Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).

BACKGROUND: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. METHODS: In this study, 382 infants born at 24+0-27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). DISCUSSION: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Pre-pregnancy weight loss in women with obesity requesting removal of their intra-uterine contraceptive device in order to conceive: a pilot study of full meal replacement.

Obesity during pregnancy is associated with increased risks of thromboembolism, gestational diabetes, pre-eclampsia, miscarriage, congenital anomaly, macrosomia and stillbirth. The current practice, directed at reducing gestational weight gain, is largely ineffective. The present pilot study was designed to assess the acceptability of a 24-week intensive weight management programme (IWMP; full meal replacement followed by partial meal replacement and weight stabilization) to achieve weight loss for women with obesity requesting removal of their intra-uterine contraceptive device in order to conceive. Twenty six (65%) of eligible participants consented to the IWMP; three received this as routine National Health Service care in the University College Hospital clinic and 14 participated in the study. The commonest reasons for not participating were dislike of milk, anxiety and lack of support from family and friends. Omitting one woman who dropped out because of problems unrelated to the intervention, the completion rate was 46.2%. Including all women who started the programme, mean body mass index decreased significantly (P = 0.005) from 37.8 to 35.3 kg/m2 . The median percentage decrease was significantly (P = 0.007) greater for women who completed the study (14.2) compared to those who dropped out (1.2). These results suggest an impressive level of weight loss in about one third of all women offered the IWMP who had to defer what they were seeking (pregnancy) while following a challenging programme that they were not seeking. However, studies of other interventions, such as partial meal replacement or commercial products, which may have higher rates of completion are still required.

Early prediction of a significant patent ductus arteriosus in infants <32 weeks gestational age.

BACKGROUND: The optimal thresholds for identification of preterm infants at greatest risk for adverse sequelae related to patent ductus arteriosus have not been well delineated. Our aim was to determine hemodynamic parameters in the first 24 hours using continuous non-invasive vital and structural measurements to predict which infants required PDA treatment in our institution. METHODS: Retrospective secondary analysis of data from infants born 23 to 32 weeks gestational age with cardiac output and stroke volume via electrical cardiometry, cerebral tissue oximetry measurements, mean arterial blood pressure (BP), heart rate, and oxygen saturation and functional echocardiography results at 12 hours of life were recorded when available (93 percent of subjects). RESULTS: A total of 292 infants, of which 55 (26±2 weeks, 862±268 grams) were treated for PDA. Treated infants demonstrated increased left ventricular output (p < 0.001) and lower mean BP (p = 0.010). The optimal area under the receiver operating characteristic curve (AUC) for predicting PDA treatment in our all gestations cohort is a mean BP at 15 hours of life of <33 mm Hg (AUC = 0.854, p < 0.001, 95% CI 0.792, 0.916). For infants <28 weeks a mean BP at 13 hours of life of <33 mm Hg (AUC = 0.741, p < 0.050, 95% CI 0.642, 0.839). CONCLUSIONS: In our cohort increased left ventricular output and lower mean BP predicted a clinically significant PDA requiring treatment.

A review of international clinical practice guidelines for the use of oxygen in the delivery room resuscitation of preterm infants.

AIM: To collate and assess international clinical practice guidelines (CPG) to determine current recommendations guiding oxygen management for respiratory stabilisation of preterm infants at delivery. METHODS: A search of public databases using the terms 'clinical practice guidelines', 'preterm', 'oxygen' and 'resuscitation' was made and complemented by direct query to consensus groups, resuscitation expert committees and clinicians. Data were extracted to include the three criteria for assessment: country of origin, gestation and initial FiO2 and target SpO2 for the first 10 minutes of life. RESULTS: A total of 45 CPGs were identified: 36 provided gestation specific recommendations (<28 to <37 weeks) while eight distinguished only between 'preterm' and 'term'. The most frequently recommended initial FiO2 were between 0.21 and 0.3 (n = 17). Most countries suggested altering FiO2 to meet SpO2 targets recommended by expert committees, However, specific five-minute SpO2 targets differed by up to 20% (70-90%) between guidelines. Five countries did not specify SpO2 targets. CONCLUSION: CPG recommendations for delivery room oxygen management of preterm infants vary greatly, particularly in regard to gestational ages, initial FiO2 and SpO2 targets and most acknowledge the lack of evidence behind these recommendations. Sufficiently large and well-designed randomised studies are needed to inform on this important practice.

Type 2 diabetes remission 2 years post Roux-en-Y gastric bypass and sleeve gastrectomy: the role of the weight loss and comparison of DiaRem and DiaBetter scores.

AIMS: The comparative efficacy of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy on Type 2 diabetes remission and the role of weight loss are unclear. The DiaRem diabetes remission prediction score uses HbA1c , age and diabetes medications but not diabetes duration. The aim of this study was to compare the DiaRem with the DiaBetter score that includes diabetes duration, upon combined (complete plus partial) 2-year post-surgery diabetes remission in people following RYGB and sleeve gastrectomy, and to investigate the relationship between weight loss and diabetes remission. METHODS: A retrospective single-centre cohort study of obese people with diabetes who underwent RYGB (107) or sleeve gastrectomy (103) and a validation cohort study (173) were undertaken. Diabetes remission, % weight loss, DiaRem, DiaBetter scores and areas under receiving operator characteristic (ROC) curves were calculated. The relationship between % weight loss and diabetes remission was investigated using logistic regression. RESULTS: The proportion of people achieving diabetes remission was highest for those with the lowest DiaBetter and DiaRem scores. Areas under the ROC curves were comparable [DiaBetter: 0.867 (95%CI: 0.817-0.916); DiaRem: 0.865 (95%CI: 0.814-0.915), P=0.856]. Two-year % weight loss was higher post RYGB [26.6 (95%CI: 24.8-28.4)] vs post-sleeve gastrectomy [20.6 (95%CI: 18.3-22.8), P<0.001]. RYGB had 151% higher odds of diabetes remission [OR 2.51 (95%CI: 1.12-5.60), P=0.025]. This association became non-significant when adjusted for % weight loss. CONCLUSION: DiaBetter and DiaRem scores predict diabetes remission following both procedures. Two-year % weight loss plays a key role in determining diabetes remission.

Commissioning guidance for weight assessment and management in adults and children with severe complex obesity.

The challenge of managing the epidemic of patients with severe and complex obesity disease in secondary care is largely unmet. In England, the National Institute of Health and Care Excellence and the National Health Service England have published guidance on the provision of specialist (non-surgical) weight management services. We have undertaken a systematic review of 'what evidence exists for what should happen in/commissioning of: primary or secondary care weight assessment and management clinics in patients needing specialist care for severe and complex obesity?' using an accredited methodology to produce a model for organization of multidisciplinary team clinics that could be developed in every healthcare system, as an update to a previous review. Additions to the previous guidance were multidisciplinary team pathways for children/adolescent patients and their transition to adult care, anaesthetic assessment and recommendations for ongoing shared care with general practitioners, as a chronic disease management pathway.

Effects of delivery room quality improvement on premature infant outcomes.

OBJECTIVE: Delivery room management interventions have been successfully implemented via collaborative quality improvement (QI) projects. However, it is unknown whether these successes translate to reductions in neonatal morbidity and mortality. STUDY DESIGN: This was a prospective pre-post intervention study of three nonrandomized hospital groups within the California Perinatal Quality Care Collaborative. A collaborative QI model (Collaborative QI) was compared with a single-site QI model (NICU QI) and a non-participant population when implementing evidence-based delivery room practices. The intervention period was between June 2011 and May 2012. Infants born with gestational age between 22 weeks 0 days and 29 weeks 6 days and birth weight ⩽1500 g were included. Outcomes were mortality and select morbidities (bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP) and necrotizing enterocolitis (NEC)). Outcomes were compared between the baseline (January 2010 to May 2011) and post-intervention period (June 2012 to May 2013) within each comparison group. RESULTS: Ninety-five hospitals were included with 4222 infants in the baseline period and 4186 infants in the post-intervention period. The Collaborative QI group had significantly reduced odds of developing BPD post-intervention (odds ratio (OR) 0.8, 95% confidence interval (CI) 0.65 to 0.99) or composite BPD-death (OR 0.83, 95% CI 0.69 to 1.00). In both the Collaborative QI and non-participants there were also reductions in IVH, severe IVH, composite severe IVH-death, severe ROP and composite severe ROP-death. CONCLUSION: Hospitals dedicated to improving delivery room practices can impact neonatal outcomes.

Interventions that cause weight loss and the impact on cardiovascular risk factors: a systematic review and meta-analysis.

Overweight and obesity increase the risks of diabetes and cardiovascular disease (CVD). This has been shown to be reversed with weight loss. A systematic review and meta-analysis were performed to determine the effect of weight loss in the primary prevention of CVD. PubMed, Embase and the Cochrane Library databases were searched electronically through to May 2013. Randomized controlled trials assessing weight loss and cardiovascular risk factors and outcomes were included. A random effects meta-analysis, with sub-group analyses for degree of weight loss, and age were performed. Because few studies reported clinical outcomes of CVD, analyses were limited to cardiovascular risk factors (83 studies). Interventions that caused any weight loss significantly reduced systolic blood pressure (-2.68 mmHg, 95% CI -3.37, -2.11), diastolic blood pressure (-1.34 mmHg, 95% CI -1.71, -0.97), low-density lipoprotein cholesterol (-0.20 mmol L(-1) , 95% CI -0.29, -0.10), triglycerides (-0.13 mmol L(-1) , 95% CI -0.22, -0.03), fasting plasma glucose (-0.32 mmol L(-1) , 95% CI -0.43, -0.22) and haemoglobin A1c(-0.40%, 95% CI -0.52, -0.28) over 6-12 months. Significant changes remained after 2 years for several risk factors. Similar results were seen in sub-group analyses. Interventions that cause weight loss are effective at improving cardiovascular risk factors at least for 2 years. © 2016 World Obesity.

Novel insights into maladaptive behaviours in Prader-Willi syndrome: serendipitous findings from an open trial of vagus nerve stimulation.

BACKGROUND: We report striking and unanticipated improvements in maladaptive behaviours in Prader-Willi syndrome (PWS) during a trial of vagus nerve stimulation (VNS) initially designed to investigate effects on the overeating behaviour. PWS is a genetically determined neurodevelopmental disorder associated with mild-moderate intellectual disability (ID) and social and behavioural difficulties, alongside a characteristic and severe hyperphagia. METHODS: Three individuals with PWS underwent surgery to implant the VNS device. VNS was switched on 3 months post-implantation, with an initial 0.25 mA output current incrementally increased to a maximum of 1.5 mA as tolerated by each individual. Participants were followed up monthly. RESULTS: Vagal nerve stimulation in these individuals with PWS, within the stimulation parameters used here, was safe and acceptable. However, changes in eating behaviour were equivocal. Intriguingly, unanticipated, although consistent, beneficial effects were reported by two participants and their carers in maladaptive behaviour, temperament and social functioning. These improvements and associated effects on food-seeking behaviour, but not weight, indicate that VNS may have potential as a novel treatment for such behaviours. CONCLUSIONS: We propose that these changes are mediated through afferent and efferent vagal projections and their effects on specific neural networks and functioning of the autonomic nervous system and provide new insights into the mechanisms that underpin what are serious and common problems affecting people with IDs more generally.

Identification of educational needs in the management of overweight and obesity: results of an international survey of attitudes and practice.

Despite the availability of a growing range of interventions to assist control of body weight for people with excess weight or obesity, only a small proportion of people achieve their weight loss goals and are able to maintain body weight reductions in the long term. Negative attitudes and beliefs are often found among physicians and others involved in treating obesity and may adversely impact the effectiveness of management. In this international study, healthcare professionals were invited to complete an online survey of their attitudes and practice in the management of excess body weight. A total of 335 clinicians completed the survey of whom approximately half were based in Europe. A key finding from the survey is that, while participants are generally confident in their ability to manage overweight and obesity effectively, they also report that most of their patients are not successful in achieving their weight loss goals. At the same time, participants tended to overestimate the effectiveness of current medical management in maintaining reductions in body weight. Educational initiatives addressing the real-life effectiveness of different weight control interventions may help to close the gap between clinicians' perceptions and reality in the management of excess body weight.

Changes in body weight and pulse: outcome events in overweight and obese subjects with cardiovascular disease in the SCOUT trial.

BACKGROUND/OBJECTIVES: The Sibutramine Cardiovascular OUTcomes (SCOUT) trial showed a significantly increased relative risk of nonfatal cardiovascular events, but not mortality, in overweight and obese subjects receiving long-term sibutramine treatment with diet and exercise. We examined the relationship between early changes (both increases and decreases) in pulse rate, and the impact of these changes on subsequent cardiovascular outcome events in both the placebo and sibutramine groups. SUBJECTS/METHODS: 9804 males and females, aged ⩾55 years, with a body mass index of 27-45 kg m(-)(2) were included in this current subanalysis of the SCOUT trial. Subjects were required to have a history of cardiovascular disease and/or type 2 diabetes mellitus with at least one cardiovascular risk factor, to assess cardiovascular outcomes. The primary outcome event (POE) was a composite of nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death. Time-to-event analyses of the POE were performed using Cox regression models. RESULTS: During the initial 6-week sibutramine treatment period, the induced pulse rate increase was related to weight change (1.9±7.7 beats per minute (bpm) with weight increase; 1.4±7.3 bpm, 0-5 kg weight loss; 0.6±7.4 bpm, ⩾5 kg weight loss). Throughout the subsequent treatment period, those continuing on sibutramine showed a consistently higher mean pulse rate than the placebo group. There was no difference in POE rates with either an increase or decrease in pulse rate over the lead-in period, or during lead-in baseline to 12 months post randomization. There was also no relationship between pulse rate at lead-in baseline and subsequent cardiovascular events in subjects with or without a cardiac arrhythmia. CONCLUSION: Baseline pulse rate and changes in pulse rate may not be an important modifier nor a clinically useful predictor of outcome in an individual elderly cardiovascular obese subject exposed to weight management.

The use of electrical cardiometry for continuous cardiac output monitoring in preterm neonates: a validation study.

BACKGROUND: Electrical cardiometry (EC) is a continuous noninvasive method for measuring cardiac output (CO), but there are limited data on premature infants. We evaluated the utility of EC monitoring by comparing the results obtained using EC to measurements of CO and systemic blood flow using echocardiography (ECHO). METHODS: In this prospective observational study, 40 preterm neonates underwent 108-paired EC and ECHO measurements. RESULTS: There were correlations between EC-CO and left ventricular output (LVO, p < 0.005) and right ventricular output (RVO, p < 0.005) but not with superior vena cava (r = 0.093, p = 0.177). Both RVO and LVO correlated with EC with and without a hemodynamically significant ductus arteriosus (p = 0.001 and 0.008, respectively). The level of agreement was decreased in infants ventilated by high-frequency oscillation ventilators (HFOV). The bias in HFOV was also positive compared with the negative biases found in other modes of ventilation. CONCLUSION: Given the correlation of EC with LVO, RVO, and lack of confounding effects of the ductus, our results suggest that EC has promise for trending CO in the preterm infant. However, given the limitations with mode of ventilation and the lack of correlation at low LVO values, further study is needed before this technology can be for routine use.

Impact of premedication on neonatal intubations by pediatric and neonatal trainees.

OBJECTIVE: To determine if premedication and training level affect the success rates of neonatal intubations. STUDY DESIGN: We retrospectively reviewed a hospital-approved neonatal intubation database from 2003 to 2010. Intubation success rate was defined as the number of successful intubations divided by the total number of attempts, and then compared by trainee's experience level and the use of premedication. Premedication regimen included anticholinergic, analgesic and muscle relaxant agents. RESULT: There were 169 trainees who completed 1071 successful intubations with 2694 attempts. The median success rate was 36% by all trainees, and improved with training level from 29% for pediatric trainees to 50% for neonatal trainees (P<0.001). Premedication was used in 58% of intubation attempts. The median success rate was double with premedication (43% versus 22%, P<0.001). CONCLUSION: Neonatal endotracheal intubation is a challenge for trainees. Intubation success rates progressively improve with experience. Premedication is associated with improved success rates for all training levels.

Association between serum bilirubin and cardiovascular disease in an overweight high risk population from the SCOUT trial.

BACKGROUND AND AIMS: An inverse relationship between (serum) total bilirubin and risk of cardiovascular disease has been reported previously, but longitudinal data on overweight and obese patients are lacking. We have investigated the relationship between total bilirubin and cardiovascular adverse events in a large group of patients with risk factors for cardiovascular disease who were enrolled in a large weight loss trial. METHODS AND RESULTS: Data from the Sibutramine Cardiovascular Outcomes (SCOUT) trial, including almost 10.000 overweight/obese high cardiovascular risk patients, were used. The relationship between total bilirubin level at screening and the primary outcome (i.e. non-fatal myocardial infarction, non-fatal stroke, resuscitated cardiac arrest or cardiovascular death) for the entire study period was investigated using Cox proportional hazards models. The population was divided into four groups based on total bilirubin levels (normal range 5-25 µmol/L). Time-dependent Cox analyses were also performed to adjust for weight loss over time. Initial analyses adjusted for sex, age and treatment allocation showed significantly reduced hazard ratios of 0.80 (95% confidence interval 0.68-0.94), 0.73 (0.62-0.86) and 0.77 (0.65-0.91), for the three higher total bilirubin groups: >8 and ≤10 µmol/L, >10 and ≤13 µmol/L and >13 µmol/L (5-95 interpercentile range for total bilirubin at screening; 6-19 µmol/L), compared to the lowest total bilirubin group ≤8 µmol/L. When adjusting for classical cardiovascular risk factors, estimates increased towards unity. Additional adjustment for indicators of liver function did not alter the results. A time-dependent Cox model, adjusted for weight loss, demonstrated a similar trend. CONCLUSION: Bilirubin was not a risk-factor independent from other traditional cardiovascular risk-factors in our population.

Evaluating retinopathy of prematurity screening guidelines for 24- to 27-week gestational age infants.

OBJECTIVE: To determine whether current retinopathy of prematurity (ROP) screening guidelines adequately identify treatable ROP in a contemporary cohort of extremely low gestation infants. STUDY DESIGN: Data from the Surfactant, Positive Pressure, and Pulse Oximetry Randomized Trial were used. Inborn infants of 24 (0)/7 to 27 (6)/7 weeks gestational age (GA) with consent before delivery were enrolled in 2005 to 2009. Severe ROP (type 1 ROP or treatment with laser, cryotherapy or bevacizumab) or death was the primary outcome for the randomized trial. Examinations followed the then current AAP (American Academy of Pediatrics) screening recommendations, beginning by 31 to 33 weeks postmenstrual age (PMA). RESULT: One thousand three hundred and sixteen infants were enrolled in the trial. Nine hundred and ninety-seven of the 1121 who survived to first eye exam had final ROP outcome determined. One hundred and thirty-seven (14% of 997) met criteria for severe ROP and 128 (93%) of those had sufficient data (without missing or delayed exams) to determine age of onset of severe ROP. PMA at onset was 32.1 to 53.1 weeks. In this referral center cohort, 1.4% (14/997) developed severe ROP after discharge. CONCLUSION: Our contemporary data support the 2013 AAP screening guidelines for ROP for infants of 24 (0)/7 to 27 (6)/7 weeks GA. Some infants do not meet treatment criteria until after discharge home. Post-discharge follow-up of infants who are still at risk for severe ROP is crucial for timely detection and treatment.

Changes in body weight and blood pressure: paradoxical outcome events in overweight and obese subjects with cardiovascular disease.

BACKGROUND/OBJECTIVES: The Sibutramine Cardiovascular OUTcomes (SCOUT) trial showed a significantly increased relative risk of nonfatal cardiovascular events, but not mortality, in overweight and obese subjects receiving long-term sibutramine treatment with diet and exercise. We examined the relationship between early changes (both increases and decreases) in body weight and blood pressure, and the impact of these changes on subsequent cardiovascular outcome events. SUBJECTS/METHODS: A total of 9804 male and female subjects, aged 55 years or older, with a body mass index of 27-45 kg m(-2) were included in this current subanalysis of the SCOUT trial. Subjects were required to have a history of cardiovascular disease and/or type 2 diabetes mellitus with at least one cardiovascular risk factor (hypertension, dyslipidemia, current smoking or diabetic nephropathy) to assess cardiovascular outcomes. Post hoc subgroup analyses of weight change (categories) and blood pressure were performed overall and by treatment group (6-week sibutramine followed by randomized placebo or continued sibutramine). The primary outcome event (POE) was a composite of nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death. Time-to-event analyses of the POE were performed using Cox regression models with factors for treatment, subgroups and interactions. RESULTS: During the initial 6-week sibutramine treatment period, systolic blood pressure decreased progressively with increasing weight loss in hypertensive subjects (-8.1±10.5 mm Hg with <5 kg weight loss to -10.8±11.0 mm Hg with ⩾5 kg weight loss). The highest POE incidence occurred mainly in groups with increases in both weight and blood pressure. However, with long-term sibutramine treatment, a markedly lower blood pressure tended to increase POEs. CONCLUSION: Modest weight loss and modest lower blood pressure each reduced the incidence of cardiovascular events, as expected. However, the combination of early marked weight loss and rapid blood pressure reduction seems to be harmful in this obese elderly cardiovascular diseased population.