ORCID Profile
0000-0002-3559-0595
Current Organisations
University of Southampton
,
Southampton University Hospitals NHS Trust
,
University of Cambridge Downing College
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Publications
Global Epidemiology of Pediatric Severe Sepsis: The Sepsis Prevalence, Outcomes, and Therapies Study
Publisher: American Thoracic Society
Date: 15-05-2015
International Survey of Critically Ill Children With Acute Neurologic Insults: The Prevalence of Acute Critical Neurological Disease in Children: A Global Epidemiological Assessment Study*
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2017
DOI: 10.1097/PCC.0000000000001093
Abstract: The international scope of critical neurologic insults in children is unknown. Our objective was to assess the prevalence and outcomes of children admitted to PICUs with acute neurologic insults. Prospective study. Multicenter ( n = 107 PICUs) and multinational (23 countries, 79% in North America and Europe). Children 7 days to 17 years old admitted to the ICU with new traumatic brain injury, stroke, cardiac arrest, CNS infection or inflammation, status epilepticus, spinal cord injury, hydrocephalus, or brain mass. None. We evaluated the prevalence and outcomes of children with predetermined acute neurologic insults. Child and center characteristics were recorded. Unfavorable outcome was defined as change in pre-post insult Pediatric Cerebral Performance Category score greater than or equal to 2 or death at hospital discharge or 3 months, whichever came first. Screening data yielded overall prevalence of 16.2%. Of 924 children with acute neurologic insults, cardiac arrest (23%) and traumatic brain injury (19%) were the most common. All-cause mortality at hospital discharge was 12%. Cardiac arrest subjects had highest mortality (24%), and traumatic brain injury subjects had the most unfavorable outcomes (49%). The most common neurologic insult was infection/inflammation in South America, Asia, and the single African site but cardiac arrest in the remaining regions. Neurologic insults are a significant pediatric international health issue. They are frequent and contribute substantial morbidity and mortality. These data suggest a need for an increased focus on acute critical neurologic diseases in infants and children including additional research, enhanced availability of clinical resources, and the development of new therapies.
Mortality in adult intensive care patients with severe systemic inflammatory response syndromes is strongly associated with the hypo-immune TNF −238A polymorphism
Publisher: Springer Science and Business Media LLC
Date: 28-08-2009
DOI: 10.1007/S00251-009-0395-6
Abstract: The systemic inflammatory response syndrome (SIRS) is associated with activation of innate immunity. We studied the association between mortality and measures of disease severity in the intensive care unit (ICU) and functional polymorphisms in genes coding for Toll-like receptor 4 (TLR4), macrophage migratory inhibitory factor (MIF), tumour necrosis factor (TNF) and lymphotoxin-alpha (LTA). Two hundred thirty-three patients with severe SIRS were recruited from one general adult ICU in a tertiary centre in the UK. DNA from patients underwent genotyping by 5' nuclease assay. Genotype was compared to phenotype. Primary outcome was mortality in ICU. Minor allele frequencies were TLR4 +896G 7%, MIF 173C 16%, TNF -238A 10% and LTA +252G 34%. The frequency of the hypoimmune minor allele TNF -238A was significantly higher in patients who died in ICU compared to those who survived (p = 0.0063) as was the frequency of the two haplotypes LTA +252G, TNF -1031T, TNF -308G, TNF -238A and LTA +252G, TNF-1031T, TNF-308A and TNF-238A (p = 0.0120 and 0.0098, respectively). These findings re-enforce the view that a balanced inflammatory/anti-inflammatory response is the most important determinant of outcome in sepsis. Genotypes that either favour inflammation or its counter-regulatory anti-inflammatory response are likely to influence mortality and morbidity.
The Association of Nutrition Status Expressed as Body Mass Index z Score With Outcomes in Children With Severe Sepsis: A Secondary Analysis From the Sepsis Prevalence, Outcomes, and Therapies (SPROUT)
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2018
DOI: 10.1097/CCM.0000000000003351
Abstract: The impact of nutrition status on outcomes in pediatric severe sepsis is unclear. We studied the association of nutrition status (expressed as body mass index z score) with outcomes in pediatric severe sepsis. Secondary analysis of the Sepsis Prevalence, Outcomes, and Therapies study. Patient characteristics, ICU interventions, and outcomes were compared across nutrition status categories (expressed as age- and sex-adjusted body mass index z scores using World Health Organization standards). Multivariable regression models were developed to determine adjusted differences in all-cause ICU mortality and ICU length of stay by nutrition status. One-hundred twenty-eight PICUs across 26 countries. Children less than 18 years with severe sepsis enrolled in the Sepsis Prevalence, Outcomes, and Therapies study ( n = 567). None. Nutrition status data were available for 417 patients. Severe undernutrition was seen in Europe (25%), Asia (20%), South Africa (17%), and South America (10%), with severe overnutrition seen in Australia/New Zealand (17%) and North America (14%). Severe undernutrition was independently associated with all-cause ICU mortality (adjusted odds ratio, 3.0 95% CI, 1.2–7.7 p = 0.02), whereas severe overnutrition in survivors was independently associated with longer ICU length of stay (1.6 d p = 0.01). There is considerable variation in nutrition status for children with severe sepsis treated across this selected network of PICUs from different geographic regions. Severe undernutrition was independently associated with higher all-cause ICU mortality in children with severe sepsis. Severe overnutrition was independently associated with greater ICU length of stay in childhood survivors of severe sepsis.
A clinical and economic evaluation of Control of Hyperglycaemia in Paediatric intensive care (CHiP): a randomised controlled trial
Publisher: National Institute for Health and Care Research
Date: 04-2014
DOI: 10.3310/HTA18260
Polymorphisms in Toll-like receptor 4 and the systemic inflammatory response syndrome
Publisher: Portland Press Ltd.
Date: 06-2003
DOI: 10.1042/BST0310652
Abstract: The systemic inflammatory response syndrome (SIRS) is a major cause of morbidity and mortality, and is thought to be due to an over- lification of an inflammatory response. The Toll-like receptor 4 (TLR4) Asp-299→Gly polymorphism has been shown to reduce lipopolysaccharide responsiveness. We examined whether this TLR4 polymorphism is associated with severity of SIRS. A trend was found between the minor allele and mortality in SIRS (odds ratio of 4.3 P=0.076), suggesting a role for TLR4 signalling in the severity of SIRS.
Protocol for a randomised pilot multiple centre trial of conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU)
Publisher: BMJ
Date: 12-2017
DOI: 10.1136/BMJOPEN-2017-019253
Abstract: Optimal targets for systemic oxygenation in paediatric critical illness are unknown. Observational data indicate that high levels of arterial oxygenation are associated with poor outcomes in resuscitation of the newborn and in adult critical illness. Within paediatric intensive care units (PICUs), staff prevent severe hypoxia wherever possible, but beyond this there is no consensus. Practice varies widely with age, diagnosis, treating doctor and local or national guidelines followed, though peripheral blood oxygen saturations (SpO 2 ) of % are often targeted. The overall aim of this pilot study is to determine the feasibility of performing a randomised trial in critically ill children comparing current practice of liberal SpO 2 targets with a more conservative target. Oxy-PICU is a pragmatic, open, pilot randomised controlled trial in infants and children requiring mechanical ventilation and receiving supplemental oxygen for abnormal gas exchange accepted for emergency admission to one of three participating UK PICUs. The study groups will be either a conservative SpO 2 target of 88%–92% (inclusive) or a liberal SpO 2 target of %. Infants and children who fulfil all inclusion criteria and none of the exclusion criteria will be randomised 1:1 by a secure web-based system to one of the two groups. Baseline demographics and clinical status will be recorded as well as daily measures of oxygenation and organ support. Discharge outcomes will also be recorded. In addition to observational data, blood and urine s les will be taken to identify biochemical markers of oxidative stress. Outcomes are targeted at assessing study feasibility with a primary outcome of adequate study recruitment (target: 120 participants). The trial received Health Research Authority approval on 1 June 2017 (16/SC/0617). Study findings will be disseminated in national and international conferences and peer-reviewed journals. NCT03040570.
Related Organisations
University Of Southampton
Location: United Kingdom of Great Britain and Northern Ireland
Southampton University Hospitals NHS Trust
Location: United Kingdom of Great Britain and Northern Ireland
University Of Cambridge Downing College
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for John Pappachan.