Central Institutional Review Board Research Articles

Effect of Losartan on Symptomatic Outpatients with COVID-19: A Randomized Clinical Trial

Background: The SARS-CoV-2 virus enters cells via the ACE2 receptor, disrupting the renin-angiotensin-aldosterone axis, potentially contributing to lung injury. Treatment with angiotensin receptor blockers(ARBs) may mitigate these effects, though induction of ACE2 expression could increase viral entry, replication, and worsen disease. Methods: This study represents a placebo-controlled blinded randomized clinical trial (RCT) to test the efficacy of losartan on outpatients with COVID-19 across three hospital systems in Minnesota, U.S. Participants included symptomatic outpatients with COVID-19 not already taking ACE-inhibitors or ARBs, enrolled within 7 days of symptom onset. Patients were randomized to losartan versus placebo for 10 days. The primary outcome was all-cause hospitalization within 15 days. Secondary outcomes included functional status, dyspnea, temperature, and viral load. Findings: From April-November 2020, 117 participants were randomized 58 to losartan and 59 to placebo. The primary outcome did not differ significantly between the two arms based on Barnard’s test [losartan arm: 3 events (5.2%; 95% CI 1.8-14.1%) versus placebo arm: 1 event (1.7% 95% CI 0.01-9.0%); proportion difference -3.5% (95% CI -12.7-4.5%); p=0.32]. Functional status, self-reported dyspnea, maximum daily temperatures, and viral load were not significantly different between treatment groups. Due to a lower than expected hospitalization rate and low likelihood of a clinically important treatment effect, the trial was terminated early. Interpretation: In this multicenter blinded RCT for outpatients with mild symptomatic COVID-19 disease, losartan did not significantly reduce hospitalizations, affect functional status or assessment of dyspnea. Viral load was not significantly affected by treatment. This study does not support initiation of losartan for low-risk outpatients. Trial Registration: The trial was conducted under the authority of the Food and Drug Administration (IND 148365), was registered on clinicaltrials.gov prior to study initialization (NCT04311177). Funding Statement: This study was supported by Minnesota Partnership for Biotechnology and Medical Genomics (CO00076883) Declaration of Interests: The authors have no financial conflicts of interest to disclose. MAP, MHN, TWS, and CJT have received additional funding from the Bill and Melinda Gates Foundation to conduct a clinical trial of losartan in inpatients with COVID-19. Ethics Approval Statement: The protocol was approved by a central institutional review board and underwent local context review. The study was conducted following good clinical practice guidelines under the oversight of an independent data safety monitoring board (DSMB).

Implementation of the Randomized Embedded Multifactorial Adaptive Platform for COVID-19 (REMAP-COVID) trial in a US health system\u2014lessons learned and recommendations

BackgroundThe Randomized Embedded Multifactorial Adaptive Platform for COVID-19 (REMAP-COVID) trial is a global adaptive platform trial of hospitalized patients with COVID-19. We describe implementation at the first US site, the UPMC health system, and offer recommendations for implementation at other sites.MethodsTo implement REMAP-COVID, we focused on six major areas: engaging leadership, trial embedment, remote consent and enrollment, regulatory compliance, modification of traditional trial management procedures, and alignment with other COVID-19 studies.ResultsWe recommend aligning institutional and trial goals and sharing a vision of REMAP-COVID implementation as groundwork for learning health system development. Embedment of trial procedures into routine care processes, existing institutional structures, and the electronic health record promotes efficiency and integration of clinical care and clinical research. Remote consent and enrollment can be facilitated by engaging bedside providers and leveraging institutional videoconferencing tools. Coordination with the central institutional review board will expedite the approval process. Protocol adherence, adverse event monitoring, and data collection and export can be facilitated by building electronic health record processes, though implementation can start using traditional clinical trial tools. Lastly, establishment of a centralized institutional process optimizes coordination of COVID-19 studies.ConclusionsImplementation of the REMAP-COVID trial within a large US healthcare system is feasible and facilitated by multidisciplinary collaboration. This investment establishes important groundwork for future learning health system endeavors.Trial registrationNCT02735707. Registered on 13 April 2016.

Early Treatment With Nitazoxanide Prevents Worsening of Mild and Moderate COVID-19 and Subsequent Hospitalization

Background: There is an urgent need for treatments to prevent the progression to severe COVID-19 and hospitalization.Methods: This is a double-blind randomized multicenter study in 36 centers in the U.S. and Puerto Rico investigating the potential of a five-day treatment with nitazoxanide 300 mg extended release tablets in 379 outpatients with mild or moderate laboratory-confirmed COVID-19 with an onset of symptoms no more than 72 hours before inclusion. Key objectives were reduction of duration of symptoms, progression to severe illness, hospitalization and viral load.Results: Time to sustained response was not reduced by nitazoxanide (median: 13.28 and 12.35 days for nitazoxanide and placebo). Nitazoxanide treatment provided an 85% reduction in the progression to severe COVID-19 (1/184, [0.5%] nitazoxanide vs. 7/195, [3.6%] placebo). In subjects at high-risk according to CDC criteria, 1/112 (0.9%) of nitazoxanide-treated subjects and 7/126 (5.6%) of placebo-treated subjects experienced progression to severe COVID-19. Treatment led to a 79% reduction in the rate of hospitalization (1/184 [0.5%] nitazoxanide vs. 5/195 [2.6%] placebo). The proportions positive for SARS-CoV-2 RNA and viral load at days 4 and 10 were not reduced. Nitazoxanide was safe and well tolerated.Conclusions: Treatment of mild or moderate COVID-19 with a five-day course of oral nitazoxanide was safe and well tolerated and was associated with an 85% reduction in the progression to severe illness. The availability of a safe, oral, scalable, host-directed antiviral for the early treatment of COVID-19 could play an important role in reducing the number of severe illnesses and hospitalizations during this ongoing major public health crisis.Trial Registration Details: ClinicalTrials.gov Identifier: NCT04486313.Funding Information: This study was funded by the Romark Institute of Medical Research.Declaration of Interests: Jean-Francois Rossignol is an employee of and owns equity interest in Romark, L.C. Matthew Bardin, Jessica Fulgencio and Dena Mogelnicki are employees of Romark, L.C.; Christian Brechot is a senior adviser for Romark, L.C., an adviser for the Theravectys, Shanghai Vivo Biosciences and the chairman of The Healthy Aging company. Ethics Approval Statement: The central institutional review board (IRB) or a local IRB at each center approved the protocol.

Higher Dose Docosahexaenoic Acid Supplementation During Pregnancy and Early Preterm Birth: A Randomised, Double-Blind, Adaptive-Design Superiority Trial

Background: Several meta analyses have concluded n-3 fatty acids, including docosahexaenoic acid (DHA), reduce early preterm birth (<34 weeks), however, the amount of DHA required is unclear. We hypothesized that 1000 mg DHA per day would be superior to 200 mg, the amount in most prenatal supplements. Methods: This randomised, multicentre, double-blind, adaptive-design, superiority trial was conducted in three USA medical centres. Women with singleton pregnancies and 12 to 20 weeks gestation were eligible. Randomisation was generated in SAS® by site in blocks of 4. The planned adaptive design periodically generated allocation ratios favoring the better performing dose. Managing study personnel were blind to treatment until 30 days after the last birth. The primary outcome was early preterm birth by dose and by enrollment DHA status (low/high). Bayesian posterior probabilities (pp) were determined for planned efficacy and safety outcomes using intention-to-treat. Findings: Eleven hundred participants (1000 mg, n=576; 200 mg, n=524) were enrolled between June 8, 2016 and March 13, 2020. 1032 (n=540 and n=492) were included in the primary analyses. The higher dose was superior for prevention of early preterm birth [1.7% (9/540) vs 2.4% (12/492), pp=0.81]. Participants with low enrollment DHA status had half the rate of early preterm birth with 1000 compared to 200 mg [2.0% (5/249) vs 4.1%, (9/219), pp=0.93]. Participants with high enrollment DHA status did not realize a dose effect [1000 mg: 1.4% (4/289); 200 mg: 1.1% (3/271), pp=0.57]. The higher dose was associated with fewer serious adverse events (maternal: chorioamnionitis, premature rupture of membranes and pyelonephritis; neonatal: feeding, genitourinary and neurologic problems, all pp>0.90). Interpretation: Physicians should consider prescribing 1000 mg DHA daily during pregnancy to reduce early preterm birth, particularly in women entering pregnancy with low DHA status. Trial Registration: The study is registered with ClinicalTrials.gov (NCT02626299) and closed to enrollment. Funding Statement: National Institutes of Health Child Health and Human Development (NICHD) R01HD083292. Declaration of Interests: SEC has received honorariums for presentations about DHA in infancy and pregnancy. CJV is an employee of RB Nutrition, which produces infant formulas and supplements, however, RB had no involvement in the study execution or analysis. She conducted this study through her role as an Adjunct Professor at The University of Cincinnati. The other authors have no competing interests. Ethics Approval Statement: The University of Kansas Medical Center granted approval under a central IRB with reliance by the other institutions (STUD3455). All participants gave written consent.

COVID-19 Disease Severity Among People With HIV Infection or Solid Organ Transplant in the United States: A Nationally-Representative, Multicenter, Observational Cohort Study

Background: Individuals with immune dysfunction, including people with HIV (PWH) or solid organ transplant recipients (SOT), might have worse outcomes from COVID-19. We compared odds of COVID-19 outcomes between patients with and without immune dysfunction.Methods: We evaluated data from the National COVID-19 Cohort Collaborative (N3C), a multicenter retrospective cohort of electronic medical record (EMR) data from across the United States, on. 1,446,913 adult patients with laboratory-confirmed SARS-CoV-2 infection. HIV, SOT, comorbidity, and HIV markers were identified from EMR data prior to SARS-CoV-2 infection. COVID-19 disease severity within 45 days of SARS-CoV-2 infection was classified into 5 categories: asymptomatic/mild disease with outpatient care; mild disease with emergency department (ED) visit; moderate disease requiring hospitalization; severe disease requiring ventilation or extracorporeal membrane oxygenation (ECMO); and death. We used multivariable, multinomial logistic regression models to compare odds of COVID-19 outcomes between patients with and without immune dysfunction.Findings: Compared to patients without immune dysfunction, PWH and SOT had a greater likelihood of having ED visits (adjusted odds ratio [aOR]: 1.28, 95% confidence interval [CI] 1.27-1.29; aOR: 2.61, CI: 2.58-2.65, respectively), requiring ventilation or ECMO (aOR: 1.43, CI: 1.43-1.43; aOR: 4.82, CI: 4.78-4.86, respectively), and death (aOR: 1.20, CI: 1.19-1.20; aOR: 3.38, CI: 3.35-3.41, respectively). Associations were independent of sociodemographic and comorbidity burden. Compared to PWH with CD4>500 cells/mm 3 , PWH with CD4Interpretation: Individuals with immune dysfunction have greater risk for severe COVID-19 outcomes. More advanced HIV disease (greater immunosuppression and HIV viremia) was associated with higher odds of severe COVID-19 outcomes. Appropriate prevention and treatment strategies should be investigated to reduce the higher morbidity and mortality associated with COVID-19 among PWH and SOT.Funding Information: NCATS U24 TR002306. ALO was supported by CTSA award No. UL1TR002649 from the National Center for Advancing Translational Sciences. Dr. Gregory Kirk is supported in part by NIAID K24AI118591. Dr. Rena C. Patel’s effort was supported by NIAID of the NIH (K23AI120855). Ms. Andersen received doctoral training support from the National Heart, Lung and Blood Institute Pharmacoepidemiology T32 Training Program (T32HL139426). Dr. Todd Brown is supported in part by NIAID K24AI120834.Declaration of Interests: None to declare. Ethics Approval Statement: The N3C Data Enclave is approved under the authority of the NIH Institutional Review Board (IRB, IRB00249128) with Johns Hopkins University School of Medicine as a central IRB for data transfer. Institutional IRB at each study site approved the study protocol or ceded to this single IRB. The current study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines.

Prevalence and Epidemiological Trends in Mortality Due to COVID-19 in Saudi Arabia

Background: Coronavirus disease of 2019 (COVID-19) created a major public health emergency and an international concern. It is an infectious respiratory illness caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The international mortality rates due to COVID-19 reached 2,748,763 on March 24, 2021. We describe the prevalence, case fatality rate, and epidemiological trends of COVID-19 mortality in Saudi Arabia in this paper.Method: A systematic approach of evaluating COVID-19 related mortalities was established in Saudi Arabia. A scientific committee that evaluated all reported cases with suspicious or confirmed COVID-19 disease using a standardized electronic form. A data registry of all deaths with all clinical parameters was built based on active reporting from all healthcare facilities in Saudi Arabia. Analysis of data using national and regional crude case fatality rate (cCFR) and death per 100,000 population was carried. Descriptive analysis of age, gender, nationality, and comorbidities. Mortality trend was plotted per week and compared to international figures.Results: The total reported number of deaths between March 23rd until April 9, 2021 was 6,737. cCFR was reported as 1.70%, and death per 100,000 population was reported as 19.24 which compared favourably to figures reported by several developed countries. Highest percentages of deaths were among individuals aged between 60-69 years, males (74%), individuals with diabetes (60%), and Hypertension (50%).Conclusion: Case fatality rate and death per 100,000 population in Saudi Arabia is among the lowest in the world due to multiple factors. Several comorbidities have been identified namely diabetes, hypertension, obesity, and cardiac arrhythmias.Funding Statement: This research project was not funded by any commercial or non-commercial organization.Declaration of Interests: The authors of this manuscript have no conflicts of interest.Ethics Approval Statement: This study was approved by the central IRB of the Saudi Ministry ofHealth.

Quantifying Utilitarian Outcomes to Inform Triage Ethics: Simulated Performance of a Ventilator Triage Protocol Under SARS-CoV-2 Pandemic Surge Conditions

Background: Equitable protocols to triage scarce life-saving resources must be specified prior to disasters in order to promote transparency, trust and consistency. The degree to which proposed utilitarian protocols may maximize lives saved is unknown.Methods: We constructed a simulation model based on New York State 2015 guidelines for ventilator triage (NYS) compared to a first-come-first-served (FCFS) method for ventilator allocation under various hypothetical ventilator shortages. We included patients with laboratory confirmed SARs-CoV-2 infection admitted with respiratory failure requiring mechanical ventilation to three acute care hospitals in New York from 3/01/2020 and 5/27/2020. We estimated (1) survival rates, (2) number of excess deaths, (3) number of patients extubated early due to capacity constraints, (4) survival rates among patients not allocated a ventilator at triage or extubated early due to capacity constraints.Findings: 807 patients were included in the study. Survival rates were similar between the NYS and FCFS policies at all the survival probabilities estimated for those triaged to removal of the ventilator. At the lowest ventilator capacity, the NYS policy has an estimated survival of 28.5% (CI: 28.4-28.6), compared to 28.1% (CI: 27.7-28.5) for the FCFS policy. The two policies had similar estimated excess deaths above historical observed deaths.Interpretation: This simulation of a SOFA-based triage protocol for distributing ventilators during the COVID-19 pandemic revealed limitations in achieving the utilitarian goals these protocols are designed to fulfill. Quantifying these outcomes can inform a better balance competing moral aims.Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Albert Einstein College of Medicine/Montefiore Medical Center IRB (IRB # 2020-12128) and the Columbia University IRB (IRB # AAAT4062).

Effects of Intranasal (S)-Ketamine on Veterans With Co-Morbid Treatment-Resistant Depression and PTSD

Objective: Ketamine is a glutamatergic drug with potent and rapid acting effects for the treatment of depression. Little is known about the effectiveness of intranasal (S)-ketamine for treating patients with comorbid depression and PTSD. Methods: We retrospectively analyzed clinical outcomes in 35 patients with both depression and PTSD referred for (S)-ketamine treatments at the VA San Diego Neuromodulation Clinic between Jan 2020 to March 2021. Outcomes were calculated across the first 8 treatments (4 weeks, induction phase) using a repeated measures ANOVA to measure change in symptoms over treatments. In a smaller sub-group (n=19) we analyzed whether (S)-ketamine continued to show effects during the maintenance period (after 4 weeks. Sub-group analyses based on antidepressant response and general linear models were also performed to identify predictors of treatment response. Results: During the induction phase of treatment there was an absolute reduction of 4.6 +/- 0.9 on the patient health questionnaire-9 (PHQ-9) rating scale for depression, from 19.6 +/- 0.8 at treatment 1 to 14.9 +/- 0.9 at treatment 8 (week 4) (F(7,238)=6, p 50%) at treatment 8. There was an absolute reduction of 12.1 +/- 2.5 on the patient checklist 5 (PCL5) rating scale for PTSD, from 54.4 +/- 2 at treatment 1 down to 42.3 +/- 2.5 at treatment 8 (F(7,238)=10.8, p 30%) for PTSD at this time-point. After transitioning to maintenance treatments, depression and PTSD symptoms remained stable or improved. Conclusions: Our results show that (S)-ketamine can improve both depression and PTSD symptoms in Veterans with dual-diagnoses. The effects of (S)-ketamine on PTSD were temporally and individually distinct from those on depression, suggesting potentially different modes of action on the two disorders. This work warrants further research in studying intranasal (S)-ketamine for PTSD. Funding Information: This work was supported by awards from the Department of Veterans Affairs, Veterans Health Administration (Career Development Award: 7IK2BX003308 to D.S.R.), and funding from the Center of Excellence for Stress and Mental Health (CESAMH) at the San Diego VA Medical Center, as well as from the National Institute of Mental Health (K23 MH119375-01 to E.E.L.) Declaration of Interests: None of the authors have any competing interests to declare, financial or otherwise. Ethics Approval Statement: This study was approved as an IRB-exemption by the VA San Diego Medical Center IRB committee.

Increasing HIV Testing and Viral Suppression via Stigma Reduction in a Social Networking Mobile Health Intervention Among Black and Latinx Young Men and Transgender Women Who Have Sex With Men (HealthMpowerment): Protocol for a Randomized Controlled Trial.

BackgroundStigma and discrimination related to sexuality, race, ethnicity, and HIV status negatively impact HIV testing, engagement in care, and consistent viral suppression (VS) among young Black and Latinx men who have sex with men and transgender women who have sex with men (YBLMT). Few interventions address the effects of intersectional stigma among youth living with HIV and those at risk for HIV within the same virtual space.ObjectiveBuilding on the success of the HealthMpowerment (HMP) mobile health (mHealth) intervention (HMP 1.0) and with the input of a youth advisory board, HMP 2.0 is an app-based intervention that promotes user-generated content and social support to reduce intersectional stigma and improve HIV-related outcomes among YBLMT. The primary objective of this study is to test whether participants randomized to HMP 2.0 report improvement in HIV prevention and care continuum outcomes compared with an information-only control arm. We will also explore whether participant engagement, as measured by paradata (data collected as users interact with an mHealth intervention, eg, time spent using the intervention), mediates stigma- and HIV care–related outcomes. Finally, we will assess whether changes in intersectional stigma and improvements in HIV care continuum outcomes vary across different types of social networks formed within the intervention study arms.MethodsWe will enroll 1050 YBLMT aged 15 to 29 years affected by HIV across the United States. Using an HIV-status stratified, randomized trial design, participants will be randomly assigned to 1 of the 3 app-based conditions (information-only app-based control arm, a researcher-created network arm of HMP 2.0, or a peer-referred network arm of HMP 2.0). Behavioral assessments will occur at baseline, 3, 6, 9, and 12 months. For participants living with HIV, self-collected biomarkers (viral load) are scheduled for baseline, 6, and 12 months. For HIV-negative participants, up to 3 HIV self-testing kits will be available during the study period.ResultsResearch activities began in September 2018 and are ongoing. The University of Pennsylvania is the central institutional review board for this study (protocol #829805) with institutional reliance agreements with the University of North Carolina at Chapel Hill, Duke University, and SUNY Downstate Health Sciences University. Study recruitment began on July 20, 2020. A total of 205 participants have been enrolled as of November 20, 2020.ConclusionsAmong a large sample of US-based YBLMT, this study will assess whether HMP 2.0, an app-based intervention designed to ameliorate stigma and its negative sequelae, can increase routine HIV testing among HIV-negative participants and consistent VS among participants living with HIV. If efficacious and brought to scale, this intervention has the potential to significantly impact the disproportionate burden of HIV among YBLMT in the United States.Trial RegistrationClinicalTrials.gov NCT03678181; https://clinicaltrials.gov/ct2/show/study/NCT03678181.International Registered Report Identifier (IRRID)DERR1-10.2196/24043

Predicting severe pneumonia in the emergency department: a global study of the Pediatric Emergency Research Networks (PERN)—study protocol

IntroductionPneumonia is a frequent and costly cause of emergency department (ED) visits and hospitalisations in children. There are no evidence-based, validated tools to assist physicians in management and disposition decisions...

COVD-30. A SNAPSHOT OF THE IMPACT OF COVID-19 ON PATIENTS WITH NERVOUS SYSTEM TUMORS

BACKGROUNDThe impact of COVID-19 on patients with nervous system tumors is not known. This population is often immunosuppressed, susceptible to neurological complications, and requiring of frequent cancer care, all of which may confer vulnerability to poorer outcomes after infection.METHODSClinical data were obtained from structured electronic medical record elements, clinical note text and laboratory RESULTS: Each source was identified, integrated and analyzed using the Palantir Foundry platform (Syntropy), part of the Context Engine Data Management System through the MD Anderson Cancer Center (MDACC) IRB approved D3CODE initiative. The population of interest was patients diagnosed with COVID-19 who had been seen at the Brain and Spine Center for nervous system tumors.RESULTS8,177 ambulatory patients were seen at the Brain and Spine Center from 3/1/20–9/1/20. COVID status was known for 1,753 (21%). Sixty-one (0.7%) were COVID-19 positive. Of these, 17 had primary nervous system tumors. Seven (41%) were treated in the emergency department or hospital for infection. Two were symptomatic but did not require further care. Eight were asymptomatic. Nine (53%) had alterations in cancer management within one week of COVID-19 diagnosis – delayed surgery (3), delayed/interrupted chemotherapy (2), delayed/interrupted radiation (2), cancer treatment discontinued (2). Eight patients (47%) had no clear impact of infection on their cancer treatment, three were on surveillance. Three (18%) unique patients had neurological symptoms attributed to/exacerbated by COVID-19 – encephalopathy (2), seizure (2), stroke (1).CONCLUSIONNo deleterious effects of alterations in cancer management after COVID-19 infection have been identified thus far, though longitudinal follow up is warranted. Our results suggest that COVID-19 infection frequently incurs medical complications or alterations in cancer treatment. The potential impacts of COVID-19 on our vulnerable neuro-oncology patient population should be further explored, and attention to these potential implications for our patients is warranted by treating clinicians.

Hemophilia Natural History Study (ATHN 7): Baseline Characteristics, Adverse Events, and Self-Reported Health Status of Individuals with Hemophilia a and B

Hemophilia Natural History Study (ATHN 7): Baseline Characteristics, Adverse Events, and Self-Reported Health Status of Individuals with Hemophilia a and B

Evaluation of Activation of a NCI National Clinical Trials Network (NCTN) Study S1826 for Hodgkin Lymphoma (HL) at Children's Oncology Group (COG) Institutions

Background: HL is an adolescent and young adult (AYA) cancer that lacks uniform approaches across medical and pediatric oncology. Differences include risk classification, chemotherapy backbone and use of radiation therapy. Heterogeneity in institutional programs and resources for AYAs adds to the gap in understanding why outcomes for AYA HL differ. In order to expedite equitable access to novel agents for AYA patients by medical and pediatric oncology providers, a NCTN facilitated trial for advanced stage HL was launched. The SWOG-led S1826 trial (NCT03907488), open to patients &amp;gt; 12 years of age, was activated in July 2019. We assessed barriers and facilitators to trial activation at COG institutions for this first in-kind approach. Methods: A web-based survey was distributed through the COG communications office to institutional principal investigators (PIs) of 216 institutions in North America. To achieve optimal response rates, the survey was distributed in four waves over a 6-week period. Branching logic differentiated questions for institutions that had opened or planned to open the trial vs. those who did not. Topics included institutional characteristics, joint partnership with medical oncologists to activate AYA trials, and specific barriers for opening this trial. Descriptive statistics were calculated using SAS v.7.1. Results: The response rate was 73% with 158 unique responses among 216 COG institutions queried. Among responding institutions 24% were freestanding children's hospitals; 18% were NCI-designated cancer centers. 55% of respondents indicated a known affiliation with another NCTN cooperative group other than COG. 31% indicated prior experience in participating in a non-COG led NCTN trial for other diseases. 42% of institutions reported a central trials infrastructure for joint pediatric and medical oncology trials. 44% indicated use of the central IRB mechanism, and 4% used a provincial IRB. While 40% had an established AYA oncology program, 30% reported regular lymphoma tumor boards with medical oncology; 8% indicated the ability to see AYA lymphoma patients in a joint pediatric and medical oncology clinic. The trial is open at 79/158 (50%) COG institutions to date and an additional 56 indicated future intent to open the trial. Among 135 COG institutions with open or intent-to-open status, 73% of institutional principal investigator (PI) were pediatric oncologists, 24% were medical oncologists and 4% were joint PIs. PI determination was based on: enrolling as a COG-only site (57%); institutional policy (5%); a discussion among investigators (23%); or other factors (14%). These were categorized as: more resources or anticipated patients in medical oncology (n=4); the trial being opened in medical oncology before pediatrics (n=11); being open in pediatrics before medical oncology (n=2); no interface for joint studies (n=1). Among the 14% of respondents who indicated the trial would not be opened, a competing trial was the reason in 35%. Other reasons included: lack of awareness of the trial, concerns about study design or chemotherapy backbone, lack of easily accessible protocol documents, anticipated lack of accrual, concerns around funding support, challenges with regulatory support, data management, or institutional process for medical and pediatric joint trials. Respondents' recommendations for facilitating activation of AYA intergroup studies include needs for: increased resources and funding; guidance on communication and navigation with medical oncologists for managing joint trials; institutional infrastructure for AYA trials; clearer rationale for a change in the chemotherapy backbone relative to prior COG studies; accessibility and consistency of protocol study naming conventions and protocol documents (i.e. therapy roadmap) on the COG electronic site. Conclusions: Successful implementation of AYA trials is germane to early access to novel agents for younger adolescents. Overall, COG institutions indicate a high level of endorsement for a NCTN AYA trial for HL with 85% indicating activation completed or planned. This survey suggests that AYA trials can be implemented successfully in a network but require education, early communication between pediatric and medical oncologists, and flexible infrastructure for all group participants. (Funding: U10CA180886, U10CA180888, and UG1CA233230) Disclosures Parsons: Seattle Genetics: Consultancy. Herrera:Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding; Merck: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Immune Design: Research Funding; AstraZeneca: Research Funding; Karyopharm: Consultancy; Pharmacyclics: Research Funding. Friedberg:Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Astellas: Consultancy; Kite Pharmaceuticals: Research Funding; Bayer: Consultancy; Seattle Genetics: Research Funding; Roche: Other: Travel expenses; Portola Pharmaceuticals: Consultancy.

Evidence supporting wound care end points relevant to clinical practice and patients' lives. Part 3: The Patient Survey.

The 2006 U.S. Food and Drug Administration Guidance for Industry emphasizes wound closure as the primary outcome for clinical trials in wound healing. Wound care professionals understand that complete wound healing is not always achievable when evaluating new treatments. FDA, Association for the Advancement of Wound Care, and Wound Healing Society are working collaboratively to identify scientifically achievable, clinically relevant, and patient-centered endpoints with sufficient support to serve as primary outcomes for clinical trials. The Opinion Survey from People with Wounds presented here addresses an important but understudied issue: the gap between clinician, healthcare insurance companies, government agencies, and patient perspectives regarding clinically meaningful and scientifically achievable primary endpoints for wound care. The survey, adapted from the clinician survey with adjustment for health literacy, was pilot tested and revised based on a limited number of patients in a single clinic. After central IRB approval, the on-line survey was administered in English and Spanish and submitted anonymously to a server with the cooperation of multiple wound clinics and societies. Four hundred and thirty-eight patients and caregivers from across the United States responded over a 10-month period. Based on this survey, the most valuable clinical endpoints were reduced infection, recurrence, and amputation. The most valuable quality of life outcomes were increased independence, reduced social isolation, and pain. The top five endpoints in terms of usefulness for measuring clinical trial success were time to heal, wound size, infection, recurrence, and pain. Narrative responses from wound patients emphasized the inability to perform activities of daily living and pain as major factors that impacted their daily lives. Engagement of patients in clinical trials and evaluation of potential treatments is critical to improving wound care. This survey provides insight into the needs of patients with wounds and provides a roadmap for structuring future clinical trials to better meet those needs.

International observational atopic dermatitis cohort to follow natural history and treatment course: TARGET-DERM AD study design and rationale

IntroductionAs new topical and systemic treatments become available for atopic dermatitis (AD), there is a need to understand how treatments are being used in routine clinical practice, their comparative effectiveness...

Developing a fidelity measure of early intervention programs for children with neuromotor disorders.

To describe the development of an intervention-specific fidelity measure and its utilization and to determine whether the newly developed Sitting Together and Reaching to Play (START-Play) intervention was implemented as intended. Also, to quantify differences between START-Play and usual early intervention (uEI) services. A fidelity measure for the START-Play intervention was developed for children with neuromotor disorders by: (1) identifying key intervention components, (2) establishing a measurement coding system, and (3) testing the reliability of instrument scores. After establishing acceptable interrater reliability, 103 intervention videos from the START-Play randomized controlled trial were coded and compared between the START-Play and uEI groups to measure five dimensions of START-Play fidelity, including adherence, dosage, quality of intervention, participant responsiveness, and program differentiation. Fifteen fidelity variables out of 17 had good to excellent interrater reliability evidence with intraclass correlation coefficients (ICCs) ranging from 0.77 to 0.95. The START-Play therapists met the criteria for acceptable fidelity of the intervention (rates of START-Play key component use ≥0.8; quality ratings ≥3 [on a scale of 1-4]). The START-Play and uEI groups differed significantly in rates of START-Play key component use and quality ratings. The START-Play fidelity measure successfully quantified key components of the START-Play intervention, serving to differentiate START-Play from uEI.

INITIAL EVALUATION OF SAFETY AND EFFICACY OF ADMINISTRATION OF ESTRADIOL (E2) BY SUBCUTANEOUS (SC) INJECTIONS TO MALE-TO-FEMALE (MTF) TRANSGENDER PATIENTS

The primary aim of this study was to determine if SC injection of E2 valerate could produce serum E2 levels within our clinic’s target therapeutic range for MTF patients (75-200 pg/mL) without causing significant adverse effects. Secondary aims were to assess: 1) if SC E2 can suppress serum total testosterone (T) levels (<50 ng/dL) as effectively as oral (PO) E2 , 2) if SC administration has less of a hepatic effect than PO, 3) if serum E2 levels remain within the target range between weekly injections and 4) if SC E2 is acceptable to patients. Retrospective chart review of MTF patients treated in Maine Medical Center Reproductive Endocrinology clinic. All charts of MTF patients seen from 2011-2020 were reviewed. Patients were allowed to choose PO, SC or transdermal (TD) administration. Inclusion criteria were age 18-79 years, PO or SC E2 therapy, and serum E2 and T levels measured by LabCorp (Calabasas CA). E2 valerate was injected SC using a 5/8’ 25g needle. 17β-E2 was administered orally. Serum E2, T, estrone (E1), and sex hormone binding globulin (SHBG) levels and fasting lipid panels were measured in SC and PO patients and values compared by Mann Whitney U test. Peak and nadir serum E2 concentrations were measured in a subgroup of SC patients. Serum sex steroid concentrations were measured by liquid chromatography/mass spectrometry. Local and systemic adverse effects were assessed by history and physical exam. The study was approved by the Maine Medical Center IRB. 102 charts were reviewed. Of 65 patients who were offered PO, TD or SC therapy (the SC option became available in May 2017), 23 choose SC. 61 patients were included in the final analysis, 23 in the SC group and 38 in the PO group. Median dose of E2 for the PO group was 4 mg/day [full range=1-12]; for SC E2 it was 4 mg/week [full range=2-6]. For the SC and PO groups the median E2 were 155.5 [75-291] (n=18) and 122 [76-208] pg/mL (n=38) respectively. Median and range of serum T levels in the SC and PO groups were 16 [4.5-82] (n=14) and 13 [4.8-515] (n=38) ng/dL respectively. E1 serum levels in the SC and PO groups were 49.0 [31.0-104.0] (n=10) and 495 [198-926] (n=12) pg/mL (p=0.003). SHBG and lipid levels did not vary significantly between the two groups (not shown). In a subgroup of SC patients, the median serum E2 decreased from 212 [158-245] to 112 [87-150] pg/mL from the day after to the day before an injection (n=12). 22/23 patients in the SC group chose to continue this method, 0/23 patients experienced a systemic reaction and 1/23 experienced a local site reaction. These preliminary data suggest that SC E2 injection is a safe and effective option for administration of E2 that appears to be well accepted by patients. It is well absorbed with minimal adverse effects and suppresses serum T levels as effectively as PO E2. SC E2 has less hepatic effect as reflected by serum E1 levels (but not SHBG or lipids in this small sample size). Serum E2 levels decrease between weekly injections and additional studies are required to refine dosing to maintain E2 values within the target range. Additional pharmacodynamic studies are also indicated.

Outcomes After Transcatheter Reintervention for Dysfunction of a Previously Implanted Transcatheter Pulmonary Valve

ObjectivesThe aim of this analysis was to evaluate outcomes following transcatheter reintervention for degenerated transcatheter pulmonary valves (TPVs). BackgroundTPV replacement (TPVR) with the Melody valve demonstrated sustained relief of right ventricular outflow tract (RVOT) obstruction and pulmonary regurgitation. MethodsAll patients who underwent TPVR with a Melody valve as part of 3 Medtronic-sponsored prospective multicenter studies were included. Transcatheter reinterventions included balloon dilation of the previously implanted Melody valve, placement of a bare-metal stent within the implanted TPV, or placement of a new TPV in the RVOT (TPV-in-TPV). Indications for reintervention, decisions to reintervene, and the method of reintervention were at physician discretion. All patients provided written informed consent to participate in the trials, and each trial was approved by local or central Institutional Review Boards or ethics committees at participating sites. ResultsA total of 309 patients who underwent TPVR were discharged from the implantation hospitalization with Melody valves in place. Transcatheter reintervention on the TPV was performed in 46 patients. The first transcatheter reintervention consisted of TPV-in-TPV in 28 patients (median 6.9 years [quartile 1 to quartile 3: 5.2 to 7.8 years] after TPVR), simple balloon dilation of the implanted Melody valve in 17 (median 4.9 years [quartile 1 to quartile 3: 4.0 to 6.0 years] after TPVR), and bare-metal stent placement alone in 1 (4.4 years after TPVR). There were no major procedural complications. Overall, 4-year freedom from explant and from any later RVOT reintervention after the first reintervention were 83% and 60%, respectively. Freedom from repeat RVOT reintervention was longer in patients undergoing TPV-in-TPV than balloon dilation (71% vs. 46% at 4 years; p = 0.027). ConclusionsTPV-in-TPV can be an effective and durable treatment for Melody valve dysfunction. Although balloon dilation of the Melody valve was also acutely effective at reducing RVOT obstruction, the durability of this therapy was limited in this cohort compared with TPV-in-TPV.

Carpal Tunnel Syndrome in Military Aviators.

The incidence of carpal tunnel syndrome (CTS) is increased in occupations exposed to repetitive motion, poor wrist posture, and vibration exposure. While all pilots are exposed to these factors, helicopter pilots are especially exposed to vibration. The study is to identify the incidence and risk factors for CTS in military aviators. Clearance was obtained from Tripler Army Medical Center IRB. The Defense Medical Epidemiological Database was queried for all new cases of CTS from 2006 to 2015. Incidence rates (IRs) were determined for helicopter pilots, fixed-wing pilots, and nonpilot officers. Poisson regression analysis was used to calculate adjusted IR in order to control for demographic factors. Race was also taken into account, where pilots would classify themselves into a white or non-white race, defined by each individual. Race was assessed in the study to see if there were any differences in IR of CTS between white and non-white pilots. We identified 7,398 new cases of CTS among 2,319,352 person-years within the study period. Increasing age, female gender, and non-white race were significantly correlated with higher IR. Fixed-wing pilots demonstrated significantly lower adjusted IR than nonpilot officers in each age group. Helicopter pilots demonstrated higher IR than fixed-wing pilots in each age group. Helicopter pilots had lower incidence of CTS early in their career compared to nonpilot officers, but by age 40+, their IR ratio was significantly higher (1.21). Analysis of the database indicates that fixed-wing pilot status is a protective factor against development of CTS among U.S. military officers. In contrast, helicopter pilots were found to be at an increased rate of CTS than their fixed-wing counterparts. Their incidence is comparable to their nonpilot officer peers early in their career, but is significantly increased at the senior level. Increasing age and female gender are risk factors in the military officer population as expected. Non-white race was found to increase risk in the military population, in contrast to reports of the civilian population.

National Institutes of Health StrokeNet During the Time of COVID-19 and Beyond.

National Institutes of Health StrokeNet During the Time of COVID-19 and Beyond.