Ivermectin Accelerates Circulating Nonstructural Protein 1 (NS1) Clearance in Adult Dengue Patients: A Combined Phase 2/3 Randomized Double-blinded Placebo Controlled Trial.

BACKGROUND: Dengue is the most significant mosquito-borne viral disease; there are no specific therapeutics. The antiparasitic drug ivermectin efficiently inhibits the replication of all 4 dengue virus serotypes in vitro. METHODS: We conducted 2 consecutive randomized, double-blind, placebo-controlled trials in adult dengue patients to evaluate safety and virological and clinical efficacies of ivermectin. After a phase 2 trial with 2 or 3 days of 1 daily dose of 400 µg/kg ivermectin, we continued with a phase 3, placebo-controlled trial with 3 days of 400 µg/kg ivermectin. RESULTS: The phase 2 trial showed a trend in reduction of plasma nonstructural protein 1 (NS1) clearance time in the 3-day ivermectin group compared with placebo. Combining phase 2 and 3 trials, 203 patients were included in the intention to treat analysis (100 and 103 patients receiving ivermectin and placebo, respectively). Dengue hemorrhagic fever occurred in 24 (24.0%) of ivermectin-treated patients and 32 (31.1%) patients receiving placebo (P = .260). The median (95% confidence interval [CI]) clearance time of NS1 antigenemia was shorter in the ivermectin group (71.5 [95% CI 59.9-84.0] hours vs 95.8 [95% CI 83.9-120.0] hours, P = .014). At discharge, 72.0% and 47.6% of patients in the ivermectin and placebo groups, respectively had undetectable plasma NS1 (P = .001). There were no differences in the viremia clearance time and incidence of adverse events between the 2 groups. CONCLUSIONS: A 3-day 1 daily dose of 400 µg/kg oral ivermectin was safe and accelerated NS1 antigenemia clearance in dengue patients. However, clinical efficacy of ivermectin was not observed at this dosage regimen.

Dialysis dose and risk factors for death among ESRD patients treated with twice-weekly hemodialysis: a prospective cohort study.

BACKGROUND/AIMS: We aimed to define the dosing and risk factors for death in patients undergoing twice-weekly hemodialysis. METHODS: A prospective multi-center cohort study was conducted with one-year observation. Patients treated with twice- or thrice-weekly hemodialysis were identified. Death and first admission were the outcomes. spKt/V was a factor of interest. RESULTS: We enrolled 504 twice-weekly and 169 thrice-weekly hemodialysis patients. The mean weekly values of spKt/V in the two groups were 3.4 and 5.1. The one-year survival rate and times to hospitalization were similar in both groups. The hazard ratios for death in higher spKt/V quartile was not associated with lower mortality, p = 0.70. The four significant predictors for death were serum albumin, HR = 2.6, current smoking, HR = 19.3, age, HR = 1.1, and the Index of Coexistent Disease [ICED], HR = 1.9. CONCLUSION: The effect of spKt/V on short-term mortality was not obvious in twice-weekly dialysis patients. Attention should be paid to patients who smoke, have hypoalbuminemia, are elderly, or have a high ICED.

Early as compared to late initiation of twice-weekly hemodialysis and short-term survival among end-stage renal disease patients.

INTRODUCTION: The impact of timing of hemodialysis (HD) for end-stage renal disease (ESRD) patients treated with twice-weekly HD remains unclear. We aimed to determine the effects of late initiation of HD on short-term mortality and hospitalization. METHODS: A multicenter cohort study was conducted in 11 HD centers in Northeastern Thailand (HEmodialysis Network of the NorthEastern Thailand study group). We recruited adult ESRD patients who were treated with twice-weekly HD for more than 3 months and had data on eGFR at HD initiation. Clinical and laboratory values at the time of recruitment were recorded. Late and early (eGFR at start <5 and >5 ml/min/1.73 m2 ) initiations were defined. Outcomes were disease-related death (excluding any accidental deaths) and first hospitalization. Data analysis was performed by multivariable cox-regression analysis. FINDINGS: A total of 407 patients who had data on eGFR at HD initiation (303 in late group and 104 in early group) were included for analysis. There were 56.8% male with a mean age of 55 years. During the 15.1 months of follow-up, there were 27 (6.6%) disease-related deaths. The 1-year survival rate was similar among late and early initiation groups. The incidence density of first hospitalization in the late group was significantly lower than those in the early group (HR adjusted, 0.63; 95% CI, 0.40-0.99, p = 0.047). Among 303 patients who were in the late start group, patients with diabetes had a higher mortality rate (HR, 3.49; 95% CI, 1.40-8.70, p = 0.007) when compared to non-diabetic patients. DISCUSSION: Early initiation of HD at eGFR >5 ml/min/1.73 m2 had no short-term survival benefit compared to the late group in ESRD patients treated with twice-weekly HD for at least 3 months in a resource-limited setting. A survival benefit from an early start of HD was found among diabetic patients.

Leptospirosis in northeastern Thailand: hypotension and complications.

During an outbreak of leptospirosis in northeastern Thailand, 148 patients with serologically diagnosed leptospirosis were seen in Loei Hospital. The clinical features were consistent with those described for the classic manifestation of the disease. However, hypotension was a common finding: noted in 94 patients (64%) upon admission or early in the course of the disease. Of these hypotensive patients, 64 (68%) had impaired renal function: 30 patients (32%) had prerenal azotemia and 34 (36%) were in renal failure. Pulmonary complications, including pulmonary edema, hemorrhage, ARDS, and interstitial pneumonitis, occurred in 22% of patients and were often associated with renal failure. A clear association existed between hypotension and renal failure and pulmonary complications. The overall mortality rate was 3.4%. The causes of death were pulmonary complications, renal failure, and sepsis. The death rate among patients with complications was 11.6%. Blood exchange, in addition to conventional treatment, was beneficial in severe leptospirosis with complications and hyperbilirubinemia.

Hypotension, renal failure, and pulmonary complications in leptospirosis.

During a recent outbreak of leptospirosis in northeastern Thailand, 148 patients with serologically diagnosed leptospirosis were seen in Loei hospital. The common serotypes were L. pyrogenes, and L. sejroe. Hypotension with a mean arterial pressure less than 70 mmHg upon admission or within 24 h after admission was observed in 94 patients or 64%. 30 patients had normal renal function; 30 patients had prerenal azotemia with mild pulmonary complication in 2; and 34 patients had acute renal failure. 29 patients with acute renal failure had pulmonary complications including pulmonary hemorrhage in 8, pulmonary edema in 3, acute respiratory distress syndrome (ARDS) in 14 and interstitial pneumonitis in 4. 54 patients had normal blood pressure. In this group 5 patients had acute renal failure; 16 had prerenal azotemia and 33 had normal renal function. Interstitial pneumonitis was noted in one patient with prerenal azotemia. Less renal complication and minimal pulmonary complication were seen in leptospirosis patients with normal blood pressure. The patients with normal renal function had no pulmonary complication. Good association existed between hypotension, renal failure and pulmonary complications.