Early clinical and laboratory risk factors of intensive care unit requirement during 2004–2008 dengue epidemics in Singapore: a matched case–control study

Background: Dengue infection can result in severe clinical manifestations requiring intensive care. Effective triage is critical for early clinical management to reduce morbidity and mortality. However, there is limited knowledge on early risk factors of intensive care unit (ICU) requirement. This study aims to identify early clinical and laboratory risk factors of ICU requirement at first presentation in hospital and 24 hours prior to ICU requirement. Method: A retrospective 1:4 matched case–control study was performed with 27 dengue patients who required ICU, and 108 dengue patients who did not require ICU from year 2004–2008, matched by year of dengue presentation. Univariate and multivariate conditional logistic regression were performed. Optimal predictive models were generated with statistically significant risk factors identified using stepwise forward and backward elimination method. Results: ICU dengue patients were significantly older (P=0.003) and had diabetes (P=0.031), compared with non-ICU dengue patients. There were seven deaths among ICU patients at median seven days post fever. At first presentation, the WHO 2009 classification of dengue severity was significantly associated (P<0.001) with ICU, but not the WHO 1997 classification. Early clinical risk factors at presentation associated with ICU requirement were hematocrit change ≥20% concurrent with platelet <50 K [95% confidence-interval (CI)=2.46-30.53], hypoproteinemia (95% CI=1.09-19.74), hypotension (95% CI=1.83-31.79) and severe organ involvement (95% CI=3.30-331). Early laboratory risk factors at presentation were neutrophil proportion (95% CI=1.04-1.17), serum urea (95% CI=1.02-1.56) and alanine aminotransferase level (95% CI=1.001-1.06). This predictive model has sensitivity and specificity up to 88%. Early laboratory risk factors at 24 hours prior to ICU were lymphocyte (95% CI=1.03-1.38) and monocyte proportions (95% CI=1.02-1.78), pulse rate (95% CI=1.002-1.14) and blood pressure (95% CI=0.92-0.996). This predictive model has sensitivity and specificity up to 88.9% and 78%, respectively. Conclusions: This is the first matched case–control study, to our best knowledge, that identified early clinical and laboratory risk factors of ICU requirement during hospitalization. These factors suggested differential pathophysiological background of dengue patients as early as first presentation prior to ICU requirement, which may reflect the pathogenesis of dengue severity. These risk models may facilitate clinicians in triage of patients, after validating in larger independent studies.Published versio

Novel, Meso-Substituted Cationic Porphyrin Molecule for Photo-Mediated Larval Control of the Dengue Vector Aedes aegypti

Dengue is a life-threatening viral disease of growing importance, transmitted by Aedes mosquito vectors. The control of mosquito larvae is crucial to contain or prevent disease outbreaks, and the discovery of new larvicides able to increase the efficacy and the flexibility of the vector control approach is highly desirable. Porphyrins are a class of molecules which generate reactive oxygen species if excited by visible light, thus inducing oxidative cell damage and cell death. In this study we aimed at assessing the potential of this photo-mediated cytotoxic mechanism to kill Aedes (Stegomyia) aegypti mosquito larvae. The selected porphyrin molecule, meso-tri(N-methylpyridyl),meso-mono(N-tetradecylpyridyl)porphine (C14 for simplicity), killed the larvae at doses lower than 1 µM, and at light intensities 50–100 times lower than those typical of natural sunlight, by damaging their intestinal tissues. The physicochemical properties of C14 make it easily adsorbed into organic material, and we exploited this feature to prepare an ‘insecticidal food’ which efficiently killed the larvae and remained active for at least 14 days after its dispersion in water. This study demonstrated that photo-sensitizing agents are promising tools for the development of new larvicides against mosquito vectors of dengue and other human and animal diseases

The dominant Anopheles vectors of human malaria in the Asia-Pacific region: occurrence data, distribution maps and bionomic précis

<p>Abstract</p> <p>Background</p> <p>The final article in a series of three publications examining the global distribution of 41 dominant vector species (DVS) of malaria is presented here. The first publication examined the DVS from the Americas, with the second covering those species present in Africa, Europe and the Middle East. Here we discuss the 19 DVS of the Asian-Pacific region. This region experiences a high diversity of vector species, many occurring sympatrically, which, combined with the occurrence of a high number of species complexes and suspected species complexes, and behavioural plasticity of many of these major vectors, adds a level of entomological complexity not comparable elsewhere globally. To try and untangle the intricacy of the vectors of this region and to increase the effectiveness of vector control interventions, an understanding of the contemporary distribution of each species, combined with a synthesis of the current knowledge of their behaviour and ecology is needed.</p> <p>Results</p> <p>Expert opinion (EO) range maps, created with the most up-to-date expert knowledge of each DVS distribution, were combined with a contemporary database of occurrence data and a suite of open access, environmental and climatic variables. Using the Boosted Regression Tree (BRT) modelling method, distribution maps of each DVS were produced. The occurrence data were abstracted from the formal, published literature, plus other relevant sources, resulting in the collation of DVS occurrence at 10116 locations across 31 countries, of which 8853 were successfully geo-referenced and 7430 were resolved to spatial areas that could be included in the BRT model. A detailed summary of the information on the bionomics of each species and species complex is also presented.</p> <p>Conclusions</p> <p>This article concludes a project aimed to establish the contemporary global distribution of the DVS of malaria. The three articles produced are intended as a detailed reference for scientists continuing research into the aspects of taxonomy, biology and ecology relevant to species-specific vector control. This research is particularly relevant to help unravel the complicated taxonomic status, ecology and epidemiology of the vectors of the Asia-Pacific region. All the occurrence data, predictive maps and EO-shape files generated during the production of these publications will be made available in the public domain. We hope that this will encourage data sharing to improve future iterations of the distribution maps.</p

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe