How much does a minimum weight at discharge delay discharge from the neonatal intensive care unit?

BACKGROUND: Current American Academy of Pediatrics guidelines recommend discharge at physiologic maturity regardless of weight; however, our institution's neonatal ICU policy requires a minimum weight of 1800 g for discharge even when infant is physiologically mature. So, we wanted to determine if discharge at physiologic maturity (PM), based on national guidelines, would decrease hospital days (HD). METHODS: We reviewed 129 infants with birthweight 1300g- 1800 g. Data were analyzed by paired t-test/ Wilcoxon-rank-sum test. RESULTS: Age at discharge vs. age at PM was 0.55d per infant higher (P-value 0.033) resulting in 71 total HD. For SGA babies, this difference was 1.47d vs 0.19d in non-SGA babies (P- value 0.0243) and this difference was an average of 2.63d (P-value < 0.001) for those who reached PM < 1800 g, contributing to 50 of 71 HD potentially saved. CONCLUSION: There was a 0.55-2.6-day difference between age at discharge and age at PM, greater in SGA infants and infants who reached PM prior to 1800 g. There might be an opportunity to send infants home earlier to their families if there is no minimum weight required.

Effects of antioxidant MnTBAP on angiogenesis in newborn mice with hyperoxic lung injury.

BACKGROUND: Oxygen toxicity mediated by reactive oxygen species (ROS) plays an essential role in the development of bronchopulmonary dysplasia in premature infants. By reducing oxidative stress, antioxidants protect the immature lung. We studied the effects of MnTBAP, a catalytic antioxidant on angiogenesis and alveolar growth following neonatal hyperoxia. METHODS: Newborn mouse litters randomized to room air (RA) or >95% O2 for 72 hours from day 4 (D4) to D7 to receive either MnTBAP (10 mg/kg/d) or saline intraperitoneally (every 24 h for three doses). Lungs harvested for angiogenic gene expression, protein expression, and histopathology post-hyperoxia exposure. Radial alveolar count (RAC), mean linear intercept (MLI) and vessel density assessed by histopathology. RESULTS: Angiogenic gene expression was significantly lower in the hyperoxia group compared to the RA group. The protein expression for VEGF and its receptor, VEGFR1, was significantly lower following treatment with MnTBAP compared to hyperoxia alone. Expression of VEGFR2, Angiopoietin-1 and TIE2, were substantially higher in the RA groups compared to hyperoxia groups with or without MnTBAP. Hyperoxia groups demonstrated alveolar simplification. MnTBAP reduced vessel density and failed to improve alveolar growth following hyperoxia. CONCLUSIONS: MnTBAP, a catalytic antioxidant, does not offer protection from hyperoxia-induced alveolar impairment. The lack of angiogenic upregulation by MnTBAP may contribute to alveolar simplification in newborn mice.

Methemoglobin and the response to inhaled nitric oxide in persistent pulmonary hypertension of the newborn.

BACKGROUND: We aimed to investigate whether the change in methemoglobin levels (ΔMHb) predicts oxygenation response to inhaled nitric oxide (iNO) in persistent pulmonary hypertension of the newborn (PPHN) with lung disease, with or without pulmonary hypoplasia. METHODS: In this prospective observational study, infants were categorized based on ΔMHb and oxygenation response (ΔPaO2/FiO2) following iNO: ΔMHb ≤0 or ΔMHb>0, and ΔPaO2/FiO2 < 20 mmHg (Non-responder) or≥20 mmHg (Responder). ΔMHb levels were compared among infants with or without pulmonary hypoplasia. RESULTS: Among infants with pulmonary hypoplasia (n = 28), ΔMHb was not associated with an oxygenation response to iNO or survival without ECMO. Among infants without hypoplasia (n = 29), subjects with ΔMHb>0 following iNO (n = 21) had a greater ΔPaO2/FiO2 (median, 64 mmHg; IQR, 127; p < 0.01) and 100% survival without extracorporeal membrane oxygenation (ECMO) when compared to infants with ΔMHb ≤0 (n = 8; median 10 mmHg; IQR, 33). CONCLUSIONS: PPHN secondary to lung disease without hypoplasia with increased ΔMHb following iNO was associated with better oxygenation response and survival without ECMO compared to subjects without an increase in MHb.

Enhancing social functioning in young people at Ultra High Risk (UHR) for psychosis: A pilot study of a novel strengths and mindfulness-based online social therapy.

BACKGROUND: Psychological and pharmacological treatments have been shown to reduce rates of transition to psychosis in Ultra High Risk (UHR) young people. However, social functioning deficits have been unresponsive to current treatments. AIMS: The study aims were to: i) describe the theoretical basis and therapeutic targets of a novel intervention targeting social functioning in UHR young people; and ii) examine its acceptability, safety and preliminary effect on social functioning. METHODS: An international, multidisciplinary team developed a new intervention (MOMENTUM) to improve social functioning in UHR young people. MOMENTUM blends two novel approaches to social recovery: strengths and mindfulness-based intervention embedded within a social media environment, and application of the self-determination theory of motivation. The acceptability and safety of MOMENTUM were tested through a 2-month pilot study with 14 UHR participants. RESULTS: System usage was high, with over 70% of users being actively engaged over the trial. All participants reported a positive experience using MOMENTUM, considered it safe and would recommend it to others. 93% reported it to be helpful. There were large, reliable improvements in social functioning (d = 1.83, p < 0.001) and subjective wellbeing (d = 0.75, p = 0.03) at follow-up. There were significant increases in the mechanisms targeted by the intervention including strengths usage (d = 0.70, p = 0.03), mindfulness skills (d = 0.66, p = 0.04) and components of social support. Social functioning improvement was significantly correlated with indicators of system usage. CONCLUSION: MOMENTUM is engaging and safe. MOMENTUM appeared to engage the hypothesized mechanisms and showed promise as a new avenue to improve social functioning in UHR young people.

Maternal Alcohol Consumption During Pregnancy and the Risk of Autism Spectrum Disorders in Offspring: A Retrospective Analysis of the Millennium Cohort Study.

The objective of this retrospective analysis of the longitudinal Millennium Cohort Study was to examine whether maternal alcohol consumption in pregnancy (MACP) is associated with the development of childhood autism spectrum disorders (ASD). Data on MACP and ASD were obtained from parental questionnaires. There were 18,168 singleton mother-child pairs with data on MACP, and 12,595 answered the question on ASD when the children were 11 years old. No statistically significant association was found between MACP and ASD for light (OR 0.78, 95% CI 0.48-1.29), moderate (OR 0.89, 95% CI 0.35-2.27), or heavy (OR 1.54, 95% CI 0.56-4.21) MACP. Alcohol consumption during pregnancy was not associated with the risk of developing ASD in this study cohort.

Preventing occupational injury among police officers: does motivation matter?

BACKGROUND: Injury prevention is an important issue for police officers, but the effectiveness of prevention initiatives is dependent on officers' motivation toward, and adherence to, recommended health and safety guidelines. AIMS: To understand effects of police officers' motivation to prevent occupational injury on beliefs about safety and adherence to injury prevention behaviours. METHODS: Full-time police officers completed a survey comprising validated psychometric scales to assess autonomous, controlled and amotivated forms of motivation (Treatment Self-Regulation Questionnaire), behavioural adherence (Self-reported Treatment Adherence Scale) and beliefs (Safety Attitude Questionnaire) with respect to injury prevention behaviours. RESULTS: There were 207 participants; response rate was 87%. Hierarchical multiple regression analyses demonstrated that autonomous motivation was positively related to behavioural adherence, commitment to safety and prioritizing injury prevention. Controlled motivation was a positive predictor of safety communication barriers. Amotivation was positively associated with fatalism regarding injury prevention, safety violation and worry. CONCLUSIONS: These findings are consistent with the tenets of self-determination theory in that autonomous motivation was a positive predictor of adaptive safety beliefs and adherence to injury prevention behaviours.

Oleoyl-L-carnitine inhibits glycine transport by GlyT2.

BACKGROUND AND PURPOSE: Concentrations of extracellular glycine in the CNS are regulated by two Na(+)/Cl(-) -dependent glycine transporters, GlyT1 and GlyT2. Selective inhibitors of GlyT1 have been developed for the treatment of schizophrenia, whilst selective inhibitors of GlyT2 are analgesic in animal models of pain. We have assessed a series of endogenous lipids as inhibitors of GlyT1 and GlyT2. EXPERIMENTAL APPROACH: Human GlyT1 and GlyT2 were expressed in Xenopus laevis oocytes, and the inhibitory actions of a series of acylcarnitines on glycine transport were measured using electrophysiological techniques. KEY RESULTS: Oleoyl-L-carnitine inhibited glycine transport by GlyT2, with an IC(50) of 340 nM, which is 15-fold more potent than the previously identified lipid inhibitor N-arachidonyl-glycine. Oleoyl-L-carnitine had a slow onset of inhibition and a slow washout. Using a series of chimeric GlyT1/2 transporters and point mutant transporters, we have identified an isoleucine residue in extracellular loop 4 of GlyT2 that conferred differences in sensitivity to oleoyl-L-carnitine between GlyT2 and GlyT1. CONCLUSIONS AND IMPLICATIONS: Oleoyl-L-carnitine is a potent non-competitive inhibitor of GlyT2. Previously identified GlyT2 inhibitors show potential as analgesics and the identification of oleoyl-L-carnitine as a novel GlyT2 inhibitor may lead to new ways of treating pain.

Effect of enhanced ultraviolet germicidal irradiation in the heating ventilation and air conditioning system on ventilator-associated pneumonia in a neonatal intensive care unit.

OBJECTIVE: The objective of this study was to test the hypothesis that enhanced ultraviolet germicidal irradiation (eUVGI) installed in our neonatal intensive care unit (NICU) heating ventilation and air conditioning system (HVAC) would decrease HVAC and NICU environment microbes, tracheal colonization and ventilator-associated pneumonia (VAP). STUDY DESIGN: The study was designed as a prospective interventional pre- and post-single-center study. University-affiliated Regional Perinatal Center NICU. Intubated patients in the NICU were evaluated for colonization, and a high-risk sub-population of infants <30 weeks gestation ventilated for ≥ 14 days was studied for VAP. eUVGI was installed in the NICU's remote HVACs. The HVACs, NICU environment and intubated patients' tracheas were cultured pre- and post-eUVGI for 12 months. The high-risk patients were studied for VAP (positive bacterial tracheal culture, increased ventilator support, worsening chest radiograph and ≥ 7 days of antibiotics). RESULT: Pseudomonas, Klebsiella, Serratia, Acinetobacter, Staphylococcus aureus and Coagulase-negative Staphylococcus species were cultured from all sites. eUVGI significantly decreased HVAC organisms (baseline 500,000 CFU cm(-2); P=0.015) and NICU environmental microbes (P<0.0001). Tracheal microbial loads decreased 45% (P=0.004), and fewer patients became colonized. VAP in the high-risk cohort fell from 74% (n=31) to 39% (n=18), P=0.04. VAP episodes per patient decreased (Control: 1.2 to eUVGI: 0.4; P=0.004), and antibiotic usage was 62% less (P=0.013). CONCLUSION: eUVGI decreased HVAC microbial colonization and was associated with reduced NICU environment and tracheal microbial colonization. Significant reductions in VAP and antibiotic use were also associated with eUVGI in this single-center study. Large randomized multicenter trials are needed.

Pilot trial of late booster doses of surfactant for ventilated premature infants.

OBJECTIVE: Many premature infants at risk for bronchopulmonary dysplasia experience episodes of surfactant dysfunction with reduced surfactant protein B (SP-B). In this study, we investigated the safety and responses to booster doses of surfactant. STUDY DESIGN: A total of 87 infants, 500 to 1250 g birth weight, who were ventilated at 7 to 10 days received 2 or 3 doses of Infasurf (Calfactant, Forest Pharmaceuticals, St Louis, MO, USA) within a 1-week period. RESULT: For 184 doses, occurrence rates of transient bradycardia (13) and plugged endotracheal tube (5) were low, and no other adverse effects were noted. Treatment transiently improved the respiratory severity score (FiO(2) × mean airway pressure), SP-B content (+75%) and surface properties of isolated surfactant. Levels of eight proinflammatory cytokines in tracheal aspirate were interrelated and unchanged from baseline after surfactant treatment. CONCLUSION: Booster doses of surfactant for premature infants with lung disease are safe and transiently improve respiratory status as well as composition and function of endogenous surfactant.

Methemoglobin to cumulative nitric oxide ratio and response to inhaled nitric oxide in PPHN.

BACKGROUND: One-third of infants with persistent pulmonary hypertension of the newborn (PPHN) do not respond to inhaled nitric oxide (iNO). If iNO is not delivered to the pulmonary vasculature because of parenchymal lung disease, it cannot interact with hemoglobin to form methemoglobin (MHb). OBJECTIVE: To study the correlation between oxygenation response to iNO in infants with PPHN secondary to parenchymal lung disease and initial MHb% to cumulative NO exposure (ppm x hours) ratio (MHb/SigmaNO). STUDY DESIGN: Retrospective chart review of neonates with PPHN secondary to parenchymal lung disease treated with iNO comparing non-responders (PaO(2)/FiO(2) ratio<10 change with iNO) with responders (>or=10 change). RESULT: Non-responders (n=16) had a PaO(2)/F(iO2) of 83+/-48 (mean+/-s.d.) and decreased to 74+/-44 after iNO. PaO(2)/FiO(2) increased from 70+/-48 to 151+/-63 with iNO among responders (n=36). The MHb/SigmaNO ratio was low (0.024+/-0.012) among non-responders compared with responders (0.07+/-0.053, P<0.005). CONCLUSION: Inadequate oxygenation response to iNO is associated with lower MHb/SigmaNO, suggesting suboptimal delivery of iNO to the pulmonary vasculature.

Galactorrhea with metoclopramide use in the neonatal unit.

We report a 3(1/2)-month-old infant with trisomy 21 presenting with galactorrhea in the neonatal intensive care unit (NICU). Endocrine work-up showed a high prolactin level (64.4 ng ml(-1)--normal: 0.5 to 30 ng ml(-1)). Cessation of therapy with metoclopramide (0.2 mg kg(-1) per dose q 6 h) resulted in the resolution of galactorrhea with a decrease in serum prolactin level (20.1 ng ml(-1)). We present this case to highlight this uncommon side effect of a commonly used medication in the NICU.

Bacterial delivery of a novel cytolysin to hypoxic areas of solid tumors.

The efficacy of current anti-cancer gene therapies is limited by the inability of gene vectors to penetrate the poorly vascularized, hypoxic regions of tumors, leaving these sites untreated. We describe a new approach for targeting gene therapy to these sites, which employs an attenuated strain of the non-pathogenic bacterium, Salmonella typhimurium, carrying an exogenous (that is, reporter or therapeutic) gene under the regulation of a new, highly hypoxia-inducible promoter (FF+20(*)). This bacterial vector was seen to rapidly migrate into, and thrive in, hypoxic areas of both mammary tumor spheroids grown in vitro and orthotopic mammary tumors after systemic injection. Using the reporter gene construct, FF+20(*)-lacZ, we show that bacterial expression of high levels of beta-galactosidase occurred only in hypoxic/necrotic sites of spheroids and tumors. We then replaced the reporter gene with one encoding a novel cytotoxic protein (HlyE) and showed that this was also expressed by bacteria only in hypoxic regions of murine mammary tumors. This resulted in a marked increase in tumor necrosis and reduced tumor growth. Our system represents a promising new strategy for delivering gene therapy to poorly vascularized regions of tumors and shows, for the first time, the efficacy of HlyE as an anti-tumor agent.

Genetic prothrombotic mutations are common in neonates but are not associated with umbilical catheter-associated thrombosis.

OBJECTIVE: To evaluate the prevalence of hereditary prothrombotic mutations, and their effect on the incidence and severity of umbilical arterial or venous catheter (UAC or UVC)-associated thrombosis. STUDY DESIGN: All neonates with a UAC or UVC were studied prospectively for the presence, severity and timing of thrombosis with duplex Doppler ultrasound scan. Genetic testing for factor V Leiden (FVL), prothrombin mutation (PTm) and methylene-tetrahydrofolate reductase (MTHFR) mutations was performed using PCR and restriction fragment length polymorphism assays. RESULT: Umbilical catheter (UC)-associated thrombosis developed in 16/53 (31%) neonates; 23% of UACs and 22% of UVCs were associated with thrombosis. The prevalence of a significant prothrombotic mutation was present in 10/51 (20%) of infants: FVL (8%), MTHFR667 homozygosity (10%), MTHFR1298 homozygosity (2%) and PTm (0%). There was no increase in the risk of UC-associated thrombus in patients carrying these prothrombotic mutations; our study had the power to detect a 2.5-fold increased risk of thrombosis for any of these significant mutations. In addition, MTHFR667 heterozygosity was found in 41% of infants and MTHFR1298 heterozygosity in 52% and also were not associated with increased risk of UC-associated thrombus. The risk of MTHFR double heterozygosity (db het) was 14%, the risk of a significant or db het was 17/51 (33%) and the risk of any mutation was 90%. CONCLUSION: Prothrombotic genetic mutations are common in our Neonatal Intensive Care Unit population but do not appear to increase the risk of UC-associated thrombosis.

Characteristics of pulmonary hypertension in preterm neonates.

OBJECTIVE: Characteristics of preterm infants who develop pulmonary hypertension (PHT) and their response to inhaled nitric oxide (iNO) are not well described. Our objective was to identify risk factors for PHT in infants <37 weeks gestational age (GA) and to evaluate their response to iNO. STUDY DESIGN: A retrospective chart review was conducted in infants <37 weeks GA born from July/2000 to October/2005 who had an echocardiographic diagnosis of PHT in the first 4 weeks of life. A comparison non-PHT group was generated matched for GA and birth date. Data on prenatal and postnatal characteristics, response to iNO and mortality were collected. RESULTS: Low Apgar scores, preterm premature rupture of membranes, oligohydramnios, pulmonary hypoplasia and sepsis were independently predictive of PHT. Mortality was significantly higher in the PHT group (26.2% versus 4.1%; P<0.0001) compared to the control group. Low birth weight, severe intraventricular hemorrhage and male sex were significantly associated with death in infants with PHT. Thirty-seven percent (23/61) of infants with PHT were treated with inhaled NO. Infants < 29-week GA had poor response to iNO and the response to iNO increased with GA (P<0.02). CONCLUSIONS: Low Apgar scores, oligohydramnios and pulmonary hypoplasia are associated with the development of PHT in premature infants. The percentage of infants responding to iNO increases with advancing GA.

White blood cell left shift in a neonate: a case of mistaken identity.

We present a full-term male infant who presented with tachypnea and an increased band count on his complete blood count (CBC) with an immature to total neutrophil (I:T) ratio of 0.6 raising suspicion of early onset sepsis. A blood culture was drawn and he was started on appropriate antibiotics. The patient's clinical condition rapidly improved; however, the white cell count 'left shift' persisted. When a detailed family history was obtained, it was discovered that the father, paternal uncle and the grandfather had been diagnosed with Pelger-Huet anomaly (PHA). As the urine, blood and CSF cultures were all negative in this now well-appearing infant, the left shift on the CBC was believed to be due to inheritance of the PHA. We present this case to emphasize that even in this age of sophisticated laboratory evaluation, a good clinical history, including family history, and clinical evaluation, are essential for accurate diagnosis.

Effects of sumatriptan on rat medullary dorsal horn neurons.

This study examined the cellular actions of the anti-migraine drug sumatriptan, on neurons in the substantia gelatinosa of the spinal trigeminal nucleus pars caudalis. Sumatriptan inhibited the miniature EPSC (mEPSC) rate in a dose dependent fashion, with an EC(50) of 250 nM. Sumatriptan (3 microM) inhibited the mEPSC rate by 36%, without altering the mEPSC amplitude. This effect was partially reversed by the 5HT(1D) specific antagonist BRL15572 (10 microM). In contrast, the 5HT(1B) agonist CP93129 (10 microm) did not alter the mEPSC rate. Furthermore, sumatriptan (3 microM) decreased the amplitude of electrically evoked EPSCs (eEPSC) by 40%. After incubating the slices in ketanserin (an antagonist which shows selectivity for 5HT(1D) over 5HT(1B) receptors) sumatriptan had little effect on eEPSC amplitude. In control conditions paired stimuli resulted in paired pulse depression (PPD; the ratio eEPSC(2)/eEPSC(1)=0.7+/-0.01), whilst in the presence of sumatriptan the PPD was blocked (ratio eEPSC(2)/eEPSC(1)=0.9+/-0.1). Sumatriptan produced no post-synaptic membrane current and had no significant effect on membrane conductance over a range of membrane potentials (-60 to -130 mV). RT-PCR experiments revealed the presence of mRNA for both 5HT(1D) and 5HT(1B) receptor subtypes in the trigeminal ganglia and subnucleus caudalis. These data suggest that sumatriptan acts pre-synaptically on trigeminal primary afferent central terminals to reduce the probability of release of glutamate, and that this action is mediated through 5HT(1D) receptors.

Effects of hyperoxia on tumor necrosis factor alpha and Grobeta expression in newborn rabbit lungs.

Chemokines have been implicated in the pathogenesis of many inflammatory processes, including bronchopulmonary dysplasia in mechanically ventilated premature infants. We hypothesized that early expression of the proinflammatory cytokine, tumor necrosis factor alpha (TNFalpha), would be followed by later expression of the downstream chemokine, Grobeta, in the oxygen-injured newborn lung. Reverse transcriptase-polymerase chain reaction (RT-PCR) and ribonuclease protection assay (RPA) were used to assess TNFalpha and Grobeta mRNA expression in lung RNA samples from newborn rabbits exposed to > 95% O2 for 8-9 days, followed by 60% O2 for a further 2-4 weeks or from control rabbits exposed to air. Four lung samples per condition were collected every 2 days from day 0 to day 14, and at days 22 and 36. Rabbit alveolar macrophages (AM) stimulated in vitro with bacterial lipopolysaccharide served as positive controls ( n = 8). Grobeta mRNA expression in rabbit lung samples increased with oxygen exposure until day 8, then returned toward baseline levels. This corresponded to previously described elevations in neutrophil number in the lungs. TNFalpha mRNA expression in lung samples was below the limit of detection by RPA and showed no upregulation in hyperoxic lung samples by RT-PCR. TNFalpha activity was assessed in lung lavage ( n = 2 samples per condition per time) using an L929 cell line bioassay and was not increased in hyperoxic animals. The expression of Grobeta mRNA without antecedent or concurrent TNFalpha mRNA expression or activity makes it unlikely that Grobeta in the hyperoxic newborn rabbit lung is elaborated in response to a stimulus by TNFalpha.