A clinical consensus guideline for nutrition in infants with congenital diaphragmatic hernia from birth through discharge.

OBJECTIVE: To develop a consensus guideline to meet nutritional challenges faced by infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: The CDH Focus Group utilized a modified Delphi method to develop these clinical consensus guidelines (CCG). Topic leaders drafted recommendations after literature review and group discussion. Each recommendation was sent to focus group members via a REDCap survey tool, and members scored on a Likert scale of 0-100. A score of > 85 with no more than 25% outliers was designated a priori as demonstrating consensus among the group. RESULTS: In the first survey 24/25 recommendations received a median score > 90 and after discussion and second round of surveys all 25 recommendations received a median score of 100. CONCLUSIONS: We present a consensus evidence-based framework for managing parenteral and enteral nutrition, somatic growth, gastroesophageal reflux disease, chylothorax, and long-term follow-up of infants with CDH.

A Multi-Institutional Study Comparing Stoma Location in Neonates With Intestinal Perforation.

INTRODUCTION: Neonates with intestinal perforation often require laparotomy and intestinal stoma creation, with the stoma placed in either the laparotomy incision or a separate site. We aimed to investigate if stoma location is associated with risk of postoperative wound complications. METHODS: A multi-institutional retrospective review was performed for neonates ≤3 mo who underwent emergent laparotomy and intestinal stoma creation for intestinal perforation between January 1, 2009 and April 1, 2021. Patients were stratified by stoma location (laparotomy incision versus separate site). Outcomes included wound infection/dehiscence, stoma irritation, retraction, stricture, and prolapse. Multivariable regression identified factors associated with postoperative wound complications, controlling for gestational age, age and weight at surgery, and diagnosis. RESULTS: Overall, 79 neonates of median gestational age 28.8 wk (interquartile range [IQR]: 26.0-34.2 wk), median age 5 d (IQR: 2-11 d) and median weight 1.4 kg (IQR: 0.9-2.42 kg) had perforated bowel from necrotizing enterocolitis (40.5%), focal intestinal perforation (31.6%), or other etiologies (27.8%). Stomas were placed in the laparotomy incision for 41 (51.9%) patients and separate sites in 38 (48.1%) patients. Wound infection/dehiscence occurred in 7 (17.1%) neonates with laparotomy stomas and 5 (13.2%) neonates with separate site stomas (P = 0.63). There were no significant differences in peristomal irritation, stoma retraction, or stoma stricture between the two groups. On multivariable regression, separate site stomas were associated with increased likelihood of prolapse (odds ratio 6.54; 95% confidence interval: 1.14-37.5). CONCLUSIONS: Stoma incorporation within the laparotomy incision is not associated with wound complications. Separate site stomas may be associated with prolapse. Patient factors should be considered when planning stoma location in neonates undergoing surgery for intestinal perforation.

Multi-center implementation of rapid whole genome sequencing provides additional evidence of its utility in the pediatric inpatient setting.

Objective: Multi-center implementation of rapid whole genome sequencing with assessment of the clinical utility of rapid whole genome sequencing (rWGS), including positive, negative and uncertain results, in admitted infants with a suspected genetic disease. Study design: rWGS tests were ordered at eight hospitals between November 2017 and April 2020. Investigators completed a survey of demographic data, Human Phenotype Ontology (HPO) terms, test results and impacts of results on clinical care. Results: A total of 188 patients, on general hospital floors and intensive care unit (ICU) settings, underwent rWGS testing. Racial and ethnic characteristics of the tested infants were broadly representative of births in the country at large. 35% of infants received a diagnostic result in a median of 6 days. The most common HPO terms for tested infants indicated an abnormality of the nervous system, followed by the cardiovascular system, the digestive system, the respiratory system and the head and neck. Providers indicated a major change in clinical management because of rWGS for 32% of infants tested overall and 70% of those with a diagnostic result. Also, 7% of infants with a negative rWGS result and 23% with a variant of unknown significance (VUS) had a major change in management due to testing. Conclusions: Our study demonstrates that the implementation of rWGS is feasible across diverse institutions, and provides additional evidence to support the clinical utility of rWGS in a demographically representative sample of admitted infants and includes assessment of the clinical impact of uncertain rWGS results in addition to both positive and negative results.

An Operationally Simple Approach to Indole Derivatives from 2-Alkenylanilines Utilizing an Oxidation-Intramolecular Cyclization-Elimination Sequence.

Herein we describe a novel route to indole derivatives from a variety of N-substituted 2-alkenylanilines. This route features three operationally simple steps: (1) oxidation to convert N-substituted 2-alkenylanilines into epoxide intermediates, (2) intramolecular cyclization, and (3) the acid-catalyzed elimination of water.

Preventing Health Disparities during COVID through Perinatal Home Screening as Black Authoritative Knowledge.

During COVID-19 epidemic, health protocols limited face-to-face perinatal visits and increased reliance on telehealth. To prevent increased health disparities among BIPOC pregnant patients in health-underserved areas, we used a pre-post survey design to pilot a study assessing (1) feasibility of transferring technology including a blood pressure (BP) cuff (BPC) and a home screening tool, (2) providers' and patients' acceptance and use of technology, and (3) benefits and challenges of using the technology. Specific objectives included (1) increasing contact points between patients and perinatal providers; (2) decreasing barriers to reporting and treating maternal hypertension, stress/depression, and intimate partner violence (IPV)/domestic violence (DV); and (3) bundling to normalize and facilitate mental, emotional, and social health monitoring alongside BP screening. Findings confirm this model is feasible. Patients and providers used this bundling model to improve antenatal screening under COVID quarantine restrictions. More broadly, home-monitoring improved antenatal telehealth communication, provider diagnostics, referral and treatment, and bolstered patient autonomy through authoritative knowledge. Implementation challenges included provider resistance, disagreement with lower than ACOG BP values to initiate clinical contact and fear of service over-utilization, and patient and provider confusion about tool symbols due to limited training. We hypothesize that routinized pathologization and projection of crisis onto BIPOC people, bodies, and communities, especially around reproduction and continuity, may contribute to persistent racial/ethnic health disparities. Further research is needed to examine whether authoritative knowledge increases use of critical and timely perinatal services by strengthening embodied knowledge of marginalized patients and, thus, their autonomy and self-efficacy to enact self-care and self-advocacy.

Extracorporeal Membrane Oxygenation Then and Now; Broadening Indications and Availability.

Extracorporeal membrane oxygenation (ECMO) is a life support technology provided to children to support respiratory failure, cardiac failure, or cardiopulmonary resuscitation after failure of conventional management. Over the decades, ECMO has expanded in use, advanced in technology, shifted from experimental to a standard of care, and evidence supporting its use has increased. The expanded ECMO indications and medical complexity of children have also necessitated focused studies in the ethical domain such as decisional authority, resource allocation, and equitable access.

Emotional and psychosexual well-being is influenced by ethnicity and birthplace in women and individuals with polycystic ovary syndrome in the UK and India.

OBJECTIVE: To assess the association of ethnicity and birthplace on emotional and psychosexual well-being in women with polycystic ovary syndrome (PCOS). DESIGN: Cross-sectional study. SETTING: Community recruitment via social media campaigns. POPULATION: Women with PCOS completing an online questionnaire in September-October 2020 (UK) and May-June 2021 (India). METHODS: The survey has five components, with a baseline information and sociodemographic section followed by four validated questionnaires: Hospital Anxiety and Depression Scale (HADS); Body Image Concern Inventory (BICI); Beliefs About Obese Persons Scale (BAOP); and Female Sexual Function Index (FSFI). MAIN OUTCOME MEASURES: We used adjusted linear and logistic regression models, adjusting for age, education, marital status and parity, to evaluate the impact of ethnicity and birthplace on questionnaire scores and outcomes (anxiety and/or depression, HADS ≥ 11; body dysmorphic disorder (BDD), BICI ≥ 72). RESULTS: A total of 1008 women with PCOS were included. Women of non-white ethnicity (613/1008) reported higher rates of depression (OR 1.96, 95% CI 1.41-2.73) and lower BDD (OR 0.57, 95% CI 0.41-0.79) than white women (395/1008). Women born in India (453/1008) had higher anxiety (OR 1.57, 95% CI 1.00-2.46) and depression (OR 2.20, 95% CI 1.52-3.18) but lower BDD rates (OR 0.42, 95% CI 0.29-0.61) than women born in the UK (437/1008). All sexual domains, excluding desire, scored lower for non-white women and women born in India. CONCLUSIONS: Non-white women and women born in India reported higher emotional and sexual dysfunction, whereas white women and women born in the UK reported higher body image concerns and weight stigma. Ethnicity and birthplace need to be considered for tailored, multidisciplinary care.

Trends in Neonatal Extracorporeal Membrane Oxygenation During a Venovenous Cannula Shortage.

OBJECTIVES: To report temporal trends in venovenous extracorporeal membrane oxygenation (ECMO) use for neonatal respiratory failure in U.S. centers before and after functional venovenous cannula shortage due to withdrawal of one dual lumen venovenous cannula from the market in 2018. DESIGN: Retrospective cohort study. SETTING: ECMO registry of the Extracorporeal Life Support Organization. PATIENTS: Infants who received neonatal (cannulated prior to 29 d of age) respiratory ECMO at a U.S. center and had a record available in the ECMO registry from January 1, 2010 to July 20, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was receipt of venovenous ECMO (vs venoarterial or other), and secondary outcomes were survival to hospital discharge and adverse neurologic outcomes. Using an interrupted time series design, we fit multivariable mixed effects logistic regression models with receipt of venovenous ECMO as the dependent variable, treatment year modeled as a piecewise linear variable using three linear splines (pre shortage: 2010-2014, 2014-2018; shortage: 2018-2021), and adjusted for center clustering and multiple covariates. We evaluated trends in venovenous ECMO use by primary diagnosis including congenital diaphragmatic hernia, meconium aspiration, pulmonary hypertension, and other. Annual neonatal venovenous ECMO rates decreased after 2018: from 2010 to 2014, adjusted odds ratio (aOR) for yearly trend 0.98 (95% CI 0.92-1.04), from 2014 to 2018, aOR for yearly trend 0.90 (95% CI 0.80-1.01), and after 2018, aOR for yearly trend 0.46 (95% CI 0.37-0.57). We identified decreased venovenous ECMO use after 2018 in all diagnoses evaluated, and we failed to identify differences in temporal trends between diagnoses. Survival and adverse neurologic outcomes were unchanged across the study periods. CONCLUSIONS: Venovenous ECMO for neonatal respiratory failure in U.S. centers decreased after 2018 even after accounting for temporal trends, coincident with withdrawal of one of two venovenous cannulas from the market.

Hypothyroidism Presenting as Adynamic Ileus Mimicking a Mechanical Small Bowel Obstruction: A Diagnostic and Management Dilemma.

Patients who present with nausea, vomiting, constipation, and abdominal pain typically undergo workups for small bowel obstruction (SBO). SBO is commonly caused by mechanical obstruction due to adhesions, inflammatory conditions, or malignancies. Hypothyroidism is primarily associated with decreased basal metabolic rate and rarely, in severe cases, gastrointestinal motility dysfunction. We report a case of a 44-year-old man who presented to the emergency department with abdominal pain, nausea, and vomiting. The workup, including computed tomography, showed a small bowel feces sign, highly suspicious for a mechanical SBO. His past medical history was significant for a poorly controlled hypothyroidism due to Hashimoto's thyroiditis with a markedly elevated thyroid stimulating hormone (TSH) level. He had no prior surgical history, and his family history was significant for a suspected inflammatory bowel disease (IBD) in his son. The patient failed initial resuscitative nonoperative management and underwent exploratory laparoscopy that revealed diffusely dilated small bowel loops with no obvious cause of mechanical obstruction. Inflammatory markers for IBD were found to be negative, and the patient's gastrointestinal motility gradually improved with daily intravenous levothyroxine.

Update on pre-ECMO evaluation and treatment for term infants in respiratory failure.

The epidemiology, diagnostic and management approach to severe hypoxemic respiratory failure in the term and near-term neonate has evolved over time, as has the need for extracorporeal membrane oxygenation (ECMO) support in this patient population. Many patients who historically would have required ECMO support now respond to less invasive therapies, with patients requiring ECMO generally representing a higher risk and more heterogenous group of underlying diagnoses. This review will highlight these changes over time and the current available evidence for the diagnosis and management of these infants, as well as the current indications and relative contraindications to ECMO support when oxygen delivery cannot meet demand with less invasive management.

Ventilation Strategies During Extracorporeal Membrane Oxygenation for Neonatal Respiratory Failure: Current Approaches Among Level IV Neonatal ICUs.

To describe ventilation strategies used during extracorporeal membrane oxygenation (ECMO) for neonatal respiratory failure among level IV neonatal ICUs (NICUs). DESIGN: Cross-sectional electronic survey. SETTING: Email-based Research Electronic Data Capture survey. PATIENTS: Neonates undergoing ECMO for respiratory failure at level IV NICUs. INTERVENTIONS: A 40-question survey was sent to site sponsors of regional referral neonatal ECMO centers participating in the Children's Hospitals Neonatal Consortium. Reminder emails were sent at 2- and 4-week intervals. MEASUREMENTS AND MAIN RESULTS: Twenty ECMO centers responded to the survey. Most primarily use venoarterial ECMO (65%); this percentage is higher (90%) for congenital diaphragmatic hernia. Sixty-five percent reported following protocol-based guidelines, with neonatologists primarily responsible for ventilator management (80%). The primary mode of ventilation was pressure control (90%), with synchronized intermittent mechanical ventilation (SIMV) comprising 80%. Common settings included peak inspiratory pressure (PIP) of 16-20 cm H2O (55%), positive end-expiratory pressure (PEEP) of 9-10 cm H2O (40%), I-time 0.5 seconds (55%), rate of 10-15 (60%), and Fio2 22-30% (65%). A minority of sites use high-frequency ventilation (HFV) as the primary mode (5%). During ECMO, 55% of sites target some degree of lung aeration to avoid complete atelectasis. Fifty-five percent discontinue inhaled nitric oxide (iNO) during ECMO, while 60% use iNO when trialing off ECMO. Nonventilator practices to facilitate decannulation include bronchoscopy (50%), exogenous surfactant (25%), and noninhaled pulmonary vasodilators (50%). Common ventilator thresholds for decannulation include PEEP of 6-7 (45%), PIP of 21-25 (55%), and tidal volume 5-5.9 mL/kg (50%). CONCLUSIONS: The majority of level IV NICUs follow internal protocols for ventilator management during neonatal respiratory ECMO, and neonatologists primarily direct management in the NICU. While most centers use pressure-controlled SIMV, there is considerable variability in the range of settings used, with few centers using HFV primarily. Future studies should focus on identifying respiratory management practices that improve outcomes for neonatal ECMO patients.

Socioeconomic deprivation, age and language are barriers to accessing personal health records: a cross-sectional study of a large hospital-based personal health record system.

OBJECTIVES: To investigate barriers to accessing a hospital-based personal health record (PHR) system. DESIGN: Retrospective cross-sectional study. SETTING: This study was conducted in a large secondary and tertiary acute care trust in Birmingham, UK. PARTICIPANTS: Data were collected from 28 637 patients who attended liver medicine, diabetes, renal medicine or endocrinology specialist outpatient clinics from 1 June 2017 to 31 May 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was sign up to and activation of the PHR. The secondary outcomes were the use of the PHR, defined as the number of logons and frequency of access of specific PHR functions. RESULTS: 8070 patients (28.2%) were signed up to the PHR and 4286 patients (53.1% of those signed up) went on to activate their PHR account. Patients aged 75 years and older were significantly less likely to be signed up (adjusted OR, aOR 0.40, 95% CI 0.36 to 0.44) or to activate (aOR 0.39, 0.32 to 0.47) their PHR than patients aged 35-54. Patients who did not need an interpreter were more likely to be signed up (aOR 1.63, 95% CI 1.33 to 1.99) and to activate (aOR 3.16, 95% CI 1.96 to 5.09) their PHR. Patients living in the least deprived areas were more than twice as likely to be signed up (aOR 2.31, 95% CI 2.04 to 2.63), and were three times more likely to activate their PHR (aOR 2.99, 95% CI 2.40 to 3.71), than those in the most deprived. CONCLUSION: Socioeconomic deprivation, older age and non-English language were significant barriers to accessing a hospital-based PHR. Strategies are needed to account for these factors to ensure that PHRs do not widen health inequalities.

Decolonising the global to local movement: Time for a new paradigm.

Mama Amaan Project (MAP) delivered perinatal education and doula services to underserved refugee and immigrant communities in Seattle, Washington. MAP presented at a 'global to local (glocal)' workshop for US-based global health agencies redirecting their experience and resources to address domestic health crises. Glocal models reference Global South anti-colonial social transformations through Primary Health Care (PHC) - 'health for all as a right' and investment in strong public sectors. As Black women working in our communities, we resisted labelling MAP glocal. Western donors and NGOs appropriate PHC's community participation narratives, meanwhile implementing World Bank/IMF economic structural adjustment health system cuts - thereby shifting austerity-related resource shortfalls to communities. In US contexts of neoliberal shrinking social safety nets and workers' rights, similar strategies to address austerity-related health disparities are promoted as 'global to local'. Projects like MAP cannot substitute quality public services. They expose gaps and build community empowerment to demand quality healthcare. Drawing on MAP and 'global health' experience in Mozambique, we call for re-embracing PHC's activist values - agitating for health as a universal human right for all, rather than putting the burden and blame on underserved communities. We propose decolonising the 'glocal' paradigm by embracing 'transnationality', 'relationality' and 'mutuality'.

Predicting treatment of pulmonary hypertension at discharge in infants with congenital diaphragmatic hernia.

OBJECTIVE: To predict pulmonary hypertension (PH) therapy at discharge in a large multicenter cohort of infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: Six-year linked records from Children's Hospitals Neonatal Database and Pediatric Health Information System were used; patients whose diaphragmatic hernia was repaired before admission or referral, who were previously home before admission or referral, and non-survivors were excluded. The primary outcome was the use of PH medications at discharge and the secondary outcome was an inter-center variation of therapies during inpatient utilization. Clinical factors were used to develop a multivariable equation randomly applied to 80% cohort; validated in the remaining 20% infants. RESULTS: A total of 831 infants with CDH from 23 centers were analyzed. Overall, 11.6% of survivors were discharged on PH medication. Center, duration of mechanical ventilation, and duration of inhaled nitric oxide were associated with the use of PH medication at discharge. This model performed well in the validation cohort area under the receiver operating characteristic curve of 0.9, goodness-of-fit χ2, p = 0.17. CONCLUSIONS: Clinical variables can predict the need for long-term PH medication after NICU hospitalization in surviving infants with CDH. This information may be useful to educate families and guide the development of clinical guidelines.

Cost-effectiveness analysis of extended extracorporeal membrane oxygenation duration in newborns with congenital diaphragmatic hernia in the United States.

BACKGROUND: The duration of extracorporeal membrane oxygenation (ECMO) has been historically confined in many centers to two weeks. We evaluated the cost-effectiveness of additional weeks on ECMO beyond two weeks for newborns with congenital diaphragmatic hernia (CDH) who may require longer stays to maximize survival potential. METHODS: We modeled lifetime outcomes using a decision tree from the US societal perspective. Survival at discharge, probability of long-term sequelae, direct medical costs, indirect costs, and quality-adjusted life years (QALY) for long-term disability were considered. Considering the nature of severity of CDH, we used $200,000 per QALY as the willingness-to-pay threshold in the base case. RESULTS: The lifetime costs per CDH infant generated from staying on ECMO for ≤2 weeks, 2-3 weeks, and >3 weeks are $473,334, $654,771, $1,007,476, respectively (2018 USD), and the total QALYs gained from each treatment arm are 1.83, 3.6, and 5.05. In the base case, the net monetary benefits are -$108,034 for ECMO ≤2 weeks, $64,258 for 2-3 weeks, and $2955 for >3 weeks. In probabilistic simulations, a duration of ≤2 weeks is dominated by a duration of 2-3 weeks in 65.3% of cases and dominated by > 3 weeks in 60.2% of cases. A duration of 2-3 weeks is more cost-effective than >3 weeks in 68.6% of simulations. CONCLUSION: Our findings suggest that 2-3 weeks of ECMO may be the most cost-effective for CDH infants that are unable to wean off at 2 weeks from the US societal perspective. Regardless of ECMO duration, ECMO use generates positive incremental NMB at WTP of $200,000 if the survival probability is greater than 0.3. Future research must be conducted to evaluate the long-term outcomes and sequelae of CDH patients post-discharge to better inform the clinical decision-making in neonatal intensive care unit.

Theoretical Prediction and Explanation of Reaction Site Selectivity in the Addition of a Phenoxy Group to Perfluoropyrimidine, Perfluoropyridazine, and Perfluoropyrazine.

Perfluoroaromatics, such as perfluoropyridine and perfluorobenzene, are privileged synthetic scaffolds in organofluorine methodology, undergoing a series of regioselective substitution reactions with a variety of nucleophiles. This unique chemical behavior allows for the synthesis of many perfluoroaromatic derived molecules with unique and diverse architectures. Recently, it has been demonstrated that perfluoropyridine and perfluorobenzene can be utilized as precursors for a variety of materials, ranging from high performance polyaryl ethers to promising drug scaffolds. In this work, using density functional theory, we investigate the possibility of perfluoropyrimidine, perfluoropyridazine, and perfluoropyrazine participating in similar substitution reactions. We have found that the first nucleophilic addition of a phenoxide group substitution on perfluoropyrimidine and on perfluoropyridazine would happen at a site para to one of the nitrogen atoms. While previous literature points to mesomeric effects as the primary cause of this phenomenon, our work demonstrates that this effect is enhanced by the fact that the transition states for these reactions result in bond angles that allow the phenoxide to π-complex with the electron-deficient diazine ring. The second substitution on perfluoropyrimidine and on perfluoropyridazine is most likely to happen at the site para to the other nitrogen. The second substitution on perfluoropyrazine is most likely to happen at the site para to the first substitution. The activation energies for these reactions are in line with those reported for perfluoropyridine and suggest that these platforms may also be worth investigation in the lab as possible monomers for high performance polymers.