Is there a sex difference in mortality rates in paediatric intensive care units?: a systematic review.

Introduction: Mortality rates in infancy and childhood are lower in females than males. However, for children admitted to Paediatric Intensive Care Units (PICU), mortality has been reported to be lower in males, although males have higher admission rates. This female mortality excess for the subgroup of children admitted in intensive care is not well understood. To address this, we carried out a systematic literature review to summarise the available evidence. Our review studies the differences in mortality between males and females aged 0 to <18 years, while in a PICU, to examine whether there was a clear difference (in either direction) in PICU mortality between the two sexes, and, if present, to describe the magnitude and direction of this difference. Methods: Any studies that directly or indirectly reported the rates of mortality in children admitted to intensive care by sex were eligible for inclusion. The search strings were based on terms related to the population (those admitted into a paediatric intensive care unit), the exposure (sex), and the outcome (mortality). We used the search databases MEDLINE, Embase, and Web of Science as these cover relevant clinical publications. We assessed the reliability of included studies using a modified version of the risk of bias in observational studies of exposures (ROBINS-E) tool. We considered estimating a pooled effect if there were at least three studies with similar populations, periods of follow-up while in PICU, and adjustment variables. Results: We identified 124 studies of which 114 reported counts of deaths by males and females which gave a population of 278,274 children for analysis, involving 121,800 (44%) females and 156,474 males (56%). The number of deaths and mortality rate for females were 5,614 (4.61%), and for males 6,828 (4.36%). In the pooled analysis, the odds ratio of female to male mortality was 1.06 [1.01 to 1.11] for the fixed effect model, and 1.10 [1.00 to 1.21] for the random effects model. Discussion: Overall, males have a higher admission rate to PCU, and potentially lower overall mortality in PICU than females. Systematic Review Registration: www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=203009, identifier (CRD42020203009).

Access to palivizumab among children at high risk of respiratory syncytial virus complications in English hospitals.

AIMS: Palivizumab is a monoclonal antibody which can prevent infection with respiratory syncytial virus (RSV). Due to its high cost, it is recommended for high-risk infants only. We aimed to determine the proportion of infants eligible for palivizumab treatment in England who receive at least one dose. METHODS: We used the Hospital Treatment Insights database, which contains hospital admission records linked to hospital pharmacy dispensing data for 43 out of 153 hospitals in England. Infants born between 2010 and 2016 were considered eligible for palivizumab if their medical records indicated chronic lung disease (CLD), congenital heart disease (CHD) or severe immunodeficiency (SCID), and they met additional criteria based on gestational age at birth and age at start of the RSV season (beginning of October). We calculated the proportion of infants who received at least one dose of palivizumab in their first RSV season, and modelled the odds of treatment according to multiple child characteristics using logistic regression models. RESULTS: We identified 3712 eligible children, of whom 2479 (67%) had complete information on all risk factors. Palivizumab was prescribed to 832 of eligible children (34%). Being born at <30 weeks' gestation, aged <6 months at the start of RSV season, and having two or more of CLD, CHD or SCID were associated with higher odds of treatment. CONCLUSION: In England, palivizumab is not prescribed to the majority of children who are eligible to receive it. Doctors managing these infants may be unfamiliar with the eligibility criteria or constrained by other considerations, such as cost.

A study of sex difference in infant mortality in UK pediatric intensive care admissions over an 11-year period.

Within the UK, child mortality from all causes has declined for all ages over the last three decades. However, distinct inequality remains, as child mortality rates are generally found to be higher in males. A significant proportion of childhood deaths in the UK occur in Paediatric Intensive Care Units (PICU). We studied the association of sex with infant mortality in PICUs. We included all infants (0 to 12 months old) admitted to UK PICUs from 01/01/2005 to 31/12/2015 using the Paediatric Intensive Care Audit Network (PICANet) dataset. We considered first admissions to PICU and fitted a cause-specific-hazard-ratio (CSHR) model, and a logistic model to estimate the adjusted association between sex and mortality in PICU. Pre-defined subgroups were children less than 56-days old, and those with a primary diagnosis of infection. Of 71,243 cases, 1,411/29,520 (4.8%) of females, and 1,809/41,723 (4.3%) of males died. The adjusted male/female CSHR was 0.87 (95%-CI 0.81 to 0.92) representing a 13% higher risk of death for females. The adjusted OR for male to female mortality is 0.86 (95%-CI 0.80 to 0.93). Analyses in subgroups yielded similar findings. In our analysis, female infants have a higher rate of PICU mortality compared to male infants.

Is there a sex difference in mortality rates for deaths occurring in paediatric intensive care units? Systematic literature review protocol.

INTRODUCTION: In the general population, female children have been reported to have a survival advantage. For children admitted to paediatric intensive care units (PICUs), mortality has been reported to be lower in males despite the higher admission rates for males into intensive care. This apparent sex reversal in PICU mortality is not well studied. To address this, we propose to conduct a systematic literature review to summarise the available evidence. Our review will study the reported differences in mortality between males and females aged 0-17, who died in a PICU, to examine if there is a difference between the two sexes in PICU mortality, and if so, to describe the magnitude and direction of this difference. METHODS AND ANALYSIS: Studies that directly or indirectly addressed the association between sex and mortality in children admitted to intensive care will be eligible for inclusion. Studies that directly address the association will be eligible for data extraction. The search strings were based on terms related to the population (children in intensive care), the exposure (sex) and the outcome (mortality). We used the databases MEDLINE (1946-2020), Embase (1980-2020) and Web of Science (1985-2020) as these cover relevant clinical publications. We will assess the reliability of included studies using the risk of bias in observational studies of exposures tool. We will consider a pooled effect if we have at least three studies with similar periods of follow up and adjustment variables. ETHICS AND DISSEMINATION: Ethical approval is not required for this review as it will synthesise data from existing studies. This manuscript is a part of a larger data linkage study, for which Ethical approval was granted. Dissemination will be via peer-reviewed journals and via public and patient groups. PROSPERO REGISTRATION NUMBER: CRD42020203009.

World Health Organization Grade II/III Glioma Molecular Status: Prediction by MRI Morphologic Features and Apparent Diffusion Coefficient.

Background A readily implemented MRI biomarker for glioma genotyping is currently lacking. Purpose To evaluate clinically available MRI parameters for predicting isocitrate dehydrogenase (IDH) status in patients with glioma. Materials and Methods In this retrospective study of patients studied from July 2008 to February 2019, untreated World Health Organization (WHO) grade II/III gliomas were analyzed by three neuroradiologists blinded to tissue results. Apparent diffusion coefficient (ADC) minimum (ADCmin) and mean (ADCmean) regions of interest were defined in tumor and normal appearing white matter (ADCNAWM). A visual rating of anatomic features (T1 weighted, T1 weighted with contrast enhancement, T2 weighted, and fluid-attenuated inversion recovery) was performed. Interobserver comparison (intraclass correlation coefficient and Cohen κ) was followed by nonparametric (Kruskal-Wallis analysis of variance) testing of associations between ADC metrics and glioma genotypes, including Bonferroni correction for multiple testing. Descriptors with sufficient concordance (intraclass correlation coefficient, >0.8; κ > 0.6) underwent univariable analysis. Predictive variables (P < .05) were entered into a multivariable logistic regression and tested in an additional test sample of patients with glioma. Results The study included 290 patients (median age, 40 years; interquartile range, 33-52 years; 169 male patients) with 82 IDH wild-type, 107 IDH mutant/1p19q intact, and 101 IDH mutant/1p19q codeleted gliomas. Two predictive models incorporating ADCmean-to-ADCNAWM ratio, age, and morphologic characteristics, with model A mandating calcification result and model B recording cyst formation, classified tumor type with areas under the receiver operating characteristic curve of 0.94 (95% confidence interval [CI]: 0.91, 0.97) and 0.96 (95% CI: 0.93, 0.98), respectively. In the test sample of 49 gliomas (nine IDH wild type, 21 IDH mutant/1p19q intact, and 19 IDH mutant/1p19q codeleted), the classification accuracy was 40 of 49 gliomas (82%; 95% CI: 71%, 92%) for model A and 42 of 49 gliomas (86%; 95% CI: 76%, 96%) for model B. Conclusion Two algorithms that incorporated apparent diffusion coefficient values, age, and tumor morphologic characteristics predicted isocitrate dehydrogenase status in World Health Organization grade II/III gliomas on the basis of standard clinical MRI sequences alone. © RSNA, 2020 Online supplemental material is available for this article.

The Impact of Chronic Health Conditions on Length of Stay and Mortality in a General PICU.

OBJECTIVES: Each year approximately 20,000 children are admitted to PICUs across the United Kingdom. It is highlighted in several international studies that 40-70% of children admitted to PICUs have at least one chronic health condition that leads to increased length of stay and higher mortality rates. The prevalence of chronic health conditions in children admitted to U.K. PICUs is unknown. The purpose of this study was to use existing clinical data to explore the prevalence and impact of chronic health conditions on length of stay and mortality in a tertiary U.K. PICU. DESIGN: Single-centre retrospective observational cohort study. SETTING: Single, tertiary referral PICU. PATIENTS: One thousand one hundred ninety-seven children 0-18 years old admitted between March 1, 2009, and February 28, 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were derived from the unit's data submitted to the Paediatric Intensive Care Audit Network, the U.K. national PICU dataset. Data included demographics, diagnosis, Pediatric Index of Mortality-2 score, PICU interventions, PICU outcomes, chronic health condition etiologies, admission, and discharge dates and times. In total, 554 of 1,197 (46.3%) had at least one chronic health condition. Of 554, 371 patients (67.1%) presented with a single chronic health condition, 126 (22.6%) with two chronic health conditions, and 57 (10.3%) with at least three chronic health conditions to a maximum of four chronic health conditions. There was a statistically significant difference in length of stay in those with a chronic health condition compared with those without (medians, 4 vs 3 d [interquartile range, 1-7 d]; Mann-Whitney U test, p < 0.001). The length of stay also increased significantly according to the number of chronic health conditions (Kruskal-Wallis test, p < 0.001). Mortality was significantly different between those with and without chronic health conditions (8.8% vs 5.4%; chi-square test, p = 0.024). Having two or at least three chronic health conditions significantly increased mortality compared with no chronic health conditions (odds ratio, 2.3 [CI, 1.2-4.55]; p = 0.013 and 2.95 [CI, 1.28-6.8]; p = 0.011), respectively. CONCLUSIONS: The increasing number of chronic healthcare conditions is associated with length of stay and mortality.

Factors Leading to Pregnancies in Stimulated Intrauterine Insemination Cycles and the Use of Consecutive Ejaculations Within a Small Clinic Environment.

INTRODUCTION: Understanding and improving IUI pregnancy rates has enormous global appeal and application. This pilot study goes one step further by utilising consecutive ejaculates from men with oligozoospermia and comparing with normozoospermic male group. MATERIALS AND METHODS: A retrospective analysis was performed on 117 IUI-stimulated treatment cycles in a small fertility clinic in North Middlesex University Hospitals Trust, UK, within a NHS setting. Risks of OHSS and multiple births are carefully controlled. RESULTS: In our cohort, several factors are associated with positive IUI pregnancies and these were: age of the woman, inseminating with ≥5 total progressive motile sperm; having ≥50 % Grade A sperm progression and having ≥1 follicle achieved with a realistic hMG dosage, hCG trigger and IUI of 29.7 h (2.5-38.4 h), with an endometrial thickness of 10.7 mm (6.6-13.4 mm). Bifollicular presence in at least half the cases along with hMG protocols added usefully to the pregnancy outcomes. CONCLUSIONS: The pregnancy rates per cycle were 19 and 23 % in the consecutive ejaculates and non-consecutive ejaculate groups, respectively, P = 0.59. For the whole cohort, the pregnancy rate was 20.51 % per cycle and 33.8 % per women. This approach if validated with large RCT will have universally beneficial effects.

A REALLY WHEEZY WAY TO SAVE MONEY.

AIM: To compare the palatability of oral non-soluble and oral soluble prednisolone tablets in paediatric patients admitted to the general paediatric wards in an acute London Trust. METHOD: As part of ongoing quality improvement initiatives, the Paediatric and Pharmacy departments compared tolerability of soluble versus non-soluble prednisolone in a group of 27 patients. Using a modified 5 point hedonic scale with 'smiley' faces we measured palatability and tolerance (swallowed versus refusal or vomiting) over two three week periods: the first period whilst soluble prednisolone was dispensed (n=17) and the second period after the switch to non-soluble prednisolone had been made (n=10). All data were collected by doctors and nurses on the two paediatrics wards. RESULTS: We found acceptance of prednisolone to be similar before and after formulations were switched: 2 non-tolerated doses before (n=17) versus 3 non-tolerated doses after the switch (n=10).We found that 'disguising' the taste of the non-soluble prednisolone within a portion of sugar free jam, or mixed with 5 ml of sugar-free blackcurrant cordial, helped with acceptance, although both soluble and non-soluble formulations were frequently reported to be "Yuk"! CONCLUSIONS: The Trust has since made the switch to non-soluble prednisolone for all paediatric inpatients and for take home medications. An information leaflet has been developed for parents or carers to understand how to crush the prednisolone tablets. We have not had any parent or carer reported difficulty in preparing or administering the medication.Children under 15 account for 37.8% (20,510 of 54,300) of annual hospital admissions for acute asthma.1 A minimum course of 3 days' oral steroids are recommended in the BTS/SIGN 2014 guideline on the management of asthma.2 This acute Trust covers a population of over 300,000 in deprived boroughs of London.A typical three-day course of soluble prednisolone (at 2 mg/kg as per guidance, or approximately 20 mg) costs £20.88, compared to £2.48 for the equivalent dose of non-soluble prednisolone dispensed with a tablet crusher. Several hospital trusts have switched to using non-soluble prednisolone in order to achieve cost savings, but there have been anecdotal reports of poor palatability, raising concerns about compliance with taking medication once discharged.The switch from a soluble to a non-soluble formulation of prednisolone represents an annual saving of more than £44,000 for this hospital alone and, at scale, could realise substantial potential savings to the NHS, without compromising patients' clinical care.

A really wheezy way to save money.

Evaluating the cost-saving potential of switching prednisolone formulation in the treatment of childhood wheeze.

Incidence and Predictors of Bacterial infection in Febrile Children with Sickle Cell Disease.

Children with sickle cell disease are at increased risk of developing bacteremia and other serious bacterial infections. Fever is a common symptom in sickle cell disease and can also occur with sickle cell crises and viral infections. We aimed to evaluate the incidence and predictors of bacteremia and bacterial infection in children with sickle cell disease presenting with fever to a district hospital and sickle cell center in London. A retrospective analysis was performed on all attendances of children (aged under 16 years) with sickle cell disease presenting with a fever of 38.5 °C or higher over a 1-year period. Confirmed bacterial infection was defined as bacteremia, bacterial meningitis, urinary tract infection (UTI), pneumonia, osteomyelitis or other bacterial infection with positive identification of organism. Children were defined as having a suspected bacterial infection if a bacterial infection was suspected clinically, but no organism was identified. Over a 1-year period there were 88 episodes analyzed in 59 children. Bacteremia occurred in 3.4% of episodes and confirmed bacterial infection in 7.0%. Suspected bacterial infection occurred in 33.0%. One death occurred from Salmonella typhirium septicemia. C-reactive protein (CRP) level and white blood cell (WBC) count were both significantly associated with bacterial infection (p = 0.004 and 0.02, respectively.) In conclusion, bacterial infections continue to be a significant problem in children with sickle cell disease. C-reactive protein was significantly associated with bacterial infections, and could be included in clinical risk criteria for febrile children with sickle cell disease.