Annual league tables of mortality in neonatal intensive care units: longitudinal study. International Neonatal Network and the Scottish Neonatal Consultants and Nurses Collaborative Study Group.[see comment]

OBJECTIVE: To assess whether crude league tables of mortality and league tables of risk adjusted mortality accurately reflect the performance of hospitals. DESIGN: Longitudinal study of mortality occurring in hospital. SETTING: 9 neonatal intensive care units in the United Kingdom. SUBJECTS: 2671 very low birth weight or preterm infants admitted to neonatal intensive care units between 1988 and 1994. MAIN OUTCOME MEASURES: Crude hospital mortality and hospital mortality adjusted using the clinical risk index for babies (CRIB) score. RESULTS: Hospitals had wide and overlapping confidence intervals when ranked by mortality in annual league tables; this made it impossible to discriminate between hospitals reliably. In most years there was no significant difference between hospitals, only random variation. The apparent performance of individual hospitals fluctuated substantially from year to year. CONCLUSIONS: Annual league tables are not reliable indicators of performance or best practice; they do not reflect consistent differences between hospitals. Any action prompted by the annual league tables would have been equally likely to have been beneficial, detrimental, or irrelevant. Mortality should be compared between groups of hospitals using specific criteria-such as differences in the volume of patients, staffing policy, training of staff, or aspects of clinical practice-after adjusting for risk. This will produce more reliable estimates with narrower confidence intervals, and more reliable and rapid conclusions

Inspired Gas Temperature in Ventilated Neonates

The warming and humidification of inspired gases for ventilated neonates are routine. There are no data on the temperature of the gas at the airway opening in ventilated neonates. Is the inspired gas temperature at the airway opening, as expected and set on the humidifier, around 37 degrees C? We aimed to measure temperature at the airway opening and compare this with the circuit temperature. This was an observational study in a neonatal intensive care unit. Twenty-five mechanically ventilated infants were studied. All had humidifiers with chamber temperature set at 36 degrees C and the circuit temperature set at 37 degrees C. Two temperature probes were inserted and rested at the circuit-exit and at the airway opening, and temperatures were measured for 2 min in each infant. At this time, the circuit temperature was also noted. The mean (SD) temperature at the airway opening in infants nursed in incubators was 34.9 (1.2) degrees C, compared with radiant warmers where the mean (SD) was 33.1 (0.5) degrees C. The mean (SD) difference in temperature from the circuit temperature probe to the airway opening was greater under radiant warmers, with a mean (SD) drop of 3.9 (0.6) degrees C compared with a mean (SD) drop of 2.0 (1.3) degrees C in the incubators. In conclusion, the temperature at the circuit temperature probe does not reflect the temperature at the airway opening. Inspired gas temperatures are lower than the expected 37 degrees C with the normal circuits and usual humidifier settings

The INIS Study. International Neonatal Immunotherapy Study: Non-specific intravenous immunoglobulin therapy for suspected or proven neonatal sepsis: An international, placebo controlled, multicentre randomised trial

Background: Sepsis is an important cause of neonatal death and perinatal brain damage, particularly in preterm infants. While effective antibiotic treatment is essential treatment for sepsis, resistance to antibiotics is increasing. Adjuvant therapies, such as intravenous immunoglobulin, therefore offer an important additional strategy. Three Cochrane systematic reviews of randomised controlled trials in nearly 6,000 patients suggest that non-specific, polyclonal intravenous immunoglobulin is safe and reduces sepsis by about 15% when used as prophylaxis but does not reduce mortality in this situation. When intravenous immunoglobulin is used in the acute treatment of neonatal sepsis, however, there is a suggestion that it may reduce mortality by 45%. However, the existing trials of treatment were small and lacked long-term follow-up data. This study will assess reliably whether treatment of neonatal sepsis with intravenous immunoglobulin reduces mortality and adverse neuro-developmental outcome. Methods and design: A randomised, placebo controlled, double blind trial. Babies with suspected or proven neonatal sepsis will be randomised to receive intravenous immunoglobulin therapy or placebo. Eligibility criteria - Babies must be receiving antibiotics and have proven or suspected serious infection AND have at least one of the following: birthweight less than 1500 g OR evidence of infection in blood culture, cerebrospinal fluid or usually sterile body fluid OR be receiving respiratory support via an endotracheal tube AND there is substantial uncertainty that intravenous immunoglobulin is indicated. Exclusion criteria - Babies are excluded if intravenous immunoglobulin has already been given OR intravenous immunoglobulin is thought to be needed OR contra-indicated. Trial treatment - Babies will be given either 10 ml/kg of intravenous immunoglobulin or identical placebo solution over 4–6 hours, repeated 48 hours later. Primary outcome - Mortality or major disability at two years, corrected for gestational age. Data collection - Data will be collected at discharge from hospital and at 2 years of age (corrected for gestation) using a parental questionnaire and a health status questionnaire completed during a face-to-face follow-up appointment with the child's paediatrician. Trial registration: Current Controlled Trials ISCRTN94984750

Systematic review and network meta-analysis with individual participant data on cord management at preterm birth (iCOMP): study protocol

Introduction Timing of cord clamping and other cord management strategies may improve outcomes at preterm birth. However, it is unclear whether benefits apply to all preterm subgroups. Previous and current trials compare various policies, including time-based or physiology-based deferred cord clamping, and cord milking. Individual participant data (IPD) enable exploration of different strategies within subgroups. Network meta-analysis (NMA) enables comparison and ranking of all available interventions using a combination of direct and indirect comparisons. Objectives (1) To evaluate the effectiveness of cord management strategies for preterm infants on neonatal mortality and morbidity overall and for different participant characteristics using IPD meta-analysis. (2) To evaluate and rank the effect of different cord management strategies for preterm births on mortality and other key outcomes using NMA. Methods and analysis Systematic searches of Medline, Embase, clinical trial registries, and other sources for all ongoing and completed randomised controlled trials comparing cord management strategies at preterm birth (before 37 weeks’ gestation) have been completed up to 13 February 2019, but will be updated regularly to include additional trials. IPD will be sought for all trials; aggregate summary data will be included where IPD are unavailable. First, deferred clamping and cord milking will be compared with immediate clamping in pairwise IPD meta-analyses. The primary outcome will be death prior to hospital discharge. Effect differences will be explored for prespecified participant subgroups. Second, all identified cord management strategies will be compared and ranked in an IPD NMA for the primary outcome and the key secondary outcomes. Treatment effect differences by participant characteristics will be identified. Inconsistency and heterogeneity will be explored. Ethics and dissemination Ethics approval for this project has been granted by the University of Sydney Human Research Ethics Committee (2018/886). Results will be relevant to clinicians, guideline developers and policy-makers, and will be disseminated via publications, presentations and media releases

Improving quality of care and outcome at very preterm birth: the Preterm Birth research programme, including the Cord pilot RCT

BACKGROUND:Being born very premature (i.e. before 32 weeks’ gestation) has an impact on survival and quality of life. Improving care at birth may improve outcomes and parents’ experiences. OBJECTIVES:To improve the quality of care and outcomes following very preterm birth. DESIGN:We used mixed methods, including a James Lind Alliance prioritisation, a systematic review, a framework synthesis, a comparative review, qualitative studies, development of a questionnaire tool and a medical device (a neonatal resuscitation trolley), a survey of practice, a randomised trial and a protocol for a prospective meta-analysis using individual participant data. SETTING:For the prioritisation, this included people affected by preterm birth and health-care practitioners in the UK relevant to preterm birth. The qualitative work on preterm birth and the development of the questionnaire involved parents of infants born at three maternity hospitals in southern England. The medical device was developed at Liverpool Women’s Hospital. The survey of practice involved UK neonatal units. The randomised trial was conducted at eight UK tertiary maternity hospitals. PARTICIPANTS:For prioritisation, 26 organisations and 386 individuals; for the interviews and questionnaire tool, 32 mothers and seven fathers who had a baby born before 32 weeks’ gestation for interviews evaluating the trolley, 30 people who had experienced it being used at the birth of their baby (19 mothers, 10 partners and 1 grandmother) and 20 clinicians who were present when it was being used; for the trial, 261 women expected to have a live birth before 32 weeks’ gestation, and their 276 babies. INTERVENTIONS:Providing neonatal care at very preterm birth beside the mother, and with the umbilical cord intact; timing of cord clamping at very preterm birth. MAIN OUTCOME MEASURES:Research priorities for preterm birth; feasibility and acceptability of the trolley; feasibility of a randomised trial, death and intraventricular haemorrhage. REVIEW METHODS:Systematic review of Cochrane reviews (umbrella review); framework synthesis of ethics aspects of consent, with conceptual framework to inform selection criteria for empirical and analytical studies. The comparative review included studies using a questionnaire to assess satisfaction with care during childbirth, and provided psychometric information. RESULTS:Our prioritisation identified 104 research topics for preterm birth, with the top 30 ranked. An ethnographic analysis of decision-making during this process suggested ways that it might be improved. Qualitative interviews with parents about their experiences of very preterm birth identified two differences with term births: the importance of the staff appearing calm and of staff taking control. Following a comparative review, this led to the development of a questionnaire to assess parents’ views of care during very preterm birth. A systematic overview summarised evidence for delivery room neonatal care and revealed significant evidence gaps. The framework synthesis explored ethics issues in consent for trials involving sick or preterm infants, concluding that no existing process is ideal and identifying three important gaps. This led to the development of a two-stage consent pathway (oral assent followed by written consent), subsequently evaluated in our randomised trial. Our survey of practice for care at the time of birth showed variation in approaches to cord clamping, and that no hospitals were providing neonatal care with the cord intact. We showed that neonatal care could be provided beside the mother using either the mobile neonatal resuscitation trolley we developed or existing equipment. Qualitative interviews suggested that neonatal care beside the mother is valued by parents and acceptable to clinicians. Our pilot randomised trial compared cord clamping after 2 minutes and initial neonatal care, if needed, with the cord intact, with clamping within 20 seconds and initial neonatal care after clamping. This study demonstrated feasibility of a large UK randomised trial. Of 135 infants allocated to cord clamping ≥ 2 minutes, 7 (5.2%) died and, of 135 allocated to cord clamping ≤ 20 seconds, 15 (11.1%) died (risk difference –5.9%, 95% confidence interval –12.4% to 0.6%). Of live births, 43 out of 134 (32%) allocated to cord clamping ≥ 2 minutes had intraventricular haemorrhage compared with 47 out of 132 (36%) allocated to cord clamping ≤ 20 seconds (risk difference –3.5%, 95% CI –14.9% to 7.8%). LIMITATIONS:Small sample for the qualitative interviews about preterm birth, single-centre evaluation of neonatal care beside the mother, and a pilot trial. CONCLUSIONS:Our programme of research has improved understanding of parent experiences of very preterm birth, and informed clinical guidelines and the research agenda. Our two-stage consent pathway is recommended for intrapartum clinical research trials. Our pilot trial will contribute to the individual participant data meta-analysis, results of which will guide design of future trials. FUTURE WORK:Research in preterm birth should take account of the top priorities. Further evaluation of neonatal care beside the mother is merited, and future trial of alternative policies for management of cord clamping should take account of the meta-analysis. STUDY REGISTRATION:This study is registered as PROSPERO CRD42012003038 and CRD42013004405. In addition, Current Controlled Trials ISRCTN21456601. FUNDING:This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 7, No. 8. See the NIHR Journals Library website for further project information

Evaluation of the Family Integrated Care model of neonatal intensive care: A cluster randomized controlled trial in Canada and Australia

Background: Admission to the neonatal intensive care unit (NICU) may disrupt parent-infant interaction with adverse consequences for infants and their families. Several family-centered care programs promote parent-infant interaction in the NICU; however, all of these retain the premise that health-care professionals should provide most of the infant\u27s care. Parents play a mainly supportive role in the NICU and continue to feel anxious and unprepared to care for their infant after discharge. In the Family Integrated Care (FICare) model, parents provide all except the most advanced medical care for their infants with support from the medical team. Our hypothesis is that infants whose families complete the FICare program will have greater weight gain and better clinical and parental outcomes compared with infants provided with standard NICU care. Methods/Design: FICare is being evaluated in a cluster randomized controlled trial among infants born at ≤ 33 weeks\u27 gestation admitted to 19 Canadian, 6 Australian, and 1 New Zealand tertiary-level NICU. Trial enrollment began in April, 2013, with a target sample size of 675 infants in each arm, to be completed by August, 2015. Participating sites were stratified by country, and by NICU size within Canada, for randomization to either the FICare intervention or control arm. In intervention sites, parents are taught how to provide most of their infant\u27s care and supported by nursing staff, veteran parents, a program coordinator, and education sessions. In control sites standard NICU care is provided. The primary outcome is infants\u27 weight gain at 21 days after enrollment, which will be compared between the FICare and control groups using Student\u27s t-test adjusted for site-level clustering, and multi-level hierarchical models accounting for both clustering and potential confounders. Similar analyses will examine secondary outcomes including breastfeeding, clinical outcomes, safety, parental stress and anxiety, and resource use. The trial was designed, is being conducted, and will be reported according to the CONSORT 2010 guidelines for cluster randomized controlled trials. Discussion: By evaluating the impact of integrating parents into the care of their infant in the NICU, this trial may transform the delivery of neonatal care. Trial registration:NCT01852695 , registered December 19, 201

Evaluation of the Family Integrated Care model of neonatal intensive care: A cluster randomized controlled trial in Canada and Australia

Background: Admission to the neonatal intensive care unit (NICU) may disrupt parent-infant interaction with adverse consequences for infants and their families. Several family-centered care programs promote parent-infant interaction in the NICU; however, all of these retain the premise that health-care professionals should provide most of the infant\u27s care. Parents play a mainly supportive role in the NICU and continue to feel anxious and unprepared to care for their infant after discharge. In the Family Integrated Care (FICare) model, parents provide all except the most advanced medical care for their infants with support from the medical team. Our hypothesis is that infants whose families complete the FICare program will have greater weight gain and better clinical and parental outcomes compared with infants provided with standard NICU care. Methods/Design: FICare is being evaluated in a cluster randomized controlled trial among infants born at ≤ 33 weeks\u27 gestation admitted to 19 Canadian, 6 Australian, and 1 New Zealand tertiary-level NICU. Trial enrollment began in April, 2013, with a target sample size of 675 infants in each arm, to be completed by August, 2015. Participating sites were stratified by country, and by NICU size within Canada, for randomization to either the FICare intervention or control arm. In intervention sites, parents are taught how to provide most of their infant\u27s care and supported by nursing staff, veteran parents, a program coordinator, and education sessions. In control sites standard NICU care is provided. The primary outcome is infants\u27 weight gain at 21 days after enrollment, which will be compared between the FICare and control groups using Student\u27s t-test adjusted for site-level clustering, and multi-level hierarchical models accounting for both clustering and potential confounders. Similar analyses will examine secondary outcomes including breastfeeding, clinical outcomes, safety, parental stress and anxiety, and resource use. The trial was designed, is being conducted, and will be reported according to the CONSORT 2010 guidelines for cluster randomized controlled trials. Discussion: By evaluating the impact of integrating parents into the care of their infant in the NICU, this trial may transform the delivery of neonatal care. Trial registration:NCT01852695 , registered December 19, 201

Does time of surgery influence the rate of false-negative appendectomies?:A retrospective observational study of 274 patients

Background Multiple disciplines have described an “after-hours effect” relating to worsened mortality and morbidity outside regular working hours. This retrospective observational study aimed to evaluate whether diagnostic accuracy of a common surgical condition worsened after regular hours. Methods Electronic operative records for all non-infant patients (age > 4 years) operated on at a single centre for presumed acute appendicitis were retrospectively reviewed over a 56-month period (06/17/2012–02/01/2017). The primary outcome measure of unknown diagnosis was compared between those performed in regular hours (08:00–17:00) or off hours (17:01–07:59). Pre-clinical biochemistry and pre-morbid status were recorded to determine case heterogeneity between the two groups, along with secondary outcomes of length of stay and complication rate. Results Out of 289 procedures, 274 cases were deemed eligible for inclusion. Of the 133 performed in regular hours, 79% were appendicitis, compared to 74% of the 141 procedures performed off hours. The percentage of patients with an unknown diagnosis was 6% in regular hours compared to 15% off hours (RR 2.48; 95% CI 1.14–5.39). This was accompanied by increased numbers of registrars (residents in training) leading procedures off hours (37% compared to 24% in regular hours). Pre-morbid status, biochemistry, length of stay and post-operative complication rate showed no significant difference. Conclusions This retrospective study suggests that the rate of unknown diagnoses for acute appendicitis increases overnight, potentially reflecting increased numbers of unnecessary procedures being performed off hours due to poorer diagnostic accuracy. Reduced levels of staffing, availability of diagnostic modalities and changes to workforce training may explain this, but further prospective work is required. Potential solutions may include protocolizing the management of common acute surgical conditions and making more use of non-resident on call senior colleagues