Poly(ortho ester) nanoparticles targeted for chronic intraocular diseases: ocular safety and localization after intravitreal injection

Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5?mg/ml and 10?mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases.     

User experiences with second-generation 32-gauge × 4 mm vs. thinner comparator pen needles: prospective randomized trial

Abstract

Objective

Two similarly designed studies compared user experiences with a second-generation extra-thin-wall, 5-bevel 32?G?×?4?mm pen needle (PN) with redesigned hub versus four thinner commercially available PNs.     

Barriers to vaccination service delivery within general practice: opportunity to make a sustainable difference in Aboriginal child health?

Objective: To identify behavioural barriers of service provision within general practice that may be impacting the vaccination coverage rates of Aboriginal children in Perth, Western Australia (WA). Methods: A purposive developed survey was distributed to 316 general practices across Perth and three key informant interviews were conducted using a mixed‐methods approach. Results: Of the surveyed participants (n=101), 67.4% were unaware of the low vaccination coverage in Aboriginal children; 64.8% had not received cultural sensitivity training in their workplace and 46.8% reported having inadequate time to follow up overdue child vaccinations. Opportunistic vaccination was not routinely performed by 30.8% of participants. Key themes identified in the interviews were awareness, inclusion and cultural safety. Conclusion: Inadequate awareness of the current rates, in association with a lack of cultural safety training, follow‐up and opportunistic practice, may be preventing greater vaccination uptake in Aboriginal children in Perth. Cultural safety is a critical component of the acceptability and accessibility of services; lack of awareness may restrict the development of strategies designed to equitably address low coverage. Implications: The findings of this study provide an opportunity to raise awareness among clinicians in general practice and inform future strategies to equitably deliver targeted vaccination services to Aboriginal children.     

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.     

Recent advances in construction of small molecule-based fluorophore-drug conjugates

As a powerful tool to advance drug discovery, molecular imaging may provide new insights into the process of drug effect and therapy at cellular and molecular levels. When compared with other detection methods, fluorescence-based strategies are highly attractive and can be used to illuminate pathways of drugs’ transport, with multi-color capacity, high specificity and good sensitivity. The conjugates of fluorescent molecules and therapeutic agents create exciting avenues for real-time monitoring of drug delivery and distribution, both in vitro and in vivo. In this short review, we discuss recent developments of small molecule-based fluorophore-drug conjugates, including non-cleavable and cleavable ones, that are capable of visualizing drug delivery.     

罗哌卡因联合舒芬太尼在剖宫产术后镇痛中的临床效果分析

目的：探讨罗哌卡因联合舒芬太尼在剖宫产术后镇痛中的临床疗效。方法方便选取2014年3月—2015年3月该院麻醉科收诊的剖宫产产妇60例,随机法分为观察组及对照组各30例,对照组术后给予罗哌卡因联合吗啡镇痛治疗,观察组术后给予罗哌卡因联合舒芬太尼镇痛治疗,记录并分析两组产妇镇痛效果。结果观察组术后2h、8h、12 h、24 hVAS评分分别为(1.98±0.81)分、(2.28±0.78)分、(1.66±0.67)分、(1.17±0.61)分,均低于对照组(3.51±1.07)分、(3.82±1.03)分、(3.24±0.95)分、(2.16±0.55)分,且差异具有统计学意义(P<0.05)；观察组术后肌力恢复正常时间和肛门排气时间分别为(7.28±1.16)h、18.49±1.71)h,均低于对照组(15.67±3.59)h、20.84±2.10)h,且差异有统计学意义(P<0.05)；③观察组产妇术后不良反应发生率为6.67%,显著低于对照组26.67%,且差异具有统计学意义(P<0.05)；结论罗哌卡因联合舒芬太尼在剖宫产术后镇痛中的效果优于罗哌卡因联合吗啡,不良反应低,能有效缓解孕妇术后疼痛。     

Percepciones y deseos sobre el parto en gestantes a término en Zamora

ObjectiveTo describe perceptions and wishes regarding childbirth in a group of full-term pregnant women in Zamora.MethodQualitative study of phenomenological character. Participants and scope of study: pregnant women (37-38 weeks), Zamora Sur and Santa Elena health centres (Zamora, Spain). Data collection: semi-structured interviews, until data saturation (16 interviews). Data analysis: analysis of thematic content.ResultsThe maternal feelings varied from joy to fear or stress. The interviewees said they did not feel capable of enduring the pain of childbirth. The needs that they felt most important were having support and accompaniment during delivery (especially of their partner) and receiving good treatment from the healthcare workers.ConclusionsThe importance and repercussion of childbirth for women are not only biological, but also largely mental, emotional and social. It is conditioned by multiple factors: maternal feelings, their ability to deal with the pain of childbirth, their needs, the changes they have made, the support they have and the health professionals who care for them.     

经皮电刺激联合导乐镇痛对分娩结局的影响及安全性分析

目的 探讨经皮电刺激联合导乐分娩镇痛对分娩结局的影响及安全性。方法 选择160例在我院住院待产的产妇作为研究对象,随机将其分为观察组与对照组,每组各80例;其中对照组予导乐分娩镇痛,观察组给予经皮电刺激联合导乐分娩镇痛。观察比较两组的VAS评分、产程时间、产后出血、剖宫产率、产妇满意度、新生儿情况、不良反应发生情况等。结果 与镇痛前比较,观察组镇痛后各时间段VAS评分降低,P＜0.05;与对照组比较,观察组的产后2 h出血量、剖宫产率降低,产妇满意度提高,P＜0.05。结论 经皮电刺激联合导乐镇痛可减轻产妇痛苦,降低剖宫产率,减少产后出血,提高产妇满意度,且无明显不良反应,值得在临床上推广应用。     

84例产褥感染的临床特点及常见致病微生物耐药性分析

目的 研究产褥感染的危险因素及常见致病微生物耐药情况，为临床治疗提供参考。方法 回顾性分析我院2017 年1 月～2019 年12 月发生的84 例产褥感染病例的临床资料，与同时期未发生产褥感染的200 例产妇进行对照研究，分析产褥感染的影响因素，并对分离获得的致病微生物进行耐药性分析。结果 感染组妊娠糖尿病、产钳助产、宫口开全后中转剖宫产患者的分布率高于对照组，差异有统计学意义（P＜0.05）；经多因素Logistic 回归分析，妊娠糖尿病是产褥感染的独立影响因素（P＜0.05）。本研究中共检出致病微生物40 株，其中革兰阴性菌13 株（占32.50%），革兰阳性菌10 株（占25.00%），支原体16 株（占40.00%），衣原体1 株（占2.50%），革兰阴性菌中以大肠埃希菌最常见，对二代头孢菌素类抗生素耐药率20%。革兰阳性菌以金黄色葡萄球菌最常见，对青霉素及头孢菌素耐药率高，未发现对亚胺培南及万古霉素耐药。结论 产钳助产、妊娠糖尿病、宫口开全后中转剖宫产是产褥感染可能的危险因素，其中，妊娠糖尿病是产褥感染的独立危险因素。目前临床常见致病微生物谱及耐药率未发生明显变化。