PURPOSE: The purpose of this study was to investigate the use of an mHealth application (app), self-management physical activity intervention FOOTFIT with an added patient-provider connectivity feature (FOOTFIT+), that was designed to strengthen the lower extremities of minimally ambulatory individuals with venous leg ulcers (VLUs). DESIGN: Randomized controlled trial. SUBJECTS AND SETTING: Twenty-four adults 18 years and older with VLUs being treated in 2 wound clinics in the Southeastern United States participated in this study. METHODS: Preliminary estimates and 95% confidence intervals for the medians of short-term functional impacts on foot function, strength, ankle range of motion, walking capacity, depression, and physical functioning were obtained pre- and postassessment after the 6-week intervention trial. RESULTS: There were negligible changes in either group for foot function. It is noted that both groups experienced substantial foot and ankle impairment at baseline. The greatest improvement in range of motion was noted in the FOOTFIT group for dorsiflexion of the right ankle (4.6 ± 5.22 lb/in2 over baseline) whereas strength decreased in both ankles for dorsiflexion and plantar flexion in the FOOTFIT+ group. No improvements were noted in walking distance or physical health for FOOTFIT (slight decrease −2.9 ± 5.6) and FOOTFIT+ (slight increase 3.0 ± 6.6) during the 6-week study period. CONCLUSIONS: In a minimally ambulatory population with VLUs, our mHealth FOOTFIT intervention composed of progressive exercise “boosts” demonstrated minimal short-term effects. We recommend engagement with the app for a longer period to determine longer-term outcomes of lower extremity function.

Aims To explore factors at the family caregiver and nursing home administrative levels that may affect participation in a clinical trial to determine the efficacy of hand feeding versus percutaneous gastrostomy tube feeding in persons with late-stage dementia. Background Decision-making regarding use of tube feeding vs. hand feeding for persons with late-stage dementia is fraught with practical, emotional and ethical issuesand is not informed by high levels of evidence. Design Qualitative case study. Methods Transcripts of focus groups with family caregivers were reviewed for themes guided by behavioral theory. Analyses of notes from contacts with nursing home administrators and staff were reviewed for themes guided by an organizational readiness model. Data were collected between the years 2009–2012. Results Factors related to caregiver willingness to participate included understanding of the prognosis of dementia, perceptions of feeding needs and clarity about research protocols. Nursing home willingness to participate was influenced by corporate approval, concerns about legal and regulatory issues and prior relationships with investigators. Conclusion Participation in rigorous trials requires lengthy navigation of complex corporate requirements and training competent study staff. Objective deliberation by caregivers will depend on appropriate recruitment timing, design of recruitment materials and understanding of study requirements. The clinical standards and policy environment and the secular trends therein have relevance to the responses of people at all levels.

Context: Exacerbated by life stressors, fatigue is the most common symptom for people living with HIV.Objective: To adapt, develop, and assess the feasibility of a CBSM mHealth (cognitive behavioral stress management mobile health) application (app) for HIV-related fatigue.Methods: This study had two phases: app development with key informants (N=5) and a randomized controlled trial (N=30). Patients randomized to the intervention group completed 10 weekly CBSM modules; those in the control group received a generic healthy lifestyle app. Measures included HIV-related fatigue, depression, anxiety, stressful life events, CD4 count, HIV viral load, credibility and acceptability of the intervention, and barriers to treatment participation. Results:We were able to recruit participants for this study, and they were able to complete the required measures. They found the intervention to be credible and acceptable, and reported few barriers to treatment participation. The direction of change in the primary outcome, a decrease in fatigue, is in the expected direction, and provides evidence of the promise of the intervention, which still needs to be tested in an adequately powered trial. For completers (randomized to the intervention group and completed at least 80% of the modules), there were significant changes (95% CI; lower scores indicate improvement) in fatigue intensity (from 64.2 to 59.7) and overall fatigue-related functioning (from 6.6 to 4.2). Conclusion:We have proof of concept as to the feasibility, acceptability, and initial signals of efficacy for an mHealth intervention to help people with HIV-related fatigue better cope with stress and reduce their fatigue.

Palliative care approaches that effectively manage distressful symptoms associated with wounds at the end of life remain elusive. This 4-week study examined a topical wound powder RGN107 for reducing pain, odor, and exudate in 50 patients with pressure ulcers, skin tears, and malignant/fungating and vascular wounds receiving hospice or palliative care and explored quality of life for the caregiver. Through an observational design, the outcomes were measured with visual analog scales, 2 pain questionnaires, and a caregiver quality-of-life instrument. Intent-to-treat analyses were used. Statistically significant reductions in pain (P = .001), odor (P = .04), and exudate (P = .00003) were observed. Caregiver quality of life remained unchanged (P = .28); however, improvements were noted in 3 subscales. Findings suggest topical RGN107 reduced pain, odor, and exudate in a highly challenged population with wounds at the end of life. A larger comparative effectiveness trial should be conducted with other wound powder comparators and usual care approaches and should include cost benefits.

BackgroundFor intervention studies that require the use of participant self-reports, the quality and accuracy of recorded data and variability in participant adherence rates to the treatment can cause significant outcome bias.PurposeTo assess the quality and accuracy of participant documentation of daily self-monitoring of leg skin temperature, adherence to a graduated cooling treatment protocol to prevent venous leg ulcers, and the potential for bias in treatment effect in a randomized controlled trial that included a population with chronic venous disease.MethodsIndividuals were randomized to a leg cooling intervention or placebo treatment group to daily self-monitor and record lower leg skin temperature over a 9-month period on monthly paper study logs. Returned study logs for the first 100 completed participants (n=54 cooling intervention, n=46 control) were reviewed for quality and accuracy. Adherence was determined from evaluating the accuracy of participant documentation. To examine potential outcome bias in treatment effect, mean between group and within group comparisons of the before and after treatment differences were conducted using an intention-to-treat (ITT) versus a modified intention-to-treat (mITT) analysis approach with an 85% accuracy cut-off rate. Data were collected in 2011–2014.ResultsOf the expected 900 study logs, 91.8% (826/900) were returned and 8.2% (74/900) were not. Non-mutually exclusive main error types in returned documentation included: 59.2% (489/826) white-outs, cross-off and/or overwrites, 34.9% (288/826) entries omitted, 29.4% (243/826) no performance of daily self-monitoring, 28.7% (237/826) no performance of the treatment intervention per the prescribed protocol regime, 26.8% (221/826) extraneous data, 8.6% (71/826) suspected fabrication, and 7.6% (63/826) questionable validity. Under ITT analysis, 38.4% (346/900) of all returned logs were <85% accurate, 25.0% (225/900) were 85%–99% accurate, and 36.6% (329/900) were 100% accurate. Mean overall participant adherence rates were: 22.0% at <85% accuracy, 53.0% at 85%–99% accuracy, and 25.0% at 100% accuracy. Under the mITT analysis, 54.0% (483/900) of returned logs were deemed adherent with ≥85% accuracy.ConclusionThis study found good rates of adherence. Under ITT analysis, 78.0% of participants were deemed adherent to the study protocol with ≥85% accuracy in documenting daily self-monitoring of skin temperatures in response to a topically applied experimental cooling cuff intervention for the prevention of venous leg ulcers.

Pain was reduced in both groups while self-efficacy did not change. Findings suggest that strictly implemented standard of CVeD care in each study group, with or without cooling, improved pain while there were no effects on self-efficacy.

Background: Vaso-occlusive crises (VOC) are the most common acute complication of sickle cell disease (SCD). Crizanlizumab, an anti-P-selectin monoclonal antibody, is an FDA-approved disease-modifying therapy (DMT) for SCD patients (pts) aged ≥16 yrs to reduce the frequency of VOC. To better understand its use and impact, the National Alliance for Sickle Cell Centers (NASCC) conducted a retrospective study of pts prescribed crizanlizumab from 11/2019-6/30/2021. NASCC is a non-profit organization formed to support SCD centers in delivering quality comprehensive care by setting and adopting specific standards and advocating for improved health outcomes in SCD. This study describes the largest real-world cohort of pts treated with crizanlizumab. Methods: This is a two-part study. Part 1 was to evaluate NASCC center crizanlizumab practice and to summarize data on insurance approval and the frequency of drug discontinuation. Part 2 includes pt level data to evaluate reasons for discontinuation and acute care utilization pre and post therapy. Acute care use includes day hospital/infusion, emergency department visits, and hospitalizations for VOC (excluding COVID-19). The index date for each pt is defined as the 1st crizanlizumab infusion date. Chart review (electronic health records) was used to identify all acute care visits 12 months pre-index and ≤12 months post index. Acute care data will be analyzed in aggregate. Evaluation of center-specific use of crizanlizumab, time to initial site level formulary approval and drug discontinuation were analyzed. Pt level data collection is ongoing to include sufficient time post index date. VOC characteristics will be summarized using medians, median differences (pre/post treatment), and 95% confidence intervals. Additional evaluation of effectiveness of crizanlizumab will include analysis based on number of doses received, pre-treatment VOC burden, concomitant hydroxyurea (HU) use and genotype. Results: Data includes pts prescribed crizanlizumab at 11 NASCC centers. Site- formulary approvals to use crizanlizumab varied from 12/2019-12/2020. As a result, the 1st pt to receive treatment at each site varied from 1/15/2020-1/20/2021. Mean time from site-level approval to first infusion was 77 days (range: 0-394). Over 50% of sites received insurance denials mainly due to "insufficient medical necessity" or "medication not covered by the prescription plan." Sites were able to successfully appeal denials for 71% of pts (Table 1). Treatment Delivery: Each site gives infusions over 30 minutes and the majority (64%) do not use pre-medication unless pts had reactions. Some sites use diphenhydramine/acetaminophen (3) or normal saline and ketorolac (1). All sites prescribe crizanlizumab to pts of all SCD genotypes. Pts Treated: 297 pts were prescribed crizanlizumab of whom 238 received ≥ 1 infusion. There was variation in number of pts/site (range 6-73, mean 21) due to time to site-level approval, insurance and pt population. Of these 238, 75 pts (32%) discontinued treatment (0-17 pts/site). Sites reported pts perceived lack of improvement or feeling their overall pain was increased, transportation issues and infusion related reactions (IRRs) characterized by pain as some of the reasons for discontinuation. Evaluation of real-world efficacy measured by changes in acute care utilization, including sub-analysis by genotype, pre-treatment VOC burden and concomitant HU use, are pending sample size dependent feasibility. Discussion: This is the first multi-center real-world analysis of crizanlizumab. Findings demonstrate some insurance barriers to therapy. The majority of pts who initiated crizanlizumab have remained on therapy; however, 1/3 of pts had lack of effect or barriers to care. Pt level data will include characteristics related to treatment failure or IRR. Improving the understanding of phenotype-specific response to novel therapies is essential in SCD. Conclusion: Post-approval therapies for rare diseases must undergo real-world evaluation to ensure study results translate to the community. NASCC uses defined criteria for multidisciplinary care for Alliance inclusion and findings reflect the use of DMT in such centers. This is the first NASCC study of DMT in SCD. Part 2 of the study will give early insights into the effectiveness of crizanlizumab; long term follow-up is needed for a full understanding of its utility in SCD. Figure 1 Figure 1. Disclosures Kanter: Fulcrum Therapeutics, Inc.: Consultancy; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Forma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beam: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Graphite Bio: Consultancy; GuidePoint Global: Honoraria; Fulcrum Tx: Consultancy. Manwani: Novartis: Consultancy. Idowu: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Forma Therapeutics, Inc.: Research Funding; Ironwood: Research Funding. Treadwell: National Alliance of Sickle Cell Centers: Other: Early Evaluation of the Use of Crizanlizumab in Sickle Cell Disease. Clay: GBT: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria. Little: Hemex Health, Inc.: Patents & Royalties; Biochip Labs: Patents & Royalties. Desai: Global Blood Therapeutics: Honoraria, Research Funding; Novartis: Research Funding, Speakers Bureau; Pfizer: Other: Publication Fee, Research Funding; Forma: Consultancy; Foundation for Sickle Cell Research: Honoraria. Lanzkron: Shire: Research Funding; Pfizer: Current holder of individual stocks in a privately-held company; Bluebird Bio: Consultancy; Teva: Current holder of individual stocks in a privately-held company; Novo Nordisk: Consultancy; GBT: Research Funding; Imara: Research Funding; CSL Behring: Research Funding; Novartis: Research Funding.

Background Individuals with venous leg ulcers (VLUs) suffer disproportionately with multiple chronic conditions, are often physically deconditioned, and demonstrate high levels of physical inactivity. Objective The primary objective of this randomized controlled trial was to establish the feasibility of a mobile health (mHealth) physical activity exercise app for individuals with VLUs to improve lower leg function. Methods In a 6-week study, adults with VLUs were recruited from 2 wound centers in South Carolina, United States, and enrolled if they were aged 18 years or older with impaired functional mobility and an ankle-brachial index between 0.8 and 1.3. Participants were randomized 1:1 to receive evidence-based, phased, nonexertive physical conditioning activities for lower leg function (FOOTFIT) or FOOTFIT+ with an added patient-provider communication feature. The mHealth Conditioning Activities for Lower Leg Function app also provided automated educational and motivational messages and user reports. Foot movement on the VLU-affected leg was tracked by a Bluetooth-enabled triaxial accelerometer. The study was guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework to assess the feasibility of reach, adherence, acceptability, implementation, and maintenance. Results A total of 24 patients were recruited, enrolled, and randomized in the study. Most patients reported difficulty following the protocol for exercising and using the accelerometer and mobile phone and did not use the provider contact feature. However, all patients were adherent to the 6-week exercise program more than 85% of the time for duration, whereas 33% (8/24) of patients adhered more than 85% for the frequency of performing the exercises. Across the three exercise levels, adherence did not differ between the two groups. Confidence limits around the difference in proportions ranged from −0.4 to 0.7. Providers in FOOTFIT+ were inconsistent in checking participant progress reports because of lack of time from competing work commitments. The technology became outdated quickly, making maintenance problematic. Participants said they would continue to exercise their foot and legs and liked being able to follow along with the demonstrations of each level of exercise provided through the app. Conclusions The findings of this study suggest that despite initial interest in using the app, several components of the program as originally designed had limited acceptability and feasibility. Future refinements should include the use of more modern technology including smaller wearable accelerometers, mobile phones or tablets with larger screens, an app designed with larger graphics, automated reporting for providers, and more engaging user features. Trial Registration ClinicalTrials.gov NTC02632695; https://clinicaltrials.gov/ct2/show/NCT02632695