Vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (ICU) and associated with worse clinical course. Trials in adult ICU demonstrate rapid restoration of vitamin D ...status using an enteral loading dose is safe and may improve outcomes. There have been no published trials of rapid normalization of VDD in the pediatric ICU.
We conducted a multicenter placebo-controlled phase II pilot feasibility randomized clinical trial from 2016 to 2017. We randomized 67 critically ill children with VDD from ICUs in Canada, Chile and Austria using a 2:1 randomization ratio to receive a loading dose of enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or placebo. Participants, care givers, and outcomes assessors were blinded. The primary objective was to determine whether the loading dose normalized vitamin D status (25(OH)D > 75 nmol/L). Secondary objectives were to evaluate for adverse events and assess the feasibility of a phase III trial.
Of 67 randomized participants, one was withdrawn and seven received more than one dose of cholecalciferol before the protocol was amended to a single loading dose, leaving 59 participants in the primary analyses (40 treatment, 19 placebo). Thirty-one/38 (81.6%) participants in the treatment arm achieved a plasma 25(OH)D concentration > 75 nmol/L versus 1/18 (5.6%) the placebo arm. The mean 25(OH)D concentration in the treatment arm was 125.9 nmol/L (SD 63.4). There was no evidence of vitamin D toxicity and no major drug or safety protocol violations. The accrual rate was 3.4 patients/month, supporting feasibility of a larger trial. A day 7 blood sample was collected for 84% of patients. A survey administered to 40 participating families showed that health-related quality of life (HRQL) was the most important outcome for families for the main trial (30, 75%).
A single 10,000 IU/kg dose can rapidly and safely normalize plasma 25(OH)D concentrations in critically ill children with VDD, but with significant variability in 25(OH)D concentrations. We established that a phase III multicentre trial is feasible. Using an outcome collected after hospital discharge (HRQL) will require strategies to minimize loss-to-follow-up.
gov NCT02452762 Registered 25/05/2015.
The vast majority of children undergoing cardiac surgery have low vitamin D levels post-operative, which may contribute to greater illness severity and worse clinical outcomes. Prior to the ...initiation of a large phase III clinical trial focused on clinical outcomes, studies are required to evaluate the feasibility of the study protocol, including whether the proposed dosing regimen can safely prevent post-operative vitamin D deficiency in this high-risk population.
We conducted a two-arm, double-blind dose evaluation randomized controlled trial in children requiring cardiopulmonary bypass for congenital heart disease. Pre-operatively, participants were randomized to receive cholecalciferol representing usual care (< 1 year = 400 IU/day, > 1 year = 600 IU/day) or a higher dose approximating the Institute of Medicine tolerable upper intake level (< 1 year = 1600 IU/day, > 1 year = 2400 IU/day). The feasibility outcomes were post-operative vitamin D status (primary), vitamin D-related adverse events, accrual rate, study withdrawal rate, blinding, and protocol non-adherence.
Forty-six children were randomized, and five withdrew prior to surgery, leaving 41 children (21 high dose, 20 usual care) in the final analysis. The high dose group had higher 25-hydroxyvitamin D concentrations both intraoperatively (mean difference + 25.9 nmol/L; 95% CI 8.3-43.5) and post-operatively (mean difference + 17.2 nmol/L; 95% CI 5.5-29.0). Fewer participants receiving high-dose supplementation had post-operative serum 25-hydroxyvitamin D concentrations under 50 nmol/L, compared with usual care (RR 0.31, 95% CI 0.11-0.87). Post-operative vitamin D status was associated with the treatment arm and the number of doses received. There were no cases of hypercalcemia, and no significant adverse events related to vitamin D. While only 75% of the target sample size was recruited (limited funding), the consent rate (83%), accrual rate (1.5 per site month), number of withdrawals (11%), and ability to maintain blinding support feasibility of a larger trial.
Pre-operative daily high-dose supplementation improved vitamin D status pre-operatively and at time of pediatric ICU admission. The protocol for a more definitive trial should limit enrollment of children with at least 30 days between randomization and surgery to allow adequate duration of supplementation or consider a loading dose.
ClinicalTrials.gov, NCT01838447. Registered on April 24, 2013.
Clinical research has recently demonstrated that vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (PICU) and associated with worse clinical course. Multiple adult ...ICU trials have suggested that optimization of vitamin D status through high-dose supplementation may reduce mortality and improve other clinically relevant outcomes; however, there have been no trials of rapid normalization in the PICU setting. The objective of this study is to evaluate the safety and efficacy of an enteral weight-based cholecalciferol loading dose regimen in critically ill children with VDD.
The VITdAL-PICU pilot study is designed as a multicenter placebo-controlled phase II dose evaluation pilot randomized controlled trial. We aim to randomize 67 VDD critically ill children using a 2:1 randomization schema to receive loading dose enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or a placebo solution. Participants, caregivers and outcome assessors will be blinded to allocation. Eligibility criteria include ICU patient, aged 37 weeks to 18 years, expected ICU length of stay more than 48 h, anticipated access to bloodwork at 7 days, and VDD (blood total 25 hydroxyvitamin D < 50 nmol/L). The primary objective is to determine whether the dosing protocol normalizes vitamin D status, defined as a blood total 25(OH)D concentration above 75 nmol/L. Secondary objectives include an examination of the safety of the dosing regimen (e.g. hypercalcemia, hypercalciuria, nephrocalcinosis), measures of vitamin D axis function (e.g. calcitriol levels, immune function), and protocol feasibility (eligibility criteria, protocol deviations, blinding).
Despite significant observational literature suggesting VDD to be a modifiable risk factor in the PICU setting, there is no robust clinical trial evidence evaluating the benefits of rapid normalization. This phase II clinical trial will evaluate an innovative weight-based dosing regimen intended to rapidly and safely normalize vitamin D levels in critically ill children. Study findings will be used to inform the design of a multicenter phase III trial evaluating the clinical and economic benefits to rapid normalization. Recruitment for this trial was initiated in January 2016 and is expected to continue until November 30, 2017.
Clinicaltrials.gov NCT02452762.
This study aimed to assess if 24-hour in-house neonatologist (NN) coverage is associated with delivery room (DR) resuscitation/stabilization and outcomes among inborn infants <29 weeks' gestational ...age (GA).
Survey-linked cohort study of 2,476 inborn infants of 23 to 28 weeks' gestation, admitted between 2014 and 2015 to Canadian Neonatal Network Level-3 neonatal intensive care units (NICUs) with a maternity unit. Exposures were classified using survey responses based on the most senior provider offering 24-hour in-house coverage: NN, fellow, and no NN/fellow. Primary outcome was death and/or major morbidity (bronchopulmonary dysplasia, severe neurological injury, late-onset sepsis, necrotizing enterocolitis, and retinopathy of prematurity). Multivariable logistic regression analysis was used to assess the association between exposures and outcomes and adjust for confounders.
Among the 28 participating NICUs, most senior providers ensuring 24-hour in-house coverage were NN (32%, 9/28), fellows (39%, 11/28), and no NN/fellow (29%, 8/28). No NN/fellow coverage and 24-hour fellow coverage were associated with higher odds of infants receiving DR chest compressions/epinephrine compared with 24-hour NN coverage (adjusted odds ratio aOR = 4.72, 95% confidence interval CI: 2.12-10.6 and aOR = 3.33, 95% CI: 1.44-7.70, respectively). Rates of mortality/major morbidity did not differ significantly among the three groups: NN, 63% (249/395 infants); fellow, 64% (1092/1700 infants); no NN/fellow, 70% (266/381 infants).
24-hour in-house NN coverage was associated with lower rates of DR chest compressions/epinephrine. There was no difference in neonatal outcomes based on type of coverage; however, further studies are needed as ecological fallacy cannot be ruled out.
· Lower rates of DR cardiopulmonary resuscitation with 24h in-house NN coverage. · The type of 24h in-house coverage was not associated with mortality and/or major morbidity.. · High-volume centers more often have 24h in-house neonatal fellow coverage.
Background/Objective:
Seizure monitoring via amplitude-integrated EEG is standard of care in many neonatal intensive care units; however, conventional EEG is the gold standard for seizure detection. ...We compared the diagnostic yield of amplitude-integrated EEG interpreted at the bedside, amplitude-integrated EEG interpreted by an expert, and conventional EEG.
Methods:
Neonates requiring seizure monitoring received amplitude-integrated EEG and conventional EEG in parallel. Clinical events and amplitude-integrated EEG were interpreted at bedside. Subsequently, amplitude-integrated EEG and conventional EEG were independently analyzed by experienced neonatology and neurology readers. Sensitivity and specificity of bedside amplitude-integrated EEG as compared to expert amplitude-integrated EEG interpretation and conventional EEG were evaluated.
Results:
Thirteen neonates were monitored for an average duration of 33 hours (range 15-94, SD 25). Fourteen seizure-like events were detected by clinical observation, and 12 others by bedside amplitude-integrated EEG analysis. One of the clinical, and none of the bedside amplitude-integrated EEG events were confirmed as seizures on conventional EEG. Post hoc expert amplitude-integrated EEG interpretation revealed eight suspected seizures, all different from the ones detected by the bedside amplitude-integrated EEG team, of which one was confirmed via conventional EEG. Eight seizures were recorded on conventional EEG. Expert amplitude-integrated EEG interpretation had a sensitivity of 13% with 46% specificity for individual seizure detection, and a sensitivity of 50% with 46% specificity for detecting patients with seizures.
Conclusion:
Real-world bedside amplitude-integrated EEG monitoring failed to detect all seizures evidenced via conventional EEG, while misclassifying other events as seizures. Even post hoc expert amplitude-integrated EEG interpretation provided limited sensitivity and specificity. Considering the poor sensitivity and specificity of bedside amplitude-integrated EEG interpretation, combined monitoring may provide limited clinical benefit.
Exposure to excessive whole-body vibration is linked to health issues and may result in increased rates of mortality and morbidity in infants. Newborn infants requiring specialized treatment at ...neonatal intensive care units often require transportation by road ambulance to specialized care centers, exposing the infants to potentially harmful vibration and noise. A standardized Neonatal Patient Transport System (NPTS) has been deployed in Ontario, Canada, that provides life saving equipment to patients and safe operation for the clinical care staff. However, there is evidence that suggests patients may experience a higher amplitude of vibration at certain frequencies when compared with the vehicle vibration. In a multi-year collaborative project, we seek to create a standardized test procedure to evaluate the levels of vibration and the effectiveness of mitigation strategies. Previous studies have looked at laboratory vibration testing of a transport system or transport incubator and were limited to single degree of freedom excitation, neglecting the combined effects of rotational motion. This study considers laboratory testing of a full vehicle and patient transport system on an MTS Model 320 Tire-Coupled Road Simulator. The simulation of road profiles and discrete events on a tire-coupled road simulator allows for the evaluation of the vibration levels of the transport system and the exploration of mitigation strategies in a controlled setting. The tire-coupled simulator can excite six degrees-of-freedom motion of the transport system for vibration evaluation in three orthogonal directions including the contributions of the three rotational degrees of freedom. The vibration data measured on the transport system during the tire-coupled testing are compared to corresponding road test data to assess the accuracy of the vibration environment replication. Three runs of the same drive file were conducted during the laboratory testing, allowing the identification of anomalies and evaluation of the repeatability. The tire-coupled full vehicle testing revealed a high level of accuracy in re-creating the road sections and synthesized random profiles. The simulation of high amplitude discrete events, such as speed hump traverses, were highly repeatable, yet yielded less accurate results with respect to the peak amplitudes at the patient. The resulting accelerations collected at the input to the manikin (sensor located under the mattress) matched well between the real-world and road simulator. The sensors used during testing included series 3741B uni-axial and series 356A01 tri-axial accelerometers by PCB Piezotronics. These results indicate a tire-coupled road simulator can be used to accurately evaluate vibration levels and assess the benefits of future mitigation strategies in a controlled setting with a high level of repeatability.
Abstract
Primary Subject area
Neonatal-Perinatal Medicine
Background
Each year, thousands of newborns are transported by air or ground ambulance to receive specialized medical care. For ...neurologically immature and physiologically compromised infants, especially preterm infants, the noise and vibration exposure during transport are high despite preventative measures, and may be an important contributor to brain injury risk.
Objectives
To develop a new tool to investigate vibrations during neonatal transport and mitigation strategies.
Design/Methods
Proof of concept study including 3 steps: 1) Characterization of the vibrations during transport. Accelerometer sensors placed on different layers of the Neonatal Patient Transport System (NPTS) (neonate manikin, mattress, incubator, deck, stretcher, and vehicle floor) with a variety of ambulance on road tests performed to capture data. 2) Experimentation - A shaker table was used to develop a standardized test environment. Vibration testing was performed, with the entire NPTS mounted on the shaker table. 3) Mitigation - Shaker table tests were repeated using different configurations of mattress and harness types on manikins with different bodyweights.
Results
1) Characterization: Road transport exposed the manikin’s head to vibrations that exceeded adult standards. Examining the frequency spectra of the accelerometer signals across different layers of the NPTS suggests that two interfaces, stretcher/vehicle floor and incubator/deck, may be critical for intervention to mitigate the vibrations, as they both showed the highest gains in vibration power.
2) Experimentation: Comparison between the on-road and shaker table tests showed that the shaker table was able to reproduce on-road transportation with acceptable fidelity. The shaker table setup can serve as a standardized environment to explore the impact of several NPTS design variables on vibrations transmitted to the patient.
3) Mitigations: Different mattresses were shown to influence the vibrations experienced by the manikin. The head restraint harness type showed an amplitude reduction of the peak frequency component for all experiment types and for most mattress types compared to a standard 5-point harness.
Conclusion
Our study demonstrated that: i) vibrations during neonatal transport can exceed adult standards; ii) acceptable fidelity simulation of road conditions can be achieved using a shaker table system; and iii) the most effective approach for vibration mitigation should consider the whole NTPS, instead of focusing solely on the isolette.
Objectives Hypoxic-ischemic encephalopathy (HIE) from perinatal asphyxia/birth depression occurs in 1 to 2 per 1000 live births. Therapeutic Hypothermia (TH) is the standard of care for newborns ...experiencing HIE. In 2015, we identified important delays in both the initiation and achievement of target temperature in patients referred to our Transport team (TT) for TH. In an effort to improve our practice and address the delays identified we undertook a number of practice change initiatives and outreach education measures. Our aim was to safely and efficiently increase the number of outborn infants reaching target temperature within the 6 hour TH target post referral. Design/Methods Retrospective cohort study of all patients referred and transported to the Children’s Hospital of Eastern Ontario (CHEO) for TH between October 2009 and December 2017, comparing the two cohorts of patients’ pre and post clinical practice changes (September 2015). Results 117 infants (mean gestational age 39.1 weeks, birth weight 3.3 kg, arterial cord pH 6.9, Apgar scores 3 and 5 at 5 and 10 minutes) were included: 82 infants pre-practice change and 35 infants post. Subsequent to the outlined practice changes in Table 1. data (pre vs post) demonstrated an increase in: the number of infants within target temperature range by 6 hours of life (49% to 68%), the number recommended for passive cooling at the referral centre (59% to 75%), of those passively cooled at the referral centre (9 to 16%) within target temperature range on arrival of the transport team. The time from birth to referral remains unchanged (median 95 vs. 92 mins). Conclusion Targeted transport team practice changes have been successful in increasing the number of patients recommended for initiation of TH at referral centers and meeting the desired time target for TH within our region. The time from birth to patient referral remains a focus for further outreach education.
We evaluated transport factors and postnatal practices to identify modifiable risk factors for SBI.
Retrospective review of Canadian Neonatal Transport Network data linked to Canadian Neonatal ...Network data for outborns <33 weeks gestational age (GA), during January 2014 to December 2015. SBI was defined as grade 3 or 4 intraventricular hemorrhage or parenchymal echogenicity, including hemorrhagic and/or ischemic lesions.
Among 781 infants, 115 (14.7%) had SBI with range 5.6-40% among transport teams. In multivariable analysis, SBI was associated with GA 0.77 (0.71, 0.85) per week, receipt of chest compressions and/or epinephrine at delivery 1.81 (1.08, 3.05) and receipt of fluid boluses 1.61 (1.00, 2.58).
Risk factors for SBI were related to the condition at birth and immediate postnatal management and not related to transport factors. These results highlight the importance of maternal transfer to perinatal centers to allow optimization of perinatal management.
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