real-world data on the tolerability of SARS-CoV-2 vaccines in PwMS are limited. We aimed at analysing vaccination reactions (VRs) and MS deterioration following SARS-CoV-2 vaccinations in German...

Background Letters dictated by healthcare professionals in routine patient care form an invaluable dataset but are difficult to access and interpret. The UK MS Register (UKMSR) previously outlined (ABN2019) usage of Natural Language Processing Algorithms (NLP-A) to harvest and transform written language into analysable data in databases. We expande...

Background We present baseline data on the first 50 participants recruited to the UK MS Pregnancy Register. Methods Data collected via questionnaires from consenting participants until 20th December 2021 were included. Results 50 participants (all with relapsing remitting MS; mean age at diagnosis 28.0 years; mean age at recruitment 33.0 years) w...

Introduction Repurposing treatments in multiple sclerosis (MS) has resulted in several candidates that are currently in phase 2 and 3 trials but to test candidate therapies requires a prolonged and costly study. Real world data offers the opportunity to assess in non-randomised data the potential of a range of commonly used therapies. The UK MS reg...

Neurological conditions present with cognitive impairment that greatly affects the quality of life of the patients and should be routinely evaluated. However, it can be difficult to detect and impractical to monitor with classic in person cognitive assessment due to limitations of sensitivity, scalability and cost. Internet- and app-based tools for...

Background and objectives: Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is...

Introduction One of the strongest predictors of successful coping in multiple sclerosis (MS) is the extent to which one can accept the diagnosis and limitations associated with the disease. Acceptance is also one of three core processes of psychological flexibility – a malleable treatment target of some psychological therapies. This is the ability...

Background Amidst the growing number of patient-reported outcome (PRO) measures of fatigue being used in multiple sclerosis (MS) clinical trials and clinics, evidence-based consensus on the most appropriate and generalizable measures across different settings would be beneficial for clinical research and patient care. The objective of this research...

Background Interferon-β, a disease-modifying therapy (DMT) for MS, may be associated with less severe COVID-19 in people with MS. Results Among 5,568 patients (83.4% confirmed COVID-19), interferon-treated patients had lower risk of severe COVID-19 compared to untreated, but not to glatiramer-acetate, dimethyl-fumarate, or pooled other DMTs. Conc...

Background: Fatigue is a widely experienced, incapacitating symptom of MS. It hinders daily functioning and has deleterious effects on quality of life. The UK MS Register is an online registry of over 20,000 participants with MS. The aim of this study was to estimate the prevalence, predictors, and impact of fatigue on people with MS using data fr...

COVID-19 is a concern in people with multiple sclerosis (MS), mostly because of their long-term physical disabilities and immunomodulatory disease-modifying therapies (DMTs). In this community-based pro- spective longitudinal study, we have been monitoring a cohort of people with MS via the web-based platform of the UK MS Register since the start o...

Introduction Global efforts in vaccine development against SARS-CoV-2 saw the Pfizer-BioNTech vaccine approved for use in the United Kingdom (UK) on 2nd December 2020. There have long been discussions around vaccination in patients with multiple sclerosis (pwMS). We conducted a patient survey as part of the UK MS Register (UKMSR), to understand pwM...

Objective To evaluate the exchange of information and communication between MS patients and the clinical team regarding decisions around disease modifying therapy (DMT) and MRI results utilising the UKMSR, an established, validated cohort of people with MS. Methods An online questionnaire was designed and then disseminated to patients in February...

Background Given the expanding utility of cerebrospinal fluid biomarkers in clinical practice and research studies, it may become desirable to offer repeat lumbar puncture (LP) beyond diagnosis. Using the United Kingdom Multiple Sclerosis Register (UKMSR), we assessed patient attitude to LP beyond the diagnostic stage. Design/ Methods An online qu...

Background The UK Multiple Sclerosis Register (UKMSR) captures data from multiple sources including directly from people with MS (pwMS) via online questionnaires. There is little research into the non-medical (personal) costs of MS. In partnership with Sanofi we investigated healthcare resource use and costs (excluding drugs), including who bears t...

Background The UK MS Register (UKMSR) has been capturing longitudinal clinical and patient reported outcomes (PROs) since 2011. As the UK population ‘locked-down’ in March 2020 it became important that clinicians could record hospitalised MS patients due to COVID-19 and record outcome. The UKMSR provided an electronic case return form, designed col...

Introduction Objective algorithms (OA; Ramanujam, 2020) identify SPMS in those with clinically assigned (CA) RRMS, suggesting SPMS is under-diagnosed in practice. It’s unclear if clinicians are aware of this evolution and escalate therapy in response to clinical worsening with highly active (HA) disease modifying treatments (DMT). Objective Assess...

Introduction The UK MS Register (UKMSR) has collected longitudinal patient reported outcomes (PROs) on pwMS regularly since 2011. Aim to assess changes in disability and quality in life (QOL) in the UKMSR before and during the pandemic Methods pwMS who answered the PROs: webEDSS to assess disability in MS and EQ5D-3L visual analogue scale for QOL,...

Background The UK Multiple Sclerosis Register (UKMSR) was established in 2011 to capture ‘real world’ data from people with MS (pwMS) and the NHS. Capturing clinical data from the NHS for research is time consuming for clinical staff, can involve complicated governance, security and data quality issues. UKMSR has implemented quality controls, valid...

Objectives Early treatment in MS often needs to be started in the absence of symptoms. This preventa- tive approach is a complex concept to convey to a naïve population. We produced a 164 second film without dialogue with the aim of assessing whether it delivered its message successfully. Methods PwMS were recruited from clinics, the UK MS Registe...

Background Provision of care to patients with Multiple Sclerosis (MS) is complex and an effective multi- disciplinary team (MDT) approach is needed. We surveyed patients’ experiences of ideal care and care actually provided. Methods We designed a questionnaire to evaluate service provision and expectation in a nationwide cohort of patients from th...

Background People with Multiple Sclerosis (PwMS) suffer from an increased risk of unemployment during the course of the disease. In recent years progress has been made in increasing the time until patients have to leave the workforce permanently. Such a retirement is often associated with MS but the driving factors including disability progression,...

Background : A valid, sensitive patient-reported outcome (PRO) measure of physical function (PF) for people with multiple sclerosis (MS) would have substantial value in routine care and clinical research. We now describe development of the PROMISnq Short Form v2.0 PF – Multiple Sclerosis 15a [PROMISnq PF(MS)15a] for assessing PF in relapsing and pr...

Background and Objectives To understand the course of recovery from coronavirus disease 2019 (COVID-19) among patients with multiple sclerosis (MS) and to determine its predictors, including patients' pre–COVID-19 physical and mental health status. Methods This prospective and longitudinal cohort study recruited patients with MS who reported COVID...

Background Deprivation can impact the access to health interventions in publicly funded health systems where cost is not the dominant barrier. In this study we examined whether deprivation affected the access to disease modifying therapies (DMTs) for multiple sclerosis (MS). Methods All English adults on the UK MS register with relapsing remitting...

Background In March 2020, the United Kingdom Multiple Sclerosis Register (UKMSR) established an electronic case return form, designed collaboratively by MS neurologists, to record data about COVID-19 infections in people with MS (pwMS). Objectives Examine how hospital admission and mortality are affected by disability, age and disease modifying tr...

The negative impact of smoking in MS is well established, however, there is much less evidence as to whether smoking cessation is beneficial to progression in MS. Adults with MS registered on the United Kingdom MS Register (2011-2020) formed this retrospective and prospective cohort study. Primary outcomes were changes in 3 patient reported outcome...

Background People with multiple sclerosis (MS) are a vulnerable group for severe COVID- 19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. Methods Data from 12 data-sources in 28 countries were aggregated (sources cou...

Background People with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. Methods Data from 12 data-sources in 28 countries were aggregated (sources coul...

Background & Methods: We conducted an online COVID-19 survey as the vaccines became available, utilising the UK MS Register, to understand people with multiple sclerosis (pwMS) views on COVID-19 vaccination and the subsequent vaccine uptake rates. Results & Conclusion: 94.4% of 3191 pwMS surveyed indicated they would get a COVID-19 vaccine, while 5...

Objectives: To assess the prevalence of and factors associated with developing long COVID among patients with multiple sclerosis (MS), a condition which shares the neurological and psychological symptomatology of long COVID Design: Community-based prospective and longitudinal observational study Setting: The United Kingdom (UK) MS Register (UKMSR)...

Background People with MS (pwMS) have had higher rates of anxiety and depression than the general population before the COVID-19 pandemic, placing them at higher risk of experiencing poor psychological wellbeing during the pandemic. Objective To assess mental health and its social/lifestyle determinants in pwMS during the first wave of the outbrea...

Objectives To capture the complexities and unique experience of a newly formed multidisciplinary and multicentre research team developing and deploying a COVID-19 study and to identify lessons learnt. Design Co-autoethnographic study. Setting Staff at two UK academic institutions, a national charity and two major UK hospitals. Participants Resea...

Background Fatigue is one of the most common and the single most disabling symptom of multiple sclerosis (MS). However, there is a lack of consensus on the most appropriate fatigue measures in clinical practice and research, based upon rigorously validated, generalizable, and publicly available instruments. The objective of this research was to gen...

Background Infections can trigger exacerbations of multiple sclerosis (MS). The effects of the coronavirus disease 2019 (COVID-19) on MS are not known. The aim of this study was to understand the impact of COVID-19 on new and pre-existing symptoms of MS. Methods The COVID-19 and MS study is an ongoing community-based, prospective cohort study cond...

Background: Infections can trigger exacerbations of multiple sclerosis (MS). The effects of the coronavirus disease 2019 (COVID-19) on MS are not known. The aim of this study was to understand the impact of COVID-19 on new and pre-existing symptoms of MS. Methods: The COVID-19 and MS study is an ongoing community-based, prospective cohort study con...

Background People with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. Methods Data from 12 data-sources in 28 countries were aggregated. Demographic...

The Multiple Sclerosis Data Alliance (MSDA), a global multi-stakeholder collaboration, is working to accelerate research insights for innovative care and treatment for people with multiple sclerosis (MS) through better use of real-world data (RWD). Despite the increasing reliance on RWD, challenges and limitations complicate the generation, collect...

Abstract Objective: The association between vitamin D deficiency and multiple sclerosis (MS) is well described. We set out to use remote sampling to ascertain vitamin D status and vitamin D supplementation in a cross-sectional study of people with MS across the UK. Methods: People with MS and matched controls were recruited from across the UK. 17...

To assess the intake of nutrients in people with Multiple Sclerosis (pwMS) compared to a control population, and to assess the pro/ anti-inflammatory properties of nutrients/ foods and their relationships with fatigue and quality of life. This was a cross sectional study in which 2410 pwMS (686 men; 1721 women, 3 n/a, mean age 53 (11 yrs)) provided...

Objective The association between vitamin D deficiency and multiple sclerosis (MS) is well described. We set out to use remote sampling to ascertain vitamin D status and vitamin D supplementation in a cross-sectional study of people with MS across the UK. Methods People with MS and matched controls were recruited from across the UK. 1768 people wi...

Background: incorporating cognitive testing into routine clinical practice is a challenge in multiple sclerosis (MS), given the wide spectrum of both cognitive and physical impairments people can have and the time that testing requires. Shortened paper and verbal assessments predominate but still are not used routinely. Computer-based tests are bec...

Background We need high-quality data to assess the determinants for COVID-19 severity in people with MS (PwMS). Several studies have recently emerged but there is great benefit in aligning data collection efforts at a global scale. Objectives Our mission is to scale-up COVID-19 data collection efforts and provide the MS community with data-driven...

Technological innovation is transforming traditional clinical practice, enabling people with multiple sclerosis (pwMS) to contribute health care outcome data remotely between clinic visits. In both relapsing and progressive forms of multiple sclerosis (MS), patients may experience variable disability accrual and symptoms throughout their disease co...

Objective To assess the feasibility of collaboration and retrospective data harmonization among three multiple sclerosis (MS) registries by investigating employment status. Methods We used the Maelstrom guidelines to facilitate retrospective harmonization of data from three MS registries, including the NARCOMS (North American Research Committee on...

BACKGROUND Incorporating cognitive testing into clinical practice is a challenge in MS, given the wide spectrum of both cognitive and physical impairments. Shortened paper and verbal assessments predominate but still are not used routinely. Computer-based tests are becoming more widespread however changes in how a paper test is implemented can impa...

Background Incorporating cognitive testing into routine clinical practice is a challenge in multiple sclerosis (MS), given the wide spectrum of both cognitive and physical impairments people can have and the time that testing requires. Shortened paper and verbal assessments predominate but still are not used routinely. Computer-based tests are beco...

Objectives: To investigate through survey and data linkage, healthcare resource use and costs (except drugs), including who bears the cost, of multiple sclerosis in the United Kingdom by disease severity and type. Methods: The United Kingdom Multiple Sclerosis Register deployed a cost of illness survey, completed by people with multiple sclerosi...

Introduction Multiple sclerosis (MS) causes long-term disability with broad socioeconomic consequences. This may influence educational attainment in children of affected individuals. We investigated whether having a mother with MS affects performance in Welsh national attainment tests. Method Anonymised lists of 1584 women with MS diagnosed in two...

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...

Christoph Thalheim, in his capacity as consultant for EU health affairs, has received consultancy fees by Gruenenthal and by PharmaGenesis. In his capacity as Director External Affairs of the European MS Platform, he served in advisory boards and/or workshops by Biogen, Merck, Novartis, Sanofi Genzyme, Servier and Takeda. His employer, the European...

Objectives The UK MS Register is a large scale observational research platform, capturing data from patients, NHS and carries out linkage with routine data from the SAIL databank. We have 14,000 People with MS (PwMS) submitting Patient Reported Outcome Measures (PRoMS) quarterly and over 3000 patients consenting at NHS Sites around the UK A differe...

Objectives Electronic healthcare records (EHR) are the main data sources that facilitate epidemiology research. Routinely collected data such as primary and secondary care are now easily linked to produce novel and high impact research. There are, however, rich data locked in the free text of clinical letters that are not otherwise translated into...

Objectives The UK MS Register is a research project that aims to capture real world data about living with Multiple Sclerosis(MS) in the UK. Launched in 2011, identified data sources were: Directly from People with MS (PwMS) via the internet, from NHS treatment centers via ‘traditional’ database capture and by linkage to routine datasets from the S...

Background: Increasingly, Government and Charity funders require public engagement in research. Invariably these research outputs describe the condition of someone with the disease of interest. We therefore sought to identify the preferred descriptor of someone with a disease, such as multiple sclerosis (MS) and to determine what descriptors are c...

Objectives: The UK MS Register is an observational research study capturing data from People with MS(PwMS), the NHS and carries out linkage with routine data. There are 14,000 PwMS submitting Patient Reported outcome Measures (PRoMS) and over 3500 patients consenting at NHS sites. A goal of the UK MS Register from the outset was that it be paperl...

Objectives: The UK MS Register captures real world data about living with Multiple Sclerosis (MS), from 3 sources: People with MS (PwMS) via the internet, the NHS via database capture and by linkage to other routine datasets. NHS data, though ‘gold standard’, is dependent on clinical staff finding the time and relevant information to enter into cl...

Maternal sun exposure in gestation and throughout the lifetime is necessary for vitamin D synthesis, and living near the sea is a population level index of seafood consumption. The aim of this study was to estimate the incidence rate of multiple sclerosis (MS) in Wales and examine its association with sun exposure, coastal living, and latitude. The...

Minimal Data to Replicate the Analysis. This is a compressed Microsoft Excel file containing lower layer super output areas in Wales, population counts by age and gender groups, sunshine levels, and an indicator for coastal status. (DOCX)

Given the potential of health internet-registers, this study examined how such registers can be made more effective and efficient. This involved investigating the actual barriers to usage experienced by those for whom such registers are established to help. To elicit responses regarding the opinions, views, and experiences of participants, concerni...