dSPRINT: predicting DNA, RNA, ion, peptide and small molecule interaction sites within protein domains.

Domains are instrumental in facilitating protein interactions with DNA, RNA, small molecules, ions and peptides. Identifying ligand-binding domains within sequences is a critical step in protein function annotation, and the ligand-binding properties of proteins are frequently analyzed based upon whether they contain one of these domains. To date, however, knowledge of whether and how protein domains interact with ligands has been limited to domains that have been observed in co-crystal structures; this leaves approximately two-thirds of human protein domain families uncharacterized with respect to whether and how they bind DNA, RNA, small molecules, ions and peptides. To fill this gap, we introduce dSPRINT, a novel ensemble machine learning method for predicting whether a domain binds DNA, RNA, small molecules, ions or peptides, along with the positions within it that participate in these types of interactions. In stringent cross-validation testing, we demonstrate that dSPRINT has an excellent performance in uncovering ligand-binding positions and domains. We also apply dSPRINT to newly characterize the molecular functions of domains of unknown function. dSPRINT's predictions can be transferred from domains to sequences, enabling predictions about the ligand-binding properties of 95% of human genes. The dSPRINT framework and its predictions for 6503 human protein domains are freely available at http://protdomain.princeton.edu/dsprint.

Increased surfactant protein-D levels in the airways of preterm neonates with sepsis indicated responses to infectious challenges.

AIM: Sepsis is multifactorial and potentially devastating for preterm neonates. Changes in surfactant protein-D (SP-D), phosphatidylcholine (PC) and PC molecular species during infection may indicate innate immunity or inflammation during sepsis. We aimed to compare these important pulmonary molecules in ventilated neonates without or with sepsis. METHODS: Endotracheal aspirates were collected from preterm neonates born at 23-35 weeks and admitted to the neonatal intensive care unit at the John Radcliffe Hospital, Oxford, UK, from October 2000 to March 2002. Samples were collected at one day to 30 days and analysed for SP-D, total PC and PC molecular species concentrations using enzyme-linked immunosorbent assay and mass spectrometry. RESULTS: We found that 8/54 (14.8%) neonates developed sepsis. SP-D (p < 0.0001), mono- and di-unsaturated PC were significantly increased (p = 0.05), and polyunsaturated PC was significantly decreased (p < 0.01) during sepsis compared to controls. SP-D:PC ratios were significantly increased during sepsis (p < 0.001), and SP-D concentrations were directly related to gestational age in neonates with sepsis (r2  = 0.389, p < 0.01). CONCLUSION: Increased SP-D levels and changes in PC molecular species during sepsis were consistent with direct or indirect pulmonary inflammatory processes. Very preterm neonates we able to mount an acute inflammatory innate immune response to infectious challenges, despite low levels of surfactant proteins at birth.

Smoking in the family is most predictive of the development of childhood asthma in preterm babies <30 weeks gestation: Results of the Respiratory Outcomes Study 2 (RESPOS2).

OBJECTIVES: The Respiratory Outcomes Study 2 (RESPOS2) investigated the relationship between neonatal outcomes (specifically, chronic lung disease [CLD]) and environmental factors on the development of asthma and atopic outcomes at primary school age for preterm babies (PBs) <30 weeks gestational age (GA). METHODS: The study included all surviving PBs <30 weeks GA admitted to the Neonatal Intensive Care Unit at Canberra Hospital, Australian Capital Territory between 2007 and 2009. Parents were sent a questionnaire regarding asthma and atopy symptoms when the PBs were aged 5-7 years old. Data were compared based on CLD status. RESULTS: There were 103 PBs included in the study with a 68.9% response rate to the respiratory questionnaire (71/103). Of these PBs, 15/71 (21.1%) received a diagnosis of CLD. There were no significant differences with regards to asthma, hay fever or eczema in PBs either with or without CLD. The most significant predictor for the development of asthma was smoking in the family (Odds Ratio [OR]: 11.66, 95% Confidence Interval [CI]: 2.01-67.56) with a trend toward significance for family history of asthma (OR: 3.83, 95% CI: 0.85-17.25). CONCLUSION: The RESPOS2 has confirmed previous reports that CLD in PBs <30 weeks GA is not associated with the development of childhood asthma, hay fever or eczema. In our group of PBs, the strongest predictor of the development of asthma was smoking in the family.

Heat and moisture exchangers versus heated humidifiers for mechanically ventilated adults and children.

BACKGROUND: Invasive ventilation is used to assist or replace breathing when a person is unable to breathe adequately on their own. Because the upper airway is bypassed during mechanical ventilation, the respiratory system is no longer able to warm and moisten inhaled gases, potentially causing additional breathing problems in people who already require assisted breathing. To prevent these problems, gases are artificially warmed and humidified. There are two main forms of humidification, heat and moisture exchangers (HME) or heated humidifiers (HH). Both are associated with potential benefits and advantages but it is unclear whether HME or HH are more effective in preventing some of the negative outcomes associated with mechanical ventilation. This review was originally published in 2010 and updated in 2017. OBJECTIVES: To assess whether heat and moisture exchangers or heated humidifiers are more effective in preventing complications in people receiving invasive mechanical ventilation and to identify whether the age group of participants, length of humidification, type of HME, and ventilation delivered through a tracheostomy had an effect on these findings. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase and CINAHL up to May 2017 to identify randomized controlled trials (RCTs) and reference lists of included studies and relevant reviews. There were no language limitations. SELECTION CRITERIA: We included RCTs comparing HMEs to HHs in adults and children receiving invasive ventilation. We included randomized cross-over studies. DATA COLLECTION AND ANALYSIS: We assessed the quality of each study and extracted the relevant data. Where possible, we analysed data through meta-analysis. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (95% CI). For continuous outcomes, we calculated the mean difference (MD) and 95% CI or standardized mean difference (SMD) and 95% CI for parallel studies. For cross-over trials, we calculated the MD and 95% CI using correlation estimates to correct for paired analyses. We aimed to conduct subgroup analyses based on the age group of participants, how long they received humidification, type of HME and whether ventilation was delivered through a tracheostomy. We also conducted sensitivity analysis to identify whether the quality of trials had an effect on meta-analytic findings. MAIN RESULTS: We included 34 trials with 2848 participants; 26 studies were parallel-group design (2725 participants) and eight used a cross-over design (123 participants). Only three included studies reported data for infants or children. Two further studies (76 participants) are awaiting classification.There was no overall statistical difference in artificial airway occlusion (RR 1.59, 95% CI 0.60 to 4.19; participants = 2171; studies = 15; I2 = 54%), mortality (RR 1.03, 95% CI 0.89 to 1.20; participants = 1951; studies = 12; I2 = 0%) or pneumonia (RR 0.93, 95% CI 0.73 to 1.19; participants = 2251; studies = 13; I2 = 27%). There was some evidence that hydrophobic HMEs may reduce the risk of pneumonia compared to HHs (RR 0.48, 95% CI 0.28 to 0.82; participants = 469; studies = 3; I2 = 0%)..The overall GRADE quality of evidence was low. Although the overall methodological risk of bias was generally unclear for selection and detection bias and low risk for follow-up, the selection of study participants who were considered suitable for HME and in some studies removing participants from the HME group made the findings of this review difficult to generalize. AUTHORS' CONCLUSIONS: The available evidence suggests no difference between HMEs and HHs on the primary outcomes of airway blockages, pneumonia and mortality. However, the overall low quality of this evidence makes it difficult to be confident about these findings. Further research is needed to compare HMEs to HHs, particularly in paediatric and neonatal populations, but research is also needed to more effectively compare different types of HME to each other as well as different types of HH.

Frenotomy for tongue-tie in newborn infants.

BACKGROUND: Tongue-tie, or ankyloglossia, is a condition whereby the lingual frenulum attaches near the tip of the tongue and may be short, tight and thick. Tongue-tie is present in 4% to 11% of newborns. Tongue-tie has been cited as a cause of poor breastfeeding and maternal nipple pain. Frenotomy, which is commonly performed, may correct the restriction to tongue movement and allow more effective breastfeeding with less maternal nipple pain. OBJECTIVES: To determine whether frenotomy is safe and effective in improving ability to feed orally among infants younger than three months of age with tongue-tie (and problems feeding).Also, to perform subgroup analysis to determine the following.• Severity of tongue-tie before frenotomy as measured by a validated tool (e.g. Hazelbaker Assessment Tool for Lingual Frenulum Function (ATLFF) scores < 11; scores ≥ 11) (Hazelbaker 1993).• Gestational age at birth (< 37 weeks' gestation; 37 weeks' gestation and above).• Method of feeding (breast or bottle).• Age at frenotomy (≤ 10 days of age; > 10 days to three months of age).• Severity of feeding difficulty (infants with feeding difficulty affecting weight gain (as assessed by infant's not regaining birth weight by day 14 or falling off centiles); infants with symptomatic feeding difficulty but thriving (greater than birth weight by day 14 and tracking centiles). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and CINAHL up to January 2017, as well as previous reviews including cross-references, expert informants and journal handsearching. We searched clinical trials databases for ongoing and recently completed trials. We applied no language restrictions. SELECTION CRITERIA: Randomised, quasi-randomised controlled trials or cluster-randomised trials that compared frenotomy versus no frenotomy or frenotomy versus sham procedure in newborn infants. DATA COLLECTION AND ANALYSIS: Review authors extracted from the reports of clinical trials data regarding clinical outcomes including infant feeding, maternal nipple pain, duration of breastfeeding, cessation of breastfeeding, infant pain, excessive bleeding, infection at the site of frenotomy, ulceration at the site of frenotomy, damage to the tongue and/or submandibular ducts and recurrence of tongue-tie. We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: Five randomised trials met our inclusion criteria (n = 302). Three studies objectively measured infant breastfeeding using standardised assessment tools. Pooled analysis of two studies (n = 155) showed no change on a 10-point feeding scale following frenotomy (mean difference (MD) -0.1, 95% confidence interval (CI) -0.6 to 0.5 units on a 10-point feeding scale). A third study (n = 58) showed objective improvement on a 12-point feeding scale (MD 3.5, 95% CI 3.1 to 4.0 units of a 12-point feeding scale). Four studies objectively assessed maternal pain. Pooled analysis of three studies (n = 212) based on a 10-point pain scale showed a reduction in maternal pain scores following frenotomy (MD -0.7, 95% CI -1.4 to -0.1 units on a 10-point pain scale). A fourth study (n = 58) also showed a reduction in pain scores on a 50-point pain scale (MD -8.6, 95% CI -9.4 to -7.8 units on a 50-point pain scale). All studies reported no adverse effects following frenotomy. These studies had serious methodological shortcomings. They included small sample sizes, and only two studies blinded both mothers and assessors; one did not attempt blinding for mothers nor for assessors. All studies offered frenotomy to controls, and most controls underwent the procedure, suggesting lack of equipoise. No study was able to report whether frenotomy led to long-term successful breastfeeding. AUTHORS' CONCLUSIONS: Frenotomy reduced breastfeeding mothers' nipple pain in the short term. Investigators did not find a consistent positive effect on infant breastfeeding. Researchers reported no serious complications, but the total number of infants studied was small. The small number of trials along with methodological shortcomings limits the certainty of these findings. Further randomised controlled trials of high methodological quality are necessary to determine the effects of frenotomy.

Increased use of heated humidified high flow nasal cannula is associated with longer oxygen requirements.

AIM: There has been an increased use of heated humidified high flow nasal canula (HFNC) in premature babies (PBs) admitted to our neonatal unit. The aim of this study is to identify clinical characteristics in PBs < 29 weeks gestational age (GA) that distinguish between those who did not or did receive HFNC. METHODS: This study compared prospectively collected data from 2010 to 2012. Comparisons were undertaken between PBs<29 weeks GA who received continuous positive airway pressure (CPAP: 44/72 (61.1%)) to those who received both CPAP and HFNC (28/72 (38.9%)). Data were analysed using general linear models. RESULTS: There were no significant differences in baseline characteristics between the groups (GA: 27.6 ± 1.1 vs. 27.5 ± 1.1 (weeks), birth weight: 1066 ± 209 vs. 1057 ± 304 (grams) respectively). When analysing outcome measures with multivariate analysis, we found the corrected GA to cease CPAP and oxygen were significantly longer in the HFNC group (31.2 ± 2.1 vs. 32.7 ± 2.0 weeks, P = 0.01 and 32.8 ± 3.5 vs. 36.5 ± 2.8 weeks, P < 0.0001 respectively). CONCLUSIONS: Increased use of HFNC has been associated with increased oxygen requirements. These findings highlight the need to review the use of HFNC in small PBs.

CeasIng Cpap At standarD criteriA (CICADA): predicting a successful outcome.

This is a retrospective analysis of a multicentre randomised controlled trial (RCT) where we concluded that CeasIng Cpap At standerD criteriA (CICADA) in premature babies (PBs) <30 weeks gestational age (GA) was the significantly better method of ceasing CPAP. To identify factors that may influence the number of attempts to cease CPAP, we reviewed the records of 50 PBs from the RCT who used the CICADA method. PBs were grouped according to number of attempts to cease CPAP (fast group ≤2 attempts and slow group >2 attempts to cease CPAP). There were 26 (fast group) and 24 (slow group) PBs included in the analysis. Results showed significant differences in mean GA (27.8 ± 0.3 vs 26.9 ± 0.3 [weeks ± SE], p = 0.03) and birth weight ([Bwt]; 1080 ± 48.8 vs 899 ± 45.8 [grams ± SE], p = 0.01) between groups. Significantly fewer PBs in the fast group had a patent ductus arteriosus (PDA) compared to the slow group (5/26 (19.2%) vs 13/24 (54.2 %), p = 0.02). Bwt was a significant negative predictor of CPAP duration (r = -0.497, p = 0.03) and CPAP ceasing attempts (r = -0.290, p = 0.04). CONCLUSION: PBs with a higher GA and Bwt without a PDA ceased CPAP earlier using the CICADA method. Bwt was better than GA for predicting CPAP duration and attempts to cease CPAP. WHAT IS KNOWN: Our previous studies showed that CeasIng Cpap At standarD criteriA (CICADA) significantly reduces CPAP time, oxygen requirements and caffeine use. Some PBs however using the CICADA method required >2 attempts to cease CPAP ('slow CICADA' group). WHAT IS NEW: PBs in the 'fast CICADA' group (<3 attempts to cease CPAP) (a) have longer gestational age and higher birth weight, (b) shorter mechanical ventilation and (c) lower incidence of patent ductus arteriosus. Attempts to cease CPAP decreased by 0.5 times per 1 week increase in GA and 0.3 times per 100-g increase in birth weight for PBs <30 weeks gestation.

CeasIng Cpap At standarD criteriA (CICADA): Implementation improves neonatal outcomes.

BACKGROUND: A previous randomised controlled trial (RCT) in babies born < 30 weeks gestation found the so-called CICADA method (ceasing continuous positive airways pressure (CPAP) with a view to remain off rather than slow weaning) significantly reduced CPAP time. Post-RCT we introduced the CICADA method and evaluated whether the improved outcomes of the CICADA method during the RCT were replicated in clinical practice. AIM: The aim of the study is to compare cardio-respiratory outcomes in PBs < 30 weeks GA over three epochs: (i) pre RCT, (ii) during RCT and (iii) post RCT implementation. METHODS: The study used prospective data to compare baseline characteristics and cardio-respiratory outcomes over the three epochs. RESULTS: There were 270/393(69%) PBs < 30 weeks GA who fulfilled the inclusion criteria over the three epochs. No significant differences were found in GA or birthweight between the three epochs (27.9 ± 1.3, 27.7 ± 1.4, 28.0 ± 1.3 (weeks ± 1 standard deviation); and 1100 ± 252, 1086 ± 251, 1094 ± 320 (grams ± 1 standard deviation)). There were significant decreases in CPAP days and corrected GA to cease CPAP post implementation (20.5 ± 2.1, 21.1 ± 2.1, 16.5 ± 1.8 (days ± SE); P = 0.006 and 33.3 ± 0.4, 33.5 ± 0.4, 32.6 ± 0.4 (weeks ± SE); P = 0.01). Compared with the pre RCT epoch, there were significant reductions in patent ductus arteriosus (36/78 (46%), 33/87 (37%), 18/103 (17%); P < 0.001) and chronic lung disease (40/78 (51%), 19/87 (21%), 30/103 (29%); P < 0.001). CONCLUSIONS: CPAP time, corrected GA to cease CPAP, patent ductus arteriosus and chronic lung disease significantly reduced following the introduction of the CICADA method. Early cessation of CPAP expedites the transition from neonatal intensive care to special care.

Tongue-tie in the newborn: Follow-up in the first 6 months.

BACKGROUND: Over the last decade, a number of studies have demonstrated that early division of tongue-tie (TT) is associated with significant feeding benefits to both mother and baby. Notwithstanding, it remains a controversial procedure. We examined the breastfeeding outcomes of a cohort of babies at 1-2 weeks (follow-up 1) and 3-5 months (follow-up 2), post-TT division. METHODS: We undertook a cohort study on all mother/baby dyads who had a TT divided at Canberra Hospital between 1 July 2013 and 30 June 2014. We contacted the mothers of both follow-up groups by telephone, focusing on breastfeeding and maternal pain. RESULTS: Follow-up 1 consisted of 116/182 (63.7%) of mothers in the study; contacted at 12.4+-7.8 days post-division. Of these, 107/116 (92.2%) were still breastfeeding, with 11/15 (73.3%) of the mothers who had ceased breastfeeding before division having re-established it at the time of follow-up (p < 0.00l). Additionally, 90/101 (89.1%) valid responses reported decreased nipple pain following TT division. Follow-up 2 consisted of 112/182 (61.5%) of all mothers in the study; contacted at 3.7+-1.8 months of age. Of these, 86/112 (76.8%) were still breastfeeding, with 11/15 (73.3%) of mothers who had ceased breastfeeding before division having re-established it at follow-up (p < 0.001). CONCLUSION: A divided TT was associated with benefits at both periods of follow-up. There was (i) an increase in overall breastfeeding rates and (ii) a decrease in maternal pain.

Respiratory outcomes study (RESPOS) for preterm infants at primary school age.

OBJECTIVE: Pulmonary function abnormalities and hospital re-admissions in survivors of neonatal lung disease remain highly prevalent. The respiratory outcomes study (RESPOS) aimed to investigate the respiratory and associated atopy outcomes in preterm infants <30 weeks gestational age (GA) and/or birth-weight (BWt) <1000 g at primary school age, and to compare these outcomes between infants with and without chronic lung disease (CLD). METHODS: In the RESPOS 92 parents of preterm infants admitted to the Neonatal unit in Canberra Hospital between 1/1/2001 and 31/12/2003 were sent a questionnaire regarding their respiratory, atopy management and follow-up. RESULTS: Fifty-three parents responded, including 28 preterm infants who had CLD and 25 who had no CLD. The gestational age was significantly lower in the CLD group compared to the non-CLD group [26.9 (26.3-27.5) CLD and 28.6 (28.3-29.0) non-CLD] [weeks [95% confidence interval (CI)]], as was the birth weight [973 (877.4-1068.8) CLD versus 1221 (1135.0-1307.0) non-CLD] [g (CI)]. CLD infants compared to non-CLD infants were significantly more likely to have been: given surfactant, ventilated and on oxygen at 28 days and 36 weeks. These neonates were also more likely to have: been discharged from the neonatal unit on oxygen, exhibit a history of PDA or sepsis and to have a current paediatrician. However, despite these differences, there was no significant difference in the proportion of asthma or atopic disease between the two groups. CONCLUSIONS: The RESPOS could not demonstrate respiratory and/or atopy differences between the CLD and the non-CLD groups at primary school age.

Tongue-tie in the newborn: early diagnosis and division prevents poor breastfeeding outcomes.

BACKGROUND: In 2011, the Centenary Hospital Neonatal Department guidelines were modified and recommended delaying the division of infant tongue-tie (TT) until after 7 days of life. This paper looks at the effect of these guidelines in practice by comparing patient characteristics and breastfeeding practices before and after the change. METHODS: We used prospective data from mothers and babies who had TT division to compare breastfeeding practices in 2008 and 2011. Data included: gestational age (GA), birth-weight (BWt), gender, age at TT division, degrees of TT and maternal feeding pre/post TT division. RESULTS: There were no significant differences between the 2 years in the rate of TT division, 115/2471 (4.7%) vs 144/2891 (5.0%) (TT divided/birth number) or GA 39.6 ± 1.2 vs 39.5 ± 1.2 (weeks); BWt 3.48 ± 0.45 vs 3.52 ± 0.50 (kg); and Male:Female 77:38 (2.0:1.0) vs 91:53 (1.7:1.0). There was, however, an increase in the age the TT was divided 6.5 ± 4.5 vs 9.7 ± 6.2 (days) p < 0.0001; and an increased number of mothers unable to continue breastfeeding and providing expressed breastmilk: 4/115 (3.5%) vs 25/144 (17.4%) p = 0.0004 (expressing/divided). A majority (> 90%) of mothers noted an immediate improvement in feeding and decreased nipple pain. No significant complications occurred. CONCLUSION: The rate of TT division did not change after the implementation of new guidelines post 2011. However, there has been a significant increase in the age at TT division and the number of mothers unable to breastfeed, primarily due to nipple pain and poor attachment. If feeding is problematic, the TT should be divided as early as possible to reduce breastfeeding cessation and improve breastfeeding satisfaction.

Tongue-tie in the newborn: what, when, who and how? Exploring tongue-tie division.

The division of tongue-tie (TT) in babies with feeding problems has become a more accepted procedure in recent years (Bowley & Arul 2013). Although case series reports had described the benefits of division in problematic breastfeeding (Ballard, Auer & Khoury et al 2002; Notestine 1990), it was not until randomised controlled trials (RCTs) provided significant evidence of improvement that the procedure became more accepted (Berry, Griffiths & Westcott 2012; Buryk, Bloom & Shope 2011; Dollberg et al 2006; Emond et al 2014; Hogan, Westcott & Griffiths 2005). However there are still several areas of debate. These include: 1) what type of TT produces problems with feeding and thus what type of TT should be divided, 2) who should have the procedure, 3) when should the TT division be performed and 4) how should the TT be divided. In this review I will discuss these areas of debate and shed some light on this very common but often devastating congenital condition.

Inspired gas humidity and temperature during mechanical ventilation with the Stephanie ventilator.

AIMS: To measure inspired gas humidity and temperature delivered by a Stephanie neonatal ventilator with variations in (i) circuit length; (ii) circuit insulation; (iii) proximal airway temperature probe (pATP) position; (iv) inspiratory temperature (offset); and (v) incubator temperatures. METHODS: Using the Stephanie neonatal ventilator, inspired gas humidity and temperature were measured during mechanical ventilation at the distal inspiratory limb and 3 cm down the endotracheal tube. Measurements were made with a long or short circuit; with or without insulation of the inspiratory limb; proximal ATP (pATP) either within or external to the incubator; at two different inspiratory temperature (offset) of 37(-0.5) and 39(-2.0)°C; and at three different incubator temperatures of 32, 34.5, and 37°C. RESULTS: Long circuits produced significantly higher inspired humidity than short circuits at all incubator settings, while only at 32°C was the inspired temperature higher. In the long circuits, insulation further improved the inspired humidity especially at 39(-2.0)°C, while only at incubator temperatures of 32 and 37°C did insulation significantly improve inspired temperature. Positioning the pATP outside the incubator did not result in higher inspired humidity but did significantly improve inspired temperature. An inspiratory temperature (offset) of 39(-2.0)°C delivered significantly higher inspired humidity and temperature than the 37(-0.5)°C especially when insulated. CONCLUSIONS: Long insulated Stephanie circuits should be used for neonatal ventilation when the infant is nursed in an incubator. The recommended inspiratory temperature (offset) of 37(-0.5)°C produced inspired humidity and temperature below international standards, and we suggest an increase to 39(-2.0)°C.

Observational cohort study of changing trends in non-invasive ventilation in very preterm infants and associations with clinical outcomes.

OBJECTIVE: To determine the change in non-invasive ventilation (NIV) use over time in infants born at <32 weeks' gestation and the associated clinical outcomes. STUDY DESIGN: Retrospective cohort study using routinely recorded data from the National Neonatal Research Database of infants born at <32 weeks admitted to neonatal units in England and Wales from 2010 to 2017. RESULTS: In 56 537 infants, NIV use increased significantly between 2010 and 2017 (continuous positive airway pressure (CPAP) from 68.5% to 80.2% in 2017 and high flow nasal cannula (HFNC) from 14% to 68%, respectively) (p<0.001)). Use of NIV as the initial mode of respiratory support also increased (CPAP, 21.5%-28.0%; HFNC, 1%-7% (p<0.001)).HFNC was used earlier, and for longer, in those who received CPAP or mechanical ventilation. HFNC use was associated with decreased odds of death before discharge (adjusted OR (aOR) 0.19, 95% CI 0.17 to 0.22). Infants receiving CPAP but no HFNC died at an earlier median chronological age: CPAP group, 22 (IQR 10-39) days; HFNC group 40 (20-76) days (p<0.001). Among survivors, HFNC use was associated with increased odds of bronchopulmonary dysplasia (BPD) (aOR 2.98, 95% CI 2.81 to 3.15) and other adverse outcomes. CONCLUSIONS: NIV use is increasing, particularly as initial respiratory support. HFNC use has increased significantly with a sevenfold increase soon after birth which was associated with higher rates of BPD. As more infants survive with BPD, we need robust clinical evidence, to improve outcomes with the use of NIV as initial and ongoing respiratory support.

Heated humidification versus heat and moisture exchangers for ventilated adults and children.

BACKGROUND: Humidification by artificial means must be provided when the upper airway is bypassed during mechanical ventilation. Heated humidification (HH) and heat and moisture exchangers (HMEs) are the most commonly used types of artificial humidification in this situation. OBJECTIVES: To determine whether HHs or HMES are more effective in preventing mortality and other complications in people who are mechanically ventilated. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 4) and MEDLINE, EMBASE and CINAHL (January, 2010) to identify relevant randomized controlled trials. SELECTION CRITERIA: We included randomized controlled trials comparing HMEs to HHs in mechanically ventilated adults and children. We included randomized crossover studies. DATA COLLECTION AND ANALYSIS: We assessed the quality of each study and extracted the relevant data. Where appropriate, results from relevant studies were meta-analyzed for individual outcomes. MAIN RESULTS: We included 33 trials with 2833 participants; 25 studies were parallel group design (n = 2710) and 8 crossover design (n = 123). Only 3 included studies reported data for infants or children. There was no overall effect on artificial airway occlusion, mortality, pneumonia, or respiratory complications; however, the PaCO(2) and minute ventilation were increased when HMEs were compared to HHs and body temperature was lower. The cost of HMEs was lower in all studies that reported this outcome. There was some evidence that hydrophobic HMEs may reduce the risk of pneumonia and that blockages of artificial airways may be increased with the use of HMEs in certain subgroups of patients. AUTHORS' CONCLUSIONS: There is little evidence of an overall difference between HMEs and HHs. However, hydrophobic HMEs may reduce the risk of pneumonia and the use of an HMEs may increase artificial airway occlusion in certain subgroups of patients. Therefore, HMEs may not be suitable for patients with limited respiratory reserve or prone to airway blockage. Further research is needed relating to hydrophobic versus hygroscopic HMEs and the use of HMEs in the pediatric and neonatal populations. As the design of HMEs evolves, evaluation of new generation HMEs will also need to be undertaken.

Heated humidification versus heat and moisture exchangers for ventilated adults and children.

BACKGROUND: Humidification by artificial means must be provided when the upper airway is bypassed during mechanical ventilation. Heated humidification (HH) and heat and moisture exchangers (HME) are the most commonly used types of artificial humidification in this situation. OBJECTIVES: To determine whether HHs or HMEs are more effective in preventing mortality and other complications in people who are mechanically ventilated. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 4) and MEDLINE, EMBASE and CINAHL (January, 2010) to identify relevant randomized controlled trials (RCTs). SELECTION CRITERIA: We included RCTs comparing heat and moisture exchangers (HMEs) to heated humidifiers (HHs) in mechanically ventilated adults and children. We included randomized crossover studies. DATA COLLECTION AND ANALYSIS: We assessed the quality of each study and extracted the relevant data. Where appropriate, results from relevant studies were meta-analysed for individual outcomes. MAIN RESULTS: We included 33 trials with 2833 participants, 25 studies were parallel group design (n = 2710) and eight crossover design (n = 123). Only three included studies reported data for infants or children. There was no overall effect on artificial airway occlusion, mortality, pneumonia, or respiratory complications; however, the PaCO(2) and minute ventilation were increased when HMEs were compared to HHs and body temperature was lower. The cost of HMEs was lower in all studies that reported this outcome. There was some evidence that hydrophobic HMEs may reduce the risk of pneumonia and that blockages of artificial airways may be increased with the use of HMEs in certain subgroups of patients. AUTHORS' CONCLUSIONS: There is little evidence of an overall difference between HMEs and HHs. However, hydrophobic HMEs may reduce the risk of pneumonia and the use of an HME may increase artificial airway occlusion in certain subgroups of patients. Therefore, HMEs may not be suitable for patients with limited respiratory reserve or prone to airway blockage. Further research is needed relating to hydrophobic versus hygroscopic HMEs and the use of HMEs in the paediatric and neonatal populations. As the design of HMEs evolves, evaluation of new generation HMEs will also need to be undertaken.

Surfactant phospholipids, surfactant proteins, and inflammatory markers during acute lung injury in children.

OBJECTIVE: To explore the pathophysiology of acute lung injury in children. DESIGN: Prospective cohort study. SETTING: Regional University Hospital, pediatric intensive care unit. PATIENTS: Children without a preexisting lung injury who developed acute lung injury and were intubated were eligible for the study. Children without lung injury and intubated for minor surgical procedures acted as controls. INTERVENTIONS: Bronchoalveolar lavage fluid and blood were collected on days 1 to 4, weekly, and immediately before extubation during acute lung injury. Molecular species compositions of phosphatidylcholine were determined by electrospray ionization mass spectrometry of lipid extracts of bronchoalveolar lavage fluid supernatants. Surfactant proteins A, B, and D and interleukin-8 were measured in bronchoalveolar lavage fluid and plasma by enzyme-linked immunosorbent assay and Western blotting. MEASUREMENTS AND MAIN RESULTS: Eighteen children with acute lung injury were enrolled in the study and compared with eight controls. In children with acute lung injury, there were significant changes in the bronchoalveolar lavage fluid phosphatidylcholine species. Bronchoalveolar lavage fluid dipalmitoyl phosphatidylcholine (PC 16:0/16:0) and palmitoyl-myristoyl phosphatidylcholine (PC 16:0/14:0) significantly deceased during acute lung injury (p < .001 and p < .001, respectively), whereas oleoyl-linoleoyl PC (18:1/18:2), palmitoyl-linoleoyl PC (16:0/18:2) and stearoyl-linoleoyl PC (18:0/18:2) characteristic of plasma PC were significantly increased (p < .05, p < .02, and p < .05 respectively), as well as palmitoyl-oleoyl PC (16:0/18:1), and stearoyl-arachidonoyl PC (18:0/20:4) which are characteristic of cell membranes (p < .02, and p < .02, respectively). There were no significant changes to bronchoalveolar lavage fluid, surfactant protein A or B levels compared with controls during acute lung injury, whereas bronchoalveolar lavage fluid, surfactant protein D, and interleukin-8 levels significantly increased (p < .05 and p < .02, respectively). In plasma during acute lung injury, there were significant increases in surfactant proteins A, B, and D, and interleukin-8 (p < .001, p < .001, p < .05, and p < .001, respectively). CONCLUSION: Changes to the phosphatidylcholine profile, surfactant proteins, and inflammatory markers of bronchoalveolar lavage fluid and plasma in children with acute lung injury are consistent with an alveolar/blood leakage and inflammatory cell membrane degradation products. These changes are due to alveolar capillary membrane damage and cellular infiltration.

Sight-Threatening Retinopathy of Prematurity: Changing Trends in Treatment.

PURPOSE: To study the incidence and treatment of severe retinopathy of prematurity (ROP) in infants younger than 30 weeks' gestational age (GA) in New South Wales and the Australian Capital Territory, Australia, from 2003 to 2008. These data were then compared to data from previously reported epochs (1986 to 1987, 1992 to 1997, and 1998 to 2002). METHODS: Data were divided into two sub-epochs (2003 to 2005 and 2006 to 2008) to study trends and combined to compare over 22 years. RESULTS: From 2003 to 2008, 2,550 of 3,004 (84.9%) infants survived, 200 (7.8%) were diagnosed as having severe ROP, and 119 (59.5%) required laser therapy. No significant difference in the incidence of severe ROP or treatment rate in infants younger than 27 and 30 weeks' GA from 2003 to 2005 and 2006 to 2008 occurred. Similarly, between 1986 and 2008 there was no difference in the incidence of severe ROP. However, the treatment rate significantly increased during this time. CONCLUSIONS: The incidence of severe ROP has been stable since 1986. However, laser treatment significantly increased to include 8 infants with stage 2 ROP from 2003 to 2008.

CeasIng Cpap At standarD criteriA (CICADA): impact on weight gain, time to full feeds and caffeine use.

INTRODUCTION: In our previous randomised controlled trial (RCT), we have shown in preterm babies (PBs) <30 weeks gestation that CeasIng Cpap At standarD criteriA (CICADA (method 1)) compared with cycling off continuous positive airway pressure (CPAP) gradually (method 2) or cycling off CPAP gradually with low flow air/oxygen during periods off CPAP (method 3) reduces CPAP cessation time in PBs <30 weeks gestation. METHOD: This retrospective study reviewed weight gain, time to reach full feeds and time to cease caffeine in PBs previously enrolled in the RCT. RESULTS: Data were collected from 162 of the 177 PBs, and there was no significant difference in the projected weight gain between the three methods. Based on intention to treat, the time taken to reach full feeds for all three methods showed no significant difference. However, post hoc analysis showed the CICADA method compared with cycling off gradually just failed significance (30.3±1.6 vs 31.1±2.4 (weeks corrected gestational age (Wks CGA±SD)), p=0.077). Analysis of time to cease caffeine showed there was a significant difference between the methods with PBs randomised to the CICADA method compared with the cycling off method ceasing caffeine almost a week earlier (33.6±2.4 vs 34.5±2.8 (Wks CGA±SD), p=0.02). CONCLUSIONS: This retrospective study provides evidence to substantiate the optimum method of ceasing CPAP; the CICADA method, does not adversely affect weight gain, time to reach full feeds and may reduce time to cease caffeine in PBs <30 weeks gestation.