Randomized controlled trial of the "WISER" intervention to reduce healthcare worker burnout.

OBJECTIVE: Test web-based implementation for the science of enhancing resilience (WISER) intervention efficacy in reducing healthcare worker (HCW) burnout. DESIGN: RCT using two cohorts of HCWs of four NICUs each, to improve HCW well-being (primary outcome: burnout). Cohort 1 received WISER while Cohort 2 acted as a waitlist control. RESULTS: Cohorts were similar, mostly female (83%) and nurses (62%). In Cohorts 1 and 2 respectively, 182 and 299 initiated WISER, 100 and 176 completed 1-month follow-up, and 78 and 146 completed 6-month follow-up. Relative to control, WISER decreased burnout (-5.27 (95% CI: -10.44, -0.10), p = 0.046). Combined adjusted cohort results at 1-month showed that the percentage of HCWs reporting concerning outcomes was significantly decreased for burnout (-6.3% (95%CI: -11.6%, -1.0%); p = 0.008), and secondary outcomes depression (-5.2% (95%CI: -10.8, -0.4); p = 0.022) and work-life integration (-11.8% (95%CI: -17.9, -6.1); p < 0.001). Improvements endured at 6 months. CONCLUSION: WISER appears to durably improve HCW well-being. CLINICAL TRIALS NUMBER: NCT02603133; https://clinicaltrials.gov/ct2/show/NCT02603133.

Hypothermia and neonatal encephalopathy.

Data from large randomized clinical trials indicate that therapeutic hypothermia, using either selective head cooling or systemic cooling, is an effective therapy for neonatal encephalopathy. Infants selected for cooling must meet the criteria outlined in published clinical trials. The implementation of cooling needs to be performed at centers that have the capability to manage medically complex infants. Because the majority of infants who have neonatal encephalopathy are born at community hospitals, centers that perform cooling should work with their referring hospitals to implement education programs focused on increasing the awareness and identification of infants at risk for encephalopathy, and the initial clinical management of affected infants.

An intervention to improve transitions from NICU to ambulatory care: quasi-experimental study.

BACKGROUND: Infants born prematurely or with complex medical problems are surviving to discharge in growing numbers and often require significant monitoring and coordination of care in the ambulatory setting. Using Healthcare Failure Modes and Effects Analysis (HFMEA), we identified a large number of potentially serious error points in this transition of care. PURPOSE To test whether a multifaceted intervention that included a health coach to assist families and an enhanced personal health record to improve the quality of information available to parents and community professionals would decrease adverse events and improve family assessment of the transition. METHODS: Using a concurrent cohort design, infants in one geographic area (pod) of the intensive care nursery received the intervention; infants in two other pods received routine discharge care. Primary outcomes included deaths, sick visits, unplanned readmissions and missed appointments within 1 month of discharge. The family assessed the transition using a modified version of the Care Transitions Measure. RESULTS: 125 intervention infants (54% boys) and 104 control infants (48% boys) were enrolled over 18 months. The groups were similar in maternal education, insurance status, language spoken and number of adults in the home, birth weight and length of stay. At least one adverse outcome occurred in 63 (50.4%) intervention infants and 56 (53.8%) control infants (p=0.55). At 24­48 h post discharge, caregivers in the intervention group had significantly higher scores on the adapted care transitions measure (3.51 vs 3.27, p<0.0001); however, at 30 days, the difference was no longer significant (3.45 vs 3.40, p=0.27). CONCLUSIONS: A multicomponent discharge intervention designed to address specific problems identified using HFMEA did not reduce certain adverse outcomes in the post-discharge period. TRIAL REGISTRATION: NCT01088945.

Childhood outcomes after hypothermia for neonatal encephalopathy.

BACKGROUND: We previously reported early results of a randomized trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy showing a significant reduction in the rate of death or moderate or severe disability at 18 to 22 months of age. Long-term outcomes are now available. METHODS: In the original trial, we assigned infants with moderate or severe encephalopathy to usual care (the control group) or whole-body cooling to an esophageal temperature of 33.5°C for 72 hours, followed by slow rewarming (the hypothermia group). We evaluated cognitive, attention and executive, and visuospatial function; neurologic outcomes; and physical and psychosocial health among participants at 6 to 7 years of age. The primary outcome of the present analyses was death or an IQ score below 70. RESULTS: Of the 208 trial participants, primary outcome data were available for 190. Of the 97 children in the hypothermia group and the 93 children in the control group, death or an IQ score below 70 occurred in 46 (47%) and 58 (62%), respectively (P=0.06); death occurred in 27 (28%) and 41 (44%) (P=0.04); and death or severe disability occurred in 38 (41%) and 53 (60%) (P=0.03). Other outcome data were available for the 122 surviving children, 70 in the hypothermia group and 52 in the control group. Moderate or severe disability occurred in 24 of 69 children (35%) and 19 of 50 children (38%), respectively (P=0.87). Attention-executive dysfunction occurred in 4% and 13%, respectively, of children receiving hypothermia and those receiving usual care (P=0.19), and visuospatial dysfunction occurred in 4% and 3% (P=0.80). CONCLUSIONS: The rate of the combined end point of death or an IQ score of less than 70 at 6 to 7 years of age was lower among children undergoing whole-body hypothermia than among those undergoing usual care, but the differences were not significant. However, hypothermia resulted in lower death rates and did not increase rates of severe disability among survivors. (Funded by the National Institutes of Health and the Eunice Kennedy Shriver NICHD Neonatal Research Network; ClinicalTrials.gov number, NCT00005772.).

Cytokines and neurodevelopmental outcomes in extremely low birth weight infants.

OBJECTIVE: To determine if selected pro-inflammatory and anti-inflammatory cytokines and/or mediators of inflammation reported to be related to the development of cerebral palsy (CP) predict neurodevelopmental outcome in extremely low birth weight infants. STUDY DESIGN: Infants with birth weights ≤1000 g (n = 1067) had blood samples collected at birth and on days 3 ± 1, 7 ± 1, 14 ± 3, and 21 ± 3 to examine the association between cytokines and neurodevelopmental outcomes. The analyses were focused on 5 cytokines (interleukin [IL] 1ß; IL-8; tumor necrosis factor-α; regulated upon activation, normal T-cell expressed, and secreted (RANTES); and IL-2) reported to be most predictive of CP in term and late preterm infants. RESULTS: IL-8 was higher on days 0-4 and subsequently in infants who developed CP compared with infants who did not develop CP in both unadjusted and adjusted analyses. Other cytokines (IL-12, IL-17, tumor necrosis factor-ß, soluble IL rα, macrophage inflammatory protein 1ß) were found to be altered on days 0-4 in infants who developed CP. CONCLUSIONS: CP in former preterm infants may, in part, have a late perinatal and/or early neonatal inflammatory origin.

Clinical benefits, costs, and cost-effectiveness of neonatal intensive care in Mexico.

BACKGROUND: Neonatal intensive care improves survival, but is associated with high costs and disability amongst survivors. Recent health reform in Mexico launched a new subsidized insurance program, necessitating informed choices on the different interventions that might be covered by the program, including neonatal intensive care. The purpose of this study was to estimate the clinical outcomes, costs, and cost-effectiveness of neonatal intensive care in Mexico. METHODS AND FINDINGS: A cost-effectiveness analysis was conducted using a decision analytic model of health and economic outcomes following preterm birth. Model parameters governing health outcomes were estimated from Mexican vital registration and hospital discharge databases, supplemented with meta-analyses and systematic reviews from the published literature. Costs were estimated on the basis of data provided by the Ministry of Health in Mexico and World Health Organization price lists, supplemented with published studies from other countries as needed. The model estimated changes in clinical outcomes, life expectancy, disability-free life expectancy, lifetime costs, disability-adjusted life years (DALYs), and incremental cost-effectiveness ratios (ICERs) for neonatal intensive care compared to no intensive care. Uncertainty around the results was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis. In the base-case analysis, neonatal intensive care for infants born at 24-26, 27-29, and 30-33 weeks gestational age prolonged life expectancy by 28, 43, and 34 years and averted 9, 15, and 12 DALYs, at incremental costs per infant of US$11,400, US$9,500, and US$3,000, respectively, compared to an alternative of no intensive care. The ICERs of neonatal intensive care at 24-26, 27-29, and 30-33 weeks were US$1,200, US$650, and US$240, per DALY averted, respectively. The findings were robust to variation in parameter values over wide ranges in sensitivity analyses. CONCLUSIONS: Incremental cost-effectiveness ratios for neonatal intensive care imply very high value for money on the basis of conventional benchmarks for cost-effectiveness analysis. Please see later in the article for the Editors' Summary.

Trends in neonatal morbidity and mortality for very low birthweight infants.

OBJECTIVE: To document the mortality and morbidity of infants weighing 501-1500 g at birth according to gestational age, birthweight, and sex. STUDY DESIGN: Prospective collection of perinatal events and neonatal course to 120 days of life, discharge, or death from January 1990 through December 2002 for infants born at 16 participating centers of the National Institute of Child Health & Human Development Neonatal Research Network. RESULTS: Compared with 1995-1996, for 1997-2002 the survival of infants with birthweight of 501-1500 g increased by 1 percentage point (from 84% to 85%). Survival without major neonatal morbidity remained static, at 70%; this includes bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC). Survival increased for multiple births (26%, up from 22%), antenatal corticosteroid use (79%, up from 71%), and maternal antibiotics (70%, up from 62%) (P < .05). From 1997 to 2002, birthweight-specific survival was 55% for infants weighing 501-750 g, 88% for 751-1000 g, 94% for 1001-1250 g, and 96% for 1251-1500 g. More females survived. The incidence of NEC (7%), severe IVH (12%), and late-onset septicemia (22%) remained essentially unchanged, but BPD decreased slightly, from 23% to 22%. The use of postnatal corticosteroids declined from 20% in 1997-2000 to 12% in 2001-2002. Growth failure (weight <10th percentile) at 36 weeks' postmenstrual age decreased from 97% in 1995-1996 to 91% in 1997-2002. CONCLUSION: There have been no significant increases in survival without neonatal and long-term morbidity among VLBW infants between 1997 and 2002. We speculate that to improve survival without morbidity requires determining, disseminating, and applying best practices using therapies currently available, and also identifying new strategies and interventions.

Neurosensory impairment after surgical closure of patent ductus arteriosus in extremely low birth weight infants: results from the Trial of Indomethacin Prophylaxis in Preterms.

OBJECTIVES: To determine whether surgical closure of a patent ductus arteriosus (PDA) is a risk factor for bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity (ROP), and neurosensory impairment in extremely low birth weight (ELBW) infants. STUDY DESIGN: We studied 426 infants with a symptomatic PDA, 110 of whom underwent PDA ligation and 316 of whom received medical therapy only. All infants participated in the multicenter Trial of Indomethacin Prophylaxis in Preterms (TIPP) and were observed to a corrected age of 18 months. RESULTS: Of the 95 infants who survived after PDA ligation, 50 (53%) had neurosensory impairment, compared with 84 of the 245 infants (34%) who survived after receiving only medical therapy (adjusted odds ratio, 1.98; 95% CI, 1.18-3.30; P = .0093). BPD (adjusted odds ratio, 1.81; 95% CI, 1.09-3.03; P = .023) and severe ROP (adjusted odds ratio, 2.20; 95% CI, 1.19-4.07; P = .012) were also more common after surgical PDA closure. CONCLUSIONS: PDA ligation may be associated with increased risks of BPD, severe ROP, and neurosensory impairment in ELBW infants.

Emotional regulation and its impact on development in extremely low birth weight infants.

The purposes of this study were to compare the Bayley Scales of Infant Development (BSID-II) scores at 8 and 18-22 months adjusted age of a cohort of 47 extremely low birth weight infants and to determine whether there was an association between changes in test scores and infant behavior as measured by the Behavioral Rating Scale of the BSID-II at 18-22 months adjusted age. Psychomotor Developmental Index scores did not differ between the two testing points (p = .17), whereas the Mental Developmental Index (MDI) scores dropped significantly (p = .006). Emotional regulation and low household income were both significantly associated with changes in MDI scores (p = .001 and p = .002, respectively). After adjusting for household income, the association between emotional regulation and changes in MDI scores remained significant (p = .02). Results suggest that infant behavioral characteristics, as well as family socioeconomic status, can adversely affect developmental outcome at 18-22 months adjusted age.

Outcome of very low birth weight infants exposed to antenatal indomethacin for tocolysis.

OBJECTIVE: Beginning in October 1995, and for several years thereafter, our institution used indomethacin as a first-line tocolytic drug. Our purpose is to compare the outcomes of very low birth weight infants who were exposed to antenatal indomethacin with those who were not exposed to this therapy. STUDY DESIGN: We used our center's component of the NICHD Neonatal Research Network's Generic Data Base which recorded the outcomes of all live born infants weighing less than 1500 g over a 5-year period. We abstracted data concerning neonatal morbidity (death, Grades III to IV intraventricular hemorrhage (IVH), necrotizing enterocolitis and patent ductus arteriosus), as well as other factors including gestational age, birth weight, antenatal corticosteroid treatment and maternal hypertension or pre-eclampsia. Univariate analysis was performed using Fisher's exact test. Multivariate analysis using logistic regression was performed to control for confounding factors. RESULTS: A total of 85 infants who were exposed to antenatal indomethacin were compared to 464 infants who were not exposed to the drug. In the univariate analysis, antenatal indomethacin exposure was not associated with a significant increase in the incidence of necrotizing enterocolitis or patent ductus arteriosus. The incidence of Grades III to IV IVH was 17.9% in those infants exposed to antenatal indomethacin compared to 7.1% in the nonexposed infants (p=0.008). The incidence of neonatal death in the exposed infants was 27.7 versus 16.4 in the nonexposed infants (p=0.02). After controlling for antenatal corticosteroids, maternal pre-eclampsia, gestational age and birth weight, antenatal indomethacin was significantly associated with an increased incidence of IVH, but not neonatal death. CONCLUSION: Antenatal indomethacin was associated with significantly higher rates of IVH. Additional studies assessing the potential risks of indomethacin tocolysis are needed before it is used as a first-line tocolytic therapy.

Neurodevelopmental outcome and growth at 18 to 22 months' corrected age in extremely low birth weight infants treated with early erythropoietin and iron.

BACKGROUND: Clinical trials evaluating the use of erythropoietin (Epo) have demonstrated a limited reduction in transfusions; however, long-term developmental follow-up data are scarce. OBJECTIVE: We compared anthropometric measurements, postdischarge events, need for transfusions, and developmental outcomes at 18 to 22 months' corrected age in extremely low birth weight (ELBW) infants treated with early Epo and supplemental iron therapy with that of placebo/control infants treated with supplemental iron alone. METHODS: The National Institute of Child Health and Human Development Neonatal Research Network completed a randomized, controlled trial of early Epo and iron therapy in preterm infants < or =1250 g. A total of 172 ELBW (< or =1000-g birth weight) infants were enrolled (87 Epo and 85 placebo/control). Of the 72 Epo-treated and 70 placebo/control ELBW infants surviving to discharge, follow-up data (growth, development, rehospitalization, transfusions) at 18 to 22 months' corrected age were collected on 51 of 72 Epo-treated infants (71%) and 51 of 70 placebo/controls (73%) by certified examiners masked to the treatment group. Statistical significance was determined using chi2 analysis. RESULTS: There were no significant differences between treatment groups in weight or length or in the percentage of infants weighing <10th percentile either at the time of discharge or at follow-up, and no difference was found in the mean head circumference between groups. A similar percentage of infants in each group was rehospitalized (38% Epo and 35% placebo/control) for similar reasons. There were no differences between groups with respect to the percentage of infants with Bayley-II Mental Developmental Index <70 (34% Epo and 36% placebo/control), blindness (0% Epo and 2% placebo/control), deafness or hearing loss requiring amplification (2% Epo and 2% placebo/control), moderate to severe cerebral palsy (16% Epo and 18% placebo/control) or the percentage of infants with any of the above-described neurodevelopmental impairments (42% Epo and 44% placebo/control). CONCLUSIONS: Treatment of ELBW infants with early Epo and iron does not significantly influence anthropometric measurements, need for rehospitalization, transfusions after discharge, or developmental outcome at 18 to 22 months' corrected age.

To tap or not to tap: high likelihood of meningitis without sepsis among very low birth weight infants.

CONTEXT: Neonatal meningitis is associated with significant morbidity and mortality. We speculated that meningitis may be underdiagnosed among very low birth weight (VLBW) infants because of the failure to perform lumbar punctures (LPs) in infants with suspected sepsis. OBJECTIVE: This study was undertaken to review the epidemiology of late-onset meningitis in VLBW (401-1500 g) infants and to evaluate the concordance of cerebrospinal fluid (CSF) and blood culture (BC) results. METHODS: VLBW infants (excluding those with intraventricular shunts) born at centers of the National Institute of Child Health and Human Development Neonatal Research Network from September 1, 1998, through December 31, 2001, were studied. Late-onset meningitis was defined by culture-based criteria and classified as meningitis with or without associated sepsis. Unadjusted comparisons were made using chi2 tests and adjusted comparisons using regression models. RESULTS: Of 9641 VLBW infants who survived >3 days, 2877 (30%) had > or = 1 LPs, and 6056 (63%) had > or = 1 BC performed after day 3. One hundred thirty-four infants had late-onset meningitis (1.4% of all patients; 5% of those with an LP). Pathogens associated with meningitis were similar to those associated with sepsis. One third (45 of 134) of the infants with meningitis had negative BCs. Lower gestational age and prior sepsis increased risk for meningitis. Compared with uninfected infants, those with meningitis had a longer time on mechanical ventilation (28 vs 18 days), had longer hospitalizations (91 vs 79 days), were more likely to have seizures (25% vs 2%), and were more likely to die (23% vs 2%). CONCLUSIONS: Meningitis is a serious complication among VLBW infants, associated with increased severity of illness and risk of death. Of note, one third of the infants with meningitis had meningitis in the absence of sepsis. Because CSF cultures were performed only half as often as BCs, this discordance in blood and CSF culture results suggests that meningitis may be underdiagnosed among VLBW infants.

Parenteral glutamine supplementation does not reduce the risk of mortality or late-onset sepsis in extremely low birth weight infants.

BACKGROUND: Glutamine is one of the most abundant amino acids in both plasma and human milk, yet it is not included in standard intravenous amino acid solutions. Previous studies have suggested that parenteral nutrition (PN) supplemented with glutamine may reduce sepsis and mortality in critically ill adults. Whether glutamine supplementation would provide a similar benefit to extremely low birth weight (ELBW) infants is not known. METHODS: We performed a multicenter, randomized, double-masked, clinical trial to assess the safety and efficacy of early PN supplemented with glutamine in decreasing the risk of death or late-onset sepsis in ELBW infants. Infants 401 to 1000 g were randomized within 72 hours of birth to receive either TrophAmine (control) or an isonitrogenous study amino acid solution with 20% glutamine whenever they received PN up to 120 days of age, death, or discharge from the hospital. The primary outcome was death or late-onset sepsis. RESULTS: Of the 721 infants who were assigned to glutamine supplementation, 370 (51%) died or developed late-onset sepsis, as compared with 343 of the 712 infants (48%) assigned to control (relative risk: 1.07; 95% confidence interval: 0.97-1.17). Glutamine had no effect on tolerance of enteral feeds, necrotizing enterocolitis, or growth. No significant adverse events were observed with glutamine supplementation. CONCLUSIONS: Parenteral glutamine supplementation as studied did not decrease mortality or the incidence of late-onset sepsis in ELBW infants. Consequently, although no harm was demonstrated, routine use of parenteral glutamine supplementation cannot be recommended in this population.

Effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants.

BACKGROUND: Glutamine is one of the most abundant amino acids in both plasma and human milk and may be conditionally essential in premature infants. However, glutamine is not provided by standard intravenous amino acid solutions. OBJECTIVE: We assessed the effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants receiving parenteral nutrition (PN). DESIGN: A total of 141 infants with birth weights of 401-1000 g were randomly assigned to receive a standard intravenous amino acid solution that did not contain glutamine or an isonitrogenous amino acid solution with 20% of the total amino acids as glutamine. Blood samples were obtained just before initiation of study PN and again after the infants had received study PN (mean intake: 2.3 +/- 1.0 g amino acids x kg(-1) x d(-1)) for approximately 10 d. RESULTS: Infants randomly assigned to receive glutamine had mean plasma glutamine concentrations that increased significantly and were approximately 30% higher than those in the control group in response to PN (425 +/- 182 and 332 +/- 148 micromol/L for the glutamine and control groups, respectively). There was no significant difference between the 2 groups in the relative change in plasma glutamate concentration between the baseline and PN samples. In both groups, there were significant decreases in plasma phenylalanine and tyrosine between the baseline and PN samples; the decrease in tyrosine was greater in the group that received glutamine. CONCLUSIONS: In extremely low-birth-weight infants, parenteral glutamine supplementation can increase plasma glutamine concentrations without apparent biochemical risk. Currently available amino acid solutions are likely to be suboptimal in their supply of phenylalanine, tyrosine, or both for these infants.

Minimal ventilation to prevent bronchopulmonary dysplasia in extremely-low-birth-weight infants.

OBJECTIVE: To determine whether minimal ventilation decreases death or bronchopulmonary dysplasia (BPD). STUDY DESIGN: Infants with birth weight 501 g to 1000 g and mechanically ventilated before 12 hours were randomly assigned to minimal ventilation (partial pressure of carbon dioxide [PCO(2)] target >52 mm Hg) or routine ventilation (PCO(2) target <48 mm Hg) and a tapered dexamethasone course or saline placebo for 10 days, using a 2 x 2 factorial design. The primary outcome was death or BPD at 36 weeks' postmenstrual age. RESULTS: After enrollment of 220 patients, the trial was halted because of unanticipated nonrespiratory adverse events related to dexamethasone therapy. The relative risk for death or BPD at 36 weeks in the minimal versus routine ventilation groups was 0.93 (95% CI, 0.77-1.12; P =.43). Ventilator support at 36 weeks was 1% in the minimal versus 16% in the routine group (P <.01). Major morbidities and long-term outcome were comparable in both treatment groups. CONCLUSIONS: With the sample size studied, minimal ventilation did not reduce the incidence of death or BPD. The reduced ventilator support at 36 weeks in the minimal ventilation group warrants further study of this intervention.