Understanding the co-construction of safety in the paediatric intensive care unit: A meta-ethnography of parents' experiences.

BACKGROUND: Children experiencing critical illness or injury may require admission to a paediatric intensive care unit (PICU) to receive life-sustaining or life-saving treatment. Studies have explored the experience of parents with a child in PICU but tend to focus on subgroups of children or specific healthcare systems. Therefore, we aimed to undertake a meta-ethnography to draw together the published research. METHODS: A systematic search strategy was developed to identify qualitative studies, which had explored the experiences of parents with a critically ill child treated in a PICU. A meta-ethnography was undertaken following the structured steps of identifying the topic; undertaking a systematic search; reading the research; determining how the studies relate and translate into each other; and synthesising and expressing the results. RESULTS: We identified 2989 articles from our search and after a systematic series of exclusions, 15 papers remaining for inclusion. We explored the original parent voices (first order) and the interpretation of the study authors (second order) to identify three third-order concepts (our interpretation of the findings), which related to technical, relational and temporal factors. These factors influenced parents' experiences, providing both barriers and facilitators to how parents and caregivers experienced the time their child was in the PICU. The dynamic and co-constructed nature of safety provided an analytical overarching frame of reference. CONCLUSION: This synthesis demonstrates novel ways in which parents and caregivers can contribute to the vital role of ensuring a co-created safe healthcare environment for their child when receiving life-saving care within the PICU.

Children born preterm admitted to paediatric intensive care for bronchiolitis: a systematic review and meta-analysis.

BACKGROUND: To undertake a systematic review of studies describing the proportion of children admitted to a paediatric intensive care unit (PICU) for respiratory syncytial virus (RSV) and/or bronchiolitis who were born preterm, and compare their outcomes in PICU with children born at term. METHODS: We searched Medline, Embase and Scopus. Citations and references of included articles were searched. We included studies published from the year 2000 onwards, from high-income countries, that examined children 0-18 years of age, admitted to PICU from the year 2000 onwards for RSV and/or bronchiolitis. The primary outcome was the percentage of PICU admissions born preterm, and secondary outcomes were observed relative risks of invasive mechanical ventilation and mortality within PICU. We used the Joanna Briggs Institute Checklist for Analytical Cross-Sectional Studies to assess risk of bias. RESULTS: We included 31 studies, from 16 countries, including a total of 18,331 children. Following meta-analysis, the pooled estimate for percentage of PICU admissions for RSV/bronchiolitis who were born preterm was 31% (95% confidence interval: 27% to 35%). Children born preterm had a greater risk of requiring invasive ventilation compared to children born at term (relative risk 1.57, 95% confidence interval 1.25 to 1.97, I2 = 38%). However, we did not observe a significant increase in the relative risk for mortality within PICU for preterm-born children (relative risk 1.10, 95% confidence interval: 0.70 to 1.72, I2 = 0%), although the mortality rate was low across both groups. The majority of studies (n = 26, 84%) were at high risk of bias. CONCLUSIONS: Among PICU admissions for bronchiolitis, preterm-born children are over-represented compared with the preterm birth rate (preterm birth rate 4.4% to 14.4% across countries included in review). Preterm-born children are at higher risk of mechanical ventilation compared to those born at term.

Impact of prematurity on long-stay paediatric intensive care unit admissions in England 2008-2018.

BACKGROUND: Survival following extreme preterm birth has improved, potentially increasing the number of children with ongoing morbidity requiring intensive care in childhood. Previous single-centre studies have suggested that long-stay admissions in paediatric intensive care units (PICUs) are increasing. We aimed to examine trends in long-stay admissions (≥28 days) to PICUs in England, outcomes for this group (including mortality and PICU readmission), and to determine the contribution of preterm-born children to the long-stay population, in children aged <2 years. METHODS: Data was obtained from the Paediatric Intensive Care Audit Network (PICANet) for all children <2 years admitted to National Health Service PICUs from 1/1/2008 to 31/12/2018 in England. We performed descriptive analysis of child characteristics and PICU outcomes. RESULTS: There were 99,057 admissions from 67,615 children. 2,693 children (4.0%) had 3,127 long-stays. Between 2008 and 2018 the annual number of long-stay admissions increased from 225 (2.7%) to 355 (4.0%), and the proportion of bed days in PICUs occupied by long-stay admissions increased from 24.2% to 33.2%. Of children with long-stays, 33.5% were born preterm, 53.5% were born at term, and 13.1% had missing data for gestational age. A considerable proportion of long-stay children required PICU readmission before two years of age (76.3% for preterm-born children). Observed mortality during any admission was also disproportionately greater for long-stay children (26.5% for term-born, 24.8% for preterm-born) than the overall rate (6.3%). CONCLUSIONS: Long-stays accounted for an increasing proportion of PICU activity in England between 2008 and 2018. Children born preterm were over-represented in the long-stay population compared to the national preterm birth rate (8%). These results have significant implications for future research into paediatric morbidity, and for planning future PICU service provision.

Is Parental Presence in the Ambulance Associated With Parental Satisfaction During Emergency Pediatric Intensive Care Retrieval? A Cross-Sectional Questionnaire Study.

OBJECTIVES: Quality standards for pediatric intensive care transport services in the U.K. state that at least one parent should be allowed to travel with their child during emergency transport to a PICU. We aimed to identify the reasons why parents do, or do not, accompany their child and whether there is an association between parental presence in the ambulance and their satisfaction with the transport. DESIGN: National cross-sectional parent questionnaire. SETTING: Pediatric Critical Care Transport (PCCT) teams and PICUs in England and Wales. PARTICIPANTS: Parents of children transferred to one of 24 participating PICUs between January 2018 and January 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A parent feedback questionnaire was completed by parents whose child received an emergency interhospital transfer. As part of the questionnaire, a brief nine-item scale was developed to summarize parental transport experience (ranging from 1 to 5). The association between parental presence in the ambulance and parental experience was analyzed. A total of 4,558 children were transported during the study. Consent was obtained from 2,838 parents, and questionnaires received in 2,084 unique transports (response rate: 45.7%). In 1,563 transports (75%), at least one parent traveled in the ambulance. Parents did not travel in 478 transports (23%) and, in most instances (442 transports; 93%), offered reasons (emotional, practical, and health-related) for declining to travel or explanations why they were not permitted to travel (mainly due to space restrictions). Most parents rated their experience with the retrieval teams very highly, and within this context, we found evidence of greater variability in experience ratings if parents were not present in the ambulance and if this was not their choice. CONCLUSIONS: Most parents who completed questionnaires rated their experience with their PCCT team highly. Parental presence and choice to travel in the ambulance were associated with a more positive experience.

A qualitative study exploring risk perception in congenital cardiac surgery: the perspective of UK surgeons.

INTRODUCTION: Managing risk is central to clinical care, yet most research focuses on patient perception, as opposed to how risk is enacted within the clinical setting by healthcare professionals. AIM: To explore how surgical risk is perceived, encountered, and managed by congenital cardiac surgeons. METHODS: Semi-structured interviews were conducted with 20 congenital cardiac surgeons representing every unit across England and Wales. All interviews were transcribed verbatim, with analysis based on the constant comparative approach. FINDINGS: Three themes were identified, reflecting the interactions between personal, institutional, and political context in which risk is encountered and managed. First, "communicating risk" highlights the complexity and variability in methods employed by surgeons to balance legal/moral obligations with parental need and expectations. Universally, surgeons described the need for flexibility in their approach in order to meet the needs of individual patients. Second, "scrutiny and accountability" captures the spectrum of opinion arising from the binary nature of the outcomes collated and the way in which they are perceived to be interpreted. Third, "nature of the job" highlights the personal and professional implications of conveying and managing risk and the impact of recent policy changes on the way this is enacted. CONCLUSION: Variations in approaches to communicating risk demonstrate a lack of consensus, compounded by insufficient evidence to determine or monitor a "best-care" approach. With current surgical outcomes suggesting little room for increasing survival rates, future care needs should shift to the "soft skills" in order to continue to drive improvements in parental and patient experience.

Development of a parent experience measure for paediatric critical care transport teams.

BACKGROUND: A third of children admitted to paediatric intensive care units (PICUs) in the United Kingdom (UK) are transported by paediatric critical care transport services (PCCTs). Parents have described the transfer journey as particularly stressful. Critical care nurses have a key role in mitigating the impact of the journey on parents. Evaluating parents' experiences is important to inform service improvements. AIM AND OBJECTIVES: Our aim was to describe the development of a new measure of parents' experiences of PCCTs, derived from data collected in the Differences in access to Emergency Paediatric Intensive Care and care during Transport (DEPICT) study. DESIGN: A descriptive cross-sectional survey was used. METHODS: As part of the DEPICT study, a 17-item transport experience questionnaire was developed and given to parents of children transported by PCCTs to 24 UK PICUs during a 12-month period. Analyses included exploratory factor analysis and a validation review by a PCCT stakeholder group. RESULTS: Families of 1722 children (1798 journeys) completed questionnaires. Five items were excluded from further analysis as correlation coefficients were <0.3. Two factors explained 53% of the variance and all 12 items loaded on one of these factors. Factor 1 (8 items) explained 47% of the variance, had excellent internal reliability and the clustered items were conceptually coherent with a specific relevance to PCCTs; these were offered for consideration, with other items possibly discarded. Twenty-eight PCCT clinicians reviewed the questions. Using a 70% agreement threshold, one additional, previously discarded, item was identified for inclusion, resulting in a nine-item experience measure. CONCLUSION: Our brief measure of parents' experience of critical care transport provides a standardized measure that can be used across all PCCTs, enabling national benchmarking of services and potentially increasing the collection and use of parent experience data to improve services. RELEVANCE TO CLINICAL PRACTICE: Being able to measure experience provides an opportunity to understand how to make services better to improve experience.

Variations in Neonatal Length of Stay of Babies Born Extremely Preterm: An International Comparison Between iNeo Networks.

OBJECTIVE: To compare length of stay (LOS) in neonatal care for babies born extremely preterm admitted to networks participating in the International Network for Evaluating Outcomes of Neonates (iNeo). STUDY DESIGN: Data were extracted for babies admitted from 2014 to 2016 and born at 24 to 28 weeks of gestational age (n = 28 204). Median LOS was calculated for each network for babies who survived and those who died while in neonatal care. A linear regression model was used to investigate differences in LOS between networks after adjusting for gestational age, birth weight z score, sex, and multiplicity. A sensitivity analysis was conducted for babies who were discharged home directly. RESULTS: Observed median LOS for babies who survived was longest in Japan (107 days); this result persisted after adjustment (20.7 days more than reference, 95% CI 19.3-22.1). Finland had the shortest adjusted LOS (-4.8 days less than reference, 95% CI -7.3 to -2.3). For each week's increase in gestational age at birth, LOS decreased by 12.1 days (95% CI -12.3 to -11.9). Multiplicity and male sex predicted mean increases in LOS of 2.6 (95% CI 2.0-3.2) and 2.1 (95% CI 1.6-2.6) days, respectively. CONCLUSIONS: We identified between-network differences in LOS of up to 3 weeks for babies born extremely preterm. Some of these may be partly explained by differences in mortality, but unexplained variations also may be related to differences in clinical care practices and healthcare systems between countries.

The effect of care provided by paediatric critical care transport teams on mortality of children transported to paediatric intensive care units in England and Wales: a retrospective cohort study.

BACKGROUND: Centralisation of paediatric intensive care units (PICUs) has the increased the need for specialist paediatric critical care transport teams (PCCT) to transport critically ill children to PICU. We investigated the impact of care provided by PCCTs for children on mortality and other clinically important outcomes. METHODS: We analysed linked national data from the Paediatric Intensive Care Audit Network (PICANet) from children admitted to PICUs in England and Wales (2014-2016) to assess the impact of who led the child's transport, whether prolonged stabilisation by the PCCT was detrimental and the impact of critical incidents during transport on patient outcome. We used logistic regression models to estimate the adjusted odds and probability of mortality within 30 days of admission to PICU (primary outcome) and negative binomial models to investigate length of stay (LOS) and length of invasive ventilation (LOV). RESULTS: The study included 9112 children transported to PICU. The most common diagnosis was respiratory problems; junior doctors led the PCCT in just over half of all transports; and the 30-day mortality was 7.1%. Transports led by Advanced Nurse Practitioners and Junior Doctors had similar outcomes (adjusted mortality ANP: 0.035 versus Junior Doctor: 0.038). Prolonged stabilisation by the PCCT was possibly associated with increased mortality (0.059, 95% CI: 0.040 to 0.079 versus short stabilisation 0.044, 95% CI: 0.039 to 0.048). Critical incidents involving the child increased the adjusted odds of mortality within 30 days (odds ratio: 3.07). CONCLUSIONS: Variations in team composition between PCCTs appear to have little effect on patient outcomes. We believe differences in stabilisation approaches are due to residual confounding. Our finding that critical incidents were associated with worse outcomes indicates that safety during critical care transport is an important area for future quality improvement work.

Does time taken by paediatric critical care transport teams to reach the bedside of critically ill children affect survival? A retrospective cohort study from England and Wales.

BACKGROUND: Reaching the bedside of a critically ill child within three hours of agreeing the child requires intensive care is a key target for Paediatric Critical Care Transport teams (PCCTs) to achieve in the United Kingdom. Whilst timely access to specialist care is necessary for these children, it is unknown to what extent time taken for the PCCT to arrive at the bedside affects clinical outcome. METHODS: Data from transports of critically ill children who were admitted to Paediatric Intensive Care Units (PICUs) in England and Wales from 1 January 2014 to 31 December 2016 were extracted from the Paediatric Intensive Care Audit Network (PICANet) and linked with adult critical care data and Office for National Statistics mortality data. Logistic regression models, adjusted for pre-specified confounders, were fitted to investigate the impact of time-to-bedside on mortality within 30 days of admission and other key time points. Negative binomial models were used to investigate the impact of time-to-bedside on PICU length of stay and duration of invasive ventilation. RESULTS: There were 9116 children transported during the study period, and 645 (7.1%) died within 30 days of PICU admission. There was no evidence that 30-day mortality changed as time-to-bedside increased. A similar relationship was seen for mortality at other pre-selected time points. In children who waited longer for a team to arrive, there was limited evidence of a small increase in PICU length of stay (expected number of days increased from: 7.17 to 7.58). CONCLUSION: There is no evidence that reducing the time-to-bedside target for PCCTs will improve the survival of critically ill children. A shorter time to bedside may be associated with a small reduction in PICU length of stay.

Isolation of the antibiotic pseudopyronine B and SAR evaluation of C3/C6 alkyl analogs.

Natural products are an abundant source of structurally diverse compounds with antibacterial activity that can be used to develop new and potent antibiotics. One such class of natural products is the pseudopyronines. Here we present the isolation of pseudopyronine B (2) from a Pseudomonas species found in garden soil in Western North Carolina, and SAR evaluation of C3 and C6 alkyl analogs of the natural product for antibacterial activity against Gram-positive and Gram-negative bacteria. We found a direct relationship between antibacterial activity and C3/C6 alkyl chain length. For inhibition of Gram-positive bacteria, alkyl chain lengths between 6 and 7 carbons were found to be the most active (IC50=0.04-3.8µg/mL) whereas short alkyl chain analogs showed modest activity against Gram-negative bacteria (IC50=223-304µg/mL). This demonstrates the potential for this class of natural products to be optimized for selective activity against either Gram-positive or Gram-negative bacteria.

Infants born late/moderately preterm are at increased risk for a positive autism screen at 2 years of age.

OBJECTIVES: To assess the prevalence of positive screens using the Modified Checklist for Autism in Toddlers (M-CHAT) questionnaire and follow-up interview in late and moderately preterm (LMPT; 32-36 weeks) infants and term-born controls. STUDY DESIGN: Population-based prospective cohort study of 1130 LMPT and 1255 term-born infants. Parents completed the M-CHAT questionnaire at 2-years corrected age. Parents of infants with positive questionnaire screens were followed up with a telephone interview to clarify failed items. The M-CHAT questionnaire was re-scored, and infants were classified as true or false positives. Neurosensory, cognitive, and behavioral outcomes were assessed using parent report. RESULTS: Parents of 634 (57%) LMPT and 761 (62%) term-born infants completed the M-CHAT questionnaire. LMPT infants had significantly higher risk of a positive questionnaire screen compared with controls (14.5% vs 9.2%; relative risk [RR] 1.58; 95% CI 1.18, 2.11). After follow-up, significantly more LMPT infants than controls had a true positive screen (2.4% vs 0.5%; RR 4.52; 1.51, 13.56). This remained significant after excluding infants with neurosensory impairments (2.0% vs 0.5%; RR 3.67; 1.19, 11.3). CONCLUSIONS: LMPT infants are at significantly increased risk for positive autistic screen. An M-CHAT follow-up interview is essential as screening for autism spectrum disorders is especially confounded in preterm populations. Infants with false positive screens are at risk for cognitive and behavioral problems.

Paediatric intensive care admissions of preterm children born <32 weeks gestation: a national retrospective cohort study using data linkage.

OBJECTIVE: Survival of babies born very preterm (<32 weeks gestational age) has increased, although preterm-born children may have ongoing morbidity. We aimed to investigate the risk of admission to paediatric intensive care units (PICUs) of children born very preterm following discharge home from neonatal care. DESIGN: Retrospective cohort study, using data linkage of National Neonatal Research Database and the Paediatric Intensive Care Audit Network datasets. SETTING: All neonatal units and PICUs in England and Wales. PATIENTS: Children born very preterm between 1 January 2013 and 31 December 2018 and admitted to neonatal units. MAIN OUTCOME MEASURES: Admission to PICU after discharge home from neonatal care, before 2 years of age. RESULTS: Of the 40 690 children discharged home from neonatal care, there were 2308 children (5.7%) with at least one admission to PICU after discharge. Of these children, there were 1901 whose first PICU admission after discharge was unplanned.The percentage of children with unplanned PICU admission varied by gestation, from 10.2% of children born <24 weeks to 3.3% born at 31 weeks.Following adjustment, unplanned PICU admission was associated with lower gestation, male sex (adjusted OR (aOR) 0.79), bronchopulmonary dysplasia (aOR 1.37), necrotising enterocolitis requiring surgery (aOR 1.39) and brain injury (aOR 1.42). For each week of increased gestation, the aOR was 0.90. CONCLUSIONS: Most babies born <32 weeks and discharged home from neonatal care do not require PICU admission in the first 2 years. The odds of unplanned admissions to PICU were greater in the most preterm and those with significant neonatal morbidity.

Characteristics of children requiring admission to neonatal care and paediatric intensive care before the age of 2 years in England and Wales: a data linkage study.

OBJECTIVE: To quantify the characteristics of children admitted to neonatal units (NNUs) and paediatric intensive care units (PICUs) before the age of 2 years. DESIGN: A data linkage study of routinely collected data. SETTING: National Health Service NNUs and PICUs in England and Wales PATIENTS: Children born from 2013 to 2018. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Admission to PICU before the age of 2 years. RESULTS: A total of 384 747 babies were admitted to an NNU and 4.8% (n=18 343) were also admitted to PICU before the age of 2 years. Approximately half of all children admitted to PICU under the age of 2 years born in the same time window (n=18 343/37 549) had previously been cared for in an NNU.The main reasons for first admission to PICU were cardiac (n=7138) and respiratory conditions (n=5386). Cardiac admissions were primarily from children born at term (n=5146), while respiratory admissions were primarily from children born preterm (<37 weeks' gestational age, n=3550). A third of children admitted to PICU had more than one admission. CONCLUSIONS: Healthcare professionals caring for babies and children in NNU and PICU see some of the same children in the first 2 years of life. While some children are following established care pathways (eg, staged cardiac surgery), the small proportion of children needing NNU care subsequently requiring PICU care account for a large proportion of the total PICU population. These differences may affect perceptions of risk for this group of children between NNU and PICU teams.

Genome-wide selection for increased copy number in Acinetobacter baylyi ADP1: locus and context-dependent variation in gene amplification.

Renewed interest in gene amplification stems from its importance in evolution and a variety of medical problems ranging from drug resistance to cancer. However, amplified DNA segments (amplicons) are not fully characterized in any organism. Here we report a novel Acinetobacter baylyi system for genome-wide studies. Amplification mutants that consume aromatic compounds were selected under conditions requiring high-level expression from three promoters in a linked set of chromosomal genes. Tools were developed to relocate these catabolic genes to any non-essential chromosomal position, and 49 amplification mutants from five genomic contexts were characterized. Amplicon size (18-271 kb) and copy number (2-105) indicated that 30% of mutants carried more than 1 Mb of amplified DNA. Amplification features depended on genomic position. For example, amplicons from one locus were similarly sized but displayed variable copy number, whereas those from another locus were differently sized but had comparable copy number. Additionally, the importance of sequence context was highlighted in one region where amplicons differed depending on the presence of a promoter mutation in the strain from which they were selected. DNA sequences at amplicon boundaries in 19 mutants reflected illegitimate recombination. Furthermore, steady-state duplication frequencies measured under non-selective conditions (10(-4) to 10(-5) ) confirmed that spontaneous gene duplication is a major source of genetic variation.

Pleiotropic effects of GacA on Pseudomonas fluorescens Pf0-1 in vitro and in soil.

Pseudomonas species can exhibit phenotypic variation resulting from gacS or gacA mutation. P. fluorescens Pf0-1 is a gacA mutant and exhibits pleiotropic changes following the introduction of a functional allele. GacA enhances biofilm development while reducing dissemination in soil, suggesting that alternative Gac phenotypes enable Pseudomonas sp. to exploit varied environments.

Modelling time to death or discharge in neonatal care: an application of competing risks.

BACKGROUND: Understanding length of stay for babies in neonatal care is vital for planning services and for counselling parents. While previous work has focused on the length of stay of babies who survive to discharge, when investigating resource use within neonatal care, it is important to also incorporate information on those babies who die while in care. We present an analysis using competing risks methodology which allows the simultaneous modelling of babies who die in neonatal care and those who survive to discharge. METHODS: Data were obtained on 2723 babies born at 24-28 weeks gestational age in 2006-10 and admitted to neonatal care. Death and discharge alive are two mutually exclusive events and can be treated as competing risks. A flexible parametric modelling approach was used to analyse these two competing events and obtain estimates of the absolute probabilities of death or discharge. RESULTS: The absolute probabilities of death or discharge are presented in graphical form showing the cause-specific cumulative incidence over time by gender, gestational age and birthweight. The discharge of babies alive generally occurred over a longer time period for babies of lower gestational age and smaller birthweight than for bigger babies. CONCLUSION: This study has presented a useful statistical method for modelling the length of stay where there are significant rates of in-unit mortality. In health care systems that are increasingly focusing on costs and resource planning, it is essential to consider not only length of stay of survivors but also for those patients who die before discharge.

Effect of national guidance on survival for babies born at 22 weeks' gestation in England and Wales: population based cohort study.

Objectives: To explore the effect of changes in national clinical recommendations in 2019 that extended provision of survival focused care to babies born at 22 weeks' gestation in England and Wales. Design: Population based cohort study. Setting: England and Wales, comprising routine data for births and hospital records. Participants: Babies alive at the onset of care in labour at 22 weeks+0 days to 22 weeks+6 days and at 23 weeks+0 days to 24 weeks+6 days for comparison purposes between 1 January 2018 and 31 December 2021. Main outcome measures: Percentage of babies given survival focused care (active respiratory support after birth), admitted to neonatal care, and surviving to discharge in 2018-19 and 2020-21. Results: For the 1001 babies alive at the onset of labour at 22 weeks' gestation, a threefold increase was noted in: survival focused care provision from 11.3% to 38.4% (risk ratio 3.41 (95% confidence interval 2.61 to 4.45)); admissions to neonatal units from 7.4% to 28.1% (3.77 (2.70 to 5.27)), and survival to discharge from neonatal care from 2.5% to 8.2% (3.29 (1.78 to 6.09)). More babies of lower birth weight and early gestational age received survival focused care in 2020-21 than 2018-19 (46% to 64% at <500g weight; 19% to 31% at 22 weeks+0 days to 22 weeks+3 days). Conclusions: A change in national guidance to recommend a risk based approach was associated with a threefold increase in 22 weeks' gestation babies receiving survival focused care. The number of babies being admitted to neonatal units and those surviving to discharge increased.

Estimated neonatal survival of very preterm births across the care pathway: a UK cohort 2016-2020.

OBJECTIVE: Currently used estimates of survival are nearly 10 years old and relate to only those babies admitted for neonatal care. Due to ongoing improvements in neonatal care, here we update estimates of survival for singleton and multiple births at 22+0 to 31+6 weeks gestational age across the perinatal care pathway by gestational age and birth weight. DESIGN: Retrospective analysis of routinely collected data. SETTING: A national cohort from the UK and British Crown Dependencies. PATIENTS: Babies born at 22+0 to 31+6 weeks gestational age from 1 January 2016 to 31 December 2020. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Survival to 28 days. RESULTS: Estimates of neonatal survival are provided for babies: (1) alive at the onset of care during the birthing process (n=43 763); (2) babies where survival-focused care was initiated (n=42 004); and (3) babies admitted for neonatal care (n=41 158). We have produced easy-to-use survival charts for singleton and multiple births. Generally, survival increased with increasing gestational age at birth and with increasing birth weight. For all births with a birthweight over 1000 g, survival was 90% or higher at all three stages of care. CONCLUSIONS: Survival estimates are a vital tool to support and supplement clinical judgement within perinatal care. These up-to-date, national estimates of survival to 28 days are provided based on three stages of the perinatal care pathway to support ongoing clinical care. These novel results are a key resource for policy and practice including counselling parents and informing care provision.

Analysis of IS1236-mediated gene amplification events in Acinetobacter baylyi ADP1.

Recombination between insertion sequence copies can cause genetic deletion, inversion, or duplication. However, it is difficult to assess the fraction of all genomic rearrangements that involve insertion sequences. In previous gene duplication and amplification studies of Acinetobacter baylyi ADP1, an insertion sequence was evident in approximately 2% of the characterized duplication sites. Gene amplification occurs frequently in all organisms and has a significant impact on evolution, adaptation, drug resistance, cancer, and various disorders. To understand the molecular details of this important process, a previously developed system was used to analyze gene amplification in selected mutants. The current study focused on amplification events in two chromosomal regions that are near one of six copies of the only transposable element in ADP1, IS1236 (an IS3 family member). Twenty-one independent mutants were analyzed, and in contrast to previous studies of a different chromosomal region, IS1236 was involved in 86% of these events. IS1236-mediated amplification could occur through homologous recombination between insertion sequences on both sides of a duplicated region. However, this mechanism presupposes that transposition generates an appropriately positioned additional copy of IS1236. To evaluate this possibility, PCR and Southern hybridization were used to determine the chromosomal configurations of amplification mutants involving IS1236. Surprisingly, the genomic patterns were inconsistent with the hypothesis that intramolecular homologous recombination occurred between insertion sequences following an initial transposition event. These results raise a novel possibility that the gene amplification events near the IS1236 elements arise from illegitimate recombination involving transposase-mediated DNA cleavage.

The probability of being identified as an outlier with commonly used funnel plot control limits for the standardised mortality ratio.

BACKGROUND: Emphasis is increasingly being placed on the monitoring of clinical outcomes for health care providers. Funnel plots have become an increasingly popular graphical methodology used to identify potential outliers. It is assumed that a provider only displaying expected random variation (i.e. 'in-control') will fall outside a control limit with a known probability. In reality, the discrete count nature of these data, and the differing methods, can lead to true probabilities quite different from the nominal value. This paper investigates the true probability of an 'in control' provider falling outside control limits for the Standardised Mortality Ratio (SMR). METHODS: The true probabilities of an 'in control' provider falling outside control limits for the SMR were calculated and compared for three commonly used limits: Wald confidence interval; 'exact' confidence interval; probability-based prediction interval. RESULTS: The probability of falling above the upper limit, or below the lower limit, often varied greatly from the nominal value. This was particularly apparent when there were a small number of expected events: for expected events ≤ 50 the median probability of an 'in-control' provider falling above the upper 95% limit was 0.0301 (Wald), 0.0121 ('exact'), 0.0201 (prediction). CONCLUSIONS: It is important to understand the properties and probability of being identified as an outlier by each of these different methods to aid the correct identification of poorly performing health care providers. The limits obtained using probability-based prediction limits have the most intuitive interpretation and their properties can be defined a priori. Funnel plot control limits for the SMR should not be based on confidence intervals.