Impact of carbapenem antibiotics on mycophenolate mofetil in hematopoietic stem cell transplant patients with interruption of the enterohepatic recycling: a retrospective study.

Background: Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is widely used in the prophylaxis for graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation (HSCT). MPA undergoes enterohepatic recycling (EHR). Oral antibiotics can affect MPA concentration by reducing intestinal flora-mediated EHR. However, the effect of intravenous antibiotics on MPA concentration is not clear, especially in patients whose EHR is already interrupted. This study was conducted to determine whether intravenous carbapenem antibiotics (CBP) influence the pre-dose plasma concentration (C0) of MPA in HSCT patients when the EHR of MPA is interrupted by cyclosporine and gut decontamination. Methods: The HSCT patients who received immunosuppressive therapy with MMF and cyclosporine, as well as treatment with CBP were screened as potential candidates. Patients who lacked MPA C0 measurements before or during CBP use, had combination therapy of rifampin with MMF, or switched from IV to oral MMF were excluded. The liver/renal function, demographic information, albumin/cyclosporine concentration, MPA C0 and medication information were collected. The changes in the MPA C0 before and during CBP use were evaluated, and the influence of related clinical factors was also estimated. Results: CBP resulted in a significant reduction in the MPA C0 from 0.65±0.33 to 0.43±0.30 µg/mL. Linear regression analysis indicated a weak correlation between the dose-normalized C0 of MPA and the dosage of CBP during CBP use (r2=0.129, P=0.009). Univariate and multivariate analysis confirmed that the MPA C0 had no relevance to rifaximin administration (P=0.249-0.700), demographics (P=0.118-0.599), fluctuation of plasma albumin (ALB, P=0.943 and 0.609) and cyclosporine concentrations (P=0.647 and 0.112), or liver and renal functions (P=0.078-0.887) no matter whether the CBP were used. However, compared with the non-gut decontamination group, larger interindividual variabilities and smaller decreases in MPA C0 (6.60% vs. 41.73%) during CBP therapy were seen in the gut decontamination group, although it was a nonsignificant trend. Conclusions: CBP decreased the MPA C0 in Chinese HSCT patients even when MMF is used in combination with cyclosporine and rifaximin. If antibiotics must be used, and CBP in particular, therapeutic drug monitoring should be performed to ensure adequate exposure.

[Network Meta-analysis of effect of traditional Chinese medicine injections in adjuvant treatment of mycoplasma pneumonia in children].

To assess the clinical efficacy of traditional Chinese medicine injection for adjuvant treatment of mycoplasma pneumoniae pneumonia in children by network Meta-analysis method. We retrieved CNKI, WanFang, CBM, Cochrane Library, PubMed from the establishment to September 2018. Two reviewers independently screened out literatures, extracted data and assessed the methodological quality of included studies. The data were analyzed by Stata 13.0 software. Totally 89 RCTs were included, involving 8 kinds of traditional Chinese medical injections and 8 936 patients. According to the results of network Meta-analysis, the order by the total effective rate from high to low was Huangqi Injection>Xiyanping Injection>Tanreqing Injection>Compound Danshen Injection>Reduning Injection>Yanhuning Injection>Qingkailing Injection>Xixinnao Injection; the order by cooling time from high to low was Reduning Injection> Yanhuning Injection>Qingkailing Injection>Tanreqing Injection>Huangqi Injection>Xiyanping Injection>Xiexinnao Injection>Compound Danshen Injection; the order by the cough disappeared time from high to low was Compound Danshen Injection>Qingkailing Injection>Xiyanping Injection>Huangqi Injection>Yanhuning Injection>Reduning Injection>Tanreqing Injection>Xixinnao Injection; the order by the rales disappearing time from high to low was Qingkailing Injection>Yanhuning Injection>Reduning Injection>Huangqi Injection>Tanreqing Injection>Xiyanping Injection>Xixinnao Injection. The results show that traditional Chinese medicine injection has a significant clinical efficacy in the adjuvant treatment of various symptoms of mycoplasma pneumoniae pneumonia in children. Due to the small sample size, more studies are required to verify the strength of evidence.

Multicenter-Based Population Pharmacokinetic Analysis of Ciclosporin in Hematopoietic Stem Cell Transplantation Patients.

PURPOSE: To explore the contribution of physiological characteristics to variability in ciclosporin pharmacokinetics in hematopoietic stem cell transplantation patients. METHODS: Clinical data from 563 patients were collected from centers in three regions. Ciclosporin concentrations were measured using immunoassays. The patients' demographics, hematological and biological indicators, coadministered drugs, region, and disease diagnosis were recorded from medical records. Data analysis was performed using NONMEM based on a one-compartment model to describe the pharmacokinetics of ciclosporin. The reliability and stability of the final model were evaluated using bootstrap resampling, goodness-of-fit plots, and prediction-corrected visual predictive checks. RESULTS: The population estimate of the clearance (CL) was 30.4 L/h, the volume of distribution (V) was 874.0 L and the bioavailability (F) was 81.1%. The between-subject variability in these parameters was 26.3, 68.0, and 110.8%, respectively. Coadministration of fluconazole, itraconazole, or voriconazole decreased CL by 17.6%, 28.4%, and 29.2%, respectively. Females' CL increased by approximately 12.0%. In addition, CL and V decreased with hematocrit, total protein, and uric acid increase, and CL also decreased with age and aspartate aminotransferase increase. However, CL increased with creatinine clearance increase. CONCLUSIONS: A multicenter-based population pharmacokinetic model of ciclosporin was established. The pharmacokinetics of ciclosporin exhibited discrepancies among different regions.

Tacrolimus Levels in the Prophylaxis of Acute Graft-Versus-Host Disease in the Chinese Early After Hematopoietic Stem Cell Transplantation.

BACKGROUND: Tacrolimus has been widely accepted as the backbone of acute graft-versus-host disease (aGVHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (alloHSCT). The present work evaluated whether tacrolimus concentrations early after transplant correlate with the incidence of aGVHD in Chinese alloHSCT recipients. METHODS: One hundred four Chinese alloHSCT recipients were included in this retrospective study. All patients received standard prophylaxis with tacrolimus and short-term methotrexate. Blood samples were taken at steady-state for those on i.v. tacrolimus (Cv) or predose (C0) and 2 hours after the last oral dose (C2). RESULTS: In the first 8 weeks after alloHSCT, significant variability in Cv, C0, and C2 of Chinese patients was observed. It was found that higher tacrolimus C0 and C2 values tended to be associated with a reduced risk of aGVHD, although this was a nonsignificant trend due to the small sample size involved. Receiver operating characteristic curve analysis indicated that Cv levels of ≥16.52 ng/mL, C0 levels of ≥5.56 ng/mL, and C2 levels of ≥7.83 ng/mL minimized the incidence of treatment failure during weeks 3-4 with intravenous administration and weeks 5-6 with oral administration. There was no statistically significant association of the patient liver and kidney function with the blood concentration of tacrolimus in the desired range of 5-20 ng/mL. CONCLUSIONS: Tacrolimus therapeutic drug monitoring improved treatment outcomes of Chinese alloHSCT recipients. Cv measurements during weeks 3-4 and C0 or C2 measurements during weeks 5-6 better predicted aGVHD (I-IV) than the concentrations measured at other time points during the first 6 weeks after alloHSCT.

[Clinical application evaluation and revision suggestions of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for upper respiratory tract infection in children].

Questionnaires and case investigation methods were taken in this paper, taking the clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for upper respiratory tract infection in children published by the Chinese Medicine Association as the research object. Doctors from 187 hospitals in 29 regions across the country were invited to evaluate the applicability of the Guideline and clinical application effects, so as to collect the opinions on revising the Guideline. Clinicians about 508 accepted the applicability survey of the Guideline, and considered that the structure and content of the Guideline were reasonable, with the proportions being as high as 98.23% and 98.03%, respectively. In the content of syndrome differentiation-based treatment, the factors with higher rationality included therapeutic principle and method (99.41%), diagnosis elements (98.82%), and syndrome differentiation classification (98.03%); while the factors with lower rationality included the rehabilitation and health preserving (97.05%) and complication prevention (97.24%). 98.03% of the clinicians considered theat the Guideline was to be fully applicable and basically applicable, and 1.97% of the clinicians considered it to be applicable after revision. By observing 491 cases, the Guide was applied for evaluation and analysis. The factors with higher compliance included diagnosis of Western medicine disease (100%) and the diagnosis of TCM disease (99.18%); while the factors with lower compliance included the treatment measures, with a compliance rate of 77.18% and 83.05% respectively for simple preparations and other treatment method. The safety and economy of the Guideline were good, 97.35%, 93.89%, respectively. The comprehensive evaluation was good, and 99.41% of the respondents were willing to follow the treatment schemes recommended in the Guideline, suitable for clinical application. The opinions on revision were mainly focused on dialectical treatment, complication prevention and rehabilitation. It indicates that only by actively and extensively soliciting opinions to revise the Guideline, can we improve the quality of the Guideline for clinical practice, so as to raise the level of clinical efficacy.

[A commentary of literature research of traditional Chinese medicine for acute upper respiratory tract infection in children].

Acute upper respiratory tract infection is the most common infectious disease in children's respiratory system. The pathogen to the main virus, can account for more than 90% of the primary upper respiratory tract infectio. However, there is no specific anti-viral drugs specifically for the disease, in addition to the existence of excessive, widespread use or even abuse of antibiotics.Long-term clinical practice has confirmed that Chinese medicine is safe and effective in treating acute upper respiratory tract infection in children. The author reviews the literatures of multiple databases, and analyzes the advantages of Chinese patent medicine in the treatment of acute upper respiratory tract infection in children from the perspective of clinical research and experimental basic research. It also puts forward the existing problems and possible research directions of Chinese patent medicine in the treatment of acute upper respiratory tract infection in children.

[Research of aeration with bio-film technology to treat urban landscape water].

Research of the aeration with bio-film technology was carried out to treat scenic water of a sanatorium in Beijing. The aim of the research was improving the water habitat by increasing the transparency and reducing the concentration of N and P. The equipments were set in a 5,000 m2 water area, which combined the plug flow jet aerator with the elastic biological filler. The research indicated that the transparency increased from 25 cm to 120 cm by the technology. The removal efficiencies of NH4(+)-N, NO3(-)-N and TP were 86.6% , 90% and 73.3%, but there was only 22.4% for TN. The concentration of DO increased from 4.3 mg/L to 7 mg/L. In a word, the aeration with bio-film technology was an effective measure to improve the water habitat by increasing the transparency.