PD13-08 Phase 1 TROPION-PanTumor01 Study Evaluating Datopotamab Deruxtecan (Dato-DXd) in Unresectable or Metastatic Hormone Receptor-Positive/HER2-Negative Breast Cancer (BC)

Background: Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate (ADC) consisting of a humanized anti-TROP2 IgG1 monoclonal antibody covalently linked to a highly potent topoisomerase I (Topo I) inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. Dato-DXd demonstrated compelling single-agent antitumor activity in heavily pretreated patients (pts) with metastatic triple-negative BC (Krop, SABCS 2021). This is the first report of results from the TROPION-PanTumor01 study in pts with unresectable or metastatic hormone receptor- positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-;including HER2-low and HER2-zero) BC. Method(s): TROPION-PanTumor01 (NCT03401385) is a phase 1, multicenter, open-label, 2-part doseescalation/expansion study evaluating Dato-DXd in previously treated pts with solid tumors. Based on previous clinical findings and exposure-response results from pts with NSCLC, Dato-DXd 6 mg/kg IV Q3W is being evaluated in pts with unresectable or metastatic HR+/HER2- BC that progressed on standard therapies. The primary objectives were safety and tolerability. Tumor responses, including ORR (complete response [CR] + partial response [PR]) and DCR (CR + PR + stable disease [SD]), were assessed per RECIST version 1.1 by blinded independent central review. Result(s): As of the April 29, 2022, data cutoff, 41 pts had received Dato-DXd (median follow-up, 10.9 mo [range, 7-13]);9 pts were ongoing. The primary cause of treatment discontinuation was disease progression (63% progressive disease [PD] or clinical progression). Median age was 57 y (range, 33- 75);54% had de novo metastatic disease. Pts were heavily pretreated (Table) with a median of 5 (range, 3-10) prior regimens in the advanced setting;95% had prior CDK4/6i (adjuvant/metastatic). Median time from initial treatment for metastatic disease to the first dose of Dato-DXd was 42.7 mo (range, 10.2-131.1). Treatment-emergent adverse events (TEAEs;all cause) were observed in 98% (any grade) and 41% (grade >=3) of pts. Most common TEAEs (any grade, grade >=3) were stomatitis (80%, 10%), nausea (56%, 0%), fatigue (46%, 2%), and alopecia (37%, 0%). Serious TEAEs were observed in 6 pts (15%);1 pt died due to dyspnea, which was not considered to be treatment related. Dose reductions occurred in 5 pts due to stomatitis (n=3), fatigue (n=2), keratitis (n=1), and decreased appetite (n=1) (>1 AE per pt);14 pts had treatment delayed due to stomatitis (n=8), retinopathy (n=1), dysphagia (n=1), fatigue (n=1), malaise (n=1), COVID-19 (n=1), cellulitis (n=1), urinary tract infection (n=1), decreased lymphocyte count (n=1), and nasal congestion (n=1;>1 AE per pt). Three pts discontinued treatment due to keratitis (n=1) and pneumonitis (n=2);1 case of pneumonitis was adjudicated as grade 2 drug-related interstitial lung disease. The ORR was 29% (11 confirmed PRs;1 pending confirmation), the DCR was 85% (35/41), and the clinical benefit rate (CR + PR + SD >=6 mo) was 41% (17/41). Conclusion(s): Dato-DXd demonstrated a manageable safety profile and encouraging antitumor activity, with high disease control in heavily pretreated pts, the majority having received prior CDK4/6i. Based on these findings, the TROPION-Breast01 (NCT05104866) randomized phase 3 study comparing 2L+ Dato-DXd vs investigator's choice chemotherapy is currently enrolling pts with HR+/HER2- BC.

Digital mental health interventions for obsessive compulsive and related disorders: A brief review of evidence-based interventions and future directions

Individuals with obsessive compulsive and related disorders (OCRDs), including obsessive compulsive disorder (OCD), body dysmorphic disorder (BDD), trichotillomania (hair-pulling disorder), excoriation (skin-picking) disorder, and hoarding disorder, suffer from distressing or impairing obsessive preoccupation and/or time-consuming compulsive behaviors. OCRDs are often severe, chronic, and associated with significant psychiatric comorbidity and functional impairment. Cognitive behavioral therapy (CBT) has been shown to be efficacious for all the OCRDs. However, most individuals with an OCRD do not receive CBT, and of those who do, not all respond or respond fully to treatment. The COVID-19 pandemic has deepened the chasm between those who need mental health care and access to clinical services. Digital mental health interventions (DMHIs) have emerged over the past two decades as a solution to the access to care gap, and acceptance of digital solutions was catalyzed by the pandemic. DMHIs have the potential to address unmet mental health needs by offering scalable, low-stigma, cost-effective solutions. This paper reviews current evidence-based DMHIs for OCRDs and describes areas for future research.

RAPIDLY PROGRESSIVE PERIMYOCARDITIS IN SARS-COV-2 INFECTION

SESSION TITLE: Extraordinary Cardiovascular Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: The COVID-19 pandemic has resulted in millions of deaths worldwide. Many cases involved a primary pulmonary process, yet myocarditis associated with COVID-19 has been observed.1 We present a novel case of rapidly progressive fulminant peri-myocarditis with minimal lung involvement in acute COVID-19 infection. CASE PRESENTATION: A 39-year-old female with no medical history presented with chest pain and dyspnea with an acute COVID-19 infection. She had a brief cardiac arrest with rapid ROSC and no intubation. Chest CT angiogram showed essentially normal pulmonary parenchyma and moderate pericardial effusion. EKG showed sinus tachycardia with global ST segment elevation. An echocardiogram showed an ejection fraction (EF) of 25% with a moderate sized pericardial effusion and right ventricle collapse. She was transferred for emergent drainage of the effusion to our institution. Her circulatory shock initially improved following pericardial drainage, yet she declined warranting increasing vasopressor and inotropic support. An emergent echo showed an EF of less than 10% and no re-accumulation of pericardial fluid. It was clear that the patient required mechanical circulatory support (MCS) and was transferred to the catheterization lab. While in the lab, the patient suffered cardiac arrest and an Impella device was placed during prolonged ACLS without achieving ROSC. Venoarterial ECMO cannulation was then performed. She was transferred to a cardiac transplant center where she later developed multi-organ failure leading to death. DISCUSSION: While COVID-19 has been shown to affect multiple organs apart from the lungs, this case was notable due to minimal pulmonary involvement. The patient's manifestation of her infection was almost entirely cardiac in nature. MCS was discussed in the catheterization lab at the time of pericardial drain insertion. The decision was made to not pursue MCS as the patient's shock had improved. Additionally, the patient did not undergo pulmonary arterial catheter (PAC) placement. Prompt placement of a PAC has been associated with early access to MCS and reduced in-hospital mortality.2 Perhaps we would have obtained MCS earlier if PAC data supported this intervention before the patient deteriorated. It will be important to consider primary cardiac manifestations of COVID-19 infection and early consideration of invasive hemodynamic monitoring to identify a need for timely MCS. CONCLUSIONS: We present the first reported case of fulminant peri-myocarditis in the absence of acute hypoxemic respiratory failure or radiographic pulmonary parenchymal lung abnormality. Isolated rapidly progressive cardiogenic shock secondary to COVID-19 associated peri-myocarditis is a phenomenon important for critical care clinicians to be aware of during this pandemic. One should have a low threshold to establish invasive hemodynamic monitoring and consideration for early MCS in these cases. Reference #1: Siripanthong B, Nazarian S, Muser D, et al. Recognizing COVID-19-related myocarditis: The possible pathophysiology and proposed guideline for diagnosis and management. doi:10.1016/j.hrthm.2020.05.001 Reference #2: Osman M, Syed M, Patel B, et al. Invasive Hemodynamic Monitoring in Cardiogenic Shock Is Associated With Lower In-Hospital Mortality. Journal of the American Heart Association J Am Heart Assoc. 2021;10:21808. doi:10.1161/JAHA.121.021808 DISCLOSURES: No relevant relationships by Samuel Bullick No relevant relationships by Jonathan Greenberg No relevant relationships by Scott Slusarenko

The Association Between Social Determinants of Health and Postpartum Length of Stay During the COVID-19 Pandemic

INTRODUCTION: To determine differences in cesarean postpartum length of stay (pLOS) before and during the COVID-19 pandemic as a function of social determinants of health. METHODS: Cesarean birth pLOS data between January 1 and June 30, 2020, were reviewed. Births after March 10, 2020, were considered pandemic births. Primary outcome was early discharge <5,760 minutes (96 hours). Rates of early discharge were analyzed by social determinants of health, with socially vulnerable patients defined as Black or Hispanic, publicly insured, or non-English-speaking. We compared rates of early discharge before and during the pandemic overall and then among socially vulnerable patients using probit regression analysis. RESULTS: There were 1,885 eligible deliveries: 694 before the start of the pandemic and 1,171 after. Median pLOS pre-pandemic was 5,696 (IQR, 4,686-6,060) minutes versus 4,655 (IQR, 3,897- 5,860) minutes during the pandemic. Of the eligible deliveries, 54% had early discharges pre-pandemic compared to 71% afterwards (P<.01). Overall, we found these variables predictive of early discharge pLOS: socially vulnerable (P<.01), payer type (P<.01), English ability (P<.01), and multiparity (P<.01). Race as a variable alone was not found to be significantly predictive of early discharge. CONCLUSION: Socially vulnerable patients are more likely to leave the hospital earlier than their counterparts both before and during the COVID-19 pandemic. Our findings suggest that increased early discharges fall disproportionately on socially vulnerable patients. Further research is needed to determine whether these results are due to provider bias or patient driven.

Evaluating participant and coordinator satisfaction with telephone assessments

BACKGROUND: In response to the COVID-19 pandemic, the Alzheimer's Disease Research Center (ADRC) at the Icahn School of Medicine at Mount Sinai began conducting evaluations for the National Alzheimer's Coordinating Center Uniform Data Set (NACC UDS) by telephone in March 2020. The ADRC designed a survey to evaluate participant and research coordinator satisfaction with telephone evaluations. METHOD: Following UDS evaluations, participants rated their satisfaction on 5 items: voice quality on telephone, respect for privacy, degree of comfort using the telephone, and confidence that the information collected was accurate. Coordinators were asked to gauge their satisfaction on similar items. To calculate satisfaction scores, responses were assigned values: "Very" = 3, "Fairly" = 2, and "Not at all" = 1. Maximum satisfaction score was 15 for participants and 18 for coordinators. RESULT: Data was available for 130 participants evaluated by telephone between March 2020 and January 2021. Of these, 68.5% were female, 53.7% were white, with an average age of 76.4 and 16 years of education. 74% of participants had a Global Clinical Dementia Rating (CDR) score of 0;22% CDR 0.5;4% CDR 1. Participants with CDR >1 were evaluated by caregiver interviews without testing, and those with CDR=1 were offered testing at the discretion of their family and examiners. Average total satisfaction rating was 14.2/15 for participants and 16.8/18 for coordinators. 98% of participants felt their privacy was "very" respected (mean 2.98/3). When looking at global CDR scores, 89.6% of participants with CDR=0 and 88.2% with CDR ≥0.5 were "very" confident in the accuracy of the information collected. In contrast, coordinators were "very" confident in the accuracy of their evaluation 84.4% of the time when participants had a CDR=0 and 67.7% of the time when participants had a CDR ≥0.5. CONCLUSION: Overall satisfaction with telephone evaluations was high, but participant and coordinator confidence in the accuracy of assessments varied, with coordinator satisfaction lower for more cognitively impaired participants. Future work will analyze satisfaction with ongoing remote assessments and evaluate the impact of additional demographic and diagnostic variables. © 2021 the Alzheimer's Association.

Recollections of the intensive care unit experience among families of patients with COVID-19

RATIONALE: Clinicians typically encourage family presence in the Intensive Care Unit (ICU) as a way to improve both patient and family outcomes. To limit the spread of the disease, families were typically prohibited from visiting the ICU during the COVID-19 pandemic. Little is known about the approach clinicians should take when engaging with families in times when they cannot visit the hospital. METHODS: Surrogates of critically ill patients with COVID-19 who participated in a clinical trial at a single academic center were contacted after ICU discharge to participate in a follow up study dealing with their ICU experience. Upon enrollment in this post-ICU discharge study, the subject (surrogate of the ICU patient) completed the Critical Care Family Needs Inventory (CCFNI) questionnaire and participated in a semi-structured telephone interview. The CCFNI questionnaire includes 14 questions dealing with aspects of the ICU experience that are important to family members. The answers to each question range from 1 (almost all the time) to 4 (none of the time), with lower scores indicating a better experience. Telephone interviews were transcribed and coded using thematic content analysis. RESULTS: Of the 58 subjects enrolled from September 2020 to December 2020, 23 (40%) respective patients were deceased. Subjects of deceased patients had higher median CCFNI scores than subjects of surviving patients, reflecting greater dissatisfaction with the ICU experience (1.82 [1.45-2.00] vs 1.45 [1.27-1.72], respectively, p=0.009). Subjects recollected that they typically received at least one medical update from the patient's ICU team each day. While many subjects felt that telephone communication with the ICU team was adequate, some believed they were unable to fully understand the patient's condition. In addition, some subjects feared the patient was clinically worsening when they did not receive frequent updates, which had a negative impact on their experience. Nearly all subjects reported that visitor restrictions made the ICU experience more difficult. Some subjects believed that the medical decisions that were made and the care the patient received were negatively impacted by not having family present at the bedside. CONCLUSION: During the COVID-19 pandemic, families of critically ill patients typically received medical updates by phone daily because they were unable to visit. These aspects of ICU care delivery had differential effects on the ICU experience of families, with more negative experiences among families of deceased patients. These data suggest that more individualized approach to family engagement is needed during times of visitor restrictions.

Psychological symptoms after discharge from the intensive care unit among families of patients with covid-19

RATIONALE: Family members of intensive care unit (ICU) patients are at high risk of developing the postintensive care syndrome - family (PICS-F), which includes increased post-traumatic stress, depression, anxiety, and complicated grief. The COVID-19 pandemic has created a number of unique and potentially traumatic stressors both during and after the ICU stay, which may have amplified the burden of psychological symptoms among families of critically ill COVID-19 patients. METHODS: Surrogate decision makers of critically ill COVID-19 patients enrolled in an ongoing clinical trial were contacted 6 months after the hospitalization and enrolled in a follow up study. Post ICU-discharge, they completed the 14-question Hospital Anxiety and Depression scale (HADS) and the 22-question Impact of Events-Revised scale (IES-R), a measure of post-traumatic stress disorder symptoms. Scores were reported as medians with interquartile ranges. They also participated in a semistructured phone interview regarding their mental health and coping. Interviews were transcribed and coded using thematic content analysis. RESULTS: Of the 58 participants enrolled from September 2020 to December 2020, 23 (40%) respective patients were deceased. Participants with deceased patients had significantly higher median HADS-anxiety, HADS-depression, and IES-R scores compared to those with patients who were alive (higher scores indicating increased severity of symptoms): 12 [7-13] vs. 6 [2-9] p=0.001, 7 [4-11] vs. 3 [1-5] p<0.001, 36 [24-53] vs. 14 [7-34] p=0.001, respectively. Regardless of patient outcome, participants reported multiple different types of stressors since hospital discharge including emotional distress, sleep disturbance, and financial concerns. Some stressors were specific to COVID-19 such as the concern for contracting COVID-19, infection among family members, and being unable to visit patients at rehabilitation facilities. The most common coping methods participants described utilizing included faith/spirituality, emotional support, and instrumental support (eg assistance or advice from others). Many participants mentioned they had referenced friends or family who were healthcare providers to better understand the patients' condition which helped to reduce their stress. Although few participants had sought out mental health services, many thought it could be beneficial. CONCLUSION: Families of critically ill patients with COVID-19 report a high prevalence of psychological symptoms after ICU discharge, particularly for patients who were deceased. Family focused interventions both during and after the ICU-stay may help lessen this burden.

Stories about risk: Media narratives of known, emerging, and novel health threats

Purpose – The authors examine framing and narrativization in news coverage of health threats to assess variations in news discourse for known, emerging and novel health risks. Methodology/Approach – Using the analytical categories of known, emerging, and novel risks the authors discuss media analyses of anti-vaccination, antimicrobial resistance (AMR), and Covid-19. Findings – Known risks are framed within a biomedical discourse in which scientific evidence underpins public health guidelines, and following these directives prevent risk exposure while non-compliance is characterized as immoral and risky. News coverage of emerging risks highlights public health guidelines but fails to convey their importance as the risks seem too distant or abstract. Media coverage of novel risks is characterized by the ubiquity of uncertainty, which emerges as a “master frame” under which all incidents and events are subsumed. Stories about novel risks highlight the fluid and changing nature of scientific knowledge, which has the unintended effect of fueling uncertainty as studies and experts contradict each other. Originality/Value – This chapter introduces a new analytical framework for examining how media stories represent public health risks, along with previously unpublished analysis of media coverage about AMR and Covid-19. This chapter provides insight about the nature of risk discourses involving media, public health officials, activists, and citizens. © 2021 by Emerald Publishing Limited.