A modified Sequential Organ Failure Assessment score for dengue: development, evaluation and proposal for use in clinical trials

Background Dengue is a neglected tropical disease, for which no therapeutic agents have shown clinical efficacy to date. Clinical trials have used strikingly variable clinical endpoints, which hampers reproducibility and comparability of findings. We investigated a delta modified Sequential Organ Failure Assessment (delta mSOFA) score as a uniform composite clinical endpoint for use in clinical trials investigating therapeutics for moderate and severe dengue. Methods We developed a modified SOFA score for dengue, measured and evaluated its performance at baseline and 48 h after enrolment in a prospective observational cohort of 124 adults admitted to a tertiary referral hospital in Vietnam with dengue shock. The modified SOFA score included pulse pressure in the cardiovascular component. Binary logistic regression, cox proportional hazard and linear regression models were used to estimate association between mSOFA, delta mSOFA and clinical outcomes. Results The analysis included 124 adults with dengue shock. 29 (23.4%) patients required ICU admission for organ support or due to persistent haemodynamic instability: 9/124 (7.3%) required mechanical ventilation, 8/124 (6.5%) required vasopressors, 6/124 (4.8%) required haemofiltration and 5/124 (4.0%) patients died. In univariate analyses, higher baseline and delta (48 h) mSOFA score for dengue were associated with admission to ICU, requirement for organ support and mortality, duration of ICU and hospital admission and IV fluid use. Conclusions The baseline and delta mSOFA scores for dengue performed well to discriminate patients with dengue shock by clinical outcomes, including duration of ICU and hospital admission, requirement for organ support and death. We plan to use delta mSOFA as the primary endpoint in an upcoming host-directed therapeutic trial and investigate the performance of this score in other phenotypes of severe dengue in adults and children

Lack of decline in Hepatitis C Virus incidence among HIV-positive men who have sex with men during 1990-2014.

BACKGROUND AND AIMS Hepatitis C virus (HCV) incidence among HIV-positive men who have sex with men (MSM) has increased since 2000, though regional differences have been documented in recent years. We aimed to 1) estimate trends in HCV incidence among HIV-positive MSM, 2) assess the association between incidence and geographical region, age and HIV-related measurements and, 3) assess temporal changes in time from HIV seroconversion to HCV infection. METHODS We used data from MSM with well-estimated dates of HIV seroconversion from the CASCADE Collaboration (1990-2014). We allowed for smoothly varying trends in HCV incidence over calendar time using restricted cubic splines. We assessed the association of calendar year, age, CD4 count (lagged), HIV RNA (lagged), geographical region and HIV infection stage (recent vs. chronic) with HCV incidence using Poisson regression. RESULTS Of 5,941 MSM, 337 acquired HCV during follow-up. HCV incidence significantly increased from 0.7/1000 person-years (py) in 1990 to 18/1000 py in 2014. Recent calendar years, younger age, recent HIV infection and higher HIV RNA levels were significantly associated with HCV incidence, while CD4 count was not. Trends differed by geographical region; while incidence appears to have stabilized in Western Europe and remained stable in Southern Europe, it continued to increase in Northern Europe in recent years. Time from HIV to HCV infection significantly decreased over calendar time (p<0.001). CONCLUSIONS HCV has continued to spread among HIV-positive MSM in recent years, but trends differ by geographical region. Interventions to decrease the risk of HCV acquisition and increase early diagnosis are warranted. LAY SUMMARY Hepatitis C virus infection continues to spread among HIV-positive men who have sex with men, especially among younger individuals. However, trends seem to differ by European region in recent years. Furthermore, men who have sex with men with a higher HIV RNA load were more likely to get infected with the hepatitis C virus. During recent HIV infection, MSM appear to be at higher risk of acquiring hepatitis C