Nasal High-Flow Therapy for Newborn Infants in Special Care Nurseries.

BACKGROUND: Nasal high-flow therapy is an alternative to nasal continuous positive airway pressure (CPAP) as a means of respiratory support for newborn infants. The efficacy of high-flow therapy in nontertiary special care nurseries is unknown. METHODS: We performed a multicenter, randomized, noninferiority trial involving newborn infants (<24 hours of age; gestational age, ≥31 weeks) in special care nurseries in Australia. Newborn infants with respiratory distress and a birth weight of at least 1200 g were assigned to treatment with either high-flow therapy or CPAP. The primary outcome was treatment failure within 72 hours after randomization. Infants in whom high-flow therapy failed could receive CPAP. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome, with a noninferiority margin of 10 percentage points. RESULTS: A total of 754 infants (mean gestational age, 36.9 weeks, and mean birth weight, 2909 g) were included in the primary intention-to-treat analysis. Treatment failure occurred in 78 of 381 infants (20.5%) in the high-flow group and in 38 of 373 infants (10.2%) in the CPAP group (risk difference, 10.3 percentage points; 95% confidence interval [CI], 5.2 to 15.4). In a secondary per-protocol analysis, treatment failure occurred in 49 of 339 infants (14.5%) in the high-flow group and in 27 of 338 infants (8.0%) in the CPAP group (risk difference, 6.5 percentage points; 95% CI, 1.7 to 11.2). The incidences of mechanical ventilation, transfer to a tertiary neonatal intensive care unit, and adverse events did not differ significantly between the groups. CONCLUSIONS: Nasal high-flow therapy was not shown to be noninferior to CPAP and resulted in a significantly higher incidence of treatment failure than CPAP when used in nontertiary special care nurseries as early respiratory support for newborn infants with respiratory distress. (Funded by the Australian National Health and Medical Research Council and Monash University; HUNTER Australian and New Zealand Clinical Trials Registry number, ACTRN12614001203640.).

Sequencing and curation strategies for identifying candidate glioblastoma treatments.

BACKGROUND: Prompted by the revolution in high-throughput sequencing and its potential impact for treating cancer patients, we initiated a clinical research study to compare the ability of different sequencing assays and analysis methods to analyze glioblastoma tumors and generate real-time potential treatment options for physicians. METHODS: A consortium of seven institutions in New York City enrolled 30 patients with glioblastoma and performed tumor whole genome sequencing (WGS) and RNA sequencing (RNA-seq; collectively WGS/RNA-seq); 20 of these patients were also analyzed with independent targeted panel sequencing. We also compared results of expert manual annotations with those from an automated annotation system, Watson Genomic Analysis (WGA), to assess the reliability and time required to identify potentially relevant pharmacologic interventions. RESULTS: WGS/RNAseq identified more potentially actionable clinical results than targeted panels in 90% of cases, with an average of 16-fold more unique potentially actionable variants identified per individual; 84 clinically actionable calls were made using WGS/RNA-seq that were not identified by panels. Expert annotation and WGA had good agreement on identifying variants [mean sensitivity = 0.71, SD = 0.18 and positive predictive value (PPV) = 0.80, SD = 0.20] and drug targets when the same variants were called (mean sensitivity = 0.74, SD = 0.34 and PPV = 0.79, SD = 0.23) across patients. Clinicians used the information to modify their treatment plan 10% of the time. CONCLUSION: These results present the first comprehensive comparison of technical and machine augmented analysis of targeted panel and WGS/RNA-seq to identify potential cancer treatments.

Accuracy of a Weight-Based Formula for Neonatal Gastric Tube Insertion Length.

BACKGROUND: Gastric tubes are used in nurseries on a daily basis. Various methods of estimating gastric tube length for insertion using anatomical landmarks are used to assist correct placement. Sometimes, however, they can be up to 55% inaccurate. In 2012, we published a weight-based formula to estimate gastric tube length for insertion. PURPOSE: This study reviews the rates of correct gastric tube placement, as confirmed by radiography, after the incorporation of this weight-based formula into bedside practice. METHODS: A 6-month prospective study was performed in a tertiary neonatal intensive care unit. The formula estimating gastric tube length for insertion had been derived in an earlier study. This was incorporated into the hospital's policies and procedures guideline for the insertion of gastric tubes. Neonates with gastric tubes who required radiography for clinical reasons were included. The infant's weight and the type (orogastric or nasogastric) and length of tube were documented. A single radiologist assessed the tube position to be high, borderline, correct, or long. RESULTS: A total of 195 chest radiographs were obtained. Correct tube position was found in 84% of instances. This was a statistically and clinically significant improvement. IMPLICATIONS FOR PRACTICE: Implementation of a simple weight-based estimate for gastric tube length improves correct position rates. IMPLICATIONS FOR RESEARCH: Further studies comparing accuracy of length/height and weight-based estimations for gastric tube insertion lengths in very preterm and extremely preterm infants are needed.

Early observations in the use of oral rotavirus vaccination in infants with functional short gut syndrome.

AIM: Universal vaccination with an oral live-attenuated rotavirus vaccine at 2, 4 and 6 months of age was introduced in Australia in July 2007. There are no data on the short-term effects of vaccination for those infants most at risk of severe complications from rotavirus infection. The aim of this study was to describe the effects of rotavirus vaccination on weight gain and gastrointestinal losses in infants with functional short gut syndrome secondary to an ileostomy. METHODS: A retrospective review of all infants with an ileostomy who received RotaTeq while hospitalised at the Royal Children's Hospital, Melbourne from July 2007 to July 2009 was performed. Daily data were collected from 1 week before to 2 weeks after vaccination. The data included type and volume of feeds, ileostomy losses, need for fluid replacement of ileostomy losses, weight, temperature, urine sodium, stool culture, suspected and confirmed sepsis. RESULTS: Nine infants (age at first RotaTeq 61-99 days) were identified. The median (range) gestational age was 26 (24, 38) completed weeks and birthweight was 737 (620, 2714) grams. Compared to the day of vaccination, the median (range) ileostomy losses 1 week before, 1 and 2 weeks after vaccination were -1.1 (-13.6, 4.9) mL/kg/day, 2 (-11.1, 25.0) mL/kg/day and 2.4 (-15.7, 27.2) mL/kg/day, respectively. One infant developed severe stomal losses after vaccination. Overall, rotavirus vaccination did not alter weight gain, temperature or urinary sodium. CONCLUSION: In this small series, oral live-attenuated rotavirus vaccination of infants with high-output ileostomy was tolerated in most cases.

Polymorphisms in the Pseudomonas aeruginosa type III secretion protein, PcrV - implications for anti-PcrV immunotherapy.

The type III secretion system of Pseudomonas aeruginosa, responsible for acute infection, is composed of over twenty proteins that facilitate cytotoxin injection directly into host cells. Integral to this process is production and secretion of PcrV. Administration of a recently developed, anti-PcrV immunoglobulin, either as a therapeutic or prophylactic has previously demonstrated efficacy against laboratory strains of P. aeruginosa in a murine model. To determine if this therapy is universally applicable to a variety of P. aeruginosa clinical isolates, genetic heterogeneity of pcrV was analyzed among strains collected from three geographically distinct regions; United States, France and Japan. Sequence analysis of PcrV demonstrated limited variation among the clinical isolates examined. Strains were grouped according to the presence of non-synonymous single nucleotide polymorphisms. Representative isolates from each mutant group were examined for the ability of anti-PcrV to bind the protein secreted by these strains. The protective effect of anti-PcrV IgG against each strain was determined using an epithelial cell line cytotoxicity assay. The majority of strains tested demonstrated reduced cytotoxicity in the presence of anti-PcrV IgG. This study provides insights into the natural sequence variability of PcrV and an initial indication of the amino acid residues that appear to be conserved across strains. It also demonstrates the protective effect of anti-PcrV immunotherapy against a multitude of P. aeruginosa strains from diverse global regions with a variety of mutations in PcrV.

What made a successful hepatitis B program for reducing liver cancer disparities: an examination of baseline characteristics and educational intervention, infection status, and missing responses of at-risk Asian Americans.

Asian Americans, compared with other racial/ethnic groups, are disproportionately affected by Hepatitis B disease. The literature suggests that knowledge and awareness of prevention strategies such as receiving hepatitis B screening and vaccination are potential factors associated with occurrence of hepatitis B and liver cancer, while it is unclear how baseline characteristics relate to these effective hepatitis B prevention strategies. In the study, five Asian-American groups in the state of Maryland completed self-administered pre- and post-test after receiving lectures on hepatitis B prevention, and participated in blood screening for Hepatitis B. T-test and one-way ANOVA were used to explore the differences of baseline characteristics among these participants. Logistic regression was employed to study the baseline factors and association with completion of tests. All groups were significantly different in socioeconomic characteristics except for gender and immunization status, and only marginally different in infection status (P = 0.089). The mean pre- and post-test scores were different by group (P < 0.01). All groups had significantly improved knowledge of prevention (F = 7.65, P < 0.01). Age and race were positively related to immunization status, with older participants are more likely to get vaccinated (OR = 1.02, CI = 1.00-1.03). Chinese, Korean and Vietnamese were more likely to receive vaccination. For infection, only gender was correlated with infection status, with odds of being HBV carriers for females being 74% less than that for males (OR = 0.26, CI = 0.07-0.90). Participants who had only high school or lower education, retired, self-employed, higher income level, and married were less likely to complete surveys. The study found correlations of gender, infection status, age and race with immunization status. Males are more likely to be HBV carriers. It reveals new findings on the relationship between baseline characteristics and the completion of pre- and post-tests and missing responses. The information may provide potential directions for improve preventive program for at-risk communities.

A structural model of alcohol use pathways among Latino youth.

OBJECTIVES: To determine the pathways to alcohol use among adolescents. METHODS: A cross-sectional study of risk and protective factors among a sample of Latino youth (aged 11-13) was conducted. RESULTS: Peer norms and school connectedness had direct pathways to alcohol use. Self-concept was related to peer norms. Youth who were less acculturated were more likely to believe that their peers drank. Family monitoring, connectedness, and academic support did not have direct pathways to alcohol use. CONCLUSIONS: Peer norms appear critical in shaping adolescent involvement with alcohol. The protective influence of family and academic support appear to be indirect.