Preliminary Efficacy Trial Research Articles

The digital MySteps intervention for abused women at risk for firearm-related injuries and homicides: Findings from the feasibility, acceptability and preliminary efficacy trial

BackgroundFirearms are the leading cause of victimization of abused women by intimate partner homicide and intimate partner homicide-suicides in the US. This calls for evidence-based intervention strategies to prevent firearm-related injuries or mortality and address the firearms-related safety needs of women in abusive relationships. My Safety Steps (MySteps) was designed to comprehensively assess women's firearm-related risks, and current safety needs and to prevent women's harm from their abuser's access or ownership of a firearm through a digitally delivered firearm-focused safety planning intervention. This paper describes the development, feasibility, acceptability, and preliminary evaluation of the digital BSHAPE intervention among women survivors of intimate partner violence (IPV). MethodsUsing a pretest post-test control group design, the study was conducted with 103 participants with 55 women randomly assigned to the MySteps arm and 48 women to the standard of care control arm. The feasibility and acceptability outcomes assessed were enrollment, adherence, and perceptions of the intervention. Preliminary evaluation outcomes included the partner's access to a firearm, women's self-efficacy beliefs, and empowerment. Further, qualitative follow-up interviews were conducted with 30 survivors of IPV in the MySteps arm to follow up on the use and helpfulness of safety strategies provided in MySteps. Results and conclusionThe intervention was found to be feasible, and acceptable and demonstrated improved outcomes for survivors of IPV at risk from their partner's firearm. Women provided feedback for further refinement. The findings of this study will be useful in further refining MySteps and testing it in a full-scale randomized controlled trial.

Selection of vaccine candidates against Pseudomonas koreensis using reverse vaccinology and a preliminary efficacy trial in Empurau (Tor tambroides)

This study marks the first utilization of reverse vaccinology to develop recombinant subunit vaccines against Pseudomonas koreensis infection in Empurau (Tor tambroides). The proteome (5538 proteins) was screened against various filters to prioritize proteins based on features that are associated with virulence, subcellular localization, transmembrane helical structure, antigenicity, essentiality, non-homology with the host proteome, molecular weight, and stability, which led to the identification of eight potential vaccine candidates. These potential vaccine candidates were cloned and expressed, with six achieving successful expression and purification. The antigens were formulated into two distinct vaccine mixtures, Vac A and Vac B, and their protective efficacy was assessed through in vivo challenge experiments. Vac A and Vac B demonstrated high protective efficacies of 100 % and 81.2 %, respectively. Histological analyses revealed reduced tissue damage in vaccinated fish after experimental infection, with Vac A showing no adverse effects, whereas Vac B exhibited mild degenerative changes. Quantitative real-time PCR results showed a significant upregulation of TNF-α and downregulation of IL-1β in the kidneys, spleen, gills, and intestine in both Vac A- and Vac B-immunized fish after challenged with P. koreensis. Additionally, IL-8 exhibits tissue-specific differential expression, with significant upregulation in the kidney, gills, and intestine, and downregulation in the spleen, particularly notable in Vac A-immunized fish. The research underscores the effectiveness of the reverse vaccinology approach in fish and demonstrates the promising potential of Vac A and Vac B as recombinant subunit vaccines.

FEASIBILITY, ACCEPTABILITY, AND EFFICACY OF A PILOT EXERCISE PHYSIOLOGY GROUP SERVICE FOR OLDER ADULTS WITH TYPE 2 DIABETES

INTRODUCTION & AIMS Type 2 diabetes prevalence increases with ageing, affecting over half a million older Australians. Medicare type 2 diabetes group interventions can support older adults’ diabetes management. However, Accredited Exercise Physiologist (AEP) delivered service feasibility and acceptability is yet to be assessed. This study aimed to assess feasibility, acceptability and preliminary efficacy of a Medicare type 2 diabetes group exercise and education intervention for older adults. METHODS This study was a single arm feasibility, acceptability, and preliminary efficacy trial of an AEP delivered type 2 diabetes group service for older adults. Participants attended the Diabetes Clinic once per week for 8 weeks, for a group exercise and education session. Attendance, participation, enjoyment, suitability, usefulness, and pre-post clinical health outcomes were assessed. RESULTS The intervention was feasible and acceptable, with 40 participants (71.8±4.5 years old, range 65-81 years, 45% female) attending 87% of sessions, with high treatment compliance within sessions (aerobic training: 86%; resistance training: 86%; education: 87%). Almost all participants (97%) strongly agreed that the program was enjoyable. Significant post intervention improvements (mean difference [95% CI]) were observed for right arm systolic blood pressure (SBP) (-7mmHg [-12, -2], p=0.007), left arm diastolic blood pressure (DBP) (-3mmHg [-5, -0], p=0.021), body weight (-0.7kg [-1.3, -0.0], p=0.039), waist circumference (-1.3cm [-2.2, -0.4], p=0.006), 6-minute walk test (22.8m, [9.1. 36.5], p=0.002), 5 times sit to stand (-0.8sec [-1.2, -0.5], p<0.001), short physical performance battery ordinal scale (0.3 [0.1, 0.5], p=0.009), and whole-body muscle strength (32.2kg [22.3, 42.1], p<0.001). CONCLUSION Older adults attended and enjoyed the AEP led Diabetes Clinic program, while also improving fitness and cardiometabolic health outcomes. Ways to enhance referrals and engage older adults in the programs warrant further investigation. The potential for additional sessions to achieve greater physical activity engagement and diabetes self-management should be further investigated.

Mental Health and Well-Being in Racial or Ethnic Minority Individuals After Using a Faith and Prayer Mobile App (Pray.com): Feasibility and Preliminary Efficacy Trial.

Research is needed on how faith and prayer apps fit within the values of racial and ethnic minority (REM) groups, as well as whether such apps are effective in promoting mental health and well-being. This study aims to determine the feasibility and preliminary effectiveness of using the mobile app Pray.com on mental health and well-being among REM participants. This study was a single-group (N=77), 4-week feasibility trial in REM groups (65/77, 84% Black or African American). Participants were asked to use the Pray.com app at no cost for at least 5 times per week for 5 minutes per day. Participants completed questionnaires at the baseline and postintervention time points. Feasibility questionnaires were only completed at the postintervention time point, including qualitative interviews (n=15). The feasibility questions included acceptability (ie, satisfaction, intent to continue use, perceived appropriateness, and fit within culture), demand (ie, self-reported app use, expressed interest, and perceived demand), and practicality (ie, ease or difficulty of use, ability to use the app, and cost-effectiveness). Frequency and descriptive statistics were used to analyze feasibility outcomes. Changes in dependent variables were analyzed using paired-sample 2-tailed t tests. Partial correlations were conducted to explore the association between app use and outcomes, controlling for baseline scores. Participants reported (54/72, 75% responded with "very likely" or "likely" to the feasibility questions) that they perceived the Pray.com app as acceptable. These findings were supported by qualitative interviews (n=15). Most participants (62/72, 86%) did not meet the app use prescription but expressed interest in using the app in the future and perceived demand for it in their communities. In addition, participants reported that the app was easy to use and perceived it to be inexpensive (US $7.99). Participants reported improved mental health (ie, stress and depressive and anxiety symptoms) and well-being (ie, satisfaction with life, spiritual well-being, religious commitment, and racial or ethnic identity development) at postintervention despite relatively low average levels and high variability of app use (average total of 45.83, SD 111.90 min over the course of the study). Greater app use was significantly associated with improvements in mental health and spiritual well-being. However, app use and study methodology limitations suggest that the study results may not accurately capture the full impact of Pray.com use. This is the first study to assess the feasibility of a faith and prayer app for mental health and well-being in a sample of REM individuals. Our findings suggest that the use of a faith and prayer app (ie, Pray.com) could be feasible and significantly impactful for the improvement of mental health symptoms and well-being in REM individuals and their communities, especially Black and African American individuals with a Christian affiliation. Further research is warranted.

Feasibility, acceptability and efficacy of a pilot exercise physiology group service for older people with type 2 diabetes.

Type 2 diabetes affects over half a million older Australians. Australian Medicare group exercise and education interventions can support older adults' diabetes management. However, the feasibility and acceptability of accredited exercise physiologist (AEP)-delivered services are yet to be assessed. This study aimed to assess the feasibility, acceptability and preliminary efficacy of a Medicare type 2 diabetes group exercise and education intervention for older adults. This study was a single-arm feasibility, acceptability and preliminary efficacy trial of an AEP-delivered type 2 diabetes group service for older adults with the condition. Participants attended the diabetes clinic once per week for eight weeks, through Medicare, for a group exercise and education session. Attendance, participation, enjoyment, suitability, usefulness and pre-post clinical health outcomes were assessed. The intervention was feasible and acceptable, with 40participants (mean [±standard deviation] age 71.8±4.5 years [range 65-81 years]; 45% female) attending 87% of sessions. Almost all participants (97%) strongly agreed that the program was enjoyable. Participants also improved fitness and cardiometabolic health outcomes. More Australians should be referred to and attend Medicare-subsidised exercise physiologist-delivered group sessions. The potential for additional sessions toachieve greater physical activity engagement and diabetes self-management should be further investigated.

Strengthening First Responders’ Coaching Proficiency through a Peer Fitness Leader Workshop: A Preliminary Efficacy Trial

Strengthening First Responders’ Coaching Proficiency through a Peer Fitness Leader Workshop: A Preliminary Efficacy Trial

Online psychoeducation and digital assessments as a first step of treatment for borderline personality disorder: A protocol for a pilot randomized controlled trial

Background Treatment trials for borderline personality disorder (BPD) have consistently demonstrated that approaches that are diagnostically tailored are superior to those which are not. Currently, gold standard treatments for BPD are highly intensive, lengthy, and specialized, leading to a critical gap between the supply and demand of effective, evidence-based treatment for patients who receive a diagnosis of BPD. Psychoeducation, which is a common component of most treatments known to be effective, is a low-cost, low-burden intervention proven to relieve symptoms. The present study builds on psychoeducation research, assessing online video prescriptions as a means of disseminating information patients need to know about their diagnosis and care. Methods This article presents the study protocol for a safety, feasibility, and preliminary efficacy trial of psychoeducational video prescriptions and online assessment with feedback for newly diagnosed individuals with BPD. We aim to recruit 100 adults recently diagnosed with BPD to be randomly assigned to receive videos about BPD or videos about non-BPD mental health topics that are matched in length in the first step of the study. All participants will complete daily surveys about their emotions, interpersonal interactions, and behaviors, as well as self-report assessments and cognitive tests at 4 different time points. Half of the participants in the intervention group will receive feedback on their symptom ratings and cognitive test performance to assess whether there is incremental value in tailoring this online set of interventions with individualized feedback unique to each participant. This study aims to assess the effects of BPD-focused psychoeducational videos with and without personalized feedback, on BPD and depressive symptom severity as well as core mechanisms of the disorder such as loneliness, rejection sensitivity, cognitive control difficulties, and self-clarity. Results will inform efforts to progress to a larger, more definitive trial. Trial registration Clinical trials registration: The protocol is registered with ClinicalTrials.gov NCT05358925.

A Positive Psychology Intervention in Allogeneic Hematopoietic Stem Cell Transplantation Survivors (PATH) to Promote Well-Being: Randomized Controlled Feasibility and Preliminary Efficacy Trial

Background: Patients with hematologic malignancies who are allogeneic hematopoietic stem cell transplantation (HSCT) survivors experience tremendous psychological symptoms (e.g., anxiety and depression symptoms) and low levels of positive psychological well-being (e.g., flourishing, gratitude), which further undermine multiple health-related outcomes such as quality of life (QOL). However, supportive oncology interventions which specifically target positive psychological well-being may buffer against psychological distress and promote QOL. Thus, we developed and piloted a novel phone-delivered positive psychology intervention (PATH) to improve QOL and symptoms of anxiety and depression in HSCT survivors transplanted for hematologic malignancies. Methods: We conducted a randomized controlled trial (NCT05147311) to assess feasibility, acceptability, and preliminary efficacy of the PATH intervention. From August 2021 to August 2022, 70 HSCT survivors who were 100-days post-HSCT were randomly assigned to either PATH or a usual care control group. The PATH group had 9 weekly 1:1 phone sessions of positive psychology exercises focused on gratitude, strengths, and meaning. The Usual care group had routine sessions with the transplant social worker. We defined feasibility as >60% of eligible participants enrolling in the study and >75% of intervention group participants completing at least 6 of the 9 positive psychology sessions. At baseline and 9 and 18 weeks after baseline, patients self-reported optimism (Life Orientation Test Revised), gratitude, (Gratitude Questionnaire-6), flourishing (Flourishing Scale), QOL (Functional Assessment of Cancer Therapy-Bone Marrow Transplant) and depression and anxiety (Hospital Anxiety and Depression Scale). We used mixed effects regression analyses to determine the potential impact of PATH on QOL and symptoms of anxiety and depression. Results: The average age (standard deviation) of participants was 56.8 (13.7) years; 50% (N=35) were female. The majority of the participants identified as White (91.4%; N=64), married or living with a partner (71.4%; N=50), had at least a college education (67.2%; N=47) and were on disability or retired (87.1%; N=67). The majority had a diagnosis of leukemia (68.6%; N=48), underwent reduced intensity conditioning (62.9%; N=44), and did not have acute graft-versus-host disease (68.6%; N=48). For our feasibility metrics, we enrolled 68.6% (72/105) of eligible patients, two of which were not randomized due to worsening physical symptoms. Additionally, 94% (95% CI: 79%-99%) of those who started the PATH intervention completed all nine intervention sessions. For acceptability, participants in the intervention group reported positive psychology exercises as easy to complete (mean [95% CI] = 7.40 [6.87, 7.92] on a scale of 0-10) and useful (mean [95% CI] = 8.23 [7.83, 8.63]). Compared with usual care, participants in the intervention group reported less symptoms of anxiety ( d=0.46, p=0.027), and demonstrated promising improvements in gratitude ( d=0.26) at 9 weeks. We did not observe significant differences in QOL and depression symptoms. Conclusions: A positive psychology intervention, PATH, is feasible, acceptable, and has potential to improve outcomes in patients with hematologic malignancies who are allogeneic HSCT survivors. Larger trials are needed to examine the impact of PATH on psychological well-being and QOL in this population.

Evaluating the feasibility and preliminary efficacy of a Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS): an update to the protocol for a feasibility cluster-randomised controlled trial

BackgroundCognitive difficulties experienced by people with multiple sclerosis (MS) impact on quality of life and daily functioning, from childcare and work to social and self-care activities. The Cognitive Occupation-Based programme for people with MS (COB-MS) was developed as a holistic, individualised cognitive rehabilitation intervention to address the wide-ranging symptoms and functional difficulties that present in MS, including the ability to maintain employment, social activities, home management and self-care. The aim of the research is to evaluate the feasibility and preliminary efficacy of COB-MS for people with MS.MethodsDue to the impacts of COVID-19, trial activities that were planned for in-person delivery were completed remotely. One hundred and twenty people with MS will be assigned to participate in either the COB-MS programme or a treatment-as-usual, wait-list control group as part of this single-blind, cluster-randomised controlled feasibility and preliminary efficacy trial of the COB-MS programme. The COB-MS group will participate in an eight-session occupational-based cognitive rehabilitation programme over 9 weeks. The COB-MS intervention was planned for in-person delivery but was delivered online by occupational therapists to small groups of people with MS. The primary outcome measure is the Goal Attainment Scaling at 12 weeks. Participants will be assessed pre-intervention, post-intervention, 12 weeks post-intervention and 6 months post-intervention. Qualitative evaluations of participants’ perspectives will also be examined as part of the feasibility study. Data, due to be collected in-person, was collected online or by post. The original study design, including the statistical analysis plan, remains unchanged despite the shift to a remote trial conduct.DiscussionResults will provide recommendations for a future definitive trial of COB-MS, with respect to both feasibility and preliminary, clinical efficacy.Trial registrationISRCTN ISRCTN11462710. Registered on 9 September 2019 and updated on 23 September 2020 to account for changes outlined here.

In Vitro Antimicrobial Effectiveness Tests Using Garlic (Allium sativum) against Salmonella enterica Subspecies enterica Serovar Enteritidis.

In recent years, there has been a more prudent use of drugs on livestock farms and alternative products have been considered, with a view of reducing the risk of the onset of antibiotic resistance. Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis) may cause disease in poultry, and it is also responsible for human food poisoning. The aim of this study was to evaluate the efficacy of garlic against S. Enteritidis and to define its Minimal Inhibitory Concentration (MIC)90 and MIC50 values. The study was carried out in vitro, testing 26 S. Enteritidis strains identified in laying hens from various farms in Southern Italy. A preliminary efficacy trial was carried out on two strains, S. Enteritidis and Escherichia coli, using a garlic concentration of 10 mg/mL (1%). Later, 26 strains of S. Enteritidis at 106 Colony Forming Unit (CFU) and 104 CFU were tested with different concentrations of garlic, ranging from 10 mg/mL to 1 mg/mL. Based on the results, intermediate concentrations of garlic, from 5 mg/mL to 4 mg/mL and 4 mg/mL to 3 mg/mL, were used to test 106 CFU and 104 CFU, respectively. The data were statistically analyzed. The MIC90 was 4.75 mg/mL for strains tested at 106 CFU and 4 mg/mL for strains tested at 104 CFU. The results highlight garlic's potential to inhibit the growth of Salmonella enterica ser. Enteritidis in vitro. Efficacy was dependent on the microbial concentration used. In vivo efficacy trials will be crucial to confirm the efficacy of garlic against S. Enteritidis and to assess whether garlic can be used in poultry flocks to prevent the spread of the bacterium in the field.

Development of a Conversational Agent for Promoting Increased Activity in Users with Traumatic Brain Injury

<h3>Research Objectives</h3> To develop and test a conversational agent-i.e., a chatbot that users communicate via text messaging-designed to augment behavioral activation treatment for reducing depression and increasing participation in individuals with moderate to severe Traumatic Brain Injury (TBI) called RehaBot <h3>Design</h3> A prototype of RehaBot was developed based on feedback from therapist and consumer focus groups and then tested in three separate user demonstration trials. A usability and preliminary efficacy trial is underway. <h3>Setting</h3> Outpatient rehabilitation. <h3>Participants</h3> Rehabilitation providers and persons with moderate to severe TBI. <h3>Interventions</h3> None. <h3>Main Outcome Measures</h3> System Usability Scale (SUS). <h3>Results</h3> Therapist focus group participants indicated that RehaBot could promote engagement with therapeutic plans and provide prompts that cue users to adhere to routines. Respondents with TBI indicated that they would be comfortable interacting with RehaBot, and most had prior experience with chatbots. They expressed a preference for a system accessible via smartphone (vs. computer/voice assistant). Goal reminders, progress updates, and encouragement were identified as beneficial features. Respondents conveyed that misunderstandings between users and chatbots would be frustrating. In demonstration trials, two of the three participants could complete 5 of 5 RehaBot tasks independently. One user completed three independently and a 4th with assistance. The average SUS rating was 4.3 (0.80) on a 5-point scale. <h3>Conclusions</h3> Preliminary evidence suggests that a chatbot augment to behavioral activation treatment-RehaBot-is acceptable and easy to use for persons with moderate to severe TBI. Further research is ongoing to establish usability in a larger sample and evaluate RehaBot's efficacy in improving therapeutic plan adherence. <h3>Author(s) Disclosures</h3> None.

Internet-Administered Emotional Awareness and Expression Therapy for Somatic Symptom Disorder With Centralized Symptoms: A Preliminary Efficacy Trial.

Background: There is growing evidence that trauma, psychosocial conflict, and difficulties with emotional processing contribute to centralized somatic symptoms. Emotional Awareness and Expression Therapy (EAET) was developed to address these factors and reduce symptoms, and EAET has shown efficacy in face-to-face formats. No trial of an internet-delivered EAET (I-EAET) exists, however, so we developed such an intervention and conducted an uncontrolled feasibility and potential efficacy trial of I-EAET for patients with Somatic Symptom Disorder (SSD) with centralized symptoms (SSD-CS).Method: After screening potential participants, a sample of 52 patients (50 women, two men; age M = 49.6, SD = 11.9) diagnosed with SSD-CS initiated treatment. I-EAET consisted of nine weekly modules focused on psychoeducation, emotional awareness and exposure, and anxiety regulation with self-compassion. Therapists communicated with each patient by email for about 20 min per week during treatment, answering questions and giving feedback on homework assignments. Patients completed measures of somatic symptoms, depression, anxiety, trauma-related symptoms, and functional disability before treatment and again at post-treatment and 4-month follow-up.Results: A large reduction in somatic symptoms (PHQ-15) occurred pre-to post-treatment (d = 1.13; 95% CI: 0.84–1.47) which was fully maintained at 4-month follow-up (d = 1.19; 95% CI: 0.88–1.56). Twenty-three percent of the patients at post-treatment and 27% at follow-up achieved a 50% or greater reduction in somatic symptoms, and about 70% achieved a minimally important clinical difference. In addition, at post-treatment, there were small to medium reductions (d's from 0.33 to 0.72) in anxiety (GAD-7), depression (PHQ-9), trauma-related symptoms (PCL-5), and functional disability (Sheehan Disability Scale). For all of these secondary outcomes, improvements were slightly to substantially larger at follow-up than at post-treatment (d's from 0.46 to 0.80).Conclusion: I-EAET appears to be a feasible treatment for adults with SSD and centralized symptoms, resulting in substantial and durable improvement not only in somatic symptoms but in other psychiatric symptoms and functioning. Controlled trials are needed determine the effects of I-EAET specifically and how this approach compares to face-to-face EAET and to other internet-delivered treatments, such as cognitive-behavioral interventions. Research should also identify treatment responders and mechanisms of change in EAET.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04122846.

Topical lipoic acid choline ester eye drop for improvement of near visual acuity in subjects with presbyopia: a safety and preliminary efficacy trial

ObjectivesThis study evaluated the safety of topical lipoic acid choline ester (UNR844, 1.5%) ophthalmic solution and its efficacy in improving distance-corrected near visual acuity (DCNVA) in subjects with presbyopia.Subjects and methodsThis was a prospective, randomized, double-masked, and multicentre clinical trial. Subjects with a diagnosis of presbyopia (n = 75) were randomized 2:1 to UNR844 or placebo. On days 1–7, all subjects were dosed unilaterally (twice a day, b.i.d.) in their non-dominant eye to ensure safety and tolerability prior to days 8–91 when dosing was changed to bilateral (b.i.d.). Clinical assessments, including DCNVA and adverse events (AEs), were recorded at each study visit. Patients who completed the study were recruited into a non-interventional follow-up study that monitored them until 7 months after their final UNR844 exposure. The primary endpoints were safety and the mean change in DCNVA from baseline in the study eye.ResultsUNR844 administration (n = 50) produced no safety concerns and was well-tolerated, with no clinically-relevant changes in best-corrected distance visual acuity, pupil size, intraocular pressure, or discontinuations due to adverse events. DCNVA improved in the study eye in the UNR844 group compared to placebo during the 91 days of treatment [UNR844 vs. placebo, mean change in LogMAR (SD); −0.159 (0.120) vs. −0.079 (0.116)]. Bilateral DCNVA improved, with 53.1% UNR844 vs. 21.7% placebo subjects gaining ≥10 letters. Improvements in DCNVA were sustained at 5 and 7 months after UNR844 dosing ceased.ConclusionsThese results support further development of UNR844 ophthalmic solution for the treatment of presbyopia.

A novel decision aid for acute myeloid leukemia: a feasibility and preliminary efficacy trial.

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by a poor prognosis but also a paradoxical possibility of cure. This renders decision-making complex and imminent. Unfortunately, many patients with AML misestimate their prognosis and treatment risk. While decision aids can improve illness understanding and reduce decisional conflict, there are no validated decision aids for AML. We developed and tested a novel AML decision aid (NCT03442452). Patients (n = 20) were recruited at Duke University from May 2018 to February 2019. Participants completed assessments of AML knowledge and decisional conflict, before and after using the electronic decision aid. The primary endpoint was feasibility (endpoint met if > 80% of study participants completed all study components). Secondary analyses of efficacy were conducted using paired t tests for dependent pre-/post-samples. The primary endpoint of feasibility was met (100% of participants completed all study components). Secondary analyses showed improved knowledge and reduced decisional conflict after using the decision aid. Knowledge scores improved from a mean of 11.8 (out of 18) correct items at baseline to 15.1 correct items after using the decision aid (mean difference 3.35; p < 0.0001). Decisional conflict scores reduced significantly from baseline to post-test as well (mean difference - 6.5; p = 0.02). These findings suggest that our AML decision aid is a useful tool to improve the patient experience and promote shared decision-making in AML. A randomized efficacy trial is planned.

Evaluating the feasibility and preliminary efficacy of a Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS): protocol for a feasibility cluster-randomised controlled trial

BackgroundCognitive difficulties experienced by people with multiple sclerosis (MS) impact their quality of life and daily functioning, from childcare and work, to social and self-care activities. Despite the high prevalence of cognitive difficulties seen in MS, there is a lack of developed programmes that target cognition, while also supporting patients by helping them to function well in everyday life. The Cognitive Occupation-Based programme for people with MS (COB-MS) was developed as a holistic, individualised cognitive rehabilitation intervention. It addresses the wide-ranging symptoms and functional difficulties that present in MS, including the ability to maintain employment, social activities, home management and self-care. The aim of the current research is to evaluate the feasibility and preliminary efficacy of COB-MS for people with MS. The focus is on feasibility outcomes as well as functioning associated with cognitive difficulty and secondary outcomes related to cognition, fatigue and quality of life.MethodsOne hundred and twenty people with MS will be assigned to participate in either the COB-MS programme or a treatment as usual, wait-list control group as part of this single-blind, cluster-randomised controlled feasibility and preliminary efficacy trial of the COB-MS programme. The COB-MS group will participate in an eight-session occupational-based cognitive rehabilitation programme over 9 weeks. The primary outcome measure is the goal attainment scaling at 12 weeks. Participants will be assessed pre-intervention, post-intervention and at 12 weeks post-intervention and 6 months post-intervention. Qualitative evaluations of participants’ perspectives will also be examined as part of the feasibility study.DiscussionResults will provide recommendations for a future definitive trial of COB-MS, with respect to both feasibility and preliminary, clinical efficacy. In the event that results indicate efficacy, study findings will suggest that COB-MS requires consideration as a means of enhancing cognitive and daily functioning in people living with MS.Trial registrationISRCTN: ISRCTN11462710. Registered on 9 September 2019.

Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy Trial of BNT411

Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy Trial of BNT411

D-Cycloserine-Augmented Behavior Therapy for Body Dysmorphic Disorder: A Preliminary Efficacy Trial

Cognitive behavioral therapy (CBT) is the leading psychotherapeutic treatment for body dysmorphic disorder (BDD), yet not all patients improve. To address the treatment response gap, CBT may be augmented with cognitive enhancers such as d-cycloserine (DCS). DCS-augmented behavior therapy has been tested with mixed results in related disorders. To initially test whether DCS may augment CBT for BDD, we conducted the first preliminary efficacy trial of DCS versus placebo-augmented CBT for BDD, via a randomized, double-blind study. We analyzed data using mixed-effects models in a modified intent-to-treat sample (N = 26). Over 10 weeks of treatment, primary (BDD severity) and secondary (insight, depression) outcomes improved significantly across both conditions, but there were no significant group differences in response. Exploratory analysis revealed that BDD-related distress, specifically, reduced significantly more in the DCS condition compared to placebo. This is the first study testing DCS-augmented CBT for BDD. Implications, limitations, and future directions are discussed. Trial registry: ClinicalTrials.gov Identifier NCT00842309

Regulatory Dendritic Cell (DCreg) Cell Infusion in Living Donor Liver Transplantation

Background Based on strong preclinical data showing that regulatory dendritic cells (DCreg) of donor origin can promote long-term graft survival in rodents and suppress allograft rejection in non-human primates, we have embarked on a first-in-human phase I/II safety and preliminary efficacy trial of donor-derived DCreg in living donor liver transplantation (LTx). Methods In the study protocol, DCreg are generated from elutriated monocytes isolated from the leukapheresed donor,14-28 days (d) before transplant. The donor-derived DCreg are infused iv (target range 2.5-10.106/kg) 7 d before transplant (d −7), while a half dose of MPA is administered from d −7 to d 0. Standard-of-care immunosuppression (steroid, MPA, tacrolimus) is administered post-LTx, and in those patients that meet eligibility criteria for weaning, immunosuppressive therapy is gradually withdrawn, starting with MPA reduction 6 mths post-LTx. Sequential immunological analyses are conducted on recipient blood and tissue samples to track the donor-derived DCreg, evaluate anti-donor reactivity and examine potential mechanisms of immune hyporesponsiveness. In the first LTx recipient (HLA-B12+) to receive donor-derived (HLA-A3+) DCreg, peripheral blood samples were obtained before and after cell infusion; native liver tissue was obtained at the time of graft implantation. Results Donor-derived DCreg generated for infusion were HLA-DR+, CD1c−, CD11c+, CD83−, IRF4lo and expressed a high programed death ligand-1 (PD-L1):CD86 ratio. In parallel small scale in vitro functional analyses, the DCreg failed to respond to LPS, and induced donor-specific hyporesponsiveness of recipient CD4 and CD8 T cells. The donor-derived DCreg (HLA-A3+) displaying a similar phenotype to that exhibited pre-infusion, were detected in whole blood immediately after completion of the cell infusion that comprised 5.106 DCreg/kg (450.106 total DCreg). No infusion reaction or cytokine release response was observed. Three days post-infusion (d −4), HLA-A3+ donor-derived DC could no longer be detected in blood, although a small population of DC co-expressing both recipient (HLA-B12) and donor MHC (HLA-A3), ie cross-dressed DC, were evident in the circulation. At the time of transplant, before graft implantation, cross-dressed (HLA-A3+B12+) DC could also be detected in non-parenchymal cell populations isolated from the diseased native liver. Using a 14-color panel of mAbs, these tissue-resident cross-dressed DC were PD-L1hi, IRF4lo and Foxp3hi Conclusions After safe infusion of donor-derived DCreg into a prospective living donor LTx recipient, cross-dressed DC were detected in the peripheral blood within a few days and in the native diseased liver at the time of graft implantation. These cross-dressed DC, that appear to have acquired donor MHC from the infused DCreg, exhibit low levels of the DC transcription/maturation factor IRF4 and high levels of PD-L1 and Foxp3, suggesting possible in vivo regulatory function.

Mindfulness-based resilience training to reduce health risk, stress reactivity, and aggression among law enforcement officers: A feasibility and preliminary efficacy trial

The primary objective of this study was to assess feasibility and gather preliminary outcome data on Mindfulness-Based Resilience Training (MBRT) for law enforcement officers. Participants (n = 61) were randomized to either an 8-week MBRT course or a no intervention control group. Self-report and physiological data were collected at baseline, post-training, and three months following intervention completion. Attendance, adherence, post-training participant feedback, and interventionist fidelity to protocol all demonstrated feasibility of MBRT for law enforcement officers. Compared to no intervention controls, MBRT participants experienced greater reductions in salivary cortisol, self-reported aggression, organizational stress, burnout, sleep disturbance, and reported increases in psychological flexibility and non-reactivity at post-training; however, group differences were not maintained at three-month follow-up. This initial randomized trial suggests MBRT is a feasible intervention. Outcome data suggest MBRT targets key physiological, psychological, and health risk factors in law enforcement officers, consistent with the potential to improve officer health and public safety. However, follow-up training or “booster” sessions may be needed to maintain training gains. A fully powered longitudinal randomized trial is warranted.

A pilot trial testing the feasibility of administering D-penicillamine to extremely low birth weight neonates

We enterally administered a 14-day course of 3-mercapto-D-valine (D-penicillamine) to five extremely low birth weight (ELBW) neonates, as a step toward assessing this therapy as a means of reducing the incidence or severity of retinopathy of prematurity (ROP). The study drug (100 mg/ml) was given by nasogastric tube at a dose of 100 mg/k every 8 h for three days, and then 50 mg/k once per day for 11 additional days. Logbooks were maintained by the bedside nurses to record signs of possible immediate intolerance. Laboratory tests assessed hepatic, renal, and hematologic toxicity. ROP was scored according to the ICROP guidelines. Comparisons were with a cohort of 139 consecutive recent neonates of the same birth weight and gestational age range. Five neonates were enrolled in the study, and all received the full course of study drug as planned. Signs of immediate intolerance of the study drug were not observed in any. The study patients did not have a higher incidence, than that of the cohort group, in creatinine elevation, thrombocytopenia, neutropenia, hyperbilirubinemia, or abnormal liver function test. Four of the five had no ROP and one developed transient stage 1, compared with a 54% occurrence of ROP in the cohort. It is feasible to enterally administer a 14-day course of 3-mercapto-D-valine to ELBW neonates and the suspension appears to be well tolerated. These results suggest that phase II safety and preliminary efficacy trials can be undertaken.