Recent Submissions

  • Developing and user-testing the online word colour task to screen for cognitive problems in people with Multiple Sclerosis

    Kontou, Eirini; das Nair, Roshan (2023)
    Introduction: Cognitive problems affect 40-60% of people with Multiple Sclerosis (pwMS), but are not routinely screened for in MS clinics in the UK due to limited resources (including personnel to deliver cognitive tests) and finances (including payment for such tests). Consequently, those with cognitive problems are not identified early and triaged to receive the appropriate level of support. To address this gap, the NEuRoMS programme (www.neuroms. org) developed a neuropsychological pathway to routinely assess all pwMS attending MS clinics for cognitive problems. The pathway has been implemented in three UK MS clinics and has screened >3000 pwMS. Objectives/Aims: This work presents the iterative design and development process of the Word Colour Task (WCT), a free, online self-administered measure of selective attention and information processing. This has been included in the NEuRoMS cognitive screening pathway to screen pwMS for cognitive problems. Method(s): We followed an iterative development process and conducted multiple rounds of user testing. Beginning with a prototype based on literature and previous research, we held three stakeholder meetings with Patient and Public Involvement members, researchers and clinicians working with pwMS (n=18) to make design decisions. Following stakeholder feedback, we developed product specifications for a technical team to develop the online WCT. We then tested usability and acceptability through cognitive interviews with eight pwMS and made revisions. A further round of user-testing was undertaken before deployment into the NEuRoMS screening pathway. Result(s): User testing and cognitive interviews suggested that the WCT was acceptable, but some usability issues were identified (e.g., clarity of instructions, practice mode, repetition of stimuli) and suggestions were made to improve user experiences. Conclusion(s): Using an iterative design approach with significant and diverse stakeholder input, we were able to develop a robust and usable online cognitive screening assessment tool. The WCT has now been deployed in three MS clinics for feasibility testing having screened 370 pwMS. Validation and norming studies are currently underway to provide further evidence of its psychometric properties and collect UK-based norms.
  • Exploring the potential of SMART for improving cognitive health in people with multiple sclerosis

    Frost, Alexandra C. (2023)
    Introduction: For people living with multiple sclerosis (MS), cognitive difficulties (including problems with attention, planning, and problem-solving) are a common and particularly debilitating and distressing consequence. The efficacy of cognitive training and rehabilitation remains unclear, leaving a need to establish suitable evidence-based treatment options. Objectives/Aims: In response to the current state of evidence, we aim to examine the feasibility of trialling SMART (Strengthening Mental Abilities with Relational Training) - a theory-based online cognitive training programme - as a treatment option for improving cognitive health in people with multiple sclerosis. Method(s): We are recruiting 60 patients with MS and cognitive impairment to a three-arm feasibility randomised-controlled trial, comparing (1) SMART + treatment-as-usual (TAU) with (2) TAU and (3) active control ('sham') training + TAU. Consenting eligible patients complete a cognitive assessment battery and questionnaires assessing the impact of living with MS, health-related quality of life, subjective cognitive difficulties, and service/ resource use. After completing baseline assessments, participants are randomly allocated to one of the three trial arms. Participants complete follow-up assessments at 3 and 6 months post-randomisation and take part in feasibility-feedback interviews. Our critical criteria for progression to a full-scale trial are around intervention acceptability ('green' = >=80% of SMART group completing >=6 sessions of SMART training), recruitment (green = >=80% of target N consented/randomised), and retention (green = >=80% of all randomised participants completing three-month follow-up). Result(s): Based on available data (53 participants enrolled to date), we are currently green on intervention acceptability (91%) and retention (97%). We appear green for recruitment (90% of target enrolled); identified latencies between consent and randomisation complicate the picture, but (in consultation with our Trial Steering Committee) we have identified ways to address latencies in full-scale trialling. Conclusion(s): Assessment against core criteria currently favours progression and indicates that a full trial would be feasible. Qualitative feedback suggests that SMART can be a usable and acceptable programme for people with MS, supporting further investigation and efficacy testing (of effects on cognitive health outcomes and broader quality of life).
  • Integrating a newly developed cognitive screening and management pathway within MS clinics in the United Kingdom: A qualitative study

    das Nair, Roshan (2023)
    Introduction: Currently in the United Kingdom, there is no routine screening for cognitive problems and sufficient provision of neuropsychological management for all people with Multiple Sclerosis (pwMS) with cognitive problems. The NEuRoMS programme (www.neuroms.org) developed a pathway for routine cognitive screening (with >3,000 already screened) and a brief cognitive rehabilitation intervention programme for mild cognitive problems in pwMS. Objectives/Aims: This study investigated how the cognitive screening pathway was integrated into routine clinical practice in MS clinics, and how the intervention was experienced by those who delivered and received it. Method(s): Multi-centre, in-depth qualitative case study across three NHS Trusts. Semi-structured interviews were conducted with 28 people: 8 pwMS with mild cognitive problems who received the cognitive screening and NEuRoMS intervention, 5 related informants, 12 clinicians (four per site), and 3 intervention providers (one per site). Interview data, transcribed verbatim and analysed using Framework Analysis, were mapped to thematic matrices of the programme theory for the screening pathway and intervention. Result(s): Overall, pwMS were able to complete screening online at home without any support. Clinicians expressed support for the pathway, indicating that it provided a clear structure to both identifying and managing cognitive problems for pwMS. However, implementation of the pathway also highlighted service gaps such as time constraints during appointments to discuss the screening results and the paucity of referral pathways to specialist psychology services. Overall, the integration of the pathway worked well within existing IT systems in the services, with processes put in place to ensure the screening results could be accessed by the clinicians. PwMS reported increased awareness of their cognitive abilities and limitations, and an increase in use of compensatory strategies following the intervention. Intervention providers identified that more time should be spent on the goal setting components of the intervention during sessions. Conclusion(s): The screening and management pathway has been revised based on recommendations from key stakeholders. The changes that have been implemented include considering those with mild and moderate cognitive problems for the NEuRoMS intervention, and modifying the intervention delivery to focus more on the goal-setting components.
  • Screening people with Multiple Sclerosis for cognitive problems does not make depression, anxiety and self-efficacy worse: Results from a multi-centre, longitudinal observational study

    das Nair, Roshan (2023)
    Introduction: There have been calls for better screening and monitoring of cognitive problems in people with MS (pwMS), but some clinicians have raised concerns that cognitive screening could have a negative impact on people's mood. The NEuRoMS programme (www.neuroms.org) developed a free, online screening tool that pwMS can complete on their electronic devices at home before their routine clinical appointments. Objectives/Aims: This study aimed to examine the potential impact of the NEuRoMS screening on pwMS' mood and self-efficacy. Method(s): This was a multi-centre, longitudinal observational study design across seven sites with MS outpatient clinics, of which three implemented the routine cognitive screening prior to clinic attendance. We compared two groups: screened (s) vs nonscreened (ns) pwMS at three time points (baseline, 2-week and 4-week follow-ups). All participants completed the Patient Health Questionnaire-8 (PHQ-8), Generalised Anxiety Disorder-7 (GAD- 7), and Multiple Sclerosis Self-Efficacy Scale (MSSE) at baseline (before screening at three screened sites) and at 2-week and 4-week follow-ups. Linear mixed models were applied for each outcome measure to assess change over time. Covariates were age and duration of MS; factors were gender, education, MS type and ethnicity; site as a random effect; time, group and time*group interaction. Result(s): There were 452 (241 s, 211 ns) pwMS who completed the outcome measures at all time points. For the PHQ-8, the mean score at baseline was 8.4 (SD=6.0) and the scores did not change significantly over time in either group. For the GAD-7, the mean score at baseline was 6.0 (SD=5.4) and the scores did not change significantly over time in either group. For MSSE, the mean score at baseline was 49.0 (SD 13.6) and the scores did not change significantly over time in either group. Conclusion(s): Our results suggest that screening pwMS for cognitive problems using the NEuRoMS screening technology does not make depression, anxiety and self-efficacy worse. The analysis did not detect a difference of a magnitude that would be considered clinically significant across time or groups. The three screened sites have screened and triaged >3000 pwMS with no adverse events reported in relation to the NEuRoMS cognitive screening. Therefore, our online cognitive screening appears safe to be used within routine clinical practice. Introduction: Cognitive problems affect 40-60% of people with Multiple Sclerosis (pwMS), but are not routinely screened for in MS clinics in the UK due to limited resources (including personnel to deliver cognitive tests) and finances (including payment for such tests). Consequently, those with cognitive problems are not identified early and triaged to receive the appropriate level of support. To address this gap, the NEuRoMS programme (www.neuroms. org) developed a neuropsychological pathway to routinely assess all pwMS attending MS clinics for cognitive problems. The pathway has been implemented in three UK MS clinics and has screened >3000 pwMS. Objectives/Aims: This work presents the iterative design and development process of the Word Colour Task (WCT), a free, online self-administered measure of selective attention and information processing. This has been included in the NEuRoMS cognitive screening pathway to screen pwMS for cognitive problems. Method(s): We followed an iterative development process and conducted multiple rounds of user testing. Beginning with a prototype based on literature and previous research, we held three stakeholder meetings with Patient and Public Involvement members, researchers and clinicians working with pwMS (n=18) to make design decisions. Following stakeholder feedback, we developed product specifications for a technical team to develop the online WCT. We then tested usability and acceptability through cognitive interviews with eight pwMS and made revisions. A further round of user-testing was undertaken before deployment into the NEuRoMS screening pathway. Result(s): User testing and cognitive interviews suggested that the WCT was acceptable, but some usability issues were identified (e.g., clarity of instructions, practice mode, repetition of stimuli) and suggestions were made to improve user experiences. Conclusion(s): Using an iterative design approach with significant and diverse stakeholder input, we were able to develop a robust and usable online cognitive screening assessment tool. The WCT has now been deployed in three MS clinics for feasibility testing having screened 370 pwMS. Validation and norming studies are currently underway to provide further evidence of its psychometric properties and collect UK-based norms. Introduction: Due to the revised 2017 McDonald diagnostic criteria, many more people undergo lumbar punctures as part of their Multiple Sclerosis (MS) diagnostic journey. This results in discomfort and additional costs. Patients often report they find the lumbar puncture painful, and it can cause unintended complications requiring hospitalisations or time off work to recover. Brain lesions with a central vein, detected with T2* MRI are thought to be characteristic of MS. The Central Vein Sign (CVS) supports the diagnosis of MS when over 40% of eligible MRI lesions have a visible central vein. The authors will present the final results from DECISIve - DiagnosE using the Central veIn SIgn (Clinical Trials reference: NCT04024969) at ECTRIMS 2023. Objectives/Aims: To investigate whether T2* MRI is a more sensitive diagnostic test than lumbar puncture with oligoclonal band examination, in people at first clinical presentation with possible MS. Method(s): A multicentre prospective single group superiority diagnostic accuracy study. Participants presenting with typical clinically isolated syndrome requiring a lumbar puncture to meet the 2017 McDonald diagnostic criteria for MS were enrolled. Trial participants had an eight-minute T2* MRI scan sequence in addition to their lumbar puncture. The final clinical diagnosis is established after at least 18 months of follow up. Result(s): Of 113 participants recruited, we were able to include 49 in a preliminary analysis. The sensitivity of the CVS to confirm a diagnosis of MS is 94% and lumbar puncture with oligoclonal band examination is 84% (McNemar test; p=0.453). Conclusion(s): The DECISIve interim analysis has shown that the sensitivity of the CVS is higher than testing for oligoclonal bands by lumbar puncture for the diagnosis of multiple sclerosis. We expect that the full DECISIve dataset will have sufficient power to confirm whether there is a clinically meaningful difference or not. There is only a single discordant result between CVS with a threshold of 40% and the 'rule of six', suggesting this could be rapidly implemented in clinical practice. Further analysis will include comparing the accuracy, speed, costs, and acceptability of the different tests and aim to establish if most lumbar punctures can be replaced by a slightly longer MRI scan.
  • Prevalence of and risk factors for cognitive problems in people with Multiple Sclerosis: A multi-centre observational study

    das Nair, Roshan (2023)
    Introduction: Cognitive problems are common among people with Multiple Sclerosis (pwMS), which can be debilitating and impact daily life. An online self-administered Symbol Substitution Task (SST), measuring information processing and working memory, was developed and deployed in three UK MS clinics to screen pwMS for cognitive problems as part of the NEuRoMS programme (www.neuroms.org). Objectives/Aims: This study aimed to explore the prevalence of cognitive problems and related risk factors in pwMS. Method(s): We used a multi-centre observational study design. The levels of cognitive problems using SST normative data were defined as follows: 1) within normal range (-1.49 standard deviations (SD) or higher); 2) mild (-2.49 SD to -1.5 SD); 3) moderate (-2.99 SD to -2.5 SD); 4) severe (-3 SD or lower). The prevalence was calculated from 1376 pwMS, and we performed ordinal logistic regression with cognitive impairment level as a dependent variable. Three models evaluated three outcome measures: 1) Patient Health Questionnaire-8 (PHQ-8), 2) Generalised Anxiety Disorder-7 (GAD-7), and 3) Multiple Sclerosis Self Efficacy Scale (MSSE). Covariates were age and duration of MS; factors were gender, education, MS type, and ethnicity; site as a random effect. Result(s): The SST threshold calculated based on SD from normative data as defined above, and prevalence from 1376 pwMS suggested that 56% were within normal range (SST score: >=35), 25% in mild (25-34), 8% in moderate (20-24) and 12% in severe (0-19) ranges. Covariates found to be significant predictors of cognitive impairment were: higher depression (PHQ-8; 1.08, p<0.001), higher anxiety (GAD-7; 1.06, p=0.01), and lower self-efficacy (MSSE; 0.96, p<0.001). For all three models age, duration of MS, gender (woman vs man), education (higher degree vs below GCSE) and MS type (relapsing-remitting vs primary progressive) had significant odds ratios, which means an increased odds of being in a higher cognitive impairment group. Conclusion(s): Cognitive problems affect 45% of pwMS attending routine clinics, with 33% having mild-moderate cognitive problems who are often left unidentified or treated. Therefore, routine monitoring for cognitive problems is crucial for identification of those who may benefit from timely support. Older, male pwMS with long disease duration, primary progressive MS, lower levels of education, low mood and low self-efficacy appear at higher risk of cognitive impairment. .
  • A qualitative study exploring how vocational rehabilitation for people with multiple sclerosis can be integrated within existing healthcare services in the United Kingdom

    das Nair, Roshan (2023)
    Introduction: The employment rate of people with multiple sclerosis (MS) in the United Kingdom (UK) is around 41% compared to 81% in people without disabilities. People with MS could benefit from vocational rehabilitation (VR) services to help them manage their symptoms at work and accommodate the impact of MS on their roles and working environment. However, there is a lack of specialist VR in the UK, and it is estimated that current services only meet the needs of 10% of the population with longterm neurological conditions. Objectives/Aims: To explore how a job retention VR intervention previously developed and tested in a community setting could be implemented within existing healthcare services for people with MS in the UK National Health Service (NHS). Method(s): We sought information regarding (1) stakeholder's VR preferences and how it could work within the NHS, (2) "Usual care" for people with MS in the NHS, (3) barriers and enablers to delivering the intervention within the NHS, and (4) intervention outcomes. Data from 37 semi-structured interviews with 22 people with MS, eight employers, and seven healthcare professionals were analysed using a framework method informed by the Consolidated Framework for Implementation Research (CIFR) and the intervention logic model. Result(s): We identified four themes relating to the intervention characteristics (e.g., individually tailored content, employer engagement), structure and resources available within the healthcare system (e.g., staff levels and skills to deliver the VR intervention), needs and beliefs of the person with MS (e.g., acceptance of MS diagnosis), and VR outcomes for relevant stakeholders such as the person with MS (e.g., improved well-being, economic independence), employers (e.g., improved ability to retain diverse workforce) and society (e.g., reduced number of people on welfare benefits). Conclusion(s): Participants perceived the NHS as a trustworthy organisation with a highly skilled workforce suited to delivering VR. However, participants suggested involving other organisations such as national charities in intervention delivery to overcome NHS barriers such as staff shortages and long waiting lists.
  • DECISIve - DiagnosE using the Central veIn SIgn

    das Nair, Roshan (2023)
    Introduction: Due to the revised 2017 McDonald diagnostic criteria, many more people undergo lumbar punctures as part of their Multiple Sclerosis (MS) diagnostic journey. This results in discomfort and additional costs. Patients often report they find the lumbar puncture painful, and it can cause unintended complications requiring hospitalisations or time off work to recover. Brain lesions with a central vein, detected with T2* MRI are thought to be characteristic of MS. The Central Vein Sign (CVS) supports the diagnosis of MS when over 40% of eligible MRI lesions have a visible central vein. The authors will present the final results from DECISIve - DiagnosE using the Central veIn SIgn (Clinical Trials reference: NCT04024969) at ECTRIMS 2023. Objectives/Aims: To investigate whether T2* MRI is a more sensitive diagnostic test than lumbar puncture with oligoclonal band examination, in people at first clinical presentation with possible MS. Method(s): A multicentre prospective single group superiority diagnostic accuracy study. Participants presenting with typical clinically isolated syndrome requiring a lumbar puncture to meet the 2017 McDonald diagnostic criteria for MS were enrolled. Trial participants had an eight-minute T2* MRI scan sequence in addition to their lumbar puncture. The final clinical diagnosis is established after at least 18 months of follow up. Result(s): Of 113 participants recruited, we were able to include 49 in a preliminary analysis. The sensitivity of the CVS to confirm a diagnosis of MS is 94% and lumbar puncture with oligoclonal band examination is 84% (McNemar test; p=0.453). Conclusion(s): The DECISIve interim analysis has shown that the sensitivity of the CVS is higher than testing for oligoclonal bands by lumbar puncture for the diagnosis of multiple sclerosis. We expect that the full DECISIve dataset will have sufficient power to confirm whether there is a clinically meaningful difference or not. There is only a single discordant result between CVS with a threshold of 40% and the 'rule of six', suggesting this could be rapidly implemented in clinical practice. Further analysis will include comparing the accuracy, speed, costs, and acceptability of the different tests and aim to establish if most lumbar punctures can be replaced by a slightly longer MRI scan.
  • A rapid realist review of clinical neuropsychology rehabilitation programmes to improve psychological wellbeing and quality of life for people with acquired brain injuries

    Thorpe, Naomi; das Nair, Roshan (2023)
    Approximately 20% of acquired brain injury (ABI) survivors experience reduced psychological wellbeing (PWB). Neuropsychological rehabilitation (NPR) is one approach supporting people with ABI to participate meaningfully in activities despite challenges. Although literature supports NPR effectiveness, little is known about change mechanisms. This systematic realist review identifies what NPR programmes have been designed, delivered, and evaluated for people with ABI to improve PWB and/or quality of life (QOL), as well as providing a context-relevant understanding of what NPR includes and how NPR might lead to positive outcomes. A rapid realist review was conducted in three phases: (1) structured retrieval and evidence extraction; (2) stakeholder consultation; (3) analysis and synthesis. Searches were completed, and findings from 35 publications and one stakeholder consultation were synthesized into a refined logic model. Six context-mechanism-outcome chains (CMOCs) were identified. Participants' relationships to internal experiences, and feelings of self-worth, mastery, and connection appeared to be mechanisms that led to improved PWB and QOL. Adaptation and individualized programmes were also key mechanisms to explain successful NPR. Embedding CMOCs into NPR could improve PWB and/or QOL for people with ABI. The logic model will inform ongoing development of a new online, group-based, NPR programme.
  • It affects everything about me: Sleep problems among children with cerebral palsy and their caregivers in Ile-Ife-a mixed-methods study

    Seun-Fadipe, Champion T. (2023)
    Background Sleep problems are common in children with cerebral palsy (CWCP). However, the effect of sleep problems in CWCP on caregivers has not been well studied. We aimed to describe the sleep problems in CWCP and their caregivers, and explore the effect of the children's sleep on the caregivers' sleep. Methods This cross-sectional, mixed-methods research was conducted at a pediatric neurology clinic in Ile-Ife, Nigeria. The Sleep Disturbance Scale for Children (SDSC) and Pittsburgh Sleep Quality Index (PSQI) were used for assessing sleep problems of the children and their caregivers, respectively. We held three focused group discussions (FGDs) involving 18 caregivers using a pretested FGD guide. We analyzed the quantitative data using Stata-15 software, while qualitative data were transcribed and managed using ATLAS.ti Software. Results We studied 71 CWCP–caregiver dyads and 69 age- and sex-matched controls. There was a male preponderance for CWCP (M:F = 1.09:1) and female preponderance for caregivers (89.5%). Sleep disturbances (SDSC > 40) occurred in 34% of CP children and poor sleep quality was seen in 39% of caregivers. When compared with age- and sex-matched typically developing peers, there was a statistically significant higher sleep disturbance in CWCP (p = 0.009). Sleep difficulties in the CWCP comprise sleep–wake transition disorders (45.0%), difficulty initiating sleep (43.3%), and sleep breathing disorders (37.5%). Caregivers experienced short sleep duration. One mother said: “It affects my sleep, health, and work. It affects everything about me.” Conclusion Sleep problems in CWCP affect the well-being of their caregivers. Interventions targeted at both the children and their caregivers are needed.
  • Theta burst stimulation of the human motor cortex modulates secondary hyperalgesia to punctate mechanical stimuli

    Lankappa, Sudheer
    OBJECTIVES: Many chronic pain conditions show evidence of dysregulated synaptic plasticity, including the development and maintenance of central sensitization. This provides a strong rationale for neuromodulation therapies for the relief of chronic pain. However, variability in responses and low fidelity across studies remain an issue for both clinical trials and pain management, demonstrating insufficient mechanistic understanding of effective treatment protocols. MATERIALS AND METHODS: In a randomized counterbalanced crossover designed study, we evaluated two forms of patterned repetitive transcranial magnetic stimulation, known as continuous theta burst stimulation (TBS) and intermittent TBS, during normal and central sensitization states. Secondary hyperalgesia (a form of use-dependent central sensitization) was induced using a well-established injury-free pain model and assessed by standardized quantitative sensory testing involving light touch and pinprick pain thresholds in addition to stimulus-response functions. RESULTS: We found that continuous TBS of the human motor cortex has a facilitatory (pronociceptive) effect on the magnitude of perceived pain to secondary hyperalgesia, which may rely on induction and expression of neural plasticity through heterosynaptic long-term potentiation-like mechanisms. CONCLUSIONS: By defining the underlying mechanisms of TBS-driven synaptic plasticity in the nociceptive system, we offer new insight into disease mechanisms and provide targets for promoting functional recovery and repair in chronic pain. For clinical applications, this knowledge is critical for development of more efficacious and mechanisms-based neuromodulation protocols, which are urgently needed to address the chronic pain and opioid epidemics.
  • Development of cancer surveillance guidelines in ataxia telangiectasia: A Delphi-based consensus survey of international experts

    Glazebrook, Cris (2023)
    BACKGROUND/OBJECTIVES: Ataxia telangiectasia (A-T) is a multiorgan disorder with increased vulnerability to cancer. Despite this increased cancer risk, there are no widely accepted guidelines for cancer surveillance in people affected by A-T. We aimed to understand the current international practice regarding cancer surveillance in A-T and agreed-upon approaches to develop cancer surveillance in A-T. DESIGN/METHODS: We used a consensus development method, the e-Delphi technique, comprising three rounds. Round 1 consisted of a Delphi questionnaire and a survey that collected the details of respondents' professional background, experience, and current practice of cancer surveillance in A-T. Rounds 2 and 3 were designed based on previous rounds and modified according to the comments made by the panellists. The pre-specified consensus threshold was ≥75% agreement. RESULTS: Thirty-five expert panellists from 13 countries completed the study. The survey indicated that the current practice of cancer surveillance varies widely between experts and centres'. Consensus was reached that evidence-based guidelines are needed for cancer surveillance in people with A-T, with separate recommendations for adults and children. Statements relating to the tests that should be included, the age for starting and stopping cancer surveillance and the optimal surveillance interval were also agreed upon, although in some areas, the consensus was that further research is needed. CONCLUSION: The international expert consensus statement confirms the need for evidence-based cancer surveillance guidelines in A-T, highlights key features that the guidelines should include, and identifies areas of uncertainty in the expert community. This elucidates current knowledge gaps and will inform the design of future clinical trials.
  • Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis

    Lankappa, Sudheer; das Nair, Roshan; Morriss, Richard K. (2023)
    Cognitive impairment in multiple sclerosis (MS) can adversely impact participation in employment, activities of daily living, and wider society. It affects 40-70% of people living with MS (pwMS). There are few effective treatments for cognitive impairment in people with MS. Neuromodulation with intermittent theta-burst stimulation (iTBS) has potential for treating cognitive impairment in pwMS. This single-centre mixed-methods feasibility randomised controlled trial (NCT04931953) will assess feasibility, acceptability, and tolerability of procedures used for applying iTBS for improving cognitive performance in pwMS. Participants will be randomised into three intervention groups with varying lengths of iTBS treatment (from 1 to 4 weeks) and a sham-control group. Quantitative data will be collected at three time points (baseline, end of intervention, and 8-week follow-up). End of the intervention semi-structured interviews will explore the views and experiences of the participants receiving the intervention, analysed using framework analysis. Quantitative and qualitative data will be synthesised to explore the impact of the iTBS intervention. Ethical approval has been received from the Health Research Authority (21/LO/0506) and recruitment started in June 2022. The results will inform the design of an RCT of the efficacy of iTBS as a therapeutic intervention for cognitive impairment in pwMS.
  • Understanding who benefits most from cognitive rehabilitation for multiple sclerosis: A secondary data analysis

    Taylor, Lauren A.; Mhizha-Murira, Jacqueline R. (2023)
    BACKGROUND: Up to 70% of people with multiple sclerosis (MS) experience cognitive difficulties. Cognitive rehabilitation is a type of therapy that helps manage cognitive problems. OBJECTIVE: The Cognitive Rehabilitation for Attention and Memory in MS (CRAMMS) trial showed some evidence of effectiveness of cognitive rehabilitation in improving cognitive function, with some participants benefitting more than others. We therefore conducted a secondary analysis of the CRAMMS data to understand who benefits most. METHODS: We grouped baseline data into four categories of possible predictors. We used regression models to identify specific factors/characteristics that could predict the likelihood that an individual will benefit from cognitive rehabilitation. RESULTS: The models predicted whether a participant improved or did not improve in neuropsychological function following cognitive rehabilitation in up to 86% of participants. Results suggest that younger participants with medium to high education, diagnosed with relapsing-remitting multiple sclerosis (RRMS) and primary-progressive multiple sclerosis (PPMS) who have not experienced any recent relapses, with mild to moderate cognitive difficulties were most likely to benefit from cognitive rehabilitation. CONCLUSION: We can predict which participants are most likely to demonstrate significant improvements in neuropsychological function following group-based cognitive rehabilitation. Clinically, this allows us to optimise limited neuropsychology resources by offering such cognitive rehabilitation to those most likely to benefit.
  • The association between the multiple sclerosis screening questionnaire and objective measures of cognition: a systematic literature review and meta-analysis

    Kontou, Eirini (2023)
    Introduction: The Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) is a self-report measure used to assess cognitive difficulties in people with Multiple Sclerosis (PwMS). The aim of this systematic review was to determine the associations between the MSNQ and: objective measures of cognition, measures of mood, and quality of life measures. Method: A comprehensive search was done across three databases (PsycINFO, MEDLINE, and CINAHL). A total of 15 studies, including 1992 participants, were selected for final inclusion. Meta-analyses were conducted to determine the pooled effect size of associations. Where data were not available for meta-analyses, a narrative synthesis approach was taken. Results: Significant, but small (r = −0.17), associations were found between the MSNQ and objective measures of cognition. Significant, moderate associations (r = 0.47) were found between the MSNQ and measures of mood. Conclusions: The small association between the MSNQ and objective measures of cognition shows that the measures do not converge well. However, their divergence may be important to map the broad construct of “cognitive ability” more fully. Limitations include a lack of reporting of non-significant effect sizes in individual studies. Clinical implications include the potential for the MSNQ to be used beyond being solely a proxy measure for objective cognition. Future research should investigate the associations between the informant version of the MSNQ and objective measures.
  • Whole-body MRI for cancer surveillance in ataxia-telangiectasia: A qualitative study of the perspectives of people affected by A-T and their families

    Glazebrook, Cris (2023)
    BACKGROUND/OBJECTIVES: Ataxia-telangiectasia (A-T) is a complex inherited disease associated with an increased risk of malignancy. Surveillance guidelines have demonstrated significant health benefits in other cancer predisposition syndromes. However, evidence-based guidelines for cancer screening are not currently used in the United Kingdom for people affected by A-T. This study aims to understand how people with A-T and their parents feel about cancer surveillance using whole-body magnetic resonance imaging (MRI) to inform the future development of cancer surveillance guidelines. DESIGN/METHODS: We conducted semistructured interviews with people affected by A-T. Data were analysed inductively using thematic analysis. RESULTS: Nine parents of children with A-T and four adults with A-T were interviewed. Five main themes emerged from the data, including (1) cancer screening was considered invaluable with the perceived value of early detection highlighted; (2) the cancer fear can increase anxiety; (3) the perceived limitations around current practice, with the responsibility for monitoring falling too strongly on parents and patients; (4) the need for effective preparation for cancer screening, including clear communication and (5) the challenges associated with MRI screening, where specific recommendations were made for improving the child's experience. CONCLUSION: This study suggests that stakeholders are positive about the perceived advantages of a cancer screening programme. Ongoing support and preparation techniques should be adopted to maximise adherence and minimise adverse psychosocial outcomes. PATIENT OR PUBLIC CONTRIBUTION: People with A-T and parents of people with A-T were actively involved in this study by giving their consent to be interviewed. An independent parent representative contributed to the study, supporting the research team in interpreting and commenting on the appropriateness of the language used in this report.
  • Thresholds for defining cognitive impairment in people with multiple sclerosis using an electronic version of a symbol substitution task

    das Nair, Roshan (2022)
    Introduction: Up to 70% of people with Multiple Sclerosis (MS) experience cognitive problems which can be debilitating and impact on day-to-day life. A digital Symbol Substitution Task (SST), a variant of the Symbol Digit Modalities Test (SDMT), was developed as part of a multi-centre project aiming to develop a neuropsychological pathway to routinely assess people with MS attending UK MS clinics for cognitive problems (NEuRoMS; www.neuroms.org). This work presents thresholds for determining cognitive impairment using the newly developed SST. Method(s): This is a cross-sectional study. Data were collected for control participants who do not have MS. The levels of cognitive impairment in people with MS were defined as follows, based on previously published work on a similar digital variant of SDMT known as Multiple Screener: 1) None evident: Score of less than 1.5 standard deviations (SD) below the mean; 2) Possibly mildly impaired: Scores of 1.5 SD or more, and less than 2 SD below the mean; 3) Probably impaired: Score of 2 SD or more below the mean. Data for the SST were also collected for people with MS as part of routine clinical care in three National Health Service (NHS) Trusts. The thresholds defined above were applied to data for people with MS to establish the prevalence of cognitive impairment. This abstract presents findings from a planned interim analysis. Data collection is ongoing. Result(s): People with MS (n=632) were mostly female and of mean age 49.1. Most people with MS had relapsing-remitting MS, and had been diagnosed an average of 18.7 years. Control participants (n=41) were mostly female with a mean age of 44.3 years. From control participants who completed the task, the mean score was 47.9, SD 8.6. The thresholds for defining that a patient is possibly mildly impaired and probably impaired are 35.1 and 30.8 respectively. Applying these thresholds to the MS cohort to establish cognitive impairment, there were 329 (52.1%) who were classified as 'None evident', 104 (16.5%) who were classified as 'Possibly mildly impaired', and 199 (31.5%) who were classified as 'Probably impaired'. Discussion(s): Pervious research has mainly categorised people into 'impaired' or 'not impaired'. This work however has generated thresholds for defining the severity of cognitive impairment in people with MS using an electronic version of the SST, enabling clinicians to interpret test results more accurately. Further data will be collected to refine these thresholds.
  • A mixed-methods feasibility case series of a job retention vocational rehabilitation intervention for people with multiple sclerosis

    das Nair, Roshan (2023)
    PURPOSE To ascertain the feasibility and acceptability of delivering a job retention vocational rehabilitation intervention [MSVR] for people with multiple sclerosis (pwMS) in a community setting. Secondary objectives included determining whether MSVR was associated with changes in quality of life, fatigue, mood, cognition, workplace accommodations, work instability, work self-efficacy, and goal attainment. METHODS Single-centre mixed-methods feasibility case series. RESULTS 15 pwMS and three employers received 8.36 (SD = 4.48) and 1.94 (SD = 0.38) hours of MSVR respectively over three months. The intervention predominantly addressed managing cognition, fatigue, and negotiating reasonable accommodations. Four healthcare professionals were recruited to clarify clinical information. The intervention was feasible to deliver, and there was a significant positive impact on goal attainment immediately following MSVR (t(14) = 7.44, p = .0001, d = 1.9), and at months 3 (t(13) = 4.81, p = .0001, d = 1.28), 6 (t(11) = 4.45, p = .001, d = 1.28), and 12 (t(9) = 5.15, p = .001, d = −2.56). There was no impact on quality of life, fatigue, mood, cognition, workplace accommodations, work instability, and work self-efficacy. In post-intervention interviews, participants reported that MSVR was acceptable. Four themes were derived regarding the context, employer engagement, empowerment through knowledge, and intervention components and attributes. CONCLUSION It was feasible and acceptable to deliver MSVR. Participants better understood their MS, became more confident managing problems at work and attained their work-related goals. IMPLICATIONS FOR REHABILITATION People with multiple sclerosis (MS) experience problems at work because of the interaction between symptoms and environmental factors (e.g., co-workers’ attitudes). Vocational rehabilitation for people with MS and their employers should be tailored in terms of content and intensity. People with MS can be empowered at work by learning about MS and how their symptoms fluctuate over time. Understanding legal responsibilities and examples of accommodations at work can be beneficial for employers. Optimising home-based rehabilitation for survivors of stroke with severe disability Cardiovascular conditions.
  • Adapted suicide safety plans to address self-harm, suicidal ideation, and suicide behaviours in autistic adults: Protocol for a pilot randomised controlled trial

    Nielsen, Emma (2023)
    BACKGROUND: Suicide prevention is a national priority for the UK government. Autistic people are at greater risk of experiencing self-harm and suicidal thoughts and behaviours than the general population. Safety plans are widely used in suicide prevention but have not yet been designed with and for autistic people. We developed the first safety plan specifically targeting suicidality in autistic adults: the Autism Adapted Safety Plan (AASP). It consists of a prioritised list of hierarchical steps that can be used prior to or during a crisis to mitigate risk of self-harm and suicidal behaviour. This is a pilot study that aims to assess the feasibility and acceptability of the AASPs and the research processes, including the response rates, potential barriers and reach of AASPs, methods of recruitment, what comprises usual care, and economic evaluation methods/tools. METHODS: This is an external pilot randomised controlled trial of a suicide prevention tool aimed at mitigating the risk of self-harm and suicidal behaviour in autistic adults: AASPs. Participants will be assessed at baseline and followed up 1 month and 6 months later. Assessments include questions about self-harm, suicidality, service use, and their experience of the AASP/taking part in the study. Autistic adults who have a clinical autism diagnosis and self-reported history of self-harm, suicidal thoughts, or suicidal behaviours within the last 6 months will be invited to take part in the study. Informed consent will be obtained. Participants will be recruited via community and third sector services (including community settings, autism charities, and mental health charities). They may also "self-refer" into the study through social media recruitment and word of mouth. Ninety participants will be randomised to either develop an AASP or receive their usual care in a 1:1 ratio. DISCUSSION: The present study will provide an evaluation of the suitability of the processes that would be undertaken in a larger definitive study, including recruitment, randomisation, methods, questionnaires, outcome measures, treatment, and follow-up assessments. TRIAL REGISTRATION: ISRCTN70594445, Protocol v4: 8/2/22.
  • Developing a patient care pathway for emotional support around the point of multiple sclerosis diagnosis: A stakeholder engagement study

    das Nair, Roshan (2023)
    BACKGROUND: Diagnosing multiple sclerosis (MS) can be a lengthy process, which can negatively affect psychological well-being, condition management, and future engagement with health services. Therefore, providing timely and appropriate emotional support may improve adjustment and health outcomes. PURPOSE: To develop a patient care pathway for providing emotional support around the point of diagnosing MS, and to explore potential barriers and facilitators to delivery and implementation. METHOD(S): Focus groups were conducted with 26 stakeholders, including 16 people living with MS, 5 carers/family members and 5 professionals working with people living with MS (3 MS nurses, 1 psychiatrist, and 1 charity staff member). Discussions were audio-recorded, transcribed verbatim and analyzed using framework analysis. RESULT(S): Participants suggested that a patient care pathway should include comprehensive information provision as a part of emotional support at diagnosis, and follow-up sessions with a healthcare professional. Barriers including increasing staff workloads and financial costs to health services were acknowledged, thus participants suggested including peer support workers to deliver additional emotional support. All participants agreed that elements of a care pathway and embedded interventions should be individually tailored, yet provided within a standardized system to ensure accessibility. CONCLUSION(S): A patient care pathway was developed with stakeholders, which included an embedded MS Nurse support intervention supplemented with peer support sessions. Participants suggested that the pathway should be delivered within a standardized system to ensure equity of service provision across the country. PATIENT OR PUBLIC CONTRIBUTION: This research was conceptualized and designed collaboratively with Nottingham Multiple Sclerosis Patient and Public Involvement and Engagement (PPIE) group members. One member is a co-author and was actively involved in every key stage of the research process, including co-design of the pathway and research protocol, data collection (including presenting to participants and moderating group discussions), analysis and write-up. Authors consulted with PPIE members at two meetings (9 and 11 PPIE attendees per meeting) where they gave feedback on the research design, findings and the resulting pathway. People living with MS and carers of people with MS were included in the focus groups as participants.
  • Remote delivery of group-based psychological interventions for people after stroke and transient ischaemic attack (TIA): a scoping review

    Kontou, Eirini; Thorpe, Naomi (2022)
    Psychological wellebeing and quality of life are frequently affected following stroke and transient ischaemic attack (TIA). Evidence suggests that psychological interventions post diagnosis can benefit individuals' mental health and physical wellbeing. The COVID-19 pandemic has meant that alternatives to traditional face-to-face interventions have come to the forefront. Remote delivery of psychological interventions can be feasible, but it is unclear whether they are best suited for group-based programmes. To our knowledge, no previous review has specifically examined the remote delivery of group psychological interventions in TIA/stroke. This scoping review intends to identify the current evidence and delivery formats of online group-based psychological and psychoeducational interventions for people after TIA and stroke. This review follows the PRISMA Extension for Scoping Reviews. Four electronic databases were searched (April 2022) for articles on online group-based psychological/psychoeducational interventions delivered in digital formats through web- and app-based methods. Four reviewers conducted the screening process, with a fifth resolving any disagreements. Screening will be completed in June 2022. Initial searches yielded 748 results. It is expected that six to eight papers will be included. As the review is underway, full results will be available at the conference. Findings summarise the published evidence on remotely-delivered group psychological interventions in TIA and stroke. This review will inform the development of future online psychological interventions for stroke/TIA and enable us to identify potential barriers and facilitators to implementation. Practice-based recommendations and future directions of research in this area will be presented.

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