Brachytherapy: An emblematic example of extreme hypofractionated regimen

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3 Gy), then ultra (dose/fraction: 5.2 to 6.1 Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20 Gy/fraction), the use of a single fraction of 19 to 23 Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors.     

Relationships Among Factors Related to Childbirth and Breastfeeding Outcomes in Primiparous Women

ObjectivesTo explore the relationships among potentially modifiable factors related to childbirth and effective breastfeeding initiation at approximately 36 hours after birth and duration and exclusivity at hospital discharge, 2 weeks, 2 months, and 6 months after birth in primiparous women and to explore whether modifiable and nonmodifiable secondary factors and covariates influenced the relationships among factors related to childbirth and these breastfeeding outcomes.DesignA prospective, longitudinal, cohort study.SettingThe postpartum units of two general hospitals in eastern Canada.ParticipantsNinety-seven mother–infant dyads.MethodsWe recorded demographic, childbirth, obstetric history, and breastfeeding data through chart review. A breastfeeding observation was completed at approximately 36 hours after birth by unit nurses. Participants maintained breastfeeding logs in hospital and for 6 months after birth and completed three self-report questionnaires before discharge. We analyzed outcomes using backward stepwise linear and logistic regression.ResultsOne childbirth factor, labor induced with oxytocin, was negatively associated with effective initiation of breastfeeding, and none was related to breastfeeding duration and exclusivity at any time point. Maternal weight; professional support; and newborn’s gestational age at birth, 5-minute Apgar score, weight loss, LATCH score, and active feeds (newborn actively suckled at the breast) were significantly associated with breastfeeding outcomes.ConclusionInduction of labor with oxytocin should be used judiciously; when used, nurses must be hypervigilant to assess the mother–infant dyad for breastfeeding issues and to intervene to prevent or remediate them.     

Assessing the impact of blood alcohol concentration on the rate of in-hospital mortality following traumatic motor vehicle crash injury: A matched analysis of the National Trauma Data Bank

Background

The purpose of this study was to compare the outcomes of trauma patients who were injured in a motor vehicle crash and tested positive for alcohol upon hospital arrival versus those who tested negative.

LC-MS/MS法测定人血浆中布康唑浓度的不确定度评定

目的：评定LC-MS/MS法测定人血浆中布康唑浓度的不确定度。方法：分析测定过程中不确定度的来源，包括对照品的称量、仪器误差、标准溶液的配制、含药血浆样品的配制、血浆样品的处理、标准曲线的拟合、基质效应、重复性等，评定各来源分量的不确定度，计算合成不确定度和扩展不确定度。结果：人血浆中低（60.0 pg·mL^-1）、中（600.0 pg·mL^-1）、高（6 400.0 pg·mL^-1）浓度布康唑的扩展不确定度分别为5.62，63.90，626.26 pg·mL^-1（k=2，P=95%）。结论：LC-MS/MS法测定人血浆中布康唑浓度的不确定度主要由基质效应、血浆样品的处理（提取回收率），仪器误差、重复性（精密度）引入。     

UPLC-MS/MS测定73例患者血中头孢哌酮与舒巴坦的浓度

目的：建立液相色谱-串联质谱法（UPLC-MS/MS）同时测定人血浆中头孢哌酮与舒巴坦的浓度，分析头孢哌酮/舒巴坦血药浓度监测结果，为临床合理用药提供参考。方法：以氯唑沙宗为内标，采用Waters BEHC₁₈柱（2.1 mm×100 mm，1.7 μm）进行分离，通过串联质谱仪，负离子检测模式下，以多反应监测（MRM）方式进行定量测定。对某院2018年以不同给药方案进行治疗的73例住院患者测定的头孢哌酮/舒巴坦血药浓度结果进行分析。结果：头孢哌酮与舒巴坦在测定条件下1~200 mg·L^-1范围内线性关系良好，两者日内精密度RSD均<10%，基质效应分别为（72.77±0.99）%与（75.72±0.11）%，提取回收率均>90%。73例患者共监测血药浓度96次，其中不同给药方案2 g，q8 h（43例次）；2 g，q12 h（26例次）；2 g，q6 h（27例次），各组头孢哌酮血药浓度的中位数分别为34.12 mg·L^-1（4.12~177.79 mg·L^-1）、31.23 mg·L^-1（1.89~251.8 mg·L^-1）、59.96 mg·L^-1（1.77~140.58 mg·L^-1），舒巴坦血药浓度的中位数分别为6.3 mg·L^-1（0.61~136.01 mg·L^-1）、28.83 mg·L^-1（0.5~133.69 mg·L^-1）、11.17 mg·L^-1（0.73~143.53 mg·L^-1）。Mann-Whitney U检验显示，头孢哌酮血药浓度结果无统计学差异（P>0.05），舒巴坦有统计学差异（P<0.05）。结论：本检测方法操作简便、快速、重复性好，可满足临床头孢哌酮与舒巴坦浓度的检测；头孢哌酮/舒巴坦在不同给药方案下血药浓度结果与个体差异相关，有必要开展血药浓度监测并依据结果适时调整用药方案，提高治疗效果减少耐药率的发生。     

Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.     

Fast CT-PRESS-based spiral chemical shift imaging at 3 Tesla.

A new sequence is presented that combines constant-time point-resolved spectroscopy (CT-PRESS) with fast spiral chemical shift imaging. It allows the acquisition of multivoxel spectra without line splitting with a minimum total measurement time of less than 5 min for a field of view of 24 cm and a nominal 1.5x1.5-cm2 in-plane resolution. Measurements were performed with 17 CS encoding steps in t1 (Deltat1=12.8 ms) and an average echo time of 151 ms, which was determined by simulating the CT-PRESS experiment for the spin systems of glutamate (Glu) and myo-inositol (mI). Signals from N-acetyl-aspartate, total creatine, choline-containing compounds (Cho), Glu, and mI were detected in a healthy volunteer with no or only minor baseline distortions within 14 min on a 3 T MR scanner.     

重度苯妥英钠中毒的药学监护

目的首先确定中毒药物,然后通过测定血药浓度以了解中毒程度,为重度苯妥英钠中毒患者临床抢救治疗提供依据。方法间隔一定时间采集患者静脉血,萃取血中药物,在211 nm处以反相高效液相色谱法定性,明确中毒药物并测定血药浓度。结果在苯妥英中毒患者中最高血药浓度为68.94 mg.L-1,接近治疗浓度上限的3.5倍。结论患者为重度中毒,危及生命,需临床药师与临床医师积极配合,施行全程药学监护。