External Validation of a Digital Pathology-based Multimodal Artificial Intelligence Architecture in the NRG/RTOG 9902 Phase 3 Trial.

BACKGROUND: Accurate risk stratification is critical to guide management decisions in localized prostate cancer (PCa). Previously, we had developed and validated a multimodal artificial intelligence (MMAI) model generated from digital histopathology and clinical features. Here, we externally validate this model on men with high-risk or locally advanced PCa treated and followed as part of a phase 3 randomized control trial. OBJECTIVE: To externally validate the MMAI model on men with high-risk or locally advanced PCa treated and followed as part of a phase 3 randomized control trial. DESIGN, SETTING, AND PARTICIPANTS: Our validation cohort included 318 localized high-risk PCa patients from NRG/RTOG 9902 with available histopathology (337 [85%] of the 397 patients enrolled into the trial had available slides, of which 19 [5.6%] failed due to poor image quality). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Two previously locked prognostic MMAI models were validated for their intended endpoint: distant metastasis (DM) and PCa-specific mortality (PCSM). Individual clinical factors and the number of National Comprehensive Cancer Network (NCCN) high-risk features served as comparators. Subdistribution hazard ratio (sHR) was reported per standard deviation increase of the score with corresponding 95% confidence interval (CI) using Fine-Gray or Cox proportional hazards models. RESULTS AND LIMITATIONS: The DM and PCSM MMAI algorithms were significantly and independently associated with the risk of DM (sHR [95% CI] = 2.33 [1.60-3.38], p < 0.001) and PCSM, respectively (sHR [95% CI] = 3.54 [2.38-5.28], p < 0.001) when compared against other prognostic clinical factors and NCCN high-risk features. The lower 75% of patients by DM MMAI had estimated 5- and 10-yr DM rates of 4% and 7%, and the highest quartile had average 5- and 10-yr DM rates of 19% and 32%, respectively (p < 0.001). Similar results were observed for the PCSM MMAI algorithm. CONCLUSIONS: We externally validated the prognostic ability of MMAI models previously developed among men with localized high-risk disease. MMAI prognostic models further risk stratify beyond the clinical and pathological variables for DM and PCSM in a population of men already at a high risk for disease progression. This study provides evidence for consistent validation of our deep learning MMAI models to improve prognostication and enable more informed decision-making for patient care. PATIENT SUMMARY: This paper presents a novel approach using images from pathology slides along with clinical variables to validate artificial intelligence (computer-generated) prognostic models. When implemented, clinicians can offer a more personalized and tailored prognostic discussion for men with localized prostate cancer.

The Use of Medical Crowdfunding to Mitigate the Personal Costs of Serious Chronic Illness: Scoping Review.

BACKGROUND: Persons diagnosed with serious chronic illnesses and their caretakers experience multiple types of financial costs that strain their income and generate financial distress. Many turn to medical crowdfunding (MCF) to mitigate the harms of these costs on their health and quality of life. OBJECTIVE: This scoping review aims to summarize the research on MCF for persons diagnosed with serious chronic illness regarding study designs and methods; the responsible conduct of research practices; and study foci as they relate to stress, stress appraisals, and the coping processes. METHODS: This review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. Eligible studies were conducted in countries designated as high income by the World Bank and focused on beneficiaries diagnosed with serious chronic illness. The findings of the included studies were summarized as they related to the key concepts in a conceptual framework derived from an established stress, appraisal, and coping framework and a conceptual model of financial toxicity in pediatric oncology. RESULTS: Overall, 26 studies were eligible for inclusion in the review. The main findings included a lack of integration of qualitative and quantitative approaches and the inconsistent reporting of the responsible conduct of research practices. The included studies focused on financial stressors that contributed to financial burden, such as out-of-pocket payments of medical bills, basic living expenses, medical travel expenses, and lost income owing to illness-related work disruptions. Few studies addressed stress appraisals as threatening or the adequacy of available financial resources. When mentioned, appraisals related to the global financial struggle during the COVID-19 pandemic or the capacity of social network members to donate funds. The consequences of MCF included the receipt of 3 forms of social support (tangible, informational, and emotional), privacy loss, embarrassment, and the propagation of scientifically unsupported information. Studies found that friends and family tended to manage MCF campaigns. Although most of the studies (21/26, 81%) focused on monetary outcomes, a few (5/26, 19%) concentrated on peoples' experiences with MCF. CONCLUSIONS: The identified methodological gaps highlight the need for more robust and reproducible approaches to using the copious data available on public MCF platforms. The integration of quantitative and qualitative methods will allow for nuanced explorations of the MCF experience. A more consistent elaboration of strategies to promote the responsible conduct of research is warranted to minimize risk to populations that are vulnerable and express concerns regarding the loss of privacy. Finally, an examination of the unanticipated consequences of MCF is critical for the development of future interventions to optimize existing supports while providing needed supports, financial and nonfinancial, that are lacking.

Cancer Screening and Treatment Delays During the COVID-19 Pandemic and the Role of Health Literacy in Care Re-engagement: Findings from an NCI-Designated Comprehensive Cancer Center sample.

The COVID-19 pandemic has led to numerous delays in cancer-related care and cancer-specific screening, but the extent is not fully understood. For those that experience a delay or disruption in care, health related self-management is required to re-engage in care pathways and the role of health literacy in this pathway has not been explored. The purpose of this analysis is to (1) report the frequency of self-reported delays in cancer treatment and preventative screening services at an academic, NCI-designated center during the COVID-19 pandemic and (2) investigate cancer-related care and screening delays among those with adequate and limited health literacy. A cross-sectional survey was administered from an NCI-designated Cancer Center with a rural catchment area during November 2020 through March 2021. A total of 1,533 participants completed the survey, and nearly 19 percent of participants were categorized as having limited health literacy. Twenty percent of those with a cancer diagnosis reported a delay in cancer-related care; and 23-30% of the sample reported a delay in cancer screening. In general, the proportions of delays among those with adequate and limited health literacy were similar with the exception of colorectal cancer screening. There was also a notable difference in the ability to re-engage in cervical cancer screening among those with adequate and limited health literacy. Thus, there is a role for those engaged in cancer-related education and outreach to offer additional navigation resources for those at risk to cancer-related care and screening disruptions. Future study is warranted to investigate the role of health literacy on cancer care engagement.

Data Science and Precision Oncology Nursing: Creating an Analytic Ecosystem to Support Personalized Supportive Care across the Trajectory of Illness.

OBJECTIVES: The authors' objective is to present an overarching framework of an analytic ecosystem using diverse data domains and data science approaches that can be used and implemented across the cancer continuum. Analytic ecosystems can improve quality practices and offer enhanced anticipatory guidance in the era of precision oncology nursing. DATA SOURCES: Published scientific articles supporting the development of a novel framework with a case exemplar to provide applied examples of current barriers in data integration and use. CONCLUSION: The combination of diverse data sets and data science analytic approaches has the potential to extend precision oncology nursing research and practice. Integration of this framework can be implemented within a learning health system where models can update as new data become available across the continuum of the cancer care trajectory. To date, data science approaches have been underused in extending personalized toxicity assessments, precision supportive care, and enhancing end-of-life care practices. IMPLICATIONS FOR NURSING PRACTICE: Nurses and nurse scientists have a unique role in the convergence of data science applications to support precision oncology across the trajectory of illness. Nurses also have specific expertise in supportive care needs that have been dramatically underrepresented in existing data science approaches thus far. They also have a role in centering the patient and family perspectives and needs as these frameworks and analytic capabilities evolve.

Application of Instrumental Variable Analysis in Pediatric End-of-Life Research: A Case Study.

Instrumental variable analysis (IVA) has been widely used in many fields, including health care, to determine the comparative effectiveness of a treatment, intervention, or policy. However, its application in pediatric end-of-life care research has been limited. This article provides a brief overview of IVA and its assumptions. It illustrates the use of IVA by investigating the comparative effectiveness of concurrent versus standard hospice care for reducing 1-day hospice enrollments. Concurrent hospice care is a relatively recent type of care enabled by the Affordable Care Act in 2010 for children enrolled in the Medicaid program and allows for receiving life-prolonging medical treatment concurrently with hospice care. The IVA was conducted using observational data from 18,152 pediatric patients enrolled in hospice between 2011 and 2013. The results indicated that enrollment in concurrent hospice care reduced 1-day enrollment by 19.3%.

Perspectives on Access to Novel Therapeutics Through Clinical Trials Among Adolescents and Young Adults with Advanced Cancer: Implications for Patient-Centered Clinical Trials.

Purpose: Adolescents and young adults (AYA) with advanced cancer have unequal access to and enrollment in clinical trials. Many AYA use online platforms to share their treatment experiences. The purpose of this analysis was to explore how AYA discuss clinical trials and their access to novel therapeutics through their blogs. Methods: We studied illness blogs from 22 AYA (ages 16-38 years old) with advanced cancer who specifically discussed experiences enrolling in a clinical trial. Nearly 500 excerpts were abstracted from their blogs, and we used qualitative descriptive methodology and thematic analysis to explore their longitudinal perspectives. Results: We describe three themes: (1) "Blinded", which represents the uncertainty in treatment pathway and underrepresentation of AYA in clinical trials, (2) "Totally healthy except for the damn cancer", which represents the numerous challenges associated with meeting eligibility criteria and lack of available clinical trials, and (3) "Go ahead and send me the bill!", which represents the precarious financial challenges associated with participating with clinical trials (both direct costs and indirect costs associated with travel, time away from work) as well as the costs of novel therapeutics. Conclusions: By studying AYA online narratives, we can outline several gaps in accessing clinical trials and generate future research priorities. AYA with advanced cancer are known to have aggressive trajectories, and there are opportunities to integrate patient-reported outcomes and supportive care frameworks embedded within clinical trial study design.

Predictors of cervical cancer screening for refugee women attending an international family medicine clinic in the United States.

PURPOSE: Cervical cancer screening (CCS) rates are lower for foreign-born women in the United States (U.S.) compared with the overall population. This study aimed to determine the CCS rate and predictors among refugees who were identified as female attending a family medicine clinic. METHODS: A retrospective chart review included refugee individuals aged 21+, seen in the previous 3 years (3/23/2015-3/20/2018), without hysterectomy (n = 525). Lab results determined CCS rate. Chi-square and logistic regression models explored predictors of CCS. RESULTS: Overall, 60.0% were up-to-date (UTD) on CCS. Individuals aged 30-49, married, and with [Formula: see text] 1 child had higher odds of being UTD. Ten or more years living in the U.S. was a significant bivariate predictor of CCS, and approached significance in the multivariate model. CONCLUSION: This study begins to fill gaps in knowledge about cervical cancer control among individuals who resettled in the U.S. as refugees and, given that CCS rates are suboptimal, informs clinical practice improvements and directions for future research.

A National Study to Compare Effective Management of Constipation in Children Receiving Concurrent Versus Standard Hospice Care.

Constipation is a distressing and uncomfortable symptom children experience at end of life. There is a gap in knowledge about how different approaches to hospice care delivery might improve pediatric symptom management of constipation. The purpose of this study was to evaluate the effectiveness of pediatric concurrent hospice versus standard hospice care to manage constipation. Medicaid data (2011-2013) were analyzed. Children who were younger than 21 years enrolled in hospice care and had a hospice enrollment between January 1, 2011, and December 31, 2013, were included. Instrumental variable analysis was used to test the effectiveness of concurrent versus standard hospice care. Among the 18 152 children, approximately 14% of participants were diagnosed or treated for constipation from a nonhospice provider during hospice enrollment. A higher proportion of children received nonhospice care for constipation in concurrent hospice care, compared with standard hospice (19.5% vs 13.2%), although this was not significant (ß = .22, P < .05) after adjusting for covariates. The findings demonstrated that concurrent care was no more effective than standard hospice care in managing pediatric constipation. Hospice and nonhospice providers may be doing a sufficient job ordering bowel regimens before constipation becomes a serious problem for children at end of life.

Pediatric End-of-Life Care in Rural America: A Systematic Review.

BACKGROUND: Families increasingly desire to bring their children home from the acute care setting at end of life. This transition includes home to rural or remote areas. Little is known about the end-of-life care for children who reside in rural areas. OBJECTIVE: The purpose of this study was to comprehensively review and summarize the evidence regarding end-of-life care for children living in rural areas, identify key findings and gaps in the literature, and make recommendations for future research. METHODS: A systematic review was conducted from 2011 to 2021 using MEDLINE and CINAHL databases. RESULTS: Nine studies met inclusion criteria. Key themes from the literature included: barriers, facilitators, and needs. Three articles identified barriers to end-of-life care for children in rural communities, which included access to end-of-life care and clinicians trained to provide pediatric care. Three studies identified and evaluated the facilitators of end-of-life care for rural children. The articles identified technology and additional training as facilitators. Four studies reported on the needs of rural children for end-of-life care with serious illness. CONCLUSIONS: We found major barriers and unmet needs in the delivery of rural pediatric end-of-life care. A few facilitators in delivery of this type of care were explored. Overall research in this area was sparse. Future studies should focus on understanding the complexities associated with delivery of pediatric end-of-life care in rural areas.

Pediatric surgical errors: A systematic scoping review.

BACKGROUND: Medical errors were largely concealed prior to the landmark report "To Err Is Human". The purpose of this systematic scoping review was to determine the extent pediatric surgery defines and studies errors, and to explore themes among papers focused on errors in pediatric surgery. METHODS: The methodological framework used to conduct this scoping study has been outlined by Arksey and O'Malley. In January 2020, PubMed, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched. Oxford Level of Evidence was assigned to each study; only studies rated Level 3 or higher were included. RESULTS: Of 3,064 initial studies, 12 were included in the final analysis: 4 cohort studies, and 8 outcome/audit studies. This data represented 5,442,000 aggregate patients and 8,893 errors. There were 6 different error definitions and 5 study methods. Common themes amongst the studies included a systems-focused approach, an increase in errors seen with increased complexity, and studies exploring the relationship between error and adverse events. CONCLUSIONS: This study revealed multiple error definitions, multiple error study methods, and common themes described in the pediatric surgical literature. Opportunities exist to improve the safety of surgical care of children by reducing errors. Original Scientific Research Type of Study: Systematic Scoping Review Level of Evidence Rating: 1.

A Comparison of Young Adults With and Without Cancer in Concurrent Hospice Care: Implications for Transitioning to Adult Health Care.

Purpose: Concurrent hospice care provides important end-of-life care for youth under 21 years. Those nearing 21 years must decide whether to shift to adult hospice or leave hospice for life-prolonging care. This decision may be challenging for young adults with cancer, given the intensity of oncology care. Yet, little is known about their needs. We compared young adults with and without cancer in concurrent hospice care. Methods: Retrospective comparative design used data from 2011 to 2013 U.S. Medicaid data files. Decedents were included if they were 20 years of age, enrolled in Medicaid hospice care, and used nonhospice medical services on the same day as hospice care based on their Medicaid claims activity dates. Results: Among 226 decedents, 21% had cancer; more than half were female (60.6%), Caucasian (53.5%), non-Hispanic (77.4%), urban dwelling (58%), and had mental/behavioral disorder (53%). Young adults with cancer were more often non-Caucasian (68.7% vs. 40.4%), technology dependent (47.9% vs. 24.2%), had comorbidities (83.3% vs. 30.3%), and lived in rural (58.3% vs. 37.6%), southern (41.7% vs. 20.8%) areas versus peers without cancer. Those with cancer had significantly fewer live discharges from hospice (5.7 vs. 17.3) and sought treatment for symptoms more often from nonhospice providers (35.4% vs. 14.0%). Conclusions: Young adults in concurrent hospice experience medical complexity, even at end-of-life. Understanding care accessed at 20 years helps providers guide young adults and families considering options in adult-focused care. Clinical and demographic differences among those with and without cancer in concurrent care highlight needs for research exploring racial and geographic equity.

Effects of Adjuvant Endocrine Therapy Adherence and Radiation on Recurrence and Survival Among Older Women with Early-Stage Breast Cancer.

BACKGROUND: The Cancer and Leukemia Group-B 9343 (CALGB 9343) trial demonstrated that women aged ≥ 70 years with early-stage breast cancer can safely omit radiation therapy (RT) and be treated with breast-conserving surgery (BCS) and adjuvant endocrine therapy (AET) alone. AET adherence is low, leaving an undertreated cohort who may be at increased risk of recurrence and death. We hypothesized that AET adherence and adjuvant treatment choice impact recurrence and survival among CALGB 9343 eligible women. PATIENTS AND METHODS: SEER-Medicare was used to identify CALGB 9343 eligible women who underwent BCS between 2007 and 2016. Medicare claims were used to identify AET use, and the proportion of days covered by AET was used to categorize adherent (PDC ≥ 0.80) versus nonadherent patients (PDC < 0.80). Recurrence-free, cancer-specific, and overall survival were assessed using Cox proportional hazards models. RESULTS: In total, 10,719 women were identified, of whom 780 (7.3%) underwent BCS alone, 1490 (13.9%) underwent BCS + RT, 1663 (15.5%) underwent BCS + AET, and 6786 (63.3%) had BCS + RT + AET. Among women treated with BCS + AET, adherent patients had lower recurrence than did nonadherent patients (HR = 0.65, 95% CI: 0.50-0.85). With respect to adjuvant treatment combinations, there was no recurrence difference between the BCS + RT + AET group and BCS + AET group (HR = 0.81, 95% CI: 0.54-1.21). There was equivalent cancer-specific but worse overall survival in the BCS + AET group versus the BCS + AET + RT group. CONCLUSIONS: While BCS + RT + AET may represent overtreatment for some, AET nonadherent women who omit RT are at risk for worse outcomes. Treatment decisions regarding RT omission should be tailored to the individual patient, taking into consideration the chances of AET nonadherence and the patients' own risk tolerance.

Predictive Monitoring-Impact in Acute Care Cardiology Trial (PM-IMPACCT): Protocol for a Randomized Controlled Trial.

BACKGROUND: Patients in acute care wards who deteriorate and are emergently transferred to intensive care units (ICUs) have poor outcomes. Early identification of patients who are decompensating might allow for earlier clinical intervention and reduced morbidity and mortality. Advances in bedside continuous predictive analytics monitoring (ie, artificial intelligence [AI]-based risk prediction) have made complex data easily available to health care providers and have provided early warning of potentially catastrophic clinical events. We present a dynamic, visual, predictive analytics monitoring tool that integrates real-time bedside telemetric physiologic data into robust clinical models to estimate and communicate risk of imminent events. This tool, Continuous Monitoring of Event Trajectories (CoMET), has been shown in retrospective observational studies to predict clinical decompensation on the acute care ward. There is a need to more definitively study this advanced predictive analytics or AI monitoring system in a prospective, randomized controlled, clinical trial. OBJECTIVE: The goal of this trial is to determine the impact of an AI-based visual risk analytic, CoMET, on improving patient outcomes related to clinical deterioration, response time to proactive clinical action, and costs to the health care system. METHODS: We propose a cluster randomized controlled trial to test the impact of using the CoMET display in an acute care cardiology and cardiothoracic surgery hospital floor. The number of admissions to a room undergoing cluster randomization was estimated to be 10,424 over the 20-month study period. Cluster randomization based on bed number will occur every 2 months. The intervention cluster will have the CoMET score displayed (along with standard of care), while the usual care group will receive standard of care only. RESULTS: The primary outcome will be hours free from events of clinical deterioration. Hours of acute clinical events are defined as time when one or more of the following occur: emergent ICU transfer, emergent surgery prior to ICU transfer, cardiac arrest prior to ICU transfer, emergent intubation, or death. The clinical trial began randomization in January 2021. CONCLUSIONS: Very few AI-based health analytics have been translated from algorithm to real-world use. This study will use robust, prospective, randomized controlled, clinical trial methodology to assess the effectiveness of an advanced AI predictive analytics monitoring system in incorporating real-time telemetric data for identifying clinical deterioration on acute care wards. This analysis will strengthen the ability of health care organizations to evolve as learning health systems, in which bioinformatics data are applied to improve patient outcomes by incorporating AI into knowledge tools that are successfully integrated into clinical practice by health care providers. TRIAL REGISTRATION: ClinicalTrials.gov NCT04359641; https://clinicaltrials.gov/ct2/show/NCT04359641. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29631.

Health Inequity in Cervical Cancer Control Among Refugee Women in the United States by Country of Origin.

Purpose: To describe cervical cancer control practices from common countries of origin for women who resettle in the United States as refugees to highlight this persistent health inequity. Methods: Describe presence/type of national cervical cancer screening program, screening coverage percentage, and human papillomavirus (HPV) vaccination program presence and coverage. Results: Nine of 15 included countries screen opportunistically. Most do not use high-performing tests, and estimates of screening coverage were limited. Only one country offers HPV vaccination. Conclusion: Countries of origin for refugee women may lack effective national cervical cancer control programs. To meet the World Health Organization (WHO)'s call to eliminate cervical cancer by 2030, focus on culturally tailored education, and continued research are paramount.

A View from the past into our collective future: the oncofertility consortium vision statement.

PURPOSE: Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. METHODS: The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. RESULTS: This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. CONCLUSION: The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future.

Congenital Melanocytic Nevus: Considerations for Neonatal Clinicians and a Parent Perspective.

Congenital melanocytic nevus (CMN) or nevi, also known as dark moles, are present at birth. While small CMN are quite common, large and giant nevi are rare and can be associated with significant psychological distress and the potential for further clinical sequelae. Neonatal clinicians can offer anticipatory guidance to families through distribution of resources and navigation to additional consultants.