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OBJECTIVE: This study aimed to describe scholarly activity training during neonatal-perinatal medicine (NPM) fellowship and factors associated with scholarship productivity. STUDY DESIGN: NPM fellowship program directors (FPDs) were surveyed between March and October 2019, as part of a larger study of all pediatric subspecialty programs, to define barriers, resources, and productivity for fellow scholarly activity. High productivity was defined as >75% of fellows in a program in the last 5 years having a manuscript accepted for publication based on fellowship scholarly work. RESULTS: Fifty-four percent (54/100) of NPM FPDs completed the survey. Nineteen fellowship programs (35%, 19/54) met the definition for high productivity. High productivity in scholarly activity was associated with a greater likelihood of having funds to conduct scholarship (p = 0.011), more protected months dedicated to scholarly activity (p = 0.03), and fellow extramural grant applications (submitted or accepted, p = 0.047). FPDs of productive programs were less likely to report lack of an adequate core research curriculum (p = 0.018), lack of adequate expertise on the fellowship scholarly oversight committee (p = 0.048), and lack of sufficient divisional mentorship (p = 0.048) as barriers to completion of scholarly activity during fellowship. CONCLUSION: Research funding, protected research time, established research mentors, and a research curriculum are associated with higher scholarly activity productivity among NPM fellowship programs. Further investment in these resources may improve scholarly activity productivity during fellowship training. KEY POINTS: · Fellow productivity depends on protected time.. · Inadequate funding impacts fellow productivity.. · Mentorship is important for fellow scholarship.. · A research curriculum impacts research outcomes..
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BACKGROUND AND OBJECTIVES: Entrustable professional activities (EPAs) will be used for initial certification by the American Board of Pediatrics by 2028. Less than half of pediatric fellowships currently use EPAs for assessment, yet all will need to adopt them. Our objectives were to identify facilitators and barriers to the implementation of EPAs to assess pediatric fellows and to determine fellowship program directors' (FPD) perceptions of EPAs and Milestones. METHODS: We conducted a survey of FPDs from 15 pediatric subspecialties. EPA users were asked about their implementation of EPAs, barriers encountered, and perceptions of EPAs. Nonusers were queried about deterrents to using EPAs. Both groups were asked about potential facilitators of implementation and their perceptions of Milestones. RESULTS: The response rate was 65% (575/883). Of these, 344 (59.8%) were EPA users and 231 (40.2%) were nonusers. Both groups indicated work burden as a barrier to implementation. Nonusers reported more barriers than users (mean [SD]: 7 [3.8] vs 5.8 [3.4], P < .001). Both groups identified training materials and premade assessment forms as facilitators to implementation. Users felt that EPAs were easier to understand than Milestones (89%) and better reflected what it meant to be a practicing subspecialty physician (90%). In contrast, nonusers felt that Milestones were easy to understand (57%) and reflected what it meant to be a practicing subspecialist (58%). CONCLUSIONS: Implementing EPA-based assessment will require a substantial investment by FPDs, facilitated by guidance and easily accessible resources provided by multiple organizations. Perceived barriers to be addressed include FPD time constraints, a need for additional assessment tools, and outcomes data.
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Bolsas de Estudo , Pediatria , Pediatria/educação , Humanos , Competência Clínica , Estados Unidos , Certificação , Inquéritos e Questionários , Masculino , FemininoRESUMO
BACKGROUND: Entrustable Professional Activities (EPA) and competencies represent components of a competency-based education framework. EPAs are assessed based on the level of supervision (LOS) necessary to perform the activity safely and effectively. The broad competencies, broken down into narrower subcompetencies, are assessed using milestones, observable behaviors of one's abilities along a developmental spectrum. Integration of the two methods, accomplished by mapping the most relevant subcompetencies to each EPA, may provide a cross check between the two forms of assessment and uncover those subcompetencies that have the greatest influence on the EPA assessment. OBJECTIVES: We hypothesized that 1) there would be a strong correlation between EPA LOS ratings with the milestone levels for the subcompetencies mapped to the EPA; 2) some subcompetencies would be more critical in determining entrustment decisions than others, and 3) the correlation would be weaker if the analysis included only milestones reported to the Accreditation Council for Graduate Medical Education (ACGME). METHODS: In fall 2014 and spring 2015, the Subspecialty Pediatrics Investigator Network asked Clinical Competency Committees to assign milestone levels to each trainee enrolled in a pediatric fellowship for all subcompetencies mapped to 6 Common Pediatric Subspecialty EPAs as well as provide a rating for each EPA based upon a 5-point LOS scale. RESULTS: One-thousand forty fellows were assessed in fall and 1048 in spring, representing about 27% of all fellows. For each EPA and in both periods, the average milestone level was highly correlated with LOS (rho range 0.59-0.74; p < 0.001). Correlations were similar when using a weighted versus unweighted milestone score or using only the ACGME reported milestones (p > 0.05). CONCLUSIONS: We found a strong relationship between milestone level and EPA LOS rating but no difference if the subcompetencies were weighted, or if only milestones reported to the ACGME were used. Our results suggest that representative behaviors needed to effectively perform the EPA, such as key subcompetencies and milestones, allow for future language adaptations while still supporting the current model of assessment. In addition, these data provide additional validity evidence for using these complementary tools in building a program of assessment.
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Educação de Pós-Graduação em Medicina , Internato e Residência , Humanos , Criança , Competência Clínica , Educação Baseada em Competências/métodos , Acreditação , IdiomaRESUMO
OBJECTIVE: Despite longstanding and recurrent calls for effective implicit bias (IB) education in health professions education as one mechanism to reduce ongoing racism and health disparities, such curricula for neonatal-perinatal medicine (NPM) are limited. We aim to determine the key curricular elements for educating NPM fellows, advanced practice providers, and attending physicians in the critical topics of IB and health disparities. STUDY DESIGN: A modified Delphi study was performed with content experts in IB and health disparities who had educational relationships to those working and training in the neonatal intensive care unit. RESULT: Three Delphi rounds were conducted from May to November 2021. Experts reached consensus on a variety of items for inclusion in the curriculum, including educational goals, learning objectives, teaching strategies, and educator principles. CONCLUSION: Essential curricular components of an IB and health disparities curriculum for neonatal medicine were defined using rigorous consensus building methodology.
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Viés Implícito , Currículo , Recém-Nascido , Humanos , Consenso , Técnica Delphi , Competência ClínicaRESUMO
OBJECTIVE: Measure the effectiveness of and preference for a standardized, national curriculum utilizing flipped classrooms (FC) in neonatal-perinatal medicine (NPM) fellowships. STUDY DESIGN: Multicentered equivalence, cluster randomized controlled trial of NPM fellowship programs randomized to receive standardized physiology education as in-class lectures (traditional didactic, TD arm) or as pre-class online videos followed by in-class discussions (FC arm). Four multiple-choice question quizzes and three surveys were administered to measure knowledge acquisition, retention, and educational preferences. RESULTS: 530 fellows from 61 NPM fellowships participated. Quiz performance was comparable between groups at all time points (p = NS, TD vs FC at 4 time points). Post intervention, more fellows in both groups preferred group discussions (pre/post FC 42% vs. 58%, P = 0.002; pre/post TD 43% vs. 60%, P = < 0.001). FC fellows were more likely to rate classroom effectiveness positively (FC/TD, 70% vs. 36%, P < 0.001). CONCLUSIONS: FCs promote knowledge acquisition and retention equivalent to TD and FC modalities are preferred by fellows.
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Currículo , Bolsas de Estudo , Recém-Nascido , Humanos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown. METHODS: We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age. RESULTS: We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups. CONCLUSIONS: In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.).
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Displasia Broncopulmonar/prevenção & controle , Glucocorticoides/uso terapêutico , Hidrocortisona/uso terapêutico , Recém-Nascido Prematuro , Extubação , Displasia Broncopulmonar/epidemiologia , Método Duplo-Cego , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/efeitos adversos , Lactente Extremamente Prematuro , Recém-Nascido , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/prevenção & controle , Oxigenoterapia , Respiração ArtificialRESUMO
OBJECTIVE: To determine the relationship between level of supervision (LOS) ratings for the Common Pediatric Subspecialty Entrustable Professional Activities (EPAs) with their associated subcompetency milestones across subspecialties and by fellowship training year. METHODS: Clinical Competency Committees (CCCs) in 14 pediatric subspecialties submitted LOS ratings for 6 Common Subspecialty EPAs and subcompetency milestone levels mapped to these EPAs. We examined associations between these subcompetency milestone levels and LOS ratings across subspecialty training year by fitting per-EPA linear mixed effects models, regressing LOS rating on milestone level and on training year. RESULTS: CCCs from 211 pediatric fellowship programs provided data for 369 first, 336 second, and 331 third year fellows. Mean subcompetency milestone levels increased similarly among subspecialties for most EPAs compared with the reference, Adolescent Medicine. Mean subcompetency milestones mapped to each EPA and mean EPA LOS ratings generally increased by training year across all subspecialties. CONCLUSIONS: Subcompetency milestones levels mapped to each Common Subspecialty EPA and the EPA LOS ratings increase similarly across subspecialties and by training year, providing validity evidence for using EPA LOS to assess pediatric subspecialty trainee performance. This study supports the development of tools to facilitated the CCC evaluation process across all pediatric subspecialties.
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Educação de Pós-Graduação em Medicina , Internato e Residência , Adolescente , Criança , Competência Clínica , Educação Baseada em Competências , Bolsas de Estudo , HumanosRESUMO
Neonatal-perinatal medicine fellows must achieve a meaningful accomplishment in scholarly activity as part of their training. Despite the requirement for scholarly training in fellowship, there is a vanishingly small number of MD-only physician-scientists pursuing a research-oriented career. Recent neonatal trainees have identified several factors that preclude their careers in research-focused academic neonatology, including lower pay in academic positions, inadequate training in research techniques, and the perception that individuals in research careers have a poor work-life balance. High competition for limited pediatric research funds also contributes to a diminishing pool of physician-scientists in neonatology. This small number of physician-scientists is threatened by a high rate of attrition among physicians who enter this career path. In order to prevent further declines in the number of neonatal physician-scientists, we need improvements in funding and strong intra- and cross-institutional mentorship to foster individuals interested in a career as a physician-scientist.
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Neonatologia , Médicos , Criança , Bolsas de Estudo , Feminino , Humanos , Recém-Nascido , GravidezRESUMO
BACKGROUND AND OBJECTIVES: Entrustable Professional Activities (EPAs) were developed to assess pediatric fellows. We previously showed that fellowship program directors (FPDs) may graduate fellows who still require supervision. How this compares with their expectations for entrustment of practicing subspecialists is unknown. METHODS: We surveyed US FPDs in 14 pediatric subspecialties through the Subspecialty Pediatrics Investigator Network between April and August 2017. For each of 7 common pediatric subspecialty EPAs, we compared the minimum level of supervision that FPDs required for graduation with the level they expected of subspecialists for safe and effective practice using the Friedman rank sum test and paired t test. We compared differences between subspecialties using linear regression. RESULTS: We collected data from 660 FPDs (response rate 82%). For all EPAs, FPDs did not require fellows to reach the level of entrustment for graduation that they expected of subspecialists to practice (P < .001). FPDs expected the least amount of supervision for the EPAs consultation and handovers. Mean differences between supervision levels for graduation and practice were smaller for clinical EPAs (consultation, handovers, lead a team) when compared with nonclinical EPAs (quality improvement, management, lead the profession and scholarship; P = .001) and were similar across nearly all subspecialties. CONCLUSIONS: Fellowship graduates may need continued development of clinical and nonclinical skills in their early practice period, underscoring a need for continued assessment and mentoring. Graduation readiness must be based on clear requirements, with alignment of FPD expectations and regulatory standards, to ensure quality care for patients.
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Competência Clínica , Pediatria/educação , Especialização , Confiança , Pessoal Administrativo/estatística & dados numéricos , Humanos , Modelos Lineares , Transferência da Responsabilidade pelo Paciente , Encaminhamento e Consulta , Inquéritos e Questionários/estatística & dados numéricos , Estados UnidosAssuntos
Competência Clínica , Bolsas de Estudo , Recém-Nascido , Intubação Intratraqueal , Currículo , Humanos , Estados UnidosRESUMO
PURPOSE: Entrustable professional activities (EPAs) are one approach to competency-based medical education (CBME), and 7 EPAs have been developed that address content relevant for all pediatric subspecialties. However, it is not known what level of supervision fellowship program directors (FPDs) deem necessary for graduation. The Subspecialty Pediatrics Investigator Network (SPIN) investigated FPD perceptions of the minimum level of supervision required for a trainee to successfully graduate. METHOD: In 2017, SPIN surveyed all FPDs of accredited fellowships for 14 subspecialties. For each EPA, the minimum supervision level for graduation (ranging from observation only to unsupervised practice) was set such that no more than 20% of FPDs would accept a lower level. RESULTS: The survey response rate was 82% (660/802). The minimum supervision level for graduation varied across the 7 EPAs from 2 (direct) to 4 (indirect for complex cases), with significant differences between EPAs. The percentage of FPDs desiring a lower minimum supervision level ranged from 3% to 17%. Compared with the 4 nonclinical EPAs (quality improvement, management, lead within the profession, scholarship), the 3 clinical EPAs (consultation, handover, lead a team) had higher minimum supervision graduation levels (P < .001), with less likelihood that an FPD would graduate a learner below their minimum level (P < .001). CONCLUSIONS: Consensus among FPDs across all pediatric subspecialties demonstrates the potential need for ongoing supervision for graduates in all 7 common pediatric subspecialty EPAs after fellowship. As CBME programs are implemented, processes and infrastructure to support new graduates are important considerations for leaders.
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Educação Baseada em Competências , Educação de Pós-Graduação em Medicina , Bolsas de Estudo , Medicina do Adolescente/educação , Endocrinologia/educação , Gastroenterologia/educação , Hematologia/educação , Humanos , Infectologia/educação , Oncologia/educação , Medicina , Neonatologia/educação , Medicina de Emergência Pediátrica/educação , Pediatria/educação , Pneumologia/educação , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: This study aimed to determine the value, strengths, and challenges of implementing an e-learning based flipped classroom (FC) educational modality as part of the standardized physiology National Neonatology Curriculum (NNC), created for neonatal-perinatal medicine (NPM) fellow learners and faculty educators. STUDY DESIGN: This is a cross-sectional study of NPM fellows and faculty educators who utilized at least one of the e-learning based NNC FC respiratory physiology programs between May and September 2018. Participants were surveyed anonymously regarding their experiences participating in the NNC, including measures of preparation time. A combination of descriptive statistics and proportion comparisons were used for data analysis. RESULTS: Among 172 respondents, the majority of fellow and faculty respondents reported positive attitudes toward the educational content and case discussions, and the majority supported national standardization of NPM physiology education (92%). Fellows reported greater preclass preparation for their FC compared with previous didactic lectures (30-60 vs. 0-15 minutes, p < 0.01). Faculty facilitators reported less preparation time before facilitating a FC compared with the time required for creating a new didactic lecture (median: 60 vs. 240 minutes, p < 0.01). Both fellows and faculty respondents preferred the FC approach to traditional didactics, with fellows showing a greater degree of preference than faculty (68 vs. 52%, respectively, p = 0.04). CONCLUSION: Fellows and faculty educators supported the FC learning, reporting peer-to-peer learning, and the establishment of a learning community which promotes adult learning and critical thinking skills. A national physiology curriculum creates equitable and engaging educational experiences for all NPM fellows while reducing individual program burden of content creation. Our findings further supported the development of an NNC using a flipped classroom modality.
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Instrução por Computador , Currículo , Educação a Distância , Neonatologia/educação , Perinatologia/educação , Fisiologia/educação , Adulto , Estudos Transversais , Educação de Pós-Graduação em Medicina , Docentes de Medicina , Bolsas de Estudo , Grupos Focais , Humanos , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Inquéritos e Questionários , Estados UnidosRESUMO
OBJECTIVES: Fellowship program directors (FPD) and Clinical Competency Committees (CCCs) both assess fellow performance. We examined the association of entrustment levels determined by the FPD with those of the CCC for 6 common pediatric subspecialty entrustable professional activities (EPAs), hypothesizing there would be strong correlation and minimal bias between these raters. METHODS: The FPDs and CCCs separately assigned a level of supervision to each of their fellows for 6 common pediatric subspecialty EPAs. For each EPA, we determined the correlation between FPD and CCC assessments and calculated bias as CCC minus FPD values for when the FPD was or was not a member of the CCC. In addition, we examined the effect of program size, FPD understanding of EPAs, and subspecialty on the correlations. Data were obtained in fall 2014 and spring 2015. RESULTS: A total of 1040 fellows were assessed in the fall and 1048 in the spring. In both periods and for each EPA, there was a strong correlation between FPD and CCC supervision levels (P < .001). The correlation was somewhat lower when the FPD was not a CCC member (P < .001). Overall bias in both periods was small. CONCLUSIONS: The correlation between FPD and CCC assignment of EPA supervision levels is strong. Although slightly weaker when the FPD is not a CCC member, bias is small, so this is likely unimportant in determining fellow entrustment level. The similar performance ratings of FPDs and CCCs support the validity argument for EPAs as competency-based assessment tools.
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Importance: Previous studies of myo-inositol in preterm infants with respiratory distress found reduced severity of retinopathy of prematurity (ROP) and less frequent ROP, death, and intraventricular hemorrhage. However, no large trials have tested its efficacy or safety. Objective: To test the adverse events and efficacy of myo-inositol to reduce type 1 ROP among infants younger than 28 weeks' gestational age. Design, Setting, and Participants: Randomized clinical trial included 638 infants younger than 28 weeks' gestational age enrolled from 18 neonatal intensive care centers throughout the United States from April 17, 2014, to September 4, 2015; final date of follow-up was February 12, 2016. The planned enrollment of 1760 participants would permit detection of an absolute reduction in death or type 1 ROP of 7% with 90% power. The trial was terminated early due to a statistically significantly higher mortality rate in the myo-inositol group. Interventions: A 40-mg/kg dose of myo-inositol was given every 12 hours (initially intravenously, then enterally when feeding; n = 317) or placebo (n = 321) for up to 10 weeks. Main Outcomes and Measures: Type 1 ROP or death before determination of ROP outcome was designated as unfavorable. The designated favorable outcome was survival without type 1 ROP. Results: Among 638 infants (mean, 26 weeks' gestational age; 50% male), 632 (99%) received the trial drug or placebo and 589 (92%) had a study outcome. Death or type 1 ROP occurred more often in the myo-inositol group vs the placebo group (29% vs 21%, respectively; adjusted risk difference, 7% [95% CI, 0%-13%]; adjusted relative risk, 1.41 [95% CI, 1.08-1.83], P = .01). All-cause death before 55 weeks' postmenstrual age occurred in 18% of the myo-inositol group and in 11% of the placebo group (adjusted risk difference, 6% [95% CI, 0%-11%]; adjusted relative risk, 1.66 [95% CI, 1.14-2.43], P = .007). The most common serious adverse events up to 7 days of receiving the ending dose were necrotizing enterocolitis (6% for myo-inositol vs 4% for placebo), poor perfusion or hypotension (7% vs 4%, respectively), intraventricular hemorrhage (10% vs 9%), systemic infection (16% vs 11%), and respiratory distress (15% vs 13%). Conclusions and Relevance: Among premature infants younger than 28 weeks' gestational age, treatment with myo-inositol for up to 10 weeks did not reduce the risk of type 1 ROP or death vs placebo. These findings do not support the use of myo-inositol among premature infants; however, the early termination of the trial limits definitive conclusions.
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Lactente Extremamente Prematuro , Doenças do Recém-Nascido/mortalidade , Inositol/uso terapêutico , Retinopatia da Prematuridade/prevenção & controle , Hemorragia Cerebral Intraventricular/prevenção & controle , Método Duplo-Cego , Feminino , Seguimentos , Idade Gestacional , Humanos , Recém-Nascido , Inositol/efeitos adversos , Terapia Intensiva Neonatal , Masculino , Retinopatia da Prematuridade/mortalidade , Falha de TratamentoRESUMO
BACKGROUND: Congenital diaphragmatic hernia (CDH) is commonly associated with pulmonary hypoplasia and pulmonary hypertension (PH). PH associated with CDH (CDH-PH) is frequently resistant to conventional pulmonary vasodilator therapy including inhaled nitric oxide (iNO) possibly due to right and left ventricular dysfunction. Milrinone is an intravenous inotrope and lusitrope with pulmonary vasodilator properties and has been shown anecdotally to improve oxygenation in PH. We developed this pilot study to determine if milrinone infusion would improve oxygenation in neonates ≥36 weeks postmenstrual age (PMA) with CDH. METHODS/DESIGN: Data on pulmonary vasodilator management and outcome of CDH patients was collected from 18 university NICUs affiliated with the Neonatal Research Network (NRN) from 2011 to 2012. The proposed pilot will be a masked, placebo-controlled, multicenter, randomized trial of 66 infants with CDH with an oxygenation index (OI) ≥10 or oxygen saturation index (OSI) ≥5. The primary outcome is the oxygenation response, as determined by change in OI at 24 h after initiation of study drug. As secondary outcomes, we will determine oxygenation at 48 h and 72 h post-infusion, right ventricular pressures on echocardiogram and the incidence of systemic hypotension, arrhythmias, intracranial hemorrhage, survival without extracorporeal membrane oxygenation, and chronic lung disease (oxygen need at 28 days postnatal age). Finally, we will evaluate the pulmonary and nutritional status at 4, 8 and 12 months of age using a phone questionnaire. RESULTS: Three hundred thirty-seven infants with CDH were admitted to NRN NICUs in 2011 and 2012 of which 275 were ≥36 weeks PMA and were exposed to the following pulmonary vasodilators: iNO (39%), sildenafil (17%), milrinone (17%), inhaled epoprostenol (6%), intravenous epoprostenol (3%), and intravenous PGE1 (1%). ECMO was required in 36% of patients. Survival to discharge was 71%. DISCUSSION: CDH is an orphan disease with high mortality with few randomized trials evaluating postnatal management. Intravenous milrinone is a commonly used medication in neonatal/pediatric intensive care units and is currently used in 17% of patients with CDH within the NRN. This pilot study will provide data and enable further studies evaluating pulmonary vasodilator therapy in CDH. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02951130; registered 14 October 2016.
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BACKGROUND: Preterm infants with respiratory distress syndrome (RDS) given inositol had reduced bronchopulmonary dysplasia (BPD), death and severe retinopathy of prematurity (ROP). We assessed the safety and pharmacokinetics of daily inositol to select a dose providing serum levels previously associated with benefit, and to learn if accumulation occurred when administered throughout the normal period of retinal vascularization. METHODS: Infants ≤ 29 wk GA (n = 122, 14 centers) were randomized and treated with placebo or inositol at 10, 40, or 80 mg/kg/d. Intravenous administration converted to enteral when feedings were established, and continued to the first of 10 wk, 34 wk postmenstrual age (PMA) or discharge. Serum collection employed a sparse sampling population pharmacokinetics design. Inositol urine losses and feeding intakes were measured. Safety was prospectively monitored. RESULTS: At 80 mg/kg/d mean serum levels reached 140 mg/l, similar to Hallman's findings. Levels declined after 2 wk, converging in all groups by 6 wk. Analyses showed a mean volume of distribution 0.657 l/kg, clearance 0.058 l/kg/h, and half-life 7.90 h. Adverse events and comorbidities were fewer in the inositol groups, but not significantly so. CONCLUSION: Multiple dose inositol at 80 mg/kg/d was not associated with increased adverse events, achieves previously effective serum levels, and is appropriate for investigation in a phase III trial.
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Inositol/farmacocinética , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Displasia Broncopulmonar/complicações , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Infusões Intravenosas , Inositol/administração & dosagem , Masculino , Segurança do Paciente , Síndrome do Desconforto Respiratório do Recém-Nascido/complicações , Retinopatia da Prematuridade/complicações , Fatores de TempoRESUMO
Despite American College of Obstetricians and Gynecologists guidelines suggesting that non-urgent planned deliveries be scheduled at/after 39 weeks; elective delivery before 39 weeks occurs often in the United States. The objective of this study is to estimate the elective delivery rate between 36(0/7) and 38(6/7) weeks gestation and compare NICU admission rates between elective and non-elective deliveries. We conducted a retrospective cohort (n = 1,577) study. Charts were reviewed for all singleton deliveries (2006-2007) between 36(0/7) and 38(6/7) weeks gestation taking place at one hospital in NYS to determine delivery status. We computed adjusted relative risks (RR) with 95% confidence intervals (CI) for elective delivery in relation to NICU admission using robust Poisson regression. 32.8% of all births were elective: 20.7% of vaginal and 55.7% of cesarean births. Elective delivery increased with increasing gestational age. After controlling for potential confounders, infants born via a vaginal elective delivery (RR = 1.40, CI: 1.00, 1.94), an elective cesarean (RR = 2.05, CI: 1.53, 2.76), or a non-elective cesarean (RR = 2.00, CI: 1.50, 2.66) are at significantly increased risk of NICU admission compared to infants born via a non-elective vaginal delivery. Elective delivery before 39 weeks is common and increases the risk of infant NICU admission.
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Parto Obstétrico/estatística & dados numéricos , Idade Gestacional , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Admissão do Paciente/estatística & dados numéricos , Adolescente , Adulto , Peso ao Nascer , Intervalos de Confiança , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Feminino , Humanos , Incidência , Recém-Nascido , Masculino , New York/epidemiologia , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Fatores de Risco , Fatores Socioeconômicos , Adulto JovemRESUMO
High tidal volume mechanical ventilation can cause inflammation and lung damage. Mechanical strain is also necessary for normal lung growth. The current work was performed to determine if mechanical ventilation with clinically utilized tidal volumes stimulates a proliferative response in the lung. Six- to 8-week-old C57/Bl6 mice, anesthetized with ketamine/xylozine, were ventilated for 6 hours with 10 mL/kg tidal volume, positive end-expiratory pressure (PEEP) 3cm H(2)O. Pulmonary function testing demonstrated decreased compliance within 3 hours of ventilation. Assessment of bronchoalveolar lavage (BAL) demonstrated no significant increase in lactate dehydrogenase, total lavagable cell number, or total protein after ventilation. There was evidence of inflammation in the lungs of ventilated mice, with an increased percentage of lymphocytes and neutrophils in BAL, and an increase in macrophage inflammatory protein (MIP)-2 and interleukin (IL)-1beta message in lung tissue. Immunohistochemistry of inflation-fixed lungs demonstrated increased alveolar cell proliferation, as measured by both proliferating cell nuclear antigen and Ki67 staining. Dual staining confirmed that proliferating cells labeled with proSP-B, demonstrating that ventilation induces proliferation of alveolar type II cells. Ventilation did not increase apoptosis in alveolar type II cells, as measured by TUNEL staining. Ventilation at low tidal volumes leads to a mild inflammatory response and alveolar epithelial cell proliferation.
Assuntos
Proliferação de Células , Células Epiteliais/patologia , Pneumonia/patologia , Alvéolos Pulmonares/patologia , Lesão Pulmonar Induzida por Ventilação Mecânica/patologia , Ventiladores Mecânicos/efeitos adversos , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Quimiocina CXCL2/genética , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Interleucina-1beta/genética , Antígeno Ki-67/metabolismo , Complacência Pulmonar , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia/etiologia , Pneumonia/imunologia , Pneumonia/fisiopatologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Precursores de Proteínas/metabolismo , Proteolipídeos/metabolismo , Alvéolos Pulmonares/imunologia , Volume de Ventilação Pulmonar , Fatores de Tempo , Lesão Pulmonar Induzida por Ventilação Mecânica/etiologia , Lesão Pulmonar Induzida por Ventilação Mecânica/imunologia , Lesão Pulmonar Induzida por Ventilação Mecânica/fisiopatologiaRESUMO
Despite its potentially adverse effects on lung development and function, supplemental oxygen is often used to treat premature infants in respiratory distress. To understand how neonatal hyperoxia can permanently disrupt lung development, we previously reported increased lung compliance, greater alveolar simplification, and disrupted epithelial development in adult mice exposed to 100% inspired oxygen fraction between postnatal days 1 and 4. Here, we investigate whether oxygen-induced changes in lung function are attributable to defects in surfactant composition and activity, structural changes in alveolar development, or both. Newborn mice were exposed to room air or 40%, 60%, 80%, or 100% oxygen between postnatal days 1 and 4 and allowed to recover in room air until 8 wk of age. Lung compliance and alveolar size increased, and airway resistance, airway elastance, tissue elastance, and tissue damping decreased, in mice exposed to 60-80% oxygen; changes were even greater in mice exposed to 100% oxygen. These alterations in lung function were not associated with changes in total protein content or surfactant phospholipid composition in bronchoalveolar lavage. Moreover, surface activity and total and hydrophobic protein content were unchanged in large surfactant aggregates centrifuged from bronchoalveolar lavage compared with control. Instead, the number of type II cells progressively declined in 60-100% oxygen, whereas levels of T1alpha, a protein expressed by type I cells, were comparably increased in mice exposed to 40-100% oxygen. Thickened bundles of elastin fibers were also detected in alveolar walls of mice exposed to > or = 60% oxygen. These findings support the hypothesis that changes in lung development, rather than surfactant activity, are the primary causes of oxygen-altered lung function in children who were exposed to oxygen as neonates. Furthermore, the disruptive effects of oxygen on epithelial development and lung mechanics are not equivalently dose dependent.