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.
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.
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.
T he Covid-19 pandemic required rapid changes to research protocols, including immediate transitions to virtual participant recruitment and informed consent. In most cases, institutional review boards (IRBs) supported these transitions and reviewed and approved modifications to studies quickly. While restrictions to essential personnel were necessary to keep staff members and potential and enrolled participants safe, many researchers were not prepared for some of the unique, complex barriers to virtual study recruitment and retention. Using a survey study among newly diagnosed cancer patients as a case study, this paper will illuminate some of these challenges and describe possible solutions and silver linings to use for future virtual recruitment and consent processes.Given that virtual recruitment is likely to continue, it is important to ensure that it facilitates, rather than hinders, equitable and just recruitment. We will provide recommendations to proactively address these recruitment and consent challenges based on our experiences, stakeholder feedback, and institutional changes implemented after working closely with our IRB to ensure both short-and long-term success of remote studies. CASE DESCRIPTIONT he case that serves as our example was a research study that was adapted from in-person to virtual recruitment beginning in the initial Covid-19 peak (April 2020 to December 2021) and involved a behavioral intervention and survey. 1 The survey assessed ABSTRACT 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.
BackgroundDecision 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.MethodsWe 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.ResultsBetween 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 (β = .82, p = .27), referrals to cost‐related resources (β = −0.36, p = .81), shared decision‐making (β = −0.79, p = .32), decisional conflict postvisit (β = −0.34, p= .70), or at follow‐up (β = −2.19, p = .16), decision regret at follow‐up (β = −9.76, p = .11), or financial toxicity postvisit (β = −1.32, p = .63) or at follow‐up (β = −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.DiscussionDespite 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 ContributionPatients 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.
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