Rituximab in the treatment of systemic sclerosis-related interstitial lung disease: a systematic review and meta-analysis.

OBJECTIVES: To assess the effect of rituximab (RTX) on the lung function parameters in SSc interstitial lung disease (SSc-ILD) patients. METHODS: PubMed and Embase were searched to identify studies on SSc-ILD treated with RTX, confined to a predefined inclusion and exclusion criteria. A systematic review and meta-analysis were performed on the included studies on changes in forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) from baseline to 6 and 12 months of follow-up. RESULTS: A total of 20 studies (2 randomized controlled trials, 6 prospective studies, 5 retrospective studies and 7 conference abstracts) were included (n = 575). RTX improved FVC from baseline by 4.49% (95% CI 0.25, 8.73) at 6 months and by 7.03% (95% CI 4.37, 9.7) at 12 months. Similarly, RTX improved DLCO by 3.47% (95% CI 0.99, 5.96) at 6 months and 4.08% (95% CI 1.51, 6.65) at 12 months. In the two studies comparing RTX with other immunosuppressants, improvement of FVC by 6 months in the RTX group was 1.03% (95% CI 0.11, 1.94) greater than controls. At the 12 month follow-up, RTX treatment was similar to controls in terms of both FVC and DLCO. Patients treated with RTX had a lower chance of developing infections compared with controls [odds ratio 0.256 (95% CI 0.104, 0.626), I2 = 0%, P = 0.47). CONCLUSIONS: Treatment with RTX in SSc-ILD was associated with a significant improvement of both FVC and DLCO during the first year of treatment. RTX use was associated with lower infectious adverse events.

Protective Efficacy of Secondary Prophylaxis Against Visceral Leishmaniasis in Human Immunodeficiency Virus Coinfected Patients Over the Past 10 Years in Eastern India.

Coinfection with visceral leishmaniasis (VL) and human immunodeficiency virus (HIV) leads to frequent treatment failure, relapse, and death. In this retrospective analysis from eastern India (2005-2015), our primary objective was to ascertain the protective efficacy of secondary prophylaxis with monthly amphotericin B (AmB) given in patients with HIV-VL coinfection toward reducing relapse and mortality rates. The secondary objective was to compare clinical features, laboratory findings, and treatment outcomes in HIV-VL patients in contrast to VL monoinfection. Overall, 53 cases of HIV-VL and 460 cases of VL monoinfection were identified after excluding incomplete records. Initial cure rate was 96.23% in HIV-VL (27 received liposomal AmB and 26 AmB deoxycholate). All patients with initial cure (N = 51) were given antiretroviral therapy. Secondary prophylaxis (N = 27) was provided with monthly 1 mg/kg AmB (15 liposomal, 12 deoxycholate). No relapse or death was noted within 6 months in the secondary prophylaxis group (relapse: none versus 18/24 [75%]; mortality: none versus 11/24 [45.8%]; P < 0.001 for both). Secondary prophylaxis remained the sole significant predictor against death in multivariate Cox regression model (hazard ratio = 0.09 [95% confidence interval = 0.03-0.31]; P < 0.001). HIV-VL patients had higher 6-month relapse rate, less relapse-free 12-month survival, and higher mortality (P < 0.001 each) than VL monoinfection. In conclusion, it appears from this study that secondary prophylaxis with monthly AmB might be effective in preventing relapse and mortality in HIV-VL.

Short-Course Treatment Regimen of Indian Visceral Leishmaniasis with an Indian Liposomal Amphotericin B Preparation (Fungisome™).

India bears the burden of about half of global visceral leishmaniasis (VL) cases with emerging problems of stibanate resistance. Liposomal preparations have improved treatment outcome through shorter duration of therapy and lower toxicity compared with conventional amphotericin B. We report the efficacy of two short-course regimens of an Indian preparation of liposomal amphotericin B (Fungisome™) for VL caused by Leishmania donovani in India. An open-label, randomized, single-center comparative study was undertaken from 2008 to 2011, involving 120 treatment naive non-human immunodeficiency virus VL patients randomly allocated to two groups. Fungisome™ was given, in groups A (N = 60), 5 mg/kg daily for 2 days and B (N = 60), 7.5 mg/kg daily for 2 days, as intravenous infusion. Initial cure rate was 100% in both the groups after 1 month posttreatment. At 6 months after completion of treatment, definitive cure rate was group A 90% (54/60, 95% confidence interval (CI): 80.55-95.72%); group B: 100% (95% CI: 95.92-100%); (P = 0.027). No serious adverse events occurred in either group. The short-course, 2-day regimen of 15 mg/kg Fungisome™ infusion is easy to administer, effective, and safe for treatment of VL caused by L. donovani in India.

Predictors of mortality in leptospirosis: an observational study from two hospitals in Kolkata, eastern India.

BACKGROUND: Leptospirosis has a mortality rate of 5-20%. Poor prognostic factors are older age; oliguria; elevated potassium, creatinine and/or bilirubin levels; and altered mental status. We conducted this retrospective study to analyse the predictors of mortality among Indian patients with leptospirosis. METHODS: Clinical, biochemical, demographic and treatment related data (time between onset of symptoms and commencement of leptospira specific antibiotics) of 101 leptospirosis patients were reviewed. Predictors identified by univariate analysis were analysed by multivariable Cox regression for survival analysis. RESULTS: Prominent clinical features were: fever (101/101, 100%), jaundice (62, 62.4%), vomiting (42, 41.6%), oliguria (35, 34.7%), cough (18, 17.8%) and dyspnoea (10, 10.0%). Common complications were acute kidney injury (22, 21.8%), cardiovascular collapse (13, 12.9%), haemorrhages (10, 10.0%), meningitis (7, 6.9%), acute respiratory distress syndrome and pancreatitis (5, 5.0% each). Seventeen patients died (16.8%). Univariate predictors of mortality were older age, delayed antibiotic therapy, higher bilirubin, aspartate aminotransferase, alkaline phosphatase, leucocyte count and aspartate/alanine aminotransferase ratio (AAR). Only AAR (HR 1.208, 95% CI 1.051-1.388) and number of days the patient was symptomatic before access to specific antibiotic therapy (HR 1.304, 95% CI 1.081-1.574) remained significant predictors after Cox regression. CONCLUSIONS: Multivariate analysis showed high AAR and delayed antibiotic therapy might be associated with fatality.