Explore the vast range of titles available.

Hyperkalemia contributes to significant mortality and limits the use of cardioprotective and renoprotective renin–angiotensin–aldosterone blockers. Current therapies are poorly tolerated and not always effective. Here we conducted a phase 2 randomized, double-blind, placebo-controlled dose-escalation study to assess safety and efficacy of ZS-9. This oral selective cation exchanger that preferentially entraps potassium in the gastrointestinal tract was given to patients with stable Stage 3 chronic kidney disease and hyperkalemia (5.0 to 6.0 mEq/l) during a 2-day period. Of 90 eligible patients with mean baseline serum potassium of 5.1 mEq/l, 30 were randomized to placebo, 12–0.3 g, 24–3 g, or 24 to 10 g of ZS-9 three times daily for 2 days with regular meals. None withdrew and ZS-9 dose-dependently reduced serum potassium. The primary efficacy end point (rate of serum potassium decline in the first 48 h) was met with significance in the 3- and 10-g cohorts. From baseline, mean serum potassium was significantly decreased by 0.92±0.52 mEq/l at 38 h. Urinary potassium excretion significantly decreased with 10-g ZS-9 as compared to placebo at day 2 (+15.8 +/- 21.8 vs. +8.9 +/- 22.9 mEq per 24h) from placebo at day 2. In this short-term study, no serious adverse events were reported; only mild constipation in the 3-g dose group was possibly related to treatment. Thus, ZS-9 was well-tolerated in patients with stable chronic kidney disease and hyperkalemia leading to a rapid, sustained reduction in serum potassium.

This study aimed to comparatively assess the clinical success and radiographic regenerative dentin formation of Platelet Rich Fibrin (PRF) and mineral trioxide aggregate (MTA) when used as direct pulp capping agents. This double-blinded two parallel armed randomized controlled clinical trial comprised the allocation of 108 patients with traumatically exposed dental pulp during the management of deep carious lesions by undergraduate students after fulfilling inclusion and exclusion criteria. Patients were randomized into two groups ( n  = 54 in each group) using computer-generated simple randomization, wherein one group Platelet Rich Fibrin (PRF) was prepared from patients’ blood samples and applied directly over exposed pulp followed by MTA application and in the other group MTA was applied directly over pulp exposure. In both groups, cavities were restored with resin-modified glass ionomer liner and resin composite restoration. The overall success of treatment was calculated at 6 and 12 months after assessing pulp sensibility, history of pain, tenderness on percussion and the existence of any periapical pathosis using in periapical radiographs. Moreover CBCT was used at 12 months to determine the presence or absence of dentin bridge as a secondary outcome. After 12 months follow-up, there was no statistically significant difference in overall success of pulp capping in both groups. As the both groups showed 92.59% success rate. CBCT evaluation of dentin bridge formation by Platelet Rich Fibrin (PRF) demonstrated a significantly higher percentage than that formed in cases treated with MTA alone ( p  < 0.001). Direct pulp capping with Platelet Rich Fibrin (PRF) exhibited a clinical and radiographic success rate comparable to that of MTA. Platelet Rich Fibrin (PRF) can be implemented as a direct pulp capping agent in forthcoming clinical applications.

Cognitive function is critical for successful prolonged performance in eSports. This double-blind placebo-controlled study examined the effect of an inositol-enhanced arginine silicate oral supplement on cognitive performance and energy in eSports athletes. Sixty healthy men and women who spent 5 or more hours a week playing video games were randomly assigned to take supplement or placebo for 7 days. On day 1 and 7, before and 15 min after dosing, subjects completed the Trail Making Test (TMT), Parts A and B; Stroop Test; and Profile of Mood States (POMS) questionnaire, and then played a video game for 60 min. Immediately after, cognitive tests were repeated. Self-reported energy levels increased, anger decreased, and TMT-B test errors decreased in the supplement group compared to placebo (p < 0.05). Fatigue, TMT-B time, and TMT B-A score improved in the supplement group compared to baseline (p < 0.05). After 60 min of gaming, supplementation decreased Stroop Test errors and TMT-A time (p < 0.05). Adverse events were minimal and not different between groups. These data appear to support the use of the studies product (nooLVL®) in eSports gamers looking to improve their accuracy, decision making, and reaction time during gaming.

The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study (NCT02181413) demonstrated improved progression-free survival with ixazomib maintenance versus placebo post autologous stem cell transplant (ASCT) in multiple myeloma patients. We report additional safety data from TOURMALINE-MM3 to inform adverse event (AE) management recommendations. Patients were randomized 3:2 to receive ixazomib (n = 395) or placebo (n = 261) on days 1, 8, and 15 of 28-day cycles for ~ 2 years or until progressive disease/toxicity. The initial 3-mg ixazomib dose was escalated to 4 mg in cycle 5, if tolerated in cycles 1–4. Safety was a secondary endpoint assessed in all treated patients; AEs were graded using Common Terminology Criteria for AEs v4.03. The rate of grade ≥ 3 AEs was higher in the ixazomib arm (19%) than in the placebo arm (5%), but the rate of discontinuation due to AEs was similar (7% vs. 5%). For AEs of clinical interest, rates were higher with ixazomib versus placebo: nausea 39% versus 15%, vomiting 27% versus 11%, diarrhea 35% versus 24%, thrombocytopenia 13% versus 3%, and peripheral neuropathy 19% versus 15%. However, the majority of events were low-grade, manageable with supportive therapy or dose reduction, and reversible, and did not result in discontinuation. There was no evidence of cumulative, long-term, or late-onset toxicity with ixazomib maintenance. Ixazomib is an efficacious and tolerable option for post-ASCT maintenance. AEs associated with ixazomib maintenance can be managed in the context of routine post-ASCT supportive care due to the limited additional toxicity. ClinicalTrials.gov NCT02181413

Inositol-stabilized arginine silicate (ASI) is an ergogenic aid that upregulates nitric oxide. Acute ASI supplementation improves working memory and processing speed in young adults but there is a lack of data examining other cognitive tasks. Therefore, the purpose of this study was to examine acute ASI effects on young healthy adults by assessing multiple cognitive domains. Nineteen young adults (20.9 ± 3.2 years) completed this randomized, double-blind, crossover study consuming ASI (1.5 g ASI + 12 g dextrose) and placebo (12 g dextrose). The participants completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and two digital cognitive assessments before consuming the supplement and then completed the same battery of tests 60 min post-supplementation. Repeated measures ANOVA demonstrated that ASI consumption significantly improved total RBANS and immediate memory scores compared to the placebo (p < 0.05). However, no significant differences were displayed between trials for other cognitive domains (p > 0.05). Acute ASI ingestion increased overall RBANS scores and immediate memory scores in young adults. More research is needed to examine the acute effects of ASI on other domains of cognition, in older populations, and its long-term effects on cognition.

Inositol stabilized arginine silicate (ASI) ingestion has been reported to increase nitric oxide levels while inositol (I) has been reported to enhance neurotransmission. The current study examined whether acute ASI + I (Inositol-enhanced bonded arginine silicate) ingestion affects cognitive function in e-sport gamers. In a double blind, randomized, placebo controlled, and crossover trial, 26 healthy male (n = 18) and female (n = 8) experienced gamers (23 ± 5 years, 171 ± 11 cm, 71.1 ± 14 kg, 20.7 ± 3.5 kg/m2) were randomly assigned to consume 1600 mg of ASI + I (nooLVL®, Nutrition 21) or 1600 mg of a maltodextrin placebo (PLA). Prior to testing, participants recorded their diet, refrained from consuming atypical amounts of stimulants and foods high in arginine and nitrates, and fasted for 8 h. During testing sessions, participants completed stimulant sensitivity questionnaires and performed cognitive function tests (i.e., Berg-Wisconsin Card Sorting task test, Go/No-Go test, Sternberg Task Test, Psychomotor Vigilance Task Test, Cambridge Brain Sciences Reasoning and Concentration test) and a light reaction test. Participants then ingested treatments in a randomized manner. Fifteen minutes following ingestion, participants repeated tests (Pre-Game). Participants then played their favorite video game for 1-h and repeated the battery of tests (Post-Game). Participants observed a 7–14-day washout period and then replicated the study with the alternative treatment. Data were analyzed by General Linear Model (GLM) univariate analyses with repeated measures using weight as a covariate, paired t-tests (not adjusted to weight), and mean changes from baseline with 95% Confidence Intervals (CI). Pairwise comparison revealed that there was a significant improvement in Sternberg Mean Present Reaction Time (ASI + I vs. PLA; p < 0.05). In Post-Game assessments, 4-letter Absent Reaction Time (p < 0.05), 6-letter Present Reaction Time (p < 0.01), 6-letter Absent Reaction Time (p < 0.01), Mean Present Reaction Time (p < 0.02), and Mean Absent Reaction Time (p < 0.03) were improved with ASI + I vs. PLA. There was a non-significant trend in Pre-Game Sternberg 4-letter Present Reaction time in ASI + I vs. PLA (p < 0.07). ASI + I ingestion better maintained changes in Go/No-Go Mean Accuracy and Reaction Time, Psychomotor Vigilance Task Reaction Time, and Cambridge Post-Game Visio-spatial Processing and Planning. Results provide evidence that ASI + I ingestion prior to playing video games may enhance some measures of short-term and working memory, reaction time, reasoning, and concentration in experienced gamers.

Inositol-stabilized arginine silicate (ASI; Nitrosigine®) has been validated to increase levels of arginine, silicon and nitric oxide production. To evaluate potential enhancement of mental focus and clarity, ASI (1500 mg/day) was tested in two double-blind placebo-controlled crossover (DBPC-X) studies using the Trail Making Test (TMT, Parts A and B). In the two studies, healthy males took ASI for 14 and 3 days, respectively. In the first study, after 14 days of dosing, TMT B time decreased significantly from baseline (28% improvement, p = 0.045). In the second study evaluating shorter-term effects, TMT B time decreased significantly compared to placebo (33% improvement, p = 0.024) in a 10-min period. After 3 days of dosing, TMT B time significantly decreased from baseline scores (35% improvement, p < 0.001). These findings show that ASI significantly improved the ability to perform complex cognitive tests requiring mental flexibility, processing speed and executive functioning.

Introduction. The aim of this study was to compare MTA with another base material, IRM, which is generally used on pulpal floor after root canal treatment, regarding their effect on the success of root canal treatment of primary teeth with furcation lesions. Materials and Methods. Fifty primary teeth with furcation lesions were divided into 2 groups. Following root canal treatment, the pulpal floor was coated with MTA in the experimental group and with IRM in the control group. Teeth were followed up considering clinical (pain, pathological mobility, tenderness to percussion and palpation, and any soft tissue pathology and sinus tract) and radiographical (pathological root resorption, reduced size or healing of existing lesion, and absence of new lesions at the interradicular or periapical area) criteria for 18 months. For the statistical analysis, Fisher’s exact test and Pearson’s chi-square tests were used and a p value of <0.05 was considered to be statistically significant. Results. Although there were no statistically significant differences between two groups in terms of treatment success, lesions healed significantly faster in the MTA group. Conclusion. In primary teeth with furcation lesions, usage of MTA on the pulpal floor following root canal treatment can be a better alternative since it induced faster healing.

Sodium zirconium cyclosilicate (SZC) is an oral potassium (K+)-lowering therapy for adults with hyperkalemia. HARMONIZE Asia (ClinicalTrials.gov identifier: NCT03528681) evaluated the efficacy and safety of SZC in Chinese patients with hyperkalemia. This Phase III, randomized, double-blind, placebo-controlled study recruited patients with serum K+ (sK+) ≥5.1 mmol/L at 35 sites in China. Patients received SZC 10 g three times daily (TID) for 24 or 48 hours during an open-label initial phase (OLP). Those patients achieving normokalemia (sK+ 3.5–5.0 mmol/L inclusive) entered a 28-day randomized (2:2:1) treatment phase (RTP) and received SZC 5 g, SZC 10 g, or placebo once daily. The primary endpoint was mean sK+ during RTP Days 8 to 29. Secondary endpoints included mean change in sK+ during the OLP, the proportion of patients who achieved normokalemia at the end of the OLP, the proportion that maintained normokalemia during the RTP, and time to recurrence of hyperkalemia. In total, 270 patients received SZC 10 g TID during the OLP; 256 (94.8%) completed the OLP. During the OLP, mean sK+ decreased by 1.1 mmol/L from baseline (5.9 mmol/L; P < 0.001) and 87.4% of patients achieved normokalemia. During the RTP, SZC 5 g and 10 g reduced mean sK+ versus placebo in a dose-dependent manner (each P < 0.001); least-squares means (95% confidence interval [CI]) sK+ were 4.9 mmol/L (4.7, 5.0), 4.4 mmol/L (4.3, 4.6), and 5.2 mmol/L (5.1, 5.4) for SZC 5 g, 10 g, and placebo, respectively. At RTP end, the proportions of patients who maintained normokalemia were 58.8% (SZC 5 g; odds ratio vs placebo, 2.5 [95% CI: 1.1, 6.1; P = 0.035]), 76.5% (SZC 10 g; odds ratio vs placebo, 6.3 [95% CI: 2.6, 15.3; P < 0.001]), and 36.8% for placebo. Risk of recurrent hyperkalemia was reduced by 61.0% and 84.0% with SZC 5 g and SZC 10 g, respectively, versus placebo (each P < 0.001). During the RTP, the incidence of adverse events was numerically higher with SZC 5 g (50.0% of patients) and 10 g (44.0%) versus placebo (36.0%); driven primarily by peripheral edema and constipation. Both SZC doses demonstrated clinically relevant and statistically significant, dose-dependent efficacy in managing sK+ levels in Chinese patients with hyperkalemia, compared with placebo. SZC tolerability was broadly aligned with the known safety profile of SZC.

Sodium zirconium cyclosilicate (Lokelma™) [hereafter referred to as SZC] is a non-absorbed, non-polymer zirconium silicate compound that preferentially exchanges hydrogen and sodium for potassium and ammonium ions in the gastrointestinal tract (GIT), thereby increasing faecal potassium excretion and lowering serum potassium levels. It is available as a powder for oral suspension (in water) and is approved in the EU and the USA for the treatment of hyperkalaemia in adults. In two multinational, phase III studies in adults with hyperkalaemia, SZC 10 g three times daily lowered serum potassium levels to within the normal range (3.5–5.0 mmol/L) during the first 48 h of treatment, and SZC 5 and 10 g once daily maintained normokalaemia over ≤ 28 days’ therapy. These beneficial effects were consistent across all patient subgroups (e.g. chronic kidney disease, diabetes, heart failure, concomitant use of RAAS inhibitor therapy), and appeared to be maintained over the longer term (≤ 12 months). SZC was generally well tolerated in adults with hyperkalaemia. Its tolerability profile was generally similar to that seen with placebo over ≤ 28 day, and its safety profile appeared to remain consistent over the longer term (≤ 12 months). Moreover, the incidence of hypokalemia was low. Current evidence indicates that SZC is a promising therapy for the management of hyperkalaemia in adults.