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.

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.

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.

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

We report on the first-in-human clinical trial using chimeric antigen receptor (CAR) T-cells targeting CD37, an antigen highly expressed in B- and T-cell malignancies (clinicaltrials.gov NCT04136275). 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 4/5 patients. Tumor responses were observed in 4/5 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 two of these patients, efforts to ablate CAR-37 T-cells (which were engineered to co-express truncated EGFR) with cetuximab, were unsuccessful. Hematopoiesis was restored in these two patients following allogeneic hematopoietic stem cell transplantation. No other severe, non-hematopoietic 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 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 relative to both cytopenic and non-cytopenic cohorts of CAR-19-treated cohorts of patients. In conclusion, CAR-37 T-cells exhibited anti-tumor 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.

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.

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.

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.

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.

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.

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.

Health care satisfaction and medical literacy habits among caregivers of individuals with Down syndrome.

Patients with Down syndrome have significant specialized health care needs. Our objective was to understand the needs, satisfaction, and online habits of caregivers as they care for persons with Down syndrome. A mixed-method survey was distributed through REDCap from April 2022 to June 2022 in the United States; a Spanish-translated version was distributed through SurveyMonkey from August 2022 to March 2023 in Mexico. We received 290 completed responses from the United States and 58 from caregivers in Mexico. We found that current health care options are not meeting the needs of many individuals with DS in both the United States (39.7%) and Mexico (46.6%). Caregivers expressed frustrations with the inaccessibility and inapplicability of health care information. In particular, they often found the volume of information overwhelming, given their limited medical background. Additionally, health care recommendations were not customized and lacked practical recommendations. Most caregivers in both the United States (72.1%) and Mexico (82.8%) believe it is not easy to find answers to medical questions about their loved ones with DS. Online platforms with customized, specific health information related to DS could offer innovative solutions to these unmet needs for families and primary care providers.

Patient-Reported Outcomes, Tumor Markers, and Survival Outcomes in Advanced GI Cancer.

Importance: Patient-reported outcomes (PROs), such as quality of life (QOL) and symptoms, are often associated with clinical outcomes in patients with cancer. In practice, oncologists use serum tumor markers (TMs) (ie, carcinoembryonic antigen [CEA] and carbohydrate antigen 19-9 [CA 19-9]) and imaging to monitor clinical outcomes in patients with gastrointestinal cancer. Objective: To examine associations of 1-month changes in PROs and TMs with treatment response and survival among patients with gastrointestinal cancer. Design, Setting, and Participants: This cohort study enrolled patients at Massachusetts General Hospital Cancer Center with at least 1 month follow-up from May 2019 to December 2020. Included patients were beginning first-line systemic therapy, aged 18 years or older, and had been diagnosed with metastatic pancreaticobiliary, colorectal, or gastroesophageal cancer. Data analyses took place from January 2021 to January 2022. Intervention: PROs were collected, including QOL (Functional Assessment of Cancer Therapy General [FACT-G]), physical symptoms (Edmonton Symptom Assessment System [ESAS]), and psychological symptoms (Patient Health Questionnaire-4 [PHQ4] total, PHQ4-depression, and PHQ4-anxiety), as well as TMs (CEA and CA 19-9), at the time of chemotherapy initiation and 1 month later. Main Outcomes and Measures: Associations of 1-month changes in PROs and TMs with treatment response (clinical benefit vs disease progression) at first scan, progression-free survival (PFS), and overall survival (OS), adjusted for baseline values using regression models. Results: This study included 159 patients, with 134 patients (84.3%) evaluable for analysis. Patients had a median (range) age of 64.0 (28.0-84.0) years and 86 (64.2%) were male. One-month PRO changes (FACT-G: OR, 1.07; 95% CI, 1.03-1.11; P = .001; ESAS-total: OR, 0.97; 95% CI, 0.94-1.00; P = .02; ESAS-physical: OR, 0.96; 95% CI, 0.92-1.00; P = .03; PHQ4-depression: OR, 0.67; 95% CI, 0.49-0.92; P = .01) were significantly associated with treatment response, but PHQ4-total or TMs were not. Changes in FACT-G (HR, 0.97; 95% CI, 0.95-0.99; P = .003), ESAS-total (HR, 1.03; 95% CI, 1.01-1.05; P = .004), ESAS-physical (HR, 1.03; 95% CI, 1.00-1.05; P = .02), PHQ4-depression (HR, 1.22; 95% CI, 1.01-1.48; P = .04), and CEA (HR, 1.00; 95% CI, 1.001-1.004; P = .001) were associated with PFS, but changes in PHQ4-total or TMs were not. Changes in ESAS-total (HR, 1.03, 95% CI, 1.01-1.06; P = .006) and ESAS-physical (HR, 1.04, 95% CI, 1.01-1.06; P = .015) were associated with OS, but changes in TMs were not associated with OS. Conclusions and Relevance: These findings suggest that 1-month changes in PROs can be associated with treatment response and survival in patients with advanced gastrointestinal cancer. Notably, 1-month changes in TMs were not consistently associated with these outcomes. These findings highlight the potential for monitoring early changes in PROs to associate with clinical outcomes while underscoring the need to address the QOL and symptom concerns of patients with advanced cancer.

Pneumonia vaccine response in individuals with Down syndrome at three specialty clinics.

Individuals with Down syndrome (DS) have been particularly impacted by respiratory conditions, such as pneumonia. However, the description of co-occurring recurrent infections, the response to pneumococcal immunization, and the association of these was previously unknown. We screened individuals with DS using an 11-item screener and prospectively collected pneumococcal titers and laboratory results. We found that the screener did not successfully predict which individuals with DS who would have inadequate pneumococcal titers. Thirty four of the 55 individuals with DS (62%) had abnormal pneumococcal titers demonstrating an inadequate response to routine immunization. In the absence of a valid screener, clinicians should consider screening all individuals with DS through the use of pneumococcal titers to 23 serotypes to assess vaccine response.

Solriamfetol for Attention-Deficit/Hyperactivity Disorder in Adults: A Double-Blind Placebo-Controlled Pilot Study.

Objective: Some individuals with attention-deficit/hyperactivity disorder (ADHD) may not tolerate or adequately respond to currently available treatments. This study examined whether solriamfetol could have a favorable pattern of effects and tolerability as a treatment for ADHD in adults.Methods: Sixty adults with DSM-5 ADHD participated from August 2021 through January 2023 in a remotely conducted, randomized, double-blind, placebo-controlled, 6-week dose-optimization trial of 75 mg or 150 mg of solriamfetol. Measures included the Adult ADHD Investigator Symptom Rating Scale (AISRS), which was our primary outcome measure, as well as the Clinical Global Impressions scale (CGI), vital signs, the Global Assessment of Functioning (GAF), the Behavior Rating Inventory of Executive Function-Adult Form (BRIEF-A), the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), and a modified Adult ADHD Self-Report Scale (MASRS).Results: Solriamfetol was well tolerated, with no significant effect on mean heart rate (+3.7 vs +2.2 bpm, P = .5609), systolic blood pressure (+2.4 vs +1.5 mm Hg, P = .6474), or diastolic blood pressure (+1.1 vs +1.5 mm Hg, P = .8117). There was no statistically significant treatment effect on occurrence of adverse events. Compared to individuals on placebo, individuals on solriamfetol treatment experienced adverse events at a rate of at least 10 percentage points higher in the categories of decreased appetite, headache, gastrointestinal, insomnia, increased energy, cardiovascular, and neurologic. Compared to individuals on placebo, by study endpoint, a greater proportion of individuals in the treatment group met the a priori-defined treatment response (CGI score indicating much or very much improved and AISRS score reduced ≥ 25%: 45% vs 6.9%, P = .0020); those treated with solriamfetol also had greater improvement in total AISRS scores by week 3 through week 6 (P = .0012; week 6 effect size = 1.09). Significantly more solriamfetol-treated adults than placebo-treated adults had 0.5-standard deviation improvement in T-score on the BRIEF-A Global Executive Composite (P = .0173); those treated with solriamfetol also had greater mean change in GAF score (-4.8 vs -0.3, P = .0006) and greater mean MASRS total score change (P = .0047; effect size = 1.23). Mean ESS score improved more with solriamfetol than with placebo (P = .0056), but this difference did not predict AISRS response (P = .3735). There was no significant association between solriamfetol and change in PSQI scores.Conclusions: Solriamfetol may be a novel and effective treatment for the management of ADHD in adults. Further replication in larger trials is indicated.Trial Registration: ClinicalTrials.gov identifier: NCT04839562.