Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients With Cancer: A Randomized Clinical Trial.

Importance: In patients with cancer who have venous thromboembolism (VTE) events, long-term anticoagulation with low-molecular-weight heparin (LMWH) is recommended to prevent recurrent VTE. The effectiveness of a direct oral anticoagulant (DOAC) compared with LMWH for preventing recurrent VTE in patients with cancer is uncertain. Objective: To evaluate DOACs, compared with LMWH, for preventing recurrent VTE and for rates of bleeding in patients with cancer following an initial VTE event. Design, Setting, and Participants: Unblinded, comparative effectiveness, noninferiority randomized clinical trial conducted at 67 oncology practices in the US that enrolled 671 patients with cancer (any invasive solid tumor, lymphoma, multiple myeloma, or chronic lymphocytic leukemia) who had a new clinical or radiological diagnosis of VTE. Enrollment occurred from December 2016 to April 2020. Final follow-up was in November 2020. Intervention: Participants were randomized in a 1:1 ratio to either a DOAC (n = 335) or LMWH (n = 336) and were followed up for 6 months or until death. Physicians and patients selected any DOAC or any LMWH (or fondaparinux) and physicians selected drug doses. Main Outcomes and Measures: The primary outcome was the recurrent VTE rate at 6 months. Noninferiority of anticoagulation with a DOAC vs LMWH was defined by the upper limit of the 1-sided 95% CI for the difference of a DOAC relative to LMWH of less than 3% in the randomized cohort that received at least 1 dose of assigned treatment. The 6 prespecified secondary outcomes included major bleeding, which was assessed using a 2.5% noninferiority margin. Results: Between December 2016 and April 2020, 671 participants were randomized and 638 (95%) completed the trial (median age, 64 years; 353 women [55%]). Among those randomized to a DOAC, 330 received at least 1 dose. Among those randomized to LMWH, 308 received at least 1 dose. Rates of recurrent VTE were 6.1% in the DOAC group and 8.8% in the LMWH group (difference, -2.7%; 1-sided 95% CI, -100% to 0.7%) consistent with the prespecified noninferiority criterion. Of 6 prespecified secondary outcomes, none were statistically significant. Major bleeding occurred in 5.2% of participants in the DOAC group and 5.6% in the LMWH group (difference, -0.4%; 1-sided 95% CI, -100% to 2.5%) and did not meet the noninferiority criterion. Severe adverse events occurred in 33.8% of participants in the DOAC group and 35.1% in the LMWH group. The most common serious adverse events were anemia and death. Conclusions and Relevance: Among adults with cancer and VTE, DOACs were noninferior to LMWH for preventing recurrent VTE over 6-month follow-up. These findings support use of a DOAC to prevent recurrent VTE in patients with cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02744092.

Adaptation of a Multimedia Chemotherapy Educational Intervention for Latinos: Letting Patient Narratives Speak for Themselves.

This study aims to adapt a video-based, multimedia chemotherapy educational intervention to meet the needs of US Latinos with advanced gastrointestinal malignancies. A five-step hybrid adaptation process involved (1) creating a multidisciplinary team with diverse Latino subject experts, (2) appraising the parent intervention, (3) identifying key cultural considerations from a systematic literature review and semi-structured Latino patient/caregiver interviews, (4) revising the intervention, highlighting culturally relevant themes through video interviews with Latino cancer patients, and (5) target population review with responsive revisions. We developed a suite of videos, booklets, and websites available in English and Spanish, which convey the risks and benefits of common chemotherapy regimens. After revising the English materials, we translated them into Spanish using a multi-step process. The intervention centers upon conversations with 12 Latino patients about their treatment experiences; video clips highlight culturally relevant themes (personalismo, familismo, faith, communication gaps, prognostic information preferences) identified during the third adaptation step. The adapted intervention materials included a new section on coping, and one titled "how to feel the best you can feel," which reviews principles of side effect management, self-advocacy, proactive communication, and palliative care. Ten Latinos with advanced malignancies reviewed the intervention and found it to be easily understandable, relatable, and helpful. A five-step hybrid model was successful in adapting a chemotherapy educational intervention for Latinos. Incorporation of video interviews with Latino patients enabled the authentic representation of salient cultural themes. Use of authentic patient narratives can be useful for cross-cultural intervention adaptations.

Assessing Patient Readiness for an Electronic Patient-Reported Outcome-Based Symptom Management Intervention in a Multisite Study.

PURPOSE: While the use of electronic patient-reported outcomes (ePROs) in routine clinical practice is increasing, barriers to patient engagement limit adoption. Studies have focused on technology access as a key barrier, yet other characteristics may also confound readiness to use ePROs including patients' confidence in using technology and confidence in asking clinicians questions. METHODS: To assess readiness to use ePROs, adult patients from six US-based health systems who started a new oncology treatment or underwent a cancer-directed surgery were invited to complete a survey that assessed access to and confidence in the use of technology, ease of asking clinicians questions about health, and symptom management self-efficacy. Multivariable ordinal logistic regression models were fit to assess the association between technology confidence, ease of asking questions, and symptom management self-efficacy. RESULTS: We contacted 3,212 individuals, and 1,043 (33%) responded. The median age was 63 years, 68% were female, and 75% reported having access to patient portals. Over 80% had two or more electronic devices. Most patients reported high technology confidence, higher ease of asking clinicians questions, and high symptom management self-efficacy (n = 692; 66%). Patients with high technology confidence also reported higher ease of asking nurses about their health (adjusted odds ratio [AOR], 4.58 [95% CI, 2.36 to 8.87]; P ≤ .001). Those who reported higher ease of asking nurses questions were more likely to report higher confidence in managing symptoms (AOR, 30.54 [95% CI, 12.91 to 72.30]; P ≤ .001). CONCLUSION: Patient readiness to use ePROs likely depends on multiple factors, including technology and communication confidence, and symptom management self-efficacy. Future studies should assess interventions to address these factors.

Effects of a change in recall period on reporting severe symptoms: an analysis of a pragmatic multisite trial.

BACKGROUND: Optimal methods for deploying electronic patient-reported outcomes to manage symptoms in routine oncologic practice remain uncertain. The electronic symptom management (eSyM) program asks chemotherapy and surgery patients to self-report 12 common symptoms regularly. Feedback from nurses and patients led to changing the recall period from the past 7 days to the past 24 hours. METHODS: Using questionnaires submitted during the 16 weeks surrounding the recall period change, we assessed the likelihood of reporting severe or moderate and severe symptoms across 12 common symptoms and separately for the 5 most prevalent symptoms. Interrupted time-series analyses modeled the effects of the change using generalized linear mixed-effects models. Surgery and chemotherapy cohorts were analyzed separately. Study-wide effects were estimated using a meta-analysis method. RESULTS: In total, 1692 patients from 6 institutions submitted 7823 eSyM assessments during the 16 weeks surrounding the recall period change. Shortening the recall period was associated with lower odds of severe symptom reporting in the surgery cohort (odds ratio = 0.65, 95% confidence interval = 0.46 to 0.93; P = .02) and lower odds of moderate and severe symptom reporting in the chemotherapy cohort (odds ratio = 0.83, 95% confidence interval = 0.71 to 0.97; P = .02). Among the most prevalent symptoms, 24-hour recall was associated with a lower rate of reporting postoperative constipation but no differences in reporting rates for other symptoms. CONCLUSION: A shorter recall period was associated with a reduction in the proportion of patients reporting moderate-severe symptoms. The optimal recall period may vary depending on whether electronic patient-reported outcomes are collected for active symptom management, as a clinical trial endpoint, or another purpose. ClinicalTrials.gov ID NCT03850912.

Strategies for Implementing an Electronic Patient-Reported Outcomes-Based Symptom Management Program Across Six Cancer Centers.

Background: Electronic patient-reported outcome (ePRO)-based symptom management improves cancer patients' outcomes. However, implementation of ePROs is challenging, requiring technical resources for integration into clinical systems, substantial buy-in from clinicians and patients, novel workflows to support between-visit symptom management, and institutional investment. Methods: The SIMPRO Research Consortium developed eSyM, an electronic health record-integrated, ePRO-based symptom management program for medical oncology and surgery patients and deployed it at six cancer centers between August 2019 and April 2022 in a type II hybrid effectiveness-implementation cluster randomized stepped-wedge study. Sites documented implementation strategies monthly using REDCap, itemized them using the Expert Recommendations for Implementation Change (ERIC) list and mapped their target barriers using the Consolidated Framework for Implementation Research (CFIR) to inform eSyM program enhancement, facilitate inter-consortium knowledge sharing and guide future deployment efforts. Results: We documented 226 implementation strategies: 35 'foundational' strategies were applied consortium-wide by the coordinating center and 191 other strategies were developed by individual sites. We consolidated these 191 site-developed strategies into 64 unique strategies (i.e., removed duplicates) and classified the remainder as either 'universal', consistently used by multiple sites (N=29), or 'adaptive', used only by individual sites (N=35). Universal strategies were perceived as having the highest impact; they addressed eSyM clinical preparation, training, engagement of patients/clinicians, and program evaluation. Across all documented SIMPRO strategies, 44 of the 73 ERIC strategies were addressed and all 5 CFIR barriers were addressed. Conclusion: Methodical collection of theory-based implementation strategies fostered the identification of universal, high-impact strategies that facilitated adoption of a novel care-delivery intervention by patients, clinicians, and institutions. Attention to the high-impact strategies identified in this project could support implementation of ePROs as a component of routine cancer care at other institutions.

Cancer Caregivers' Prognostic and End-of-Life Communication Needs and Experiences and their Impact.

CONTEXT: Family caregivers of patients with advanced cancer are integrally involved in communications regarding prognosis and end-of-life (EOL) planning and care. Yet little research has examined caregivers' communication experiences or the impact of these experiences on patients and caregivers at EOL. OBJECTIVES: Investigate cancer caregivers' communication experiences and potential impact on patient and caregiver outcomes. METHODS: Semistructured interviews with bereaved family cancer caregivers (N=19) about their communication needs and experiences as their loved one approached EOL and died. Audiotaped interviews were transcribed and thematically analyzed for communication-related themes. RESULTS: Caregivers described fulfilling many important communication roles including information gathering and sharing, advocating, and facilitating-often coordinating communication with multiple partners (e.g., patient, family, oncology team, hospital team). Caregivers reported that, among the many topics they communicated about, prognosis and EOL were the most consequential and challenging. These challenges arose for several reasons including caregivers' and patients' discordant communication needs, limited opportunity for caregivers to satisfy their personal communication needs, uncertainty regarding their communication needs and responsibilities, and feeling unacknowledged by the care team. These challenges negatively impacted caregivers' abilities to satisfy their patient-related communication responsibilities, which shaped many outcomes including end-of-life decisions, care satisfaction, and bereavement. CONCLUSION: Caregivers often facilitate essential communication for patients with advanced cancers yet face challenges successfully fulfilling their own and patients' communication needs, particularly surrounding prognostic and end-of-life conversations. Future research and interventions should explore strategies to help caregivers navigate uncertainty, create space to ask sensitive questions, and facilitate patient-caregiver discussions about differing informational needs.

The Longitudinal Implementation Strategy Tracking System (LISTS): feasibility, usability, and pilot testing of a novel method.

BACKGROUND: Systematic approaches are needed to accurately characterize the dynamic use of implementation strategies and how they change over time. We describe the development and preliminary evaluation of the Longitudinal Implementation Strategy Tracking System (LISTS), a novel methodology to document and characterize implementation strategies use over time. METHODS: The development and initial evaluation of the LISTS method was conducted within the Improving the Management of SymPtoms during And following Cancer Treatment (IMPACT) Research Consortium (supported by funding provided through the NCI Cancer MoonshotSM). The IMPACT Consortium includes a coordinating center and three hybrid effectiveness-implementation studies testing routine symptom surveillance and integration of symptom management interventions in ambulatory oncology care settings. LISTS was created to increase the precision and reliability of dynamic changes in implementation strategy use over time. It includes three components: (1) a strategy assessment, (2) a data capture platform, and (3) a User's Guide. An iterative process between implementation researchers and practitioners was used to develop, pilot test, and refine the LISTS method prior to evaluating its use in three stepped-wedge trials within the IMPACT Consortium. The LISTS method was used with research and practice teams for approximately 12 months and subsequently we evaluated its feasibility, acceptability, and usability using established instruments and novel questions developed specifically for this study. RESULTS: Initial evaluation of LISTS indicates that it is a feasible and acceptable method, with content validity, for characterizing and tracking the use of implementation strategies over time. Users of LISTS highlighted several opportunities for improving the method for use in future and more diverse implementation studies. CONCLUSIONS: The LISTS method was developed collaboratively between researchers and practitioners to fill a research gap in systematically tracking implementation strategy use and modifications in research studies and other implementation efforts. Preliminary feedback from LISTS users indicate it is feasible and usable. Potential future developments include additional features, fewer data elements, and interoperability with alternative data entry platforms. LISTS offers a systematic method that encourages the use of common data elements to support data analysis across sites and synthesis across studies. Future research is needed to further adapt, refine, and evaluate the LISTS method in studies with employ diverse study designs and address varying delivery settings, health conditions, and intervention types.

Implementation of patient-reported outcomes for symptom management in oncology practice through the SIMPRO research consortium: a protocol for a pragmatic type II hybrid effectiveness-implementation multi-center cluster-randomized stepped wedge trial.

BACKGROUND: Many cancer patients experience high symptom burden. Healthcare in the USA is reactive, not proactive, and doctor-patient communication is often suboptimal. As a result, symptomatic patients may suffer between clinic visits. In research settings, systematic assessment of electronic patient-reported outcomes (ePROs), coupled with clinical responses to severe symptoms, has eased this symptom burden, improved health-related quality of life, reduced acute care needs, and extended survival. Implementing ePRO-based symptom management programs in routine care is challenging. To study methods to overcome the implementation gap and improve symptom control for cancer patients, the National Cancer Institute created the Cancer-Moonshot funded Improving the Management of symPtoms during And following Cancer Treatment (IMPACT) Consortium. METHODS: Symptom Management IMplementation of Patient Reported Outcomes in Oncology (SIMPRO) is one of three research centers that make up the IMPACT Consortium. SIMPRO, a multi-disciplinary team of investigators from six US health systems, seeks to develop, test, and integrate an electronic symptom management program (eSyM) for medical oncology and surgery patients into the Epic electronic health record (EHR) system and associated patient portal. eSyM supports real-time symptom tracking for patients, automated clinician alerts for severe symptoms, and specialized reports to facilitate population management. To rigorously evaluate its impact, eSyM is deployed through a pragmatic stepped wedge cluster-randomized trial. The primary study outcome is the occurrence of an emergency department treat-and-release event within 30 days of starting chemotherapy or being discharged following surgery. Secondary outcomes include hospitalization rates, chemotherapy use (time to initiation and duration of therapy), and patient quality of life and satisfaction. As a type II hybrid effectiveness-implementation study, facilitators and barriers to implementation are assessed throughout the project. DISCUSSION: Creating and deploying eSyM requires collaboration between dozens of staff across diverse health systems, dedicated engagement of patient advocates, and robust support from Epic. This trial will evaluate eSyM in routine care settings across academic and community-based healthcare systems serving patients in rural and metropolitan locations. This trial's pragmatic design will promote generalizable results about the uptake, acceptability, and impact of an EHR-integrated, ePRO-based symptom management program. TRIAL REGISTRATION: ClinicalTrials.gov NCT03850912 . Registered on February 22, 2019. Last updated on November 9, 2021.

eSyM: An Electronic Health Record-Integrated Patient-Reported Outcomes-Based Cancer Symptom Management Program Used by Six Diverse Health Systems.

PURPOSE: Collecting patient-reported outcomes (PROs) can improve symptom control and quality of life, enhance doctor-patient communication, and reduce acute care needs for patients with cancer. Digital solutions facilitate PRO collection, but without robust electronic health record (EHR) integration, effective deployment can be hampered by low patient and clinician engagement and high development and deployment costs. The important components of digital PRO platforms have been defined, but procedures for implementing integrated solutions are not readily available. METHODS: As part of the NCI's IMPACT consortium, six health care systems partnered with Epic to develop an EHR-integrated, PRO-based electronic symptom management program (eSyM) to optimize postoperative recovery and well-being during chemotherapy. The agile development process incorporated user-centered design principles that required engagement from patients, clinicians, and health care systems. Whenever possible, the system used validated content from the public domain and took advantage of existing EHR capabilities to automate processes. RESULTS: eSyM includes symptom surveys on the basis of the PRO-Common Terminology Criteria for Adverse Events (PRO-CTCAE) plus two global wellness questions; reminders and symptom self-management tip sheets for patients; alerts and symptom reports for clinicians; and population management dashboards. EHR dependencies include a secure Health Insurance Portability and Accountability Act-compliant patient portal; diagnosis, procedure and chemotherapy treatment plan data; registries that identify and track target populations; and the ability to create reminders, alerts, reports, dashboards, and charting shortcuts. CONCLUSION: eSyM incorporates validated content and leverages existing EHR capabilities. Build challenges include the innate technical limitations of the EHR, the constrained availability of site technical resources, and sites' heterogenous EHR configurations and policies. Integration of PRO-based symptom management programs into the EHR could help overcome adoption barriers, consolidate clinical workflows, and foster scalability and sustainability. We intend to make eSyM available to all Epic users.

The Effect of Disclosing Life Expectancy Information on Patients' Prognostic Understanding: Secondary Outcomes From a Multicenter Randomized Trial of a Palliative Chemotherapy Educational Intervention.

CONTEXT: Many advanced patients with cancer have unrealistic prognostic expectations. OBJECTIVES: We tested whether offering life expectancy (LE) statistics within palliative chemotherapy (PC) education promotes realistic expectations. METHODS: In this multicenter trial, patients with advanced colorectal and pancreatic cancers initiating first or second line PC were randomized to usual care versus a PC educational tool with optional LE information. Surveys at two weeks and three months assessed patients' review of the LE module and their reactions; at three months, patients estimated their LE and reported occurrence of prognosis and end-of-life (EOL) discussions. Wilcoxon tests and proportional odds models evaluated between-arm differences in LE self-estimates, and how realistic those estimates were (based on cancer type and line of treatment). RESULTS: From 2015 to 2017, 92 patients were randomized to the intervention and 94 to usual care. At baseline most patients (80.9%) wanted "a lot" or "as much information as possible" about the impact of chemotherapy on LE. Among patients randomized to the intervention, 52.0% reviewed the LE module by two weeks and 66.7% by three months-of whom 88.2% reported the information was important, 31.4% reported it was upsetting, and 3.9% regretted reviewing it. Overall, patients' LE self-estimates were very optimistic; 71.4% of patients with colorectal cancer estimated greater than five years; 50% pancreatic patients estimated greater than two years. The intervention had no effect on the length or realism of patients' LE self-estimates, or on the occurrence of prognostic or EOL discussions. CONCLUSIONS: Offering LE information within a PC educational intervention had no effect on patients' prognostic expectations.

Effectiveness of a Multimedia Educational Intervention to Improve Understanding of the Risks and Benefits of Palliative Chemotherapy in Patients With Advanced Cancer: A Randomized Clinical Trial.

Importance: Despite requirements of informed consent, patients with advanced cancer often receive palliative chemotherapy (PC) without understanding that the likelihood of cure is remote. Objective: To determine whether a PC educational video and booklet at treatment initiation could improve patients' understanding of its benefits and risks. Interventions: Regimen-specific PC videos and booklets presenting information about logistics, potential benefits, life expectancy (optional), adverse effects, and alternatives. Videos featured authentic patients sharing diverse experiences. After receiving treatment recommendations, research assistants distributed materials to patients for independent review. Design, Setting, and Participants: Multicenter randomized clinical trial of patients with advanced colorectal or pancreatic cancer starting first-line or second-line PC in 5 US cancer centers with enrollment from June 2015 to September 2017 and follow-up to December 2019. Main Outcomes and Measures: The primary outcome was accurate expectations of chemotherapy benefits at 3 months, defined as responding "not at all likely" to "What is your understanding of how likely the chemotherapy is to cure your cancer?" (from the Cancer Care Outcomes Research and Surveillance study). Secondary outcomes included understanding of adverse effects, decisional conflict (SURE test), regret (Decisional Regret Scale), and distress (Functional Assessment of Cancer Therapy-General emotional well-being subscale). Results: Among 186 patients with advanced colorectal or pancreatic cancer who were starting first-line or second-line PC (94 randomized to usual care, 92 to intervention; mean [SD] age, 59.3 [12.6] [range, 28-86] years; 107 [58%] male; 118 [63.4%] colorectal and 68 [36.6%] pancreatic cancer), most patients wanted "a lot" of information or "as much information as possible" about adverse effects (149, 80.1%), likelihood of cure (148, 79.6%), and prognosis (148, 79.6%). Among the intervention arm, 59 (78%) reviewed the booklet and 30 (40%) reviewed the video within 2 weeks. The primary outcome did not differ between intervention and control arms (52.6%; 95% CI, 40.3%-65.0%; vs 55.5%; 95% CI, 45.1%-66.0%). Accurate adverse effect understanding was more common among intervention than control patients (56.0%; 95% CI, 44.3%-67.7%; vs 40.2%; 95% CI, 29.5%-50.9%; P = .05), although this did not meet the threshold for statistical significance. The intervention did not increase distress, despite frank prognostic information. Other secondary outcomes were similar. Conclusions and Relevance: Provision of an educational video and booklet did not alter patients' expectation of cure from PC. Alternative delivery strategies, such as integration with nurse teaching, could be explored in future studies. Trial Registration: ClinicalTrials.gov Identifier: NCT02282722.

A stakeholder-driven approach to improve the informed consent process for palliative chemotherapy.

OBJECTIVE: Patients often anticipate cure from palliative chemotherapy. Better resources are needed to convey its risks and benefits. We describe the stakeholder-driven development and acceptability testing of a prototype video and companion booklet supporting informed consent (IC) for a common palliative chemotherapy regimen. METHODS: Our multidisciplinary team (researchers, advocates, clinicians) employed a multistep process of content development, production, critical evaluation, and iterative revisions. Patient/clinician stakeholders were engaged throughout using stakeholder advisory panels, featuring their voices within the intervention, conducting surveys and qualitative interviews. A national panel of 57 patient advocates, and 25 oncologists from nine US practices critiqued the intervention and rated its clarity, accuracy, balance, tone, and utility. Participants also reported satisfaction with existing chemotherapy IC materials. RESULTS: Few oncologists (5/25, 20%) or advocates (10/22, 45%) were satisfied with existing IC materials. In contrast, most rated our intervention highly, with 89-96% agreeing it would be useful and promote informed decisions. Patient voices were considered a key strength. Every oncologist indicated they would use the intervention regularly. CONCLUSION: Our intervention was acceptable to advocates and oncologists. A randomized trial is evaluating its impact on the chemotherapy IC process. PRACTICE IMPLICATIONS: Stakeholder-driven methods can be valuable for developing patient educational interventions.

Binding, inactivation, and adhesion forces between antimicrobial peptide cecropin P1 and pathogenic E. coli.

The antimicrobial peptide cecropin P1 (CP1) exhibits broad spectrum activity against planktonic bacteria, including Escherichia coli (E. coli). However, its activity when attached to a substrate has not been thoroughly studied. We immobilized CP1 to gold or silicon nitride, and studied how the method of attachment of peptide to the surface affected peptide interaction with and killing of the bacteria. Using the quartz crystal microbalance with dissipation monitoring (QCM-D), we characterized non-specific binding between CP1 to silicon nitride and gold, and covalent binding of cysteine-terminated CP1 (CP1-cys) to gold. The density of CP1-cys adsorbed on gold was more than the density of CP1 on silicon nitride, and activity against E. coli also depended on the method of attachment used to anchor the peptide to the surface. Twelve E. coli strains with known lipopolysaccharide (LPS) structures were studied. Bacterial adhesion with CP1 was strongest for E. coli with long O-antigens, as determined by atomic force microscopy (AFM). This may be caused by CP1 interacting with the hydrophilic part of the LPS, while control bacteria or those with short O-antigens had their hydrophobic lipid A region more exposed. Killing of E. coli due to contact with CP1 was dependent on the method by which the peptide was immobilized. Four out of 12 E. coli strains were killed when contacted with CP1-cys bound to gold via a thiol bond, while all 12 strains could be killed when in contact with CP1 on silicon nitride. In summary, both QCM-D adsorption experiments and adhesion forces measured by AFM showed a relationship between bacteria LPS length and binding or interaction with the antimicrobial peptide, but killing of E. coli by the peptide was most strongly dependent on how the peptide was attached to the surface.