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Patel A.J.,St Georges Medical School | Som R.,John Radcliffe Hospital
Interactive Cardiovascular and Thoracic Surgery | Year: 2013

A best evidence topic was written according to a structured protocol. The question addressed was what is the optimum prophylaxis against gastrointestinal haemorrhage for patients undergoing adult cardiac surgery: histamine receptor antagonists (H2RA) or proton-pump inhibitors? A total of 201 papers were found; of which, 8 represented the best evidence. The authors, date, journal, study type, population, main outcome measures and Results were tabulated. Only one randomized controlled trial (RCT) with relevant clinical outcomes was identified. The rest of the studies consisted of five prospective studies and two retrospective studies. In the RCT, there were no reported cases of gastrointestinal haemorrhage in the proton-pump inhibitor cohort, whereas 4 patients taking H2RA developed it. The rate of active gastrointestinal ulceration was higher in the H2RA cohort in comparison with the proton-pump inhibitor cohort (21.4 vs 4.3%). A prospective study followed 2285 consecutive patients undergoing cardiac surgery who received either no prophylaxis, or a proton-pump inhibitor. Chi-squared analysis showed the risk of bleeding to be lower in those receiving the proton-pump inhibitor (P < 0.05). Another study of 6316 patients undergoing coronary artery bypass grafting demonstrated a reduced risk of gastrointestinal bleed with prophylactic intravenous omeprazole (odds ratio = 0.2; confidence intervals = 0.1-0.8; P < 0.05). One study successfully showed that proton-pump inhibitors are effective in adequately suppressing gastric acid levels, regardless of Helicobacter pylori infection status; conversely, this study suggested that H2RAs were not. The evidence for H2RAs is marginal, with no study showing a clear benefit. One study showed that ulcer prophylaxis with H2RA did not correlate with the clinical outcome. Another study demonstrated gastric ulceration to be a common gastrointestinal complication in spite of regular H2RA use. There is also evidence to suggest that acid suppression increases the risk of nosocomial pneumonia, although open heart surgery may be a confounding factor in this association. Two RCTs showed that H2RAs may augment the immune system and reducing stress following cardiac surgery. Proton-pump inhibitors appear to be the superior agent for prophylaxis against gastrointestinal bleed in patients undergoing cardiac surgery, although rigorous comparative data are sparse. Furthermore, level-I evidence would confirm this. © 2012 The Author.


Charles E.,St. Georges Medical School | Scales A.,DoNation | Scales A.,Great Ormond St Childrens Hospital Nhs Foundation Trust | Brierley J.,Great Ormond St Childrens Hospital Nhs Foundation Trust
Archives of Disease in Childhood: Fetal and Neonatal Edition | Year: 2014

Objective: Neonatal organ donation does not occur in the UK. Unlike in other European countries, Australasia and the USA death verification/ certification standards effectively prohibit use of neurological criteria for diagnosing death in infants between 37 weeks' gestation and 2 months of age and therefore donation after neurological determination of death. Neonatal donation after circulatory definition of death is also possible but is not currently undertaken. There is currently no specific information about the potential neonatal organ donation in the UK; this study provides this in one tertiary children's hospital. Design: Retrospective mortality database, clinical document database and patient notes review. Setting: Neonatal and Paediatric Intensive Care in a tertiary children's hospital. Patients: Infants dying between 37 weeks' gestation and 2 months of age between 1 January 2006 and 31 October 2012. Potential assessed using current UK guidelines for older children and neonatal criteria elsewhere. Results: 84 infants died with 45 (54%) identified as potential donors. 34 (40%) were identified as potential donors after circulatory de finition of death and 11 (13%) were identified as being theoretical potential donors after neurological determination of death. 10 (12%) were identified as unlikely donors due to relative contraindications and 39 (46%) were definitely not potential donors. Conclusions: With around 60 paediatric organ donors in the UK annually, there does appear significant potential for donation within the neonatal population. Reconsideration of current infant brain stem death guidelines is required to allow parents the opportunity of donation after neurological determination of death, together with mandatory training in organ donation for neonatal teams, which will also facilitate donation after circulatory definition of death.


Irkulla S.,University of Surrey | Ujam B.,University of Surrey | Gaze D.,St Georges Medical School | Kumar D.,St Georges Medical School | Mendall M.A.,University of Surrey
Journal of Inflammation (United Kingdom) | Year: 2013

Background: Obesity and serum C-reactive protein (CRP) (a sensitive marker of inflammatory activity) are associated with most chronic diseases. Abdominal adiposity along with age is the strongest determinant of baseline CRP levels in healthy subjects. The mechanism of the association of serum CRP with disease is uncertain. We hypothesized that baseline serum CRP is a marker of inflammatory responsiveness to injury and that abdominal adiposity is the main determinant of this responsiveness. We studied the effect of abdominal adiposity, age and other environmental risk factors for chronic disease on the CRP response to a standardised surgical insult, unilateral hernia repair to not only test this hypothesis but to inform the factors which must be taken into account when assessing systemic inflammatory responses to surgery. Methods. 102 male subjects aged 24-94 underwent unilateral hernia repair by a single operator. CRP was measured at 0, 6, 24 and 48 hrs. Response was defined as the peak CRP adjusted for baseline CRP. Results: Age and waist:hip ratio (WHR) were associated both with basal CRP and CRP response with similar effect sizes after adjustment for a wide-range of covariates. The adjusted proportional difference in CRP response per 10% increase in WHR was 1.50 (1.17-1.91) p = 0.0014 and 1.15(1.00-1.31) p = 0.05 per decade increase in age. There was no evidence of important effects of other environmental cardiovascular risk factors on CRP response. Conclusion: Waist:hip ratio and age need to be considered when studying the inflammatory response to surgery. The finding that age and waist:hip ratio influence baseline and post-operative CRP levels to a similar extent suggests that baseline CRP is a measure of inflammatory responsiveness to casual stimuli and that higher age and obesity modulate the generic excitability of the inflammatory system leading to both higher baseline CRP and higher CRP response to surgery. The mechanism for the association of baseline CRP and waist:hip ratio to chronic disease outcomes could be through this increase in inflammatory system excitability. © 2013 Irkulla et al.; licensee BioMed Central Ltd.


Mendall M.A.,Mayday University Hospital | Viran Gunasekera A.,Mayday University Hospital | Joseph John B.,Mayday University Hospital | Kumar D.,St. Georges Medical School
Digestive Diseases and Sciences | Year: 2011

Background: Obesity is associated with a proinflammatory state. Aim: To determine whether obesity at diagnosis is a risk factor for Crohn's disease vs. ulcerative colitis and also vs. community controls and whether there is a U-shaped relationship between body mass index at diagnosis and risk of Crohn's disease versus ulcerative colitis. Methods: A total of 524 consecutive inflammatory bowel disease patients attending gastroenterology clinics were administered a questionnaire inquiring about weight at diagnosis and height as well as other risk factors for inflammatory bowel disease. An opportunistic control group of 480 community controls aged 50-70 were randomly selected from the registers of four local general practices as part of another study. Results: Obesity at diagnosis was more common in subjects with Crohn's disease versus ulcerative colitis odds ratio 2.02 (1.18-3.43) p = 0.0096 and also Crohn's disease versus community controls in the 50-70 year age group (odds ratio 3.22 (1.59-6.52) p = 0.001). There was evidence of a 'dose response' with increasing degrees of obesity associated with increased risk. Low BMI at diagnosis was also associated with risk of Crohn's disease versus ulcerative colitis. A U-shaped relationship between BMI and risk of Crohn's was supported by the strong inverse association of BMI at diagnosis (p = 0.0001) and positive association of BMI at diagnosis squared (p = 0.0002) when they were fitted together into the model. Conclusions: Obesity may play a role in the pathogenesis of Crohn's disease and it may be that obesity-related enteropathy is a distinct entity or a sub-type of Crohn's disease. © 2011 Springer Science+Business Media, LLC.


Ellis H.C.,Royal Brompton Hospital | Cowman S.,Royal Brompton Hospital | Cowman S.,Imperial College London | Fernandes M.,St Georges Medical School | And 4 more authors.
European Respiratory Journal | Year: 2016

The clinical course of bronchiectasis is unpredictable, posing a challenge both in clinical practice and in research. Two mortality prediction scores, the bronchiectasis severity index (BSI) and FACED scores, have recently been developed. The aim of this study was to assess the ability of these scores to predict long-term mortality and to compare the two scores. The study was a single-centre retrospective cohort analysis consisting of 91 subjects originally recruited in 1994. BSI and FACED scores were calculated at the time of enrolment and long-term mortality ascertained. Data was available for 74 patients with a median of 18.8 years of follow-up. Both scoring systems had similar predictive power for 5-year mortality (area under receiver operator characteristic curve (AUC) 0.79 for BSI and 0.8 for FACED). Both scores were able to predict 15-year mortality with the FACED score showing slightly superior predictive power (AUC 0.82 versus 0.69, p=0.0495). This study provides further validation of the FACED and BSI scores for the prediction of mortality in bronchiectasis and demonstrates their utility over a longer period than originally described. Whilst both scores had excellent predictive power, the FACED score was superior for 15-year mortality. Copyright © 2016 by the European Respiratory Society.


Utomi V.,Liverpool John Moores University | Oxborough D.,Liverpool John Moores University | Whyte G.P.,Liverpool John Moores University | Somauroo J.,Liverpool John Moores University | And 5 more authors.
Heart | Year: 2013

Context: The athlete's heart (AH) remains a popular topic of study. Controversy related to training-specific cardiac adaptation in male athletes, and continuing developments in imaging technology and scaling prompted this systematic review and meta-analysis. Objective: To provide new insight in relation to: 1) cardiac adaptation to divergent training patterns in male athletes, 2) a developing research database using cardiac magnetic resonance (CMR) in athletes; 3) functional data derived from tissue-Doppler analysis as well as right ventricular (RV) and left atrial (LA) measurements in athletes; and 4) an awareness of the impact of body size on cardiac dimensions. Study design: Systematic review and meta-analysis of prospective trials. Data extraction performed by two researchers. Data sources: Pub Med, Medline, Scopus and ISI Web of knowledge scholarly data base. Study selection: Prospective studies were included if they were echocardiographic or CMR trials of elite young male athletes, with clear indication of type of sports and passed a quality criteria checklist. Results: All left ventricular (LV) structural parameters were higher in athletes than in controls. Only LV end-diastolic diameter and volume were higher in endurance athletes than in resistance athletes: 54.8 mm (95% CI 54.1 to 55.6) vs 52.4 mm (95% CI 51.2 to 53.6); p<0.001 and 171 ml (95% CI 157 to 185) vs 131 ml (95% CI 120 to 142); p<0.001, respectively. RV end-diastolic volume, mass and LA diameter were higher in endurance athletes than controls. LV end-diastolic volume was larger when CMR was used rather than echocardiography: 178 ml (95% CI Q7 162 to 194) vs 135 ml (95% CI 128 to 142); p<0.001. Meta-analysis regression models demonstrated positive and significant associations between body surface area (BSA) and LV mass, RV mass and LA diameter. Conclusions: Morphological features of the male AH were noted in both athlete groups. A training-specific pattern of concentric hypertrophy was not discerned in resistance athletes. Both imaging mode and BSA can have a significant impact on the interpretation of AH data.


Kaye G.C.,University of Queensland | Linker N.J.,James Cook University | Marwick T.H.,Menzies Research Institute | Pollock L.,Medtronic | And 4 more authors.
European Heart Journal | Year: 2015

Aim: Chronic right ventricle (RV) apical (RVA) pacing is standard treatment for an atrioventricular (AV) block but may be deleterious to left ventricle (LV) systolic function. Previous clinical studies of non-apical pacing have produced conflicting results. The aim of this randomized, prospective, international, multicentre trial was to compare change in LV ejection fraction (LVEF) between right ventricular apical and high septal (RVHS) pacing over a 2-year study period. Methods and results: We randomized 240 patients (age 74 ± 11 years, 67% male) with a high-grade AV block requiring >90% ventricular pacing and preserved baseline LVEF >50%, to receive pacing at the RVA (n = 120) or RVHS (n = 120). At 2 years, LVEF decreased in both the RVA (57 ± 9 to 55 ± 9%, P = 0.047) and the RVHS groups (56 ± 10 to 54 ± 10%, P = 0.0003). However, there was no significant difference in intra-patient change in LVEF between confirmed RVA (n = 85) and RVHS (n = 83) lead position (P = 0.43). There were no significant differences in heart failure hospitalization, mortality, the burden of atrial fibrillation, or plasma brain natriutetic peptide levels between the two groups. A significantly greater time was required to place the lead in the RVHS position (70 ± 25 vs. 56 ± 24 min, P < 0.0001) with longer fluoroscopy times (11 ± 7 vs. 5 ± 4 min, P < 0.0001). Conclusion: In patients with a high-grade AV block and preserved LV function requiring a high percentage of ventricular pacing, RVHS pacing does not provide a protective effect on left ventricular function over RVA pacing in the first 2 years. © 2014 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014.


Amin K.,St Georges Medical School
BMJ case reports | Year: 2011

The authors present two patients referred by colleagues after traumatic hand injury. However, upon closer inspection, both patients had pigmented lesions under the nail bed, which upon biopsy showed proven subungual malignant melanoma. The authors wish to emphasise the importance of this diagnosis, especially in emergency care.


Clayton-Smith J.,St Marys Hospital | O'Sullivan J.,St Marys Hospital | Daly S.,St Marys Hospital | Bhaskar S.,St Marys Hospital | And 20 more authors.
American Journal of Human Genetics | Year: 2011

Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS or Ohdo syndrome) is a multiple anomaly syndrome characterized by severe intellectual disability, blepharophimosis, and a mask-like facial appearance. A number of individuals with SBBYSS also have thyroid abnormalities and cleft palate. The condition usually occurs sporadically and is therefore presumed to be due in most cases to new dominant mutations. In individuals with SBBYSS, a whole-exome sequencing approach was used to demonstrate de novo protein-truncating mutations in the highly conserved histone acetyltransferase gene KAT6B (MYST4/MORF)) in three out of four individuals sequenced. Sanger sequencing was used to confirm truncating mutations of KAT6B, clustering in the final exon of the gene in all four individuals and in a further nine persons with typical SBBYSS. Where parental samples were available, the mutations were shown to have occurred de novo. During mammalian development KAT6B is upregulated specifically in the developing central nervous system, facial structures, and limb buds. The phenotypic features seen in the Qkf mouse, a hypomorphic Kat6b mutant, include small eyes, ventrally placed ears and long first digits that mirror the human phenotype. This is a further example of how perturbation of a protein involved in chromatin modification might give rise to a multisystem developmental disorder. © 2011 The American Society of Human Genetics.


PubMed | Royal Brompton Hospital, St Georges Medical School and Imperial College London
Type: Journal Article | Journal: The European respiratory journal | Year: 2016

The clinical course of bronchiectasis is unpredictable, posing a challenge both in clinical practice and in research. Two mortality prediction scores, the bronchiectasis severity index (BSI) and FACED scores, have recently been developed. The aim of this study was to assess the ability of these scores to predict long-term mortality and to compare the two scores.The study was a single-centre retrospective cohort analysis consisting of 91 subjects originally recruited in 1994. BSI and FACED scores were calculated at the time of enrolment and long-term mortality ascertained. Data was available for 74 patients with a median of 18.8years of follow-up.Both scoring systems had similar predictive power for 5-year mortality (area under receiver operator characteristic curve (AUC) 0.79 for BSI and 0.8 for FACED). Both scores were able to predict 15-year mortality with the FACED score showing slightly superior predictive power (AUC 0.82 versus 0.69, p=0.0495).This study provides further validation of the FACED and BSI scores for the prediction of mortality in bronchiectasis and demonstrates their utility over a longer period than originally described. Whilst both scores had excellent predictive power, the FACED score was superior for 15-year mortality.

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