Intravenous fluid therapy in hospitalized adult dengue patients without shock: Impact on subsequent severe dengue and potential adverse effects.

There is a lack of evidence on the optimal administration of intravenous (IV) fluids in hospitalized adult dengue patients without compensated and hypotensive shock. This study utilized a well-established cohort of dengue patients to compare risks of progressing to severe dengue (SD) over time for patients who were administered IV fluid versus others who were not. We included adult patients (n = 4781) who were hospitalized for dengue infection from 2005 to 2008. Cases were patients who developed SD (n = 689) and controls were patients who did not up until discharge (n = 4092). We estimated the hazard ratios (HRs) and risk of SD over time between groups administered different volumes of IV fluids versus the no IV fluid comparison group using Cox models with time-dependent covariates. The doubly-robust estimation approach was used to control for the propensity of fluid administration given clinical characteristics of patients. Subgroup analyses by age, sex, and dengue warning signs before IV fluid administration were conducted. High (>2000 mL/day) IV fluids volume was associated with a higher risk of development of SD for those who had warning signs (HR: 1.77 [1.05-2.97], p: 0.0713) and for those below 55 years old (HR: 1.53 [1.04-2.25], p: 0.0713). Low (<1000 mL/day) IV fluids volume was protective against SD for patients without warning signs (HR: 0.757 [0.578-0.990], p: 0.0883), no lethargy (HR: 0.770 [0.600-0.998], p: 0.0847), and females (HR: 0.711 [0.516-0.980], p: 0.0804). Over the course of hospitalization, there were no significant differences in IV fluid administration and SD risk in most subgroups, except in those who experienced lethargy and were administered IV fluid volume or quantity. Administering high volumes of IV fluids may be associated with an increased risk of SD during hospitalization for adult dengue patients without shock. Judicious use of IV fluids as supportive therapy is warranted.

Improved outcomes from HIV/TB co-infection in Singapore following a switch to earlier anti-retroviral therapy.

INTRODUCTION: Recent clinical trials have provided clear evidence to support early anti-retroviral therapy (ART) in patients with HIV/TB co-infection and low CD4 counts. We investigated how this has changed treatment and outcomes in Singapore. MATERIALS AND METHODS: A retrospective review was performed with inpatient and outpatient records for all subjects diagnosed with HIV/TB co-infection from 2006 to 2011 attending the Tuberculosis Control Unit, Tan Tock Seng Hospital, Singapore. Data for subjects with a presenting CD4<200 cell/mm(3) were extracted and split into two groups, "Delayed": ART more than 8/52 after starting TB treatment, and "Early": ART within 8/52 of starting TB treatment. RESULTS: One hundred thirty-four out of 180 subjects in the database met the inclusion criteria for this study, 89 in the delayed group and 45 in the early. No statistically significant differences in baseline demographics between the two groups were identified. Both groups presented with markedly low CD4 counts, with overall 60% <50cells/mm(3). Median CD4 counts were lower in the delayed ART group (37 vs 50, p=0.015). Prevalence of other opportunistic infections at TB diagnosis was not significantly different (20%), but TB in the early ART group was more likely to include extra-pulmonary disease (46% vs 57%, p=0.038). Four cases were culture negative, 2 multi-drug resistant and 10 (7.8%) were isoniazid mono-resistant. There was a significant trend to earlier ART with more recent TB diagnosis (p<0.001). In the first 365 days after TB diagnosis, 11 deaths occurred in the delayed ART group, and 0 in the early (p=0.033). A Kaplan-Meier time-to-event analysis demonstrated a clear separation in the frequency of death or opportunistic infections at eight weeks (Figure 1, p<0.001). Immune reconstitution disease was significantly more likely in the early ART group, but did not result in death (9% vs 38%, p<0.001). Treatment interruptions due to adverse drug events (ADE) developed in a median of 25 days (IQR 15-43). Interestingly, early ART was associated with a significantly lower number of treatment interruptions attributed to ADEs, with a higher proportion of patients completing two months of pyrazinamide induction (66% vs 85%, p=0.054) and rifampicin consolidation (79% vs 95%, p=0.03) - after excluding resistance or death. A trend to longer duration TB treatment was observed with delayed ART. CONCLUSIONS: Significant improvements in HIV/TB infection outcomes correlate with the switch to earlier ART.

Dengue infections in HIV patients.

A retrospective review of hospital admission records was conducted on patients who were admitted to the Communicable Disease Center (CDC)/Tan Tock Seng Hospital, Singapore from 1 January 2004 to 31 December 2005. There were 5 HIV patients who were admitted with dengue infection during the study period. Their symptoms were generally mild and recovery was uneventful. None of the patients developed dengue hemorrhagic fever or dengue shock syndrome. The symptoms and signs of dengue infection in HIV patients are nonspecific. It is important for healthcare workers to maintain a high index of suspicion in order to make the diagnosis. Interactions between pathogenesis pathways or with antiviral treatments may have contributed to the apparently less severe dengue infections in HIV patients. This observation needs to be explored further.

Fatal dengue hemorrhagic fever in adults during a dengue epidemic in Singapore.

BACKGROUND: Dengue fever has seen a significant re-emergence in Southeast Asia. Associated with the rise of dengue has been the increase in dengue-associated mortality. To better understand the predictors of mortality, we conducted a review of hospitalized adult dengue infections within our institution. METHODS: This was a retrospective case-control study of dengue-associated deaths at a large tertiary care hospital. RESULTS: In 2004, of 3186 cases of dengue fever (DF)/hemorrhagic dengue fever (DHF) admitted to our institution, there were 130 cases of DHF and seven dengue-associated deaths (case-fatality rate 5.4%). At least three of the seven fatal cases had serological evidence of primary dengue infection. All dengue-mortality cases had rapidly progressive clinical deterioration at an average of day 4 of fever with intensive care admission occurring on a mean of 5.6 days of fever. Adult respiratory distress syndrome, disseminated intravascular coagulopathy, and multi-organ failure were the most common causes of death despite early hospitalization, intravenous fluid, and blood-product support. CONCLUSION: Dengue is associated with severe disease, and deaths do occur despite current supportive management. Fatal DHF/dengue shock syndrome (DSS) does occur in adults and in primary dengue infection. Better early predictors of disease severity and clinical interventions are needed.

Using autoregressive integrated moving average (ARIMA) models to predict and monitor the number of beds occupied during a SARS outbreak in a tertiary hospital in Singapore.

BACKGROUND: The main objective of this study is to apply autoregressive integrated moving average (ARIMA) models to make real-time predictions on the number of beds occupied in Tan Tock Seng Hospital, during the recent SARS outbreak. METHODS: This is a retrospective study design. Hospital admission and occupancy data for isolation beds was collected from Tan Tock Seng hospital for the period 14th March 2003 to 31st May 2003. The main outcome measure was daily number of isolation beds occupied by SARS patients. Among the covariates considered were daily number of people screened, daily number of people admitted (including observation, suspect and probable cases) and days from the most recent significant event discovery. We utilized the following strategy for the analysis. Firstly, we split the outbreak data into two. Data from 14th March to 21st April 2003 was used for model development. We used structural ARIMA models in an attempt to model the number of beds occupied. Estimation is via the maximum likelihood method using the Kalman filter. For the ARIMA model parameters, we considered the simplest parsimonious lowest order model. RESULTS: We found that the ARIMA (1,0,3) model was able to describe and predict the number of beds occupied during the SARS outbreak well. The mean absolute percentage error (MAPE) for the training set and validation set were 5.7% and 8.6% respectively, which we found was reasonable for use in the hospital setting. Furthermore, the model also provided three-day forecasts of the number of beds required. Total number of admissions and probable cases admitted on the previous day were also found to be independent prognostic factors of bed occupancy. CONCLUSION: ARIMA models provide useful tools for administrators and clinicians in planning for real-time bed capacity during an outbreak of an infectious disease such as SARS. The model could well be used in planning for bed-capacity during outbreaks of other infectious diseases as well.