Algorithmic approach to finding people with multiple sclerosis using routine healthcare data in Wales.

BACKGROUND: Identification of multiple sclerosis (MS) cases in routine healthcare data repositories remains challenging. MS can have a protracted diagnostic process and is rarely identified as a primary reason for admission to the hospital. Difficulties in identification are compounded in systems that do not include insurance or payer information concerning drug treatments or non-notifiable disease. AIM: To develop an algorithm to reliably identify MS cases within a national health data bank. METHOD: Retrospective analysis of the Secure Anonymised Information Linkage (SAIL) databank was used to identify MS cases using a novel algorithm. Sensitivity and specificity were tested using two existing independent MS datasets, one clinically validated and population-based and a second from a self-registered MS national registry. RESULTS: From 4 757 428 records, the algorithm identified 6194 living cases of MS within Wales on 31 December 2020 (prevalence 221.65 (95% CI 216.17 to 227.24) per 100 000). Case-finding sensitivity and specificity were 96.8% and 99.9% for the clinically validated population-based cohort and sensitivity was 96.7% for the self-declared registry population. DISCUSSION: The algorithm successfully identified MS cases within the SAIL databank with high sensitivity and specificity, verified by two independent populations and has important utility in large-scale epidemiological studies of MS.

Mental health of people with multiple sclerosis during the COVID-19 outbreak: A prospective cohort and cross-sectional case-control study of the UK MS Register.

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 outbreak in the United Kingdom. METHODS: This is a community-based, prospective longitudinal cohort and cross-sectional case-control online questionnaire study. It includes 2010 pwMS from the UK MS Register and 380 people without MS. RESULTS: The Hospital Anxiety and Depression Scale scores of pwMS for anxiety and depression during the outbreak did not change from the previous year. PwMS were more likely to have anxiety (using General Anxiety Disorder-7) and/or depression (using Patient Health Questionnaire-9) than controls during the outbreak (OR: 2.14, 95% CI: 1.58-2.91). PwMS felt lonelier (OR: 1.37, 95% CI: 1.04-1.80) reported worse social support (OR: 1.90, 95% CI: 1.18-3.07) and reported worsened exercise habits (OR: 1.65, 95% CI: 1.18-2.32) during the outbreak than controls. CONCLUSION: Early in the pandemic, pwMS remained at higher risk of experiencing anxiety and depression than the general population. It is important that multidisciplinary teams improve their support for the wellbeing of pwMS, who are vulnerable to the negative effects of the pandemic on their lifestyle and social support.

Recovery From COVID-19 in Multiple Sclerosis: A Prospective and Longitudinal Cohort Study of the United Kingdom Multiple Sclerosis Register.

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-19 from March 17, 2020, to March 19, 2021, as part of the United Kingdom MS Register (UKMSR) COVID-19 study. Participants used online questionnaires to regularly update their COVID-19 symptoms, recovery status, and duration of symptoms for those who fully recovered. Questionnaires were date stamped for estimation of COVID-19 symptom duration for those who had not recovered at their last follow-up. The UKMSR holds demographic and up-to-date clinical data on participants as well as their web-based Expanded Disability Status Scale (web-EDSS) and Hospital Anxiety and Depression Scale (HADS) scores. The association between these factors and recovery from COVID-19 was assessed using multivariable Cox regression analysis. RESULTS: Of the 7,977 patients with MS who participated in the UKMSR COVID-19 study, 599 reported COVID-19 and prospectively updated their recovery status. Twenty-eight hospitalized participants were excluded. At least 165 participants (29.7%) had long-standing COVID-19 symptoms for ≥4 weeks and 69 (12.4%) for ≥12 weeks. Participants with pre-COVID-19 web-EDSS scores ≥7, participants with probable anxiety and/or depression (HADS scores ≥11) before COVID-19 onset, and women were less likely to report recovery from COVID-19. DISCUSSION: Patients with MS are affected by postacute sequelae of COVID-19. Preexisting severe neurologic impairment or mental health problems appear to increase this risk. These findings can have implications in tailoring their post-COVID-19 rehabilitation.

SARS-CoV-2 vaccination in patients with multiple sclerosis in Germany and the United Kingdom: Gender-specific results from a longitudinal observational study.

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 and United Kingdom (UK) PwMS, especially regarding gender-specific differences. Methods: The German Multiple Sclerosis Society and the UK MS Registry acquired health data via an online system following the first (X1) and second SARS-CoV-2 vaccination (X2), respectively: sociodemographic and clinical data, vaccines used, VRs, MS deterioration (worsened or new MS symptoms, Germany only) and relapses (Germany only). The frequencies of VRs and MS deterioration were analysed stratified by gender. Findings: Following X1 (X2), 2346 (1835) German PwMS and 3796 (683) UK PwMS participated in the study. The most frequent vaccination scheme was two-dose tozinameran for Germany (77·1%, 1424/1847) and two-dose AZD1222 for the UK (61·3%, 419/683). The most common VRs were fatigue, headache and pain (at the injection site) and occurred more often in women compared with men. German PwMS reported VRs more frequently after X2 vs. X1 (65·4% [1201/1835] vs. 61·2% [1435/2346]), while for UK patients it was the opposite (X1 vs. X2: 48·7% [1849/3796] vs. 30·0% [205/683]). MS deterioration occurred in 19·0% (445/2346) of the German PwMS without resulting in gender-specific differences. Fatigue and gait impairment were the most frequent deteriorated MS symptoms. Interpretation: Female PwMS reported experiencing VRs more often than men. Longitudinal data are needed to enable valid statements regarding long-term MS deterioration and long-lasting VRs. Funding: German Multiple Sclerosis Society (DMSG Bundesverband e.V.), Biogen, Bristol Myers Squibb, Merck Serono, Mylan, Novartis, Roche and Sanofi.

COVID-19 is associated with new symptoms of multiple sclerosis that are prevented by disease modifying therapies.

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 conducted as part of the United Kingdom MS Register. People with MS and COVID-19 were invited by email to complete a questionnaire about their MS symptoms during the infection. An MS exacerbation was defined as developing new MS symptoms and/or worsening of pre-existing MS symptoms. RESULTS: Fifty-seven percent (230/404) of participants had an MS exacerbation during their infection; 82 developed new MS symptoms, 207 experienced worsened pre-existing MS symptoms, and 59 reported both. Disease modifying therapies (DMTs) reduced the likelihood of developing new MS symptoms during the infection (OR 0.556, 95%CI 0.316-0.978). Participants with a higher pre-COVID-19 webEDSS (web-based Expanded Disability Status Scale) score (OR 1.251, 95%CI 1.060-1.478) and longer MS duration (OR 1.042, 95%CI 1.009-1.076) were more likely to experience worsening of their pre-existing MS symptoms during the infection. CONCLUSION: COVID-19 infection was associated with exacerbation of MS. DMTs reduced the chance of developing new MS symptoms during the infection.

Willingness to receive a COVID-19 vaccine in people with multiple sclerosis - UK MS Register survey.

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 5.6% would not. PwMS who have previously had an influenza vaccine, increasing age and the perception of having sufficient information about the vaccine were associated with increased likelihood of getting a vaccine. 51.7% of 3191 pwMS completed a follow-up survey indicating they received at least 1 dose of a COVID-19 vaccine. The proportion having had the vaccination based on their prior opinions was 53.2% in 'Yes' group and 27.0% in 'No' group, the latter reflecting a change based on their initial views. More information on COVID-19 vaccine safety in pwMS would be helpful for people to make informed decisions.

Personal and societal costs of multiple sclerosis in the UK: A population-based MS Registry study.

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 sclerosis and linked this with data within the United Kingdom Multiple Sclerosis Register and from their hospital records. Resource consumption was categorised as being medical or non-medical and costed by National Health Service and social services estimates for 2018. RESULTS: We calculated £509,003 in non-medical costs over a year and £435,488 in medical costs generated over 3 months. People with multiple sclerosis reported self-funding 75% of non-medical costs with non-medical interventions having long-term potential benefits. Costs increased with disability as measured by patient-reported Expanded Disability Status Score and Multiple Sclerosis Impact Scale, with Multiple Sclerosis Impact Scale physical being a more powerful predictor of costs than the patient-reported Expanded Disability Status Score. Two distinct groups were identified: medical and non-medical interventions (n = 138); and medical interventions only (n = 399). The medical and non-medical group reported increased disease severity and reduced employment but incurred 80% more medical costs per person than the medical-only group. CONCLUSIONS: The importance of disability in driving costs is illustrated with balance between medical and non-medical costs consistent with the United Kingdom health environment. People with multiple sclerosis and their families fund a considerable proportion of non-medical costs but non-medical interventions with longer term impact could affect future medical costs.

How to refer to people with disease in research outputs: The disconnection between academic practise and that preferred by people with multiple sclerosis.

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 currently used by academics. METHODS: Several surveys were undertaken: one from the Research Network of the MS Society (MSSRN), a major MS Charity within the United Kingdom, who are involved in reviewing grant applications, priority setting and research governance (n=146), and surveys from both the United Kingdom MS register (MSR; n=1713) and the North American Research Committee on Multiple Sclerosis (NARCOMS) registry (n=518). People were asked to rate descriptors of someone affected with MS. These were compared to that used by academic experimenters in basic science and clinical science research papers. RESULTS: Although the frequency of responses varied between surveys the overall findings showed many consistencies. This included use of person/people with MS (pwMS) as the preferred descriptor for someone with MS for social media and scientific publications. This was the preferred choice in about 55-60% people from the MRS and in over 70% in the NARCOMS and the MSSRN, respectively. Although MSer was the second preferred-choice for use in social media, there was as a large range of preferences from the 'most-preferred' to the 'most-disliked.' This reflected an earlier survey by UK-based research blogs using the term MSer (n=173). In contrast, pwMS had few 'dislikes' and results were skewed towards the 'liked' and 'most-preferred' choices. Client and sufferer were generally disliked terms, although there was some regional variation in levels of choice. Patient was generally seen as a neutral term that was neither strongly liked nor disliked. However, patient gained more public support for use within scientific publications (~20-25%) compared to social media (~10-15%). This descriptor was however most commonly used (98-99%) within both pre-clinical (searched in 6-month output of preclinical autoimmune MS models; n=161) and in clinical publications (specialist MS journals; n=220), whereas pwMS was not reported in over 75% of papers published in some specialised MS journals, and did not appear in the pre-clinical animal studies examined. CONCLUSION: There is a clear disconnection between preferences by individuals living with MS and current academic practise. As pwMS are increasingly reading primary research publications and are involved in patient and public involvement in research and grant review activities, the sensitivities of lay readers should be considered when writing research outputs. This issue may affect other diseases and a change in writing style could be adopted to show that we respect the wishes of the people that we study and wish to help.

Physical disability, anxiety and depression in people with MS: an internet-based survey via the UK MS Register.

INTRODUCTION: People with Multiple Sclerosis are known to have a relatively high prevalence of both anxiety and depression. Studies of the relationship between physical disability and mental health in people with MS have reported mixed results, showing the need for further work. METHODS: Between May 2011 and April 2012, 4516 people completed the MSIS-29 (v.1) and HADS scales via the dedicated internet site of the UK MS Register within a 7 day time window. These responses were linked with basic demographic and descriptive data and analysed in SPSS (v.20). RESULTS: The proportions of people experiencing anxiety or depression increased with physical disability such that 38.0% of respondents with low, and 66.7% with high disability reported at least mild anxiety, and 17.1% of people with low, and 71.7% with high disability experienced at least mild depression. The multiple regression model explained 18.4% of the variance in anxiety with MSIS-29-PHYS score being the strongest predictor of anxiety. The model for depression explained 37.8% of the variance with MSIS-29-PHYS score being the strongest predictor. Some of the other variables included showed negative associations with anxiety and depression, indicating that the influence of physical disability on mental wellbeing could be underestimated. CONCLUSIONS: This study indicates that there is a positive relationship between physical disability and anxiety and depression, that physical disability impacts on anxiety and depression to differing extents, and that the effects vary with gender, age, disease course and disease duration. We have shown that physical disability is a predictor of anxiety and depression, and that other factors may mask the extent of this effect. Whether the causes of anxiety and depression are reactive, organic or a combination, it is essential that mental wellbeing is given due attention in caring for people with MS so that all their health needs can be met.

Desirability and expectations of the UK MS Register: views of people with MS.

BACKGROUND: Internet-based health registers are increasingly commonly used for health promotion and medical research, yet little is known about what the patient groups who help form the basis of such registers expect from these tools. Mismatches between patient expectations and the register design may limit the long-term utility of such registers. OBJECTIVE: This study elicited the views of people with Multiple Sclerosis (PwMS) on the desirability and expectations regarding a UK Register for MS. METHODS: Participants were recruited through a range of traditional means (newsletters, adverts, word of mouth), as well as via the Internet, to obtain a broad sample of PwMS. Semi-structured interviews were conducted over the telephone, and the questions asked about: the desirability of the Register; what the participants envisaged the Register actually being used for; and what they hoped the Register could be used for. RESULTS: The majority of individuals' points postulated that a UK MS Register would be useful, but a range of potential concerns were identified by the sample, such as security, accessibility for all PwMS, and the validity of self-report data. Analysis of the responses revealed a difference between what PwMS thought the Register would be used for, and how they wanted it to be used, particularly in relation to a desired social contact, exchange, and networking function. CONCLUSIONS: The security and accessibility of the website, the validity of the data, and mismatches between the expected and actual uses, are all issues of importance in the development of e-health tools, if PwMS are to be successfully engaged over time.

The physical and psychological impact of multiple sclerosis using the MSIS-29 via the web portal of the UK MS Register.

INTRODUCTION: The MSIS-29 was developed to assess the physical and psychological impact of MS. The aims of this study were to use the responses to the MSIS-29 via the web portal of the UK MS Register to: examine the internal properties of the scale delivered via the internet, profile the cohort, and assess how well the scale measures impact of disability on the potential workforce. METHODS: Between May 2011 and April 2012, 4558 people with MS completed the MSIS-29(v.1). The responses were collated with basic demographic and descriptive MS data and the resulting dataset was analysed in SPSS(v.20). RESULTS: Internal consistency was high (Cronbach's alpha 0.97 MSIS-29-PHYS, 0.92 MSIS-29-PSYCH). The mean MSIS-29-PHYS score was 60.5 (50.6%) with a median of 62 and the mean MSIS-29-PSYCH score was 24.8 (43.8%) with a median of 24. Physical scores increased with age and disease duration (p<0.001, p<0.001), but there was a weak negative relationship between psychological scores and age (p<0.001). The odds of people having an employment status of sick/disabled were 7.2 (CI 5.5, 9.4, p<0.001) for people with a moderate physical score, and 22.3 (CI 17.0, 29.3, p<0.001) for people with a high physical score (relative to having a low physical score). CONCLUSIONS: This largest known study of its kind has demonstrated how the MSIS-29 can be administered via the internet to characterise a cohort, and to predict the likely impact of disability on taking an active part in the workforce, as a reasonable proxy for the effects of MS on general activities. The findings examining MSIS-29-PHYS and MSIS-29-PSYCH scores against age support the use of two sub-scales, not a combined score. These results underline the importance of using a scale such as this to monitor disability levels regularly in guiding MS care to enable people to be as active as possible.

How people with multiple sclerosis rate their quality of life: an EQ-5D survey via the UK MS register.

INTRODUCTION: The EQ-5D is a widely-used, standardised, quality of life measure producing health profiles, indices and states. The aims of this study were to assess the role of various factors in how people with Multiple Sclerosis rate their quality of life, based on responses to the EQ-5D received via the web portal of the UK MS Register. METHODS: The 4516 responses to the EQ-5D (between May 2011 and April 2012) were collated with basic demographic and descriptive MS data and the resulting dataset was analysed in SPSS (v.20). RESULTS: The mean health state for people with MS was 59.73 (SD 22.4, median 61), compared to the UK population mean of 82.48 (which is approximately 1SD above the cohort mean). The characteristics of respondents with high health states (at or above +1SD) were: better health profiles (most predictive dimension: Usual Activities), higher health indices, younger age, shorter durations of MS, female gender, relapsing-remitting MS, higher educational attainment and being in paid employment (all p-values<0.001). Conversely, the characteristics of respondents with low health states (at or below -1SD) were: poorer health profiles (most predictive dimension: Mobility), lower health indices, older age, longer durations of MS, male gender, progressive MS, lower educational attainment and having an employment status of sick/disabled (p = 0.0014 for age, all other p-values<0.001). Particular living arrangements were not associated with either the high or low health status groups. CONCLUSIONS: This large-scale study has enabled in-depth analyses on how people with MS rate their quality of life, and it provides new knowledge on the various factors that contribute to their self-assessed health status. These findings demonstrate the impact of MS on quality of life, and they can be used to inform care provision and further research, to work towards enhancing the quality of life of people with MS.

A large-scale study of anxiety and depression in people with Multiple Sclerosis: a survey via the web portal of the UK MS Register.

INTRODUCTION: Studies have found that people with Multiple Sclerosis experience relatively high rates of anxiety and depression. Although methodologically robust, many of these studies had access to only modest sample sizes (N<200). The aims of this study were to use responses gained via the web portal of the UK MS Register (N>4000) to: describe the depression and anxiety profiles of people with MS; to determine if anxiety and depression are related to age or disease duration; and to assess whether the levels of anxiety and depression differ between genders and types of MS. METHODS: From its launch in May 2011 to the end of December 2011, 7786 adults with MS enrolled to take part in the UK MS Register via the web portal. The responses to the Hospital Anxiety and Depression Scale (HADS) were collated with basic demographic and descriptive MS data provided at registration and the resulting dataset was analysed in SPSS (v.16). RESULTS: The mean HADS score among the 4178 respondents was 15.7 (SE 0.117, SD 7.55) with a median of 15.0 (IQR 11). Anxiety and depression rates were notably high, with over half (54.1%) scoring ≥ 8 for anxiety and 46.9% scoring ≥ 8 for depression. Women with relapsing-remitting MS were more anxious than men with this type (p<0.001), and than women with other types of MS (p = 0.017). Within each gender, men and women with secondary progressive MS were more depressed than men or women with other types of MS (p<0.001, p<0.001). CONCLUSIONS: This largest known study of its kind has shown that anxiety and depression are highly prevalent in people with MS, indicating that their mental health needs could be better addressed. These findings support service planning and further research to provide the best care for people with MS to help alleviate these debilitating conditions.