Effect of dexamethasone in patients with ARDS and COVID-19 (REMED trial)—study protocol for a prospective, multi-centre, open-label, parallel-group, randomized controlled trial

Background Since December 2019, SARS-CoV-2 virus has infected millions of people worldwide. In patients with COVID-19 pneumonia in need of oxygen therapy or mechanical ventilation, dexamethasone 6 mg per day is currently recommended. However, the dose of 6 mg of dexamethasone is currently being reappraised and may miss important therapeutic potential or may prevent potential deleterious effects of higher doses of corticosteroids. Methods REMED is a prospective, open-label, randomised controlled trial testing the superiority of dexamethasone 20 mg (dexamethasone 20 mg on days 1–5, followed by dexamethasone 10 mg on days 6–10) vs 6 mg administered once daily intravenously for 10 days in adult patients with moderate or severe ARDS due to confirmed COVID-19. Three hundred participants will be enrolled and followed up for 360 days after randomization. Patients will be randomised in a 1:1 ratio into one of the two treatment arms. The following stratification factors will be applied: age, Charlson Comorbidity Index, CRP levels and trial centre. The primary endpoint is the number of ventilator-free days (VFDs) at 28 days after randomisation. The secondary endpoints are mortality from any cause at 60 days after randomisation; dynamics of the inflammatory marker, change in WHO Clinical Progression Scale at day 14; and adverse events related to corticosteroids and independence at 90 days after randomisation assessed by the Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days. The study will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. Discussion We aim to compare two different doses of dexamethasone in patients with moderate to severe ARDS undergoing mechanical ventilation regarding efficacy and safety. Trial registration EudraCT No. 2020-005887-70. ClinicalTrials.gov NCT04663555. Registered on December 11, 2020

Moving Toward and Through Trauma: Participant Experiences of Multi-Modal Motion-Assisted Memory Desensitization and Reconsolidation (3MDR)

Introduction: Military members and Veterans are at risk of developing combat-related, treatment-resistant posttraumatic stress disorder (TR-PTSD) and moral injury (MI). Conventional trauma-focused therapies (TFTs) have shown limited success. Novel interventions including Multi-modal Motion-assisted Memory Desensitization and Reconsolidation therapy (3MDR) may prove successful in treating TR-PTSD.Objective: To qualitatively study the experiences of Canadian military members and Veterans with TR-PTSD who received the 3MDR intervention.Methods: This study explored qualitative data from a larger mixed-method waitlist control trial testing the efficacy of 3MDR in military members and veterans. Qualitative data were recorded and collected from 3MDR sessions, session debriefings and follow-up interviews up to 6 months post-intervention; the data were then thematically analyzed.Results: Three themes emerged from the data: (1) the participants' experiences with 3MDR; (2) perceived outcomes of 3MDR; and (3) keys to successful 3MDR treatment. Participants expressed that 3MDR provided an immersive environment, active engagement and empowerment. The role of the therapist as a coach and “fireteam partner” supports the participants' control over their therapy. The multi-modal nature of 3MDR, combining treadmill-walking toward self-selected trauma imagery with components of multiple conventional TFTs, was key to helping participants engage with and attribute new meaning to the memory of the traumatic experience.Discussion: Preliminary thematic analysis of participant experiences of 3MDR indicate that 3MDR has potential as an effective intervention for combat-related TR-PTSD, with significant functional, well-being and relational improvements reported post-intervention.Conclusion: Military members and Veterans are at risk of developing TR-PTSD, with worse outcomes than in civilians. Further research is needed into 3MDR and its use with other trauma-affected populations.

A randomised controlled trial testing the efficacy of Fit after COVID, a cognitive behavioural therapy targeting severe post-infectious fatigue following COVID-19 (ReCOVer): study protocol

Background Coronavirus disease 2019 (COVID-19) results in debilitating long-term symptoms, often referred to as Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), in a substantial subgroup of patients. One of the most prevalent symptoms following COVID-19 is severe fatigue. Prompt delivery of cognitive behavioural therapy (CBT), an evidence-based treatment that has shown benefit in reducing severe fatigue in other conditions, may reduce post-COVID-19 fatigue. Based on an existing CBT protocol, a blended intervention of 17 weeks, Fit after COVID, was developed to treat severe fatigue after the acute phase of infection with SARS-CoV-2. Method The ReCOVer study is a multicentre 2-arm randomised controlled trial (RCT) to test the efficacy of Fit after COVID on severe post-infectious fatigue. Participants are eligible if they report severe fatigue 3 up to and including 12 months following COVID-19. One hundred and fourteen participants will be randomised to either Fit after COVID or care as usual (ratio 1:1). The primary outcome, the fatigue severity subscale of the Checklist Individual Strength (CIS-fatigue), is assessed in both groups before randomisation (T0), directly post CBT or following care as usual (T1), and at follow-up 6 months after the second assessment (T2). In addition, a long-term follow-up (T3), 12 months after the second assessment, is performed in the CBT group only. The primary objective is to investigate whether CBT will lead to a significantly lower mean fatigue severity score measured with the CIS-fatigue across the first two follow-up assessments (T1 and T2) as compared to care as usual. Secondary objectives are to determine the proportion of participants no longer being severely fatigued (operationalised in different ways) at T1 and T2 and to investigate changes in physical and social functioning, in the number and severity of somatic symptoms and in problems concentrating across T1 and T2. Discussion This is the first trial testing a cognitive behavioural intervention targeting severe fatigue after COVID-19. If Fit after COVID is effective in reducing fatigue severity following COVID-19, this intervention could contribute to alleviating the long-term health consequences of COVID-19 by relieving one of its most prevalent and distressing long-term symptoms. Trial registration Netherlands Trial Register NL8947. Registered on 14 October 2020.

Comparison of Recruitment Strategies for Engaging Older Minority Adults: Results From Take Heart

Few studies report best practices for recruiting older adults from minority, low SES communities for behavioral interventions. In this presentation, we describe recruitment processes and numbers for Take Heart, a randomized controlled trial testing the effectiveness of an adapted heart disease self-management program for primarily African American, low SES adults 50 years or older in Detroit. Community-based (CB), electronic medical record (EMR), and in-person hospital clinic (HC) recruitment methods were implemented. Within 22 months, 453 participants were enrolled, with an overall recruitment yield of 37%. The CB method had the highest yield (49%), followed by HC (36%) and EMR (16%). The average cost of recruiting and enrolling one participant was $142. Face-to-face interactions and employing a community health worker were particularly useful in engaging this population. Further research is needed to confirm these findings in other minority and low SES populations and share lessons learned about recruitment challenges and successes.

Interpersonal Associations Between Affect and Depressive Symptoms in Persons With Early Dementia and Their Spouses

Positive and negative affect have independent effects on health and occur frequently in close relationships. No research to our knowledge has examined self-reported affective experiences of persons with dementia (PWD) and their spouses and interpersonal associations with their psychological health. Secondary analysis of baseline interviews from a randomized clinical trial testing a stress reduction intervention in 45 couples (n=90) examined whether individuals’ positive and negative affect were associated with their own depressive symptoms (actor effects) as well as their partner’s depressive symptoms (partner effects) and whether these associations differed for PWD and spouses. Actor partner interdependence model results showed that for PWDs and spouses, one’s own positive affect was related to one’s own lower depressive symptoms (B=-3.10, SE=.59, df=58.70, p<.001), and one’s own negative affect was associated with one’s own greater depressive symptoms (B=6.62, SE=.60, df=65.67, p<.001). These effects were independent from each other. Partner effects were not significant.

Recruitment Challenges and Strategies for Multimodal Intervention Trials

Determining ways to improve hip fracture recovery in older adults is important, however recruitment of this target population into clinical trials is challenging. Multimodal interventions that target multiple mechanisms of recovery may improve outcomes, but each component presents unique recruitment barriers. While exercise interventions have been shown to be beneficial for hip fracture recovery, offering exercise following completion of conventional physical therapy can be viewed as a burdensome time commitment. Hormone replacement therapy may hold promise for overcoming anabolic resistance, but concern about adverse side effects can also deter participation. STEP-HI is a multisite trial testing whether exercise and testosterone can improve hip fracture recovery in older women. In this talk, recruitment barriers experienced in STEP-HI and strategies employed to overcome these barriers will be discussed. Strategies include: partnering with hospitals, skilled nursing facilities and orthopedic surgeons. providing talks and education materials; and featuring past participant testimonials in recruitment materials.

The Virtualization of a Movement and Social Group-Activity Intervention for Older Adults and Their Caregivers

COVID-related safety concerns mandated suspension of our ongoing trial testing the effects of movement and social engagement in older adults with early-stage dementia and their caregivers (dyads). Participant vulnerability and the requirement for group social interaction complicated intervention resumption. We present results from a successful pilot to rapidly and iteratively optimize study interventions for remote delivery targeting intervention mediators (social connection, movement) based on participant feedback. Three-dyad groups (n=6 individuals) completed cycles of intervention via Zoom immediately followed by an interview with open-ended and quantitative feedback. Cycles were repeated until no new information was solicited, then repeated with new participants. Optimization revealed needs for technological support, more intensive movement, and social connection. Specifically, the inability to make eye contact, see others’ full body, and technology-associated timing asynchronies impeded social connection in the movement group. We will present practical tips for crafting remote group interventions for caregiver/person living with dementia dyads.

Antifungal Activities of Ageratum conyzoides L. Extract against Rice Pathogens Pyricularia oryzae Cavara and Rhizoctonia solani Kühn

Blast disease and sheath blight disease caused by infection with Pyricularia oryzae and Rhizoctonia solani, respectively, are serious fungal diseases in paddy fields. Although synthetic fungicides have been used to control these diseases, the development of ecologically friendly alternatives is required because fungicides can cause health problems and environmental pollution. Natural herbs possessing antifungal activities are among the candidates as alternatives. Ageratum conyzoides is known to contain antifungal compounds, such as precocene II and polymethoxyflavones. Here, we report the antifungal activities of five compounds isolated after ethanol extraction from Ageratum conyzoides against Pyricularia oryzae and Rhizoctonia solani in vitro. Further, we demonstrated the protective effect of the extract on rice from Pyricularia oryzae infection by field trial testing in a shaded net-house.