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.     

SEPT9在结直肠癌早期检测中的研究进展

SEPT9是13个Septin同源基因家族之一，参与调控众多过程，包括细胞分裂、细胞极化、细胞迁移以及线粒体分裂等。研究表明在众多肿瘤中，SEPT9都发挥着作用，尤其在结直肠肿瘤研究领域，外周血SEPT9基因甲基化检测更是研究热点，其检测的敏感度和特异度相对于其他糖蛋白肿瘤标志物、粪便隐血试验和粪便免疫化学测试等更具有优势，相对于结直肠镜等侵入性检查更节约成本，同时有着更好的依从性。本文对SEPT9的功能、与结直肠癌之间的关系以及对结直肠肿瘤的筛查及诊断价值做一综述。     

Utility of the Tétanos Quick Stick® in the vaccine catch-up of adult migrants without proof of prior vaccination

BackgroundUnknowing immunity status make migrants vaccine catch-up difficult. The interest of using a rapid tetanus immunotest as the Tétanos Quick Stick® (TQS®) to assess immunity status against tetanus has been evaluated in emergency rooms and it is now commonly used. The study aim was to evaluate TQS® as a tool for migrants’ vaccine catch-up.MethodsFrom December 2018 to February 2019, a prospective study was performed and included consecutively migrants who attented to the primary medicine outconsultation of a health care centre in Paris. Migrants above 18, without any records of tetanus immunization were included and a TQS® was performed during a medical consultation. Adapted vaccine catch-up was then proposed. Immunity against tetanus among migrants, factors associated with positive TQS® and costs savings were evaluated.ResultsTQS® test was positive for 32% of the 310 included patients. In the univariable analysis, factors associated to the presence of a positive TQS® test were a female gender (OR = 1.69 CI95% [1.02–2.80]) and an urban living in the country of origin (OR = 1.79 CI95% [1.07–3.02]). In the multivariable analysis, these factors were not significantly associated to a positive TQS®. Anamnesis was not correlated to the immunity status: only 26% of the migrants who reported vaccinations in childhood, adolescence and adulthood had a positive TQS® test. The use of TQS® test allowed savings of 6,522 US$ as compared to the immediate catch-up strategy for the 310 patients.ConclusionThe TQS® test is an acceptable, simple, rapid and cost saving test that could find a place in the migrants’ vaccine catch-up.     

Addressing Substance Use in Adolescents: Screening,Brief Intervention,and Referral to Treatment

Adolescent substance use is a national public health crisis. The most commonly used substances among adolescents are nicotine, alcohol, and marijuana. Use of these substances during adolescence has serious adverse effects on brain development, with impairments that can endure into adulthood. Advanced practice nurses in primary care can address substance use in the adolescent population with the use of evidence-based interventions, such as Screening, Brief Intervention, and Referral to Treatment (SBIRT). This article describes trends in adolescent substance use and use of the SBIRT intervention for low, medium, and high-risk use in this population.     

Prognostic and clinicopathological utility of programmed death-ligand 1 in malignant pleural mesothelioma: A meta-analysis

ObjectiveProgrammed death ligand 1 (PD-L1) has been reported to be connected to prognosis in individuals with malignant pleural mesothelioma (MPM), although there is no consensus based on data from previous studies. Accordingly, this quantitative meta-analysis investigated prognostic and clinicopathological utility of PD-L1 in patients with MPM.MethodsA comprehensive search of the PubMed, Web of Science, Embase, and Cochrane Library databases for articles published up to October 4, 2019 was performed. Studies using immunohistochemical techniques to detect/quantify the expression of PD-L1 in MPM tissue were enrolled in the analysis. The combined hazard ratio (HR) and corresponding 95% confidence interval (CI) was applied to assess the association between PD-L1 expression and overall survival (OS).ResultsA total of 11 studies comprising 1606 patients was included in the present meta-analysis. For OS, pooled data revealed an HR of 1.50 (95% CI 1.32–1.70; p < 0.001), suggesting that patients with PD-L1 overexpression experience inferior OS. Subgroup analysis revealed that elevated PD-L1 remained a significant prognostic indicator for worse OS, irrespective of sample size, cut-off value, ethnicity, and Newcastle-Ottawa Scale score. Moreover, PD-L1 overexpression was associated with non-epithelioid histology (odds ratio 4.30 [95% CI 1.89–9.74]; p < 0.001).ConclusionsResults of this meta-analysis show that elevated expression of PD-L1 could be a factor predicting poorer survival in patients with MPM.     

Personal trauma among healthcare providers: implications for screening practices

ABSTRACT

Screening rates for trauma are low in health care settings. We examined the association between health care providers’ (HCPs) experience of physical or sexual trauma and their screening of female patients for trauma. HCPs at an urban academic medical institution were surveyed from September through November 2016. The Brief Trauma (BTQ) and Sexual and Physical Abuse History Questionnaires (SPAHQ) assessed their own experiences of trauma. The Screening Practices Questionnaire (SPQ) assessed HCPs trauma screening. Multiple regression analyses were performed. Among 212 respondents aged 22–67 years, most were female (78.3%) and white (76.1%). Nurses (41.0%) were the largest occupational group. Overall, 85.8% reported having experienced trauma. No significant difference was observed in median SPQ scores between HCPs who had experienced trauma (3.88 [Interquartile Range (IQR) 3.44–4.31]) and those who had not (4.00 [IQR 3.47–4.33], p = .645). In an adjusted model, screening policy awareness and having an obstetrics & gynecology or psychiatry specialty were associated with higher SPQ scores (p < .001). The prevalence of trauma experience in this sample was high, but not associated with screening. Screening policy awareness and practice specialty were associated with screening. HCP factors associated with greater trauma screening should be explored.