Pharmacokinetics,biocompatibility and bioavailability of a controlled release monoclonal antibody formulation

The sustained and localized delivery of monoclonal antibodies has become highly relevant, because of the increasing number of investigated local delivery applications in recent years. As the local delivery of antibodies is associated with high technological hurdles, very few successful approaches have been reported in the literature so far. Alginate-based delivery systems were previously described as promising sustained release formulations for monoclonal antibodies (mAbs). In order to further investigate their applicability, a single-dose animal study was conducted to compare the biocompatibility, the pharmacokinetics and the bioavailability of a human monoclonal antibody liquid formulation with two alginate-based sustained delivery systems after subcutaneous administration in rats. 28 days after injection, the depot systems were still found in the subcutis of the animals. A calcium cross-linked alginate formulation, which was injected as a hydrogel, was present as multiple compartments separated by subcutaneous tissue. An in situ forming alginate formulation was recovered as a single compact and cohesive structure. It can be assumed that the multiple compartments of the hydrogel formulation led to almost identical pharmacokinetic profiles for all tested animals, whereas the compact nature of the in situ forming system resulted in large interindividual variations in pharmacokinetics. As compared to the liquid formulation the hydrogel formulations led to lower mAb serum levels, and the in situ forming system to a shift in the time to reach the maximum mAb serum concentration (T_max) from 2 to 4 days. Importantly, it was shown that after 28 days only marginal amounts of residual mAb were present in the alginate matrix and in the tissue at the injection site indicating nearly complete release. In line with this finding, systemic drug bioavailability was not affected by using the controlled release systems. This study successfully demonstrates the suitability and underlines the potential of polyanionic systems for local and controlled mAb delivery.     

目标性培训在消毒供应中心培训中的应用

目的 探讨目标性培训方法在消毒供应中心岗位人员器械培训中的应用效果。方法 本研究为随机对照试验。选取2021年4月至7月在揭阳市人民医院消毒供应中心从事手术组工作的 20名 33～45岁女性岗位人员作为培训对象，采用随机数字表法将其分为对照组和观察组，各 10名。 对照组应用传统的培训方法，观察组应用目标性培训方法。培训后比较两组人员操作技能考核成绩、 培训满意度、负责清洗包装腹腔镜基础器械包的清洗质量和包装质量合格率。符合正态分布的计量资料采用均数±标准差（xˉ ± s）表示，组间比较采用独立样本t检验；计数资料采用例数或率（%）表示， 组间比较采用卡方检验；P＜0.05为差异有统计学意义。结果 观察组考核成绩、培训满意度及其负责清洗包装的腹腔镜基础器械包清洗质量、包装质量合格率明显高于对照组［（90.2±6.1）分比（77.0± 7.5）分、（90.0±6.0）分比（72.1±9.8）分、487（97.4%）比453（90.6%）、492（98.4%）比472（94.4%）］，差异有统计学意义（均P＜0.05）。结论 在消毒供应中心岗位人员器械培训时应用目标性培训方法，可有效提高岗位人员考核成绩及培训满意度及其负责清洗包装的腹腔镜基础器械包清洗质量、包装质量合 格率，保障患者安全。     

Medical equipment libraries: implementation,experience and user satisfaction

Abstract

The hospital-wide pooling and sharing of certain types of medical equipment can lead to both significant improvements in patient safety and financial advantages when compared with a department or ward-level equipment ownership system. In September 2003, a Medical Equipment Loan Service (MELS) was established, focusing initially on infusion pumps. The aims and expected benefits included; improving availability of equipment for both patients and clinical users, managing and reducing clinical risk, reducing equipment diversity, improving equipment management and reducing the overall cost of equipment provision. A user survey was carried out in 2005 and repeated in 2011. The results showed wide and continued satisfaction with the service. The process and difficulties of establishing the service and its development to include additional types of equipment are described. The benefits of managing medical equipment which is in widespread general use, through a MELS as part of a Clinical Engineering Department, are presented.     

With how many users should you test a medical infusion pump? Sampling strategies for usability tests on high-risk systems

Usability testing is recognized as an effective means to improve the usability of medical devices and prevent harm for patients and users. Effectiveness of problem discovery in usability testing strongly depends on size and representativeness of the sample. We introduce the late control strategy, which is to continuously monitor effectiveness of a study towards a preset target.A statistical model, the LNB_zt model, is presented, supporting the late control strategy. We report on a case study, where a prototype medical infusion pump underwent a usability test with 34 users. On the data obtained in this study, the LNB_zt model is evaluated and compared against earlier prediction models.The LNB_zt model fits the data much better than previously suggested approaches and improves prediction. We measure the effectiveness of problem identification, and observe that it is lower than is suggested by much of the literature. Larger sample sizes seem to be in order. In addition, the testing process showed high levels of uncertainty and volatility at small to moderate sample sizes, partly due to users’ individual differences. In reaction, we propose the idiosyncrasy score as a means to obtain representative samples. Statistical programs are provided to assist practitioners and researchers in applying the late control strategy.     

半球骨瓣减压结合控制性减压治疗特重型颅脑损伤

目的：探讨半球骨瓣减压结合控制性减压治疗特重型颅脑损伤的临床疗效。方法采用去半球大骨瓣彻底减压技术，结合硬脑膜网状切开和有限渐次减压法等控制性减压，对60例特重型颅脑损伤患者进行手术治疗，术后6个月进行GOS评分评价，3～4分为良好，2分为中度残废，1分为重度残废。结果死亡25例（病死率为41．7％），存活35例，其中恢复良好10例，中度残废1例，重度残废14例。结论去半球骨瓣伴控制性减压技术具有显露好、减压充分等优点，可有效降低手术病死率。     

Inference for Clinical Trials with Some Protocol Amendments

ABSTRACT

The use of adaptive methods in clinical development has become very popular in recent years due to its flexibility in modifying trial procedures and/or statistical procedures of on-going clinical trials. Modifications to trial procedures are usually documented by protocol amendments. However, the actual patient population after protocol amendments could deviate from the originally targeted patient population. In addition, protocol amendments made based on accrued data of the on-going trial may distort the sampling distribution of the statistic designed for the case of no protocol change. In this article, we model the population deviations due to protocol amendments using some covariates and study how to develop a valid statistical inference procedure. An example concerning an asthma trial is presented for illustration.     

控制性降压下俯卧位脊柱手术全麻患者眼内压及眼底动脉血液动力学的变化

目的实时监测控制性降压对俯卧位脊柱手术全麻患者眼内压及眼底动脉血液动力学的影响,以探讨其安全阈值。方法随机选取预行俯卧位脊柱全麻手术的60例外科患者为研究对象,麻醉过程中采用硝酸甘油控制性降压。选择诱导前10 min(T0)、诱导后10 min(T1)、俯卧位后10 min(T2)、控制性降压10%(T3)、20%(T4)、30%(T5)、恢复正常血压10 min(T6)、术毕平卧位后10 min(T7)、拔出气管导管后10 min(T8)9个时间点,使用笔式眼压计测量眼内压(IOP),使用彩色多普勒超声仪测定右眼视网膜中央动脉和睫状后动脉的血流动力学特征收缩期最高流速(PSV)、舒张末期最低流速(EDV)、阻力指数(RI)及搏动指数(PI)。结果患者诱导麻醉后,IOP、RI及PI随着麻醉时间的延长呈升高趋势,PSV及EDV呈降低趋势,T5时,各指标差异性最大,均较T0有显著差异(P0.05或0.001)。T6后,各指标有所恢复,T8各指标较T0无统计学差异(P0.05)。另外,T5时4例患者出现视网膜中央动脉闭塞(CRAO)征象,其MAP均低于患者该时段平均水平(64.8±8.66 mmHg)。结论控制性降压对俯卧位脊柱手术全麻患者的眼内压及眼底动脉血液动力学指征有所影响,血压降低水平控制在基线水平的30%以内,且保证目标MAP65 mmHg,可有效保护患者视神经。     

Effect of exposure factors on image quality in screening mammography

IntroductionThe aim of this research was to study the effect of exposure factors on image quality for digital screening mammography units in Kuwait which use Tungsten (W) targets with Rhodium (Rh) and Silver (Ag) as filters.MethodsMammography Accreditation Phantom Model 015 was imaged using a Hologic Selenia Digital mammography unit with W targets and Rh and Ag filters. Four images, each at 26, 28, 30, and 32 kVp, were obtained using each target-filter combination (W/Rh and W/Ag). The images were evaluated by five senior technologists for the number of specks, fibers and masses visible on each image. Statistical analysis was carried out using non-parametric tests at p = 0.05 level.ResultsThere were significant changes in the visibility of fibers and specks between different kVp values with W/Rh (p < 0.001). However, with W/Ag combination, significant differences were observed in the fibers only (p < 0.001). Among the kVp values used, 28 kV emerged as the optimal value. Comparison of images obtained with the two filter materials, led to significant differences in the visibility of fibers and specks (p < 0.008). At 32 kVp, there were significant differences in the visibility of specks only (p < 0.008).ConclusionA W/Rh target-filter combination provides better image quality than that provided by W/Ag. In particular, 30 and 32 kVp X-ray beams produce higher quality images than the lower kV values.     

Magnetic-based multi-layer microparticles for endothelial progenitor cell isolation,enrichment, and detachment

Although endothelial progenitor cells (EPCs) are useful in many applications including cell-based therapies, their use is still limited due to issues associated with cell culture techniques like a low isolation efficiency, use of harmful proteolytic enzymes in cell cultures, and difficulty in ex vivo expansion. Here, we report a tool to simultaneously isolate, enrich, and detach EPCs without the use of harmful chemicals. In particular, we developed magnetic-based multi-layer microparticles (MLMPs) that (1) magnetically isolate EPCs via anti-CD34 antibodies to avoid the use of Ficoll and harsh shear forces; (2) provide a 3D surface for cell attachment and growth; (3) produce sequential releases of growth factors (GFs) to enrich ex vivo expansion of cells; and (4) detach cells without using trypsin. MLMPs were successful in isolating EPCs from a cell suspension and provided a sequential release of GFs for EPC proliferation and differentiation. The cell enrichment profiles indicated steady cell growth on MLMPs in comparison to commercial Cytodex3 microbeads. Further, the cells were detached from MLMPs by lowering the temperature below 32 °C. Results indicate that the MLMPs have potential to be an effective tool towards efficient cell isolation, fast expansion, and non-chemical detachment.     

The potential of an automated system to identify the upper limb component of a controlled sitting posture

Full trunk control in sitting is demonstrated only when the head-trunk are aligned and upper limbs remain free of contact from mechanical support. These components represent a Controlled Kinetic Chain and can be evaluated in people with neuromotor disability using the Segmental Assessment of Trunk Control (SATCo) when a therapist provides manual trunk support at different segmental levels. However, the SATCo, as with other clinical assessments of control, is subjective. The SATCo was translated to objective rules relating the position of the hands and elbows to the head-trunk and then tested to determine the extent to which this automated objective method replicated the clinical judgement.Clinical evaluation used video to determine whether the upper limb was free of mechanical support while the objective evaluation used 3D motion capture of the trunk and upper limbs with a classification rule. The agreement between clinical and objective classification was calculated for three conditions of a distance-from-support-surface threshold parameter in five healthy adults and five children with cerebral palsy.The unfitted (zero-threshold values) method replicated the clinical judgement in part (68.26% ± 15.7, adults, 48.3% ± 33.9 children). The fitted (level-of-support determined) agreement showed that the process could be refined using trial specific parameters (88.32% ± 5.3 adults, 89.84% ± 10.2 children). The fixed-values agreement showed high values when using general group parameters (80.80% ± 3.1 adults, 74.31% ± 21.5 children).This objective classification of the upper limb component of trunk control largely captures the clinical evaluation. It provides the first stages in development of a clinically-friendly fully automated method.