Per-collection analysis for <i>PLCE1</i> rs3740360.

<p>Number: Number of cases</p><p>MAF cases: minor allele frequency in dengue cases</p><p>MAF controls: minor allele frequency in controls</p><p>OR: per-allele odds ratio.</p><p>SE: Standard error of the OR</p><p>Weight: study-specific weight when meta-analyzed, not calculated for infants and DSS collections, which were not meta-analyzed.</p><p><i>P</i>: <i>P</i>-value for association with disease (unadjusted).</p

Per-collection analysis for <i>MICB</i> rs3132468.

<p>Number: Number of cases</p><p>MAF cases: minor allele frequency in dengue cases</p><p>MAF controls: minor allele frequency in controls</p><p>OR: per-allele odds ratio.</p><p>SE: Standard error of the OR</p><p>Weight: study-specific weight when meta-analyzed, not calculated for infants and DSS collections, which were not meta-analyzed.</p><p><i>P</i>: <i>P</i>-value for association with disease (unadjusted).</p

Cardio-haemodynamic assessment and venous lactate in severe dengue: Relationship with recurrent shock and respiratory distress

<div><p>Background</p><p>Dengue can cause plasma leakage that may lead to dengue shock syndrome (DSS). In approximately 30% of DSS cases, recurrent episodes of shock occur. These patients have a higher risk of fluid overload, respiratory distress and poor outcomes. We investigated the association of echocardiographically-derived cardiac function and intravascular volume parameters plus lactate levels, with the outcomes of recurrent shock and respiratory distress in severe dengue.</p><p>Methods/Principle findings</p><p>We performed a prospective observational study in Paediatric and adult ICU, at the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, Vietnam. Patients with dengue were enrolled within 12 hours of admission to paediatric or adult ICU. A haemodynamic assessment and portable echocardiograms were carried out daily for 5 days from enrolment and all interventions recorded.</p><p>102 patients were enrolled; 22 patients did not develop DSS, 48 had a single episode of shock and 32 had recurrent shock. Patients with recurrent shock had a higher enrolment pulse than those with 1 episode or no shock (median: 114 vs. 100 vs. 100 b/min, P = 0.002), significantly lower Stroke Volume Index (SVI), (median: 21.6 vs. 22.8 vs. 26.8mls/m², P<0.001) and higher lactate levels (4.2 vs. 2.9 vs. 2.2 mmol/l, P = 0.001). Higher SVI and worse left ventricular function (higher Left Myocardial Performance Index) on study days 3–5 was associated with the secondary endpoint of respiratory distress. There was an association between the total IV fluid administered during the ICU admission and respiratory distress (OR: 1.03, 95% CI 1.01–1.06, P = 0.001). Admission lactate levels predicted patients who subsequently developed recurrent shock (P = 0.004), and correlated positively with the total IV fluid volume received (rho: 0.323, P = 0.001) and also with admission ALT (rho: 0.764, P<0.001) and AST (rho: 0.773, P<0.001).</p><p>Conclusions/Significance</p><p>Echo-derived intravascular volume assessment and venous lactate levels can help identify dengue patients at high risk of recurrent shock and respiratory distress in ICU. These findings may serve to, not only assist in the management of DSS patients, but also these haemodynamic endpoints could be used in future dengue fluid intervention trials.</p></div

Forest plot illustrating the association between <i>PLCE1</i> rs3740360 and susceptibility to dengue.

<p>06DX, DR, FG and MD were cohort studies of children. and 09DX, D001 and FL were cohort studies of adults. The oblongs represent point estimates (referring to the per-allele odds ratio, expressed on the horizontal axis), with the height of the oblongs inversely proportional to the standard error of the point estimates. Horizontal lines indicate the 95% confidence interval for each point estimate. Meta-analysis of children, adults, as well as children and adults with uncomplicated dengue are reflected by blue diamonds. Data from our previously reported GWAS on DSS is reflected by the purple diamond.<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059067#pone.0059067-Khor1" target="_blank">[6]</a> The width of the diamonds indicates their 95% confidence intervals. Each meta-analysis is accompanied by a test of heterogeneity between the sample collections summarized by it (expressed as <i>P</i>_het).</p

Summary of the cohort studies used in the analysis.

<p>Summary of the cohort studies used in the analysis.</p

Enrollment cardio-haemodynamic and laboratory variables for predicting recurrent shock.

<p>Enrollment cardio-haemodynamic and laboratory variables for predicting recurrent shock.</p

Enrollment cardiac function and Haemodynamics in dengue patients on admission to the Intensive Care Unit.

<p>Enrollment cardiac function and Haemodynamics in dengue patients on admission to the Intensive Care Unit.</p

“Stroke Volume Index over ICU admission in patients with no shock, shock and recurrent shock.”

<p>Graph showing the dynamics of SVI by study day for 87 patients. Grey lines are changes of SVI for each patient. Colored lines connect medians of SVI on each study day for each patient group.</p