Free From Falls education and exercise program for reducing falls in people with multiple sclerosis: A randomized controlled trial.

BACKGROUND: People with multiple sclerosis (PwMS) fall frequently. Community-delivered exercise and education reduce falls in older adults, but their efficacy in multiple sclerosis (MS) is unknown. OBJECTIVES: To evaluate the impact of the Free From Falls (FFF) group education and exercise program on falls in PwMS. METHODS: This was a prospective, assessor-blinded, two-arm parallel randomized controlled trial. Ninety-six participants were randomized to FFF (eight weekly 2 hour sessions) or the control condition (a fall prevention brochure and informing their neurologist of their fall history). Participants counted falls prospectively from enrollment through 6 months following intervention. Effects on fall frequency were evaluated by the Bayesian analysis. RESULTS: The modeled mean fall frequency pre-intervention was 1.2 falls/month in the FFF group (95% credible intervals (CIs) = 0.8-2.0) and 1.4 falls/month in the control group (95% CI = 0.9-2.1). Fall frequency decreased by 0.6 falls/month in both groups over time (nadir 4-6 months post-intervention: FFF 0.6 falls/month (95% CI = 0.4-0.9); control 0.8 falls/month (95% CI = 0.5-1.1)). CONCLUSION: In-person group exercise and education are not superior to written education and neurologist-initiated interventions for preventing falls in PwMS.

ADSTEP: Preliminary Investigation of a Multicomponent Walking Aid Program in People With Multiple Sclerosis.

OBJECTIVE: To evaluate the effect of the Assistive Device Selection, Training and Education Program (ADSTEP) on falls and walking and sitting activity in people with multiple sclerosis (PwMS). DESIGN: Randomized controlled trial. SETTING: Veterans affairs medical center. PARTICIPANTS: PwMS (N=40) using a walking aid at baseline who had fallen in the previous year. INTERVENTIONS: Participants were randomly assigned to ADSTEP or control. ADSTEP had 6 weekly, 40-minute, 1-on-1 sessions with a physical therapist, starting with walking aid selection and fitting, followed by task-oriented progressive gait training. Control was usual medical care with the option of ADSTEP after the study. MAIN OUTCOME MEASURES: The following were assessed at baseline, intervention completion, and 3 months later: falls, timed Up and Go, timed 25-foot walk, 2-minute walk, Four Square Step Test, International Physical Activity Questionnaire, Quebec User Evaluation of Satisfaction with Assistive Technologies, Multiple Sclerosis Walking Scale-12, Activities-Specific Balance Confidence Scale, and Multiple Sclerosis Impact Scale-29. Effect on these outcomes was estimated by a 2-by-2 repeated measures general linear model. RESULTS: Fewer ADSTEP than control participants fell (χ2=3.96, P<.05. number needed to treat =3.3). Time spent sitting changed significantly differently with ADSTEP than with control from baseline to intervention completion (F=11.16, P=.002. ADSTEP: reduced 87.00±194.89min/d; control: increased 103.50±142.21min/d; d=0.88) and to 3-month follow-up (F=9.25, P=.004. ADSTEP: reduced 75.79±171.57min/d; control: increased 84.50±149.23min/d; d=0.79). ADSTEP yielded a moderate effect on time spent walking compared to control at 3-month follow-up (P>.05. ADSTEP 117.53±148.40min/d; control 46.43±58.55min/d; d=0.63). CONCLUSIONS: ADSTEP prevents falls, reduces sitting, and may increase walking in PwMS.

Feasibility and acceptability for LION, a fully remote, randomized clinical trial within the VA for light therapy to improve sleep in Veterans with and without TBI: An MTBI2 sponsored protocol: LION: A remote RCT protocol within VA.

Sleep-wake disturbances frequently present in Veterans with mild traumatic brain injury (mTBI). These TBI-related sleep impairments confer significant burden and commonly exacerbate other functional impairments. Therapies to improve sleep following mTBI are limited and studies in Veterans are even more scarce. In our previous pilot work, morning bright light therapy (MBLT) was found to be a feasible behavioral sleep intervention in Veterans with a history of mTBI; however, this was single-arm, open-label, and non-randomized, and therefore was not intended to establish efficacy. The present study, LION (light vs ion therapy) extends this preliminary work as a fully powered, sham-controlled, participant-masked randomized controlled trial (NCT03968874), implemented as fully remote within the VA (target n=120 complete). Randomization at 2:1 allocation ratio to: 1) active: MBLT (n=80), and 2) sham: deactivated negative ion generator (n=40); each with identical engagement parameters (60-min duration; within 2-hrs of waking; daily over 28-day duration). Participant masking via deception balanced expectancy assumptions across arms. Outcome measures were assessed following a 14-day baseline (pre-intervention), following 28-days of device engagement (post-intervention), and 28-days after the post-intervention assessment (follow-up). Primary outcomes were sleep measures, including continuous wrist-based actigraphy, self-report, and daily sleep dairy entries. Secondary/exploratory outcomes included cognition, mood, quality of life, circadian rhythm via dim light melatonin onset, and biofluid-based biomarkers. Participant drop out occurred in <10% of those enrolled, incomplete/missing data was present in <15% of key outcome variables, and overall fidelity adherence to the intervention was >85%, collectively establishing feasibility and acceptability for MBLT in Veterans with mTBI.

Drug-Induced Sleep Endoscopy Differences by Age in Surgically Naive Children With Sleep-Disordered Breathing.

Importance: Drug-induced sleep endoscopy (DISE) is increasingly used to guide treatment decisions in children with sleep-disordered breathing (SDB). Previous reports of DISE findings in children have typically included a broad age range, but it is unclear how these patterns of obstruction vary with age. Objective: To compare patterns of airway obstruction observed during DISE in 3 age groups of surgically naive children with SDB. Design, Setting, and Participants: This cross-sectional analysis of a prospective cohort of surgically naive nonsyndromic children with SDB or obstructive sleep apnea [OSA] at risk for residual disease after adenotonsillectomy (defined as having at least 1 of these criteria: severe OSA, older than 7 years, obesity, or Black race) who were recruited between May 1, 2015, and February 28, 2020, was conducted at a tertiary children's hospital. Data analysis was conducted from September 2021 to February 2022. Exposures: DISE. Main Outcomes and Measures: DISE findings were rated at 6 anatomic sites using the Sleep Endoscopy Rating Scale (SERS). The association between age and severity of obstruction at each anatomic site and overall were compared using correlation (Kendall τ) and ordinal logistic regression analysis. Results: Data from 288 children (144 girls [50%]; 20 American Indian/Alaska Native [7%], 4 Asian [1%], 19 Black [7%], 93 Hispanic [33%], 2 Middle Eastern [1%], 6 Native Hawaiian/Pacific Islander [2%], and 203 White [70%] individuals; median [IQR] age, 9.2 [7.0-11.7] years) were stratified by participant age into preschool (age 2-5 years; 27 [9%]), younger school-aged (age 5-10 years; 146 [51%]), and older school-aged (age 10-18 years; 115 [40%]). Among these subgroups, the prevalence of multilevel obstruction was 59%, 51%, and 30%, respectively. Increasing age was inversely correlated with obstruction of the nasal airway (τb, -0.19; 95% CI, -0.29 to -0.09), nasopharynx (τb, -0.20; 95% CI, -0.31 to -0.10), velopharynx (τb, -0.16; 95% CI, -0.26 to -0.06), and overall obstruction (SERS total score: τb, -0.24; 95% CI, -0.33 to -0.14). An adjusted analysis demonstrated an inverse association between age and nasopharyngeal obstruction (odds ratio [OR], 0.84; 95% CI, 0.76 to 0.92), SERS total score (OR, 0.83; 95% CI, 0.76 to 0.90), and the number of sites of complete obstruction (OR, 0.87; 95% CI, 0.87 to 0.95). Conclusions and Relevance: This cross-sectional analysis of data from a prospective cohort study of surgically naive children with SDB found that preschool-aged children had more frequent multilevel obstruction, more severe overall obstruction, and nasopharyngeal obstruction compared with older children. Understanding the most common sites of obstruction and expected changes with age could inform personalized treatment for children with SDB.

Self-assessed Dynamic Gait Index correlates with physical therapist assessed Dynamic Gait Index in people with multiple sclerosis.

BACKGROUND: The Dynamic Gait Index (DGI) is a clinical measure of walking ability comprised of eight walking tasks. In people with multiple sclerosis (PwMS) the DGI has demonstrated validity, reliability, and ability to identify fallers. A self-assessed version of the DGI that demonstrates concurrent validity with the original DGI in people with MS would be valuable for remote assessment of walking ability. We therefore developed a questionnaire-based self-assessed version of the DGI (sDGI) that asks participants to self-rate their predicted ability to perform the eight DGI walking tasks. The purpose of this study was to determine the validity and internal consistency of the sDGI in people with MS who had self-reported gait impairment. METHODS: We enrolled 53 ambulatory people with MS with self-reported gait impairment. Participants completed the sDGI, the Multiple Sclerosis Walking Scale-12 (MSWS-12), the Telephone Interview for Cognitive Status (TICS), and self-reported their number of falls in the past 3 months. Then, up to 4 weeks later, they completed the DGI by in-person evaluation by a physical therapist (PT). We calculated the internal consistency of the sDGI and concordance between the sDGI and DGI. To determine if cognition impacted concordance, we calculated concordance in the cognitively impaired and non-impaired groups and also tested the difference between groups. We also calculated correlation between the sDGI and the DGI and the MSWS-12. The ability of the sDGI and the DGI to identify fallers was evaluated using receiver operating characteristic curves. RESULTS: 51 participants completed the study. They had a mean age of 60.9 (SD 11.5) years, median PDDS of 4.0 (interquartile range 3, 5), 32 % used walking aids, 25 % were cognitively impaired, and 62 % were female. The sDGI was internally consistent (Cronbach's alpha 0.85, 95 % CI 0.76, 0.90) but was not concordant (CCC = 0.45, 95 % CI: 0.28-0.60) with the DGI. Concordance between the sDGI and DGI was not different for cognitively intact versus cognitively impaired individuals. The sDGI was moderately correlated with the DGI (R = 0.64, p < 0.01) and strongly correlated with the MSWS-12 (R = -0.71, p < 0.01). Neither the sDGI nor the DGI identified fallers in this sample. CONCLUSION: The moderate to strong correlation among the sDGI, DGI and MSWS-12 supports the validity of the sDGI as a measure of walking ability in people with MS. However, because there is poor concordance between the sDGI and the DGI performed in clinic by a PT in both cognitively intact and cognitively impaired participants, the sDGI should not be used as a substitute for the DGI. The sDGI could be used as a screening tool because most participants underestimated their walking performance compared to assessment by a PT so the sDGI would be unlikely to miss poor walking ability. As neither the sDGI nor the DGI identified fallers in this sample, our results do not support using these tools to identify fallers in people with MS and self-reported gait impairment.

Risky movement: Assessing fall risk in people with multiple sclerosis with wearable sensors and beacon-based smart-home monitoring.

BACKGROUND: People with multiple sclerosis (PwMS) fall frequently causing injury, social isolation, and decreased quality of life. Identifying locations and behaviors associated with high fall risk could help direct fall prevention interventions. Here we describe a smart-home system for assessing how mobility metrics relate to real-world fall risk in PwMS. METHODS: We performed a secondary analysis of a dataset of real-world falls collected from PwMS to identify patterns associated with increased fall risk. Thirty-four individuals were tracked over eight weeks with an inertial sensor comprising a triaxial accelerometer and time-of-flight radio transmitter, which communicated with beacons positioned throughout the home. We evaluated associations between locations in the home and movement behaviors prior to a fall compared with time periods when no falls occurred using metrics including gait initiation, time-spent-moving, movement length, and an entropy-based metric that quantifies movement complexity using transitions between rooms in the home. We also explored how fall risk may be related to the percent of times that a participant paused while walking (pauses-while-walking). RESULTS: Seventeen of the participants monitored sustained a total of 105 falls that were recorded. More falls occurred while walking (52%) than when stationary despite participants being largely sedentary, only walking 1.5±3.3% (median ± IQR) of the time that they were in their home. A total of 28% of falls occurred within one second of gait initiation. As the percentage of pauses-while-walking increased from 20 to 60%, the likelihood of a fall increased by nearly 3 times from 0.06 to 0.16%. Movement complexity, which was quantified using the entropy of room transitions, was significantly higher in the 10 min preceding falls compared with other 10-min time segments not preceding falls (1.15 ± 0.47 vs. 0.96 ± 0.24, P = 0.02). Path length was significantly longer (151.3 ± 156.1 m vs. 95.0 ± 157.2 m, P = 0.003) in the ten minutes preceding a fall compared with non-fall periods. Fall risk also varied among rooms but not consistently across participants. CONCLUSIONS: Movement metrics derived from wearable sensors and smart-home tracking systems are associated with fall risk in PwMS. More pauses-while-walking, and more complex, longer movement trajectories are associated with increased fall risk. FUNDING: Department of Veterans Affairs (RX001831-01A1). National Science Foundation (#2030859).

Protocol for an exploratory, randomised, single-blind clinical trial of aerobic exercise to promote remyelination in multiple sclerosis.

INTRODUCTION: There is an urgent need for remyelinating therapies that restore function in people with multiple sclerosis (pwMS). Aerobic exercise is a promising remyelinating strategy because it promotes remyelination in animal models both independently and synergistically with medications. Here, in this study, we present an innovative, randomised, single-blind, clinical trial designed to explore: the relationship between demyelination and mobility (part 1), and if 24 weeks of aerobic exercise promotes remyelination in pwMS (part 2). METHODS AND ANALYSIS: Sedentary participants (n=60; aged 18-64 years) with stable MS will undergo a baseline visit with the following outcomes to assess associations between demyelination and mobility (part 1): spinal cord demyelination (somatosensory-evoked potentials, SSEPs), mobility (6-Minute Timed Walk, Timed 25-Foot Walk, Timed Up and Go, 9-Hole Peg Test) and patient-reported outcomes (PROs). After baseline testing, participants with significantly prolonged SSEP latency will advance to the clinical exercise trial (part 2) and will be randomised 1:1 to active or control conditions for 24 weeks. The active condition will be aerobic stationary cycling three times per week with graded virtual supervision. The control condition will be monthly virtual MS symptom education groups (six sessions). SSEP latency (remyelination endpoint), mobility outcomes and PROs will be measured at 12 and 24 weeks in all clinical trial participants. A subset of 11 active and 11 control participants will undergo a brain MRI with quantitative T1 myelin water fraction at baseline and 24 weeks (exploratory remyelination endpoint). ETHICS AND DISSEMINATION: Ethical approval was obtained from the Oregon Health & Science University Institutional Review Board (#21045). Dissemination of findings will include peer-reviewed publications, conference presentations and media releases. The proposed study will inform the feasibility, study design and sample size for a fully powered clinical trial of aerobic exercise to promote remyelination in pwMS. TRIAL REGISTRATION NUMBER: NCT04539002.

The association between preconception cannabis use and depression and anxiety during pregnancy.

OBJECTIVE: Cannabis use among individuals of reproductive age has increased with cannabis legalization and heightened stress during the COVID-19 pandemic. Our study provides data on preconception cannabis use and cannabis use disorder (CUD) during the pandemic and models the association between preconception cannabis use and depression and anxiety during pregnancy. METHODS: Data on substance use and depression and anxiety symptoms were collected from questionnaires and the Structured Clinical Interview for DSM-5 (SCID-5) from pregnant individuals in Oregon in 2019-2022. Linear regression was used to model the association between the frequency of preconception cannabis use and scores on the Center for Epidemiological Studies of Depression-Revised (CESD-R) and Beck Anxiety Inventory (BAI). RESULTS: The prevalence of preconception cannabis use was 27.8% among 227 study participants. CUD was diagnosed in 19% of cannabis users, or 5.3% of the overall sample. Daily cannabis use, compared to rare/never use, was associated with increases in CESD-R (ß = 6.22, p 0.029) and BAI (ß = 4.71, p 0.045) scores. CONCLUSIONS: Cannabis use and CUD are common among individuals of reproductive age. Given the association between preconception cannabis use and depression and anxiety during pregnancy, more attention is needed on screening and counseling of cannabis use among people of reproductive age.

Processing speed and memory test performance are associated with different brain region volumes in Veterans and others with progressive multiple sclerosis.

Background: Cognitive dysfunction and brain atrophy are both common in progressive multiple sclerosis (MS) but are seldom examined comprehensively in clinical trials. Antioxidant treatment may affect the neurodegeneration characteristic of progressive MS and slow its symptomatic and radiographic correlates. Objectives: This study aims to evaluate cross-sectional associations between cognitive battery components of the Brief International Cognitive Assessment for Multiple Sclerosis with whole and segmented brain volumes and to determine if associations differ between secondary progressive (SPMS) and primary progressive (PPMS) MS subtypes. Design: The study was based on a baseline analysis from a multi-site randomized controlled trial of the antioxidant lipoic acid in veterans and other people with progressive MS (NCT03161028). Methods: Cognitive batteries were conducted by trained research personnel. MRIs were processed at a central processing site for maximum harmonization. Semi-partial Pearson's adjustments evaluated associations between cognitive tests and MRI volumes. Regression analyses evaluated differences in association patterns between SPMS and PPMS cohorts. Results: Of the 114 participants, 70% had SPMS. Veterans with MS made up 26% (n = 30) of the total sample and 73% had SPMS. Participants had a mean age of 59.2 and sd 8.5 years, and 54% of them were women, had a disease duration of 22.4 (sd 11.3) years, and had a median Expanded Disability Status Scale of 6.0 (with an interquartile range of 4.0-6.0, moderate disability). The Symbol Digit Modalities Test (processing speed) correlated with whole brain volume (R = 0.29, p = 0.01) and total white matter volume (R = 0.33, p < 0.01). Both the California Verbal Learning Test (verbal memory) and Brief Visuospatial Memory Test-Revised (visual memory) correlated with mean cortical thickness (R = 0.27, p = 0.02 and R = 0.35, p < 0.01, respectively). Correlation patterns were similar in subgroup analyses. Conclusion: Brain volumes showed differing patterns of correlation across cognitive tasks in progressive MS. Similar results between SPMS and PPMS cohorts suggest combining progressive MS subtypes in studies involving cognition and brain atrophy in these populations. Longitudinal assessment will determine the therapeutic effects of lipoic acid on cognitive tasks, brain atrophy, and their associations.

Immediate impact of yogic breathing on pulsatile cerebrospinal fluid dynamics.

Cerebrospinal fluid (CSF), a clear fluid bathing the central nervous system (CNS), undergoes pulsatile movements. Together with interstitial fluid, CSF plays a critical role for the removal of waste products from the brain, and maintenance of the CNS health. As such, understanding the mechanisms driving CSF movement is of high scientific and clinical impact. Since pulsatile CSF dynamics is sensitive and synchronous to respiratory movements, we are interested in identifying potential integrative therapies such as yogic breathing to regulate CSF dynamics, which has not been reported before. Here, we investigated the pre-intervention baseline data from our ongoing randomized controlled trial, and examined the impact of four yogic breathing patterns: (i) slow, (ii) deep abdominal, (iii) deep diaphragmatic, and (iv) deep chest breathing with the last three together forming a yogic breathing called three-part breath. We utilized our previously established non-invasive real-time phase contrast magnetic resonance imaging approach using a 3T MRI instrument, computed and tested differences in single voxel CSF velocities (instantaneous, respiratory, cardiac 1st and 2nd harmonics) at the level of foramen magnum during spontaneous versus yogic breathing. In examinations of 18 healthy participants (eight females, ten males; mean age 34.9 ± 14 (SD) years; age range: 18-61 years), we observed immediate increase in cranially-directed velocities of instantaneous-CSF 16-28% and respiratory-CSF 60-118% during four breathing patterns compared to spontaneous breathing, with the greatest changes during deep abdominal breathing (28%, p = 0.0008, and 118%, p = 0.0001, respectively). Cardiac pulsation was the primary source of pulsatile CSF motion except during deep abdominal breathing, when there was a comparable contribution of respiratory and cardiac 1st harmonic power [0.59 ± 0.78], suggesting respiration can be the primary regulator of CSF depending on the individual differences in breathing techniques. Further work is needed to investigate the impact of sustained training yogic breathing on pulsatile CSF dynamics for CNS health.

Evaluating the Impact of the COVID-19 Pandemic on Postpartum Depression.

Objective: Studies examining the impact of natural disasters noted that in the setting of stable rates of depression, postpartum depression (PPD) increased in vulnerable subgroups. Coronavirus disease 2019 (COVID-19) may similarly impact maternal health. This study aimed to characterize the effect of COVID-19 on the incidence of PPD and to identify vulnerable subgroups. Methods: Retrospective chart review of maternal-newborn dyads was conducted over two epochs: pre-COVID-19 (January 1-June 1, 2019) and during-COVID-19 (January 1-June 1, 2020). PPD was defined as an Edinburgh Postnatal Depression Scale score of ≧ 10 at any postnatal appointment. Prevalence of depression and anxiety was recorded. Data were analyzed using chi-square, Mann-Whitney, and t-tests. Results: Among 1061 dyads (557 in the 2019 epoch, 504 in the 2020 epoch), the epochs had similar clinical and demographic characteristics. Incidence proportion of PPD was similar (16.9% to 18.1%, p = 0.67). In subgroup analyses, this outcome was also similar among primiparous mothers (17.4% to 22.2%, p = 0.22) and publicly insured mothers (23.9% to 25.9%, p = 0.78). The 2020 epoch exhibited higher prevalence of current depression (9.9% to 14.3%, p = 0.03) and anxiety (10.1% to 18.7%, p < 0.001). However, incidence proportion of PPD decreased among women with current mental health diagnoses (41.5% to 31.3%, p = 0.19). Conclusions: A stable PPD incidence despite increased prevalence of current mood disorders highlights the complexity of the biopsychosocial milieu contributing to PPD. Further study of psychiatric care access and treatment is an important next step in understanding relationships between current mood disorders and PPD during the pandemic.

Relationship between balance confidence and social engagement in people with multiple sclerosis.

OBJECTIVE: To evaluate the relationships among patient-reported balance confidence and social satisfaction and social participation in people with multiple sclerosis (pwMS). METHODS: 75 ambulatory pwMS who had sustained at least two falls or near falls in the prior two months self-reported their balance confidence (Activities-specific Balance Confidence (ABC) questionnaire) and social satisfaction and participation (Patient Reported Outcomes Measurement Information System (PROMIS) measures). Correlations between the ABC and PROMIS measures were examined using Spearman's rank correlation. RESULTS: In a cross-sectional analysis, ABC scores and PROMIS scores for social satisfaction and social participation were statistically significantly correlated (ρ 0.37-0.54, p ≤ 0.001). The correlation between balance confidence and social satisfaction was consistently stronger at each time point than between balance confidence and social participation. CONCLUSION: Self-reported balance confidence is associated with both social satisfaction and social participation in pwMS who fall. The causal direction of this relationship remains uncertain.

Cannabis for medical purposes: A cross-sectional analysis of health care professionals' knowledge.

BACKGROUND: Legalization of cannabis use and the evidence base supporting both risks and benefits of cannabinoids are expanding, but our understanding of health care professionals' (HCPs) knowledge about cannabis for medical purposes is limited. Understanding of the knowledge base and knowledge gaps about medical cannabis use is critical to advanced practice registered nurses (APRNs) because they are increasingly called on to manage patients taking multiple drugs, including prescribed and unprescribed cannabis and prescription cannabinoids. PURPOSE: The purpose of this study was to examine HCPs' knowledge of clinical cannabis, including laws and regulations; risks and harms; pharmacology; and effects on pain, multiple sclerosis spasticity, and seizures as assessed with written tests before an in-person, continuing medical education program. METHODS: Total scores and differences among professions and topics were compared. RESULTS: A total of 178 of the 226 program attendees completed the test (79%) (107 [47%] physicians, 30 [13%] APRNs, and 18 [8%] registered nurses). The mean test score was 63.2% (SD = 12.7%) without significant differences among professions (F(3, 174) = 1.53; p = .21) but with significant differences among topics (χ2(7, 1068) = 201.13; p < .001). The score was lowest for effects on seizures (43.8%) and with scores below 70% for all other areas except laws and regulations (85.7%). IMPLICATIONS FOR PRACTICE: There are substantial gaps in HCPs' knowledge about the clinical effects of cannabis, especially about risks and harms, pharmacology, and the effects on pain, multiple sclerosis spasticity, and seizures. Further education may help HCPs to understand the risks and benefits of cannabis and cannabinoids across conditions.

Comparing fall detection methods in people with multiple sclerosis: A prospective observational cohort study.

Background Falls occur across the population but are more common, and have more negative sequelae, in people with multiple sclerosis (MS). Given the prevalence and impact of falls, accurate measures of fall frequency are needed. This study compares the sensitivity and false discovery rates of three methods of fall detection: the current gold standard, prospective paper fall calendars, real-time self-reporting and automated detection, the latter two from a novel body-worn device. Methods Falls in twenty-five people with MS were recorded for eight weeks with prospective fall calendars, real-time body-worn self-report, and an automated body-worn detector concurrently. Eligible individuals were adults with MS enrolled in a randomized controlled trial of a fall prevention intervention. Entry criteria were at least two falls or near-falls in the previous two months, Expanded Disability Status Scale ≤ 6.0, community dwelling, and no MS relapse in the previous month. The sensitivity (proportion of true falls detected) and false discovery rates (proportion of false reports generated) of the fall detection methods were compared. A true fall was a fall reported by at least two methods. A false report was a fall reported by only one method. The trial is registered on ClinicalTrials.gov (NCT02583386) and is closed. Results In the 1,276 person-days of fall counting with all three methods in use simultaneously there were 1344 unique fall events. Of these, 8.5% (114) were true falls and 91.5% (1230) were false reports. Fall calendars had the lowest sensitivity (0.614) and the lowest false discovery rate (0.067). The automated detector had the highest sensitivity (0.921) and the highest false discovery rate (0.919). All methods generated under one false report per day. There were no fall detection-related adverse events. Conclusion Fall calendars likely underestimate fall frequency by around 40%. The automated detector evaluated here misses very few falls but likely overestimates the number of falls by around one fall per day. Additional research is needed to produce an ideal fall detection and counting method for use in clinical and research applications. Funding United States Department of Veterans Affairs, Rehabilitations Research and Development Service.

A cross-sectional survey of cannabis use by people with MS in Oregon and Southwest Washington.

BACKGROUND: Evidence supports that cannabinoids reduce self-reported spasticity and neuropathic pain in people with MS (PwMS), and legal access to cannabis for medical and recreational use continues to rise. However, there are limited data regarding patterns of cannabis use and perceived benefits of cannabis among PwMS in the US. This study describes the prevalence of cannabis use, routes of administration, perceived benefit of cannabis for MS, and characteristics associated with cannabis use and perception of benefit among a population of PwMS living in two states where cannabis is legal for both medical and recreational use. METHODS: A survey about treatments used by PwMS, focusing on complementary and alternative medicine (CAM), was sent to PwMS living in Oregon and Southwest Washington. This survey included questions about current and past cannabis use, route of cannabis administration, and perceived benefits, as well as personal demographics. RESULTS: Of the 1188 returned surveys, 1000 had at least 75% complete survey responses and also completed the questions about current and past cannabis use. Thirty percent (n=303) of respondents reported currently using cannabis, 21% (n=210) used in the past but not currently, and 49% (n=487) had never used cannabis. Among current users, rates of use by smoking, vaping, topicals, tinctures and oils, or edibles were similar (35-46%), and most (59%) reported using multiple routes of administration. Most (64-78%, varying by route) current and past users reported cannabis being very or somewhat beneficial for their MS. The odds of current cannabis use were higher in PwMS who: 1) were younger (OR 2.24 [95% CI 1.39-3.61] for those age 18-40 compared with age >60]; 2) had lower household income (OR 3.94 [95% CI 2.55-6.09] with annual income <$25k compared with those with >$100k); 3) had secondary progressive MS (OR 1.77 [95% CI 1.07-2.92]); and 4) had more than minimal MS disability (OR 2.05 [95% CI 1.03-4.10] for those using a walker compared to those with none/minimal disability). The odds of perceiving cannabis as beneficial for MS were higher in: 1) younger individuals (OR 5.61 [95% CI 2.62-11.98] for those age 18-40 compared with age >60); 2) those with lower household income (OR 3.35 [95% CI 1.65-6.80] with annual income <$25k compared with those with >$100k), 3) those not currently using disease modifying therapies (OR 2.32 [95% CI 1.30-4.13]), and 4) those with the greatest disability (OR 17.96; [95% CI 2.00-161.22]). CONCLUSION: In this survey, 30% of PwMS reported currently using cannabis for their MS, mostly by multiple routes of administration, and most of these people report this being helpful for their MS. People who were younger, had lower household income, had progressive disease, and had more than minimal disability were more likely to use cannabis and report it was beneficial for their MS. People who were not using disease modifying therapies were also more likely to report benefit from cannabis use.

Automated Detection of Real-World Falls: Modeled From People With Multiple Sclerosis.

Falls are a major health problem with one in three people over the age of 65 falling each year, oftentimes causing hip fractures, disability, reduced mobility, hospitalization and death. A major limitation in fall detection algorithm development is an absence of real-world falls data. Fall detection algorithms are typically trained on simulated fall data that contain a well-balanced number of examples of falls and activities of daily living. However, real-world falls occur infrequently, making them difficult to capture and causing severe data imbalance. People with multiple sclerosis (MS) fall frequently, and their risk of falling increases with disease progression. Because of their high fall incidence, people with MS provide an ideal model for studying falls. This paper describes the development of a context-aware fall detection system based on inertial sensors and time of flight sensors that is robust to imbalance, which is trained and evaluated on real-world falls in people with MS. The algorithm uses an auto-encoder that detects fall candidates using reconstruction error of accelerometer signals followed by a hyper-ensemble of balanced random forests trained using both acceleration and movement features. On a clinical dataset obtained from 25 people with MS monitored over eight weeks during free-living conditions, 54 falls were observed and our system achieved a sensitivity of 92.14%, and false-positive rate of 0.65 false alarms per day.

Cannabis use in people with multiple sclerosis and spasticity: A cross-sectional analysis.

BACKGROUND: Growing evidence supports that cannabinoids relieve MS-related spasticity but little is known about cannabis use among people with MS (PwMS) and spasticity. OBJECTIVE: To characterize cannabis use among PwMS and spasticity. METHODS: As part of baseline data collection for a spasticity intervention trial in Oregon, PwMS and self-reported spasticity answered questions about cannabis use. RESULTS: 54% reported ever using cannabis and 36% currently use. 79% use multiple routes of administration, 58% use at least daily. 79% find cannabis helpful for spasticity and 26% use cannabis and prescribed oral antispasticity medications. CONCLUSIONS: Many PwMS and spasticity use cannabis and report it helps their spasticity.

Cannabis use for symptom relief in multiple sclerosis: A cross-sectional survey of webinar attendees in the US and Canada.

BACKGROUND: With the expansion of medical and recreational legalization of cannabis, there is growing interest in cannabis use by people with multiple sclerosis (MS). Research supports that cannabis relieves MS-related pain and spasticity, two common symptoms of MS. However, there is limited information available about cannabis use in people with MS across the United States and Canada. METHODS: 1,015 people with MS in the US and Canada participated in an informational webinar on cannabis for the control of MS symptoms. Attendees were presented with three questions about their use of cannabis for MS symptoms and their knowledge of the medical legality of cannabis in their state. Demographics and MS characteristics were obtained from webinar registration. The legality of cannabis (not legal, legal for medical use only, and legal for recreational and medical use) and the number of years since medical legalization at the time of this webinar were determined for all states. Using logistic regression, we analyzed associations between individual characteristics (demographics, disease severity and legal status), cannabis use, and knowledge of legality. RESULTS: Of the 1,015 webinar registrants, 54% (n = 548) answered the question, "Have you used marijuana in the past year to help control your MS symptoms?" and were included in the analyses. Statistically significant associations were seen between cannabis use and local legal status of cannabis (recreational vs. not legal: OR 4.55, 95% CI: [1.70-12.14], p = 0.002), years since medical legalization of cannabis (for each year since legalization: OR 1.06, 95% CI: [1.02 - 1.10], p = 0.004), disease severity (severe vs. mild disability: OR 3.41, 95% CI: [1.23 - 9.46] p = 0.018) and gender (male vs. female: OR 2.33, 95% CI: [1.10-4.94], p = 0.027). Accuracy of knowledge of local cannabis legality was significantly associated with cannabis use in the past year (users vs. non-users: OR 2.52, p = 0.014), local legal status of cannabis (medical only vs. not legal: OR 0.30, p = 0.001; recreational vs. not legal: OR 4.98, p = 0.039), years since legalization of cannabis (for each increased year since legalization: OR 1.15, p < 0.001), and country of residence (Canada vs. USA: OR 0.42, p = 0.021). CONCLUSIONS: This study supports that cannabis use for MS symptoms is more common in states where cannabis laws are more permissive and where cannabis has been legal for longer, in those with more severe MS, and in men. Accurate knowledge of local cannabis legality is more common in those who report using cannabis for their MS in the past year. Those living in states where cannabis is legal for medical use only are less likely to be aware of legal status than those in either recreationally-legal or non-legal states, but awareness of legal status increases with time since medical legalization. Canadians are less likely than Americans to be accurate in their perception of the legal status of cannabis.

Enlarged perivascular spaces are not associated with vascular co-morbidities, clinical outcomes, and brain volumes in people with secondary progressive multiple sclerosis.

In secondary progressive multiple sclerosis (SPMS) significance of enlarged perivascular spaces (ePVS) is unknown. Objectives, Methods: Analysis of associations between vascular co-morbidities, clinical outcomes, and volumetrics with categorical ePVS scores in midbrain, basal ganglia (BG), and centrum semiovale (CSO) in SPMS(n-46). Results, Conclusion: In BG, advancing age (Z = 2.68) and lower Expanded Disability Status Scale (Z = -2.04) were associated with increasing ePVS score. In CSO, advancing age (Z = 2.66) and male gender (Z = 2.45) were associated with increasing ePVS score. No associations between ePVS score and vascular co-morbidities or volumetrics existed; ePVS may not be an informative marker for SPMS.

Phase I randomized trial of liothyronine for remyelination in multiple sclerosis: A dose-ranging study with assessment of reliability of visual outcomes.

BACKGROUND: Thyroid hormone promotes remyelination in multiple sclerosis (MS) animal models through a variety of mechanisms. Liothyronine (L-T3) is a short-acting thyroid hormone with demonstrated safety and tolerability for short-term and chronic use in euthyroid adults with other health conditions, but has not been studied in people with MS. The objectives of this single-center, phase I, placebo-controlled, clinical trial were to determine the safety, tolerability, and optimal dosing of L-T3 in people with MS in preparation for a phase 2 remyelination clinical trial. Secondary goals included exploration of the reliability of functional and clinical measurements of myelination in the anterior visual pathway over one week. METHODS: Groups of six clinically stable people with MS were randomized in a 4:2 ratio to receive L-T3 or placebo. The first group received 50 mcg total daily dose (TDD) of L-T3, with escalating doses of L-T3 in subsequent groups, up to potentially 150 mcg TDD in the final group. Prior to enrollment for the next dose-escalated group, all safety measures for the prior dose were reviewed. The maximum tolerated dose (MTD) was considered to be the dose below which two or more participants experienced dose limiting symptoms or one participant experienced a serious adverse event. After the MTD was reached, no further patients were enrolled. Visual evoked potentials (VEP) P100 latency with two different check sizes (17' and 34') and Sloan low contrast letter acuity (LCLA) were measured pre- and post-treatment. To determine whether there was a treatment effect, the placebo and L-T3 groups were compared using a clustered bootstrap regression estimation. A linear mixed effects model was used to determine test-retest reliability of VEP and LCLA in all eyes. RESULTS: Between May 2016 and November 2016, 15 people with MS were randomized to L-T3 (n = 10) or placebo (n = 5). Subjects were adherent to the study drug and the MTD was 75 mcg TDD. No serious adverse events were observed and the most common adverse events were poor sleep and loose stools. No treatment effect of L-T3 was observed over one week. Therefore, data from patients on L-T3 and placebo were pooled to explore VEP and LCLA reliability. The intraclass correlations of VEP 17', VEP 34' and LCLA were 0.836, 0.860, and 0.932, respectively. The mean differences in values between visits 1 and 2 for VEP 17' and 34' and LCLA were 1.9 ms/eye (SD 6.5), 0.4 ms/eye (6.3), and 0.8/eye (3.6), respectively. CONCLUSIONS: This study confirms the short-term safety and tolerability of L-T3 in people with MS, with 75 mcg TDD as the MTD. Our results also support that, despite small variations over one week, VEP with various check sizes and Sloan LCLA are reliable functional and clinical outcome measures that could be used in remyelination clinical trials in MS. A future phase 2 clinical trial to investigate the efficacy of L-T3 as a remyelination therapy may be warranted. This trial was registered on clinicaltrials.gov (NCT02760056).