Evaluation of a tiered in vitro testing strategy for assessing the ocular and dermal irritation/corrosion potential of pharmaceutical compounds for worker safety

Introduction: Irritation reactions are a frequently reported occupational illness. The potential adverse effects of pharmaceutical compounds (PCs) on eye and skin can now be assessed using validated in vitro methods.

Objectives: Our overall aim is to reduce animal testing by replacing the historically utilized in vivo test methods with validated in vitro test methods which accurately determine the ocular and dermal irritation/corrosion potential of PCs to inform worker safety within the pharmaceutical space. Bristol–Myers Squibb (BMS) and the Institute for In Vitro Sciences (IIVS) have therefore conceptualized and internally qualified a tiered in vitro testing strategy to inform occupational hazards regarding eye and skin irritation and corrosivity of PCs. For the small scale pre-qualification phase, we paired historical in vivo and newly generated in vitro data for 15 PCs to determine the predictive capacity of in vitro assays already validated for the eye and skin irritation/corrosion endpoints and accepted for certain regulatory submissions. During the post-qualification phase, a group of 24 PCs were subjected exclusively to the developed tiered testing strategy, which is based on three Organisation for Economic Co-operation and Development (OECD) in vitro methods.

Materials and methods: The qualified in vitro testing strategy utilizes the Corrositex^® assay for the corrosivity (OECD TG 435), the Bovine Corneal Opacity and Permeability (BCOP) assay for ocular irritation (OECD TG 437), and the EpiDerm? tissue model-based Skin Irritation Test (SIT) for dermal irritation (OECD TG 439). In the first step, the pH of each PC was determined. For compounds with pH extremes ≥11 or ≤2, the Corrositex^® assay was generally conducted first. For compound(s) that were incompatible with or were negative in the Corrositex^® assay or had pH values between 2 and 11, the BCOP assay and SIT were performed first.

Results: The results of the tiered testing strategy’s qualification phase demonstrated that the BCOP assay is sensitive enough to identify a wide range of eye irritation/corrosion potentials and its over-prediction rate was considered acceptable to inform occupational hazards and ensure the proper handling practices of PCs. The SIT correctly predicted the skin irritation potential of 14 out of the 15 PCs included in the qualification phase, only over-predicting one PC. In the post-qualification phase, four PCs out of four tested were predicted corrosive by the Corrositex^® assay and thus no further testing was needed or conducted. The rest of the PCs were evaluated in the BCOP assay (both neat and as a 20% dilution), with the higher response being used for hazard classification. Four PCs were determined to be severe eye irritants, 1 a moderate irritant, 8 were mild irritants, and 8 were non-irritants. The same set of PCs was evaluated using the SIT and were classified as non-irritants to skin. These results are consistent with the BMS historical in vivo results showing a very low number of PCs as skin irritants.

Conclusions: This tiered in vitro testing strategy, which replaces the use of animal studies, was found to be reasonably accurate in its predictive capacity when compared to historical in vivo results and represents a conservative and reliable platform that can be utilized for the prediction of ocular and dermal irritation/corrosion potential of PCs and for subsequent GHS classification and worker safety hazard communications.     

护生对手术室职业防护的认知性调查

目的 了解护生对手术室职业防护的认知,为临床带教提供依据,提高护生自我防护意识,落实职业防护措施,减少职业暴露发生,促进身心健康.方法 自行设计调查问卷对80名实习护生进行手术室职业防护的认知性调查.结果 不同学历的认知比较,对比组之间的差异有统计学意义(P＜0.05),28.7％对手术室职业暴露认识不足,58.7％自我保护意思不强,48.7％职业防护措施不落实,88.7％认为有必要接受职业防护培训,大部分护生在手术室实习期间身心健康有不同程度的影响.结论 护生对手术室的职业防护知识欠缺与学历有关,带教上应严格选择优秀的带教老师,根据不同学历因人施教,加强对手术室实习护生职业防护知识培训,加强日常护理行为的督查,予必要心理辅导,实行人文关怀,将有利于提高护生职业防护意识,减少职业暴露发生,促进身心健康.     

以社区为基础招募的乌鲁木齐市吸毒者首次吸毒发生情况的调查

目的:在横断面调查的基础上,采用生存分析方法(survivalanalysis)探讨乌鲁木齐市社区吸毒人群发生首次吸毒的情况及其影响因素。方法:于2005年4-6月,以应答驱动抽样为主要招募方式,在社区招募吸毒者参加调查;应用结构式问卷调查吸毒者的社会人口学特征、首次口吸和静脉注射毒品时间、方式,首次吸毒前的个人成瘾性行为(如吸烟、饮酒)及家庭成员、亲友吸毒情况等。结果:401名静脉注射毒品者进入本次横断面调查,首次吸毒方式为口吸和静脉注射毒品者分别为95·0%(381/401)和5·0%(20/401),首次使用的毒品均为海洛因,首次吸毒年龄19·8a±s5·0a,首次吸毒年龄最小值为6·4a,15a以前开始吸毒者占14·2%(57/401)。从出生到首次吸毒的发生率为5·0/100人年(95%CI:4·5-5·5),影响首次吸毒发生的变量为:维族(HR=2·161,95%CI:1·713-2·726)、15a以前开始吸烟(HR=1·273,95%CI:1·006-1·610)、16a以前开始饮酒(HR=1·774,95%CI:1·387-2·269)、有亲戚吸毒(HR=1·411,95%CI:1·032-1·928)。从出生到发生首次吸毒的时间分别为:维族17·9(95%CI:17·2-18·5)a,15a以前开始吸烟者为20·0(95%CI:20·0-20·8)a,16a以前开始饮酒者为17·0(95%CI:16·6-17·7)a,有亲戚吸毒者为19·2(95%CI:18·6-20·0)a。结论:提示吸毒流行严重地区,吸毒低龄化可能会加速艾滋病的流行。在青少年早期开展个人成瘾性行为(如吸烟、饮酒)的干预教育及艾滋病知识的宣传教育非常必要,维族青少年应该是重点干预人群。     

The effect of tightened hearing protection regulations on military noise-induced tinnitus

The objective of this study was to investigate the effect of tightened hearing protection regulations on tinnitus in the Finnish Defence Forces. The initial study group comprised 252 officers and non-commissioned officers (NCOs), of which 229 were included in the final study group. Subjective symptoms of tinnitus and audiometric test results for these officers and NCOs examined before retirement, from 1984 to 1986 (Period I), and 2003 to 2005 (Period II), were reviewed. Changes in tinnitus reports between the two time periods, during which regulations had been revised, were investigated. Prevalence of tinnitus showed a decline both in officers (from 68% to 63%) and in NCOs (from 76% to 72%) between the two study periods, in accordance with tightened hearing protection regulations. The Cox regression analysis showed a significantly decreased hazard ratio for constant or disturbing tinnitus for Period II. Tinnitus prevalence, especially constant or disturbing tinnitus, in the Finnish Defence Forces was diminished by tightened hearing protection regulations. Tinnitus might be more persistent than hearing loss and does not necessarily improve in direct relation to hearing loss after protective measures.     

个体化作业治疗对精神分裂症患者作业表现的影响

目的 探讨个体化作业治疗对精神分裂症患者作业表现的影响.方法 2016年至2018年,选取北京安定医院超过1年的住院精神分裂症患者30例,随机分为对照组(n=15)和试验组(n=15).对照组进行常规小组作业活动,试验组实施个体化作业治疗,每次30 min,每天1次,每周5 d,共4周.治疗前后采用综合性作业治疗评估量...     

医护人员对医院感染知识掌握程度的调查分析

目的调查医、护人员对医院感染知识的掌握程度,为有针对性的开展院内感染知识提供依据。方法采用问卷调查的方法和实地检查相结合,对120名在岗的医护人员掌握院感相关知识进行调查。结果医护人员对院内感染知识知晓率低,而且医生、护士对医院感染知识掌握程度不同,护士在职业防护方面优于医生,差异有统计学意义（x^2=13．88,P〈0．01）。结论医护人员对医院感染知识重视不够,职业防护意识不强,故加强医护人员医院感染知识的培训和学习非常重要。     

优质护理服务工程实施中精神科护士压力现状调查分析

目的了解优质护理服务工程实施以来精神科护士压力及相关因素分析。方法采用护士压力源量表对西安市精神卫生中心临床护士进行调查,并采用SSPS19.0软件包进行统计学分析。结果 78名护士整体压力水平为中度,首要压力为护理专业及工作方面问题,其次为患者护理方面的问题,并且男护士、倒班护士、非在编护士压力比较高,差异有统计学意义(P<0.05)。结论了解优质护理服务工程实施中精神科护士压力情况,给予个人、护理管理者及医院管理层以支持,有利于缓解压力,提高生活和工作质量。     

深矿井煤矿作业对工人健康的影响

目的调查深矿井煤矿作业对工人健康的影响。方法对2478名深矿井煤矿工人进行职业健康查体,统计其各查体项目的异常人次率及职业病患病情况。结果所有工人中,检出各类异常者为467人次,检出率为18.8%,且工龄越长,患病危险性越大。不同工种间各项目检查的异常人次率不同,差异具有统计学意义（χ2=46.390,P〈0.001）。职业性中暑者21人次,发病人次率为0.8%;职业性尘肺的工人共有3人,占0.1%,患职业性噪声聋的工人共有6人,占0.2%。结论深矿井煤矿工人的健康存在较多问题,中暑是发病率较高的职业病。     

二甲双胍联合DPP-4抑制剂对比二甲双胍联合磺脲类药物对2型糖尿病患者心血管疾病风险、心血管相关死亡率和/或全因死亡率影响的荟萃分析

目的:由于目前多个临床试验在评估二甲双胍+DPP-4抑制剂与二甲双胍+磺酰脲类药物在降低2型糖尿病患者心血管病风险、心血管病死亡率和/或全因死亡率的结果上有所冲突,因此我们荟萃评价二甲双胍分别联合两类药物对2型糖尿病患者心血管病风险、心血管病死亡率和/或全因死亡率的影响.方法:按英文限定词系统搜索Medline/PubMed、EMBASE和互联网数据库(从2000年~2015年9月)发布的与二甲双胍联合DPP-4抑制剂或两类磺酰脲类药物对2型糖尿病患者心血管病风险、心血管病死亡率和/或全因死亡率的影响研究.从203篇相关报道中,最终判定纳入8篇进行分析.在这些研究中,对二甲双胍+磺酰脲类和二甲双胍+DPP-4抑制剂联合治疗的心血管病风险事件,心血管病死亡率和或全因死亡率进行了报道,并调整相对危险度(RR)或同等(危险比和优势比)和相应的方差.结果:二甲双胍联合DPP-4抑制剂相比二甲双胍联合磺酰脲类治疗的非致死性心血管事件合并相关风险RRs(95%CIs)为0.71(0.56~0.90),致死性心血管事件合并相关风险RRs为1.001(0.85~1.18),心血管病死亡率RRs为0.58(0.41~0.82).结论:二甲双胍联合DPP-4抑制剂相比二甲双胍联合磺酰脲类治疗能显著降低2型糖尿病患者的非致死性心血管事件风险(RR),心血管死亡率和全因死亡率.但是两种治疗方法在致命性心血管事件(心衰)上没有统计学差异.     

某浮式生产储油和卸油装置职业病危害控制效果

目的通过了解浮式生产储油和卸油装置（以下简称FPSO）项目存在的职业病危害因素及其控制效果,提出职业病危害的关键控制点和防护的进一步改进措施。方法对项目进行职业卫生调查,对作业场所进行职业病危害因素检测分析。结果该项目正常生产过程中存在的职业病危害因素主要有甲烷、非甲烷总烃、苯、甲苯、二甲苯、硫化氢、异丙醇、乙酸、一氧化碳、氮氧化物、噪声、高温、微波辐射、工频电场等。生产过程中各现场操作岗位均可接触到上述有害因素。检测正戊烷、正己烷、正庚烷、苯、甲苯、二甲苯、异丙醇、乙酸、一氧化碳、氮氧化物的浓度均符合国家职业卫生标准;检测的15个工种中仅有5个工种的个体噪声水平符合国家标准,微波辐射和工频电场的测量结果均符合国家标准。结论该项目针对其产生职业病危害因素所采取的防护措施,制定的规章、制度有效可行,其职业病防护设施满足职业卫生验收要求。