NeuroCARE: A Randomized Controlled Trial of a Psychological Intervention for Caregivers of Patients With Primary Malignant Brain Tumors.

PURPOSE: Caregivers of patients with primary malignant brain tumors (PMBT) experience significant psychological distress. We assessed the effect of a psychological intervention (NeuroCARE) on anxiety symptoms among PMBT caregivers. METHODS: We conducted a randomized trial of NeuroCARE versus usual care in PMBT caregivers with elevated anxiety (Generalized Anxiety Disorder-7 score ≥5) within 6 months of the patient's diagnosis. NeuroCARE was developed for PMBT caregivers and consists of six telehealth sessions with a behavioral health specialist. Participants completed surveys at baseline, 11-week (postintervention), and 16-week (1-month postintervention) time points. The primary outcome was 11-week anxiety symptoms (Hospital Anxiety and Depression Scale [HADS]-Anxiety Subscale). We also measured depression symptoms (HADS-Depression Subscale), quality of life (QOL; Caregiver QOL survey), caregiver burden (Caregiver Reaction Assessment), self-efficacy (Lewis Cancer Self-Efficacy Scale), coping (Measure of Current Status), and post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist for DSM-5). We conducted analysis of covariance and linear mixed-effects regression analyses to examine intervention effects on study outcomes. RESULTS: We enrolled 120 caregivers (60/group) between October 2019 and June 2022; 105 were evaluable for the primary outcome. At 11 weeks, NeuroCARE participants reported significantly lower anxiety symptoms than usual care participants (M, 8.87 v 10.69; P = .008). NeuroCARE caregivers also reported significantly lower depression symptoms (M, 6.08 v 7.77; P = .004), and better self-efficacy (M, 128.81 v 111.17; P < .001) and coping (M, 32.25 v 25.65; P < .001) at 11 weeks. Study groups did not differ significantly in 11-week QOL, caregiver burden, or PTSD symptoms. In longitudinal analyses, intervention effects on depression symptoms, self-efficacy, and coping were sustained. CONCLUSION: A novel, population-specific psychological intervention led to improved anxiety and depression symptoms, self-efficacy, and coping among PMBT caregivers.

Telehealth vs In-Person Early Palliative Care for Patients With Advanced Lung Cancer: A Multisite Randomized Clinical Trial.

Importance: Numerous studies show that early palliative care improves quality of life and other key outcomes in patients with advanced cancer and their caregivers, although most lack access to this evidence-based model of care. Objective: To evaluate whether delivering early palliative care via secure video vs in-person visits has an equivalent effect on quality of life in patients with advanced non-small cell lung cancer (NSCLC). Design, Setting, and Participants: Randomized, multisite, comparative effectiveness trial from June 14, 2018, to May 4, 2023, at 22 US cancer centers among 1250 patients within 12 weeks of diagnosis of advanced NSCLC and 548 caregivers. Intervention: Participants were randomized to meet with a specialty-trained palliative care clinician every 4 weeks either via video visit or in person in the outpatient clinic from the time of enrollment and throughout the course of disease. The video visit group had an initial in-person visit to establish rapport, followed by subsequent virtual visits. Main Outcomes and Measures: Equivalence of the effect of video visit vs in-person early palliative care on quality of life at week 24 per the Functional Assessment of Cancer Therapy-Lung questionnaire (equivalence margin of ±4 points; score range: 0-136, with higher scores indicating better quality of life). Participants completed study questionnaires at enrollment and at weeks 12, 24, 36, and 48. Results: By 24 weeks, participants (mean age, 65.5 years; 54.0% women; 82.7% White) had a mean of 4.7 (video) and 4.9 (in-person) early palliative care encounters. Patient-reported quality-of-life scores were equivalent between groups (video mean, 99.7 vs in-person mean, 97.7; difference, 2.0 [90% CI, 0.1-3.9]; P = .04 for equivalence). Rate of caregiver participation in visits was lower for video vs in-person early palliative care (36.6% vs 49.7%; P < .001). Study groups did not differ in caregiver quality of life, patient coping, or patient and caregiver satisfaction with care, mood symptoms, or prognostic perceptions. Conclusions and Relevance: The delivery of early palliative care virtually vs in person demonstrated equivalent effects on quality of life in patients with advanced NSCLC, underscoring the considerable potential for improving access to this evidence-based care model through telehealth delivery. Trial Registration: ClinicalTrials.gov Identifier: NCT03375489.

Effects of Adjuvant Endocrine Therapy-Specific Perceptions on Response to a Behavioral Intervention for Adjuvant Endocrine Therapy Adherence in Patients With Breast Cancer.

PURPOSE: Adjuvant endocrine therapy (AET) is a life-saving medication for patients with hormone-sensitive breast cancer, yet many struggle with adherence, warranting behavioral intervention. In our recent trial, participation in a group cognitive behavioral intervention (STRIDE) for symptom management and adherence was associated with improvements in symptom distress, coping, quality of life, and mood. We now explore whether baseline patient- and medication-specific factors-which may be modifiable by clinician-led discussions-moderated the effect of STRIDE on adherence rates. METHODS: From October 2019 to June 2021, 100 patients with early-stage breast cancer reporting AET-related distress were enrolled and randomly assigned to STRIDE or a medication monitoring (MM) control group. All patients stored their AET in electronic pill bottles to track objective adherence. Patients also self-reported their adherence on the Medication Adherence Report Scale-5 and their perceptions of AET on the Cancer Therapy Satisfaction Questionnaire at baseline. We conducted hierarchical linear modeling to test moderators of intervention effects on objective adherence rates. We report the time × group × moderator effects. RESULTS: Among patients reporting greater perceived difficulties with AET adherence at baseline, STRIDE participants had higher adherence rates over time compared with MM (b = -13.80; SE = 4.56; P < .01). Patients with greater expectations of therapeutic benefit from AET also had improved adherence rates if they were assigned to STRIDE, versus MM (b = 0.25; SE = 0.10; P = .01). Patients who perceived taking AET as convenient and had been taking their AET for less time had higher adherence rates in STRIDE, versus MM. CONCLUSION: The current study identified patient- and medication-specific factors that may augment AET adherence interventions and may be modifiable through clinician-led discussions, such as perceptions of adherence problems, therapeutic efficacy, and convenience of AET.

Prognosis of Transplant-Ineligible Patients with Cirrhosis and Acute Kidney Injury Who Initiate Renal Replacement Therapy.

BACKGROUND: Data to guide dialysis decision-making for transplant-ineligible patients with cirrhosis are lacking. AIMS: We aimed to describe the processes, predictors, and outcomes of renal replacement therapy (RRT) initiation for transplant-ineligible patients with cirrhosis at a single liver transplantation center. METHODS: We conducted a mixed-methods study of a retrospective cohort of 372 transplant-ineligible inpatients with cirrhosis with acute kidney injury (AKI) due to hepatorenal syndrome (HRS-AKI) or acute tubular necrosis (ATN) between 2008 and 2015. We performed survival analyses to evaluate 6-month survival and renal recovery and examined end-of-life care outcomes. We used a consensus-driven medical record review to characterize processes leading to RRT initiation. RESULTS: We identified 266 (71.5%) patients who received RRT and 106 (28.5%) who did not receive RRT (non-RRT). Median survival was 12.5 days (RRT) vs. 2.0 days (non-RRT) (HR 0.36, 95%CI 0.28-0.46); 6-month survival was 15% (RRT) vs. 0% (non-RRT). RRT patients were more likely to die in the intensive care unit (88% vs. 32%, p < 0.001). HRS-AKI patients were more likely to be RRT dependent at 6 months than ATN patients (86% vs. 27%, p = 0.007). The most common reasons for RRT initiation were unclear etiology of AKI on presentation (32%) and belief of likely reversibility of ATN (82%). CONCLUSION: Most transplant-ineligible patients who were initiated on RRT experienced very short-term mortality and received intensive end-of-life care. However, approximately 1 in 6 were alive at 6 months. Our findings underscore the critical need for structured clinical processes to support high-quality serious illness communication and RRT decision-making for this population.

CONTINUUM: A Post-Discharge Supportive Care Intervention for Hospitalized Patients with Advanced Cancer.

CONTEXT: Patients with advanced cancer are at increased risk for multiple hospitalizations and often have considerable needs post-discharge. Interventions to address patients' needs after transitioning home are lacking. OBJECTIVES: We sought to demonstrate the feasibility and acceptability of a post-discharge intervention for this population. METHODS: We conducted a single-arm pilot trial (n=54) of a post-discharge intervention, consisting of a video visit with an oncology nurse practitioner (NP) within three days of discharge to address symptoms, medications, hospitalization-related issues, and care coordination. We enrolled English-speaking adults with advanced breast, gastrointestinal, genitourinary, or thoracic cancers experiencing an unplanned hospitalization and preparing for discharge home. The intervention was deemed feasible if ≥70% of approached patients enrolled and ≥70% of enrolled patients completed the intervention within three days of discharge. Two weeks after discharge, patients rated the ease and usefulness of the video technology on a 0-10 scale (higher scores indicate greater ease of use). NPs completed post-intervention surveys to assess protocol adherence. RESULTS: We enrolled 54 of 75 approached patients (77.3%). Of enrolled patients (median age=65.0 years), 83.3% participated in the intervention within three days of discharge. The median ease of participating in the intervention was 9.0 (IQR: 6.0-10.0) and the median usefulness of the intervention was 7.0 (IQR: 4.5-8.0). The majority of visits focused on symptom management (85.7%), followed by post-hospital medical issues (69.0%). CONCLUSION: An oncology NP-delivered intervention immediately after hospital discharge is a feasible and acceptable approach to providing post-discharge care for hospitalized patients with advanced cancer.

Using Restricted Interests in Cognitive Behavioral Therapy for Children With Autism Spectrum Disorder: Results From a Preliminary Randomized Controlled Trial.

Children with autism spectrum disorder (ASD) exhibit significant deficits in social communication and emotion regulation skills. While cognitive behavioral therapy (CBT) applications appear promising, trials to date have largely excluded social communication skill development and have not been designed to include a wider range of emotional challenges. To our knowledge, the present study is the first to pilot a uniquely modified CBT program targeting emotion regulation, including social communication training, and explicitly focusing on the child's areas of circumscribed interest in order to teach skills and promote generalization. Forty participants were randomly assigned to either the CBT group or a waitlist control (WLC) group, resulting in 20 school-aged children in each group. The treatment approach was determined to be feasible and acceptable, and therapy engagement and attendance were reasonably high. Caregivers expressed high satisfaction with the program, qualitatively citing gains in skills such as social problem-solving, emotion identification, and identifying and processing cognitive distortions. The primary outcome of postintervention changes was not significantly different between the groups (CBT vs. WLC). The mean Social Skills Improvement System score decreased by 0.44 points (95% confidence interval [CI]: -5.04, 4.15) in the CBT group and increased by 0.41 points (95% CI: -4.23, 5.04) in the WLC group, and the postintervention changes were not significantly different between the groups (difference: -0.85; 95% CI: -7.29, 5.60; p = .79). The estimated rate of emotional dysregulation episodes decreased by a factor of 0.94 (95% CI: 0.57, 1.56) in the CBT group and increased by a factor of 1.07 (95% CI: 0.51, 2.24) for WLC (p = .74). Among those who reported emotional dysregulation episodes, the mean duration decreased by 1.39 minutes (95% CI: -3.90, 6.67) less for CBT than waitlist (p = .60). Although satisfaction, acceptability, and emotional dysregulation outcome results from this preliminary CBT treatment for ASD are promising, sample size and measurement limitations will be important considerations to inform future trials.

Stepped Palliative Care for Patients With Advanced Lung Cancer: A Randomized Clinical Trial.

Importance: Despite the evidence for early palliative care improving outcomes, it has not been widely implemented in part due to palliative care workforce limitations. Objective: To evaluate a stepped-care model to deliver less resource-intensive and more patient-centered palliative care for patients with advanced cancer. Design, Setting, and Participants: Randomized, nonblinded, noninferiority trial of stepped vs early palliative care conducted between February 12, 2018, and December 15, 2022, at 3 academic medical centers in Boston, Massachusetts, Philadelphia, Pennsylvania, and Durham, North Carolina, among 507 patients who had been diagnosed with advanced lung cancer within the past 12 weeks. Intervention: Step 1 of the intervention was an initial palliative care visit within 4 weeks of enrollment and subsequent visits only at the time of a change in cancer treatment or after a hospitalization. During step 1, patients completed a measure of quality of life (QOL; Functional Assessment of Cancer Therapy-Lung [FACT-L]; range, 0-136, with higher scores indicating better QOL) every 6 weeks, and those with a 10-point or greater decrease from baseline were stepped up to meet with the palliative care clinician every 4 weeks (intervention step 2). Patients assigned to early palliative care had palliative care visits every 4 weeks after enrollment. Main Outcomes and Measures: Noninferiority (margin = -4.5) of the effect of stepped vs early palliative care on patient-reported QOL on the FACT-L at week 24. Results: The sample (n = 507) mostly included patients with advanced non-small cell lung cancer (78.3%; mean age, 66.5 years; 51.4% female; 84.6% White). The mean number of palliative care visits by week 24 was 2.4 for stepped palliative care and 4.7 for early palliative care (adjusted mean difference, -2.3; P < .001). FACT-L scores at week 24 for the stepped palliative care group were noninferior to scores among those receiving early palliative care (adjusted FACT-L mean score, 100.6 vs 97.8, respectively; difference, 2.9; lower 1-sided 95% confidence limit, -0.1; P < .001 for noninferiority). Although the rate of end-of-life care communication was also noninferior between groups, noninferiority was not demonstrated for days in hospice (adjusted mean, 19.5 with stepped palliative care vs 34.6 with early palliative care; P = .91). Conclusions and Relevance: A stepped-care model, with palliative care visits occurring only at key points in patients' cancer trajectories and using a decrement in QOL to trigger more intensive palliative care exposure, resulted in fewer palliative care visits without diminishing the benefits for patients' QOL. While stepped palliative care was associated with fewer days in hospice, it is a more scalable way to deliver early palliative care to enhance patient-reported outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03337399.

Phase 1 study of CAR-37 T cells in patients with relapsed or refractory CD37+ lymphoid malignancies.

ABSTRACT: We report a first-in-human clinical trial using chimeric antigen receptor (CAR) T cells targeting CD37, an antigen highly expressed in B- and T-cell malignancies. Five patients with relapsed or refractory CD37+ lymphoid malignancies were enrolled and infused with autologous CAR-37 T cells. CAR-37 T cells expanded in the peripheral blood of all patients and, at peak, comprised >94% of the total lymphocytes in 4 of 5 patients. Tumor responses were observed in 4 of 5 patients with 3 complete responses, 1 mixed response, and 1 patient whose disease progressed rapidly and with relative loss of CD37 expression. Three patients experienced prolonged and severe pancytopenia, and in 2 of these patients, efforts to ablate CAR-37 T cells, which were engineered to coexpress truncated epidermal growth factor receptor, with cetuximab were unsuccessful. Hematopoiesis was restored in these 2 patients after allogeneic hematopoietic stem cell transplantation. No other severe, nonhematopoietic toxicities occurred. We investigated the mechanisms of profound pancytopenia and did not observe activation of CAR-37 T cells in response to hematopoietic stem cells in vitro or hematotoxicity in humanized models. Patients with pancytopenia had sustained high levels of interleukin-18 (IL-18) with low levels of IL-18 binding protein in their peripheral blood. IL-18 levels were significantly higher in CAR-37-treated patients than in both cytopenic and noncytopenic cohorts of CAR-19-treated patients. In conclusion, CAR-37 T cells exhibited antitumor activity, with significant CAR expansion and cytokine production. CAR-37 T cells may be an effective therapy in hematologic malignancies as a bridge to hematopoietic stem cell transplant. This trial was registered at www.ClinicalTrials.gov as #NCT04136275.

Development and validation of the caregiver Burden from infant home NGT care instrument.

OBJECTIVE: To design and validate an age and condition-specific health status instrument to best reflect the parental experience caring for these children with complex needs and home Nasogastric Tube (NGT) placement. STUDY DESIGN: Combined Qualitative and Quantitative design, testing and implementation for item production and reduction, followed by formal validation by evaluating validity, reliability, and establishing a clinically meaningful change score. SETTINGS: Tertiary care, multi-disciplinary aerodigestive center. PARTICIPANTS: All caregivers whose infant met criteria for eligibility for discharge home from the NICU or Special Care Nursery (SCN) with NGT in place were offered inclusion in this group. Intervention/Exposure: Structured qualitative interviews of these caregivers to explore and define these concepts and domains, to item generate and then reduce, and then psychometric analyses. METHODS: Structured, moderated qualitative interviews with parents/caregivers of children who have undergone home NGT care of their children for item creation, design, and then reduction. Reliability was assessed by Cronbach alpha analysis. Construct validity and clinically meaningful change score was assessed using various query methods. MAIN OUTCOME MEASURES: Cronbach's alpha to assess reliability, a priori hypotheses validity analyses, and minimally important clinical difference calculation. RESULTS: Scaled scores of this condition specific instrument ranged from 14 to 74 where higher scores indicate better QOL related to managing the NGT. Cronbach's alpha with all 14 items was 0.93. Validity was assessed by a self-assessment question to discriminate between change (95% CI: 8.5-14.1; p < 0.0001) as well as by other comparators to identify the instrument's ability to discriminate among populations where parents felt a difference in experience. The minimally important difference was calculated at 18 points. CONCLUSION: This represents the initial validation of the first condition and age-specific health status instrument to assess parent experience of caring for infants requiring a home NGT for dysphagia.

Hypofractionated Radiotherapy-Related Lymphopenia Is Associated With Worse Survival in Unresectable Intrahepatic Cholangiocarcinoma.

OBJECTIVE: The aim of this study was to evaluate the incidence of radiotherapy (RT)-related lymphopenia, its predictors, and association with survival in unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated-RT (HF-RT). METHODS: Retrospective analysis of 96 patients with unresectable ICC who underwent HF-RT (median 58.05 Gy in 15 fractions) between 2009 and 2022 was performed. Absolute lymphocyte count (ALC) nadir within 12 weeks of RT was analyzed. Primary variable of interest was severe lymphopenia, defined as Grade 3+ (ALC <0.5 k/µL) per CTCAE v5.0. Primary outcome of interest was overall survival (OS) from RT. RESULTS: Median follow-up was 16 months. Fifty-two percent of patients had chemotherapy pre-RT, 23% during RT, and 40% post-RT. Pre-RT, median ALC was 1.1 k/µL and 5% had severe lymphopenia. Post-RT, 68% developed RT-related severe lymphopenia. Patients who developed severe lymphopenia had a significantly lower pre-RT ALC (median 1.1 vs. 1.5 k/µL, P =0.01) and larger target tumor volume (median 125 vs. 62 cm 3 , P =0.02). In our multivariable Cox model, severe lymphopenia was associated with a 1.7-fold increased risk of death ( P =0.04); 1-year OS rates were 63% vs 77% ( P =0.03). Receipt of photon versus proton-based RT (OR=3.50, P =0.02), higher mean liver dose (OR=1.19, P <0.01), and longer RT duration (OR=1.49, P =0.02) predicted severe lymphopenia. CONCLUSIONS: HF-RT-related lymphopenia is an independent prognostic factor for survival in patients with unresectable ICC. Patients with lower baseline ALC and larger tumor volume may be at increased risk, and use of proton therapy, minimizing mean liver dose, and avoiding treatment breaks may reduce RT-related lymphopenia.

Isatuximab, carfilzomib, lenalidomide, and dexamethasone in patients with newly diagnosed, transplantation-eligible multiple myeloma (SKylaRk): a single-arm, phase 2 trial.

BACKGROUND: Isatuximab is a CD38 monoclonal antibody approved for relapsed or refractory multiple myeloma. We aimed to evaluate the addition of isatuximab to weekly carfilzomib (K), lenalidomide (R), and dexamethasone (d; Isa-KRd) in transplant-eligible patients with newly diagnosed multiple myeloma and stratified maintenance by cytogenetic risk. METHODS: This single-arm phase 2 trial was done at three cancer centres (two hospitals and a cancer institute) in Boston (MA, USA). Eligible patients were aged at least 18 years and had transplant-eligible newly diagnosed multiple myeloma and an ECOG performance status of 2 or less. Patients received four 28-day cycles of Isa-KRd, including isatuximab 10 mg/kg intravenously weekly for 8 weeks, then every other week for 16 weeks, and every 4 weeks thereafter; carfilzomib 56 mg/m2 intravenously on days 1, 8, and 15 (20 mg/m2 for cycle 1 day 1); lenalidomide 25 mg orally on days 1-21; and dexamethasone 20 mg orally the day of and day after all doses of carfilzomib and isatuximab. Consolidation involved either upfront haematopoietic stem-cell transplantation (HSCT) with two additional cycles or deferred HSCT with four additional cycles of treatment. The primary endpoint was complete response after four cycles of treatment. Analyses were by intention-to-treat. All patients who received one dose of study drug were included in the safety analyses. This study was registered at ClinicalTrials.gov, NCT04430894, and has completed enrolment. FINDINGS: Between July 31, 2020 and Jan 31, 2022, 50 patients were enrolled. Median age was 59 years (range 40-70), 54% (27 of 50 patients) were male, and 44 (88%) were White. 46% (23 of 50) of patients had high-risk cytogenetics. Median follow-up was 26 months (IQR 20·7-30·1). 32% (16 of 50 patients) achieved a complete response after four cycles. The overall response rate (ORR) was 90% (45 patients) and 78% (39 patients) achieved a very good partial response (VGPR) or better. After completion of consolidation, 58% (29 patients) achieved a complete response; the ORR was 90% (45 patients) and 86% (43 patients) achieved a VGPR or better. The most common grade 3 or 4 side-effects (≥two patients) included neutropenia (13 [26%] of 50 patients), elevated alanine aminotransferase (six [12%] patients), fatigue (three [6%] patients), thrombocytopenia (three [6%] patients), acute kidney injury (two [4%] patients), anaemia (two [4%] patients), and febrile neutropenia (two [4%] patients). Grade 1-2 infusion-related reactions were seen in 20% (ten patients), with none grade 3. Grade 1-2 hypertension was seen in 14% (seven patients) with one grade 3 (one [2%] patient). There were two deaths assessed as unrelated to treatment. INTERPRETATION: Although the study did not achieve the prespecified complete response threshold, Isa-KRd induced deep and durable responses in transplant-eligible patients with newly diagnosed multiple myeloma. The treatment proved safe and consistent with similar regimens in this setting. FUNDING: Amgen, Sanofi, and Adaptive.

Physician Coaching by Professionally Trained Peers for Burnout and Well-Being: A Randomized Clinical Trial.

Importance: Physician burnout is problematic despite existing interventions. More evidence-based approaches are needed. Objective: To explore the effect of individualized coaching by professionally trained peers on burnout and well-being in physicians. Design, Setting, and Participants: This randomized clinical trial involved Mass General Physician Organization physicians who volunteered for coaching from August 5 through December 1, 2021. The data analysis was performed from February through October 2022. Interventions: Participants were randomized to 6 coaching sessions facilitated by a peer coach over 3 months or a control condition using standard institutional resources for burnout and wellness. Main Outcomes and Measures: The primary outcome was burnout as measured by the Stanford Professional Fulfillment Index. Secondary outcomes included professional fulfillment, effect of work on personal relationships, quality of life, work engagement, and self-valuation. Analysis was performed on a modified intention-to-treat basis. Results: Of 138 physicians enrolled, 67 were randomly allocated to the coaching intervention and 71 to the control group. Most participants were aged 31 to 60 years (128 [93.0%]), women (109 [79.0%]), married (108 [78.3%]), and in their early to mid career (mean [SD], 12.0 [9.7] years in practice); 39 (28.3%) were Asian, 3 (<0.1%) were Black, 9 (<0.1%) were Hispanic, 93 were (67.4%) White, and 6 (<0.1%) were of other race or ethnicity. In the intervention group, 52 participants underwent coaching and were included in the analysis. Statistically significant improvements in burnout, interpersonal disengagement, professional fulfillment, and work engagement were observed after 3 months of coaching compared with no intervention. Mean scores for interpersonal disengagement decreased by 30.1% in the intervention group and increased by 4.1% in the control group (absolute difference, -0.94 poimys [95% CI, -1.48 to -0.41 points; P = .001), while mean scores for overall burnout decreased by 21.6% in the intervention group and increased by 2.5% in the control group (absolute difference, -0.79 points; 95% CI, -1.27 to -0.32 points; P = .001). Professional fulfillment increased by 10.7% in the intervention group compared with no change in the control group (absolute difference, 0.59 points; 95% CI, 0.01-1.16 points; P = .046). Work engagement increased by 6.3% in the intervention group and decreased by 2.2% in the control group (absolute difference, 0.33 points; 95% CI, 0.02-0.65 points; P = .04). Self-valuation increased in both groups, but not significantly. Conclusions and Relevance: The findings of this hospital-sponsored program show that individualized coaching by professionally trained peers is an effective strategy for reducing physician burnout and interpersonal disengagement while improving their professional fulfillment and work engagement. Trial Registration: ClinicalTrials.gov Identifier: NCT05036993.

The Edmonton Symptom Assessment System is a valid, reliable, and responsive tool to assess symptom burden in decompensated cirrhosis.

BACKGROUND: While there is a growing need for interventions addressing symptom burden in patients with decompensated cirrhosis (DC), the lack of validated symptom assessment tools is a critical barrier. We investigated the psychometric properties of the revised Edmonton Symptom Assessment System (ESAS-r) in a longitudinal cohort of patients with DC. METHODS: Adult outpatients with DC were prospectively recruited from a liver transplant center and completed ESAS-r at baseline and week 12. We examined reliability, floor/ceiling effects, structural validity, and known-groups validity. We examined the convergent and predictive validity of ESAS-r with health-related quality of life using the Short Form Liver Disease Quality of Life (SF-LDQOL) and responsiveness to changes in anxiety and depression using the Hospital Anxiety and Depression Scale and Patient Health Questionnaire-9 from baseline to week 12. RESULTS: From August 2018 to September 2022, 218 patients (9% Child-Pugh A, 59% Child-Pugh B, and 32% Child-Pugh C) were prospectively recruited and completed the ESAS-r, SF-LDQOL, Patient Health Questionnaire-9, and Hospital Anxiety and Depression Scale at baseline and week 12 (n = 135). ESAS-r had strong reliability (Cronbach's alpha 0.86), structural validity (comparative fit index 0.95), known-groups validity (Child-Pugh A: 25.1 vs. B: 37.5 vs. C: 41.4, p = 0.006), and convergent validity (r = -0.67 with SF-LDQOL). Floor effects were 9% and ceiling effects were 0.5%. Changes in ESAS-r scores from baseline to week 12 significantly predicted changes in SF-LDQOL (ß = -0.36, p < 0.001), accounting for 30% of the variation. ESAS-r was strongly responsive to clinically meaningful changes in SF-LDQOL, Patient Health Questionnaire-9, and Hospital Anxiety and Depression Scale. CONCLUSIONS: ESAS-r is a reliable, valid, and responsive tool for assessing symptom burden in patients with DC and can predict changes in health-related quality of life. Future directions include its implementation as a key outcome measure in cirrhosis care and clinical trials.

Racism and Nursing Leadership in Massachusetts: A Mixed-Methods Study.

BACKGROUND: Nursing in the United States has evolved within the same historical context that has reproduced and spread racism worldwide. Nurse administrators are integral to the quality of nurses' practice and play a key role in eliminating racial injustice in places of work. PURPOSE: Using a feminist and critical race feminist framework, this study examined Massachusetts nurses' experiences of racism in their places of work, focusing on nurse administrators' influence on the nonadministrator (staff nurse) experience of racism experiences before and after George Floyd's death. METHODS: An investigator-developed, electronic survey was sent to Massachusetts professional nursing organizations for distribution to their members in 2021. Two hundred nineteen nurse respondents completed Likert-scale and open-ended branching logic survey questions to yield the quantitative and qualitative data analyzed for this mixed-methods study. FINDINGS: Nurse administrators were: 1) more likely than staff nurses to state that policies and meetings to address racism and diversity, equity, and inclusion had taken place before and after George Floyd's murder; and 2) less likely than staff nurses to directly experience racism at the hands of a colleague or a superior. Nurse administrators influence staff nurses' experiences of racism.

Financial burden following adult liver transplantation is common and associated with adverse recipient outcomes.

The financial impact of liver transplantation has been underexplored. We aimed to identify associations between high financial burden (≥10% annual income spent on out-of-pocket medical costs) and work productivity, financial distress (coping behaviors in response to the financial burden), and financial toxicity (health-related quality of life, HRQOL) among adult recipients of liver transplant. Between June 2021 and May 2022, we surveyed 207 adult recipients of liver transplant across 5 US transplant centers. Financial burden and distress were measured by 25 items adapted from national surveys of cancer survivors. Participants also completed the Work Productivity and Activity Impairment and EQ-5D-5L HRQOL questionnaires. In total, 23% of recipients reported high financial burden which was significantly associated with higher daily activity impairment (32.9% vs. 23.3%, p =0.048). In adjusted analyses, the high financial burden was significantly and independently associated with delayed or foregone medical care (adjusted odds ratio, 3.95; 95% CI, 1.85-8.42) and being unable to afford basic necessities (adjusted odds ratio, 5.12; 95% CI: 1.61-16.37). Recipients experiencing high financial burden had significantly lower self-reported HRQOL as measured by the EQ-5D-5L compared to recipients with low financial burden (67.8 vs. 76.1, p =0.008) and an age-matched and sex-matched US general population (67.8 vs. 79.1, p <0.001). In this multicenter cohort study, nearly 1 in 4 adult recipients of liver transplant experienced a high financial burden, which was significantly associated with delayed or foregone medical care and lower self-reported HRQOL. These findings underscore the need to evaluate and address the financial burden in this population before and after transplantation.

Concurrent factors associated with adherence to adjuvant endocrine therapy among women with non-metastatic breast cancer.

PURPOSE: Adjuvant endocrine therapy (AET) reduces breast cancer morbidity and mortality, yet women often report suboptimal adherence. Though correlates of AET adherence are well-documented, few studies examine the relative importance of multi-level factors associated with adherence. The aim of this study was to identify factors most strongly associated with AET adherence in women with breast cancer. METHODS: Between 10/2019 and 6/2021, women (N = 100) with non-metastatic, hormone receptor-positive breast cancer, taking AET who reported AET-related distress enrolled into a clinical trial. Participants completed baseline measures, including the Medication Adherence Rating Scale-5, sociodemographics, and validated measures of anxiety, depression, medication-taking self-efficacy, social support, and treatment satisfaction. We created a latent factor and tested associations between sociodemographic, medical, and psychosocial characteristics and adherence. Associated predictors (p < .10) were entered into a structural model, which was corroborated via multivariate regression modeling. RESULTS: A four-indicator latent adherence factor demonstrated good model fit. Participants (Mage = 56.1 years, 91% White) who were unemployed (B = 0.27, SE = 0.13, p = .046) and reported greater treatment convenience (B = 0.01, SE = 0.01, p = .046) reported greater adherence. Scores of participants who reported greater medication-taking self-efficacy (p = .097) and social support (p = .062) approached better adherence. Greater medication-taking self-efficacy (B = 0.08, SE = 0.02, p < .001) and being unemployed (B = 0.28, SE = .14, p = .042) were most strongly associated with greater adherence, independent of other predictors. Multivariate modeling confirmed similar findings. CONCLUSIONS: Medication-taking self-efficacy and employment status were associated with AET adherence above other related factors. IMPLICATIONS FOR CANCER SURVIVORS: Enhancing patients' confidence in their ability to take AET for breast cancer may represent an important intervention target to boost adherence.

Biomarkers of pembrolizumab efficacy in advanced anal squamous cell carcinoma: analysis of a phase II clinical trial and a cohort of long-term responders.

BACKGROUND: Recent trials suggest that programmed cell death 1 (PD-1)-directed immunotherapy may be beneficial for some patients with anal squamous cell carcinoma and biomarkers predictive of response are greatly needed. METHODS: This multicenter phase II clinical trial (NCT02919969) enrolled patients with metastatic or locally advanced incurable anal squamous cell carcinoma (n=32). Patients received pembrolizumab 200 mg every 3 weeks. The primary endpoint of the trial was objective response rate (ORR). Exploratory objectives included analysis of potential predictive biomarkers including assessment of tumor-associated immune cell populations with multichannel immunofluorescence and analysis of circulating tumor tissue modified viral-human papillomavirus DNA (TTMV-HPV DNA) using serially collected blood samples. To characterize the clinical features of long-term responders, we combined data from our prospective trial with a retrospective cohort of patients with anal cancer treated with anti-PD-1 immunotherapy (n=18). RESULTS: In the phase II study, the ORR to pembrolizumab monotherapy was 9.4% and the median progression-free survival was 2.2 months. Despite the high level of HPV positivity observed with circulating TTMV-HPV DNA testing, the majority of patients had low levels of tumor-associated CD8+PD-1+ T cells on pretreatment biopsy. Patients who benefited from pembrolizumab had decreasing TTMV-HPV DNA scores and a complete responder's TTMV-HPV DNA became undetectable. Long-term pembrolizumab responses were observed in one patient from the trial (5.3 years) and three patients (2.5, 6, and 8 years) from the retrospective cohort. Long-term responders had HPV-positive tumors, lacked liver metastases, and achieved a radiological complete response. CONCLUSIONS: Pembrolizumab has durable efficacy in a rare subset of anal cancers. However, despite persistence of HPV infection, indicated by circulating HPV DNA, most advanced anal cancers have low numbers of tumor-associated CD8+PD-1+ T cells and are resistant to pembrolizumab.

Experiences of bias in a multidisciplinary hospital medicine group.

ABSTRACT: Clinicians report experiencing bias at work. Although previous studies have characterized these experiences among trainees and clinical faculty, ours is the first to describe experiences of bias within a multidisciplinary hospital medicine group. In our study, 82.5% of surveyed nurse practitioners (NPs), physician assistants (PAs), and physicians reported experiencing gender, racial, or other forms of bias in the workplace. In addition to women reporting higher rates of gender bias and Asian/Black/Latinx/multiracial/other race respondents reporting higher rates of racial bias, half of participants reported experiencing other forms of bias related to gender expression, perceived sexual orientation, body habitus, age, accent, country of origin, or perceived socioeconomic status. Respondents infrequently addressed bias with the person expressing it. Our study expands on the existing literature about experiences of bias by studying a large, multidisciplinary, academic hospital medicine group. With the increasing inclusion of NPs and PAs in hospital medicine, understanding their experiences will enable development of tailored interventions to reduce harm from experiences of bias.

Identification of patient subgroups who benefit from a behavioral intervention to improve adjuvant endocrine therapy adherence: a randomized-controlled trial.

PURPOSE: Adjuvant endocrine therapy (AET) reduces breast cancer morbidity and mortality; however, adherence is suboptimal. Interventions exist, yet few have improved adherence. Patient characteristics may alter uptake of an intervention to boost adherence. We examined moderators of the effect of a virtual intervention (STRIDE; #NCT03837496) on AET adherence after breast cancer. METHODS: At a large academic medical center, patients taking AET (N = 100; Mage = 56.1, 91% White) were randomized to receive STRIDE versus medication monitoring. All stored their medication in digital pill bottles (MEMS Caps) which captured objective adherence. Participants self-reported adherence (Medication Adherence Report Scale) at 12 weeks post-baseline. Moderators included age, anxiety, and depressive symptoms (Hospital Anxiety and Depression Scale), AET-related symptom distress (Breast Cancer Prevention Trial Symptom Scale), and AET-specific concerns (Beliefs about Medications Questionnaire). We used hierarchical linear modeling (time × condition × moderator) and multiple regression (condition × moderator) to test the interaction effects on adherence. RESULTS: Age (B = 0.05, SE = 0.02, p = 0.003) and AET-related symptom distress (B = -0.04, SE = 0.02, p = 0.02) moderated condition effect on self-reported adherence while anxiety (B = -1.20, SE = 0.53, p = 0.03) and depressive symptoms (B = -1.65, SE = 0.65, p = 0.01) moderated objective adherence effects. AET-specific concerns approached significance (B = 0.91, SE = 0.57, p = 0.12). Participants who received STRIDE and were older or presented with lower anxiety and depressive symptoms or AET-related symptom distress exhibited improved adherence. Post hoc analyses revealed high correlations among most moderators. CONCLUSIONS: A subgroup of patients who received STRIDE exhibited improvements in AET adherence. The interrelatedness of moderators suggests an underlying profile of patients with lower symptom burden who benefitted most from the intervention. STUDY REGISTRATION: NCT03837496.

Managing Symptom Distress: Key Factors for Patients on Adjuvant Endocrine Therapy for Breast Cancer.

CONTEXT: Patients with breast cancer taking adjuvant endocrine therapy (AET) experience significant symptoms impacting mood, quality of life (QOL), and AET adherence and satisfaction. OBJECTIVES: The aim of this study was to examine the extent to which coping ability and self-efficacy for symptom management moderate the relationships between patients' symptom distress and their mood, QOL, and AET adherence and satisfaction. METHODS: As part of a randomized controlled trial, participants completed baseline measures including: sociodemographics, symptom distress (breast cancer prevention trial symptom checklist), coping skills (measure of current status), self-efficacy (self-efficacy for managing symptoms), anxiety and depression (hospital anxiety and depression scale), QOL (functional assessment of cancer therapy - general), AET adherence (medication adherence report scale), and AET satisfaction (cancer therapy satisfaction questionnaire). We conducted moderated regression analyses to examine whether coping and self-efficacy moderated the associations of symptom distress with baseline measures. RESULTS: Coping skills moderated the associations of symptom distress with depression and QOL. Among those with lower coping, higher symptom distress was associated with worse depression symptoms (p=.04) and worse QOL (p < 0.001). Self-efficacy moderated the associations of symptom distress with depression symptoms and AET adherence and satisfaction. Among those with higher self-efficacy, higher symptom distress was associated with worse depression symptoms (p < 0.001), worse AET adherence (p < 0.001), and less AET satisfaction (p = 0.01). CONCLUSION: Coping skills may buffer the effect of AET symptom distress. Findings indicate the relationship between symptom distress and self-efficacy is more nuanced and requires further research to better understand.