Stability of probiotics with antibiotics via gastric tube by simple suspension method: An in vitro study

Data on the stability of probiotics with antibiotics delivered via gastric tube using the simple suspension method (SSM) are limited. Therefore, we investigated bacterial survivability in probiotics treated with antibiotics prepared by the SSM in vitro. Probiotics and antibiotics were suspended in 20 mL of sterilized hot water (55 °C) and then 1-mL of the suspensions were taken each at 10, 60, 120, 180 and 360 min. Thereafter, the samples were inoculated on 3 media and cultured at 37 °C for 24 h. Survival of probiotic strains was measured in colony-forming units. The growth of Clostridium butyricum did not change without antibiotics at all experimental times, but in the case of Enterococcus faecium tended to increase. On the other hand, the viable bacterial number of C. butyricum was decreased significantly by treatment with cefdinir, tosufloxacin, clarithromycin, or azithromycin, but was not altered by levofloxacin, minocycline, or vancomycin. The viable bacterial number of E. faecium was significantly decreased by treatment with tosufloxacin, levofloxacin, minocycline, vancomycin, or azithromycin, and was significantly increased by clarithromycin. In conclusion, our results suggest that the efficacy of probiotic therapies might be reduced by the SSM when specific antibiotics are used. Moreover, antibiotics might inhibit probiotic growth, although some probiotics are spore-forming and have high minimum inhibitory concentrations. Additionally, early administration of non-spore-forming bacteria might be desirable. Therefore, when patients are administered therapy combining probiotics and antibiotics by the SSM, we should consider the characteristics of the probiotics and the administration times.     

益气活血通络法对气虚血瘀型慢性阻塞性肺疾病急性发作(AECOPD)血小板活化指标的影响

目的评价对气虚血瘀型慢性阻塞性肺疾病急性发作(AECOPD)患者应用益气活血通络法的临床价值以及对其血小板活化指标的影响。方法选取2017年9月～2019年5月我院收治的136例慢性阻塞性肺疾病急性发作患者为研究对象,采用数字随机表法将其分成2组(试验组与对照组),每组68例。其中对照组运用临床常规治疗措施,试验组在此基础上运用益气活血通络法治疗。对其治疗前后血小板活化指标、中医症候积分等数据进行统计分析。结果①试验组与对照组治疗前中医证候积分比较,差异无统计学意义(P0.05),治疗后试验组评分低于对照组同等数据评分,差异有统计学意义(P0.05);②两组患者治疗前D-二聚体、PAC-1、CD62p比较,差异无统计学意义(P0.05),治疗后试验组D-二聚体、PAC-1、CD62p等均低于对照组,差异有统计学意义(P0.05);③试验组治疗总有效率97.06%(66/68)高于对照组治疗总有效率88.24%(60/68),差异有统计学意义(P0.05)。结论针对慢性阻塞性肺疾病急性发作患者给予常规治疗基础之上开展益气活血通络法治疗,相比常规治疗效果显著,对改善其血小板活化指标具有重要帮助,是临床治疗该种疾病的有效措施。     

Composite interaction tree for simultaneous learning of optimal individualized treatment rules and subgroups

Treatment response heterogeneity has long been observed in patients affected by chronic diseases. Administering an individualized treatment rule (ITR) offers an opportunity to tailor treatment strategies according to patient-specific characteristics. Overly complex machine learning methods for estimating ITRs may produce treatment rules that have higher benefit but lack transparency and interpretability. In clinical practices, it is desirable to derive a simple and interpretable ITR while maintaining certain optimality that leads to improved benefit in subgroups of patients, if not on the overall sample. In this work, we propose a tree-based robust learning method to estimate optimal piecewise linear ITRs and identify subgroups of patients with a large benefit. We achieve these goals by simultaneously identifying qualitative and quantitative interactions through a tree model, referred to as the composite interaction tree (CITree). We show that it has improved performance compared to existing methods on both overall sample and subgroups via extensive simulation studies. Lastly, we fit CITree to Research Evaluating the Value of Augmenting Medication with Psychotherapy trial for treating patients with major depressive disorders, where we identified both qualitative and quantitative interactions and subgroups of patients with a large benefit.     

Core-Shell Arginine-Containing Chitosan Microparticles for Enhanced Transcorneal Permeation of Drugs

Chitosan oligosaccharide (C) was functionalized with l-arginine (A) and short hydrocarbon chains (C₈) to design an amphiphilic copolymer, henceforth CAC₈, leading to microparticles (MPs) consisting of an arginine-decorated hydrophilic shell and inner hydrophobic domains allowing the encapsulation of high amount hydrophobic drugs such as sorafenib tosylate (>10% w/w). l-arginine side chains were selected in order to impart the final MPs enhanced transcorneal penetration properties, thus overcoming the typical biological barriers which hamper the absorption of drugs upon topical ocular administration. The mucoadhesive properties and drug release profile of the CAC₈ MPs (CAC₈-MPs) were studied, showing that CAC₈-MPs can strongly interact with mucin, and thus gradually release their payload in situ to potentially improve the bioavailability of the drug after topical administration. In vitro transcorneal studies also showed that CAC₈-MPs are endowed with effective permeation enhancer ability combined with negligible toxicity.     

Attenuation Coefficient Estimation of Normal Placentas

Attenuation coefficient estimation has the potential to be a useful tool for placental tissue characterization. A current challenge is the presence of inhomogeneities in biological tissue that result in a large variance in the attenuation coefficient estimate (ACE), restricting its clinical utility. In this work, we propose a new Attenuation Estimation Region Of Interest (AEROI) selection method for computing the ACE based on the (i) envelope signal-to-noise ratio deviation and (ii) coefficient of variation of the transmit pulse bandwidth. The method was first validated on a tissue-mimicking phantom, for which an 18%–21% reduction in the standard deviation of ACE and a 14%–24% reduction in the ACE error, expressed as a percentage of reported ACE, were obtained. A study on 59 post-delivery clinically normal placentas was then performed. The proposed AEROI selection method reduced the intra-subject standard deviation of ACE from 0.72 to 0.39 dB/cm/MHz. The measured ACE of 59 placentas was 0.77 ± 0.37 dB/cm/MHz, which establishes a baseline for future studies on placental tissue characterization.     

不同麻醉方法对超高龄髋部骨折手术患者围术期血压的影响

目的探讨不同麻醉方法对超高龄髋部骨折患者围术期血流动力学的影响。方法选择2017年5月～2019年2月在我院行髋部骨折手术的患者92例,年龄≥90岁,随机分为全身麻醉(general anesthesia,GA)组和硬膜外麻醉(epidural anesthesia,EA)组,每组46例。GA组患者行全身麻醉,EA组患者行硬膜外麻醉。记录术前静息血压(T0)、麻醉诱导或硬膜外起效后血压(T1)、切皮时血压(T2)和术后当天(Day 0)、术后第1天(Day 1)、术后第2天(Day 2)的血压及术中低血压次数。用查尔森合并症指数(Charlson Comorbidity Index,CCI)比较有和无分层情况下两组各时间点的平均动脉血压(MAP)及术中低血压次数。结果 T1、T2时间点GA组MAP低于EA组(P0.05),其余时间点MAP无统计学差异。EA组患者低血压次数少于GA组(P0.05)。亚组分析中,CCI≥3时,Day 0时间点EA组MAP低于GA组(P0.05),其余时间点MAP无统计学差异(P0.05)。CCI≥3时,两组低血压次数无统计学差异(P0.05)。结论超高龄髋部骨折手术患者硬膜外麻醉较全身麻醉在血流动力学上更稳定。但在有多个合并症的患者中,两者差异并不明显,且硬膜外麻醉术后当天容易发生低血压。     

Using Discretely Integrated Condition Event Simulation To Construct Quantitative Benefit–Risk Models: The Example of Rotavirus Vaccination in France

PurposeAlthough quantitative benefit–risk models (qBRms) are indisputably valuable tools for gaining comprehensive assessments of health care interventions, they are not systematically used, probably because they lack an integrated framework that provides methodologic structure and harmonization. An alternative that allows all stakeholders to design operational models starting from a standardized framework was recently developed: the discretely integrated condition event (DICE) simulation. The aim of the present work was to assess the feasibility of implementing a qBRm in DICE, using the example of rotavirus vaccination.MethodsA model of rotavirus vaccination was designed using DICE and implemented in spreadsheet software with 3 worksheets: Conditions, Events, and Outputs. Conditions held the information in the model; this information changed at Events, and Outputs were special Conditions that stored the results collected during the analysis. A hypothetical French birth cohort was simulated for the assessment of rotavirus vaccination over time. The benefits were estimated for up to 5 years, and the risks in the 7 days following rotavirus vaccination versus no vaccination were assessed, with the results expressed as benefit–risk ratios.FindingsThis qBRm model required 8 Events, 38 Conditions, and 9 Outputs. Two Events cyclically updated the rates of rotavirus gastroenteritis (RVGE) and intussusception (IS) according to age. Vaccination occurred at 2 additional Events, according to the vaccination scheme applied in France, and affected the occurrence of the other Events. Outputs were the numbers of hospitalizations related to RVGE and to IS, and related deaths. The entire model was specified in a small set of tables contained in a 445-KB electronic workbook. Analyses showed that for each IS-related hospitalization or death caused, 1613 (95% credible interval, 1001–2800) RVGE-related hospitalizations and 787 (95% credible interval, 246–2691) RVGE-related deaths would be prevented by vaccination. These results are consistent with those from a published French study using similar inputs but a very different modeling approach.ImplicationsA limitation of the DICE approach was the extended run time needed for completing the sensitivity analyses when implemented in the electronic worksheets. DICE provided a user-friendly integrated framework for developing qBRms and should be considered in the development of structured approaches to facilitate benefit–risk assessment.