A digital therapeutic application (ePAL) to manage pain in patients with advanced cancer: A randomized controlled trial.

BACKGROUND: Patients with advanced cancer often experience immense cancer pain that negatively impacts their quality of life. Interventions to address cancer-related pain are limited. METHODS: We conducted a randomized trial of a digital therapeutic app (ePAL) for patients with advanced cancer receiving care in a specialty palliative care clinic at a tertiary care hospital. Patients were randomized to ePAL or usual care. ePAL included 1) active pain monitoring; 2) artificial intelligence algorithm to triage patient symptoms; and 3) patient education to address barriers to pain management. Participants were instructed to use ePAL over 8 weeks. Patient-reported pain symptoms were assessed at baseline, week-4, and week-8 (primary endpoint) using the Brief Pain Inventory. Secondary outcomes include pain-related hospitalizations by week-8. RESULTS: We enrolled 112 patients who were randomly assigned to ePAL (N=56) or usual care (N=56). Patients utilized ePAL on average 2.1 times per week to report pain symptoms, and 47.6% reported their pain at least once per week over eight weeks. Patients randomized to ePAL reported lower pain scores at week-4 (mean: 3.16 vs. 4.28, P=0.010) and week-8 (mean:2.99 vs. 4.05, P=0.017), compared to those receiving usual care. Participants randomized to ePAL were less likely to experience a pain-related hospitalization compared to those in the usual care group (7.1% vs. 23.2% P=0.018) CONCLUSIONS: ePAL was associated with lower patient-reported pain and fewer pain-related hospitalizations compared to usual care in patients with advanced cancer. This study demonstrates the promise of digital therapeutics for improving patients' symptoms while reducing burdensome hospitalizations.

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.

Why and How to Integrate Early Palliative Care Into Cutting-Edge Personalized Cancer Care.

Early palliative care, palliative care integrated with oncology care early in the course of illness, has myriad benefits for patients and their caregivers, including improved quality of life, reduced physical and psychological symptom burden, enhanced prognostic awareness, and reduced health care utilization at the end of life. Although ASCO and others recommend early palliative care for all patients with advanced cancer, widespread implementation of early palliative care has not been realized because of barriers such as insufficient reimbursement and a palliative care workforce shortage. Investigators have recently tested several implementation strategies to overcome these barriers, including triggers for palliative care consultations, telehealth delivery, navigator-delivered interventions, and primary palliative care interventions. More research is needed to identify mechanisms to distribute palliative care optimally and equitably. Simultaneously, the transformation of the oncology treatment landscape has led to shifts in the supportive care needs of patients and caregivers, who may experience longer, uncertain trajectories of cancer. Now, palliative care also plays a clear role in the care of patients with hematologic malignancies and may be beneficial for patients undergoing phase I clinical trials and their caregivers. Further research and clinical guidance regarding how to balance the risks and benefits of opioid therapy and safely manage cancer-related pain across this wide range of settings are urgently needed. The strengths of early palliative care in supporting patients' and caregivers' coping and centering decisions on their goals and values remain valuable in the care of patients receiving cutting-edge personalized cancer care.

Single Cell Analysis of Proteoforms.

We introduce single cell Proteoform imaging Mass Spectrometry (scPiMS), which realizes the benefit of direct solvent extraction and MS detection of intact proteins from single cells dropcast onto glass slides. Sampling and detection of whole proteoforms by individual ion mass spectrometry enable a scalable approach to single cell proteomics. This new scPiMS platform addresses the throughput bottleneck in single cell proteomics and boosts the cell processing rate by several fold while accessing protein composition with higher coverage.

Group Coping Intervention in Patients With Chronic Graft-Versus-Host Disease: A Pilot Randomized Clinical Trial.

BACKGROUND: More than half the long-term survivors of allogeneic hematopoietic cell transplantation develop chronic graft-versus-host disease (GVHD), a debilitating inflammatory syndrome. Supportive interventions to assist survivors in coping with chronic GVHD are critically needed. PATIENTS AND METHODS: We conducted a pilot randomized clinical trial of a multidisciplinary group intervention (Horizons Program; n=39) versus minimally enhanced usual care (n=41) for patients with moderate or severe chronic GVHD. Horizons participants received 8 weekly sessions about GVHD and coping co-led by a transplant clinician and a behavioral health expert via a secure videoconferencing platform. Participants completed the following surveys before randomization, at 10 weeks, and at 18 weeks: Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT) for quality of life (QoL), Lee Symptom Scale for symptom burden, and Hospital Anxiety and Depression Scale-Depression Symptoms (HADS) for mood. The primary endpoint was feasibility (≥50% enrollment, ≥80% attendance in half the sessions for the Horizons arm only, and ≥80% retention). We also explored preliminary efficacy of the Horizons intervention on changes in patient-reported outcomes with linear mixed effects models and estimates of effect size at 10 weeks. RESULTS: We enrolled and registered 80 (67.2%) of 119 eligible patients (mean age, 62 years; 48.8% female). Of the participants in the Horizons Program, 84.6% attended at least half the sessions. Of registered participants, 91.3% completed assessment follow-ups (Horizons, 35/39 [89.7%]; minimally enhanced usual care, 38/41 [92.7%]). Horizons participants reported improvements in QoL (b = 2.24; d=0.53), anxiety symptoms (b = -0.10; d=0.34), and depression symptoms (b = -0.71; d=0.44) compared with participants who received minimally enhanced usual care. CONCLUSIONS: Participation in a multidisciplinary group intervention study was feasible for patients with chronic GVHD, with promising signals for improving QoL and mood. A full-scale efficacy trial is needed to confirm effects on patient-reported outcomes.

Using Multiphase Optimization Strategy and Human-Centered Design to Create an Integrated Model of Palliative Care Skills in Home-Based Physical Therapy for Advanced Heart Failure.

Background: Many older adults with advanced heart failure receive home health rehabilitation after hospitalization. Yet, integration of palliative care skills into rehabilitation is limited. Objective: Describe using the Multiphase Optimization Strategy (MOST) framework with human-centered design principles to engage clinical partners in the Preparation phase of palliative physical therapy intervention development. Design: We convened a home-based physical therapy advisory team (four clinicians, three clinical leaders) to identify physical therapist needs and preferences for incorporating palliative care skills in rehabilitation and design an intervention prototype. Results: Between 2022 and 2023, we held five advisory team meetings. Initial feedback on palliative care skill preferences and training needs directly informed refinement of our conceptual model and skills in the intervention prototype. Later feedback focused on reviewing and revising intervention content, delivery strategy, and training considerations. Conclusion: Incorporating human-centered design principles within the MOST provided a useful framework to partner with clinical colleagues in intervention design.

Dyspnea-Related Dimensions And Self-Efficacy: Associations With Well-Being in Advanced Lung Cancer.

CONTEXT: Dyspnea is a complex, multidimensional symptom comprising sensory-perceptual, affective, and functional domains that commonly persists in patients with lung cancer and impairs mental health and quality of life (QOL). However, data are lacking on how dyspnea's dimensions or self-efficacy to manage dyspnea are associated with patient outcomes. OBJECTIVES: To assess the associations of dyspnea dimensions (dyspnea-related sensory-perceptual experience, affective distress, and functional impact) and dyspnea self-efficacy with depression, anxiety, and QOL in patients with advanced lung cancer reporting dyspnea. METHODS: We conducted a secondary analysis of baseline clinical trial data testing a supportive care intervention for dyspnea. Patients with advanced lung cancer reporting at least moderate dyspnea (≥2 on the Modified Medical Research Council Dyspnea Scale) self-reported dyspnea and patient outcome measures. Hierarchical regressions tested the associations of the dyspnea dimensions with depressive and anxiety symptoms (Hospital Anxiety and Depression Scale) and QOL (Functional Assessment of Cancer Therapy-Lung) while adjusting for variables known to affect these outcomes. RESULTS: The sensory-perceptual experience of dyspnea (effort) was associated with worse depressive symptoms (b = 0.21, P < 0.01) and QOL (b = -0.53, P = 0.01). Dyspnea self-efficacy was associated with improved depressive (b = -1.26, P < 0.01) and anxiety symptoms (b = -1.72, P < 0.01) and QOL (b = 3.66, P < 0.01). The affective and functional dimensions of dyspnea were not associated with the patient outcomes in the final models. CONCLUSIONS: Dyspnea-related sensory-perceptual experience and self-efficacy were associated with mental health and QOL outcomes in patients with lung cancer. Examining the individual contributions of dyspnea's multiple dimensions provides a nuanced understanding of its patient impact.

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.

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.

Protocol for multi-site randomized trial of inpatient palliative care for patients with hematologic malignancies undergoing hematopoietic stem cell transplantation.

BACKGROUND: Patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT) commonly experience debilitating physical and psychological symptoms during a 3-4-week-hospitalization. During hospitalization, caregivers (i.e., family and friends) also endure immense emotional stress as they witness their loved one struggle with HSCT toxicities. Yet interventions to improve quality of life (QOL) and reduce psychological distress during HSCT are limited. METHODS: We are conducting a multi-site randomized controlled trial of inpatient integrated palliative and transplant care versus usual care in 360 patients hospitalized for HSCT and their caregivers at three academic centers. Intervention participants meet with a palliative care clinician at least twice weekly during the HSCT hospitalization to address their physical and psychological symptoms. Patients assigned to usual care receive all supportive care measures provided by the HSCT team and could be seen by palliative care upon request. We assess patient QOL (Functional Assessment of Cancer Therapy (FACT) - Bone Marrow Transplant), depression and anxiety symptoms (Hospital Anxiety and Depression Scale), post-traumatic stress (PTSD) symptoms (PTSD checklist), symptom burden (Edmonton Symptom Assessment Scale), and fatigue (FACT-Fatigue) as well as caregiver-reported outcomes at baseline, 2 weeks, 3-months, 6-months, and 12-months post-HSCT. The primary endpoint is to compare QOL at week-2 during HSCT hospitalization between the two groups when patients typically experience their QOL nadir during HSCT. CONCLUSIONS: This multi-site trial will define the role of palliative care for improving QOL and care for patients with hematologic malignancies undergoing HSCT and their caregivers.

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.

Clinician Perceptions of Barriers and Facilitators for Delivering Early Integrated Palliative Care via Telehealth.

Early integrated palliative care (EIPC) significantly improves clinical outcomes for patients with advanced cancer. Telehealth may be a useful tool to deliver EIPC sustainably and equitably. Palliative care clinicians completed a survey regarding their perceptions of the barriers, facilitators, and benefits of using telehealth video visits for delivering EIPC for patients with advanced lung cancer. Forty-eight clinicians across 22 cancer centers completed the survey between May and July 2022. Most (91.7%) agreed that telehealth increases access to EIPC and simplifies the process for patients to receive EIPC (79.2%). Clinicians noted that the elderly, those in rural areas, and those with less-resourced backgrounds have greater difficulty using telehealth. Perceived barriers were largely patient-based factors, including technological literacy, internet and device availability, and patient preferences. Clinicians agreed that several organizational factors facilitated telehealth EIPC delivery, including technological infrastructure (85.4%), training (83.3%), and support from study coordinators (81.3%). Other barriers included systems-based factors, such as insurance reimbursement and out-of-state coverage restrictions. Patient-, organization-, and systems-based factors are all important to providing and improving access to telehealth EIPC services. Further research is needed to investigate the efficacy of telehealth EIPC and how policies and interventions may improve access to and dissemination of this care modality.

Study protocol for NeuroCARE: a randomised controlled trial of a psychological intervention for caregivers of patients with primary malignant brain tumours.

INTRODUCTION: Caregivers of patients with primary malignant brain tumours experience substantial psychological distress while caring for someone with a progressive, life-limiting neurological illness. However, there are few interventions aimed at addressing the psychosocial needs of this population. We developed and are testing a population-specific, evidence-based, telehealth intervention (NeuroCARE) to reduce anxiety symptoms and improve psychosocial functioning in this caregiver population. METHODS AND ANALYSIS: This study is a non-blinded, randomised controlled trial of a psychological intervention for caregivers of patients with primary malignant brain tumours receiving care at the Massachusetts General Hospital Cancer Center or Dana-Farber Cancer Institute. We will enrol 120 caregivers who screen positive for heightened anxiety. Participants will be randomised 1:1 to the NeuroCARE intervention or a usual care control condition. Caregivers assigned to NeuroCARE will complete six individual telehealth sessions with a trained behavioural health specialist over 12 weeks. Caregivers randomised to the control condition will receive usual care, including possible referral to social work or other appropriate resources. Participants will complete self-report questionnaires at baseline and 11 weeks and 16 weeks postrandomisation. The primary outcome is anxiety symptoms at 11 weeks among NeuroCARE participants, compared with usual care. Secondary outcomes include caregiver-reported depressive symptoms, quality of life, caregiver burden, caregiving self-efficacy, perceived coping skills and post-traumatic stress disorder symptoms. We also will explore potential mediators of the NeuroCARE effect on caregiver anxiety symptoms. ETHICS AND DISSEMINATION: The study is funded by a Career Development Award from Conquer Cancer, the American Society of Clinical Oncology Foundation (award number 2019CDA-7743456038) and approved by the Dana-Farber/Harvard Cancer Center Institutional Review Board (Protocol #19-250 V.10.1). The study will be reported in accordance with the Consolidated Standards of Reporting Trials statement for non-pharmacological trials. Results will be presented at scientific meetings and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04109209.

Orbitrap Mass Spectrometry and High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) Enable the in-Depth Analysis of Human Serum Proteoforms.

Blood serum and plasma are arguably the most commonly analyzed clinical samples, with dozens of proteins serving as validated biomarkers for various human diseases. Top-down proteomics may provide additional insights into disease etiopathogenesis since this approach focuses on protein forms, or proteoforms, originally circulating in blood, potentially providing access to information about relevant post-translational modifications, truncations, single amino acid substitutions, and many other sources of protein variation. However, the vast majority of proteomic studies on serum and plasma are carried out using peptide-centric, bottom-up approaches that cannot recapitulate the original proteoform content of samples. Clinical laboratories have been slow to adopt top-down analysis, also due to higher sample handling requirements. In this study, we describe a straightforward protocol for intact proteoform sample preparation based on the depletion of albumin and immunoglobulins, followed by simplified protein fractionation via polyacrylamide gel electrophoresis. After molecular weight-based fractionation, we supplemented the traditional liquid chromatography-tandem mass spectrometry (LC-MS2) data acquisition with high-field asymmetric waveform ion mobility spectrometry (FAIMS) to further simplify serum proteoform mixtures. This LC-FAIMS-MS2 method led to the identification of over 1000 serum proteoforms < 30 kDa, outperforming traditional LC-MS2 data acquisition and more than doubling the number of proteoforms identified in previous studies.

Advancing Intact Protein Quantitation with Updated Deconvolution Routines.

Analysis of intact proteins by mass spectrometry enables direct quantitation of the specific proteoforms present in a sample and is an increasingly important tool for biopharmaceutical and academic research. Interpreting and quantifying intact protein species from mass spectra typically involves many challenges including mass deconvolution and peak processing as well as determining optimal spectral averaging parameters and matching masses to theoretical proteoforms. Each of these steps can present informatic hurdles, as parameters often need to be tailored specifically to the data sets. To reduce intact mass deconvolution data analysis burdens, we built upon the widely used "sliding window" mass deconvolution technique with several additional concepts. First, we found that how spectra are averaged and the overlap in spectral windows can be tuned to favor either sensitivity or speed. A multiple window averaging approach was found to be the most effective way to increase mass detection and yielded a >2-fold increase in the number of masses detected. We also developed a targeted feature-finding routine that boosted sensitivity by >2-fold, decreased coefficient of variation across replicates by 50%, and increased the quality of mass elution profiles through 3-fold more detected time points. Lastly, we furthered existing approaches for annotating detected masses with potential proteoforms through spectral fitting for possible proteoform family modifications and network viewing. These proteoform annotation approaches ultimately produced a more accurate way of finding related, but previously unknown proteoforms from intact mass-only data. Together, these quantitation workflow improvements advance the information obtainable from intact protein mass spectrometry analyses.

Study protocol for a randomized trial of a supportive care mobile application to improve symptoms, coping, and quality of life in patients with advanced non-small cell lung cancer.

Patients with advanced non-small cell lung cancer (NSCLC) often experience burdensome symptoms, emotional distress, and poor quality of life (QOL). While national guidelines recommend early palliative care to address these supportive care needs, most patients with advanced NSCLC lack access to such comprehensive care. Our aim in the current study is to test a novel model of palliative care delivery and use of innovative technology to evaluate the feasibility, acceptability, and preliminary efficacy of a supportive care mobile application (app) for improving symptom management and adaptive coping in patients with advanced NSCLC. We will enroll 120 patients with unresectable Stage III or IV NSCLC diagnosed within the past 12 weeks receiving care with palliative intent at a major academic comprehensive cancer center and its community affiliates. The study will take place in two phases, the first of which will be dedicated to adapting an evidence-based, early palliative care treatment guide and prior supportive care mobile app intervention to address the specific symptom management and coping needs of patients with advanced NSCLC. The second phase of the study will be a two-group, randomized controlled trial. Study patients will complete baseline self-report measures of symptoms, mood, coping skills, and QOL, after which they will be randomized to receive either the mobile app intervention combined with usual oncology care or usual oncology care alone. Intervention patients will use a tablet computer to self-administer the mobile app, which consists of six modules that teach evidence-based skills for managing burdensome symptoms and coping effectively with advanced cancer and its treatment. At 12 weeks follow up, patients in both groups will repeat the same self-report measures. We will use descriptive statistics to determine feasibility metrics of enrollment and retention rates. For secondary self-report measures, we will use linear regression controlling for baseline values. The results of the present study will contribute to a growing body of evidence regarding the supportive care needs of patients with advanced cancer and will have implications for how best to use innovative technology to widely disseminate comprehensive supportive care services to all patients who may benefit. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier[NCT04629300].

An acceptance and commitment therapy-based intervention for opioid use disorder risk in individuals with cancer: A treatment development study.

This paper describes the iterative development of an evidence-based behavioral intervention for individuals with cancer at risk for opioid use disorder, using the National Institutes of Health Stage Model for Behavioral Intervention Development. Adult patients with cancer from an outpatient palliative care clinic at an academic cancer center, with moderate to high risk of opioid misuse, were enrolled in a treatment development study that aimed to increase psychological flexibility. In this intervention, psychological flexibility is the posited mechanism of change for reduction of opioid use disorder risk. Patients completed baseline (pre-intervention) assessments, a six-session behavioral intervention based in Acceptance and Commitment Therapy, post-intervention assessments, and a semi-structured exit interview. Ten patients with moderate to high risk of opioid misuse completed the intervention. Patients rated the intervention as highly acceptable and were generally highly satisfied. Patients reported finding the coping skills helpful (e.g., mindfulness, cognitive defusion) and reported a preference for more sessions. These treatment development efforts have implications for the development and design of acceptance- and mindfulness-based, targeted interventions for individuals with cancer, receiving palliative care and at risk for opioid use disorder. Specifically, this six-session behavioral intervention to increase psychological flexibility was acceptable to patients and ready to be studied in a pilot RCT.

Shifting behavioral intervention research to virtual methods: Challenges and solutions in practice, during and after the COVID-19 pandemic.

Behavioral medicine researchers have rapidly adapted study procedures and interventions to telehealth modalities during the pandemic. We rely heavily on telehealth research methods to avoid study delays and mitigate risk to chronically ill patients our studies aim to support. We implemented methods to virtually recruit, enroll, and retain patients and their families on clinical trials, and virtually deliver study interventions. These adaptations are likely to become permanent amid ongoing virus variants and surges in cases. However, little has been written about how remote methods apply in practice. This paper documents these processes to maximize efficiency across our research studies and systems and highlights the strengths and challenges of transitioning our research protocols to telehealth. We outline solutions to using remote methods across the entire span of the research process, including study recruitment, data collection, and intervention delivery. We offer insight into the implications of these transitions on research staff and interventionists. In providing a transparent review of the advantages and challenges of implementing remote methods, we encourage discourse around remote methods implementation, share the lessons we learned, and inform the design of future trials. Further research is needed to review the clinical feasibility and acceptability of these procedures.

Improved Label-Free Quantification of Intact Proteoforms Using Field Asymmetric Ion Mobility Spectrometry.

The high-throughput quantification of intact proteoforms using a label-free approach is typically performed on proteins in the 0-30 kDa mass range extracted from whole cell or tissue lysates. Unfortunately, even when high-resolution separation of proteoforms is achieved by either high-performance liquid chromatography or capillary electrophoresis, the number of proteoforms that can be identified and quantified is inevitably limited by the inherent sample complexity. Here, we benchmark label-free quantification of proteoforms of Escherichia coli by applying gas-phase fractionation (GPF) via field asymmetric ion mobility spectrometry (FAIMS). Recent advances in Orbitrap instrumentation have enabled the acquisition of high-quality intact and fragmentation mass spectra without the need for averaging time-domain transients prior to Fourier transform. The resulting speed improvements allowed for the application of multiple FAIMS compensation voltages in the same liquid chromatography-tandem mass spectrometry experiment without increasing the overall data acquisition cycle. As a result, the application of FAIMS to label-free quantification based on intact mass spectra substantially increases the number of both identified and quantified proteoforms without penalizing quantification accuracy in comparison to traditional label-free experiments that do not adopt GPF.