A randomized controlled trial of oral antipyretic treatment to reduce overheating during exercise in adults with multiple sclerosis.

BACKGROUND: Some people with multiple sclerosis (pwMS) avoid exercise due to overheating. Evidence from a variety of cooling treatments shows benefits for pwMS. OBJECTIVE: Conduct a randomized controlled trial of antipyretic treatment before exercise in pwMS. METHODS: Adults over age 18 diagnosed with relapsing-remitting MS reporting heat sensitivity during exercise were randomly assigned to one of six sequences counterbalancing aspirin, acetaminophen, placebo. At each of three study visits separated by ≥ one week, participants received 650-millograms of aspirin, acetaminophen, or placebo before completing a maximal exercise test. Primary outcomes were body temperature change and total time-to-exhaustion (TTE), secondary outcomes were physiological and patient-reported outcomes (PROs). RESULTS: Sixty participants were enrolled and assigned to treatment sequence; 37 completed ≥ one study visit. After controlling for order effects, we found that body temperature increase was reduced after aspirin (+ 0.006 ± 0.32 degrees Fahrenheit, p < 0.001) and after acetaminophen (+ 0.31 ± 0.35; p = 0.004) compared to placebo (+ 0.68 ± 0.35). TTE after aspirin (331.6 ± 76.6 s) and acetaminophen (578.2 ± 82.1) did not differ significantly from placebo (551.0 ± 78.4; p's > 0.05). Aspirin benefited all secondary outcomes compared to placebo (all p's < 0.001); acetaminophen showed broadly consistent benefits. CONCLUSION: These results support antipyretic treatment as effective for reducing overheating during exercise in pwMS and failed to support antipyretics for increasing TTE in the context of a maximal exercise test. Benefits were shown for physiological markers of exercise productivity and PROs of fatigue, pain, and perceived exertion.

The impact of socioeconomic status on subsequent neurological outcomes in multiple sclerosis.

BACKGROUND: To examine whether lower neighborhood-level and individual-level indicators of socioeconomic status (SES) are associated with subsequently worse neurological disability in people with MS (pwMS). METHODS: In a multi-center study using prospectively collected data from discovery cohorts (University of Pittsburgh, N=1316) and replication cohorts (Columbia University, N=488), we calculated a neighborhood SES indicator, area deprivation index (ADI), based on participants' residence at enrollment, and we derived an individual SES indicator based on participants' household income. Patient-reported neurological outcomes included the Multiple Sclerosis Rating Scale-Revised (MSRS-R), Patient-Determined Disease Steps (PDDS), and Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function scores from 2018 to 2020. We performed covariate-adjusted regression analyses in each cohort and then random-effects meta-analyses. RESULTS: Higher ADI (lower SES) in 2015 was associated with subsequently worse neurological outcomes during 2018-2020 (discovery: MSRS-R, ß=0.62, 95%CI [0.36,0.89], p<0.001; PDDS, ß=0.11, 95%CI [0.02,0.20], p=0.02 | replication: MSRS-R, ß=0.46, 95%CI [0.21,0.72], p<0.001; PDDS, ß=0.12, 95%CI [0.03,0.21], p=0.009, PROMIS, ß=-0.60, 95%CI [-1.12,-0.08], p=0.025). Lower neighborhood percent with college education (MSRS-R, ß=-7.31, 95%CI [-8.99,-5.64], p<0.001; PDDS, ß=-1.62, 95%CI [-2.20,-1.05], p<0.001; PROMIS, ß=9.31, 95%CI [5.73,12.89], p<0.001), neighborhood median household income (MSRS-R, ß=-3.80e-05, 95%CI [-5.05e-05,-2.56e-05], p<0.001; PDDS, ß=-8.58e-06, 95%CI [-1.28e-05,-4.32e-06], p<0.001; PROMIS, ß=2.55e-05, 95%CI [5.96e-07,5.05e-05], p=0.045), and neighborhood median home value (MSRS-R, ß=-6.50e-06, 95%CI [-8.16e-06,-4.84e-06], p<0.001; PDDS, ß=-1.54e-06, 95%CI [-2.11e-06,-9.65e-07], p<0.001; PROMIS, ß=4.98e-06, 95%CI [1.81e-06,8.14e-06], p=0.002) drove the association between higher ADI and subsequently worse neurological disability (in joint analyses). Neighborhood percent of population with Medicaid, but not private insurance, significantly mediated the observed covariate-adjusted associations. Higher individual-level household income bracket was associated with better neurological outcomes in joint analyses (MSRS-R: R=-0.39, p<0.001; PDDS: R=-0.35, p<0.001; PROMIS: R=0.37, p<0.001), independent of ADI. CONCLUSIONS: Lower neighborhood SES is associated with subsequently worse neurological outcomes in pwMS. Future testing of targeted intervention through public policies that improve SES are warranted.

Feasibility trial of a telehealth support group intervention to reduce anxiety in multiple sclerosis.

OBJECTIVE: Anxiety is common among persons with MS (PwMS), but widely accepted treatments are lacking. Group-based interventions delivered via telehealth are an accessible treatment option requiring clinical trial evidence to support feasibility and initial efficacy. We conducted a pilot feasibility trial of an online support group intervention to reduce anxiety in PwMS. METHODS: A non-randomized, parallel arm clinical trial was conducted. A total of 31 PwMS were enrolled: 20 completed a 12-week telehealth-delivered support group intervention and 11 were assigned to a survey-only control group. Primary feasibility outcomes were adherence and completion rates. Primary efficacy outcome was anxiety, secondary outcomes were depression, loneliness, distress, self-efficacy, stress, and quality of life. RESULTS: Twenty-six participants completed the study. Intervention group adherence (75%) and completion (85%) rates were acceptable. Results indicated a medium size between-group effect, suggesting a greater reduction in anxiety in the intervention group compared to the control group [U = 39.50, p = 0.045, r = 0.39]. No group differences in other outcomes were observed. CONCLUSION: A telehealth-delivered support group intervention appears feasible for further study and shows initial efficacy for the reduction of anxiety in PwMS.

RCT of a Telehealth Group-Based Intervention to Increase Physical Activity in Multiple Sclerosis: eFIT.

OBJECTIVE: To conduct a pilot randomized controlled trial to determine whether participation in a group-based structured telehealth intervention increases physical activity in people with multiple sclerosis (MS). METHODS: In this parallel-arms trial, all study procedures were administered remotely. Adults diagnosed with MS (any subtype) were randomized to one of two 12-week (1 h/wk) active conditions: eFIT, online moderated structured groups; or eJournal, online independent journaling. For comparison, a treatment-as-usual (TAU; i.e., no eFIT/eJournal) group was enrolled. The primary outcome was feasibility (completion and adherence). The secondary efficacy outcomes included self-reported physical activity level (International Physical Activity Questionnaire, IPAQ). RESULTS: Participants were 37 adults with MS. The sample was diverse: 66.7% female; age range 23-64 years; 17.5% Hispanic, 12.5% Black; and progressive and relapsing-remitting disease subtypes. Regarding feasibility, 70.7% completed; average adherence was 74.9%. Physical activity in active groups increased by 34.2% (baseline IPAQ = 2,406.8 ± 1,959.7, follow-up = 3,229.4 ± 2,575.2) and decreased in the TAU group by 17.4% (baseline = 2,519.9 ± 1,500.1, follow-up = 2,081.2 ± 1,814.9); group × time interaction was not statistically significant [F(2,25) = 1.467, p = 0.250; partial η2 = 0.105]. CONCLUSIONS: Telehealth represents an accessible, acceptable vehicle to deliver targeted behavioral treatments to a neurologic population. eFIT may be an effective intervention for increasing physical activity, a historically intractable treatment target, in individuals with MS. In addition, these results provide evidence for feasibility of conducting fully remote clinical trial research. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for people with MS, participation in a group-based structured telehealth intervention compared with TAU resulted in a (non-significant) increase in self-reported physical activity level. The percentage of participants who completed follow-up questionnaires did not differ between groups. The trial was registered at ClinicalTrials.gov (NCT03829267).

Manifestations and impact of the COVID-19 pandemic in neuroinflammatory diseases.

OBJECTIVE: To report initial results of a planned multicenter year-long prospective study examining the risk and impact of COVID-19 among persons with neuroinflammatory disorders (NID), particularly multiple sclerosis (MS). METHODS: In April 2020, we deployed online questionnaires to individuals in their home environment to assess the prevalence and potential risk factors of suspected COVID-19 in persons with NID (PwNID) and change in their neurological care. RESULTS: Our cohort included 1115 participants (630 NID, 98% MS; 485 reference) as of 30 April 2020. 202 (18%) participants, residing in areas with high COVID-19 case prevalence, met the April 2020 CDC symptom criteria for suspected COVID-19, but only 4% of all participants received testing given testing shortages. Among all participants, those with suspected COVID-19 were younger, more racially diverse, and reported more depression and liver disease. PwNID had the same rate of suspected COVID-19 as the reference group. Early changes in disease management included telemedicine visits in 21% and treatment changes in 9% of PwNID. After adjusting for potential confounders, increasing neurological disability was associated with a greater likelihood of suspected COVID-19 (ORadj  = 1.45, 1.17-1.84). INTERPRETATIONS: Our study of real-time, patient-reported experience during the COVID-19 pandemic complements physician-reported MS case registries which capture an excess of severe cases. Overall, PwNID seem to have a risk of suspected COVID-19 similar to the reference population.

ASPIRE trial: study protocol for a double-blind randomised controlled trial of aspirin for overheating during exercise in multiple sclerosis.

INTRODUCTION: The many benefits of exercise for persons with multiple sclerosis (MS) are well established, yet patients often refrain from exercise due to overheating and exhaustion. The present randomised controlled trial tests aspirin (acetylsalicylic acid (ASA)) as a convenient method to prevent overheating and improve exercise performance in persons with MS. The effects of ASA are compared with those of acetaminophen (APAP) and placebo. METHODS AND ANALYSIS: Participants are seen for a laboratory maximal exercise test on 3 separate days separated by at least 1 week. At each session, body temperature is measured before oral administration of a standard adult dose (650 mg) of ASA, APAP or placebo. One hour after drug administration, participants perform a maximal ramp test on a cycle ergometer. Primary outcomes are (a) time to exhaustion (that is, time spent cycling to peak exertion) and (b) body temperature change. Crossover analyses will include tests for effects of treatment, period, treatment-period interaction (carryover effect) and sequence. ETHICS AND DISSEMINATION: Ethical approval was granted by the institutional review board at Columbia University Irving Medical Center (reference: AAAS2529). Results of the trial will be published in peer-reviewed scientific journals and presented at national and international conferences. Neurologists, physiatrists, primary care physicians and physiotherapists are important stakeholders and will be targeted during dissemination. Positive trial results have the potential to promote aspirin therapy, an inexpensive and readily available treatment, to reduce overheating and allow more persons with MS to benefit from exercise. TRIAL REGISTRATION NUMBER: NCT03824938.

"Knocking on Doors that Don't Open": experiences of caregivers of children living with disabilities in Iquitos and Lima, Peru.

Background: More than one billion people worldwide live with a disability. Despite advances in recognising inequalities experienced by people with disabilities, barriers to services and stigmatisation still exist. The aims of this study were to explore: (1) perceptions and experiences of services specifically available to people with disabilities and their caregivers and (2) the perception of disability. Methods: In-depth interviews were conducted with 20 caregivers of persons with a disability and 14 key informants in two cities in Peru; Lima and Iquitos. The social-ecological model was used as a framework to analyse and present data, stratifying the key barriers and opportunities at each level. Results: At the individual level, interviewees reported a lack of support at the time of diagnosis, poor coping strategies, and communicated their desire for, and willingness to participate in support groups if they were established. On the community level, education and awareness were reportedly lacking and acts of discrimination and stigmatisation were common. Participants described opportunities for community-level campaigns to increase exposure and awareness of disability rights and inclusion. A dissatisfaction with government programmes was reported, as services were not available to everyone, in part due to geographical and socio-economic barriers. Conclusions: The main findings were the lack of emotional, informational, and tangible support available to caregivers of people with disabilities, often exacerbated by lower socio-economic status; a lack of transparency of care pathways available to people with disabilities; and a lack of visibility of people with disability in both Lima and Iquitos. Implications for Rehabilitation Support groups could offer additional support to caregivers of people with disabilities in Lima, mitigating existing gaps in services for people with disabilities, and their families. Education campaigns implemented on a community level could start to curb discrimination and stigmatisation of people with disabilities in Lima and Iquitos. A national census with inclusive language and methodology specifically designed to capture the percentage of the population currently living with a disability would give a real indication of what services are needed in Peru. The provision of clear, publically available routes of attention would assist caregivers and families to access services for people with disabilities.

"Zika is everywhere": A qualitative exploration of knowledge, attitudes and practices towards Zika virus among women of reproductive age in Iquitos, Peru.

Zika virus was reported in the rainforest city of Iquitos, Peru in 2016. The potential associations between Zika and fetal neurological disorders were reported extensively in the media regarding neighboring Brazil, and led to great concern about the impact Zika could have on people's health in Iquitos when it arrived. The aim of this study was to explore the knowledge, attitudes, and preventative practices related to Zika virus and its transmission among women of childbearing age in Iquitos, Peru. Six focus group discussions with 46 women of ages 20-35 from an Iquitos district with confirmed Zika cases were conducted to explore: 1) knowledge of Zika transmission, its symptoms, and treatment, 2) attitudes regarding Zika, including perceptions of risk for and severity of Zika, and 3) preventative practices, including awareness of health promotion activities. Participants were knowledgeable about Zika symptoms and knew it was transmitted by mosquitoes, and about half had heard about the association between Zika and microcephaly, but most lacked knowledge about the associated neurological disorders in adults, its sexual transmission, and ways to prevent infection. They expressed concern for pregnant women exposed to the virus and the impact on the fetus. Participants felt at risk of contracting the Zika virus, yet had not changed preventive practices, possibly in part because their perception of the severity of this disease was low. This study reveals knowledge gaps that could be addressed via health promotion messages that might improve prevention practices to help community members protect themselves from Zika virus during this outbreak.