Sodium zirconium cyclosilicate and metabolic acidosis: Potential mechanisms and clinical consequences.

Metabolic acidosis is frequent in chronic kidney disease (CKD) and is associated with accelerated progression of CKD, hypercatabolism, bone disease, hyperkalemia, and mortality. Clinical guidelines recommend a target serum bicarbonate ≥ 22 mmol/L, but metabolic acidosis frequently remains undiagnosed and untreated. Sodium zirconium cyclosilicate (SZC) binds potassium in the gut and is approved to treat hyperkalemia. In clinical trials with a primary endpoint of serum potassium, SZC increased serum bicarbonate, thus treating CKD-associated metabolic acidosis. The increase in serum bicarbonate was larger in patients with more severe pre-existent metabolic acidosis, was associated to decreased serum urea and was maintained for over a year of SZC therapy. SZC also decreased serum urea and increased serum bicarbonate after switching from a potassium-binding resin in normokalemic individuals. Mechanistically, these findings are consistent with SZC binding the ammonium ion (NH4+) generated from urea by gut microbial urease, preventing its absorption and, thus, preventing the liver regeneration of urea and promoting the fecal excretion of H+. This mechanism of action may potentially result in benefits dependent on corrected metabolic acidosis (e.g., improved well-being, decreased catabolism, improved CKD mineral bone disorder, better control of serum phosphate, slower progression of CKD) and dependent on lower urea levels, such as decreased protein carbamylation. A roadmap is provided to guide research into the mechanisms and clinical consequences of the impact of SZC on serum bicarbonate and urate.

Understanding influenza immunization uptake rates among the Hispanic LGBTQIA community.

OBJECTIVES: Most national-level data regarding lesbian, gay, bisexual, transgender, queer/questioning, intersex, and allies (LGBTQIA) immunizations are limited. The primary objective of this study was to identify factors that influence behaviors, attitudes, and perceptions toward the uptake of the influenza vaccine within the Hispanic LGBTQIA community. METHODS: This was a prospective survey that assessed vaccine acceptability and practices regarding the influenza vaccine within the LGBTQIA community. Collection of data occurred through the use of social media platforms from July 2016 to May 2018. A total of 126 participants (mean age 32.03 ± 11.68 years) completed a 15-minute, 26-item, English/Spanish survey. A number of outcome measures assessed perceptions of vaccine effectiveness and safety. In addition, perceived severity of influenza symptoms and perceived susceptibility to contract influenza was assessed. RESULTS: A logistic regression model assessed the impact of several factors on influenza vaccine uptake. Perceived susceptibility of contracting influenza from the vaccine (P = 0.015) and perceived ease of receiving the influenza vaccine (P = 0.005) were the strongest predictors of vaccine uptake. Results showed no association between disclosure of sexual orientation and influenza immunization uptake (χ2= 3.55; P = 0.17). Exploratory analyses revealed that non-Hispanic patients were more likely to perceive that their health care providers were aware of their sexual orientation compared with Hispanic patients (χ2= 8.66; P = 0.013). CONCLUSION: Several factors emerged as predictors of influenza vaccine uptake in the LGBTQIA population. Further studies are needed to explore additional factors such as disclosure of sexual orientation and variation of uptake based on vaccine type (STD vs. non-STD vaccines).

Relapse prevention in adults with major depressive disorder treated with vilazodone: a randomized, double-blind, placebo-controlled trial.

This randomized withdrawal study assessed relapse prevention with vilazodone in adults with major depressive disorder. After 20 weeks of open-label treatment with vilazodone 40 mg/day, responders were randomized (1 : 1 : 1) to 28 weeks of double-blind, fixed-dose treatment with vilazodone 20 mg/day, vilazodone 40 mg/day, or placebo. The primary efficacy endpoint was time to first relapse, defined as Montgomery-Åsberg Depression Rating Scale total score of at least 18 and meeting major depressive episode criteria, Montgomery-Åsberg Depression Rating Scale total score of at least 18 at two consecutive visits, or discontinuation for an insufficient therapeutic response. Of 1204 patients who received open-label treatment, 564 completed treatment and were randomized (placebo=192, vilazodone 20 mg/day=185, vilazodone 40 mg/day=187). No significant difference was detected in time to relapse during the double-blind period (P>0.05). The crude percentage of patients that relapsed was similar between treatment groups (placebo=12.6%; vilazodone 20 mg/day=11.4%; vilazodone 40 mg/day=13.4%). The most common treatment-emergent adverse events were diarrhea (29.6%), nausea (24.0%), and headache (14.0%) during open-label treatment and headache (8.9%), nasopharyngitis (8.4%), and diarrhea (7.5%) during double-blind treatment in the combined vilazodone groups (20 and 40 mg/day). In conclusion, time to relapse with vilazodone was not statistically different from placebo. Vilazodone was generally well tolerated in adults with major depressive disorder.