Evaluating the feasibility of a multicenter teleneonatology clinical effectiveness trial.

BACKGROUND: Our research consortium is preparing for a prospective multicenter trial evaluating the impact of teleneonatology on the health outcomes of at-risk neonates born in community hospitals. We completed a 6-month pilot study to determine the feasibility of the trial protocol. METHODS: Four neonatal intensive care units ("hubs") and four community hospitals ("spokes") participated in the pilot-forming four hub-spoke dyads. Two hub-spoke dyads implemented synchronous, audio-video telemedicine consultations with a neonatologist ("teleneonatology"). The primary outcome was a composite feasibility score that included one point for each of the following: site retention, on-time screening log completion, no eligibility errors, on-time data submission, and sponsor site-dyad meeting attendance (score range 0-5). RESULTS: For the 20 hub-spoke dyad months, the mean (range) composite feasibility score was 4.6 (4, 5). All sites were retained during the pilot. Ninety percent (18/20) of screening logs were completed on time. The eligibility error rate was 0.2% (3/1809). On-time data submission rate was 88.4% (84/95 case report forms). Eighty-five percent (17/20) of sponsor site-dyad meetings were attended by both hub and spoke site staff. CONCLUSIONS: A multicenter teleneonatology clinical effectiveness trial is feasible. Learnings from the pilot study may improve the likelihood of success of the main trial. IMPACT: A prospective, multicenter clinical trial evaluating the impact of teleneonatology on the early health outcomes of at-risk neonates born in community hospitals is feasible. A multidimensional composite feasibility score, which includes processes and procedures fundamental to completing a clinical trial, is useful for quantitatively measuring pilot study success. A pilot study allows the investigative team to test trial methods and materials to identify what works well or requires modification. Learnings from a pilot study may improve the quality and efficiency of the main effectiveness trial.

Provider Perspectives on the Acceptability, Appropriateness, and Feasibility of Teleneonatology.

OBJECTIVE: We aimed to measure provider perspectives on the acceptability, appropriateness, and feasibility of teleneonatology in neonatal intensive care units (NICUs) and community hospitals. STUDY DESIGN: Providers from five academic tertiary NICUs and 27 community hospitals were surveyed using validated implementation measures to assess the acceptability, appropriateness, and feasibility of teleneonatology. For each of the 12 statements, scale values ranged from 1 to 5 (1 = strongly disagree; 5 = strongly agree), with higher scores indicating greater positive perceptions. Survey results were summarized, and differences across respondents assessed using generalized linear models. RESULTS: The survey response rate was 56% (203/365). Respondents found teleneonatology to be acceptable, appropriate, and feasible. The percent of respondents who agreed with each of the twelve statements ranged from 88.6 to 99.0%, with mean scores of 4.4 to 4.7 and median scores of 4.0 to 5.0. There was no difference in the acceptability, appropriateness, and feasibility of teleneonatology when analyzed by professional role, years of experience in neonatal care, or years of teleneonatology experience. Respondents from Level I well newborn nurseries had greater positive perceptions of teleneonatology than those from Level II special care nurseries. CONCLUSION: Providers in tertiary NICUs and community hospitals perceive teleneonatology to be highly acceptable, appropriate, and feasible for their practices. The wide acceptance by providers of all roles and levels of experience likely demonstrates a broad receptiveness to telemedicine as a tool to deliver neonatal care, particularly in rural communities where specialists are unavailable. KEY POINTS: · Neonatal care providers perceive teleneonatology to be highly acceptable, appropriate, and feasible.. · Perceptions of teleneonatology do not differ based on professional role or years of experience.. · Perceptions of teleneonatology are especially high in smaller hospitals with well newborn nurseries..

Clinical Outcomes of Neonatal Intensive Care Unit Graduates with Bridled Nasogastric Feeding Tubes.

OBJECTIVE: The aim of this study was to describe clinical outcomes of bridled nasogastric tube (NGT) program implementation for infants requiring assisted home feeding (AHF) to discharge from the neonatal intensive care unit (NICU). STUDY DESIGN: This was a descriptive prospective analysis of a pilot cohort of infants after implementation of a bridled NGT AHF program to facilitate discharge from level III and IV NICUs from March 2019 to October 2020. RESULTS: Of 29 attempts in infants, 22 infants were discharged with bridled NGTs over 18 months. Bridle placement was unsuccessful in three patients, and four bridles were removed before discharge. Bridle use ranged from 7 to 125 days, with a median duration of 37 days. Dislodgement rate was 0.69 per 100 days. Seventeen infants (77%) achieved full oral feeds, while five (23%) discharged with bridled NGTs later converted to gastrostomy tubes. CONCLUSION: Implementation of a bridled NGT program is feasible for level III and IV NICUs to facilitate discharging infants who require feeding support to transition home. KEY POINTS: · Bridled NGT use after NICU is typically 1 month.. · Infants have low bridle NGT dislodgement.. · Most bridled NGT NICU grads attain full oral feeds..

Efficacy of Levetiracetam and Phenobarbital as First-Line Treatment for Neonatal Seizures.

High neonatal seizure burden is associated with worsened neurodevelopmental outcomes. We compared the efficacy of initial treatment with levetiracetam vs phenobarbital for maintaining low seizure burden in a retrospective cohort of 25 neonates monitored with video electroencephalography (EEG). Video EEG tracing were reviewed and paired with medication bolus times to determine seizure burden after treatment. Initial cumulative dose of phenobarbital was 20 mg/kg in all but 1 case; initial cumulative dose of levetiracetam ranged from 50 to 100 mg/kg. Eleven of 17 (65%) patients sustained seizure burden <10% following initial treatment with levetiracetam, compared with 5 of 8 (63%) with phenobarbital. Thirteen (76%) patients treated with levetiracetam had sustained seizure burden <20% compared with 6 (75%) treated with phenobarbital. The phenobarbital group showed a larger absolute reduction in average seizure burden in the hour before and after treatment (-24.3  vs -14.2 minutes/h). Six of 17 (35%) patients treated with levetiracetam remained seizure free after initial treatment, compared with 2 of 8 (25%) patients treated with phenobarbital. Initial treatment with levetiracetam was associated with shorter average time to seizure freedom (15 vs 21 hours). None of these results were statistically significant. Cumulative doses of levetiracetam 100 mg/kg were well tolerated and associated with substantial decrease in seizure burden in several cases. Levetiracetam remains a promising first-line treatment for neonatal seizures; additional randomized controlled trials evaluating the effects of high-dose levetiracetam on seizure burden and long-term outcomes are warranted.

Accuracy of Simulated Research Tasks by Community Hospitals Participating in a Multicenter Telemedicine Trial.

Background/Aims: Clinical trials evaluating facility-to-facility telemedicine may include sites that have limited research experience. For the trial to be successful, these sites must correctly perform research-related tasks. This study aimed to determine whether health care professionals at community hospitals could accurately identify simulated study eligible patients and submit data to a research coordinating center. Methods: Twenty-seven community hospitals in the United States and Canada participated in this study. An electronic survey was sent to one designated health care professional at each site. The survey included a description of trial eligibility criteria and five written neonatal resuscitation scenarios. For each scenario, the participant determined whether the neonate was study eligible. One scenario required participants to submit 14 data elements to the coordinating center. Accuracy of study eligibility and data submission was summarized using standard descriptive statistics. Results: The survey response rate was 100% (27/27). Overall accuracy in determining study eligibility was 89% (120/135), and accuracy varied across the five scenarios (range 82-93%). Overall accuracy of data submission was 92% (310/336). Data were >95% accurate for 9 of the 14 data elements, with 100% accuracy achieved for 6 data elements. These results were used to clarify eligibility criteria, inform database design, and improve training materials for the subsequent clinical trial. Conclusions: Health care professionals at community hospitals accurately determined trial eligibility and submitted study data based on written clinical scenarios. Research teams conducting telemedicine trials with community hospitals should consider completing pre-trial simulation activities to identify opportunities for improving trial processes and materials.

Neurally-Adjusted Ventilatory Assist Can Facilitate Extubation in Neonates With Congenital Diaphragmatic Hernia.

BACKGROUND: Congenital diaphragmatic hernia is associated with a high risk of neonatal mortality and long-term morbidity due to lung hypoplasia, pulmonary hypertension, and prolonged exposure to positive-pressure ventilation. Ventilator-associated lung injury may be reduced by using approaches that facilitate the transition from invasive ventilation to noninvasive ventilation (NIV), such as with neurally-adjusted ventilatory assist (NAVA). We reported our use of NAVA in neonatal patients with congenital diaphragmatic hernia during the transition from invasive ventilation to NIV. METHODS: A retrospective analysis of neonatal subjects with congenital diaphragmatic hernia admitted to a tertiary care children's hospital between December 2015 and May 2018 was conducted. Subject data and factors that affected the use of NAVA were analyzed. RESULTS: Ten neonatal subjects with congenital diaphragmatic hernia were placed on NAVA, and 6 were successfully transitioned, after surgery, from pressure control synchronized intermittent mandatory ventilation to invasive ventilation with NAVA and then to NIV with NAVA without the need for re-intubation. The transition from pressure control synchronized intermittent mandatory ventilation to invasive ventilation with NAVA resulted in a decrease in peak inspiratory pressure, mean airway pressure, and [Formula: see text]. Barriers to the use of NAVA included symptomatic pleural effusion or chylothorax and pulmonary sequestration. CONCLUSIONS: Both invasive ventilation with NAVA and NIV with NAVA were used successfully in subjects with congenital diaphragmatic hernia during the transition from invasive ventilation to NIV. The transition to NAVA was associated with a decrease in peak inspiratory pressure, mean airway pressure, and the need for supplemental oxygen. A prospective trial is needed to determine the short- and long-term impacts of this mode of ventilation in neonates with congenital diaphragmatic hernia.

Amplitude-integrated EEG use in neonatal abstinence syndrome: a pilot study.

Objective: Though central nervous system irritability is a well-established consequence of neonatal drug withdrawal, brain function in infants with neonatal abstinence syndrome (NAS) is not well understood. Amplitude-integrated electroencephalography (aEEG) is a bedside tool used for monitoring brain activity and seizures. We describe the prevalence of abnormal aEEG background patterns in infants with NAS.Methods: In this pilot, observational study primary outcomes were aEEG findings, Finnegan scores, and length of hospital stay in NAS patients. Subjects underwent an initial aEEG and a repeat study following pharmacologic treatment. Two independent reviewers analyzed aEEGs post discharge.Results: Six out of nine infants had abnormal aEEGs demonstrating lack of sleep-wake cycling (SWC) (50%), discontinuity (41.7%), and low voltage (8.3%). Seizures were not detected. NAS scores were lower for infants with continuous aEEGs versus those whose aEEGs were not continuous (5.83 versus 9.17; p = .054). Length of stay was 7.8 ± 4.4 days in infants with continuous aEEGs versus 26 ± 10.5 days in infants without continuous aEEGs (p = .003).Conclusions: Infants exposed to opioids in utero are at increased risk for discontinuity and abnormal SWC detectable on aEEG. Infants with abnormal aEEGs are more likely to have higher NAS scores, require pharmacologic treatment and have longer lengths of stay.

Changes in mean arterial blood pressure during sildenafil use in neonates with meconium aspiration syndrome or sepsis.

The aim of this study was to evaluate changes in mean blood pressure (MBP) in late preterm and term newborns with meconium aspiration syndrome (MAS) or sepsis who, in addition to inhaled nitric oxide (iNO), received enteral sildenafil for treatment of persistent pulmonary hypertension of the newborn. Data on sildenafil dosing, MBP, and vasopressor/inotrope use were collected for 72 hours after initiation of sildenafil. Groups were compared between "low dose" (<3 mg·kg·d) versus "high dose" (≥ 3 mg·kg·d) and "early" (<7 postnatal days) versus "late" (≥ 7 postnatal days) administration of sildenafil. Seventeen patients were identified. Ten and 7 patients received "low-dose" and "high-dose" sildenafil, respectively, and 8 and 9 patients were started on sildenafil "early" and "late," respectively. At the doses used, sildenafil treatment of infants with MAS and sepsis was not associated with changes in MBP. In addition, vasopressor/inotropic support was weaned in all groups. During the first 72 hours of enteral sildenafil administration in neonates with pulmonary hypertension of the newborn secondary to MAS or sepsis, no significant decrease in MBP or increase in vasopressor/inotrope requirement occurred.

Functional cloning using pFB retroviral cDNA expression libraries.

Retroviral cDNA expression libraries allow the efficient introduction of complex cDNA libraries into virtually any mitotic cell type for screening based on gene function. The cDNA copy number per cell can be easily controlled by adjusting the multiplicity of infection, thus cell populations may be generated in which >90% of infected cells contain one to three cDNAs. We describe the isolation of two known oncogenes and one cell-surface receptor from a human Burkitt's lymphoma (Daudi) cDNA library inserted into the high-titer retroviral vector pFB.