Mindfulness-Based App to Reduce Stress in Caregivers of Persons With Alzheimer Disease and Related Dementias: Protocol for a Single-Blind Feasibility Proof-of-Concept Randomized Controlled Trial.

BACKGROUND: Informal caregivers (ie, individuals who provide assistance to a known person with health or functional needs, often unpaid) experience high levels of stress. Caregiver stress is associated with negative outcomes for both caregivers and care recipients. Mindfulness-based interventions (MBIs) show promise for improving stress, emotional distress, and sleep disturbance in caregivers of persons with Alzheimer disease and related dementias (ADRD). Commercially available mobile mindfulness apps can deliver MBIs to caregivers of persons with ADRD in a feasible and cost-effective manner. OBJECTIVE: We are conducting a single-blind feasibility proof-of-concept randomized controlled trial (RCT; National Institutes of Health [NIH] stage 1B) comparing 2 free mobile apps: the active intervention Healthy Minds Program (HMP) with within-app text tailored for addressing stress among caregivers of persons with ADRD, versus Wellness App (WA), a time- and dose-matched educational control also tailored for caregivers of persons with ADRD. METHODS: We aim to recruit 80 geographically diverse and stressed caregivers of persons with ADRD. Interested caregivers use a link or QR code on a recruitment flyer to complete a web-based eligibility screener. Research assistants conduct enrollment phone calls, during which participants provide informed consent digitally. After participants complete baseline surveys, we randomize them to the mindfulness-based intervention (HMP) or educational control podcast app (WA) and instruct them to listen to prescribed content for 10 minutes per day (70 minutes per week) for 12 weeks. Caregivers are blinded to intervention versus control. The study team checks adherence weekly and contacts participants to promote adherence as needed. Participants complete web-based self-report measures at baseline, posttest, and follow-up; weekly process measures are also completed. Primary outcomes are a priori set feasibility benchmarks. Secondary outcomes are stress, emotional distress, sleep disturbance, caregiver burden, mindfulness, awareness, connection, insight, and purpose. We will calculate 1-sided 95% CI to assess feasibility benchmarks. Effect sizes of change in outcomes will be used to examine the proof of concept. RESULTS: Recruitment started on February 20, 2023. We have enrolled 27 caregivers (HMP: n=14; WA: n=13) as of June 2023. Funding began in August 2022, and we plan to finish enrollment by December 2023. Data analysis is expected to begin in May 2024 when all follow-ups are complete; publication of findings will follow. CONCLUSIONS: Through this trial, we aim to establish feasibility benchmarks for HMP and WA, as well as establish a proof of concept that HMP improves stress (primary quantitative outcome), emotional distress, sleep, and mindfulness more than WA. Results will inform a future efficacy trial (NIH stage II). HMP has the potential to be a cost-effective solution to reduce stress in caregivers of persons with ADRD, benefiting caregiver health and quality of care as well as patient care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05732038; https://clinicaltrials.gov/study/NCT05732038. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50108.

Addressing the Chronic Pain-Early Cognitive Decline Comorbidity Among Older Adults: Protocol for the Active Brains Remote Efficacy Trial.

BACKGROUND: Chronic pain and early cognitive decline, which are costly to treat and highly prevalent among older adults, commonly co-occur, exacerbate one another over time, and can accelerate the development and progression of Alzheimer disease and related dementias. We developed the first mind-body activity program (Active Brains [AB]) tailored to the needs of older adults with chronic pain and early cognitive decline. Results from our previous study strongly supported the feasibility of conducting AB remotely and provided evidence for improvements in outcomes. OBJECTIVE: We are conducting a single-blinded, National Institutes of Health stage-2, randomized clinical trial to establish the efficacy of AB versus a time-matched and dose-matched education control (Health Enhancement Program [HEP]) in improving self-reported and objective outcomes of physical, cognitive, and emotional functions in 260 participants. The methodology described in this paper was informed by the lessons learned from the first year of the trial. METHODS: Participants are identified and recruited through multidisciplinary clinician-referred individuals (eg, pain psychologists and geriatricians), the Rally Research platform, social media, and community partnerships. Interested participants complete eligibility screening and electronic informed consent. Baseline assessments include self-report, performance-based measures (eg, 6-min walk test) and objective measures (eg, Repeatable Battery for the Assessment of Neuropsychological Status). Participants are mailed a wrist-worn ActiGraph device (ActiGraph LLC) to passively monitor objective function (eg, steps) during the week between the baseline assessment and the beginning of the programs, which they continue to wear throughout the programs. After baseline assessments, participants are randomized to either AB or HEP and complete 8 weekly, remote, group sessions with a Massachusetts General Hospital psychologist. The AB group receives a Fitbit (Fitbit Inc) to help reinforce increased activity. Assessments are repeated after the intervention and at the 6-month follow-up. Coprimary outcomes include multimodal physical function (self-report, performance based, and objective). Secondary outcomes are cognitive function (self-report and objective), emotional function, and pain. RESULTS: We began recruitment in July 2022 and recruited 37 participants across 4 cohorts. Of them, all (n=37, 100%) have completed the baseline assessment, 26 (70%) have completed the posttest assessment, and 9 (24%) are actively enrolled in the intervention (total dropout: n=2, 5%). In the three cohorts (26/37, 70%) that have completed the AB or HEP, 26 (100%) participants completed all 8 group sessions (including minimal makeups), and watch adherence (1937/2072, 93.48%, average across ActiGraph and Fitbit devices) has been excellent. The fourth cohort is ongoing (9/37, 24%), and we plan to complete enrollment by March 2026. CONCLUSIONS: We aim to establish the efficacy of the AB program over a time-matched and dose-matched control in a live video-based trial and test the mechanisms through theoretically driven mediators and moderators. Findings will inform the development of a future multisite effectiveness-implementation trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05373745; https://classic.clinicaltrials.gov/ct2/show/NCT05373745. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47319.

Effect of Mind-Body Skills Training on Quality of Life for Geographically Diverse Adults With Neurofibromatosis: A Fully Remote Randomized Clinical Trial.

Importance: Neurofibromatoses (NF; NF1, NF2, and schwannomatosis) are hereditary tumor predisposition syndromes with a risk for poor quality of life (QOL) and no evidence-based treatments. Objective: To compare a mind-body skills training program, the Relaxation Response Resiliency Program for NF (3RP-NF), with a health education program (Health Enhancement Program for NF; HEP-NF) for improvement of quality of life among adults with NF. Design, Setting, and Participants: This single-blind, remote randomized clinical trial randomly assigned 228 English-speaking adults with NF from around the world on a 1:1 basis, stratified by NF type, between October 1, 2017, and January 31, 2021, with the last follow-up February 28, 2022. Interventions: Eight 90-minute group virtual sessions of 3RP-NF or HEP-NF. Main Outcomes and Measures: Outcomes were collected at baseline, after treatment, and at 6-month and 1-year follow-up. The primary outcomes were physical health and psychological domain scores of the World Health Organization Quality of Life Brief Version (WHOQOL-BREF). Secondary outcomes were the social relationships and environment domain scores of the WHOQOL-BREF. Scores are reported as transformed domain scores (range, 0-100, with higher scores indicating higher QOL). Analysis was performed on an intention-to-treat basis. Results: Of 371 participants who underwent screening, 228 were randomized (mean [SD] age, 42.7 [14.5] years; 170 women [75%]), and 217 attended 6 or more of 8 sessions and provided posttest data. Participants in both programs improved from baseline to after treatment in primary outcomes of physical health QOL score (3RP-NF, 5.1; 95% CI, 3.2-7.0; P < .001; HEP-NF, 6.4; 95% CI, 4.6-8.3; P < .001) and psychological QOL score (3RP-NF, 8.5; 95% CI, 6.4-10.7; P < .001; HEP-NF, 9.2; 95% CI, 7.1-11.2; P < .001). Participants in the 3RP-NF group showed sustained improvements after treatment to 12 months; posttreatment improvements for the HEP-NF group diminished (between-group difference for physical health QOL score, 4.9; 95% CI, 2.1-7.7; P = .001; effect size [ES] = 0.3; and psychological QOL score, 3.7; 95% CI, 0.2-7.6; P = .06; ES = 0.2). Results were similar for secondary outcomes of social relationships and environmental QOL. There were significant between-group differences from baseline to 12 months in favor of the 3RP-NF for physical health QOL score (3.6; 95% CI, 0.5-6.6; P = .02; ES = 0.2), social relationships QOL score (6.9; 95% CI, 1.2-12.7; P = .02; ES = 0.3), and environmental QOL score (3.5; 95% CI, 0.4-6.5; P = .02; ES = 0.2). Conclusions and Relevance: In this randomized clinical trial of 3RP-NF vs HEP-NF, benefits from 3RP-NF and HEP-NF were comparable after treatment, but at 12 months from baseline, 3RP-NF was superior to HEP-NF on all primary and secondary outcomes. Results support the implementation of 3RP-NF in routine care. Trial Registration: ClinicalTrials.gov Identifier: NCT03406208.

Virtual Tai Chi program for patients with irritable bowel syndrome with constipation: Proof-of-concept feasibility trial.

BACKGROUND: Satisfaction with current treatment options for irritable bowel syndrome with constipation (IBS-C) is low, with many patients turning to complementary treatments. Tai Chi is a mind-body medicine practice with proven efficacy in other functional disorders. As a proof-of-concept, we tested the feasibility and preliminary clinical outcomes associated with a Tai Chi program designed for IBS-C. METHODS: A total of 27 IBS-C patients participated in a single-arm trial of 8 sessions of Tai Chi delivered weekly over 7 weeks via live videoconferencing in group format. Clinical improvement was assessed via change in IBS Symptom Severity Score (IBS-SSS) from baseline to 4 weeks posttreatment (week 11) with secondary outcomes exploring symptom ratings, IBS-related quality of life (IBS-QOL), GI-specific anxiety, abdominal distention, and psychological factors. KEY RESULTS: Despite substantial dropout (n = 7; 26%), the treatment protocol had moderate to excellent feasibility for other criteria. Treatment satisfaction was excellent. Exit interviews confirmed high satisfaction with the program among completers, but a high burden of data collection was noted. One participant experienced an adverse event (mild, exacerbation of sciatica). There was a significant improvement in intra-individual IBS-SSS between baseline and posttreatment (average change -66.5, 95% CI -118.6 to -14.3, p = 0.01). Secondary outcomes were notable for improvements in other IBS symptom scoring measures, IBS-QOL, measured abdominal diameter, and leg strength. CONCLUSIONS AND INFERENCES: Our data provide preliminary evidence of the feasibility of a Tai Chi intervention for IBS-C, show promise for improving outcomes, and identify more streamlined data collection as an area for further program improvement.

The Impact of Tai Chi Exercise on Health Care Utilization and Imputed Cost in Residents of Low-Income Senior Housing.

BACKGROUND/OBJECTIVES: This study was designed to test the impact of Tai Chi (TC) on healthcare utilization and cost in older adults living in low-income senior housing. We hypothesized that TC would improve overall health enough to reduce the use of emergency department (ED) and inpatient services. DESIGN: Cluster randomized controlled trial with randomization at the housing site level. SETTING: Greater Boston, Massachusetts. PARTICIPANTS: The study includes 6 sites with 75 individuals in the TC treatment condition and 6 sites with 67 individuals in the health education control condition. INTERVENTION: Members of the treatment group received up to a year-long intervention with twice weekly, in-person TC exercise sessions along with video-directed exercises that could be done independently at home. The comparison group received monthly, in-person healthy aging education classes (HE). Study recruitment took place between August, 2015 and October, 2017. Key outcomes included acute care utilization (inpatient stays, observation stays and emergency department visits). In addition, the cost of utilization was estimated using the age, sex and race adjusted allowed amount from Medicare claims for a geographically similar population aged ≥ 65. RESULTS: The results suggested a possible reduction in the rate of ED visits in the TC group vs. controls (rate ratio = 0.476, p-value = 0.06), but no findings achieved statistical significance. Adjusted estimates of imputed costs of ED and hospital care were similar between TC and HE, averaging approximately $3,000 in each group. CONCLUSION: ED utilization tended to be lower over 6 to 12 months of TC exercises compared to HE in older adults living in low-income housing, although estimated costs of care were similar.

Multimodal chiropractic care for migraine: A pilot randomized controlled trial.

BACKGROUND: Spinal manipulation may reduce migraine frequency, but effects of multimodal chiropractic care on migraine frequency have not been evaluated. METHODS: We conducted a pilot randomized controlled trial comparing multimodal chiropractic care + enhanced usual care (MCC+) versus enhanced usual care alone (EUC) among adult women with episodic migraine. EUC was comprised of usual medical care and migraine education literature. MCC+ participants received 10 sessions of chiropractic care over 14 weeks. Primary aims evaluated feasibility of recruitment, retention, protocol adherence, and safety. Change in migraine days was a secondary aim. RESULTS: Of 422 patients screened, 61 were randomized over 20 months. Fifty-seven (93%) completed daily migraine logs during the intervention, 51 (84%) completed final follow-up, and 45 (74%) completed all assessments. Twenty-four of 29 MCC+ participants (83%) attended > 75% of the chiropractic sessions. Ninety-eight non-serious adverse events were reported by 26 participants (43%) with 39 events among 11 EUC participants and 59 events among 15 MCC+ participants. MCC+ participants experienced greater reductions in migraine days (-2.9 days for MCC+ vs. -1.0 days for EUC, difference = -1.9; 95% confidence interval: -3.5, -0.4). CONCLUSIONS: Pre-specified feasibility criteria were not met, but deficits were remediable. Preliminary data support a definitive trial of MCC+ for migraine. TRIAL REGISTRATION: This study is registered at Clinicaltrials.gov (NCT03177616).

Effects of a mind-body program on symptoms of depression and perceived stress among adults with neurofibromatosis type 2 who are deaf: A live-video randomized controlled trial.

INTRODUCTION: Neurofibromatosis type 2 (NF2) is a rare, progressive and incurable genetic disorder associated with progressive hearing loss and eventual deafness. As a group, patients with NF report high levels of stress and depressive symptoms. However, no studies have explored improvement in these symptoms after psychosocial interventions. We have previously shown that a mind-body program tailored to adults with NF2 who are deaf (the Relaxation Response and Resiliency Program for Deaf NF2, d3RP-NF2) improves quality of life and resiliency over and above a Health Enhancement program when both are delivered via live-video and assisted by Communication Access Realtime Translation (CART). Here we tested the effects of the programs on depression and perceived stress. METHODS: Forty-five patients with NF2 and significant hearing loss were randomized to the d3RP-NF2 or Health-Enhancement program and completed measures of depression (PHQ-9) and perceived stress (PSS-10) at baseline, post-intervention, and six-month follow-up. RESULTS: Patients randomized to the d3RP-NF2 program, but not to the control condition, experienced significant decreases on both measures from baseline to post-test, which were maintained at follow-up (within group tests). However, improvements following the d3RP-NF2 program was not significantly higher than those observed in the control group (between group tests). CONCLUSION: Results provide the first evidence of improvement in symptoms of depression and perceived stress among deaf patients living with NF2 who participate in a virtual mind-body program.

Feasibility and Efficacy of a Resiliency Intervention for the Prevention of Chronic Emotional Distress Among Survivor-Caregiver Dyads Admitted to the Neuroscience Intensive Care Unit: A Randomized Clinical Trial.

Importance: To our knowledge, there are no evidence-based interventions to prevent chronic emotional distress (ie, depression, anxiety, and posttraumatic stress [PTS]) in critical care survivors and their informal caregivers. Objective: To determine the feasibility and preliminary effect of the novel dyadic resiliency intervention Recovering Together (RT) on reducing symptoms of depression, anxiety, and PTS among hospitalized patients and their informal caregivers. Design, Setting, and Participants: This single-blind, pilot randomized clinical trial of RT vs an educational control was conducted among 58 dyads in which either the survivor or caregiver endorsed clinically significant symptoms of depression, anxiety, or PTS. The study was conducted in the neuroscience intensive care unit at Massachusetts General Hospital. Data were collected from September 2019 to March 2020. Interventions: Both RT and control programs had 6 sessions (2 at bedside and 4 via live video after discharge), and both survivor and caregiver participated together. Main Outcomes and Measures: The primary outcomes were feasibility of recruitment and intervention delivery, credibility, and satisfaction. The secondary outcomes included depression and anxiety (measured by the Hospital Depression and Anxiety Scale), PTS (measured by the PTSD Checklist-Civilian Version), and intervention targets (ie, mindfulness, measured by the Cognitive and Affective Mindfulness Scale-Revised; coping, measured by the Measure of Current Status-Part A; and dyadic interpersonal interactions, measured by the Dyadic Relationship Scale). Main outcomes and targets were assessed at baseline, 6 weeks, and 12 weeks. Results: The 58 dyads were randomized to RT (29 dyads [50.0%]; survivors: mean [SD] age, 49.3 [16.7] years; 9 [31.0%] women; caregivers: mean [SD] age, 52.4 [14.3] years; 22 [75.9%] women) or control (29 dyads [50.0%]; survivors: mean [SD] age, 50.3 [16.4] years; 12 [41.3%] women; caregivers, mean [SD] age, 52.1 [14.9], 17 [58.6%] women). Feasibility (recruitment [76%], randomization [100%], and data collection [83%-100%]), adherence (86%), fidelity (100%; κ = 0.98), satisfaction (RT: 57 of 58 [98%] with scores >6; control: 58 of 58 [100%] with scores >6), credibility (RT: 47 of 58 [81%] with scores >6; control: 46 of 58 [80%] with scores >6), and expectancy (RT: 49 of 58 [85%] with scores >13.5; 51 of 58 [87%] with scores >13.5) exceeded benchmarks set a priori. Participation in RT was associated with statistically and clinically significant improvement between baseline and postintervention in symptoms of depression (among survivors: -4.0 vs -0.6; difference, -3.4; 95% CI, -5.6 to -1.3; P = .002; among caregivers: -3.8 vs 0.6; difference, -4.5; 95% CI, -6.7 to -2.3; P < .001), anxiety (among survivors: -6.0 vs 0.3; difference, -6.3; 95% CI, -8.8 to -3.8; P < .001; among caregivers: -5.0 vs -0.9; difference, -4.1; 95% CI, -6.7 to -1.5, P = .002), and PTS (among survivors: -11.3 vs 1.0; difference, -12.3; 95% CI, -18.1 to -6.5, P < .001; among caregivers, -11.4 vs 5.0; difference, -16.4, 95% CI, -21.8 to -10.9; P < .001). Improvements sustained through the 12-week follow-up visit. We also observed RT-dependent improvement in dyadic interpersonal interactions for survivors (0.2 vs -0.2; difference, 0.4; 95% CI, 0.0 to 0.8; P = .04). Conclusions and Relevance: In this pilot randomized clinical trial, RT was feasible and potentially efficacious in preventing chronic emotional distress in dyads of survivors of the neuroscience intensive care unit and their informal caregivers. Trial Registration: ClinicalTrials.gov Identifier: NCT03694678.

Improvement in resiliency factors among adolescents with neurofibromatosis who participate in a virtual mind-body group program.

PURPOSE: To examine effects of a virtual mind-body group for adolescents with neurofibromatoses (NF1 and NF2; Resilient Youth with Neurofibromatosis; RY-NF) on multiple resiliency factors against a health education attention control (Health Education for Youth with Neurofibromatosis; HE-NF) using data from a randomized controlled trial. Specifically, our research question was whether adolescents randomized to the RY-NF (versus the HE-NF) would have greater improvements in resiliency factors at post-intervention and whether these gains would be maintained at 6-month follow-up. METHODS: Adolescents with NF (n = 51; M age 12-17) were randomly assigned to RY-NF (n = 27) or HE-NF (n = 24). Resiliency factors (mindfulness, coping, gratitude, optimism, and social support) were collected at baseline, post-intervention (88%), and 6-month follow-up (82%). RESULTS: Participation in the RY-NF was associated with greater pre-to-post improvements in gratitude (Mdifference = 4.38; 95% CI-0.52-8.23; p = .027) and mindfulness (Mdifference= 9.41; 95% CI 4.40-14.42.; p < .001) compared to HE-NF; improvements sustained at 6 months. There were no group differences on any additional resiliency factors. However, participation in the RY-NF was associated with pre-to-post- improvements in coping (Mdifference= 9.16; 95% CI 2.93-15.39; p = .005), and social support (Mdifference= 6.79; 95% CI 1.96-11.63; p = .007); improvements sustained at 6 months. CONCLUSIONS: Participation in the RY-NF resulted in sustained improvement in several resiliency factors. Promoting resiliency may help adolescents successfully navigate challenges associated with NF.

Randomized, Placebo-Controlled Trial of Ferrous Sulfate to Treat Insomnia in Children With Autism Spectrum Disorders.

BACKGROUND: Insomnia and low iron stores are common in children with autism spectrum disorders, and low iron stores have been associated with sleep disturbance. METHODS: We performed a randomized placebo-controlled trial of oral ferrous sulfate to treat insomnia in children with autism spectrum disorders and low normal ferritin levels. Twenty participants who met inclusion criteria and whose insomnia did not respond to sleep education were randomized to 3 mg/kg/day of ferrous sulfate (n = 9) or placebo (n = 11) for three months. RESULTS: Iron supplementation was well tolerated, and no serious adverse events were reported. Iron supplementation improved iron status (+18.4 ng/mL active versus -1.6 ng/mL placebo, P = 0.044) but did not significantly improve the primary outcome measures of sleep onset latency (-11.0 minutes versus placebo, 95% confidence interval -28.4 to 6.4 minutes, P = 0.22) and wake time after sleep onset (-7.7 minutes versus placebo, 95% confidence interval -22.1 to 6.6 min, P = 0.29) as measured by actigraphy. Iron supplementation was associated with improvement in the overall severity score from the Sleep Clinical Global Impression Scale (-1.5 points versus placebo, P = 0.047). Changes in measures of daytime behavior did not differ between groups. CONCLUSION: This trial demonstrated no improvement in primary outcome measures of insomnia in subjects treated with ferrous sulfate compared with placebo. Interpretation was limited by low enrollment.

Virtual mind-body treatment for geographically diverse youth with neurofibromatosis: A pilot randomized controlled trial.

OBJECTIVE: To examine the feasibility, acceptability, preliminary effect, and durability of a mind-body videoconferencing program for youth with neurofibromatosis (Resilient Youth with NF; RY-NF) against an experimental educational control (Health Education for NF; HE-NF) via a single-blind pilot RCT. METHOD: Adolescents with NF (N = 51; age 12-17) completed baseline assessments and were randomized (1:1/ to intervention or experimental educational control). The multiple primary outcomes were physical health and psychological quality of life (QoL). Secondary outcomes were social relations QoL, environmental QoL, depression, anxiety, pain intensity and pain interference. Posttreatment and at 6-month follow-up assessments were collected. RESULTS: Forty-five adolescents (88%) completed posttreatment, and 37 (82%) completed 6-month follow-up. Satisfaction was high in both conditions. The RY-NF showed greater baseline to posttreatment improvements in physical health QoL (10.18; 95% CI: 0.47-19.90; p = .040), psychological QoL (9.45; 95% CI: 0.78-18.11; p = .033), social relations QoL (13.19; 95% CI: 1.87-24.50; p = .023), and environmental QoL (9.26; 95% CI: 3.49-15.49; p = .002), compared to the HE-NF (between group effects). Improvements were clinically meaningful and maintained through follow-up. CONCLUSIONS: The RY-NF was well accepted, highly feasible and resulted in sustained improvement in QoL, demonstrating adolescents are receptive to and benefit from learning resiliency skills in groups via live video.

Cultivating resiliency in patients with neurofibromatosis 2 who are deafened or have severe hearing loss: a live­video randomized control trial.

INTRODUCTION: Patients with NF2 who are deaf or have significant hearing loss face numerous and unique challenges which lead to poor quality of life, and thus may benefit from resiliency programs. METHODS: We performed secondary data analyses on a single blind, randomized controlled trial of an 8 week mind-body resiliency program (the Relaxation Response and Resiliency program for Deaf NF2; d3RP-NF2) versus a health education control (Health Enhancement Program for Deaf NF2;dHEP-NF2) which showed improvement in quality of life (Funes in JAMA 2019, https://doi.org/10.1007/s11060-019-03182-3). Here we report on improvements in resiliency factors (i.e. optimism, gratitude, perceived social support, mindfulness, and perceived coping abilities) assessed at baseline, post-test and 6-month follow-up. Both programs were delivered via Skype using Communication Access Real-Time Translation. RESULTS: Patients who were randomized to the d3RP-NF2 program exhibited significant improvements from baseline to post-program in gratitude (Mdifference = 4.04, 95% CI 1.58-6.50; p = 0.002), perceived social support (Mdifference = 16.36, 95% CI 9.20-23.51; p < 0.001), mindfulness (Mdifference = 4.02, 95% CI 1.10-6.94; p = 0.008), perceived coping (Mdifference = 15.25, 95% CI 10.21-20.28; p < 0.001), and a non-significant trend of improvement in optimism (Mdifference = 1.15, 95% CI -0.14-12.44; p = 0.079). These improvements were all maintained through the 6-month follow up. Improvements in perceived coping (Mdifference = 12.34, 95% CI 4.75-19.93; p = 0.002), social support (Mdifference = 13.11, 95% CI 2.19-24.03; p = 0.02), and gratitude (Mdifference = 4.59, 95% CI 0.83-8.36; p = 0.018) were over and above the changes observed in those randomized to dHEP-NF2. CONCLUSION: The d3RP-NF2 sustainably improves multiple dimensions of resiliency. Promoting resiliency may be of utmost importance for this uderserved population.

A Cluster Randomized Trial of Tai Chi vs Health Education in Subsidized Housing: The MI-WiSH Study.

OBJECTIVES: Tai Chi (TC) may benefit older adults with a variety of diseases and disabilities. We tested the hypothesis that TC improves physical function in older adults living in low-income housing facilities. DESIGN: Cluster randomized controlled trial. SETTING: Subsidized housing facilities in Boston, Massachusetts, and neighboring communities. PARTICIPANTS: Volunteers were recruited from 15 facilities. The 180 randomized participants were 60 years of age or older, able to understand English and participate in TC, expected to remain in the facility for 1 year, and able to walk independently. INTERVENTION: TC classes were conducted in the housing facilities twice/week for 1 year and compared with monthly health promotion educational classes and social calls. MEASUREMENTS: The primary outcome was physical function measured by the Short Physical Performance Battery (SPPB). Secondary outcomes included other aspects of physical and cognitive function, and falls. RESULTS: An interim analysis revealed less improvement over 12 months in SPPB scores among TC participants (+.20 units; 95% confidence interval [CI] = -.20 to +.60; P = .69) vs control participants (+.51 units; 95% CI = +.15 to +.87; P = .007), a difference of -.31 units (95% CI = -.66 to .04; P = .082). This met the criterion for futility, and the Data Safety Monitoring Board recommended trial termination. No differences were found in 6- or 12-month changes favoring TC in any secondary outcomes or adverse events. CONCLUSION: In older adults with multiple chronic conditions living in subsidized housing facilities, 6 and 12 months of twice/week TC classes were not associated with improvements in functional health. J Am Geriatr Soc 67:1812-1819, 2019.

Dissociation between urate and blood pressure in mice and in people with early Parkinson's disease.

BACKGROUND: Epidemiological, laboratory and clinical studies have established an association between elevated urate and high blood pressure (BP). However, the inference of causality remains controversial. A naturally occurring antioxidant, urate may also be neuroprotective, and urate-elevating treatment with its precursor inosine is currently under clinical development as a potential disease-modifying strategy for Parkinson's disease (PD). METHODS: Our study takes advantage of a recently completed phase II trial evaluating oral inosine in de novo non-disabling early PD with no major cardiovascular and nephrological conditions, and of three lines of genetically engineered mice: urate oxidase (UOx) global knockout (gKO), conditional KO (cKO), and transgenic (Tg) mice with markedly elevated, mildly elevated, and substantially reduced serum urate, respectively, to systematically investigate effects of urate-modifying manipulation on BP. FINDINGS: Among clinical trial participants, change in serum urate but not changes in systolic, diastolic and orthostatic BP differed by treatment group. There was no positive correlation between urate elevations and changes in systolic, diastolic and orthostatic BP ((p = .05 (in inverse direction), 0.30 and 0.63, respectively)). Between UOx gKO, cKO, or Tg mice and their respective wildtype littermates there were no significant differences in systolic or diastolic BP or in their responses to BP-regulating interventions. INTERPRETATION: Our complementary preclinical and human studies of urate modulation in animal models and in generally healthy early PD do not support a hypertensive effect of urate elevation or an association between urate and BP. FUND: U.S. Department of Defense, RJG Foundation, Michael J. Fox Foundation LEAPS program, National Institutes of Health, American Federation for Aging Research, Parkinson's Disease Foundation Advancing Parkinson's Therapies initiative.

Tai Chi for Reducing Dual-task Gait Variability, a Potential Mediator of Fall Risk in Parkinson's Disease: A Pilot Randomized Controlled Trial.

OBJECTIVES: To assess the feasibility and inform design features of a fully powered randomized controlled trial (RCT) evaluating the effects of Tai Chi (TC) in Parkinson's disease (PD) and to select outcomes most responsive to TC assessed during off-medication states. DESIGN: Two-arm, wait-list controlled RCT. SETTINGS: Tertiary care hospital. SUBJECTS: Thirty-two subjects aged 40-75 diagnosed with idiopathic PD within 10 years. INTERVENTIONS: Six-month TC intervention added to usual care (UC) versus UC alone. OUTCOME MEASURES: Primary outcomes were feasibility-related (recruitment rate, adherence, and compliance). Change in dual-task (DT) gait stride-time variability (STV) from baseline to 6 months was defined, a priori, as the clinical outcome measure of primary interest. Other outcomes included: PD motor symptom progression (Unified Parkinson's Disease Rating Scale [UPDRS]), PD-related quality of life (PDQ-39), executive function (Trail Making Test), balance confidence (Activity-Specific Balance Confidence Scale, ABC), and Timed Up and Go test (TUG). All clinical assessments were made in the off-state for PD medications. RESULTS: Thirty-two subjects were enrolled into 3 sequential cohorts over 417 days at an average rate of 0.08 subjects per day. Seventy-five percent (12/16) in the TC group vs 94% (15/16) in the UC group completed the primary 6-month follow-up assessment. Mean TC exposure hours overall: 52. No AEs occurred during or as a direct result of TC exercise. Statistically nonsignificant improvements were observed in the TC group at 6 months in DT gait STV (TC [20.1%] vs UC [-0.1%] group [effect size 0.49; P = .47]), ABC, TUG, and PDQ-39. UPDRS progression was modest and very similar in TC and UC groups. CONCLUSIONS: Conducting an RCT of TC for PD is feasible, though measures to improve recruitment and adherence rates are needed. DT gait STV is a sensitive and logical outcome for evaluating the combined cognitive-motor effects of TC in PD.

The impact of a mind-body program on multiple dimensions of resiliency among geographically diverse patients with neurofibromatosis.

The neurofibromatoses (NF) are incurable genetic disorders that can cause nerve sheath tumors, chronic pain, and disfiguration. Patients with NF report lower quality of life and greater distress, and may benefit from programs that promote resiliency. To test effects of an 8-week mind-body program (Relaxation Response Resiliency Program for NF [3RP-NF]) on resiliency, using data derived from a larger randomized controlled trial of the 3RP-NF versus attention placebo control (Vranceanu et al. in Neurology 87:806-814, 2016). Participants (N = 63; 46 female; 52 White) were randomized to 3RP-NF (n = 32, M age = 42.86) or control (n = 31, M age = 39.90), completed intervention sessions via group videoconferencing, and provided self-report measures of resiliency (i.e., perceived coping abilities, perceived social support, gratitude, optimism, spiritual well-being, mindfulness) at baseline, post-intervention, and 6-month follow-up. All participants attended at least 6/8 sessions and 83% (N = 52) provided 6-month follow-up data. The 3RP-NF (vs. control) produced greater improvements from pre- to post-intervention in perceived coping abilities (M difference = 6.68; p = .008), perceived social support (M difference = 9.16; p = .032), and mindfulness (M difference = 2.23; p = .035), which were maintained at 6-month follow up. We did not observe group differences in spiritual well-being, optimism, or gratitude. The 3RP-NF produced sustained increases in multiple dimensions of resiliency (perceived coping abilities, perceived social support, and mindfulness). Promoting resiliency may be particularly important for a population that is underserved and living with a chronic, incurable illness.

Can Tai Chi training impact fractal stride time dynamics, an index of gait health, in older adults? Cross-sectional and randomized trial studies.

PURPOSE: To determine if Tai Chi (TC) has an impact on long-range correlations and fractal-like scaling in gait stride time dynamics, previously shown to be associated with aging, neurodegenerative disease, and fall risk. METHODS: Using Detrended Fluctuation Analysis (DFA), this study evaluated the impact of TC mind-body exercise training on stride time dynamics assessed during 10 minute bouts of overground walking. A hybrid study design investigated long-term effects of TC via a cross-sectional comparison of 27 TC experts (24.5 ± 11.8 yrs experience) and 60 age- and gender matched TC-naïve older adults (50-70 yrs). Shorter-term effects of TC were assessed by randomly allocating TC-naïve participants to either 6 months of TC training or to a waitlist control. The alpha (α) long-range scaling coefficient derived from DFA and gait speed were evaluated as outcomes. RESULTS: Cross-sectional comparisons using confounder adjusted linear models suggest that TC experts exhibited significantly greater long-range scaling of gait stride time dynamics compared with TC-naïve adults. Longitudinal random-slopes with shared baseline models accounting for multiple confounders suggest that the effects of shorter-term TC training on gait dynamics were not statistically significant, but trended in the same direction as longer-term effects although effect sizes were very small. In contrast, gait speed was unaffected in both cross-sectional and longitudinal comparisons. CONCLUSION: These preliminary findings suggest that fractal-like measures of gait health may be sufficiently precise to capture the positive effects of exercise in the form of Tai Chi, thus warranting further investigation. These results motivate larger and longer-duration trials, in both healthy and health-challenged populations, to further evaluate the potential of Tai Chi to restore age-related declines in gait dynamics. TRIAL REGISTRATION: The randomized trial component of this study was registered at ClinicalTrials.gov (NCT01340365).

The Mind Body-Wellness in Supportive Housing (Mi-WiSH) study: Design and rationale of a cluster randomized controlled trial of Tai Chi in senior housing.

Supporting the health of growing numbers of frail older adults living in subsidized housing requires interventions that can combat frailty, improve residents' functional abilities, and reduce their health care costs. Tai Chi is an increasingly popular multimodal mind-body exercise that incorporates physical, cognitive, social, and meditative components in the same activity and offers a promising intervention for ameliorating many of the conditions that lead to poor health and excessive health care utilization. The Mind Body-Wellness in Supportive Housing (Mi-WiSH) study is an ongoing two-arm cluster randomized, attention-controlled trial designed to examine the impact of Tai Chi on functional indicators of health and health care utilization. We are enrolling participants from 16 urban subsidized housing facilities (n=320 participants), conducting the Tai Chi intervention or education classes and social calls (attention control) in consenting subjects within the facilities for one year, and assessing these subjects at baseline, 6months, and 1year. Physical function (quantified by the Short Physical Performance Battery), and health care utilization (emergency visits, hospitalizations, skilled nursing and nursing home admissions), assessed at 12months are co-primary outcomes. Our discussion highlights our strategy to balance pragmatic and explanatory features into the study design, describes efforts to enhance site recruitment and participant adherence, and summarizes our broader goal of post study dissemination if effectiveness and cost-effectiveness are demonstrated, by preparing training and protocol manuals for use in housing facilities across the U.S.

Acupuncture for Chemoradiation Therapy-Related Dysphagia in Head and Neck Cancer: A Pilot Randomized Sham-Controlled Trial.

INTRODUCTION: Dysphagia is common in head and neck cancer patients after concurrent chemoradiation therapy (CRT). This study evaluated the feasibility of conducting a randomized sham-controlled trial and collected preliminary data on safety and efficacy of acupuncture. PATIENTS AND METHODS: Head and neck cancer (HNC) patients with stage III-IV squamous cell carcinoma were randomized to 12 sessions of either active acupuncture (AA) or sham acupuncture (SA) during and following CRT. Patients were blinded to treatment assignment. Swallowing-related quality of life (QOL) was assessed using the MD Anderson Dysphagia Inventory (MDADI) total and subscale scores. RESULTS: Multiple aspects of trial feasibility were confirmed. Forty-two of 196 patients screened (21%) were enrolled and randomized to receive AA (n = 21) or SA (n = 21); 79% completed at least 10 of 12 planned acupuncture sessions; 81% completed the study follow-ups. The majority of patients reported uncertainty regarding their treatment assignment, with no difference between the AA and SA groups. Audits confirmed both AA and SA treatments were delivered with high fidelity. No serious acupuncture-related side effects were observed. MDADI total scores significantly improved from baseline to 12 months post-CRT in both groups (AA: +7.9; SA +13.9; p = .044, p < .001). Similar patterns were observed for the MDADI global subscale (AA: +25.0; SA +22.7; p = .001, p = .002). Intent-to-treat analyses suggested no difference between the treatment groups (p = .17, p = .76 for MDADI total and global scores, respectively). CONCLUSION: A sham-controlled randomized trial evaluating acupuncture in dysphagia-related QOL in HNC found the procedure to be feasible and safe. Further investigation is required to evaluate efficacy. IMPLICATIONS FOR PRACTICE: Dysphagia or swallowing difficulty is an important and common condition after concurrent chemoradiation therapy in head and neck cancer patients. In addition to current available supportive care, acupuncture may offer potential for treating dysphagia. This study demonstrated that both active acupuncture and sham acupuncture are safe and were associated with improved dysphagia-related quality of life from baseline to 12 months after concurrent chemoradiation therapy. This study was not designed to inform underlying specific versus nonspecific effects. Future larger-scale pragmatic clinical trials evaluating the effectiveness of acupuncture versus standard of care are warranted, and further mechanistic research is needed to understand how active versus purportedly sham acupuncture procedures affect dysphagia-related symptoms.

Mind-body therapy via videoconferencing in patients with neurofibromatosis: An RCT.

OBJECTIVE: To test, within a single-blind randomized controlled trial, the feasibility, acceptability, efficacy, and durability of a mind-body program (the Relaxation Response Resiliency Program for neurofibromatosis [3RP-NF]) vs an attention placebo control (Health Enhancement Program for NF [HEP-NF]), both delivered via group videoconferencing. METHODS: Sixty-three patients completed baseline assessments and were randomized. Primary outcomes were physical health and psychological quality of life (QoL), measured by the WHOQOL-BREF (World Health Organization QoL abbreviated instrument). Secondary outcomes were social relations and environment QoL, depression, anxiety, pain intensity, and pain interference. RESULTS: Sixty-three participants completed the intervention (100%) and 52 the 6-month follow-up (82.5%). Acceptability was 4.1 (5-point scale). Patients in the 3RP-NF showed greater improvement in physical health QoL (7.69; 95% confidence interval [CI]: 0.29-15.10; p = 0.040), psychological QoL (5.57; 95% CI: 0.17-11.34; p = 0.056), social relations QoL (10.95; 95% CI: 1.57-20.31; p = 0.021), environment QoL (8.02; 95% CI: 2.57-13.48; p = 0.005), and anxiety (-2.32; 95% CI: -3.96 to 0.69; p = 0.006) compared to those in HEP-NF, and gains were maintained at follow-up. Patients in the 3RP-NF did not improve more than those in HEP-NF on depression, with both groups showing improvement. Patients in the 3RP-NF with baseline pain ≥5 of 10 showed improvement in pain intensity from baseline to posttest (1.30; 95% CI: -2.26 to -0.34; p = 0.009) with effects maintained at follow-up; this improvement was not greater than that in HEP-NF. There were more treatment responders in the 3RP-NF group (p < 0.05). CONCLUSIONS: The 3RP-NF delivered via videoconferencing was highly feasible and accepted by patients, and resulted in sustained improvement in QoL. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with NF, a mind-body program is superior to an attention placebo control in improving QoL.