Pharmacokinetics and pharmacodynamics of intravenous delafloxacin in healthy subjects: model-based dose optimization.

Delafloxacin, a fluoroquinolone antibiotic to treat skin infections, exhibits a broad-spectrum antimicrobial activity. The first randomized, open-label phase I clinical trial was conducted to assess the safety and pharmacokinetics (PK) of intravenous delafloxacin in the Chinese population. A population pharmacokinetic (PopPK) model based on the clinical trial was conducted by NONMEM software. Monte Carlo simulation was performed to evaluate the antibacterial effects of delafloxacin at different doses in different Chinese populations. The PK characteristics of delafloxacin were best described by a three-compartment model with mixed linear and nonlinear clearance. Body weight was included as a covariate in the model. We simulated the AUC0-24h in a steady state at five doses in patient groups of various weights. The results indicated that for patients weighing 70 kg and treated with methicillin-resistant Staphylococcus aureus (MRSA) infections, a minimum dose of 300 mg achieved a PTA > 90% at MIC90 of 0.25 µg/mL, suggesting an ideal bactericidal effect. For patients weighing less than 60 kg, a dose of 200 mg achieved a PTA > 90% at MIC90 of 0.25 µg/mL, also suggesting an ideal bactericidal effect. Additionally, this trial demonstrated the high safety of delafloxacin in single-dose and multiple-dose groups of Chinese. Delafloxacin (300 mg, q12h, iv) was recommended for achieving optimal efficacy in Chinese bacterial skin infections patients. To ensure optimal efficacy, an individualized dose of 200 mg (q12h, iv) could be advised for patients weighing less than 60 kg, and 300 mg (q12h, iv) for those weighing more than 60 kg.

ePIANNO: ePIgenomics ANNOtation tool.

Recently, with the development of next generation sequencing (NGS), the combination of chromatin immunoprecipitation (ChIP) and NGS, namely ChIP-seq, has become a powerful technique to capture potential genomic binding sites of regulatory factors, histone modifications and chromatin accessible regions. For most researchers, additional information including genomic variations on the TF binding site, allele frequency of variation between different populations, variation associated disease, and other neighbour TF binding sites are essential to generate a proper hypothesis or a meaningful conclusion. Many ChIP-seq datasets had been deposited on the public domain to help researchers make new discoveries. However, researches are often intimidated by the complexity of data structure and largeness of data volume. Such information would be more useful if they could be combined or downloaded with ChIP-seq data. To meet such demands, we built a webtool: ePIgenomic ANNOtation tool (ePIANNO, http://epianno.stat.sinica.edu.tw/index.html). ePIANNO is a web server that combines SNP information of populations (1000 Genomes Project) and gene-disease association information of GWAS (NHGRI) with ChIP-seq (hmChIP, ENCODE, and ROADMAP epigenomics) data. ePIANNO has a user-friendly website interface allowing researchers to explore, navigate, and extract data quickly. We use two examples to demonstrate how users could use functions of ePIANNO webserver to explore useful information about TF related genomic variants. Users could use our query functions to search target regions, transcription factors, or annotations. ePIANNO may help users to generate hypothesis or explore potential biological functions for their studies.

Effect of Angiotensin-Converting Enzyme Inhibitors on Physical Function in Elderly Subjects: A Systematic Review and Meta-Analysis.

BACKGROUND: Sarcopenia has been accepted as a new geriatric syndrome, which will become a common and important public health challenge. And angiotensin-converting enzyme inhibitors (ACEIs) have been shown to improve exercise capacity in elderly without heart failure. OBJECTIVES: To evaluate the effect of angiotensin-converting enzyme inhibitors (ACEIs) on physical function in elderly. DATA SOURCES: The Cochrane Library, PubMed, EMBASE and Web of Science were searched. ELIGIBILITY CRITERIA: All researches included were randomized controlled trials (RCTs) which compared any kind of ACEIs with placebo or other anti-hypertensives in elderly, and provided empirical data of grip strength and 6-min walk distance change from baseline. STUDY APPRAISAL AND SYNTHESIS METHODS: Risk of bias was systematically assessed by using the Cochrane risk of bias tool. Data of grip strength and 6-min walk distance change from baseline were collected and mean differences (MDs) were calculated along with 95% CI (confidence interval) by using a random effects model. RESULTS: In 3 RCTs including 337 elderly participants, ACEIs (n = 178) did not significantly improved 6-min walk distance (13.45, 95% CI: -16.71 to 43.61; P = 0.38) versus placebo or other antihypertensives (n = 159). In 3 RCTs including 499 elderly participants, grip strength was not significantly different (-0.67, 95% CI: -1.53 to 0.19; P = 0.12) between ACEIs (n = 260) and placebo or other antihypertensives (n = 239). LIMITATIONS: There exists only 4 RCTs and the number of participants is limited. Pooling of data were from different trials including different participant characteristics. And intervention is not strictly consistent. CONCLUSION: This study shows that ACEIs can not significantly improve walk distance or the age-related decline of muscle strength for older participants in clinical trials.