Desidustat in Anemia due to Non-Dialysis-Dependent Chronic Kidney Disease: A Phase 3 Study (DREAM-ND).

BACKGROUND: Desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is being developed to treat anemia in patients with chronic kidney disease (CKD) without dialysis dependency. METHODS: In total, 588 patients with a clinical diagnosis of anemia due to CKD without dialysis need and with baseline hemoglobin of 7.0-10.0 g/dL (inclusive) were randomized in a 1:1 ratio to receive either desidustat 100 mg oral tablets thrice a week for 24 weeks or biosimilar darbepoetin subcutaneous injection 0.75 µg/kg once in 2 weeks for 24 weeks. The primary outcome was the change from baseline in hemoglobin to evaluation period of Weeks 16-24. Key secondary outcomes included the number of patients with hemoglobin response, changes in the hepcidin levels, changes in the vascular endothelial growth factor (VEGF) levels, and changes in the lipid and lipoprotein profiles. RESULTS: Hemoglobin change from baseline to Weeks 16-24 was 1.95 g/dL in the desidustat group and 1.83 g/dL in the darbepoetin group (difference: 0.11 g/dL; 95% CI: -0.12, 0.34), which met prespecified non-inferiority margin (-0.75 g/dL). The hemoglobin responders were significantly higher (p = 0.0181) in the desidustat group (196 [77.78%]) compared to the darbepoetin group (176 [68.48%]). The difference of change in hepcidin from baseline to Week 12 and Week 24 (p = 0.0032 at Week 12, p = 0.0016 at Week 24) and the difference of change in low-density lipoprotein from baseline to Week 24 (p value = 0.0269) between the two groups was statistically significant. The difference of change from baseline in VEGF to Weeks 12 and 24 between the two groups was not statistically significant. CONCLUSION: Desidustat is non-inferior to darbepoetin in the treatment of anemia due to non-dialysis dependent CKD and it is well-tolerated.

Efficacy and safety of glycopyrronium/formoterol delivered via a dry powder inhaler in patients with moderate to severe chronic obstructive pulmonary disease: Results from a multi-centre, open-label, randomised study.

Background: We designed this randomised, open-label, parallel group, multi-centre study to investigate the efficacy and safety of glycopyrronium/formoterol, a long-acting muscarinic antagonist/long-acting ß2-agonist fixed dose combination, delivered through a dry powder inhaler (DPI) in patients with chronic obstructive pulmonary disease (COPD). Material and Methods: We randomised (1:1) patients with moderate to severe COPD (N = 356) to receive glycopyrronium 25 µg/formoterol 12 µg via DPI twice daily (GF-DPI) or glycopyrronium 50 µg monotherapy via DPI once daily (G-DPI). The primary study endpoint was the mean change from the baseline in pre-dose trough-forced expiratory volume in one second (FEV1) at 12 weeks. Results: At week 12, the mean increase from the baseline in pre-dose trough FEV1 was higher in the GF-DPI group (120 ml) than in the G-DPI (60 ml) group. The mean difference (MD) between treatment groups was 0.06 L (95% CI: 0.00-0.12 L, P < 0.0001 for non-inferiority). At week 12, the mean pre-dose forced vital capacity (FVC), 1 hour post-dose FEV1, and post-dose FVC increased significantly from the baseline only in the GF-DPI group (p < 0.0001). The reduction in the COPD assessment test score was greater in the GF-DPI group (p = 0.0379). The average daily number of puffs of rescue medication and the reduction in mean modified Medical Research Council scale, COPD, and Asthma Sleep Impact Scale score at week 12 were similar between groups (p > 0.05). Overall, 35 adverse events and two serious adverse events unrelated to study drugs were reported. Both groups had similar results for overall drug safety. Conclusion: The results demonstrate efficacy and safety of GF-DPI in Indian patients with moderate to severe COPD. Treatment with GF-DPI significantly improved the lung function and quality of life and was well tolerated.

Bacillus coagulans Unique IS2 in Constipation: A Double-Blind, Placebo-Controlled Study.

Functional constipation has a high prevalence in both adults and children affecting quality of life. Evidence suggests that probiotics can reduce the symptoms of constipation. As the effects of probiotics are strain specific, the efficacy of Bacillus coagulans Unique IS2 in the treatment of functional constipation in adults was evaluated. Subjects (n = 100) diagnosed with functional constipation were supplemented with either B. coagulans Unique IS2 (2 billion CFU) or placebo capsules once daily for 4 weeks. Subjects were evaluated for treatment success (defined as three or more spontaneous stools per week), stool consistency, difficulty of defecation, defecation and abdominal pain. By the end of the fourth week, there was a statistically significant (p < 0.001) increase in number of bowel movements in the probiotic treated group as compared to placebo. Ninety eight percent of subjects in the probiotic group achieved normal stool consistency as compared to placebo (74%). Moreover, there was relief from symptoms of incomplete evacuation, painful defecation and abdominal pain associated with constipation in probiotic treated group as compared to placebo. In conclusion, B. coagulans Unique IS2 significantly decreased the symptoms of constipation indicating effectiveness of the strain in the treatment of constipation.Trial registration: CTRI/2017/11/010539.

A new class of PANI-Ag core-shell nanorods with sensing dimensions.

A single-step, cost-effective and eco-safe synthesis of a new class of homogeneous silver-polyaniline (PANI-Ag) core-shell nanorods is carried out via mild photolysis by ultraviolet radiation from sunlight (SUN UV-radiation). X-ray diffraction (XRD) of these core-shell nanorods gives two additional peaks from PANI centered at 2θ = 20.5° and 24. 9°. A validation of the core-shell structural information is given by transmission electron spectroscopy (TEM) whereas the tubular shape morphology is determined by scanning electron microscopy (SEM). UV-Vis. absorption shows a strong blue-shift along with photoluminescence emission. Fourier transform-infrared spectroscopy (FT-IR) and energy dispersive X-ray spectroscopy (EDX) also support the core-shell formation. Thermogravimetric analysis (TGA) shows good thermal stability and allows excellent detection of hydrogen peroxide and hydrazine. The cyclic voltammetry (CV) results show excellent electro-activation, indicating its promising potential in sensing of clinical and environmental analytes.

Green synthesis of nanosilver as a sensor for detection of hydrogen peroxide in water.

Present "green" synthesis is an efficient, easy-going, fast, renewable, inexpensive, eco-friendly and non-toxic approach for nanosilver formation, which offers numerous benefits over physiochemical approaches. The X-ray diffraction (XRD) pattern suggests the formation and crystallinity of nanosilver. The average particle size of silver nanoparticles was 8.25±1.37 nm as confirmed by transmission electron microscopy (TEM). The UV-vis absorption spectrum shows a characteristic absorption peak of silver nanoparticles at 410 nm. FTIR confirms Azadirachtin as reducing and stabilizing agent for nanosilver formation. In addition, the nanosilver modified electrode (Ag/GC) exhibited an excellent electro-catalytic activity toward the reduction of hydrogen peroxide (H(2)O(2)). The produced nanosilver is stable and comparable in size. These silver nanoparticles show potential applications in the field of sensors, catalysis, fuel cells and nanodevices.