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BACKGROUND: This study aimed to determine whether paromomycin plus miltefosine (PM/MF) is noninferior to sodium stibogluconate plus paromomycin (SSG/PM) for treatment of primary visceral leishmaniasis in eastern Africa. METHODS: An open-label, phase 3, randomized, controlled trial was conducted in adult and pediatric patients at 7 sites in eastern Africa. Patients were randomly assigned to either 20 mg/kg paromomycin plus allometric dose of miltefosine (14 days), or 20 mg/kg sodium stibogluconate plus 15 mg/kg paromomycin (17 days). The primary endpoint was definitive cure after 6 months. RESULTS: Of 439 randomized patients, 424 completed the trial. Definitive cure at 6 months was 91.2% (155 of 170) and 91.8% (156 of 170) in the PM/MF and SSG/PM arms in primary efficacy modified intention-to-treat analysis (difference, 0.6%; 97.5% confidence interval [CI], -6.2 to 7.4), narrowly missing the noninferiority margin of 7%. In the per-protocol analysis, efficacy was 92% (149 of 162) and 91.7% (155 of 169) in the PM/MF and SSG/PM arms (difference, -0.3%; 97.5% CI, -7.0 to 6.5), demonstrating noninferiority. Treatments were well tolerated. Four of 18 serious adverse events were study drug-related, and 1 death was SSG-related. Allometric dosing ensured similar MF exposure in children (<12 years) and adults. CONCLUSIONS: PM/MF and SSG/PM efficacies were similar, and adverse drug reactions were as expected given the drugs safety profiles. With 1 less injection each day, reduced treatment duration, and no risk of SSG-associated life-threatening cardiotoxicity, PM/MF is a more patient-friendly alternative for children and adults with primary visceral leishmaniasis in eastern Africa. Clinical Trials Registration. NCT03129646.

Chlorinated poly(vinyl chloride) (CPVC)/calcium carbonate nanocomposites were successfully prepared by the incorporation of calcium carbonate (CaCO3) nanoparticles into the CPVC matrix. The compatibility between the two phases was obtained by surface modification of the CaCO3 nanoparticles with stearic acid, leading to improved material performance. The effects of the addition of different amounts of CaCO3 nanoparticles to the CPVC on the thermal, mechanical, and morphological characteristics of the CPVC/CaCO3 nanocomposites were investigated. The thermal stability of the CPVC/CaCO3 nanocomposites was evaluated by thermogravimetric analysis and differential scanning calorimetry. In addition, the surface texture of the CPVC and the dispersion of the CaCO3 were evaluated using scanning electron microscopy. Important enhancements in the thermal and mechanical properties of the modified CPVC/CaCO3 nanocomposites were obtained by incorporating different amounts (2.00%, 3.75%, and 5.75%) of surface-modified CaCO3 nanoparticles within the CPVC polymer matrix. The results reveal that 3.75% of CaCO3 was the optimum amount, where the CPVC/CaCO3 nanocomposite shows the highest impact strength, the highest tensile strength, the highest thermal stability, and the lowest elongation percentage. Replacement of the commercial impact modifier used in industry with the prepared surface-modified CaCO3 nanoparticles for the development of CPVC was successfully achieved.

This work deals with the preparation, characterization and in vitro release study of IBU-loaded gel graft copolymer nanoparticles.