Browsing by Author "Gavin C K W Koh"

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    In the critically ill patient, diabetes predicts mortality independent of statin therapy but is not associated with acute lung injury: A cohort study
    (2012-06-01) Gavin C K W Koh; Alexander P J Vlaar; Jorrit J. Hofstra; H. Katrien De Jong; Samuel Van Nierop; Sharon J. Peacock; W. Joost Wiersinga; Marcus J. Schultz; Nicole P. Juffermans; Academic Medical Centre, University of Amsterdam; Mahidol University; Addenbrooke's Hospital; Heartlands Hospital; University of Amsterdam
    Objectives: Patients with diabetes mellitus form 23%-30% of published cohorts of critically ill patients. Conflicting published evidence links diabetes mellitus to both higher and lower mortality. Other cohort studies suggest that diabetes mellitus protects against acute lung injury. We hypothesized that diabetes mellitus is an independent risk factor for mortality. We further hypothesized that diabetes mellitus is a risk factor for cardiac overload and not for acute lung injury. Design: Retrospective cohort study. Setting: The intensive care unit of a tertiary referral hospital. Patients: From November 1, 2004, to October 1, 2007, a cohort of patients admitted ≥48 hrs to the intensive care unit. Interventions: None. Measurements and Main Results: Of 2,013 patients, 317 had diabetes mellitus. Ninety-day mortality was higher in the diabetes mellitus patients compared to patients without diabetes mellitus (hazard ratio 1.53, 95% confidence interval 1.29-1.80). This association strengthened after adjusting for confounders and for medication (hazard ratio 1.53, 95% confidence interval 1.07-2.17).We found no association between diabetes mellitus and acute lung injury (relative risk ratio 1.01, 95% confidence interval 0.78-1.32; adjusted relative risk ratio 0.99, 95% confidence interval 0.75-1.31), but diabetes mellitus was a risk factor for cardiac overload (relative risk ratio 1.91, 95% confidence interval 1.30-2.81; adjusted relative risk ratio 1.45, 95% confidence interval 0.97-2.18). Statins were associated with both a reduced risk of mortality (hazard ratio 0.74, 95% confidence interval 0.63-0.87; adjusted hazard ratio 0.53, 95% confidence interval 0.44-0.64) and a decreased risk of developing acute lung injury (relative risk ratio 0.71, 95% confidence interval 0.56-0.89; adjusted relative risk ratio 0.61, 95% confidence interval 0.47-0.79). Conclusions: Diabetes mellitus is an independent risk factor for mortality in critically ill patients and failure to adjust for statins underestimates the size of this association. Diabetes mellitus is not associated with acute lung injury but is associated with cardiac overload. A diagnosis of cardiac overload excludes a diagnosis of acute lung injury. Investigators who do not account for cardiac overload as a competing alternative outcome may therefore falsely conclude that diabetes mellitus protects from acute lung injury. © 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.
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    Melioidosis vaccines: A systematic review and appraisal of the potential to exploit biodefense vaccines for public health purposes
    (2012-01-01) Sharon J. Peacock; Direk Limmathurotsakul; Yoel Lubell; Gavin C K W Koh; Lisa J. White; Nicholas P J Day; Richard W. Titball; Mahidol University; University of Cambridge; Nuffield Department of Clinical Medicine; University of Exeter
    Background: Burkholderia pseudomallei is a Category B select agent and the cause of melioidosis. Research funding for vaccine development has largely considered protection within the biothreat context, but the resulting vaccines could be applicable to populations who are at risk of naturally acquired melioidosis. Here, we discuss target populations for vaccination, consider the cost-benefit of different vaccination strategies and review potential vaccine candidates. Methods and Findings: Melioidosis is highly endemic in Thailand and northern Australia, where a biodefense vaccine might be adopted for public health purposes. A cost-effectiveness analysis model was developed, which showed that a vaccine could be a cost-effective intervention in Thailand, particularly if used in high-risk populations such as diabetics. Cost-effectiveness was observed in a model in which only partial immunity was assumed. The review systematically summarized all melioidosis vaccine candidates and studies in animal models that had evaluated their protectiveness. Possible candidates included live attenuated, whole cell killed, sub-unit, plasmid DNA and dendritic cell vaccines. Live attenuated vaccines were not considered favorably because of possible reversion to virulence and hypothetical risk of latent infection, while the other candidates need further development and evaluation. Melioidosis is acquired by skin inoculation, inhalation and ingestion, but routes of animal inoculation in most published studies to date do not reflect all of this. We found a lack of studies using diabetic models, which will be central to any evaluation of a melioidosis vaccine for natural infection since diabetes is the most important risk factor. Conclusion: Vaccines could represent one strand of a public health initiative to reduce the global incidence of melioidosis. © 2012 Peacock et al.
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    Prospective observational study of the frequency and features of intra-abdominal abscesses in patients with melioidosis in northeast Thailand
    (2012-10-01) Rapeephan R. Maude; Teerapon Vatcharapreechasakul; Pitchayanant Ariyaprasert; Richard J. Maude; Maliwan Hongsuwan; Prayoon Yuentrakul; Direk Limmathurotsakul; Gavin C K W Koh; Wipada Chaowagul; Nicholas P J Day; Sharon J. Peacock; Mahidol University; Sappasitthiprasong Hospital; Nuffield Department of Clinical Medicine; University of Cambridge
    Retrospective case series from Thailand have reported the presence of intra-abdominal abscesses in around half of patients with melioidosis, a much higher rate than our clinical experience would suggest. We performed a prospective, observational study of 230 adult patients with culture-confirmed melioidosis in which all patients underwent abdominal ultrasound. One or more abscesses were detected in the liver and/or spleen in 77 (33%) cases. These were often multiple (70%, 31/44 in hepatic abscesses and 88%, 50/57 in splenic abscesses) and clinically silent (27% of cases with abscesses presenting with abdominal pain). The mortality rate at 4 weeks post-discharge was lower in patients who were abscess-positive vs abscess-negative (10%, 8/77 vs 20%, 31/153). © 2012 Royal Society of Tropical Medicine and Hygiene.
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    Survey of antimicrobial resistance in clinical Burkholderia pseudomallei isolates over two decades in Northeast Thailand
    (2011-11-01) Vanaporn Wuthiekanun; Premjit Amornchai; Natnaree Saiprom; Narisara Chantratita; Wirongrong Chierakul; Gavin C K W Koh; Wipada Chaowagul; Nicholas P J Day; Direk Limmathurotsakul; Sharon J. Peacock; Mahidol University; Sappasitthiprasong Hospital; Nuffield Department of Clinical Medicine; University of Cambridge
    A 21-year survey conducted in northeast Thailand of antimicrobial resistance to parenteral antimicrobial drugs used to treat melioidosis identified 24/4,021 (0.6%) patients with one or more isolates resistant to ceftazidime (n ∇ 8), amoxicillin-clavulanic acid (n ∇ 4), or both drugs (n ∇ 12). Two cases were identified at admission, and the remainder were detected a median of 15 days after starting antimicrobial therapy. Resistance to carbapenem drugs was not detected. These findings support the current prescribing recommendations for melioidosis. Copyright © 2011 American Society for Microbiology. All Rights Reserved.