Cerebral Oximetry Monitoring in Extremely Preterm Infants.

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.).

Respiratory effects of prolonged prednisolone use in infants with evolving and established Bronchopulmonary dysplasia.

BACKGROUND: Current literature focuses on systemic corticosteroids for prevention of bronchopulmonary dysplasia (BPD) in preterm infants with limited data on use for pulmonary disease after the first month of life. Prednisolone may be a reasonable option for late treatment given its desirable pharmacologic properties and use in other pediatric disease states. AIMS: To characterize a premature population that received an extended prednisolone course and determine the effect on respiratory and anthropometric outcomes over time. STUDY DESIGN: Single-center, retrospective study. SUBJECTS: Preterm infants who received ≥30 days of prednisolone or methylprednisolone for treatment of respiratory complications following preterm birth. OUTCOMES MEASURES: Assessment of pulmonary severity score (PSS), weight, length, and occipital frontal circumference weekly during the first 4 weeks of prednisolone and after discontinuation. RESULTS: Thirty-four infants with a mean gestational age of 26.5 ± 2.5 weeks and birth weight of 846 ± 353 g were identified. Nine patients were on invasive mechanical ventilation and 25 patients were on non-invasive respiratory support at prednisolone initiation. Prednisolone was initiated at a mean post-menstrual age of 41.7 ± 5 weeks and a mean dose of 1.7 ± 0.6 mg/kg/day. A significant decrease in PSS was seen over time (p < 0.001) without rebound following discontinuation. Eleven patients decreased the mode of respiratory support during prednisolone treatment. No significant impact in anthropometric outcomes were identified. CONCLUSION: Prolonged prednisolone use was associated with a sustained decrease in PSS without adverse effects on growth measurements. These results suggest potential benefit of prednisolone on respiratory outcomes in a subset of preterm infants.

Mining reported adverse events induced by potential opioid-drug interactions.

OBJECTIVE: Opioid-based analgesia is routinely used in clinical practice for the management of pain and alleviation of suffering at the end of life. It is well-known that opioid-based medications can be highly addictive, promoting not only abuse but also life-threatening overdoses. The scope of opioid-related adverse events (AEs) beyond these well-known effects remains poorly described. This exploratory analysis investigates potential AEs from drug-drug interactions between opioid and nonopioid medications (ODIs). MATERIALS AND METHODS: In this study, we conduct an initial exploration of the association between ODIs and severe AEs using millions of AE reports available in FDA Adverse Event Reporting System (FAERS). The odds ratio (OR)-based analysis and visualization are proposed for single drugs and pairwise ODIs to identify associations between AEs and ODIs of interest. Moreover, the multilabel (multi-AE) learning models are employed to evaluate the feasibility of AE prediction of polypharmacy. RESULTS: The top 12 most prescribed opioids in the FAERS are identified. The OR-based analysis identifies a diverse set of AEs associated with individual opioids. Moreover, the results indicate many ODIs can increase the risk of severe AEs dramatically. The area under the curve values of multilabel learning models of ODIs for oxycodone varied between 0.81 and 0.88 for 5 severe AEs. CONCLUSIONS: The proposed data analysis and visualization are useful for mining FAERS data to identify novel polypharmacy associated AEs, as shown for ODIs. This approach was successful in recapitulating known drug interactions and also identified new opioid-specific AEs that could impact prescribing practices.

Racial disparities in calculated risk for bronchopulmonary dysplasia: a dataset.

Bronchopulmonary dysplasia (BPD) is a severe pulmonary complication of prematurity and is associated with significant morbidity or death. Early use of systemic corticosteroids may alter the trajectory of the disease and improve outcomes. A BPD Outcomes estimator, developed by the NICHD using a large population dataset, can be used to calculate individual risk. Risk above a certain threshold may indicate that the benefits of corticosteroids outweigh the risks. Empiric analysis of this calculator by systematic entry of synthetic patient information reveals a marked racial disparity; black infants have lower risk of moderate/severe BPD due to a higher risk of death despite equivalent severity of illness. Interpretation and analysis of this finding can be found in "The challenge of risk stratification of preterm infants in the setting of competing and disparate healthcare outcomes" [1]. In this report, we provide the underlying data used in this analysis. Calculator output for 108 example patients, systematically varied by sex, birthweight, race, type of ventilator, and fraction of inspired oxygen (FiO2), is reported.

Early red cell transfusion is associated with development of severe retinopathy of prematurity.

OBJECTIVE: To evaluate the association between early (within 10 d) pRBC transfusion and the development of severe ROP. STUDY DESIGN AND METHODS: This was a single-center retrospective study. Inclusion criteria were preterm infants born ≤32 weeks gestation or weighing ≤1500 g. Severe ROP was defined as infants requiring retinal laser ablation or bevacizumab injection. Logistic regression was used to identify the association between transfusions and severe ROP. RESULTS: A total of 1635 infants were included in the final analysis. The severe ROP incidence was 8% (126/1635). Ninety-one percent (115/126) of infants who developed severe ROP received a pRBC transfusion in the first 10 d. Early transfusion was associated with severe ROP; adjusted odds ratio of 3.8 (95% CI: 1.8-8.1). CONCLUSION: pRBC transfusions in the first 10 days of life are associated with an almost four-fold increased risk of severe ROP, independent of gestational age at birth or bronchopulmonary dysplasia (BPD) status.

A Web-Based Calculator for the Prediction of Severe Neurodevelopmental Impairment in Preterm Infants Using Clinical and Imaging Characteristics.

Although the most common forms of brain injury in preterm infants have been associated with adverse neurodevelopmental outcomes, existing MRI scoring systems lack specificity, do not incorporate clinical factors, and are technically challenging to perform. The objective of this study was to develop a web-based, clinically-focused prediction system which differentiates severe neurodevelopmental outcomes from normal-moderate outcomes at two years. Infants were retrospectively identified as those who were born ≤30 weeks gestation and who had MRI imaging at term-equivalent age and neurodevelopmental testing at 18⁻24 months. Each MRI was scored on injury in three domains (intraventricular hemorrhage, white matter injury, and cerebellar hemorrhage) and clinical factors that were strongly predictive of an outcome were investigated. A binary logistic regression model was then generated from the composite of clinical and imaging components. A total of 154 infants were included (mean gestational age = 26.1 ± 1.8 weeks, birth weight = 889.1 ± 226.2 g). The final model (imaging score + ventilator days + delivery mode + antenatal steroids + retinopathy of prematurity requiring surgery) had strong discriminatory power for severe disability (AUC = 0.850), with a PPV (positive predictive value) of 76% and an NPV (negative predictive value) of 90%. Available as a web-based tool, it can be useful for prognostication and targeting early intervention services to infants who may benefit the most from such services.

Re-examining the arterial cord blood gas pH screening criteria in neonatal encephalopathy.

OBJECTIVE: Screening criteria for neonatal encephalopathy remain a complex combination of subjective and objective criteria. We examine the utility of universal cord blood gas testing and mandatory encephalopathy evaluation for infants with pH ≤7.10 on umbilical cord arterial blood gas (cABG) as a single screening measure for timely identification of moderate/severe encephalopathy. DESIGN, SETTING, PATIENTS: Infants born at a single centre between 2008 and 2015, who were ≥36 weeks, had no congenital anomalies and had a cABG pH ≤7.10 were identified for a retrospective cohort study. Maternal/perinatal and patient factors were collected. RESULTS: 27 028 infants were born during the study period; 412 met all inclusion criteria. Of those, 35/85 infants with pH <7.00 and 34/327 infants with pH between 7.00 and 7.10 had moderate/severe encephalopathy. Encephalopathy was identified on the basis of pH and examination alone (no other perinatal criteria present) in 5/35 and 13/34 infants in the two pH groups, respectively.A cABG pH threshold of ≤7.10 was associated with a sensitivity of 74.2% and a specificity of 98.7% for detection of moderate/severe encephalopathy. Based on these data, 25 infants with cABG pH between 7.00 and 7.10 will need to be screened to identify one neonate with moderate/severe encephalopathy, who might have otherwise been missed using conventional screening, a 15% increase in appropriate selection and treatment over current methods. CONCLUSION: Universal cord blood gas screening with a pH threshold ≤7.10 and mandatory encephalopathy examination results in greater detection of infants with moderate/severe encephalopathy and timely initiation of therapeutic hypothermia.

Minoxidil-associated anorexia in an infant with refractory hypertension.

Minoxidil is a potent antihypertensive used as an adjunctive agent in refractory hypertension. It exerts an antihypertensive effect through two mechanisms: selective arterial vasodilation by activation of potassium channels in the vascular smooth muscle and stimulation of carotid and aortic baroreceptors, leading to downstream release of renin and norepinephrine. Although frequently cited in reviews of antihypertensive agents, limited data about the use of minoxidil in neonates are available. We describe an infant girl, born at 35 weeks of gestation, who was diagnosed with idiopathic hypertension after extensive diagnostic evaluation. Adequate blood pressure control was not achieved with captopril, amlodipine, and clonidine. Oliguria secondary to captopril and rapid-onset congestive heart failure due to persistent hypertension led to the introduction of intravenous agents labetalol and nitroprusside. Although adequate blood pressure control was achieved, attempts to transition back to oral agents were unsuccessful, prompting the use of minoxidil as an alternative agent. Although good blood pressure control was achieved, the infant's oral intake plummeted from 210 to 63 ml/kg/day. The anorexia quickly resolved after stopping minoxidil, and she was discharged home at 5 months of age receiving propranolol, amlodipine, and doxazosin. Use of the Naranjo adverse drug reaction probability scale indicated a definite relationship (score of 10) between the patient's development of anorexia and minoxidil therapy. To our knowledge, there have been no previous reports of minoxidil-associated anorexia in preterm or term infants. Clinicians should be aware that anorexia is a possible adverse effect of minoxidil in this patient population when initiating the drug in similar patients.

Neuro-Behçets in a Child.

We describe a case of neuro-Behçet disease diagnosed in a 12-year-old girl. This patient presented with recurrent oral ulcers, incontinence, spastic gait, blurry vision, and asymmetrical lower extremity hypertonia. Extensive testing revealed punctate lesions through the central nervous system, vitritis, papillitis, and uveitis. A thorough infectious and neoplastic workup was negative. She was treated with pulse steroids and azathioprine with gradual improvement in her gait and ophthalmologic findings. Although rare, primary neuro-Behçet should be considered in pediatric patients with neurologic abnormalities and recurrent aphthous ulcers without other explanation.

Quantitative image analysis of estrogen receptors in breast fine needle aspiration biopsies.

OBJECTIVE: To establish whether the results of quantitative evaluation of estrogen receptors (ERs) in cytologic fine needle aspiration (FNA) biopsies of the breast are comparable to the results obtained on excised breast tumors and therefore suitable for making a clinical decision on tamoxifen treatment in women who are not candidates for surgery. STUDY DESIGN: We performed a retrospective review of 118 breast FNA specimens that were positive for adenocarcinoma cells, had adequate cell block cellularity and provided subsequent surgical resection tissue. Quantification of ERs was performed on cell block material and follow-up tissue sections by the Chromavision Automated Imaging System, San Juan Capistrano, California, U.S.A. RESULTS: Quantitative image analysis provided consistently reliable, comparable results when evaluating for the presence or absence of ERs (at a 5% staining cutoff level), with 98.3% agreement between FNA cytology and histology specimens. Quantitative measurements of FNA samples showed the best agreement with the values derived from the subsequent surgical specimens at high-end (> 85% staining) and low-end (< 10% staining) values. However, a direct linear correlation of values was not observed. In the great majority of parallel measures, ERs were either strongly positive (> 75% staining) or had a zero value, particularly in the surgical specimens, with more "in-between" values identified in FNA specimens. CONCLUSION: Quantitative image analysis of FNA of ER results are comparable to those of surgical excision specimens and can be used for therapeutic decision making. The utility and advantages of quantitative ERs by image analysis include providing the patient and physician with important early prognostic and diagnostic information before planning a surgical approach. Additionally, FNA ERs are useful in determining therapy alternatives in patients who are not surgical candidates and in evaluating the preoperative hormone status of patients receiving chemotherapy prior to surgery.