Leslie Lewis

Towards continuous monitoring of pulse rate in neonatal intensive care unit with a webcam.

We describe a novel method to monitor pulse rate (PR) on a continuous basis of patients in a neonatal intensive care unit (NICU) using videos taken from a high definition (HD) webcam. We describe algorithms that determine PR from videoplethysmographic (VPG) signals extracted from multiple regions of interest (ROI) simultaneously available within the field of view of the camera where cardiac signal is registered. We detect motion from video images and compensate for motion artifacts from each ROI. Preliminary clinical results are presented on 8 neonates each with 30 minutes of uninterrupted video. Comparisons to hospital equipment indicate that the proposed technology can meet medical industry standards and give improved patient comfort and ease of use for practitioners when instrumented with proper hardware.

Comparative efficacy and safety of caffeine and aminophylline for apnea of prematurity in preterm (≤34 weeks) neonates: A randomized controlled trial

ObjectiveTo compare the efficacy and safety of standard doses of Caffeine and Aminophylline for Apnea of prematurity.Study designRandomized controlled trial.SettingTertiary-care referral centre and a teaching institution in Southern India. Trial was conducted from February 2012 to January 2015.Participants240 preterm (≤34 wk) neonates with apnea of prematurity.InterventionsNeonates randomized into two groups: Caffeine group received loading dose of caffeine citrate (20 mg/kg) followed by 5 mg/kg/day maintenance dose every 24 hour. Aminophylline group received loading dose of Aminophylline–5 mg/kg and maintenance dose of 1.5 mg/kg 8-hourly.Outcome measuresDifference in apneic spells, associated respiratory morbidity, and acute adverse events were assessed. Association of efficacy with therapeutic drug levels was also evaluated.ResultsInfants on aminophylline experienced less apnea spells in 4-7 days of therapy (P=0.03). Mean apnea rate and isolated desaturations were similar in 1-3, 4-7 and 8-14 days of therapy. No difference was noted in duration of Neonatal Intensive Care Unit stay and hospital stay. Mean heart rate was significantly high in Aminophylline group (P<0.001). Risk of developing tachycardia was less (RR 0.30; 95% CI range 0.15 to 0.60; P<0.001) in Caffeine- over Aminophylline-treated infants.ConclusionAminophylline is as effective as caffeine for prevention of apneic spells in preterm neonates; however, dosage optimization needs to be done to reduce toxicity.

Phase Changing Material for Therapeutic Hypothermia in Neonates with Hypoxic Ischemic Encephalopathy — A Multi-centric Study

ObjectiveTo assess the feasibility and safety of cooling asphyxiated neonates using phase changing material based device across different neonatal intensive care units in India.DesignMulti-centric uncontrolled clinical trial.Setting11 level 3 neonatal units in India from November 2014 to December 2015.Participants103 newborn infants with perinatal asphyxia, satisfying pre-defined criteria for therapeutic hypothermia.InterventionTherapeutic hypothermia was provided using phase changing material based device to a target temperature of 33.5±0.5ºC, with a standard protocol. Core body temperature was monitored continuously using a rectal probe during the cooling and rewarming phase and for 12 hours after the rewarming was complete.Outcome measuresFeasibility measure - Time taken to reach target temperature, fluctuation of the core body temperature during the cooling phase and proportion of temperature recordings outside the target range. Safety measure - adverse events during coolingResultsThe median (IQR) of time taken to reach target temperature was 90 (45, 120) minutes. The mean (SD) deviation of temperature during cooling phase was 33.5 (0.39) ºC. Temperature readings were outside the target range in 10.8% (5.1% of the readings were <33°C and 5.7% were >34°C). Mean (SD) of rate of rewarming was 0.28 (0.13)°C per hour. The common adverse events were shock/hypotension (18%), coagulopathy (21.4%), sepsis/probable sepsis (20.4%) and thrombocytopenia (10.7%). Cooling was discontinued before 72 hours in 18 (17.5%) babies due to reasons such as hemodynamic instability/refractory shock, persistent pulmonary hypertension or bleeding. 7 (6.8%) babies died during hospitalization.ConclusionUsing phase changing material based cooling device and a standard protocol, it was feasible and safe to provide therapeutic hypothermia to asphyxiated neonates across different neonatal units in India. Maintenance of target temperature was comparable to standard servo-controlled equipment.

Report of four novel variants in ASNS causing asparagine synthetase deficiency and review of literature: Asparagine synthetase deficiency

Asparagine synthetase deficiency (ASNSD, MIM 615574) is a recently delineated rare neurometabolic disorder caused by mutations in ASNS (MIM 108370) (Ruzzo et al., 2013). It is characterized by congenital and/or postnatal progressive microcephaly, global developmental delay, seizures, growth retardation, cerebral atrophy and simplified gyral pattern.

Development and Validation of GC-MS Bioanalytical Method to Detect Organic Acidemia in Neonatal/Pediatric Urine Samples

This work was aimed at developing an analytical tool for the simultaneous quantification of methylmalonic acid, glutaric acid, succinyl acetone, homogentisic acid, and pipecolic acid in pediatric urine samples. Organic acids were isolated from urine by liquid-liquid extraction. The extracted samples were then derivatized by using BSTFA + 1% TMCS solution, which resulted in the formation of trimethylsilyl ester derivatives. These analytes were quantified by GC-MS, and this bioanalytical method was validated according to the USFDA guidelines. The proposed method was applied to several clinically suspected organic acidemia samples. The linearity range is within 5 – 100 μg/mL for methylmalonic acid and glutaric acid, 20 – 100 μg/mL for succinyl acetone and homogentisic acid, and 10 – 100 μg/mL for pipecolic acid. Mean % recovery of QC samples of methylmalonic acid, glutaric acid, succinyl acetone, homogentisic acid, and pipecolic acid was found to be 92.06, 92.21, 90.92, 93.17, 90.71%, respectively, and that of tropic acid was 96.57%. All organic acids were stable at room temperature for 8 h. The stability of succinyl acetone, homogentisic acid, and pipecolic acid stored for 30 days at 8°C was found to be lower. The proposed method was applied to the analysis of samples obtained from 23 patients.

Partition and Hierarchical Based Clustering Techniques for Analysis of Neonatal Data

With the increase of data in the medical domain over the years, it is extremely crucial that we analyze useful information and recognize patterns that can be used by the clinicians for better diagnosis of diseases. Clustering is a Machine Learning technique that can be used to categorize data into compact and dissimilar clusters to gain some meaningful insight. This paper uses partition and hierarchical based clustering techniques to cluster neonatal data into different clusters and identify the role of each cluster. Clustering discovers hidden knowledge which helps neonatologists in identifying neonates who are at risk and also helps in neonatal diagnosis. In addition, this paper also evaluates the number of clusters to be formed for the techniques using Silhouette Coefficient.

Biomarker Profiling for Pyridoxine Dependent Epilepsy in Dried Blood Spots by HILIC-ESI-MS

Pyridoxine dependent epilepsy is a condition where the affected infant or child has prolonged seizures (status epilepticus), which are nonresponsive to anticonvulsant therapy but can be treated with pharmacological doses of pyridoxine. If identified earlier and treated prophylactically with pyridoxine, severe brain damage due to seizures can be prevented. Alpha-amino adipic semialdehyde (AASA), piperidine-6-carboxylic acid (P6C), and pipecolic acid (PA) are known biomarkers of pyridoxine dependent epilepsy. We report the development and validation of a hydrophilic interaction liquid chromatography (HILIC) hyphenated with mass spectroscopy for the quantification of the above analytes from dried blood spot samples. The samples were extracted using methanol and analysed on a iHILIC fusion plus column with formic acid buffer (pH 2.5): acetonitrile (20:80) at a flow rate of 0.5 mL/min within 3 minutes. The method demonstrated a LOD of 10 ng/mL, LOQ of 50 ng/mL, linearity of r2 ≥ 0.990, and recovery of 92-101.98% for all analytes. The intra- and interday precision CVs were < 8% and 6%, respectively. Extensive stability studies demonstrated that the analytes were stable in stock solution and in matrix when stored at -80°C. We performed method comparison studies of the developed method with the literature reported method using normal samples and matrix matched spiked samples at pathological concentrations to mimic clinical validity. The Bland-Altman analysis for comparison of the analytical suitability of the method for the biomarkers in healthy and spiked samples with the literature reported method revealed a bias which suggested that the method was comparable. The newly developed method involves no derivatisation and has a simple sample preparation and a low run time enabling it to be easily automated with a high sample throughput in a cost-effective manner.

Effectiveness of Indian classical music on developmental responses of preterm infants - A randomized controlled trial protocol

Background: The highly sophisticated Neonatal Intensive Care Unit (NICU) exposes preterm infants to constant unexpected stimuli especially noise, impacting their growth and development. Modifying the environment of the NICU by provision of patterned stimuli like music is essential. There is a paucity of data from large and well-conducted trials on Indian Classical music, which limit the evidence for use of music as therapy for preterm infants.Methodology: A randomized controlled trial with repeated measures design will be conducted. A sample size of 132 preterm infants who are admitted to the NICU, will be assessed for eligibility to be included in the study. The parent(s) of the preterm infants will be approached for informed proxy consent. A study assistant will manage the allocation of participants and the provision of the intervention independently. The investigators who perform the outcome assessment will be blinded to the allocation of participants to the intervention and control arm of the study.Outcome measures will be assessed at baseline (day 3 of life). Following the administration of the intervention in the experimental group, the outcome measures will be assessed after completion of one week of intervention (day 10 of life) and after completion of two weeks of intervention (day 17 of life)

Prediction of Apnea of Prematurity in neonates using Support Vector Machines and Random Forests

Machine Learning has a wide array of applications in the healthcare domain and has been used extensively for analyzing data. Apnea of Prematurity is a breathing disorder commonly observed in preterm infants. This paper compares the usage of Support Vector Machines and Random Forests, which are supervised learning algorithms, to predict Apnea of Prematurity at the end of the first week of the childs birth using data collected during the first three days of neonatal life. This paper also uses an optimization method called Synthesized Minority Oversampling Technique (SMOTE) to resolve the class imbalance problem observed in the data. Principal Component Analysis and one-hot encoding have been implemented for feature extraction and data preprocessing respectively. Among the results obtained, an AUC of 0.72 using the amalgamation of Random Forests and SMOTE is found to be the most accurate model.

Cerebral Abscess due to Serratia marcescens

To the Editor: A 4-mo-old boy, who had stormy neonatal course, presented to us with increasing head size. There was no history of irritability, excessive sleepiness or vomiting. Examination revealed bulging anterior fontanelle, sunset sign, proptosis on right side and head circumference (HC) of 39 cm (4 cm increase over 1 mo). Neurological examination and systemic examination were normal. Hewas born at 32wk gestation, weighed 1.3 kgwith HC of 28.5 cm and received surfactant. Sepsis work up on 10th day for frequent apnea, revealed elevated Band: Neutrophil ratio (0.63) and blood culture grew Serratia marcescens. Cerebrospinal fluid analysis was normal and culture was sterile. He was treated with piperacillin-tazobactam and amikacin for 14 d. Repeat blood culture was sterile. He required ventilator support and parenteral nutrition through peripherally inserted central catheter (PICC) for 2 wk. He was discharged on day 42 with HC of 31 cm. First and fourth week neurosonograms were normal. Neurosonogram, currently, revealed an encapsulated right frontal lobe abscess. Magnetic resonance imaging brain further confirmed the abscess (Fig. 1a). Abscess was drained and S. marcescens with similar antibiogram as that of previous blood culture grew in pus. Piperacillin-tazobactam and amikacin were given and Computed tomography (CT) brain 2 wk later showed recollection of abscess requiring drainage twice again. Intravenous antibiotics were given for 6 wk, and he was discharged with HC and weight of 40 cm and 4,545 g respectively. He was conscious, recognizing mother and had normal tone and deep tendon reflexes. The proptosis had subsided. He was given oral cotrimoxazole and ciprofloxacin