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Amber R Salter,1 Ruth Ann Marrie,2,3 Neetu Agashivala,4 Daniel A Belletti,4 Edward Kim,4 Gary R Cutter,1 Stacey S Cofield,1 Tuula Tyry51Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Internal Medicine, 3Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada; 4Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 5Division of Neurology, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USAIntroduction: The evolving landscape of disease-modifying therapies (DMTs) for multiple sclerosis raises important questions about why patients change DMTs. Physicians and patients could benefit from a better understanding of the reasons for switching therapy. Purpose: To investigate the reasons patients switch DMTs and identify characteristics associated with the decision to switch.Method: The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry conducted a supplemental survey among registry participants responding to the 2011 update survey. The supplemental survey investigated reasons for switching DMT, origin of the discussion of DMT change, and which factors influenced the decision. Chi-square tests, Fisher’s exact tests, and logistic regression were used for the analyses. Results: Of the 691 eligible candidates, 308 responded and met the inclusion criteria (relapsing disease course, switched DMT after September 2010). The responders were 83.4% female, on average 52 years old, with a median (interquartile range) Patient-Determined Disease Steps score of 4 (2–5). The most recent prior therapy included first-line injectables (74.5%), infusions (18.1%), an oral DMT (3.4%), and other DMTs (4.0%). The discussion to switch DMT was initiated almost equally by physicians and participants. The primary reason for choosing the new DMT was based most frequently on physician’s recommendation (24.5%) and patient perception of efficacy (13.7%). Conclusion: Participants frequently initiated the discussion regarding changing DMT, although physician recommendations regarding the specific therapy were still weighed highly. Long-term follow-up of these participants will provide valuable information on their disease trajectory, satisfaction with, and effectiveness of their new medication. Keywords: multiple sclerosis, health communication

Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a

Background: Interactive multimedia programs derived from the Sunny Days, Healthy Ways (SDHW) sun safety curriculum were evaluated with children aged 5-13.Methods: A randomized pretest to posttest 3-group study was conducted with 871 students in 12 primary schools in the western United States comparing computer programs alone, teacher-led presentation, or both combined.Results: Computer programs with teacher-led presentation improved knowledge over either treatment individually (P = .001). The combination improved self-reported sun protection in lower but not higher grades over teacher-led presentation (P = .005).Conclusions: Computer-based sun safety instruction used with teacher instruction in primary schools may improve sun safety, especially with younger children. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The prevalence of helmet use by alpine skiers and snowboarders was estimated and self-reports on risk taking were assessed to test for potential risk compensation when using helmets in these sports. SETTING: Skiers and snowboarders were observed and interviewed at 34 resorts in the western United States and Canada. SUBJECTS: Respondents were 1779 adult skiers and snowboarders in the 2003 ski season. OUTCOME MEASURES: Observations of helmet use and questions about perceived speed and degree of challenge when not wearing a helmet (helmet wearers) or in previous ski seasons (non-helmet wearers). RESULTS: Helmet wearers reported that they skied/snowboarded at slower speeds (OR = 0.64, p<0.05) and challenged themselves less (OR = 0.76, p<0.05) than non-helmet wearers. Adoption of safety helmets in 2003 (23%) continued to increase over 2002 (OR = 0.46, p<0.05) and 2001 (OR = 0.84, p<0.05). CONCLUSIONS: No evidence of risk compensation among helmet wearers was found. Decisions to wear helmets may be part of a risk reduction orientation. Helmet use continues to trend upwards but adoption may be slowing. [ABSTRACT FROM AUTHOR]

Health communication campaigns intended to reduce chronic and severe exposure to ultraviolet radiation in sunlight and prevent skin cancer are a national priority. Outdoor workers represent an unaddressed, high-risk population. Go Sun Smart (GSS), a worksite sun safety program largely based on the diffusion-of-innovations theory, was evaluated in a pair-matched, group-randomized, pretest-posttest controlled design enrolling employees at 26 ski areas in Western North America. Employees at the intervention ski areas were more aware of GSS (odds ratio [OR] = 8.27, p < .05) and reported less sunburning (adjusted OR = 1.63, p < .05) at posttest than employees at the control areas. A dose response was evident (OR = 1.46, p < .05) with greater observed program implementation associated with fewer sunburns among employees. Program awareness per se was not predictive (p > .05) of reduced sunburning in a mediational analysis. Analyses of nonrespondents, including intent-to-treat analyses, further supported the success of GSS. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To understand mammographers' perception of individual women's breast cancer risk. MATERIALS AND METHODS: Radiologists interpreting screening mammography examinations completed a mailed survey consisting of questions pertaining to demographic and clinical practice characteristics, as well as 2 vignettes describing different risk profiles of women. Respondents were asked to estimate the probability of a breast cancer diagnosis in the next 5 years for each vignette. Vignette responses were plotted against mean recall rates in actual clinical practice. RESULTS: The survey was returned by 77% of eligible radiologists. Ninety-three percent of radiologists overestimated risk in the vignette involving a 70-year-old woman; 96% overestimated risk in the vignette involving a 41-year-old woman. Radiologists who more accurately estimated breast cancer risk were younger, worked full-time, were affiliated with an academic medical center, had fellowship training, had fewer than 10 years experience interpreting mammograms, and worked more than 40% of the time in breast imaging. However, only age was statistically significant. No association was found between radiologists' risk estimate and their recall rate. CONCLUSION: U.S. radiologists have a heightened perception of breast cancer risk. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to examine diffusion of and predictors of helmet use among skiers and snowboarders in the Western United States and Canada. DESIGN: 6400 skiers and snowboarders at 29 ski resorts in the Western United States and Canada were interviewed on chair lifts and observed for helmet use during two consecutive ski seasons (winters 2001 and 2002). SETTING: Skiers and snowboarders were observed and interviewed at 29 ski resorts in Alaska, California, Colorado, Idaho, Montana, New Mexico, Nevada, Oregon, Utah, and British Columbia as part of a sun protection project. SUBJECTS: Participants completing the survey consisted of 3525 adult skiers and snowboarders in the 2002 season and 2978 adult skiers and snowboarders in the 2001 season. MAIN OUTCOME MEASURE: The outcome measure for all analyses was prevalence of helmet use by skiers and snowboarders. RESULTS: Helmet use by skiers and snowboarders is increasing and is most prevalent among snowboarders, experts, and more frequent skiers/snowboarders. No evidence was found for the hypothesis that helmet use is diffusing more rapidly among earlier adopters of helmets than later adopters. CONCLUSIONS: Although controversy remains, helmets are rapidly diffusing as a safety device at western North American ski resorts. Expert and more frequent skiers and snowboarders are more likely to wear helmets, which may indicate that helmets are recognized as a safety device. [ABSTRACT FROM AUTHOR]

Numerous predictive equations have evolved for the estimation of resting energy expenditure (REE) since it is not generally practical or feasible to use indirect calorimetry in practice settings. Recently, the Mifflin-St Jeor Equation (MSJE), derived from a population of 498 healthy subjects and published in 1990, was recommended as the standard for calculating REE by the Application of Indirect Calorimetry in ADA Evidence-Based Guides for Practice Expert Consensus Panel of the American Dietetic Association. Although no equation can replace the accuracy of a personalized indirect calorimetry measurement, this equation reportedly explained a substantial amount of the variation of the measured REE (R2 = 0.71) and provided the most accurate estimate (78% within +/-10% limit) of actual REE in the largest percentage of nonobese and obese in a defined test population. Importantly, the MSJE was derived on a diverse sample of healthy adults (N = 498), including females (n = 247) and males (n = 251), subjects aged 19 to 78 (45 +/- 14) years, and nonobese (n = 264) and obese (n = 234) individuals. This article presents 2 charts by gender from which an estimated REE can be easily derived from known height (inches) and weight (pounds) with an individual adjustment of -5 kcal/year of age. The charts are limited to the source sample from which the data were derived since the estimated REE for individuals falling within these parameters will be more accurate. Extrapolated REEs beyond this population are available and may be useful, but will require further study. [ABSTRACT FROM AUTHOR]

Background: The performance of diagnostic mammography for women with signs or symptoms of breast cancer has not been well studied. We evaluated whether age, breast density, self-reported breast lump, and previous mammography influence the performance of diagnostic mammography.Methods: From January 1996 through March 1998, prospective diagnostic mammography data from women aged 25-89 years with no previous breast cancer were linked to cancer outcomes data in six mammography registries participating in the Breast Cancer Surveillance Consortium. We used the final mammographic assessment at the end of the imaging work-up to determine abnormal mammographic examination rate, positive predictive value (PPV), sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve. We used age, breast density, prior mammogram, and self-reported breast lump jointly as predictors of performance. All statistical tests were two-sided.Results: Of 41 427 diagnostic mammograms, 6279 (15.2%) were judged abnormal. The overall PPV was 21.8%, sensitivity was 85.8%, and specificity was 87.7%. Multivariate analysis showed that sensitivity and specificity generally declined as breast density increased (P =.007 and P<.001, respectively), that previous mammography decreased sensitivity (odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.36 to 0.74; P<.001) but increased specificity (OR = 1.43, 95% CI = 1.31 to 1.57; P<.001), and that a self-reported breast lump increased sensitivity (OR = 1.64, 95% CI = 1.13 to 2.38; P =.013) but decreased specificity (OR = 0.54, 95% CI = 0.49 to 0.59; P<.001). ROC analysis showed that higher breast density and previous mammography were negatively related to accuracy (P<.001 for both).Conclusions: Diagnostic mammography in women with signs or symptoms of breast cancer shows higher sensitivity and lower specificity than screening mammography does. Higher breast density and previous mammographic examination appear to impair performance. [ABSTRACT FROM AUTHOR]

Background: Unprotected and excessive exposure to ultraviolet radiation (UVR) is the primary risk factor for skin cancer.Design: A pair-matched, group-randomized, pre-test/post-test, quasi-experimental design, with ski resorts as the unit of randomization, tested the effectiveness of Go Sun Smart, a multi-channel skin cancer prevention program. Independent samples of guests were taken at baseline (2001) and follow-up (2002); data were analyzed in 2006.Setting and Participants: A total of 6516 adult guests at 26 ski areas in the western U.S. and Canada were recruited, consented, and interviewed on chairlifts. This study was nested within an occupational intervention for ski area workers.Intervention: Ski areas were pair-matched and randomized to receive Go Sun Smart, which consisted of print, electronic, visual, and interpersonal skin cancer prevention messages.Main Outcome Measures: Sun-protection behaviors, sunburning, recall of sun-protection messages, and the association of message exposure to sun protection.Results: The difference in recall of all sun-protection messages, messages on signs and posters, and the Go Sun Smart logo was significant between the intervention and control resorts. Reported use of sun-protection practices was higher by guests at intervention ski areas using more (a higher dose of) Go Sun Smart materials. Intervention-group guests who recalled a sun-safety message were more likely to practice sun safety than intervention-group guests who did not recall a message and control-group guests.Conclusions: While the mere implementation of Go Sun Smart did not produce sun-safety improvements, Go Sun Smart appeared to be effective for guests who encountered and remembered it. Many factors can work against message exposure. Signage seemed to produce the greatest increase in exposure to sun-safety messages. [ABSTRACT FROM AUTHOR]

Background: Inhaled nitric oxide improves oxygenation and lessens the need for extracorporeal-membrane oxygenation in full-term neonates with hypoxaemic respiratory failure and persistent pulmonary hypertension, but potential adverse effects are intracranial haemorrhage and chronic lung disease. We investigated whether low-dose inhaled nitric oxide would improve survival in premature neonates with unresponsive severe hypoxaemic respiratory failure, and would not increase the frequency or severity of intracranial haemorrhage or chronic lung disease.Methods: We did a double-blind, randomised controlled trial in 12 perinatal centres that provide tertiary care. 80 premature neonates (gestational age < or = 34 weeks) with severe hypoxaemic respiratory failure were randomly assigned inhaled nitric oxide (n=48) or no nitric oxide (n=32, controls). Our primary outcome was survival to discharge. Analysis was by intention to treat. We studied also the rate and severity of intracranial haemorrhage, pulmonary haemorrhage, duration of ventilation, and chronic lung disease at 36 weeks' postconceptional age.Findings: The two groups did not differ for baseline characteristics or severity of disease. Inhaled nitric oxide improved oxygenation after 60 min (p=0.03). Survival at discharge was 52% in the inhaled-nitric-oxide group and 47% in controls (p=0.65). Causes of death were mainly related to extreme prematurity and were similar in the two groups. The two groups did not differ for adverse events or outcomes (intracranial haemorrhage grade 2-4, 28% inhaled nitric oxide and 33% control; pulmonary haemorrhage 13% and 9%; chronic lung disease 60% and 80%).Interpretation: Low-dose inhaled nitric oxide improved oxygenation but did not improve survival in severely hypoxaemic premature neonates. Low-dose nitric oxide in the most critically ill premature neonates does not increase the risk of intracranial haemorrhage, and may decrease risk of chronic lung injury. [ABSTRACT FROM AUTHOR]

Background and Objectives: Exposure to natalizumab, an efficacious treatment for relapsing-remitting multiple sclerosis (RRMS), is associated with increased risk of progressive multifocal leukoencephalopathy (PML). Compared with every-4-week (Q4W) dosing, extended-interval dosing of natalizumab is associated with decreased risk of PML. Clinical efficacy was maintained in the majority of patients switched to every-6-week (Q6W) dosing in the phase 3b NOVA clinical trial. In this article, we report pharmacokinetics (PK) and pharmacodynamics (PD) of Q6W vs Q4W dosing in NOVA., Methods: In NOVA study Part 1, participants with RRMS (aged 18-60 years) and Expanded Disability Status Scale score <5.5, who were stable on IV natalizumab Q4W dosing for ≥12 months, were randomized to continue IV Q4W dosing or switched to IV Q6W dosing of natalizumab and followed for 72 weeks. Exploratory outcomes were measurements of trough serum natalizumab concentration, α4-integrin saturation, and soluble vascular cell adhesion molecule-1 (sVCAM-1) concentration. A mixed model of repeated measures was used to estimate mean treatment differences between groups. Patient-level PK and PD data were examined in those with relapse or radiologic disease activity., Results: In NOVA, 486 (Q6W, n = 245; Q4W, n = 241) and 487 (Q6W, n = 246; Q4W, n = 241) participants were included in the PK and PD populations, respectively. Mean trough natalizumab concentrations ranged from 10 to 21 μg/mL (Q6W) and 33-38 μg/mL (Q4W), and mean α4-integrin saturation remained above 65.5% (Q6W) and above 77.9% (Q4W). In the Q6W group, mean sVCAM-1 levels increased 23.6% by week 24 and remained elevated throughout the study, while mean sVCAM-1 levels remained generally stable in the Q4W group. Most participants with T2 lesion activity or relapse activity, in either treatment arm, maintained trough natalizumab levels >10 μg/mL and trough α4-integrin saturation >50%., Discussion: Compared with Q4W dosing, Q6W dosing was associated with a 60%-70% decrease in mean trough natalizumab levels and a 9%-16% decrease in mean α4-integrin saturation. At the patient level, neither natalizumab concentration nor α4-integrin saturation was consistently predictive of lesion or relapse activity, suggesting that trough natalizumab and α4-integrin saturation measurements should be interpreted with caution in clinical practice., Trial Registration Information: ClinicalTrials.gov, NCT03689972; EudraCT, 2018-002145-11. Submitted 2018-09-27. First patient enrolled: 2018-12-26. https://clinicaltrials.gov/study/NCT03689972.

Background and Objectives: Despite their high health care use, it is unclear whether the health care needs of people with MS are being met and what their priorities are. We assessed priorities for access to, and affordability of care, by people living with MS in the United States. We also tested the association between perceived inadequate access to care and health-related quality of life (HRQoL)., Methods: In Fall 2022, we conducted a cross-sectional survey of participants in the North American Research Committee on Multiple Sclerosis Registry about access to care and HRQoL (Health Utilities Index Mark III). We used multivariable polytomous logistic regression to test sociodemographic and clinical factors associated with access to care. We used multivariable linear regression analysis to test the association between access to care and HRQoL., Results: We included 4,914 respondents in the analysis, of whom 3,974 (80.9%) were women, with a mean (SD) age 64.4 (9.9) years. The providers who were most reported as needed but inaccessible were complementary providers (35.5%), followed by allied health providers (24.2%), occupational therapists (22.7%), and mental health providers (20.7%). Over 80% of participants reported that it was important or very important to be able to get an appointment with their primary MS health care provider when needed, to have sufficient time in their appointments to explain their concerns, to see their neurologist if their status changed, and that their health care providers communicated to coordinate their care. Participants who reported needing to see the provider but not having access or seeing the provider but would like to see them more often had lower HRQOL (ranging from -0.059 to -0.176) than participants who saw the provider as much as needed., Discussion: Gaps in access to care persist for people with MS in the United States and substantially affect HRQoL. Improving access to care for people with MS should be a health system priority., Competing Interests: R.A. Marrie receives research funding from CIHR, Research Manitoba, MS Canada, Multiple Sclerosis Scientific Foundation, Crohn's and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense, and is a coinvestigator on studies receiving funding from Biogen Idec and Roche Canada. She holds the Waugh Family Chair in Multiple Sclerosis and serves on the editorial board of Neurology. S. Lancia has nothing to disclose. G.R. Cutter serves on Data and Safety Monitoring Boards for Applied Therapeutics, AI therapeutics, AMO Pharma, Astra-Zeneca, Avexis Pharmaceuticals, Biolinerx, Brainstorm Cell Therapeutics, Bristol Meyers Squibb/Celgene, CSL Behring, Galmed Pharmaceuticals, Green Valley Pharma, Horizon Pharmaceuticals, Immunic, Karuna Therapeutics, Mapi Pharmaceuticals LTD, Merck, Mitsubishi Tanabe Pharma Holdings, Opko Biologics, Prothena Biosciences, Novartis, Regeneron, Sanofi-Aventis, Reata Pharmaceuticals, Teva Pharmaceuticals, NHLBI (Protocol Review Committee), University of Texas Southwestern, University of Pennsylvania, Visioneering Technologies, Inc., Consulting or Advisory Boards for Alexion, Antisense Therapeutics, Biogen, Clinical Trial Solutions LLC, Entelexo Biotherapeutics, Inc., Genzyme, Genentech, GW Pharmaceuticals, Immunic, Immunosis Pty Ltd, Klein-Buendel Incorporated, Merck/Serono, Novartis, Perception Neurosciences, Protalix Biotherapeutics, Regeneron, Roche, SAB Biotherapeutics. He is employed by the University of Alabama at Birmingham and President of Pythagoras, Inc., a private consulting company located in Birmingham AL. R.J. Fox receives personal consulting fees from AB Science, Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Immunic, INmune Bio, Janssen, Lily, Novartis, Sanofi, Siemens, and TG Therapeutics; clinical trial contract and research grant funding from Biogen, Novartis, and Sanofi. A. Salter receives research funding from Multiple Sclerosis Society of Canada, National Multiple Sclerosis Society, CMSC and the Department of Defense Congressionally Directed Medical Research Program, and is a member of editorial board for Neurology. She serves as a consultant for Gryphon Bio, LLC. She is a member of the Data and Safety Monitoring Board for Premature Infants Receiving Milking or Delayed Cord Clamping (PREMOD2), Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis (CAVS-MS), and Ocrelizumab for Preventing Clinical Multiple Sclerosis in Individuals With Radiologically Isolated Disease (CELLO). She holds the Kenney Marie Dixon‐Pickens Distinguished Professorship in Multiple Sclerosis Research. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2024 American Academy of Neurology.)

Objective: Two methods for scaling up an evidence-based occupational sun protection program were compared., Methods: Regional districts (n = 138) in 21 state Departments of Transportation throughout the United States were randomized to receive the Go Sun Smart at Work program via in-person or digital scalability methods in 2019-2022 in 1:2 ratio. Managers completed pretest and posttest surveys and employees completed posttest surveys. Due to the COVID pandemic, only posttest measures were analyzed (n = 255 managers; n = 1387 employees)., Results: After scale-up, more employees reported training (b = 0.381, p = 0.021) and communication (b = 0.112, p = 0.049) at workplaces in in-person rather than digital strategy. There were no differences in managers' reports of sun protection training, communication, or actions by scalability method (p > 0.05)., Conclusions: Occupational sun protection was implemented during program scale up and employees recalled training/communication more in the in-person than digital strategy., Competing Interests: Conflict of Interest for All Authors: D. Buller receives a salary from Klein Buendel, Inc. And his spouse is an owner of Klein Buendel, Inc. M.K. Buller receives a salary from Klein Buendel, Inc. And she is an owner of Klein Buendel, Inc. G. Cutter Board membership, advisory board fees from Alexion, Antisense Therapeutics, Avotres, Biogen, Clene Nanomedicine, Clinical Trial Solutions LLC, Endra Life Sciences, Cognito Therapeutics, Entelexo Biotherapeutics, Inc., Genzyme, Genentech, GW Pharmaceuticals, Hoya Corporation, Immunic, Immunosis Pty Ltd, Klein Buendel Inc., Linical, Merck/Serono, Novartis, Perception Neurosciences, Protalix Biotherapeutics, Regeneron, Roche, SAB Biotherapeutics, and Sapience Therapeutics., and data and safety monitoring board fees from Applied Therapeutics, AI therapeutics, AMO Pharma, Astra-Zeneca, Avexis Pharmaceuticals, Bristol Meyers Squibb/Celgene, CSL Behring, Cynata Therapeutics, Diametica Therapeutics, Horizon Pharmaceuticals, Immunic, Karuna Therapeutics, Kezar Life Sciences, Medtronic, Mapi Pharmaceuticals LTD, Medtronic, Merck, Mitsubishi Tanabe Pharma Holdings, Opko Biologics, Prothena Biosciences, Novartis, Pipeline Therapeutics, Regeneron, Sanofi-Aventis, Reata Pharmaceuticals, Teva Pharmaceuticals, United BioSource LLC, University of Texas Southwestern, University of Pennsylvania, and Visioneering Technologies, Inc. outside the submitted work. J. Berteletti, A. Kinsey, I. Adjei, and N. Chirico receive a salary from Klein Buendel, Inc. R. Meenan and K. Henry report None Declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

Introduction: Following NOVA (part 1) and the approval of the subcutaneous (SC) route of administration of natalizumab by the European Medicines Agency, an extension phase of the NOVA phase IIIb study (part 2) was initiated to collect patient preference data for SC versus intravenous (IV) dosing in patients receiving every-6-week (Q6W) dosing of natalizumab. This study was performed to evaluate patient preference for SC versus IV natalizumab administration and explore the efficacy, safety, and pharmacology characteristics of both routes of administration., Methods: In part 2, participants received natalizumab (Tysabri ® ) 300 mg via IV infusion Q6W for 36 weeks and then were randomized to 48 weeks of crossover treatment (24 weeks SC Q6W and 24 weeks IV Q6W, or vice versa). The primary endpoint was the proportion of participants who indicated a preference for natalizumab SC administration on the Patient Preference Questionnaire., Results: A total of 153 participants were randomized in NOVA part 2. Of 123 with patient preference data, 108 (87.8%) preferred the SC route of administration for natalizumab over the IV route; 102 (82.9%) specified "requires less time in the clinic" as the reason for the SC preference., Conclusion: In NOVA (part 2), most participants on Q6W dosing of natalizumab preferred SC administration versus IV administration., Clinicaltrials: GOV: NCT03689972. INFOGRAPHIC., (© 2024. The Author(s).)

Acute ingestion of exogenous ketone supplements in the form of a (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (R-BD R-βHB) ketone monoester (KME) can attenuate declines in oxygen availability during hypoxic exposure and might impact cognitive performance at rest and in response to moderate-intensity exercise. In a single-blind randomized crossover design, 16 males performed assessments of cognitive performance before and during hypoxic exposure with moderate exercise [2 × 20 min weighted ruck (∼22 kg) at 3.2 km/h at 10% incline] in a normobaric altitude chamber (4572 m, 11.8% O 2 ). The R-BD R-βHB KME (573 mg/kg) or a calorie- and taste-matched placebo (∼50 g maltodextrin) were co-ingested with 40 g of dextrose before exposure to hypoxia. The R-βHB concentrations were rapidly elevated and sustained (>3 mM; P < 0.001) by KME. The decline in oxygen saturation during hypoxic exposure was attenuated in KME conditions by 2.4%-4.2% (P < 0.05) compared with placebo. Outcomes of cognitive performance tasks, in the form of the Defense Automated Neurobehavioral Assessment (DANA) code substitution task, the Stroop color and word task, and a shooting simulation, did not differ between trials before and during hypoxic exposure. These data suggest that the acute exogenous ketosis induced by KME ingestion can attenuate declining blood oxygen saturation during acute hypoxic exposure both at rest and during moderate-intensity exercise, but this did not translate into differences in cognitive performance before or after exercise in the conditions investigated., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background and Objectives: Disease-modifying treatments (DMTs) are a major unmet need in Parkinson disease (PD). To date, trials investigating DMT candidates in PD most often used a randomized controlled trial (RCT) design. Unfortunately, RCTs to date have not led to a breakthrough, in part because of the large sample sizes and length of follow-up required. In the interest of testing DMT candidates in a more efficient manner, it may be worthwhile to perform futility trials, which are smaller clinical trials that have originally been developed as phase 2 trials in oncology and more recently been used in progressive multiple sclerosis. In this investigation, we used original, patient-level data from DATATOP and PRECEPT, 2 large RCTs in early PD, to explore the feasibility of using the Simon 2-Stage futility trial design in early PD., Methods: This is a post hoc analysis of original, patient-level data from the DATATOP and PRECEPT RCTs in early PD. In our analyses, we use descriptive statistics, survival analysis, and binary logistic regression to explore thresholds of change in the Unified Parkinson Disease Rating Scale (UPDRS) motor score as the primary outcome measure, length of follow-up, inclusion and exclusion criteria, and projected sample sizes for Simon 2-Stage futility trials in early PD. We also performed bootstrapping experiments to illustrate the ability of trials using the Simon 2-Stage futility design to identify selegiline as nonfutile and tocopherol as futile., Results: PRECEPT included 806 participants (mean age 59.7 years, SD 10.3, 64.4% male), and DATATOP included 800 participants (mean age 61.1 years, SD 9.5, 64.4% male). Our analyses suggest that futility trials using the Simon 2-Stage methodology are feasible in PD. We propose a 5-point worsening on the UPDRS motor score as the primary outcome measure and a length of follow-up of 12 months. Trial simulations based on these data suggest the required sample size for such clinical trials to be lower than 200 participants., Discussion: Based on our analysis of DATATOP and PRECEPT, phase 2 clinical trials using the Simon 2-Stage methodology are feasible in PD and may offer an opportunity to expedite the discovery of promising treatments in early PD.

Physical activity, including structured exercise, is associated with favorable health-related chronic disease outcomes. Although there is evidence of various molecular pathways that affect these responses, a comprehensive molecular map of these molecular responses to exercise has not been developed. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a multicenter study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. MoTrPAC contains both a preclinical and human component. The details of the human studies component of MoTrPAC that include the design and methods are presented here. The human studies contain both an adult and pediatric component. In the adult component, sedentary participants are randomized to 12 wk of Control, Endurance Exercise Training, or Resistance Exercise Training with outcomes measures completed before and following the 12 wk. The adult component also includes recruitment of highly active endurance-trained or resistance-trained participants who only complete measures once. A similar design is used for the pediatric component; however, only endurance exercise is examined. Phenotyping measures include weight, body composition, vital signs, cardiorespiratory fitness, muscular strength, physical activity and diet, and other questionnaires. Participants also complete an acute rest period (adults only) or exercise session (adults, pediatrics) with collection of biospecimens (blood only for pediatrics) to allow for examination of the molecular responses. The design and methods of MoTrPAC may inform other studies. Moreover, MoTrPAC will provide a repository of data that can be used broadly across the scientific community. NEW & NOTEWORTHY The Molecular Transducers of Physical Activity Consortium (MoTrPAC) will be the first large trial to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. By generating a compendium of the molecular responses to exercise, MoTrPAC will lay the foundation for a new era of biomedical research on Precision Exercise Medicine. Presented here is the design, protocols, and procedures for the MoTrPAC human studies.

Estimating the densities of marine prey observed in animal-borne video loggers when encountered by foraging predators represents an important challenge for understanding predator-prey interactions in the marine environment. We used video images collected during the foraging trip of one chinstrap penguin (Pygoscelis antarcticus) from Cape Shirreff, Livingston Island, Antarctica to develop a novel approach for estimating the density of Antarctic krill (Euphausia superba) encountered during foraging activities. Using the open-source Video and Image Analytics for a Marine Environment (VIAME), we trained a neural network model to identify video frames containing krill. Our image classifier has an overall accuracy of 73%, with a positive predictive value of 83% for prediction of frames containing krill. We then developed a method to estimate the volume of water imaged, thus the density (N·m-3) of krill, in the 2-dimensional images. The method is based on the maximum range from the camera where krill remain visibly resolvable and assumes that mean krill length is known, and that the distribution of orientation angles of krill is uniform. From 1,932 images identified as containing krill, we manually identified a subset of 124 images from across the video record that contained resolvable and unresolvable krill necessary to estimate the resolvable range and imaged volume for the video sensor. Krill swarm density encountered by the penguins ranged from 2 to 307 krill·m-3 and mean density of krill was 48 krill·m-3 (sd = 61 krill·m-3). Mean krill biomass density was 25 g·m-3. Our frame-level image classifier model and krill density estimation method provide a new approach to efficiently process video-logger data and estimate krill density from 2D imagery, providing key information on prey aggregations that may affect predator foraging performance. The approach should be directly applicable to other marine predators feeding on aggregations of prey., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

The role of immunosenescence, particularly the natural process of thymic involution during aging, is increasingly acknowledged as a factor contributing to the development of autoimmune diseases and cancer. Recently, a concern has been raised about deleterious consequences of the surgical removal of thymic tissue, including for patients who undergo thymectomy for myasthenia gravis (MG) or resection of a thymoma. This review adopts a multidisciplinary approach to scrutinize the evidence concerning the long-term risks of cancer and autoimmunity postthymectomy. We conclude that for patients with acetylcholine receptor antibody-positive MG and those diagnosed with thymoma, the removal of the thymus offers prominent benefits that well outweigh the potential risks. However, incidental removal of thymic tissue during other thoracic surgeries should be minimized whenever feasible.

Background: Inebilizumab, an anti-CD19 B-cell-depleting antibody, demonstrated safety and efficacy in neuromyelitis optica spectrum disorder in the randomised controlled period of the N-MOmentum trial. Here, end-of-study data, including the randomised controlled period and open-label extension period, are reported., Methods: In the double-blind, randomised, placebo-controlled, phase 2/3 N-MOmentum trial, adults aged 18 years and older with an neuromyelitis optica spectrum disorder diagnosis, Expanded Disability Status Scale score of 8·0 or less, and history of either at least one acute inflammatory attack requiring rescue therapy in the past year or two attacks requiring rescue therapy in the past 2 years, were recruited from 81 outpatient specialty clinics or hospitals in 24 countries. Eligible participants were randomly assigned (3:1), using a central interactive voice system or interactive web response system, and a permuted block randomisation scheme (block size of 4), to receive intravenous inebilizumab (300 mg) or identical placebo on days 1 and 15 of the randomised period, which lasted up to 197 days. Participants and all study staff were masked to treatment assignment. The primary endpoint of the randomised period of the trial was time to onset of adjudicated neuromyelitis optica spectrum disorder attack on or before day 197. Participants in the randomised controlled period who had an adjudicated attack, completed 197 days in the study, or were in the randomised controlled period when enrolment stopped, could voluntarily enter the open-label period. In the open-label period, participants either initiated inebilizumab if assigned placebo (receiving 300 mg on days 1 and 15 of the open-label period) or continued treatment if assigned inebilizumab (receiving 300 mg on day 1 and placebo on day 15, to maintain B-cell depletion and masking of the randomised controlled period). All participants subsequently received inebilizumab 300 mg every 6 months for a minimum of 2 years. The end-of-study analysis endpoints were time to adjudicated attack and annualised attack rate (assessed in all participants who received inebilizumab at any point during the randomised controlled period or open-label period [any inebilizumab population] and the aquaporin-4 [AQP4]-IgG seropositive subgroup [any inebilizumab-AQP4-IgG seropositive population]) and safety outcomes (in all participants who were exposed to inebilizumab, analysed as-treated). This study is registered with ClinicalTrials.gov, NCT02200770, and is now complete., Findings: Between Jan 6, 2015, and Sept 24, 2018, 467 individuals were screened, 231 were randomly assigned, and 230 received at least one dose of inebilizumab (n=174) or placebo (n=56). Between May 19, 2015, and Nov 8, 2018, 165 (95%) of 174 participants in the inebilizumab group and 51 (91%) of 56 in the placebo group entered the open-label period (mean age 42·9 years [SD 12·4], 197 [91%] of 216 were female, 19 [9%] were male, 115 [53%] were White, 45 [21%] were Asian, 19 [9%] were American Indian or Alaskan Native, and 19 [9%] were Black or African American). As of data cutoff for this end of study analysis (Dec 18, 2020; median exposure 1178 days [IQR 856-1538], total exposure of 730 person-years) 225 participants formed the any inebilizumab population, and 208 (92%) participants were AQP4-IgG seropositive. Overall, 63 adjudicated neuromyelitis optica spectrum disorder attacks occurred in 47 (21%) of 225 treated participants (60 attacks occurred in 44 [21%] of 208 in the AQP4-IgG seropositive subgroup); 40 (63%) of 63 attacks occurred in 34 (15%) of 225 treated participants during the first year of treatment. Of individuals who had an adjudicated attack while receiving inebilizumab, 36 (77%) of 47 were subsequently attack-free at the end of 4 years. Annualised attack rates decreased year-on-year, with end-of-study adjusted annualised attack rates being similar in the any inebilizumab-AQP4-IgG seropositive subgroup (0·097 [95% CI 0·070-0·14]) and any inebilizumab populations (0·092 [0·067-0·13]). Overall, 208 (92%) of 225 participants who received any inebilizumab had at least one treatment-emergent adverse event, the most frequent of which were urinary tract infection (59 [26%]), nasopharyngitis (47 [21%]), and arthralgia (39 [17%]). Infection rates did not increase over 4 years. Three (1%) of 225 participants in the any inebilizumab population died during the open-label period (one each due to a CNS event of unknown cause and pneumonia, respiratory insufficiency resulting from an neuromyelitis optica spectrum disorder attack and viral pneumonia related to COVID-19), all of which were deemed to be unrelated to treatment., Interpretation: Data from the end-of-study analysis of the N-MOmentum trial showed continued and sustained clinical benefits of long-term inebilizumab treatment in individuals with neuromyelitis optica spectrum disorder, which supports the role of inebilizumab as a CD19+ B-cell-depleting therapy in neuromyelitis optica spectrum disorder., Funding: MedImmune and Viela Bio/Horizon Therapeutics, now part of Amgen., Competing Interests: Declaration of interests BACC reports personal fees for consulting from Alexion, Atara, Autobahn, Avotres, Biogen, Boston Pharma, EMD Serono, Gossamer Bio, Hexal/Sandoz, Horizon Therapeutics, Neuron23, Novartis, Sanofi, Siemens, TG Therapeutics, and Therini Bio, and has received research support from Genentech. HJK has received a grant from the National Research Foundation of Korea and research support from AprilBio, Eisai, and UCB; consultancy or speaker fees from Alexion, Altos Biologics, AstraZeneca, Biogen, Daewoong Pharmaceutical, Eisai, GC Pharma, Handok Pharmaceuticals, Kaigene, Kolon Life Science, MDimune, Merck Serono, Mitsubishi Tanabe Pharma, Roche, and Sanofi Genzyme; serves on a steering committee for MedImmune/Viela Bio; and is a co-editor for the Multiple Sclerosis Journal and an associate editor for the Journal of Clinical Neurology. BGW receives payments for serving as chair of attack adjudication committees for clinical trials in neuromyelitis optica spectrum disorder for Alexion, MedImmune, UCB Bioscience, and Viela Bio/Horizon Therapeutics; has consulted with CANbridge Pharmaceuticals, Chugai, Genentech, Horizon Therapeutics, Mitsubishi Tanabe Pharma, and Roche Pharmaceuticals; has received payments for speaking for Genentech, Horizon Therapeutics, and Roche; and has a patent for NMO-IgG for diagnosis of neuromyelitis optica, with royalties paid by Hospices Civils de Lyon, MVZ Labor PD Dr Volkmann und Kollegen GbR, RSR Limited, and the University of Oxford. SJP reports grants, personal fees, and non-financial support from Alexion; grants from Autoimmune Encephalitis Alliance and Grifols; grants, personal fees, and non-financial support from MedImmune and Viela Bio/Horizon Therapeutics; consulting support from Astellas, Genentech, and Sage Therapeutics; personal fees for consulting services from for F Hoffman-La Roche AG, Genentech, and UCB; and has a patent #9,891,219 (Application#12-573942) “Methods for Treating Neuromyelitis Optica (NMO) by Administration of Eculizumab to an individual that is Aquaporin-4 (AQP4)-IgG Autoantibody positive”. DMW reports personal fees from Alexion, AstraZeneca, Bristol Myers Squibb, Genentech, Horizon Therapeutics, Imcyse, Merck, Novartis, and Reistone Biopharma; serves on a clinical trial adjudication committee for MedImmune, Viela Bio/Horizon Therapeutics, and UCB Pharma; and serves on a data and safety monitoring board for Alexion and Abscuro. KF serves on scientific advisory boards for Alexion, Bayer Schering, Biogen, Chugai, MedImmune, Merck Serono, Mitsubishi Tanabe Pharma, Nihon Pharmaceutical, Novartis, Ono Pharmaceutical, and Viela Bio/Horizon Therapeutics; has received funding for travel and speaker fees from Asahi Kasei Medical, Astellas, Bayer Schering, Biogen, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Mitsubishi Tanabe Pharma, Nihon Pharmaceutical, Novartis, and Takeda; and research support from Asahi Kasei Medical, Bayer Schering, Biogen, Chemo-Sero-Therapeutic Research Institute, Chugai, Genzyme Japan, the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Ministry of Health, Welfare, and Labor of Japan, Mitsubishi Tanabe Pharma, Nihon Pharmaceutical, Ono Pharmaceutical, Teijin, and Teva. FP has received research support, speaker fees, and travel reimbursement from Bayer, Biogen, Merck Serono, Novartis, Sanofi Genzyme, and Teva; is supported by the German Competence Network for Multiple Sclerosis and the German Research Council (DFG Exc 257); has received travel reimbursement from the Guthy–Jackson Charitable Foundation; and serves on the steering committee of the OCTiMS study sponsored by Novartis. GRC has received personal fees for participation on data and safety monitoring boards from AI Therapeutics, AMO Pharma, Applied Therapeutics, AstraZeneca, Avexis Pharmaceuticals, BioLineRx, Brainstorm Cell Therapeutics, Bristol Myers Squibb/Celgene, CSL Behring, Galmed Pharmaceuticals, Green Valley Pharma, Horizon Therapeutics, Immunic Therapeutics, Karuna Therapeutics, Mapi Pharma, Merck, Mitsubishi Tanabe Pharma, the National Heart, Lung, and Blood Institute (US; Protocol Review Committee), Novartis, OPKO Biologics, Prothena Biosciences, Reata Pharmaceuticals, Regeneron, Sanofi-Aventis, Teva Pharmaceuticals, the University of Texas Southwestern, the University of Pennsylvania, and Visioneering Technologies; personal fees for consulting or advisory board participation from Alexion, Antisense Therapeutics, Biogen, Clinical Trial Solutions, Entelexo Biotherapeutics, Genentech, Genzyme, GW Pharmaceuticals, Immunic Therapeutics, Immunosis, Klein Buendel, Merck/Serono, Novartis, Osmotica Pharmaceuticals, Perception Neurosciences, Protalix BioTherapeutics, Recursion/CereXis, Regeneron, Roche, and SAB Biotherapeutics. GRC is employed by the University of Alabama at Birmingham and is President of Pythagoras, a private consulting company based in Birmingham, AL, USA. RM serves on scientific advisory boards for MedImmune and Viela Bio/Horizon Therapeutics; and has received funding for travel and fees from Alexion, Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, Teva, and Viela Bio/Horizon Therapeutics. AJG reports grants from the Conrad N Hilton Foundation and the Tom Sherak MS Hope Foundation; other financial relationships for activities as expert witness, associate editor, advisory board or steering committee participation, and endpoint adjudication with Bionure, Inception Sciences, JAMA Neurology, MedImmune/Viela Bio, Mylan, Synthon, and Trims Pharma; and personal fees from Pipeline Therapeutics. OA reports grants from the German Ministry of Education and Research (known as BMBF) and the German Research Foundation (known as DFG); grants and personal fees from Bayer HealthCare, Biogen, Genzyme, Novartis, Teva, and Viela Bio/Horizon Therapeutics; and personal fees from Alexion, Almirall, Horizon Therapeutics, Merck Serono, Roche, and Zambon. H-PH has received fees for consulting, speaking, and serving on steering committees from Bayer HealthCare, Biogen, Celgene Receptos, CSL Behring, GeNeuro, Genzyme, MedDay, MedImmune, Merck Serono, Novartis, Roche, Sanofi, TG Therapeutics, and Viela Bio with approval by the Rector of Heinrich Heine University Düsseldorf. DS, WR, MS, and DC hold stock or are employees of Viela Bio/Horizon Therapeutics, or both. EK was an employee of Viela Bio/Horizon Therapeutics during the preparation of this manuscript. JLB reports payment for study design or consultation from MedImmune/Viela Bio; personal fees from AbbVie, Alexion, Antigenomycs, BeiGene, Chugai, Clene Nanomedicine, EMD Serono, Genentech, Genzyme, Horizon Therapeutics, Mitsubishi Tanabe Pharma, Novartis, Reistone Biopharma, Roche, and TG Therapeutics; grants and personal fees from Novartis; grants from Alexion, the Guthy–Jackson Charitable Foundation, Mallinckrodt, and the National Institutes of Health; and has a patent for aquaporumab issued (US10654916B2: Compositions and methods for the treatment of neuromyelitis optica)., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: People with progressive multiple sclerosis (PMS) present motor (eg, walking) and cognitive impairments, and report fatigue. Fatigue encompasses fatigability which is objectively measured by the capacity to sustain a motor or cognitive task., Objective: To investigate the prevalence of walking and cognitive fatigability (CF) and the associated clinical characteristics in a large sample of PMS patients., Methods: PMS patients (25-65 years old) were included from 11 sites (Europe and North America), having cognitive impairment (1.28 standard deviation below normative data for the symbol digit modality test [SDMT]). Walking fatigability (WF) was assessed using the distance walk index (DWI) and CF using the SDMT (scores from the last 30 seconds compared to the first 30 seconds). Additional measures were: cognitive assessment-Brief International Cognitive Assessment for multiple sclerosis (MS), cardiorespiratory fitness, 6-minute walk, physical activity, depressive symptoms, perceived fatigue-Modified Fatigue Impact Scale (MFIS), MS impact-MSIS-29, and walking ability., Results: Of 298 participants, 153 (51%) presented WF (DWI = -28.9 ± 22.1%) and 196 (66%) presented CF (-29.7 ± 15%). Clinical characteristics (EDSS, disease duration, and use of assistive device) were worse in patients with versus without WF. They also presented worse scores on MSIS-29 physical, MFIS total and physical and reduced physical capacity. CF patients scored better in the MSIS-29 physical and MFIS psychosocial, compared to non-CF group. Magnitude of CF and WF were not related., Conclusions: Half of the cognitively-impaired PMS population presented WF which was associated with higher disability, physical functions, and fatigue. There was a high prevalence of CF but without strong associations with clinical, cognitive, and physical functions., Trial Registration Number: The "CogEx-study," www.clinicaltrial.gov identifier number: NCT03679468., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Most states prohibit sales of alcohol to customers who are apparently intoxicated, and many require training in responsible beverage service (RBS), with the aim of reducing driving while intoxicated (DWI) and other harms. Sales to apparently intoxicated patrons were assessed in onsite alcohol sales establishments and compared across three states., Method: A sample of 180 licensed onsite alcohol establishments was selected in California ( n = 60), New Mexico ( n = 60), and Washington State ( n = 60). States had different RBS training histories, content, and procedures. Research confederates, trained to feign cues of intoxication, visited each establishment twice. The pseudo-intoxicated patron (PP) ordered an alcoholic beverage while displaying intoxication cues. Sale of alcohol was the primary outcome., Results: At 179 establishments assessed, PPs were served alcohol during 56.5% of 356 visits (35.6% of establishments served and 22.6% did not serve at both visits). Alcohol sales were less frequent in New Mexico (47.9% of visits; odds ratio [OR] = 0.374, p = .008) and Washington State (49.6%; OR = 0.387, p = .012) than in California (72.0%). Servers less consistently refused service at both visits (6.8%) in California than New Mexico (33.9%) or Washington (27.1%), χ 2 (4, n = 177) = 16.72, p = .002. Alcohol sales were higher when intoxication cues were less obvious ( p < .001)., Conclusions: Overservice of alcohol to apparently intoxicated customers was frequent and likely elevated risk of DWI and other harms. The lower sales in New Mexico and Washington than California may show that a policy approach prohibiting sales to intoxicated customers combined with well-established RBS training can reduce overservice. Further efforts are needed to reduce overservice., Competing Interests: Dr. Buller, Dr. Woodall, Ms. Martinez, Ms. Small, and Mr. Chirico receive a salary from Klein Buendel, Inc. Dr. Buller's spouse is an owner of Klein Buendel Inc. Dr. Buller and Dr. Woodall are owners of Wedge Communications LLC, the distributor of the WayToServe online responsible beverage service training. An active management plan is in place at Klein Buendel to manage this conflict of interest. Dr. Cutter is employed by the University of Alabama at Birmingham and reports personal fees from Pythagoras Board membership; advisory board fees from Alexion, Antisense Therapeutics, Avotres, Biogen, Clene Nanomedicine, Clinical Trial Solutions LLC, Entelexo Biotherapeutics, Inc., Genzyme, Genentech, GW Pharmaceuticals, Hoya Corporation, Immunic, Immunosis Pty Ltd, Klein-Buendel Incorporated, Linical, Merck/Serono, Novartis, Perception Neurosciences, Protalix Biotherapeutics, Regeneron, Roche, SAB Biotherapeutics; and data and safety monitoring board fees from Applied Therapeutics, AI therapeutics, AMO Pharma, Astra-Zeneca, Avexis Pharmaceuticals, Bristol Meyers Squibb/Celgene, CSL Behring, Horizon Pharmaceuticals, Immunic, Karuna Therapeutics, Kezar Life Sciences, Mapi Pharmaceuticals Ltd, Merck, Mitsubishi Tanabe Pharma Holdings, Opko Biologics, Prothena Biosciences, Novartis, Regeneron, Sanofi-Aventis, Reata Pharmaceuticals, Teva Pharmaceuticals, NHLBI (Protocol Review Committee), University of Texas Southwestern, University of Pennsylvania, Visioneering Technologies Inc. outside the submitted work. Dr. Saltz has no conflicts.

Background: We reported that a social cognitive theory-based (SCT), Internet-delivered behavioral intervention increased device-measured minutes/day of moderate-to-vigorous physical activity (MVPA) over a 6-month period among persons with multiple sclerosis (MS). This paper examined the pattern and predictors of heterogeneity in change for MVPA. Based on previous research, we hypothesized that mild MS disability, fewer MS symptoms, lower baseline MVPA, and positive SCT characteristics (e.g., high exercise self-efficacy) would be associated with greater change in MVPA., Method: Persons with MS (N = 318) were randomized into behavioral intervention (n = 159) or attention/social contact control (n = 159) conditions that were administered via Internet websites and supported with behavioral coaching. Demographic, clinical, symptom, behavioral, and SCT data were from before the 6-month period of delivering the conditions, and MVPA data were from before and after the 6-month period. We examined heterogeneity based on waterfall plots, box plots, and the Levene statistic. We identified predictors of MVPA change using bivariate correlation and multiple, linear regression analyses per condition., Results: The Levene statistic indicated statistically significant heterogeneity of variances for MVPA change between conditions (p = .003), and the waterfall plots and box plots indicated greater heterogeneity in MVPA change for the behavioral intervention. MVPA change score was correlated with baseline MVPA (r =  - .33 and r =  - .34, p = .0004 and p = .0001) in both conditions and walking impairment (r =  - .188, p = .047) and race (r = .233, p = .014) in the behavioral intervention condition. The regression analysis indicated that baseline MVPA (Standardized B =  - .449, p = .000002), self-reported walking impairment (Standardized B =  - .310, p = .0008), and race (Standardized B = .215, p = .012) explained 25.6% of variance in MVPA change for the behavioral intervention condition., Conclusion: We provide evidence for walking impairment, baseline MVPA, and race as predictors of the heterogeneity in the pattern of MVPA change with a behavioral intervention., (© 2024. International Society of Behavioral Medicine.)

Background: Clinical practice, expert opinion, and evidence-based guidelines recommend daily stretching as first-line treatment for multiple sclerosis (MS) spasticity, but this has not been evaluated by fully powered clinical trials., Objective: To determine whether MS Spasticity: Take Control (STC), a guideline-based program of spasticity education and stretching exercises has different effects on the impact of spasticity than a control program of different spasticity education and range of motion (ROM) exercises., Methods: Ambulatory people with self-reported MS spasticity were randomly assigned to STC or ROM, delivered in same duration, facilitator-led, group classes, face-to-face (F2F) initially and later virtually, due to coronavirus disease 2019 (COVID-19). Multiple Sclerosis Spasticity Scale (MSSS) scores were compared between groups at 1 (primary outcome) and 6 months after interventions., Results: A total of 231 people enrolled. There was no significant difference in MSSS scores between STC and ROM at 1 month (mean difference = 0.28, 95% (confidence interval (CI)) = [-9.45 to 10.01], p = 0.955). There were significant group mean improvements in MSSS scores and most other outcomes at 1 and 6 months., Conclusion: Education with stretching exercises, the first-line recommended treatment for MS spasticity, and education with ROM exercises may both improve MS spasticity to a similar degree. This study debunks the belief that stretching is essential to managing MS spasticity., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.