Comparison of time to clinically meaningful improvement in quality of life in neurological disorders in patients treated with natalizumab versus ocrelizumab.

Aim: To assess time to improvement in Quality of Life in Neurological Disorders (Neuro-QoL) domains for patients treated with natalizumab versus ocrelizumab. Methods: Patients enrolled in the MS PATHS network who initiated treatment with either natalizumab or ocrelizumab rated the Neuro-QoL domains of physical function, symptoms, emotional health, cognitive function and social ability. Results: Time to clinically meaningful improvement was significantly shorter with natalizumab versus ocrelizumab for cognitive function (event time ratio [95% CI]: 0.37 [0.24-0.57]; p < 0.001), sleep disturbance (0.45 [0.28-0.72]; p = 0.001), social role participation (0.37 [0.21-0.66]; p = 0.001) and social role satisfaction (0.5 [0.31-0.8]; p = 0.004). Conclusion: Natalizumab had shorter time to clinically meaningful improvement in cognitive, sleep, and social role Neuro-QoL domains versus ocrelizumab.

Knowledge of treatment-related benefits associated with medication choices, including improvement of quality of life (QoL), are strong influential factors for patients to start and continue their therapies. Little is known about patient-reported time to onset of functional improvement upon the initiation of medications for multiple sclerosis (MS). The Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) network, a repository of collaborative international data on routine MS management, includes patient-reported information on the health-related QoL using the Quality of Life in Neurological Disorders (Neuro-QoL) measure. This study included data from 883 eligible patients enrolled in MS PATHS, with the aim of assessing and comparing the time to improvement in physical, mental and social health for patients treated with natalizumab versus ocrelizumab using Neuro-QoL. Natalizumab and ocrelizumab are both high-efficacy treatment options for relapsing forms of MS. The results demonstrated that, compared with ocrelizumab, natalizumab treatment led to faster effect on mental and social health, as well as quicker improvements in physical functioning in the arms and hands. Overall, it took shorter time for natalizumab-treated patients to achieve better QoL compared with ocrelizumab. These findings highlight the importance of QoL in disease management and provide a patient perspective for healthcare providers when making decisions about high-efficacy treatments for their patients with MS.

Addressing the Needs of Multiple Sclerosis Caregivers From Diagnosis Onward: The Development of a Comprehensive Online Caregiver Protocol.

BACKGROUND: Caregivers of individuals with multiple sclerosis (MS) have emotional, instrumental, wellness, and social needs beginning with their partner's diagnosis and continuing throughout the disease course. Their feelings of grief, anxiety, depression, isolation, and fatigue, as well as the limited time they have for their own self-care, impact their health and quality of life; yet caregiver needs often go unrecognized by health care providers, extended family, friends, and employers. This project creates an online caregiver resource that will benefit caregivers, enable MS clinicians to offer caregivers the support and resources they need in a timely and time-efficient way, and thereby benefit individuals with MS as well. METHODS: We assembled a caregiver advisory board to help us identify caregiver needs and corresponding resources starting from diagnosis and continuing throughout the disease course. We then surveyed the larger MS caregiver community for validation and refinement of the resource list. Each of the identified resources was then vetted for quality and accuracy by the authors. RESULTS: The caregiver resources are now ready to be put into a dedicated website that will allow easy access to information, support, tools, and resources as needed. CONCLUSIONS: The process of creating this caregiver resource confirmed longstanding findings in the literature about the caregiving role. The resource that has been created will benefit caregivers of individuals with MS, their loved ones, and MS clinicians.

Teach, Learn, Do, Repeat: Service Learning Curriculum that Drives Public Health Education while Improving Community Health Outcomes.

The integration of service learning into public health curriculum allows students to apply and ultimately better understand often abstract but important theoretical concepts. We provide lessons learned and practical advice on how to plan and implement an experiential learning project over a two-semester period for upper level undergraduate public health students. Through application of program planning pedagogy, students obtained real-world experience while simultaneously improving mental health for college students. We also discuss how experiential curriculum also provides faculty the opportunity to engage with community stakeholders and organizations to build sustainable partnerships that positively impact students and the community at large.

Long-term trajectories of ambulatory impairment in multiple sclerosis.

BACKGROUND: Ambulatory impairment is a common and complex manifestation of multiple sclerosis (MS), and longitudinal patterns are not well understood. OBJECTIVE: To characterize longitudinal walking speed trajectories in a general MS patient population and in those with early disease (⩽ 5 years from onset), identify subgroups with similar patterns, and examine associations with individual attributes. METHODS: Using a retrospective cohort study design, latent class growth analysis was applied to longitudinal timed 25-foot walk (T25-FW) data from 7683 MS patients, to determine T25-FW trajectories. Associations were evaluated between trajectory assignment and individual attributes. Analyses were repeated for 2591 patients with early disease. RESULTS: In the general patient population, six trajectories were discerned, ranging from very minimal to very high impairment at baseline, with variability in impairment accrual. The clusters with moderate to very high walking impairment were associated with being female, older and Black American, longer symptom duration, progressive course, and depressive symptoms. In the early disease subset, eight trajectories were discerned that included two subgroups that rapidly accrued impairment. CONCLUSION: We identified novel subgroups of MS patients will distinct long-term T25-FW trajectories. These results underscore that socially disadvantaged and economically marginalized MS patients are the most vulnerable for severe ambulatory impairment.

Components of a successful community-based exercise program for individuals with Parkinson's disease: Results from a participant survey.

OBJECTIVES: The aim of the project was to examine the personal beliefs, motivators, and barriers in people with Parkinson's disease (PwPD) relating to their participation in a year-round community-based cycling program, Pedaling for Parkinson's (PFP). DESIGN: Cross-sectional survey from a 12-month pragmatic study. SETTING: Five community-based PFP sites. MAIN OUTCOME MEASURES: A survey was designed to capture the attitudes and beliefs of those participating in a PFP program. Survey responses were rated on a 5-point Likert scale (1-5; higher number representing a more positive response) assessing the subdomains of Personal Beliefs and Knowledge, Health and Disability, Program, and Fitness Environment following a 12-month exercise observational period. RESULTS: A total of 40 PwPD completed the survey. Mean subdomain scores were as follows: 4.37 (0.41) for Personal Beliefs and Knowledge, 4.25 (0.65) for Health and Disability, 4.11 (0.53) for Program, and 4.35 (0.44) for Fitness Environment. There were no significant correlations between survey subdomains and demographic variables (age, years of education, years since diagnosis, years attending the PFP program, and disease severity) or subdomains and exercise behavior (cadence, attendance, and heart rate). CONCLUSIONS: Regardless of demographic variables and disease severity, PwPD who attended a PFP program enjoyed the class, felt that their PD symptoms benefited from exercise, and were motivated to exercise by their PD diagnosis. Factors such as location of the gym, cost, and transportation were important. With the growing body of PD literature supporting the role of exercise in potentially altering the disease trajectory, it is critical that communities adopt and implement exercise programs that meet the needs of PwPD and facilitate compliance.

Association of socioeconomic disadvantage and neighborhood disparities with clinical outcomes in multiple sclerosis patients.

BACKGROUND: Socioeconomic disadvantage may be an important contributor to clinical outcomes in MS but is not well understood. Our objective was to examine the associations between Area Deprivation Index (ADI), a validated measure of neighborhood-level disadvantage, with clinical outcomes. METHODS: We assessed the longitudinal association between MS Performance Test (MSPT) and quality of life in Neurological Disorders (Neuro-QoL) measures with ADI quartiles (Q1: lowest deprivation - Q4 highest deprivation) in relapsing remitting MS (RRMS) and progressive MS cohorts. RESULTS: Our study included 2,921 patients (65.8% RRMS and 34.1% progressive MS) with 13,715 visits. Patients living in the most disadvantaged areas had almost universal worsening on baseline MSPT and Neuro-QoL scores (p < 0.05) when compared to patients living in areas of lowest deprivation. Manual Dexterity Test (MDT) illustrated particular disparity as RRMS patients living in the greatest area of deprivation had MDT score which averaged 2.9 seconds longer than someone living in areas of least deprivation. Longitudinal analysis illustrated less favorable MSPT and Neuro-QoL outcomes across visits between Q1 versus Q4 ADI quartiles within in the RRMS cohort but not within the progressive MS cohort. After adjustment, linearly increasing area deprivation scores reflected less favorable Processing Speed Test (PST) and six Neuro-QoL outcomes among the RRMS cohort. Within the progressive cohort, higher deprivation was associated less favorable MDT, PST and 11 of 12 Neuro-QoL outcome measures. CONCLUSIONS: This study provides evidence for socioeconomic disadvantage as a risk factor for disability accrual in MS and may be targeted to improve care while informing resource allocation.

Clinical perspective on clinical outcome assessments in neurosarcoidosis.

BACKGROUND: There are no validated clinical outcome assessments (COAs) used in neurosarcoidosis. OBJECTIVE: We surveyed clinicians who treat patients with neurosarcoidosis to determine: 1) current approaches to assessment of neurologic impairment, and 2) clinicians' needs regarding future COA development. METHODS: Physician contacts from the Foundation for Sarcoidosis Research and Neurosarcoidosis Consortium Group were sent an online survey. RESULTS: For 43/143 responders, COAs were used in a minority of settings. Apart from time for administration, the biggest barriers to implementation were lack of validated, disease-specific measures. CONCLUSIONS: Lack of validated, disease-specific measures is a barrier to monitoring neurological impairment in neurosarcoidosis.

Impact of natalizumab on quality of life in a real-world cohort of patients with multiple sclerosis: Results from MS PATHS.

BACKGROUND: Optimizing multiple sclerosis treatment warrants understanding of changes in physical, mental, and social health. OBJECTIVE: To assess the impact of natalizumab on Quality of Life in Neurological Disorders (Neuro-QoL) scores. METHODS: Annualized change in T-scores and likelihood of ≥5-point improvement over baseline were calculated for each Neuro-QoL domain after natalizumab initiation. Comparisons with ocrelizumab-treated patients were conducted after propensity score weighting and adjustment for relevant co-medications, year, and drug-year interaction. RESULTS: Among 164 natalizumab patients analyzed, 8 of 12 Neuro-QoL domains improved significantly, with greater improvement in patients with abnormal baseline Neuro-QoL. In the subgroup comparison of natalizumab-treated (n = 145) and ocrelizumab-treated (n = 520) patients, significant improvement occurred in 9 of 12 and 4 of 12 domains, respectively. The difference between groups was statistically significant for positive affect and well-being (p = 0.02), sleep (p = 0.003), and satisfaction with social roles and activities (SRA) (p = 0.03) in the overall population and for emotional and behavioral dyscontrol (p = 0.01), participation in SRA (p = 0.0001), and satisfaction with SRA (p = 0.02) in patients with abnormal baseline Neuro-QoL. CONCLUSIONS: Natalizumab can produce clinically meaningful improvements in mental and social health. Such improvements are unlikely to be primarily driven by expectation bias, as their magnitude exceeded improvements with another high-efficacy therapy, ocrelizumab.

Stopping disease-modifying therapy in relapsing and progressive multiple sclerosis.

PURPOSE OF REVIEW: To assess the reasons for considering discontinuation of disease-modifying therapies (DMTs)in patients with multiple sclerosis (MS). Relevant aspects of the natural history, pathology, and immunology are analyzed. RECENT FINDINGS: A number of retrospective observational studies in aggregate indicate that stopping DMTs may be attempted in older individuals with stable disease. Prognostic factors have been identified informing about the risk of recurrence of disease activity after DMT discontinuation. SUMMARY: Several clinical scenarios provide a rationale to stop DMTs in people with MS. Cumulative evidence has been gathered recently allowing us to more precisely weigh the risks against the benefits. This information aids in the decision process.

A Phenology Model for Simulating Oobius agrili (Hymenoptera: Encyrtidae) Seasonal Voltinism and Synchrony With Emerald Ash Borer Oviposition.

In North America, the emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), continues to spread, and its egg parasitoid, Oobius agrili Zhang and Huang (Hymenoptera: Encyrtidae), is being released for emerald ash borer biocontrol well beyond their endemic climatic ranges in China. We developed a multiple cohort rate summation model to simulate O. agrili F0, F1, and F2 generations, and emerald ash borer oviposition for examining host-parasitoid synchrony across a north-south gradient from Duluth, MN (latitude 46.8369, longitude -92.1833) to Shreveport, LA (latitude 32.4469, longitude -93.8242). Temporal occurrences of critical day length for O. agrili diapause induction were integrated into the model. We used O. agrili and emerald ash borer trapping data from south central and northwestern Lower Michigan for model validation. Simulations demonstrated that 1) F0 adult emergence consistently occurred 2-5 d before emerald ash borer oviposition began; 2) F1 adult emergence was most synchronized with peak emerald ash borer oviposition compared with other generations; and 3) emerald ash borer oviposition was complete, or near so, when F2 adult emergence was predicted across the north-south gradient. Comparison of O. agrili trap captures with model simulations demonstrated that primarily two adult O. agrili generations (F0 and F1) emerged per year in Michigan and almost all F2 larvae entered diapause despite day lengths longer than critical day length in south central Michigan. Critical day length varied temporally across the north-south gradient during emergence of O. agrili generations. Determining day lengths perceived by O. agrili larvae in the field should improve model realism for examining spatiotemporal variation in O. agrili population dynamics.

Assessing Access to Five Types of Insurance by People with Multiple Sclerosis Using a Cross-sectional Online Survey.

BACKGROUND: Many individuals with multiple sclerosis (MS) depart the workforce prematurely. In the United States, access to insurance, including health, disability income, long-term care, and life insurance, is largely employment-based or purchased from earnings. Many individuals we see in the clinic experience financial hardship because of a lack of insurance, even if working. We sought to determine the proportion of workers who are financially protected through insurance coverage and the sources of this coverage in a large sample. METHODS: We developed an online survey and opened it to individuals aged 18 to 65 years registered with the North American Research Committee on Multiple Sclerosis, iConquerMS, or the National Multiple Sclerosis Society Minority Advisory Council. Data collected included demographic and disease characteristics, current information about each insurance type (coverage vs no coverage), and when the current insurance policies were obtained relative to MS diagnosis. RESULTS: Of 2507 survey respondents, 82.9% were female, 3.8% Hispanic/Latino, and 91.2% White. The mean ± SD age was 53.5 ± 8.5 years and disease duration was 16.4 ± 8.5 years after diagnosis. The most frequently held insurance types were health (96.3%) and life (58.8%). Only 9.7% of respondents had long-term care insurance. Except for life insurance, most current policies were obtained after MS diagnosis. CONCLUSIONS: Individuals with MS might not prioritize the possible short- and long-term benefits of these types of insurance. Health care providers can direct patients to nonprofit agencies that educate about of these insurance types and emphasize that others with MS have obtained these insurance types after their diagnosis.

A Scoring Algorithm for Deriving Utility Values from the Neuro-QoL for Patients with Multiple Sclerosis.

INTRODUCTION: The Neuro-QoL is a standardized approach to assessing health-related quality of life in people with neurological conditions, including multiple sclerosis (MS). Item banks were developed with item response theory (IRT) methodology so items are calibrated along a continuum of each construct. The purpose of this study was to develop a preference-based scoring algorithm for the Neuro-QoL to derive utilities that could be used in economic modeling. METHODS: With input from neurologists, 6 Neuro-QoL domains were selected based on relevance to MS and used to define health states for a utility elicitation study in the United Kingdom. General population participants and individuals with MS valued the health states and completed questionnaires (including Neuro-QoL short forms). The Neuro-QoL Utility Scoring System (NQU) was derived based on multi-attribute utility theory using data from the general population sample. Single-attribute disutility functions for 6 Neuro-QoL domains were estimated using isotonic regression with linear interpolation and then combined with a multiplicative model. NQU validity was assessed using MS participant data. RESULTS: Interviews were completed with 203 general population participants (50.2% female; mean age = 45.0 years) and 62 participants with MS (62.9% female; mean age = 46.1 years). Mean (SD) NQU scores were 0.94 (0.06) and 0.82 (0.13) for the general population and MS samples, respectively. The NQU demonstrated known-groups validity by differentiating among subgroups categorized based on level of disability. The NQU demonstrated convergent validity via correlations with generic measures (0.66 and 0.63 with EQ-5D-5L and Health Utilities Index Mark 3, respectively; both P < 0.001). DISCUSSION: With the NQU, utilities can be derived from any MS treatment group, subgroup, or patient sample who completes items from 6 Neuro-QoL domains. Because the Neuro-QoL is frequently used with MS patients, the NQU greatly expands the options for quantifying outcomes in cost-utility analyses conducted to inform allocation of resources for MS treatment.

Obtaining Patient Priorities in a Multiple Sclerosis Comprehensive Care Center: Beyond Patient-Reported Outcomes.

BACKGROUND: In order to provide patient center care, our multiple sclerosis (MS) clinic assesses patient concerns before clinical encounters, first by asking the optional qualitative question "What is the most important thing you what your health-care provider to know today" (most important concern of the patient [MIPC]) and then completing quantitative patient-reported outcome measures (PROMs) including Quality of Life in Neurological Disorders (Neuro-QoL). Both sets of questions are designed to facilitate encounters that address patients' values and preferences. OBJECTIVE: Determine whether the qualitative MIPC responses provided unique information not included in PROMs or clinical assessments. METHODS: We randomly selected 400 first-time MIPC responders and 400 first-time MIPC nonresponders from 2788 participants in our database. We categorized MIPC responses by content and number of unique concerns and appended them to the Neuro-QoL framework. Nonresponders were compared to those who provided 1 and 2 or more responses. RESULTS: Several MIPCs MS symptoms categories were added to the Neuro-QoL Physical domain. Most important concern of the patients work and cost-of-care categories were added to the Social Domain. Domains regarding treatment satisfaction and disease management were added. Two hundred thirty (58%) MIPC respondents reported 1 concern, 140 (35%) expressed 2 to 6 concerns, and 30 (7%) reported MS-unrelated concerns and not analyzed. Physical symptoms were the most common MIPC (69.9%). Respondents with more concerns were more likely African American, lacked private insurance, and worse disability. CONCLUSIONS: Importantly, MIPC responders described idiosyncratic symptoms, disease management, and social concerns not included in the PROMS, suggesting the MIPC question offered patients a unique opportunity to share specific concerns with their providers.

Technology-enabled assessments to enhance multiple sclerosis clinical care and research.

BACKGROUND: Comprehensive and efficient assessments are necessary for clinical care and research in chronic diseases. Our objective was to assess the implementation of a technology-enabled tool in MS practice. METHOD: We analyzed prospectively collected longitudinal data from routine multiple sclerosis (MS) visits between September 2015 and May 2018. The MS Performance Test, comprising patient-reported outcome measures (PROMs) and neuroperformance tests (NPTs) self-administered using a tablet, was integrated into routine care. Descriptive statistics, Spearman correlations, and linear mixed-effect models were used to examine the implementation process and relationship between patient characteristics and completion of assessments. RESULTS: A total of 8022 follow-up visits from 4199 patients (median age 49.9 [40.2-58.8] years, 32.1% progressive course, and median disease duration 13.6 [5.9-22.3] years) were analyzed. By the end of integration, the tablet version of the Timed 25-Foot Walk was obtained in 89.0% of patients and the 9-Hole Peg Test in 94.8% compared with 74.2% and 64.3%, respectively before implementation. The greatest increase in data capture occurred in processing speed and low-contrast acuity assessments (0% prior vs 78.4% and 36.7%, respectively, following implementation). Four PROMs were administered in 41%-98% of patients compared with a single depression questionnaire with a previous capture rate of 70.6%. Completion rates and time required to complete each NPT improved with subsequent visits. Younger age and lower disability scores were associated with shorter completion time and higher completion rates. CONCLUSIONS: Integration of technology-enabled data capture in routine clinical practice allows acquisition of comprehensive standardized data for use in patient care and clinical research.

Achieving effective patient and public involvement in international clinical trials in neurology.

There is a growing need for patient and public involvement (PPI) to inform the way that research is developed and performed. International randomized controlled trials are particularly likely to benefit from PPI, but guidance is lacking on how or when it should be incorporated. In this article, we describe the PPI process that occurred during the design and initiation of an international treatment clinical trial in MS. PPI was incorporated using a structured approach, aiming to minimize bias and achieve equivalence in study design, implementation, and interpretation. Methods included PPI representation within the study research team, and the use of focus groups, analyzed using thematic framework analysis. We report the outcomes of PPI and make recommendations on its use in other neurology clinical trials. By sharing our model for PPI, we aim to maximize effectiveness of future public involvement and to allow its effect to be better evaluated.

Experience of a novel community testing programme for COVID-19 in London: Lessons learnt.

We describe the London community testing programme developed for COVID-19, audit its effectiveness and report patient acceptability and patient adherence to isolation guidance, based upon a survey conducted with participants.Any patients meeting the Public Health England (PHE) case definition for COVID-19 who did not require hospital admission were eligible for community testing. 2,053 patients with suspected COVID-19 were tested in the community between January and March 2020. Of those tested, 75 (3.6%) were positive. 88% of patients that completed a patient survey felt safe and 82% agreed that community testing was preferable to hospital admission. 97% were able to remain within their own home during the isolation period but just 41% were able to reliably isolate from other members of their household.The London community testing programme allowed widespread testing for COVID-19 while minimising patient transport, hospital admissions and staff exposures. Community testing was acceptable to patients and preferable to admission to hospital. Patients were able to reliably isolate in their home but not from household contacts. The authors believe in the importance, feasibility and acceptability of community testing for COVID-19 as a part of a package of interventions to mitigate a second wave of infection.

A bundled intervention lowers surgical site infection in hysterectomy for benign and malignant indications.

OBJECTIVE: To evaluate the impact of a surgical site infection (SSI) prevention bundle on SSI rates after hysterectomy for benign and malignant indications at an urban academic medical center. METHODS: The bundled invention was implemented for all abdominal gynecologic surgeries at Prentice Women's Hospital, Chicago, USA, from August 2016 to January 2017, and officially incorporated in department-wide policy from February 1, 2017. SSI data were prospectively collected for any open, vaginal, laparoscopic, or robotic hysterectomy for benign or malignant indications performed from February 2017 to January 2018. A retrospective review of all hysterectomies performed from February 2015 to January 2016 was conducted to establish baseline pre-bundle SSI data. RESULTS: Among 532 hysterectomies performed post-bundle implementation, there were two SSIs. By contrast, there were 14 SSIs among 515 hysterectomies in the same period before bundle implementation, representing a decrease in SSI rate from 2.7% to 0.4% (odds ratio, 7.41; 95% confidence interval, 1.67-32.75). The two SSIs in the post-bundle period occurred in open hysterectomies, whereas 8 (57.1%) SSIs in the pre-bundle period occurred in minimally invasive hysterectomies. CONCLUSION: An SSI prevention bundle was effective for reducing the SSI rate in hysterectomy for both benign and malignant indications.

Exploring the Impact of Fatigue in Progressive Multiple Sclerosis: A Mixed-Methods Analysis.

BACKGROUND: Patient-focused literature on fatigue in progressive forms of multiple sclerosis (MS) is sparse. This study aimed to explore progressive MS patients' experiences of fatigue. METHODS: Adult patients in the United States with primary progressive MS (n=21) and secondary progressive MS (n=23), recruited from research panels, completed the following PRO measures: Patient Global Impression of Severity (Fatigue) (PGI-F); Fatigue Scale of Motor and Cognitive Functions (FSMC); Modified Fatigue Impact Scale (MFIS); Patient Health Questionnaire, two-item version (PHQ-2); and Patient Determined Disease Steps (PDDS). Patients subsequently participated in a 45-minute semistructured telephone interview and were asked to describe their MS symptoms and to comment on how MS affected their day-to-day lives. More detailed questions followed on the nature of their fatigue, including symptoms, impacts, frequency, and bothersomeness. RESULTS: Patients' mean age was 52.5 years, mean time since diagnosis was 14.7 years, and 81.8% were female. 79.5% of patients were unemployed and/or receiving disability benefits. Of all spontaneously reported MS symptoms, fatigue was the most common (n=38, 86.4%), followed by ambulation problems (n=31, 70.5%) and muscle weakness (n=25, 56.8%). Patients used the words "tired," "exhausted," "wiped out," and having "little or no energy" to describe their fatigue. More patients rated fatigue as their "most troubling symptom" (n=17, 38.6%) compared with other MS-related symptoms. Half of patients reported feeling constantly fatigued, and more than 90% reported experiencing fatigue at least daily. The top three most frequently reported negative impacts of fatigue were social functioning, emotional well-being, and cognitive functioning (all >80%). Patients described themselves as "homebodies," as fatigue limited their social interactions with friends and family and impacted the types of activities they could participate in. Patients attributed their inability to think clearly or focus for long periods of time to their fatigue. Patients also reported experiencing depression and anxiety because of their fatigue, which would often have further negative effects on their relationships with friends and family. On the fatigue PRO measures, mean (standard deviation) scores were 75.2 (14.7) on the FSMC and 55.0 (15.2) on the MFIS. Most participants scored in the "high" fatigue category on the FSMC (84.1%) and above the clinically significant fatigue threshold (86.4%). MFIS and FSMC total scores correlated with PGI-F (polyserial correlations r=0.74 and r=0.62, both p<0.01) and PHQ-2 (r=0.56 and r=0.57, both p<0.01), but not with PDDS (r=0.09 and r=0.02, both p>0.05). CONCLUSIONS: Fatigue is a common, troublesome, and disabling symptom which has a profound impact on patients' daily lives, as evidenced by qualitative analyses and high scores on established fatigue measures observed in this sample. These findings provide insights into the burden of fatigue and can inform its measurement in both clinical and research settings. Treatments that improve the symptoms of fatigue or prevent exacerbations are needed for patients with progressive MS.

Determining the effectiveness of early intensive versus escalation approaches for the treatment of relapsing-remitting multiple sclerosis: The DELIVER-MS study protocol.

Multiple Sclerosis (MS) is a common cause of neurological disability among young adults and has a high economic burden. Currently there are 18 disease modifying agents for relapsing MS, which were tested in clinical trials versus placebo or an active comparator in a pairwise manner. However, there is currently no consensus on the fundamental principles of treatment approach and initial therapy selection. These factors result in variable use of disease modifying therapies. Here we describe the study protocol for Determining the Effectiveness of earLy Intensive Versus Escalation approaches for the Treatment of Relapsing-remitting Multiple Sclerosis (DELIVER-MS). The main objective of the study is to determine whether an early highly effective treatment approach, defined as use of one of four monoclonal antibodies as initial therapy, is more effective than an escalation treatment approach (any other approved medication as initial therapy with subsequent escalation to higher efficacy treatments guided by radiological and clinical evaluation). The primary endpoint of the study is reduction in normalized brain volume loss from baseline visit to month 36 visit using MRI. Brain volume loss was selected as the best short-term predictor of long-term clinical disability. A total of 400 participants will be randomized 1:1 using minimization to account for age and sex by site, and 400 will be enrolled into a parallel observational cohort. The study results will help guide overall treatment philosophy and will have important implications for patient choice, clinical practice, and treatment access.