A mixed-method approach to generate and deliver rapid-cycle evaluation feedback: lessons learned from a multicenter implementation trial in pediatric surgery.

BACKGROUND: Rapid-cycle feedback loops provide timely information and actionable feedback to healthcare organizations to accelerate implementation of interventions. We aimed to (1) describe a mixed-method approach for generating and delivering rapid-cycle feedback and (2) explore key lessons learned while implementing an enhanced recovery protocol (ERP) across 18 pediatric surgery centers. METHODS: All centers are members of the Pediatric Surgery Research Collaborative (PedSRC, www.pedsrc.org ), participating in the ENhanced Recovery In CHildren Undergoing Surgery (ENRICH-US) trial. To assess implementation efforts, we conducted a mixed-method sequential explanatory study, administering surveys and follow-up interviews with each center's implementation team 6 and 12 months following implementation. Along with detailed notetaking and iterative discussion within our team, we used these data to generate and deliver a center-specific implementation report card to each center. Report cards used a traffic light approach to quickly visualize implementation status (green = excellent; yellow = needs improvement; red = needs significant improvement) and summarized strengths and opportunities at each timepoint. RESULTS: We identified several benefits, challenges, and practical considerations for assessing implementation and using rapid-cycle feedback among pediatric surgery centers. Regarding potential benefits, this approach enabled us to quickly understand variation in implementation and corresponding needs across centers. It allowed us to efficiently provide actionable feedback to centers about implementation. Engaging consistently with center-specific implementation teams also helped facilitate partnerships between centers and the research team. Regarding potential challenges, research teams must still allocate substantial resources to provide feedback rapidly. Additionally, discussions and consensus are needed across team members about the content of center-specific feedback. Practical considerations include carefully balancing timeliness and comprehensiveness when delivering rapid-cycle feedback. In pediatric surgery, moreover, it is essential to actively engage all key stakeholders (including physicians, nurses, patients, caregivers, etc.) and adopt an iterative, reflexive approach in providing feedback. CONCLUSION: From a methodological perspective, we identified three key lessons: (1) using a rapid, mixed method evaluation approach is feasible in pediatric surgery and (2) can be beneficial, particularly in quickly understanding variation in implementation across centers; however, (3) there is a need to address several methodological challenges and considerations, particularly in balancing the timeliness and comprehensiveness of feedback. TRIAL REGISTRATION: NIH National Library of Medicine Clinical Trials. CLINICALTRIALS: gov Identifier: NCT04060303. Registered August 7, 2019, https://clinicaltrials.gov/ct2/show/NCT04060303.

Disparities in Utilization of Same-Day Discharge Following Appendectomy in Children.

INTRODUCTION: Disparities in the delivery of pediatric surgical care exist for racial and ethnic minority groups. Utilization of same-day discharge (SDD) following appendectomy for acute, uncomplicated appendicitis is increasing; however, rates among diverse populations have not been explored to evaluate equitable care delivery and healthcare utilization. Our objective was to determine whether race and ethnicity are associated with rates of SDD and postdischarge healthcare utilization. We hypothesized that racial and ethnic minority groups would have lower rates of SDD. METHODS: This retrospective cohort study used data from the 2015-2019 American College of Surgeons National Surgical Quality Improvement Program-Pediatric clinical registry and included children who underwent appendectomy. Patients with complicated appendicitis were excluded. Primary exposure was racial or ethnic group. The primary outcome was SDD, and secondary outcomes included postdischarge emergency department visits and hospital readmissions. RESULTS: Of 37,579 simple appendicitis patients, SDD after appendectomy occurred in 10,012 (26.6%). On multivariable analysis, Black or African American race was associated with lower likelihood of SDD (adjusted odds ratio [aOR]: 0.85; 95% confidence interval [95% CI]:0.79-0.92; P < 0.0001). Hispanic ethnicity was associated with higher likelihood of SDD (aOR: 1.19; 95% CI: 1.12-1.25; P < 0.0001). Likelihood of postoperative emergency department visits was higher in Black or African American patients (aOR: 1.36; 95% CI: 1.14-1.62; P < 0.001) and Hispanic patients (aOR: 1.37; 95% CI: 1.12-1.58; P < 0.0001). Hospital readmission rates were similar across groups. CONCLUSIONS: Rates of SDD following appendectomy vary among racial and ethnic groups. Interventions to achieve equitable healthcare delivery including SDD after appendectomy are needed.

Wee1 Kinase Inhibitor AZD1775 Effectively Sensitizes Esophageal Cancer to Radiotherapy.

PURPOSE: Esophageal cancer is a deadly malignancy with a 5-year survival rate of only 5% to 20%, which has remained unchanged for decades. Esophageal cancer possesses a high frequency of TP53 mutations leading to dysfunctional G1 cell-cycle checkpoint, which likely makes esophageal cancer cells highly reliant upon G2-M checkpoint for adaptation to DNA replication stress and DNA damage after radiation. We aim to explore whether targeting Wee1 kinase to abolish G2-M checkpoint sensitizes esophageal cancer cells to radiotherapy. EXPERIMENTAL DESIGN: Cell viability was assessed by cytotoxicity and colony-forming assays, cell-cycle distribution was analyzed by flow cytometry, and mitotic catastrophe was assessed by immunofluorescence staining. Human esophageal cancer xenografts were generated to explore the radiosensitizing effect of AZD1775 in vivo. RESULTS: The IC50 concentrations of AZD1775 on esophageal cancer cell lines were between 300 and 600 nmol/L. AZD1775 (100 nmol/L) as monotherapy did not alter the viability of esophageal cancer cells, but significantly radiosensitized esophageal cancer cells. AZD1775 significantly abrogated radiation-induced G2-M phase arrest and attenuation of p-CDK1-Y15. Moreover, AZD1775 increased radiation-induced mitotic catastrophe, which was accompanied by increased γH2AX levels, and subsequently reduced survival after radiation. Importantly, AZD1775 in combination with radiotherapy resulted in marked tumor regression of esophageal cancer tumor xenografts. CONCLUSIONS: Abrogation of G2-M checkpoint by targeting Wee1 kinase with AZD1775 sensitizes esophageal cancer cells to radiotherapy in vitro and in mouse xenografts. Our findings suggest that inhibition of Wee1 by AZD1775 is an effective strategy for radiosensitization in esophageal cancer and warrants clinical testing.