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"Baines, Paul"
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Title NMR-based metabolic profiling provides diagnostic and prognostic information in critically ill children with suspected infection
Sepsis, defined as life-threatening organ dysfunction caused by infection is difficult to distinguish clinically from infection or post-operative inflammation. We hypothesized that in a heterogeneous group of critically ill children, there would be different metabolic profiles between post-operative inflammation, bacterial and viral infection and infection with or without organ dysfunction. 1D
H nuclear magnetic resonance spectra were acquired in plasma samples from critically ill children. We included children with bacterial (n = 25) and viral infection (n = 30) and controls (n = 58) (elective cardiac surgery without infection). Principal component analysis was used for data exploration and partial least squares discriminant analysis models for the differences between groups. Area under receiver operating characteristic curve (AUC) values were used to evaluate the models. Univariate analysis demonstrated differences between controls and bacterial and viral infection. There was excellent discrimination between bacterial and control (AUC = 0.94), and viral and control (AUC = 0.83), with slightly more modest discrimination between bacterial and viral (AUC = 0.78). There was modest discrimination (AUC = 0.73) between sepsis with organ dysfunction and infection with no organ dysfunction. In critically ill children, NMR metabolomics differentiates well between those with a post-operative inflammation but no infection, and those with infection (bacterial and viral), and between sepsis and infection.
Journal Article
Which ethical values underpin England’s National Health Service reset of paediatric and maternity services following COVID-19: a rapid review
ObjectiveTo identify ethical values guiding decision making in resetting non-COVID-19 paediatric surgery and maternity services in the National Health Service (NHS).DesignA rapid review of academic and grey literature sources from 29 April to 31 December 2020, covering non-urgent, non-COVID-19 healthcare. Sources were thematically synthesised against an adapted version of the UK Government’s Pandemic Flu Ethical Framework to identify underpinning ethical principles. The strength of normative engagement and the quality of the sources were also assessed.SettingNHS maternity and paediatric surgery services in England.ResultsSearches conducted 8 September–12 October 2020, and updated in March 2021, identified 48 sources meeting the inclusion criteria. Themes that arose include: staff safety; collaborative working – including mutual dependencies across the healthcare system; reciprocity; and inclusivity in service recovery, for example, by addressing inequalities in service access. Embedded in the theme of staff and patient safety is embracing new ways of working, such as the rapid roll out of telemedicine. On assessment, many sources did not explicitly consider how ethical principles might be applied or balanced against one another. Weaknesses in the policy sources included a lack of public and user involvement and the absence of monitoring and evaluation criteria.ConclusionsOur findings suggest that relationality is a prominent ethical principle informing resetting NHS non-COVID-19 paediatric surgery and maternity services. Sources explicitly highlight the ethical importance of seeking to minimise disruption to caring and dependent relationships, while simultaneously attending to public safety. Engagement with ethical principles was ethics-lite, with sources mentioning principles in passing rather than explicitly applying them. This leaves decision makers and healthcare professionals without an operationalisable ethical framework to apply to difficult reset decisions and risks inconsistencies in decision making. We recommend further research to confirm or refine the usefulness of the reset phase ethical framework developed through our analysis.
Journal Article
Edmund Curll, Bookseller
Edmund Curll was a notorious figure among the publishers of the early eighteenth century: for his boldness, his lack of scruple, his publication of work without authors' consent, and his taste for erotic and scandalous publications. He was in legal trouble on several occasions for piracy and copyright infringement, unauthorised publication of the works of peers, and for seditious, blasphemous, and obscene publications. He stood in the pillory in 1728 for seditious libel. Above all, he was the constant target of the greatest poet and satirist of his age, Alexander Pope, whose work he pirated whenever he could and who responded with direct physical revenge (an emetic slipped into a drink) and persistent malign caricature. The war between Pope and Curll typifies some of the main cultural battles being waged between creativity and business. The story has normally been told from the poet's point of view, though more recently Curll has been celebrated as a kind of literary freedom-fighter. This book seeks to give a balanced and thoroughly-researched account of Curll's career in publishing between 1706 and 1747, untangling the mistakes and misrepresentations that have accrued over the years and restoring a clear sense of perspective to Curll's dealings in the literary marketplace. It examines the full range of Curll's output, including his notable antiquarian series, and uses extensive archive material to detail Curll's legal and other troubles, telling what is known about this strange and awkward figure.
eBook
Identifying critically ill children at high risk of acute kidney injury and renal replacement therapy
Acute kidney injury (AKI), a common complication in paediatric intensive care units (PICU), is associated with increased morbidity and mortality. In this single centre, prospective, observational cohort study, neutrophil gelatinase-associated lipocalin in urine (uNGAL) and plasma (pNGAL) and renal angina index (RAI), and combinations of these markers, were assessed for their ability to predict severe (stage 2 or 3) AKI in children and young people admitted to PICU. In PICU children and young people had initial and serial uNGAL and pNGAL measurements, RAI calculation on day 1, and collection of clinical data, including serum creatinine measurements. Primary outcomes were severe AKI and renal replacement therapy (RRT). Secondary outcomes were length of stay, hospital acquired infection and mortality. The area under the Receiver Operating Characteristic (ROC) curves and Youden index was used to determine biomarker performance and identify optimum cut-off values. Of 657 children recruited, 104 met criteria for severe AKI (15∙8%) and 47 (7∙2%) required RRT. Severe AKI was associated with increased length of stay, hospital acquired infection, and mortality. The area under the curve (AUC) for severe AKI prediction for Day 1 uNGAL, Day 1 pNGAL and RAI were 0.75 (95% Confidence Interval [CI] 0∙69, 0∙81), 0∙64 (95% CI 0∙56, 0∙72), and 0.73 (95% CI 0∙65, 0∙80) respectively. The optimal combination of measures was RAI and day 1 uNGAL, giving an AUC of 0∙80 for severe AKI prediction (95% CI 0∙71, 0∙88). In this heterogenous PICU cohort, urine or plasma NGAL in isolation had poorer prediction accuracy for severe AKI than in previously reported homogeneous populations. However, when combined together with RAI, they produced good prediction for severe AKI.
Journal Article
Procalcitonin, C-reactive protein, neutrophil gelatinase-associated lipocalin, resistin and the APTT waveform for the early diagnosis of serious bacterial infection and prediction of outcome in critically ill children
Bacterial Infections remains a leading cause of death in the Paediatric Intensive Care Unit (PICU). In this era of rising antimicrobial resistance, new tools are needed to guide antimicrobial use. The aim of this study was to investigate the accuracy of procalcitonin (PCT), neutrophil gelatinase-associated lipocalin (NGAL), resistin, activated partial thromboplastin time (aPTT) waveform and C-reactive protein (CRP) for the diagnosis of serious bacterial infection (SBI) in children on admission to PICU and their use as prognostic indicators.
A regional PICU in the United Kingdom.
Consecutive PICU admissions between October 2010 and June 2012.
Blood samples were collected daily for biomarker measurement. The primary outcome measure was performance of study biomarkers for diagnosis of SBI on admission to PICU based on clinical, radiological and microbiological criteria. Secondary outcomes included durations of PICU stay and invasive ventilation and 28-day mortality. Patients were followed up to day 28 post-admission.
A total of 657 patients were included in the study. 92 patients (14%) fulfilled criteria for SBI. 28-day mortality was 2.6% (17/657), but 8.7% (8/92) for patients with SBI. The combination of PCT, resistin, plasma NGAL and CRP resulted in the greatest net reclassification improvement compared to CRP alone (0.69, p<0.005) with 10.5% reduction in correct classification of patients with SBI (p 0.52) but a 78% improvement in correct classification of patients without events (p <0.005). A statistical model of prolonged duration of PICU stay found log-transformed maximum values of biomarkers performed better than first recorded biomarkers. The final model included maximum values of CRP, plasma NGAL, lymphocyte and platelet count (AUC 79%, 95% CI 73.7% to 84.2%). Longitudinal profiles of biomarkers showed PCT levels to decrease most rapidly following admission SBI.
Combinations of biomarkers, including PCT, may improve accurate and timely identification of SBI on admission to PICU.
Journal Article
NMR-based metabolic profiling provides diagnostic and prognostic information in critically ill children with suspected infection
Sepsis, defined as life-threatening organ dysfunction caused by infection is difficult to distinguish clinically from infection or post-operative inflammation. We hypothesized that in a heterogeneous group of critically ill children, there would be different metabolic profiles between post-operative inflammation, bacterial and viral infection and infection with or without organ dysfunction. 1D
1
H nuclear magnetic resonance spectra were acquired in plasma samples from critically ill children. We included children with bacterial (n = 25) and viral infection (n = 30) and controls (n = 58) (elective cardiac surgery without infection). Principal component analysis was used for data exploration and partial least squares discriminant analysis models for the differences between groups. Area under receiver operating characteristic curve (AUC) values were used to evaluate the models. Univariate analysis demonstrated differences between controls and bacterial and viral infection. There was excellent discrimination between bacterial and control (AUC = 0.94), and viral and control (AUC = 0.83), with slightly more modest discrimination between bacterial and viral (AUC = 0.78). There was modest discrimination (AUC = 0.73) between sepsis with organ dysfunction and infection with no organ dysfunction. In critically ill children, NMR metabolomics differentiates well between those with a post-operative inflammation but no infection, and those with infection (bacterial and viral), and between sepsis and infection.
Journal Article
Developing and evaluating multimedia information resources to improve engagement of children, adolescents, and their parents with trials (TRECA study): Study protocol for a series of linked randomised controlled trials
Background
Randomised controlled trials are widely established as the best method for testing health interventions whilst minimising bias. However, recruitment and subsequent retention of children and adolescents in healthcare trials is challenging. Participant information sheets are often lengthy and difficult to read and understand. Presenting key information using multimedia may help to overcome these limitations and better support young people and their parents in deciding whether to participate in a clinical trial.
Methods
The TRECA (TRials Engagement in Children and Adolescents) study has two phases. The first phase involves a qualitative study with children and adolescents and their parents to inform the development of multimedia information resources and iterative user testing to refine the resources. The second phase will embed the use of the multimedia information resources into six host trials in the United Kingdom. Patients and parents approached to participate in the host trials will be randomly allocated to either use the multimedia information resource in conjunction with standard participant information sheets, the multimedia information resource alone, or the standard participant information sheets alone. The primary outcome will be the effect of the multimedia information resources on recruitment into trials. Other outcomes measured include the effect of multimedia information resources on retention of participants into the host trials and the impact on family members’ decision-making processes, when compared to standard participant information sheets alone.
Discussion
This study will inform whether multimedia information resources, when developed using participatory design principles, are able to increase recruitment and retention of children and adolescents into trials. There is also the potential for patients to make better informed decisions through the use of multimedia information resources. The multimedia information resources also have the potential to assist with providing information on other healthcare decisions outside of clinical trials.
Trial registration
ISRCTN registry:
ISRCTN73136092
(doi:
10.1186/ISRCTN73136092
). Registered on 24 August 2016.
Journal Article
Meningococcal Disease in Children in Merseyside, England: A 31 Year Descriptive Study
Meningococcal disease (MCD) is the leading infectious cause of death in early childhood in the United Kingdom, making it a public health priority. MCD most commonly presents as meningococcal meningitis (MM), septicaemia (MS), or as a combination of the two syndromes (MM/MS). We describe the changing epidemiology and clinical presentation of MCD, and explore associations with socioeconomic status and other risk factors. A hospital-based study of children admitted to a tertiary children's centre, Alder Hey Children's Foundation Trust, with MCD, was undertaken between 1977 to 2007 (n = 1157). Demographics, clinical presentations, microbiological confirmation and measures of deprivation were described. The majority of cases occurred in the 1-4 year age group and there was a dramatic fall in serogroup C cases observed with the introduction of the meningococcal C conjugate (MCC) vaccine. The proportion of MS cases increased over the study period, from 11% in the first quarter to 35% in the final quarter. Presentation with MS (compared to MM) and serogroup C disease (compared to serogroup B) were demonstrated to be independent risk factors for mortality, with odds ratios of 3.5 (95% CI 1.18 to 10.08) and 2.18 (95% CI 1.26 to 3.80) respectively. Cases admitted to Alder Hey were from a relatively more deprived population (mean Townsend score 1.25, 95% CI 1.09 to 1.41) than the Merseyside reference population. Our findings represent one of the largest single-centre studies of MCD. The presentation of MS is confirmed to be a risk factor of mortality from MCD. Our study supports the association between social deprivation and MCD.
Journal Article