Umbilical Venous Catheter Position: The Value of Acquiring a Lateral in Addition to a Frontal Chest Radiograph.

Introduction Umbilical venous catheters (UVCs) are standardly used for central venous access in acutely sick neonates. Complications associated with UVCs include thrombosis, infection, diffuse intravascular coagulopathy, arrhythmia, tamponade, and liver injury, many of which are related to misplacement of the catheters. Therefore, this study aimed to institute a policy of obtaining lateral and frontal radiographs to improve the determination of the UVC position. Methods We retrospectively reviewed UVC placement from 132 radiographs. We compared interpretations by different reviewers of frontal versus frontal and lateral chest radiographs for the most accurate determination of the UVC position. The reviewers completed questionnaires indicating their assessment of the catheter tip position, as well as the appropriate catheter manipulation required for optimal positioning. Their assessment was derived from frontal chest radiographs followed by frontal plus lateral view radiographs a week later. Results The reviewers (junior neonatology fellow, senior neonatology fellow, pediatric radiology fellow, and senior pediatric radiologist) revised their assessment with regard to the UVC positioning between frontal and frontal plus lateral radiographs in 24.6%, 22.7%, 19.6%, and 15.9% of cases, respectively, and indicated that the lateral view was helpful in 18%, 13.6%, 19.6%, and 31% of the cases, respectively. UVCs were placed appropriately at the first attempt in only 13.6% of the cases. Conclusion Correct initial placement of a UVC is uncommon. A lateral radiograph is beneficial in determining the UVC position. Hence, we suggest the inclusion of a lateral view along with the frontal chest radiograph for the evaluation of the UVC position if real-time ultrasound cannot be performed before UVC usage.

"Mild'' Hypoxic-Ischaemic Encephalopathy and Therapeutic Hypothermia: A Survey of Clinical Practice and Opinion from 35 Countries.

INTRODUCTION: We aimed to determine global professional opinion and practice for the use of therapeutic hypothermia (TH) for treating infants with mild hypoxic-ischaemic encephalopathy (HIE). METHODS: A web-based survey (REDCap) was distributed via emails, social networking sites, and professional groups from October 2020 to February 2021 to neonatal clinicians in 35 countries. RESULTS: A total of 484 responses were obtained from 35 countries and categorized into low/middle-income (43%, LMIC) or high-income (57%, HIC) countries. Of the 484 respondents, 53% would provide TH in mild HIE on case-to-case basis and only 25% would never cool. Clinicians from LMIC were more likely to routinely offer TH in mild HIE (25% v HIC 16%, p < 0.05), have a unit protocol for providing TH (50% v HIC 26%, p < 0.05), use adjunctive tools, e.g., aEEG (49% v HIC 32%, p < 0.001), conduct an MRI post TH (48% v HIC 40%, p < 0.05) and less likely to use neurological examinations as a HIE severity grading tool (80% v HIC 95%, p < 0.001). The majority of respondents (91%) would support a randomized controlled trial that was sufficiently large to examine neurodevelopmental outcomes in mild HIE after TH. CONCLUSIONS: This is the first survey of global opinion for TH in mild HIE. The overwhelming majority of professionals would consider "cooling" an infant with mild HIE, but LMIC respondents were more likely to routinely cool infants with mild HIE and use adjunctive tools for diagnosis and follow-up. There is wide practice heterogeneity and a sufficiently large RCT designed to examine neurodevelopmental outcomes, is urgently needed and widely supported.

Reference values for diaphragm electrical activity (Edi) in newborn infants.

BACKGROUND: Neurally adjusted ventilatory assist is an emerging mode of respiratory support that uses the electrical activity of the diaphragm (Edi) to provide synchronised inspiratory pressure support, proportional to an infant's changing inspiratory effort. Data on Edi reference values for neonates are limited. The objective of this study was to establish reference Edi values for preterm and term neonates who are not receiving respiratory support. METHODS: This was a prospective observational study of newborn infants breathing spontaneously in room air. The Edi waveform was monitored by a specialised naso/orogastric feeding tube with embedded electrodes positioned at the level of the diaphragm. Edi minimums and peaks were recorded continuously for 4 h without changes to routine clinical handling. RESULTS: Twenty-four newborn infants (16 preterm [< 37 weeks' gestation]; 8 term) were studied. All infants were breathing comfortably in room air at the time of study. Edi data were successfully captured in all infants. The mean (±SD) Edi minimum was 3.02 (±0.94) µV and the mean Edi peak was 10.13 (±3.50) µV. In preterm infants the mean (±SD) Edi minimum was 3.05 (±0.91) µV and the mean Edi peak was 9.36 (±2.13) µV. In term infants the mean (±SD) Edi minimum was 2.97 (±1.05) µV and the mean Edi peak was 11.66 (±5.14) µV. CONCLUSION: Reference Edi values were established for both preterm and term neonates. These values can be used as a guide when monitoring breathing support and when using diaphragm-triggered modes of respiratory support in newborn infants.

Neurodevelopmental outcomes of preterm infants after randomisation to initial resuscitation with lower (FiO2 <0.3) or higher (FiO2 >0.6) initial oxygen levels. An individual patient meta-analysis.

OBJECTIVE: To determine the effects of lower (≤0.3) versus higher (≥0.6) initial fractional inspired oxygen (FiO2) for resuscitation on death and/or neurodevelopmental impairment (NDI) in infants <32 weeks' gestation. DESIGN: Meta-analysis of individual patient data from three randomised controlled trials. SETTING: Neonatal intensive care units. PATIENTS: 543 children <32 weeks' gestation. INTERVENTION: Randomisation at birth to resuscitation with lower (≤0.3) or higher (≥0.6) initial FiO2. OUTCOME MEASURES: Primary: death and/or NDI at 2 years of age.Secondary: post-hoc non-randomised observational analysis of death/NDI according to 5-minute oxygen saturation (SpO2) below or at/above 80%. RESULTS: By 2 years of age, 46 of 543 (10%) children had died. Of the 497 survivors, 84 (17%) were lost to follow-up. Bayley Scale of Infant Development (third edition) assessments were conducted on 377 children. Initial FiO2 was not associated with difference in death and/or disability (difference (95% CI) -0.2%, -7% to 7%, p=0.96) or with cognitive scores <85 (2%, -5% to 9%, p=0.5). Five-minute SpO2 >80% was associated with decreased disability/death (14%, 7% to 21%) and cognitive scores >85 (10%, 3% to 18%, p=0.01). Multinomial regression analysis noted decreased death with 5-minute SpO2 ≥80% (odds (95% CI) 09.62, 0.98 to 0.96) and gestation (0.52, 0.41 to 0.65), relative to children without death or NDI. CONCLUSION: Initial FiO2 was not associated with difference in risk of disability/death at 2 years in infants <32 weeks' gestation but CIs were wide. Substantial benefit or harm cannot be excluded. Larger randomised studies accounting for patient differences, for example, gestation and gender are urgently needed.

A risk-adjusted and anatomically stratified cohort comparison study of open surgery, endovascular techniques and medical management for juxtarenal aortic aneurysms-the UK COMPlex AneurySm Study (UK-COMPASS): a study protocol.

INTRODUCTION: In one-third of all abdominal aortic aneurysms (AAAs), the aneurysm neck is short (juxtarenal) or shows other adverse anatomical features rendering operations more complex, hazardous and expensive. Surgical options include open surgical repair and endovascular aneurysm repair (EVAR) techniques including fenestrated EVAR, EVAR with adjuncts (chimneys/endoanchors) and off-label standard EVAR. The aim of the UK COMPlex AneurySm Study (UK-COMPASS) is to answer the research question identified by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme: 'What is the clinical and cost-effectiveness of strategies for the management of juxtarenal AAA, including fenestrated endovascular repair?' METHODS AND ANALYSIS: UK-COMPASS is a cohort study comparing clinical and cost-effectiveness of different strategies used to manage complex AAAs with stratification of physiological fitness and anatomical complexity, with statistical correction for baseline risk and indication biases. There are two data streams. First, a stream of routinely collected data from Hospital Episode Statistics and National Vascular Registry (NVR). Preoperative CT scans of all patients who underwent elective AAA repair in England between 1 November 2017 and 31 October 2019 are subjected to Corelab analysis to accurately identify and include every complex aneurysm treated. Second, a site-reported data stream regarding quality of life and treatment costs from prospectively recruited patients across England. Site recruitment also includes patients with complex aneurysms larger than 55 mm diameter in whom an operation is deferred (medical management). The primary outcome measure is perioperative all-cause mortality. Follow-up will be to a median of 5 years. ETHICS AND DISSEMINATION: The study has received full regulatory approvals from a Research Ethics Committee, the Confidentiality Advisory Group and the Health Research Authority. Data sharing agreements are in place with National Health Service Digital and the NVR. Dissemination will be via NIHR HTA reporting, peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: ISRCTN85731188.

Outcomes of delivery room resuscitation of bradycardic preterm infants: A retrospective cohort study of randomised trials of high vs low initial oxygen concentration and an individual patient data analysis.

OBJECTIVE: To determine whether hospital mortality (primary outcome) is associated with duration of bradycardia without chest compressions during delivery room (DR) resuscitation in a retrospective cohort study of randomized controlled trials (RCTs) in preterm infants assigned low versus high initial oxygen concentration. METHODS: Medline and EMBASE were searched from 01/01/1990 to 12/01/2020. RCTs of low vs high initial oxygen concentration which recorded serial heart rate (HR) and oxygen saturation (SpO2) during resuscitation of infants <32 weeks gestational age were eligible. Individual patient level data were requested from the authors. Newborns receiving chest compressions in the DR and those with no recorded HR in the first 2 min after birth were excluded. Prolonged bradycardia (PB) was defined as HR < 100 bpm for ≥2 min. Individual patient data analysis and pooled data analysis were conducted. RESULTS: Data were collected from 720 infants in 8 RCTs. Neonates with PB had higher odds of hospital death before [OR 3.8 (95% CI 1.5, 9.3)] and after [OR 1.7 (1.2, 2.5)] adjusting for potential confounders. Bradycardia occurred in 58% infants, while 38% had PB. Infants with bradycardia were more premature and had lower birth weights. The incidence of bradycardia in infants resuscitated with low (≤30%) and high (≥60%) oxygen was similar. Neonates with both, PB and SpO2 < 80% at 5 min after birth had higher odds of hospital mortality. [OR 18.6 (4.3, 79.7)]. CONCLUSION: In preterm infants who did not receive chest compressions in the DR, prolonged bradycardia is associated with hospital mortality.

Early PARacetamol (EPAR) Trial: A Randomized Controlled Trial of Early Paracetamol to Promote Closure of the Ductus Arteriosus in Preterm Infants.

INTRODUCTION: This study aimed to investigate whether early treatment with paracetamol reduces the number of infants requiring intervention for patent ductus arteriosus (PDA) and assess the safety profile of paracetamol during the early postnatal period. METHODS: This was a double-blind, parallel, randomized, placebo-controlled trial. Preterm infants born at <29-week gestation with a ductus arteriosus >0.9 mm at 6 h of life were randomized to either (1) intravenous paracetamol (15 mg/kg initially and then 7.5 mg/kg every 6 h) or (2) intravenous dextrose for 5 days. The primary outcome was the need for any intervention for PDA up to 5 days. Secondary outcomes included ductal closure at 5 days, ductal size at 48 h, ductal reopening, mortality, and significant morbidities. RESULTS: Of 58 infants randomized, 29 were allocated to the intervention and 29 to the control group. The trial was stopped for benefit at 50% recruitment after reaching the prespecified stopping criteria. Less infants in the intervention group required intervention for PDA up to 5 days (6 [21%] vs. 17 [59%] infants [p = 0.003]; relative risk reduction 0.35 [95% CI 0.16-0.77; NNT 2.6]). The intervention group had a higher rate of ductal closure (20 [69%] vs. 8 [28%] infants [p = 0.002]) and smaller ductal size (1.0 mm [±0.8] vs. 1.4 mm [±0.9]; p = 0.04). Three deaths occurred (2 in the intervention group), which were not attributed to the intervention. No other adverse events were reported. DISCUSSION/CONCLUSION: Early paracetamol treatment reduced the number of infants requiring intervention for PDA. Short-term safety data were reassuring, acknowledging the small number of infants involved in the study.

Diaphragm-triggered non-invasive respiratory support in preterm infants.

BACKGROUND: Diaphragm-triggered non-invasive respiratory support, commonly referred to as NIV-NAVA (non-invasive neurally adjusted ventilatory assist), uses the electrical activity of the crural diaphragm to trigger the start and end of a breath. It provides variable inspiratory pressure that is proportional to an infant's changing inspiratory effort. NIV-NAVA has the potential to provide effective, non-invasive, synchronised, multilevel support and may reduce the need for invasive ventilation; however, its effects on short- and long-term outcomes, especially in the preterm infant, are unclear. OBJECTIVES: To assess the effectiveness and safety of diaphragm-triggered non-invasive respiratory support in preterm infants (< 37 weeks' gestation) when compared to other non-invasive modes of respiratory support (nasal intermittent positive pressure ventilation (NIPPV); nasal continuous positive airway pressure (nCPAP); high-flow nasal cannulae (HFNC)), and to assess preterm infants with birth weight less than 1000 grams or less than 28 weeks' corrected gestation at the time of intervention as a sub-group. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 5), MEDLINE via PubMed (1946 to 10 May 2019), Embase (1947 to 10 May 2019), and CINAHL (1982 to 10 May 2019). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compared diaphragm-triggered non-invasive versus other non-invasive respiratory support in preterm infants. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trial quality and extracted data from included studies. We performed fixed-effect analyses and expressed treatment effects as mean difference (MD), risk ratio (RR), and risk difference (RD) with 95% confidence intervals (CIs). We used the generic inverse variance method to analyse specific outcomes for cross-over trials. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: There were two small randomised controlled trials including a total of 23 infants eligible for inclusion in the review. Only one trial involving 16 infants included in the analysis reported on either of the primary outcomes of the review. This found no difference in failure of modality between NIV-NAVA and NIPPV (RR 0.33, 95% CI 0.02 to 7.14; RD -0.13, 95% CI -0.41 to 0.16; 1 study, 16 infants; heterogeneity not applicable). Both trials reported on secondary outcomes of the review, specific for cross-over trials (total 22 infants; 1 excluded due to failure of initial modality). One study involving seven infants reported a significant reduction in maximum FiO2 with NIV-NAVA compared to NIPPV (MD -4.29, 95% CI -5.47 to -3.11; heterogeneity not applicable). There was no difference in maximum electric activity of the diaphragm (Edi) signal between modalities (MD -1.75, 95% CI -3.75 to 0.26; I² = 0%) and a significant increase in respiratory rate with NIV-NAVA compared to NIPPV (MD 7.22, 95% CI 0.21 to 14.22; I² = 72%) on a meta-analysis of two studies involving a total of 22 infants. The included studies did not report on other outcomes of interest. AUTHORS' CONCLUSIONS: Due to limited data and very low certainty evidence, we were unable to determine if diaphragm-triggered non-invasive respiratory support is effective or safe in preventing respiratory failure in preterm infants. Large, adequately powered randomised controlled trials are needed to determine if diaphragm-triggered non-invasive respiratory support in preterm infants is effective or safe.

Early PARacetamol (EPAR) trial: a study protocol for a randomised controlled trial of early paracetamol to promote closure of the ductus arteriosus in preterm infants.

INTRODUCTION: The optimal management of patent ductus arteriosus (PDA) remains contentious. The medications used to treat PDA are often non-steroidal anti-inflammatory drugs, which are associated with a number of unwanted adverse effects. Paracetamol is a medication with an excellent safety profile in infants and has been suggested as a safe alternative medication in situations where other medications have failed or are contraindicated. There are limited data on the use of early, intravenous paracetamol in preterm infants. METHODS AND ANALYSIS: This trial aims to address whether early treatment with paracetamol will reduce the number of infants requiring intervention for PDA. This is a randomised, double-blind, placebo-controlled trial in preterm infants <29 weeks' gestation. At 6 hours of life, infants with a ductus arteriosus >0.9 mm will be randomised to receive either (1) intravenous paracetamol at a dose of 15 mg/kg initially, followed by every 6 hours at a dose of 7.5 mg/kg for 5 days; or (2) intravenous 5% dextrose every 6 hours for 5 days. The primary outcome is the need for any intervention for management of PDA up to 5 days. Secondary outcomes include closure of the ductus arteriosus at 5 days, size of the ductus arteriosus, ductal reopening, systemic blood flow, mortality and significant morbidities. The target sample size of 100 infants yields >80% power, at the two-sided 5% level significance, to detect a 50% reduction in the need for intervention assuming that approximately 60% of infants in this study would otherwise have required intervention for PDA. ETHICS AND DISSEMINATION: A report on the results of the planned analyses will be prepared. The results of the primary analysis of all end points will be presented at medical conferences and submitted for publication in peer-reviewed journals. Separate manuscripts pertaining to the second aim of the study may be written, and these will also be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12616001517460.

Monogenic causes of chronic kidney disease in adults.

Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology services in Ireland, we conducted whole exome sequencing (WES) in a multi-centre cohort of 114 families including 138 affected individuals with CKD. Affected adults were recruited from 78 families with a positive family history, 16 families with extra-renal features, and 20 families with neither a family history nor extra-renal features. We detected a pathogenic mutation in a known CKD gene in 42 of 114 families (37%). A monogenic cause was identified in 36% of affected families with a positive family history of CKD, 69% of those with extra-renal features, and only 15% of those without a family history or extra-renal features. There was no difference in the rate of genetic diagnosis in individuals with childhood versus adult onset CKD. Among the 42 families in whom a monogenic cause was identified, WES confirmed the clinical diagnosis in 17 (40%), corrected the clinical diagnosis in 9 (22%), and established a diagnosis for the first time in 16 families referred with CKD of unknown etiology (38%). In this multi-centre study of adults with CKD, a molecular genetic diagnosis was established in over one-third of families. In the evolving era of precision medicine, WES may be an important tool to identify the cause of CKD in adults.

Admission temperature and hospital outcomes in extremely preterm infants.

AIM: To evaluate trends in admission temperature and its effect on mortality and short-term morbidities in extremely preterm infants. METHODS: A regional cohort study of infants born at 23-28 weeks' gestation and admitted to the 10 neonatal intensive care units in New South Wales and the Australian Capital Territory between 1994 and 2012. Hypothermia was defined as skin temperature <36°C on admission to the neonatal intensive care unit. The primary outcome was hospital mortality. RESULTS: In total, 6267 infants were included. Mean admission temperatures improved significantly from 35.6°C in 1994 to 36.4°C in 2012 (R < 0.88). The incidence of hypothermia was 29.5 and 13.9% between 1994-2005 and 2006-2012, respectively. In comparison with normothermic infants, hypothermic infants had lower gestational age at birth (26 vs. 27 weeks) and lower birthweight (800 vs. 976 g). In-hospital mortality was higher in hypothermic infants (28.5 vs. 12.9%; odds ratio (OR) 2.69, 95% confidence interval (CI) 2.37-3.06). Severe intraventricular haemorrhage (12.1 vs. 8.5%, OR 1.48, 95% CI 1.25-1.75), necrotising enterocolitis (NEC) (11.0 vs. 7.5%; OR 1.54, 95% CI 1.29-1.83) and severe retinopathy of prematurity (16.5 vs. 8.9%; OR 2.02, 95% CI 1.70-2.39) were significantly higher in hypothermic infants. Multivariate regression analysis showed hypothermia was an independent risk factor for increased mortality (AOR (adjusted odds ratio ) 1.50, 95% CI 1.29-1.74, P < 0.001) and NEC (AOR 1.28, 95% CI 1.05-1.55, P = 0.01). CONCLUSIONS: Admission temperatures improved during the time period. Hypothermia at admission was associated with a significant increase in mortality and NEC.

Preterm Infant Outcomes after Randomization to Initial Resuscitation with FiO2 0.21 or 1.0.

OBJECTIVE: To determine rates of death or neurodevelopmental impairment (NDI) at 2 years corrected age (primary outcome) in children <32 weeks' gestation randomized to initial resuscitation with a fraction of inspired oxygen (FiO2) value of 0.21 or 1.0. STUDY DESIGN: Blinded assessments were conducted at 2-3 years corrected age with the Bayley Scales of Infant and Toddler Development, Third Edition or the Ages and Stages Questionnaire by intention to treat. RESULTS: Of the 290 children enrolled, 40 could not be contacted and 10 failed to attend appointments. Among the 240 children for whom outcomes at age 2 years were available, 1 child had a lethal congenital anomaly, 1 child had consent for follow-up withdrawn, and 23 children died. The primary outcome, which was available in 238 (82%) of those randomized, occurred in 47 of the 117 (40%) children assigned to initial FiO2 0.21 and in 38 of the 121 (31%) assigned to initial FiO2 1.0 (OR, 1.47; 95% CI, 0.86-2.5; P = .16). No difference in NDI was found in 215 survivors randomized to FiO2 0.21 vs 1.0 (OR, 1.26; 95% CI, 0.70-2.28; P = .11). In post hoc exploratory analyses in the whole cohort, children with a 5-minute blood oxygen saturation (SpO2) <80% were more likely to die or to have NDI (OR, 1.85; 95% CI, 1.07-3.2; P = .03). CONCLUSIONS: Initial resuscitation of infants <32 weeks' gestation with initial FiO2 0.21 had no significant effect on death or NDI compared with initial FiO2 1.0. Further evaluation of optimum initial FiO2, including SpO2 targeting, in a large randomized controlled trial is needed. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Network Registry ACTRN 12610001059055 and the National Malaysian Research Registry NMRR-07-685-957.

Trends in late-onset sepsis in a neonatal intensive care unit following implementation of infection control bundle: A 15-year audit.

AIM: Late-onset sepsis (LOS) is a frequent and important cause of morbidity and mortality in newborn infants admitted to neonatal intensive care units (NICUs). The objective of this study is to evaluate the impact of various infection control quality measures introduced as a bundle on the trends of the LOS in a NICU. METHODS: This was a prospective quality improvement study involving all neonates admitted to a NICU over a 15-year period between 2002 and 2016. The main focus areas of the bundle included collaborative team effort, hand hygiene, education, central line insertion and maintenance bundles and parenteral nutrition. The main outcome measures were LOS and central line-associated bloodstream infections. RESULTS: Yearly admissions increased during study period, from 776 in 2002 to 952 in 2016. There was a progressive decrease in LOS rate, from 4.3 to 1.6 per 1000 patient days (B coefficient -0.17, 95% confidence interval -0.25, -0.09; P < 0.001), and the central line-associated bloodstream infection rate dropped from 25 in 2003 to 5 in 2016 per 1000 central line days (B coefficient -1.20, 95% confidence interval -1.84, -0.56; P = 0.001). Hand hygiene compliance rates remained consistent, over 80%. During the study period, coagulase-negative staphylococcus caused 56% and Gram-negative organisms 18% of the total infections. CONCLUSION: Multifaceted infection control bundle practices with a concerted team effort in the implementation, with continuing education, feedback and reinforcement of best infection control practices, can sustain the gains achieved by infection control for a long period of time.

What does the world think of ankyloglossia?

AIM: The diagnosis of tongue-tie (or ankyloglossia) has increased more than 10-fold in some countries. Whether this is a global phenomenon or related to cultural and professional differences is uncertain. METHODS: An online survey in English, Japanese, Chinese and Spanish was disseminated between May and November 2016 via 27 international professional bodies to >30 clinical professions chosen a priori to represent occupations involved in the management of neonatal ankyloglossia. RESULTS: A total of 1721 responses came from nursing (51%), medical (40%), dental (6%) and allied health (4%) clinicians. Nurses (40%) and allied health (34%) professionals were more likely than doctors (8%) to consider ankyloglossia as important for lactation problems, as were western (83%) compared to Asian (52%) clinicians. Referrals to clinicians for ankyloglossia management originated mainly from parents (38%). Interprofessional referrals were not clearly defined. Frenectomies were most likely to be performed by surgeons (65%) and dentists (35%), who were also less likely to be involved in lactation support. Clinicians performing frenectomies were more likely to consider analgesia as important compared to those not performing frenectomies. CONCLUSION: The diagnosis and treatment of ankyloglossia vary considerably around the world and between professions. Efforts to standardise management are required.

A Systematic Review of the Patient- and Carer-Related Factors Affecting the Experience of Pain for Advanced Cancer Patients Cared for at Home.

CONTEXT: Effective pain management is a priority in the palliative care of advanced cancer patients. A body of research is emerging examining the factors that influence the management and experience of pain for such individuals. Identifying such factors should allow for the development of targeted interventions to improve pain management in the home while ultimately reducing unnecessary suffering for the patient. OBJECTIVES: The objective of this study was to identify relevant patient- and carer-related factors which have an effect on the pain experienced by advanced cancer patients cared for at home. METHOD: This is a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) statement guidelines. Studies were retrieved from the CINAHL, MEDLINE, and Web of Science and assessed independently by two reviewers with discrepancies assessed by a third before quality assessment and data extraction. A narrative synthesis was produced. RESULTS: Our search strategy produced 720 hits, of which 10 studies were retained for the final analysis. The factors identified included carer knowledge of cancer pain management, carer burden, carer and patient distress, pain rating disparity, patient well-being, patient depression, patient affective experience, patient body image, and satisfaction with palliative/medical care. All factors identified are supported by only some evidence with many having only been explored in single studies. CONCLUSIONS: There is a lack of quantitative research in the area of factors influencing the experience of pain for advanced cancer patients cared for at home. Such findings would be useful in developing theories of change that would underpin interventions aimed at improving pain outcomes for this population.

Outcomes of oxygen saturation targeting during delivery room stabilisation of preterm infants.

OBJECTIVE: To determine the association between SpO2 at 5 min and preterm infant outcomes. DESIGN: Data from 768 infants <32 weeks gestation from 8 randomised controlled trials (RCTs) of lower (≤0.3) versus higher (≥0.6) initial inspiratory fractions of oxygen (FiO2) for resuscitation, were examined. SETTING: Individual patient analysis of 8 RCTs INTERVENTIONS: Lower (≤0.3) versus higher (≥0.6) oxygen resuscitation strategies targeted to specific predefined SpO2 before 10 min of age. PATIENTS: Infants <32 weeks gestation. MAIN OUTCOME MEASURES: Relationship between SpO2 at 5 min, death and intraventricular haemorrhage (IVH) >grade 3. RESULTS: 5 min SpO2 data were obtained from 706 (92%) infants. Only 159 (23%) infants met SpO2 study targets and 323 (46%) did not reach SpO280%. Pooled data showed decreased likelihood of reaching SpO280% if resuscitation was initiated with FiO2 <0.3 (OR 2.63, 95% CI 1.21 to 5.74, p<0.05). SpO2 <80% was associated with lower heart rates (mean difference -8.37, 95% CI -15.73 to -1.01, *p<0.05) and after accounting for confounders, with IVH (OR 2.04, 95% CI 1.01 to 4.11, p<0.05). Bradycardia (heart rate <100 bpm) at 5 min increased risk of death (OR 4.57, 95% CI 1.62 to 13.98, p<0.05). Taking into account confounders including gestation, birth weight and 5 min bradycardia, risk of death was significantly increased with time taken to reach SpO280%. CONCLUSION: Not reaching SpO280% at 5 min is associated with adverse outcomes, including IVH. Whether this is because of infant illness or the amount of oxygen that is administered during stabilisation is uncertain and needs to be examined in randomised trials.

Applying Computer Models to Realize Closed-Loop Neonatal Oxygen Therapy.

BACKGROUND: Within the context of automating neonatal oxygen therapy, this article describes the transformation of an idea verified by a computer model into a device actuated by a computer model. Computer modeling of an entire neonatal oxygen therapy system can facilitate the development of closed-loop control algorithms by providing a verification platform and speeding up algorithm development. METHODS: In this article, we present a method of mathematically modeling the system's components: the oxygen transport within the patient, the oxygen blender, the controller, and the pulse oximeter. Furthermore, within the constraints of engineering a product, an idealized model of the neonatal oxygen transport component may be integrated effectively into the control algorithm of a device, referred to as the adaptive model. Manual and closed-loop oxygen therapy performance were defined in this article by 3 criteria in the following order of importance: percent duration of SpO2 spent in normoxemia (target SpO2 ± 2.5%), hypoxemia (less than normoxemia), and hyperoxemia (more than normoxemia); number of 60-second periods <85% SpO2 and >95% SpO2; and number of manual adjustments. RESULTS: Results from a clinical evaluation that compared the performance of 3 closed-loop control algorithms (state machine, proportional-integral-differential, and adaptive model) with manual oxygen therapy on 7 low-birth-weight ventilated preterm babies, are presented. Compared with manual therapy, all closed-loop control algorithms significantly increased the patients' duration in normoxemia and reduced hyperoxemia (P < 0.05). The number of manual adjustments was also significantly reduced by all of the closed-loop control algorithms (P < 0.05). CONCLUSIONS: Although the performance of the 3 control algorithms was equivalent, it is suggested that the adaptive model, with its ease of use, may have the best utility.

Targeted Oxygen in the Resuscitation of Preterm Infants, a Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Lower concentrations of oxygen (O2) (≤30%) are recommended for preterm resuscitation to avoid oxidative injury and cerebral ischemia. Effects on long-term outcomes are uncertain. We aimed to determine the effects of using room air (RA) or 100% O2 on the combined risk of death and disability at 2 years in infants <32 weeks' gestation. METHODS: A randomized, unmasked study designed to determine major disability and death at 2 years in infants <32 weeks' gestation after delivery room resuscitation was initiated with either RA or 100% O2 and which were adjusted to target pulse oximetry of 65% to 95% at 5 minutes and 85% to 95% until NICU admission. RESULTS: Of 6291 eligible patients, 292 were recruited and 287 (mean gestation: 28.9 weeks) were included in the analysis (RA: n = 144; 100% O2: n = 143). Recruitment ceased in June 2014, per the recommendations of the Data and Safety Monitoring Committee owing to loss of equipoise for the use of 100% O2. In non-prespecified analyses, infants <28 weeks who received RA resuscitation had higher hospital mortality (RA: 10 of 46 [22%]; than those given 100% O2: 3 of 54 [6%]; risk ratio: 3.9 [95% confidence interval: 1.1-13.4]; P = .01). Respiratory failure was the most common cause of death (n = 13). CONCLUSIONS: Using RA to initiate resuscitation was associated with an increased risk of death in infants <28 weeks' gestation. This study was not a prespecified analysis, and it was underpowered to address this post hoc hypothesis reliably. Additional data are needed.

Clinicians in 25 countries prefer to use lower levels of oxygen to resuscitate preterm infants at birth.

AIM: This study determined current international clinical practice and opinions regarding initial fractional inspired oxygen (FiO2 ) and pulse oximetry (SpO2 ) targets for delivery room resuscitation of preterm infants of less than 29 weeks of gestation. METHODS: An online survey was disseminated to neonatal clinicians via established professional clinical networks using a web-based survey programme between March 9 and June 30, 2015. RESULTS: Of the 630 responses from 25 countries, 60% were from neonatologists. The majority (77%) would target SpO2 between the 10th to 50th percentiles values for full-term infants. The median starting FiO2 was 0.3, with Japan using the highest (0.4) and the UK using the lowest (0.21). New Zealand targeted the highest SpO2 percentiles (median 50%). Most respondents agreed or did not disagree that a trial was required that compared the higher FiO2 of 0.6 (83%), targeting the 50th SpO2 percentile (60%), and the lower FiO2 of 0.21 (80%), targeting the 10th SpO2 percentile (78%). Most (65%) would join this trial. Many considered that evidence was lacking and further research was needed. CONCLUSION: Clinicians currently favour lower SpO2 targets for preterm resuscitation, despite acknowledging the lack of evidence for benefit or harm, and 65% would join a clinical trial.