Anti-IL17A, Ixekizumab, for treatment-resistant chronic venous leg ulcers: A phase II randomized, double-blind, placebo-controlled pilot trial

Chronic venous leg ulcers cause significant morbidity in patients and the majority reoccur after resolution. The current standard of care, double layer compression, is not effective in all patients. Interleukin 17A (IL17) antagonist therapy has been shown to promote healing in murine models of chronic wounds. This has not previously been explored in humans. Therefore, we aim to undertake a phase II randomized, double-blinded, placebo-controlled pilot trial to assess whether Ixekizumab, an anti-IL17A therapy, is effective at reducing chronic venous ulcer size. In addition, to determine the feasibility and safety of undertaking a randomized control trial. Patients with a venous leg ulcer not responsive to 4 weeks of compression therapy were recruited. Participant were randomized to receive either Ixekizumab (80mg) or placebo injected subcutaneously every fortnight for 12 weeks while continuing standard of care. From 30 eligible, 4 patients consented, were enrolled and randomized. Initially, COVID-19 risk, medical history and distance from recruiting site were the main causes of exclusion or refusal to participate. All participants completed the 12-week treatment period. At completion, two participants in the Ixekizumab group reduced by >40% and one completely resolved their ulcer. Ulcers in the Ixekizumab group reduced by an average size of 955mm2 to 529mm2at baseline to final review respectively (p-value 0.12). The placebo group reduced in size by <5%.There were no adverse events related to the intervention. This pilot clinical trial investigated a novel treatment for chronic venous ulcers and showed IL17 inhibition does not impede and may improve chronic wound healing. It also showed a lack of major safety issues in using anti-IL17A therapy in this population. Moreover, the findings reinforce the feasibility of a larger trial to more accurately evaluate anti-inflammatory strategies in chronic wounds.Copyright © 2023

Healthcare Providers as Cultural Guests of Patients and Their Loved Ones During the Dual Pandemic of COVID-19 and Racism: Establishing Trust in the ICU (Sci233)

Outcomes: 1. Learners will identify cultural barriers to the establishment of trust between patients' loved ones and the healthcare provider team and integrate methods to reduce cultural barriers. 2. Through this presentation healthcare providers will strengthen ability to understand how to be a cultural guest of patients, and their loved ones, in healthcare settings. In the stressful environment of the intensive care unit (ICU), cultural differences between healthcare providers and patients' loved ones can prevent the establishment of trust. Healthcare providers can address this barrier by respecting cultural practices utilized as comfort mechanisms by patients and their loved ones. The objective of this research is to determine how healthcare providers can be genuine cultural guests of patients and their loved ones in the ICU setting. We employed a qualitative descriptive design with 22 family caregivers. Semi-structured, audio-recorded phone interviews were conducted between February 2021 and October 2021, with caregivers whose family member had been in the ICU between May 2019 and August 2020. The sample included a majority of female (87%), Black (53%) caregivers with an average age of 53. The research team employed a conventional and directed qualitative content analysis to code transcribed interviews, followed by the development of a formative categorization matrix, and theoretical labeling of the main categories and subcategories. We identify four pillars that facilitate the cultural guest mindset: form genuine connection, build trust, establish expectations, and respect culture. The formation of genuine connection entails healthcare provider investment, specifically by keeping the patient's family regularly updated on the patient's condition. Building trust also necessitates that healthcare providers engage in frequent open communication with the family, while avoiding the use of complex medical jargon. Establishing expectations requires healthcare providers to assess the culture of patients and their loved ones in order to understand how to best support the family's needs. Finally, respect of cultural practices can foster a sense of collaboration with patients and their families, who may feel that the healthcare providers are on an opposing team. Implementing these practices, healthcare providers can provide medical services in a way that complement patients' culture, enhancing the patient and caregivers' ICU experience.Copyright © 2023

Milrinone-induced platelet inhibition in patients supported on veno-aterial extracorporal membrane oxygenation: a case series

Case Report: Purpose: Milrinone is an inodilator that is used in the treatment of cardiogenic dysfunction and shock. It causes increased cardiac output by stimulating myocardial contractility, enhancing cardiac relaxation, and reducing afterload via phosphodiesterase III inhibition, preventing cyclic adenosine monophosphate (cAMP) degradation. Increased cAMP concentrations are known to inhibit platelet aggregation. Veno-arterial-extracorporeal membrane oxygenation (VA-ECMO) is an extracorporeal treatment option for inotrope-refractory cardiogenic shock and is often used in conjunction with inodilators. Often, patients supported on ECMO require systemic anticoagulation to prevent clotting complications. Therefore, thromboelastography (TEG) with platelet mapping is used to help gauge a patient's clotting status and gives clinicians information about the degree of platelet inhibition present. We present the case of two patients, both supported on VA-ECMO, who developed platelet inhibition with clinically significant bleeding while on milrinone, requiring the cessation of the milrinone infusion. Cases: First, we present an adult female in her fourth decade of life who required VA-ECMO for Covid-19 ARDS and cardiogenic shock. TEG platelet mapping was obtained for clinically significant bleeding from her trachea and gastrointestinal tract. Ten days after starting milrinone, adenosine-5'-diphosphate (ADP) inhibition was elevated at 67.4% and arachidonic acid (AA) inhibition normal at 1.8%. Twenty days after starting milrinone, ADP inhibition was 93.3% and AA inhibition was 76.4%. Milrinone discontinued and repeat TEG platelet mapping (10 days after discontinuation) showed ADP inhibition of 76.8% and AA inhibition of 0%. Her lowest ADP inhibition was 41.9%, approximately 1 month after milrinone discontinuation. Milrinone again attempted and ADP inhibition was 87.9% and AA inhibition 89.2% within 24 hours of initiation. No data available for platelet inhibition prior to starting milrinone. Next, we present a 9 year old female with acute myeloid leukemia who required VA-ECMO for septic shock. Initial TEG platelet mapping, obtained 2 days after milrinone initiation, showed ADP inhibition of 43.6% and AA inhibition of 98.7%. Two days after discontinuation of milrinone, her ADP inhibition was 19.6% but AA inhibition remained elevated at 91.9%. However, after 4 days off milrinone, her ADP inhibition was normal at 15.5% and AA inhibition mildly elevated at 33.6%. No data available for platelet inhibition prior to starting milrinone. Conclusion(s): Milrinone is a known platelet inhibitor due to increased intracellular cAMP concentrations. For patients on ECMO and milrinone, care should be given to the degree of platelet inhibition and potential risk of clinically significant bleeding. Further studies are needed to further investigate the correlation between milrinone, platelet inhibition, and clinically significant bleeding in ECMO patients. Copyright © 2023 Southern Society for Clinical Investigation.

TOWARD AN AUDIENCE-CENTERED APPROACH: Rhetorical Analysis of University Crisis Communication Emails

Responding to the COVID-19 pandemic, colleges around the country alerted their student bodies about evolving protocols through email messages. Despite the need for clarity and precision, these messages were often poorly optimized, enacting blame and prompting further confusion for students. In this chapter, we present a rhetorical analysis of one such email message, providing practical solutions for the writing, design, and usability of important communications from university administrators. The learning objective for this chapter is to begin the work of interrogating institutional crisis communication and responding to a case sample that lacked consideration for the embodied realities of student audiences, followed by discussion questions and assignments that continue this work. © 2022 Taylor and Francis.

A Self-Guided App-Based Adaptive Coping Skills Training Intervention for Patients with Cardiorespiratory Failure: The Blueprint Pilot RCT

Rationale: Cardiorespiratory diseases are common causes of persistent psychological distress symptoms. To fill this gap, we developed Blueprint, a month-long mobile app-based adaptive coping skills training intervention based on lessons learned about intervention delivery and population targeting from a multicenter RCT of a hybrid telephone- and web-based intervention (Figure). However, Blueprint requires further testing before broader use. Methods: The objectives were to (1) Optimize the usability of the new Blueprint system by incorporation of features based on lessons learned and (2) Test two Blueprint iterations vs. usual care in a pilot 3-arm RCT with 3-month follow up among a targeted sample of 45 patients. Usability was assessed using the Systems Usability Scale (SUS). The two Blueprint iterations differed by their response to weekly changes in Hospital Anxiety and Depression Scale (HADS) scores within the app (app-based response with additional digital content vs. therapist response). The key inclusion criterion was hospitalization in an ICU or stepdown unit with a need for cardiorespiratory support (e.g., ventilation, vasopressors) plus a HADS total score ≥8 just after arrival home. Method of minimization was used to balance across strata (ICU service, baseline HADS, age). The 1-month HADS score was the primary outcome, with secondary outcomes at 1 and 3 months including HADS, Post-Traumatic Stress Scale (PTSS), and physical symptoms (PHQ-10) Results: Usability testing was performed among 5 patients asked to perform core tasks in the Blueprint app. The mean (SD) SUS score was 83.5 (9.5), exceeding the benchmark target of 80. Subsequently, the RCT was initiated. A total of 1,133 were screened, 416 (37%) appeared to be eligible, 229 (55%) were approached, 65 (28%) consented, and 45 (69%) randomized in a 1:1:1 ratio by group. A total of 19 (29%) were excluded post-consent for low baseline HADS scores. To date, 25 have completed the trial and 20 are still active in the protocol. The relatively high refusal rate reflects the conduct of the RCT by the study team completely by distance via telephone and SMS texting (including screening and consenting) during the COVID pandemic. Conclusion: We successfully transformed an adaptive coping skills intervention into a highly usable, fully self-guided, mobile app-based version called Blueprint that delivers content responsive to weekly changes in psychological distress symptoms. We reached the target sample size and follow-up for the RCT continues. We anticipate completion by January 2022 with full results ready for presentation by the time of ATS 2022.

Mobile Mindfulness Intervention to Reduce Emotional Distress and Burnout in Frontline Healthcare Workers: The LIFT-HCW Pilot RCT

Background: The COVID-19 pandemic has led to extremely high levels of emotional distress and burnout amongst frontline healthcare workers. Rapidly deployable and scalable interventions are desperately needed to help combat the burgeoning mental health crisis among frontline healthcare works. Methods: We designed a prospective, randomized, waitlist-controlled pilot study assessing the impact of a mobile mindfulness app (LIFT) among nurses working in COVID-19 units. Participants were randomized in a 2:1 fashion to receive access to mobile mindfulness content (intervention) or to a waitlist to receive access to mobile mindfulness content outside the study period (control). All patients completed a survey that includes the Patient Health Questionairre-9 (PHQ-9), The General Anxiety Disorder-7 (GAD-7), the Perceived Stress Scale-4 (PSS-4), and the Maslach Burnout Index (MBI) at baseline (T1) and at the end of the study period (28 days after enrollment, T2). Primary outcomes are feasibility as assessed by the number of participants completing all 4 weeks of mindfulness therapy as well as the total number of daily mindfulness sessions completed. Secondary outcomes included change in PHQ-9, GAD-7, PSS-4, and MBI scores from T1 to T2. Results: Enrollment began in May of 2021. To date 82 participants have been enrolled and randomized, 56 to intervention and 24 to waitlist, with a target enrollment of 100. Median PHQ-9 scores in each group were 8 (IQR 6-11.25) and 7 (IQR 5-10) indicating moderate amounts of emotional distress in each group. Enrollment and follow-up are ongoing, with enrollment planned to be completed in December 2021. Conclusions: We have successfully enrolled 82 participants in an ongoing randomized, waitlist-controlled trial testing the clinical impact of a mobile mindfulness intervention on emotional distress and burnout in frontline healthcare workers. Final results will be presented at ATS International Meeting.

COVID-19 ARDS with Concurrent Methicillin-Sensitive Staphylococcus aureus Bacterial Infection Requiring Extracorporeal Membrane Oxygenation

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes the disease entity COVID- 19. Initially, reports showed children had generally mild disease, with few requiring hospitalization. However, as of December 2021 in Arkansas, USA, children and young adults aged 24 years and younger accounted for approximately 166,000 cases with over 1,800 hospitalizations and 27 deaths (3 deaths under age 17). Comparatively, there have been over 6 million cases nationally in children and young adults, with over 1,000 deaths. Bacterial, viral, and fungal co-infections are known complications of viral respiratory illnesses that can lead to increased mortality. There have been multiple reports in adults on the incidence and type of co-infections seen with COVID-19, but few in pediatric patients. Adult data shows that co-infections are present in approximately 13-45% of patients with COVID-19, most commonly with bacterial pathogens of Mycoplasma pneumoniae and Haemophilus influenzae. Methods: We describe four patients with acute SARS-CoV-2 infection, requiring intubation, mechanical ventilation, and extracorporeal membrane oxygenation (ECMO), all of whom had methicillin-sensitive Staphylococcus aureus(MSSA) infections discovered within 24 hours of escalating respiratory support. This case series was determined as exempt by the Institutional Review Board at our institution. Results: Our cohort includes 4 patients with a median age of 18 years (range 16-19 years), all of whom required ECMO for acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 pneumonia. The median time from intubation to ECMO cannulation was 139 hours (range 3-319 hours). All patients received targeted COVID-19 therapy with dexamethasone, remdesivir, and either tociluzimab or baricitinib during their hospitalization. These patient also all had culture positive MSSA infections from blood and mini-BAL cultures. Three of the four patients had a positive culture within 24 hours of requiring ECMO and one patient had a positive culture within 24 hours of requiring intubation. All of the patients were initially placed on venovenous (V-V) ECMO and three (75%) later required transition to venoarterial venous (VA-V) ECMO for worsening hemodynamics. All were initially cannulated with dual site femoral-internal jugular configuration. Femoral arterial cannulas were used for the transition to VA-V. Complications encountered during ECMO for these patients included GI bleeding (n=1), atrial flutter requiring cardioversion (n=1), lower extremity compartment syndrome (n=1), and dislodgement of a venous ECMO cannula (n=1). One patient received a tracheostomy while on ECMO. The median ECMO duration was 19.35 days (range 11-48.5 days). All patients were successfully decannulated from ECMO and all were discharged from the hospital alive, except one who is still requiring inpatient rehabilitation services. Discussion: We describe 4 pediatric patients with acute SARS-CoV-2 respiratory infections who were found to have MSSA co-infection within 24 hours of escalating respiratory support, all of whom eventually required ECMO support. In a recently published study, Pickens, et al reported that 25% of recently intubated adult COVID-19 patients have a bacterial co-infection. Limited data is available in pediatric patients. Staphylococcus aureus infections are among the most common bacterial infections worldwide. They are responsible for over 100,000 infections in the United States each year and lead to increased morbidity and mortality. All of our patients received immunemodulating therapies with either tociluzimab or baricitinib, which carry the risk of secondary infections due to immunosuppressive effects. Clinicians should maintain a high index of suspicion and be aware of the possibility of secondary bacterial infections in COVID- 19 patients, especially in those treated with immune-modulators. MSSA co-infection can lead to increased morbidity and mortality in patients with SARS-CoV-2, as seen in our cohort. More investigation s needed to further describe co-infections in patients with COVID- 19 and to identify risk factors for the development of co-infections.

Adherence to inhaled corticosteroids in asthma (ARICA): A randomized controlled pilot study

Background: ARICA (AdheRence to Inhaled Corticosteroids in Asthma) is a comprehensive inhaled corticosteroid (ICS) adherence intervention designed to remediate each patient's unique reason for not taking their ICS as prescribed. Objective: The primary objective was to evaluate the feasibility and acceptability of implementing ARICA in a health system. Methods: 29 Black adults who self-reported ICS nonadherence, had uncontrolled persistent asthma, and a Duke Primary Care provider visit within the past 3 years were randomly assigned to intervention (N=15) or control (N=14) in a waitlist randomized controlled pilot trial. Participants were assigned to 1-3 ARICA components based on adherence barriers selected by participants;including, an asthma selfmanagement program, financial assistance referral program, and/or objective feedback on asthma control. All participants received weekly texts and emails dispelling asthma myths. Activities were delivered virtually due to COVID-19. Primary outcomes were feasibility (e.g., process outcomes) and acceptability (e.g., patient exit interviews) measured at 12 weeks. Secondary asthma (e.g., ACT) and adherence outcomes (e.g., DOSEnonadherence) were measured. Results: Most participants were female (N=27, 93%), nonsmokers (N=26, 70%), poorly controlled with ACT <15 (N=14, 48%), and mean age 49.8. Most (N=14, 93%) completed all assigned intervention components and reported mean 4.8 of 5 on Weiner feasibility, acceptability, and appropriateness of intervention. The intervention group had a greater and statistically significant improvement in ACT (Δ-3.5, CI 6.0,0.96) and Marks AQLQ (Δ 11.5, CI 5.5,17.4) when compared to changes in the control ACT (Δ-2.5, CI-5.2,0.05) and Marks AQLQ (Δ5.7, CI-1.3,12.8), respectively. The improvement in ACT in the intervention group was clinically significant. The intervention group also reported a greater and statistically significant decrease in degree of nonadherence (DOSE Δ 0.74, CI 0.2,1.3) than control (DOSE Δ 0.36, CI-0.04,0.75) and a greater decrease in the number of adherence barriers identified in the intervention group (Δ 2.1, CI 1.2,3.0) versus control group (Δ1.6, CI 0.3,3.0). The study was not powered to assess a statistically significant change between groups. Conclusion: The implementation of ARICA in a cohort of Black adults was feasibly deployed in a health system and acceptable to participants. There was a trend in improvement in asthma control and asthma quality of life and a decrease in nonadherence and barriers to adherence.

Addressing anti-semitism in social work education

Antisemitism, one of the oldest forms of prejudice and oppression is surging throughout the world. It ranges from verbal abuse to the destruction of property to murder. In the last two years, attacks against Jews in the United States were the overwhelming target of religion-based hate crimes. Stereotypes and myths continue to fuel prejudice and antisemitism in society. Factors such as anti-Israel sentiments, remarks by persons in power, the use of social media, white nationalism, and even the Covid 19 pandemic have contributed to its escalation.As a result of the increasing violence, the U.S. legislature held a hearing on confronting antisemitic terrorism with one outcome being that social workers and community advocates were needed to join law enforcement in the effort to heal and work for justice. Social work with its mandate to promote social justice and human rights and challenge oppression cannot ignore antisemitism and its impact on individuals and societies. However, the subject is basically ignored in the curriculum. This paper offers a brief history of antisemitism and presents guidelines and models for integrating it into social work programs. © 2021 Taylor & Francis.