A Randomized Controlled Trial of the Implementation of BREASTChoice, a Multilevel Breast Reconstruction Decision Support Tool With Personalized Risk Predictiona.

OBJECTIVE: To implement the BREASTChoice decision tool into the electronic health record and evaluate its effectiveness. BACKGROUND: BREASTChoice, is a multilevel decision tool that: 1) educates patients about breast reconstruction; 2) estimates personalized risk of complications; 3) clarifies patient preferences; and 4) informs clinicians about patients' risk and preferences. METHODS: A multisite randomized controlled trial enrolled adult women with stage 0-III breast malignancy undergoing mastectomy. Participants were randomized to BREASTChoice or a control website. A survey assessed knowledge, preferences, decisional conflict, shared decision-making, preferred treatment, and usability. We conducted intent-to-treat (ITT), per-protocol (PP) analyses (those randomized to BREASTChoice who accessed the tool), and stratified analyses. RESULTS: 23/25 eligible clinicians enrolled. 369/761 (48%) contacted patients enrolled and were randomized. Patients' average age was 51 years; 15% were older than 65. BREASTChoice participants had higher knowledge than control participants (ITT: mean 70.6 vs. 67.4, P=0.08; PP: mean 71.4 vs. 67.4, P=0.03), especially when stratified by site (ITT: P=0.04, PP: P=0.01), age (ITT: P=0.04, PP: P=0.02), and race (ITT: P=0.04, PP: P=0.01). BREASTChoice did not improve decisional conflict, match between preferences and treatment, or shared decision-making. In PP analyses, fewer high-risk patients using BREASTChoice chose reconstruction. BREASTChoice had high usability. CONCLUSIONS: BREASTChoice is a novel decision tool incorporating risk prediction, patient education, and clinician engagement. Patients using BREASTChoice had higher knowledge; older adults and those from racially minoritized backgrounds especially benefitted. There was no impact on other decision outcomes. Future studies should overcome implementation barriers and specifically examine decision outcomes among high-risk patients.

The impact of adding cost information to a conversation aid to support shared decision making about low-risk prostate cancer treatment: Results of a stepped-wedge cluster randomised trial.

BACKGROUND: Decision aids help patients consider the benefits and drawbacks of care options but rarely include cost information. We assessed the impact of a conversation-based decision aid containing information about low-risk prostate cancer management options and their relative costs. METHODS: We conducted a stepped-wedge cluster randomised trial in outpatient urology practices within a US-based academic medical center. We randomised five clinicians to four intervention sequences and enroled patients newly diagnosed with low-risk prostate cancer. Primary patient-reported outcomes collected postvisit included the frequency of cost conversations and referrals to address costs. Other patient-reported outcomes included: decisional conflict postvisit and at 3 months, decision regret at 3 months, shared decision-making postvisit, financial toxicity postvisit and at 3 months. Clinicians reported their attitudes about shared decision-making pre- and poststudy, and the intervention's feasibility and acceptability. We used hierarchical regression analysis to assess patient outcomes. The clinician was included as a random effect; fixed effects included education, employment, telehealth versus in-person visit, visit date, and enrolment period. RESULTS: Between April 2020 and March 2022, we screened 513 patients, contacted 217 eligible patients, and enroled 117/217 (54%) (51 in usual care, 66 in the intervention group). In adjusted analyses, the intervention was not associated with cost conversations (ß = .82, p = .27), referrals to cost-related resources (ß = -0.36, p = .81), shared decision-making (ß = -0.79, p = .32), decisional conflict postvisit (ß = -0.34, p= .70), or at follow-up (ß = -2.19, p = .16), decision regret at follow-up (ß = -9.76, p = .11), or financial toxicity postvisit (ß = -1.32, p = .63) or at follow-up (ß = -2.41, p = .23). Most clinicians and patients had positive attitudes about the intervention and shared decision-making. In exploratory unadjusted analyses, patients in the intervention group experienced more transient indecision (p < .02) suggesting increased deliberation between visit and follow-up. DISCUSSION: Despite enthusiasm from clinicians, the intervention was not significantly associated with hypothesised outcomes, though we were unable to robustly test outcomes due to recruitment challenges. Recruitment at the start of the COVID-19 pandemic impacted eligibility, sample size/power, study procedures, and increased telehealth visits and financial worry, independent of the intervention. Future work should explore ways to support shared decision-making, cost conversations, and choice deliberation with a larger sample. Such work could involve additional members of the care team, and consider the detail, quality, and timing of addressing these issues. PATIENT OR PUBLIC CONTRIBUTION: Patients and clinicians were engaged as stakeholder advisors meeting monthly throughout the duration of the project to advise on the study design, measures selected, data interpretation, and dissemination of study findings.

Developing an Educational and Decision Support Tool for Stage I Lung Cancer Using Decision Science.

BACKGROUND: Guidelines recommend shared decision-making about treatment options for high-risk, operable stage I lung cancer. Patient decision aids can facilitate shared decision-making; however, their development, implementation, and evaluation in routine clinical practice presents numerous challenges and opportunities. METHODS: The purpose of this review is to reflect on the process of tool development; identify the challenges associated with meeting the needs of patients, clinicians from multiple disciplines, and institutional workflow during implementation; and propose recommendations for future clinicians who wish to develop, refine, or implement similar tools into routine care. RESULTS: In this review, we: (1) discuss guidelines for decision aid development; (2) describe how we applied those to create an education and decision support tool for patients with clinical stage I lung cancer deciding between radiation therapy and surgical resection; and (3) highlight challenges in implementing and evaluating the tool. CONCLUSIONS: We provide recommendations for those seeking to develop, refine, or implement similar tools into routine care.

Challenges and Possible Solutions to Adapting to Virtual Recruitment: Lessons Learned from a Survey Study during the Covid-19 Pandemic.

The Covid-19 pandemic required rapid changes to research protocols, including immediate transitions to recruiting research participants and conducting the informed consent process virtually. This case study details the challenges our research team faced adapting an in-person, behavioral-intervention and survey study to virtual recruitment. We reflect on the impact of these rapid changes on recruitment and retention, discuss protocol changes we made to address these challenges and the needs of potential and enrolled participants, and propose recommendations for future work. Using computer technology to display professional return phone numbers, being flexible by contacting potential participants through various means, minimizing email communication due to added regulatory requirements, and partnering with the institutional review board to shorten and improve the consent document and process were critical to study success. This case study can offer insight to other researchers as they navigate similar processes. Virtual recruitment is likely to continue; it is important to ensure that it facilitates, rather than hinders, equitable and just recruitment practices.

A case study of adapting a health insurance decision intervention from trial into routine cancer care.

OBJECTIVE: This study adapted Improving Cancer Patients' Insurance Choices (I Can PIC), an intervention to help cancer patients navigate health insurance decisions and care costs. The original intervention improved knowledge and confidence making insurance decisions, however, users felt limited by choices provided in insurance markets. Using decision trees and frameworks to guide adaptations, we modified I Can PIC to focus on using rather than choosing health insurance. The COVID-19 pandemic introduced unforeseen obstacles, prompting changes to study protocols. As a result, we allowed users outside of the study to use I Can PIC (> 1050 guest users) to optimize public benefit. This paper describes the steps took to conduct the study, evaluating both the effectiveness of I Can PIC and the implementation process to improve its impact. RESULTS: Although I Can PIC users had higher knowledge and health insurance literacy compared to the control group, results were not statistically significant. This outcome may be associated with systems-level challenges as well as the number and demographic characteristics of participants. The publicly available tool can be a resource for those navigating insurance and care costs, and researchers can use this flexible approach to intervention delivery and testing as future health emergencies arise.

Neonatal necrotizing enterocolitis-associated DNA methylation signatures in the colon are evident in stool samples of affected individuals.

Aim: Neonatal necrotizing enterocolitis (NEC) is a deadly and unpredictable gastrointestinal disease, for which no biomarker exists. We aimed to describe the methylation patterns in stool and colon from infants with NEC. Methods: We performed a high-resolution genome-wide epigenomic analysis using solution-phase hybridization and next-generation sequencing of bisulfite-converted DNA. Results: Our data reveal significant genomic hypermethylation in NEC tissues compared with non-NEC controls. These changes were more pronounced in regions outside CpG islands and gene regulatory elements, suggesting that NEC-specific hypermethylation is not a nonspecific global phenomenon. Conclusions: This study provides evidence of a methylomic signature associated with NEC that is detectable noninvasively and provides a new opportunity for the development of a novel diagnostic method for NEC.

Evaluation of the Neonatal Sequential Organ Failure Assessment and Mortality Risk in Preterm Infants With Late-Onset Infection.

Importance: Infection in neonates remains a substantial problem. Advances for this population are hindered by the absence of a consensus definition for sepsis. In adults, the Sequential Organ Failure Assessment (SOFA) operationalizes mortality risk with infection and defines sepsis. The generalizability of the neonatal SOFA (nSOFA) for neonatal late-onset infection-related mortality remains unknown. Objective: To determine the generalizability of the nSOFA for neonatal late-onset infection-related mortality across multiple sites. Design, Setting, and Participants: A multicenter retrospective cohort study was conducted at 7 academic neonatal intensive care units between January 1, 2010, and December 31, 2019. Participants included 653 preterm (<33 weeks) very low-birth-weight infants. Exposures: Late-onset (>72 hours of life) infection including bacteremia, fungemia, or surgical peritonitis. Main Outcomes and Measures: The primary outcome was late-onset infection episode mortality. The nSOFA scores from survivors and nonsurvivors with confirmed late-onset infection were compared at 9 time points (T) preceding and following event onset. Results: In the 653 infants who met inclusion criteria, median gestational age was 25.5 weeks (interquartile range, 24-27 weeks) and median birth weight was 780 g (interquartile range, 638-960 g). A total of 366 infants (56%) were male. Late-onset infection episode mortality occurred in 97 infants (15%). Area under the receiver operating characteristic curves for mortality in the total cohort ranged across study centers from 0.71 to 0.95 (T0 hours), 0.77 to 0.96 (T6 hours), and 0.78 to 0.96 (T12 hours), with utility noted at all centers and in aggregate. Using the maximum nSOFA score at T0 or T6, the area under the receiver operating characteristic curve for mortality was 0.88 (95% CI, 0.84-0.91). Analyses stratified by sex or Gram-stain identification of pathogen class or restricted to infants born at less than 25 weeks' completed gestation did not reduce the association of the nSOFA score with infection-related mortality. Conclusions and Relevance: The nSOFA score was associated with late-onset infection mortality in preterm infants at the time of evaluation both in aggregate and in each center. These findings suggest that the nSOFA may serve as the foundation for a consensus definition of sepsis in this population.

Global hypermethylation of intestinal epithelial cells is a hallmark feature of neonatal surgical necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) remains one of the overall leading causes of death in premature infants, and the pathogenesis is unpredictable and not well characterized. The aim of our study was to determine the molecular phenotype of NEC via transcriptomic and epithelial cell-specific epigenomic analysis, with a specific focus on DNA methylation. METHODS: Using laser capture microdissection, epithelial cell-specific methylation signatures were characterized by whole-genome bisulfite sequencing of ileal and colonic samples at the time of surgery for NEC and after NEC had healed at reanastomosis (n = 40). RNA sequencing was also performed to determine the transcriptomic profile of these samples, and a comparison was made to the methylome data. RESULTS: We found that surgical NEC has a considerable impact on the epigenome by broadly increasing DNA methylation levels, although these effects are less pronounced in genomic regions associated with the regulation of gene expression. Furthermore, NEC-related DNA methylation signatures were influenced by tissue of origin, with significant differences being noted between colon and ileum. We also identified numerous transcriptional changes in NEC and clear associations between gene expression and DNA methylation. CONCLUSIONS: We have defined the intestinal epigenomic and transcriptomic signatures during surgical NEC, which will advance our understanding of disease pathogenesis and may enable the development of novel precision medicine approaches for NEC prediction, diagnosis and phenotyping.