Building a NICU quality & safety infrastructure.

The American Academy of Pediatrics (AAP) Standards for Levels of Neonatal Care, published in 2023, highlights key components of a Neonatal Patient Safety and Quality Improvement Program (NPSQIP). A comprehensive Neonatal Intensive Care Unit (NICU) quality and safety infrastructure (QSI) is based on four foundational domains: quality improvement, quality assurance, safety culture, and clinical guidelines. This paper serves as an operational guide for NICU clinical leaders and quality champions to navigate these domains and develop their local QSI to include the AAP NPSQIP standards.

Human milk derived fortifiers are associated with glucose, phosphorus, and calcium derangements.

OBJECTIVE: In 2017, our Level IV NICU switched from providing bovine-derived (BOV-fort) to human milk-derived fortifiers (HM-fort) and donor human milk (DHM) to premature infants born ≤ 30 weeks or ≤1250 g. Following this change, providers anecdotally observed increased hypoglycemia, hypercalcemia, and hyperphosphatemia. This study investigated potential laboratory differences between infants fed Bovine vs. Human milk derived fortifier. METHODS: Lab measurements from 402 infants (232 BOV-fort, 170 HM-fort) born between 2015 and 2019 were compared between groups. RESULTS: The proportion of infants ever having a blood glucose ≤ 45 mg/dL (p < 0.0001) was higher in the HM-fort group. The proportion of infants ever experiencing a phosphorus > 8.0 mg/dL were higher in the HM-fort group (p < 0.0001). The proportion of infants ever experiencing calcium > 11.4 mg/dL was higher in the HM-Fort group (p = 0.019). CONCLUSIONS: Provision of HM-Fort and DHM to extremely premature infants is associated with metabolic derangements.

A guide to critical appraisal of quality improvement reports.

Quality improvement (QI) has become an integral part of healthcare. Despite efforts to improve the reporting of QI through frameworks such as the SQUIRE 2.0 guidelines, there is no standard or well-accepted guide to evaluate published QI for rigor, validity, generalizability, and applicability. User's Guides for evaluation of published clinical research have been employed routinely for over 25 years; however, similar tools for critical appraisal of QI are limited and uncommonly used. In this article we propose an approach to guide the critical review of QI reports focused on evaluating the methodology, improvement results, and applicability and feasibility for implementation in other settings. The resulting Quality Improvement Critical Knowledge (QUICK) Tool can be used by those reviewing manuscripts submitted for publication, as well as healthcare providers seeking to understand how to apply published QI to their local context.

Reducing Unplanned Intubations in the Neonatal Intensive Care Unit After Children's Surgery: A Quality Improvement Project.

BACKGROUND: Unplanned intubation following children's surgery is associated with increased postoperative mortality. In response to being a National Surgical Quality Improvement Program - Pediatric (NSQIP-P) high outlier for postoperative unplanned intubation, we aimed to reduce postoperative unplanned intubation events by 25% in one year. METHODS/INTERVENTION: A multidisciplinary team of stakeholders was assembled in 2018. Most unplanned intubation events occurred in the neonatal intensive care unit (NICU). Based on apparent causes of unplanned intubations identified in case reviews, an extubation readiness checklist and a postoperative pain management guideline emphasizing non-opioid analgesics were implemented for NICU patients in September 2019. Postoperative unplanned intubation events were tracked prospectively and evaluated using quality improvement statistical process control methods. RESULTS: Unplanned intubations in the NICU decreased from 0.27 to 0.07 events per patient in the post-intervention group (September 2019-June 2022, n = 145) compared to the pre-intervention group (January 2016-August 2019, n = 200), representing a 76% reduction. Postoperative opioid administration decreased significantly, while acetaminophen usage increased significantly over time. Balancing measures of postoperative pneumonia rate (1.5% vs 0.0%, p = 0.267) and median hospital length of stay [40 (IQR 51) days vs 27 (IQR 60), p = 0.124] were not different between cohorts. The 30-day mortality rate for postoperative patients in the NICU significantly declined [6.5% (n = 13) vs 0.7% (n = 1), p < 0.001]. CONCLUSIONS: Postoperative unplanned intubation rates for NICU patients decreased following a quality improvement effort focused on opioid stewardship and extubation readiness. TYPE OF STUDY: Prospective Quality Improvement. LEVEL OF EVIDENCE: Level III.

Shift-to-shift handoffs in the NICU: lessons learned from a large scale audit.

OBJECTIVE: Describe the frequency of best practice behaviors during NICU provider and nursing shift-to-shift handoffs and identify strengths and opportunities for improvement. STUDY DESIGN: Observational study of handoff characteristics among 40 centers participating in a learning collaborative over a 10-month period. Data were gathered using a handoff audit tool that outlined best practices. Comparisons of behaviors between nurse-to-nurse and provider-to-provider handoffs were made where appropriate. RESULTS: Overall, 946 audits of shift-to-shift handoffs were analyzed. While many behaviors were demonstrated reliably, differences between nurse-to-nurse vs provider-to-provider handoffs were noted. Families were present for 5.9% of handoffs and, among those who were present, 48.2% participated by contributing information, asking questions, and sharing goals. CONCLUSIONS: Observation and measurement of handoff behaviors can be used to identify opportunities to improve handoff communication, family participation, and human factors that support handoff. Auditing handoffs is feasible and necessary to improve these critical transitions in infants' care.

Sleep and cancer recurrence and survival in patients with resected Stage III colon cancer: findings from CALGB/SWOG 80702 (Alliance).

BACKGROUND: We sought to assess the influences of sleep duration, sleep adequacy, and daytime sleepiness on survival outcomes among Stage III colon cancer patients. METHODS: We conducted a prospective observational study of 1175 Stage III colon cancer patients enrolled in the CALGB/SWOG 80702 randomised adjuvant chemotherapy trial who completed a self-reported questionnaire on dietary and lifestyle habits 14-16 months post-randomisation. The primary endpoint was disease-free survival (DFS), and secondary was overall survival (OS). Multivariate analyses were adjusted for baseline sociodemographic, clinical, dietary and lifestyle factors. RESULTS: Patients sleeping ≥9 h-relative to 7 h-experienced a worse hazard ratio (HR) of 1.62 (95% confidence interval (CI), 1.01-2.58) for DFS. In addition, those sleeping the least (≤5 h) or the most (≥ 9 h) experienced worse HRs for OS of 2.14 (95% CI, 1.14-4.03) and 2.34 (95% CI, 1.26-4.33), respectively. Self-reported sleep adequacy and daytime sleepiness showed no significant correlations with outcomes. CONCLUSIONS: Among resected Stage III colon cancer patients who received uniform treatment and follow-up within a nationwide randomised clinical trial, very long and very short sleep durations were significantly associated with increased mortality. Interventions targeting optimising sleep health among indicated colon cancer patients may be an important method by which more comprehensive care can be delivered. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01150045.

Human milk-derived fortifiers are linked with feed extension due to Hypoglycemia in infants <1250 g or <30 weeks: a matched retrospective chart review.

OBJECTIVE: To investigate differences in hypoglycemia and extended feed prescriptions among premature infants provided bovine-derived human milk fortifiers (Bov-fort) with mother's milk or formula vs human milk-derived human milk fortifiers (HM-fort) with mother's milk or donor human milk. STUDY DESIGN: This was a retrospective chart review (n = 98). Infants receiving HM-fort were matched with infants receiving Bov-fort. Blood glucose values and feed orders were retrieved from the electronic medical record. RESULTS: Prevalence of ever having blood glucose <60 mg/dL was 39.1% in the HM-fort group vs. 23.9% in the Bov-fort group (p = 0.09). Blood glucose ≤45 mg/dL occurred in 17.4% of HM-fort vs 4.3% in Bov-fort (p = 0.07). Feeds were extended for any reason in 55% of HM-fort vs. 20% of Bov-fort (p < 0.01). Feed extension due to hypoglycemia occurred in 24% of HM-fort vs. 0% of Bov-fort (p < 0.01). CONCLUSION: Predominately HM-based feeds are associated with feed extension due to hypoglycemia. Prospective research is warranted to elucidate underlying mechanisms.

Value Added from Same-day Discharge after Appendectomy for Children with Simple Appendicitis.

Same-day discharge of children after appendectomy for simple appendicitis is safe and associated with enhanced parent satisfaction. Our general pediatric surgeons aimed to improve the rate of same-day discharge after appendectomy for simple appendicitis. Methods: We implemented a clinical practice guideline in September 2019. A surgeon-of-the-week service model and the urgent operating room started in November 2019 and January 2020, respectively. Data for children with simple appendicitis from our academic medical center were gathered prospectively using National Surgical Quality Improvement Program-Pediatric. Patient outcomes before intervention implementation (n = 278) were compared with patients following implementation (n = 264). Results: The average monthly percentage of patients discharged on the day of surgery increased in the postimplementation group (32% versus 75%). Median postoperative length of stay decreased [16.5 hours (interquartile range, 15.9) versus 4.4 hours (interquartile range, 11.7), P < 0.001], and the proportion of patients discharged directly from the postoperative anesthesia care unit increased (22.8% versus 43.6%; P < 0.001). There were no differences in balancing measures, including the return to the emergency department and readmission. Fewer children were discharged home on oral antibiotics after implementation (6.8% versus 1.5%, P = 0.002), and opioid prescribing at discharge remained low (2.5% versus 1.1%, P = 0.385). Conclusions: Using quality improvement methodology and care standardization, we significantly improved the rate of same-day discharge after appendectomy for simple appendicitis without impacting emergency department visits or readmissions. As a result, our health care system saved 140 hospital days over the first 21 months.

Prognostic Impact of Early Treatment and Oxaliplatin Discontinuation in Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 11 Adjuvant Trials.

PURPOSE: Oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (CC) for 6 months remains a standard in high-risk stage III patients. Data are lacking as to whether early discontinuation of all treatment (ETD) or early discontinuation of oxaliplatin (EOD) could worsen the prognosis. MATERIALS AND METHODS: We studied the prognostic impact of ETD and EOD in patients with stage III CC from the ACCENT/IDEA databases, where patients were planned to receive 6 months of infusional fluorouracil, leucovorin, and oxaliplatin or capecitabine plus oxaliplatin. ETD was defined as discontinuation of treatment and EOD as discontinuation of oxaliplatin only before patients had received a maximum of 75% of planned cycles. Association between ETD/EOD and overall survival and disease-free survival (DFS) were assessed by Cox models adjusted for established prognostic factors. RESULTS: Analysis of ETD and EOD included 10,447 (20.9% with ETD) and 7,243 (18.8% with EOD) patients, respectively. Compared with patients without ETD or EOD, patients with ETD or EOD were statistically more likely to be women, with Eastern Cooperative Oncology Group performance status ≥ 1, and for ETD, older with a lower body mass index. In multivariable analyses, ETD was associated with a decrease in disease-free survival and overall survival (hazard ratio [HR], 1.61, P < .001 and HR, 1.73, P < .001), which was not the case for EOD (HR, 1.07, P = .3 and HR, 1.13, P = .1). However, patients who received < 50% of the planned cycles of oxaliplatin had poorer outcomes. CONCLUSION: In patients treated with 6 months of oxaliplatin-based chemotherapy for stage III CC, ETD was associated with poorer oncologic outcomes. However, this was not the case for EOD. These data favor discontinuing oxaliplatin while continuing fluoropyrimidine in individuals with significant neurotoxicity having received > 50% of the planned 6-month chemotherapy.

Experiences of a Regional Quality Improvement Collaborative to Reduce Unplanned Extubations in the Neonatal Intensive Care Unit.

BACKGROUND: Unplanned extubations (UEs) occur frequently in the neonatal intensive care unit (NICU). These events can be associated with serious short-term and long-term morbidities and increased healthcare costs. Most quality improvement (QI) initiatives focused on UE prevention have concentrated efforts within individual NICUs. METHODS: We formed a regional QI collaborative involving the four regional perinatal center (RPC) NICUs in upstate New York to reduce UEs. The collaborative promoted shared learning and targeted interventions specific to UE classification at each center. RESULTS: There were 1167 UEs overall during the four-year project. Following implementation of one or more PDSA cycles, the combined UE rate decreased by 32% from 3.7 to 2.5 per 100 ventilator days across the collaborative. A special cause variation was observed for the subtype of UEs involving removed endotracheal tubes (rETTs), but not for dislodged endotracheal tubes (dETTs). The center-specific UE rates varied; only two centers observed significant improvement. CONCLUSIONS: A collaborative approach promoted knowledge sharing and fostered an overall improvement, although the individual centers' successes varied. Frequent communication and shared learning experiences benefited all the participants, but local care practices and varying degrees of QI experience affected each center's ability to successfully implement potentially better practices to prevent UEs.

Conversion of non-inferiority margin from hazard ratio to restricted mean survival time difference using data from multiple historical trials.

The restricted mean survival time measure has gained a lot of interests for designing and analyzing oncology trials with time-to-event endpoints due to its intuitive clinical interpretation and potentially high statistical power. In the non-inferiority trial literature, restricted mean survival time has been used as an alternative measure for reanalyzing a completed trial, which was originally designed and analyzed based on traditional proportional hazard model. However, the reanalysis procedure requires a conversion from the non-inferiority margin measured in hazard ratio to a non-inferiority margin measured by restricted mean survival time difference. An existing conversion method assumes a Weibull distribution for the population survival time of the historical active control group under the proportional hazard assumption using data from a single trial. In this article, we develop a methodology for non-inferiority margin conversion when data from multiple historical active control studies are available, and introduce a Kaplan-Meier estimator-based method for the non-inferiority margin conversion to relax the parametric assumption. We report extensive simulation studies to examine the performances of proposed methods under the Weibull data generative models and a piecewise-exponential data generative model that mimic the tumor recurrence and survival characteristics of advanced colon cancer. This work is motivated to achieve non-inferiority margin conversion, using historical patient-level data from a large colon cancer clinical database, to reanalyze an internationally collaborated non-inferiority study that evaluates 6-month versus 3-month duration of adjuvant chemotherapy in stage III colon cancer patients.

A Quality Improvement Initiative to Reduce Bronchopulmonary Dysplasia in a Level 4 NICU-Golden Hour Management of Respiratory Distress Syndrome in Preterm Newborns.

BACKGROUND: Prevention of chronic lung disease (CLD) requires a multidisciplinary approach spanning from the delivery room to Neonatal Intensive Care Unit (NICU) discharge. In 2018, a quality improvement (QI) initiative commenced in a level 4 NICU with the goal of decreasing chronic lung disease rates below the Vermont Oxford Network (VON) average of 24%. METHODS: Improvement strategies focused on addressing the primary drivers of ventilation strategies, surfactant administration, non-invasive ventilation, medication use, and nutrition/fluid management. The primary outcome was VON CLD, defined as need for mechanical ventilation and/or supplemental oxygen use at 36 weeks postmenstrual age. Statistical process control charts were used to display and analyze data over time. RESULTS: The overall CLD rate decreased from 33.5 to 16.5% following several interventions, a 51% reduction that has been sustained for >18 months. Changes most attributable to this include implementation of the "golden hour" gestational age (GA) based delivery room protocol that encourages early surfactant administration and timely extubation. Fewer infants were intubated across all GA groups with the largest improvement among infants 26-27 weeks GA. CONCLUSIONS: Our efforts significantly decreased CLD through GA-based respiratory guidelines and a comprehensive, rigorous QI approach that can be applicable to other teams focused on improvement.

Randomized Phase II Trial of Polyphenon E versus Placebo in Patients at High Risk of Recurrent Colonic Neoplasia.

Polyphenon E (Poly E) is a green tea polyphenol preparation whose most active component is epigallocatechin gallate (EGCG). We studied the cancer preventive efficacy and safety of Poly E in subjects with rectal aberrant crypt foci (ACF), which represent putative precursors of colorectal cancers. Eligible subjects had prior colorectal advanced adenomas or cancers, and had ≥5 rectal ACF at a preregistration chromoendoscopy. Subjects (N = 39) were randomized to 6 months of oral Poly E (780 mg EGCG) daily or placebo. Baseline characteristics were similar by treatment arm (all P >0.41); 32 of 39 (82%) subjects completed 6 months of treatment. The primary endpoint was percent reduction in rectal ACF at chromoendoscopy comparing before and after treatment. Among 32 subjects (15 Poly E, 17 placebo), percent change in rectal ACF number (baseline vs. 6 months) did not differ significantly between study arms (3.7% difference of means; P = 0.28); total ACF burden was also similar (-2.3% difference of means; P = 0.83). Adenoma recurrence rates at 6 months were similar by arm (P > 0.35). Total drug received did not differ significantly by study arm; 31 (79%) subjects received ≥70% of prescribed Poly E. Poly E was well tolerated and adverse events (AE) did not differ significantly by arm. One subject on placebo had two grade 3 AEs; one subject had grade 2 hepatic transaminase elevations attributed to treatment. In conclusion, Poly E for 6 months did not significantly reduce rectal ACF number relative to placebo. Poly E was well tolerated and without significant toxicity at the dose studied. PREVENTION RELEVANCE: We report a chemoprevention trial of polyphenon E in subjects at high risk of colorectal cancer. The results show that polyphenon E was well tolerated, but did not significantly reduce the number of rectal aberrant crypt foci, a surrogate endpoint biomarker of colorectal cancer.

Duration of Adjuvant Doublet Chemotherapy (3 or 6 months) in Patients With High-Risk Stage II Colorectal Cancer.

PURPOSE: As oxaliplatin results in cumulative neurotoxicity, reducing treatment duration without loss of efficacy would benefit patients and healthcare providers. PATIENTS AND METHODS: Four of the six studies in the International Duration of Adjuvant Chemotherapy (IDEA) collaboration included patients with high-risk stage II colon and rectal cancers. Patients were treated (clinician and/or patient choice) with either fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) and randomly assigned to receive 3- or 6-month treatment. The primary end point is disease-free survival (DFS), and noninferiority of 3-month treatment was defined as a hazard ratio (HR) of < 1.2- v 6-month arm. To detect this with 80% power at a one-sided type one error rate of 0.10, a total of 542 DFS events were required. RESULTS: 3,273 eligible patients were randomly assigned to either 3- or 6-month treatment with 62% receiving CAPOX and 38% FOLFOX. There were 553 DFS events. Five-year DFS was 80.7% and 83.9% for 3-month and 6-month treatment, respectively (HR, 1.17; 80% CI, 1.05 to 1.31; P [for noninferiority] .39). This crossed the noninferiority limit of 1.2. As in the IDEA stage III analysis, the duration effect appeared dependent on the chemotherapy regimen although a test of interaction was negative. HR for CAPOX was 1.02 (80% CI, 0.88 to 1.17), and HR for FOLFOX was 1.41 (80% CI, 1.18 to 1.68). CONCLUSION: Although noninferiority has not been demonstrated in the overall population, the convenience, reduced toxicity, and cost of 3-month adjuvant CAPOX suggest it as a potential option for high-risk stage II colon cancer if oxaliplatin-based chemotherapy is suitable. The relative contribution of the factors used to define high-risk stage II disease needs better understanding.

Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration): final results from a prospective, pooled analysis of six randomised, phase 3 trials.

BACKGROUND: A prospective, pooled analysis of six randomised phase 3 trials was done to investigate disease-free survival regarding non-inferiority of 3 months versus 6 months of adjuvant chemotherapy for patients with stage III colon cancer; non-inferiority was not shown. Here, we report the final overall survival results. METHODS: In this prospective, pooled analysis of six randomised phase 3 trials, we included patients with stage III colon cancer aged at least 18 years with an Eastern Cooperative Oncology Group performance status of 0-1 recruited between June 20, 2007, and Dec 31, 2015, across 12 countries in the CALGB/SWOG 80702, IDEA France, SCOT, ACHIEVE, TOSCA, and HORG trials, who started any treatment (modified intention-to-treat). Patients in all trials were randomly assigned to 3 months or 6 months of adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) every 2 weeks or capecitabine and oxaliplatin (CAPOX) in different doses and methods every 3 weeks, at the treating physician's discretion. The primary endpoint was disease-free survival (time to relapse, secondary colorectal primary tumour, or death due to all causes), and overall survival (time to death due to all causes) was the prespecified secondary endpoint. The non-inferiority margin for overall survival was set as a hazard ratio (HR) of 1·11. Pre-planned subgroup analyses included regimen and risk group. Non-inferiority was declared if the one-sided false discovery rate adjusted (FDRadj) p value was less than 0·025. FINDINGS: With median follow-up of 72·3 months (IQR 72·2-72·5), 2584 deaths among 12 835 patients were observed. 5064 (39·5%) patients received CAPOX and 7771 (60·5%) received FOLFOX. 5-year overall survival was 82·4% (95% CI 81·4-83·3) with 3 months of therapy and 82·8% (81·8-83·8) with 6 months of therapy (HR 1·02 [95% CI 0·95-1·11]; non-inferiority FDRadj p=0·058). For patients treated with CAPOX, 5-year overall survival was 82·1% (80·5-83·6) versus 81·2% (79·2-82·9; HR 0·96 [0·85-1·08]); non-inferiority FDRadj p=0·033), and for patients treated with FOLFOX 5-year overall survival was 82·6% (81·3-83·8) and 83·8% (82·6-85·0; HR 1·07 [0·97-1·18]; non-inferiority FDRadj p=0·34). Updated disease-free survival results confirmed previous findings (HR 1·08 [95% CI 1·02-1·15]; non-inferiority FDRadj p=0·25). Data on adverse events were not further recorded. INTERPRETATION: Non-inferiority of 3 months versus 6 months of adjuvant chemotherapy for patients with stage III colon cancer was not confirmed in terms of overall survival, but the absolute 0·4% difference in 5-year overall survival should be placed in clinical context. Overall survival results support the use of 3 months of adjuvant CAPOX for most patients with stage III colon cancer. This conclusion is strengthened by the substantial reduction of toxicities, inconveniencies, and cost associated with a shorter treatment duration. FUNDING: US National Cancer Institute.

A Quality Improvement Initiative To Optimize Antibiotic Use in a Level 4 NICU.

BACKGROUND: Given the risks associated with antibiotics, efforts to reduce unnecessary antibiotic use in the NICU have become increasingly urgent. In 2016, a comprehensive 3-year quality improvement (QI) initiative was conducted in a level 4 NICU that sought to decrease the antibiotic use rate (AUR) by 20%. METHODS: This local QI initiative was conducted in the context of a multicenter learning collaborative focused on decreasing unnecessary antibiotic use. Improvement strategies focused on addressing gaps in the core elements of antibiotic stewardship programs. Outcome measures included the AUR and the percent of infants discharged without antibiotic exposure. Process measures included the percent of infants evaluated for early-onset sepsis (EOS) and duration of antibiotics used for various infections. Statistical process control charts were used to display and analyze data over time. RESULTS: The AUR decreased from 27.6% at baseline to 15.5%, a 43% reduction, and has been sustained for >18 months. Changes most attributable to this decrease include implementation of the sepsis risk calculator, adopting a 36-hour rule-out period for sepsis evaluations, a 36-hour antibiotic hard stop, and novel guideline for EOS evaluation among infants <35 weeks. The percent of infants discharged without antibiotic exposure increased from 15.8% to 35.1%. The percent of infants ≥36 weeks undergoing evaluation for EOS decreased by 42.3% and for those <35 weeks by 26%. CONCLUSIONS: Our efforts significantly reduced antibiotic use and exposure in our NICU. Our comprehensive, rigorous approach to QI is applicable to teams focused on improvement.

Clinical Outcomes in Patients With Colon Cancer With Microsatellite Instability of Sporadic or Familial Origin Treated With Adjuvant FOLFOX With or Without Cetuximab: A Pooled Analysis of the PETACC8 and N0147 Trials.

PURPOSE: The microsatellite instability (MSI) or deficient mismatch repair (dMMR) phenotype is usually regarded as a single biologic entity, given the absence of comparative analyses regarding prognosis and response to chemotherapy between sporadic and familial dMMR cancers. PATIENTS AND METHODS: Patients with stage III colon cancers were randomly assigned to FOLFOX (leucovorin, fluorouracil, and oxaliplatin) with or without cetuximab in 2 large adjuvant phase III trials (N = 5,577). Among patients with MSI and KRAS exon 2 wild-type (WT) tumors, the prognostic and predictive impacts of sporadic versus familial dMMR cancers and BRAF V600E mutational status were determined. Multivariable Cox proportional hazards models were used to assess disease-free survival (DFS) by treatment arm, adjusting for age, sex, tumor grade, Eastern Cooperative Oncology Group performance status, pT/pN stage, and primary tumor location. RESULTS: Among patients with MSI status with complete data for dMMR mechanism analysis (n = 354), 255 (72%) had sporadic (BRAF mutation and/or MLH1 methylation) and 99 (28%) had familial tumors (BRAF WT and unmethylated MLH1 or loss of MSH2/MSH6/PMS2 protein expression). A large proportion of dMMR sporadic tumors were mutated for BRAF (n = 200). In patients treated with FOLFOX, DFS did not differ statistically by dMMR mechanism, whereas in patients treated with FOLFOX plus cetuximab, those with sporadic tumors had worse DFS than those with familial cancers (multivariable hazard ratio, 2.69; 95% CI, 1.02 to 7.08; P = .04). Considering the predictive utility, the interaction between treatment and dMMR mechanism was significant (P = .03). Furthermore, a nonsignificant trend toward a deleterious effect of adding cetuximab to FOLFOX was observed in patients with BRAF-mutant but not BRAF WT tumors. CONCLUSION: The addition of cetuximab to adjuvant FOLFOX was associated with shorter DFS in patients with sporadic dMMR colon cancer. Additional studies are needed to validate these results in metastatic disease.

Variability in the systems of care supporting critical neonatal intensive care unit transitions.

OBJECTIVE: Assess practices supporting care transitions for infants and families in the neonatal intensive care unit (NICU) using a model of four key drivers: communication, teamwork, family integration, and standardization. STUDY DESIGN: Single-day audit among NICUs in the Vermont Oxford Network Critical Transitions collaborative addressing policies and practices supporting the four key drivers during admission, discharge, shift-to-shift handoffs, within hospital transfers, and select changes in clinical status. RESULTS: Among 95 NICUs, the median hospital rate of audited policies in place addressing the four key drivers were 47% (inter-quartile range (IQR) 35-65%) for communication, 67% (IQR 33-83%) for teamwork, 50% (IQR 33-61%) for family integration, and 70% (IQR 56-85%) for standardization. Of the 2462 infants included, 1066 (43%) experienced ≥1 specified transition during the week prior to the audit. CONCLUSIONS: We identified opportunities for improving NICU transitions in areas of communication, teamwork, family integration, and standardization.