Young men who have sex with men’s awareness,acceptability, and willingness to participate in HIV vaccine trials: Results from a nationwide online pilot study

BackgroundNew cases of human immunodeficiency virus (HIV) among young men who have sex with men (YMSM) underscore the need to examine their willingness to use biomedical prevention methods, including an acceptable and efficacious HIV vaccine. We examined whether YMSM’s vaccine altruism and vaccine-related socials concerns factors were associated with HIV vaccine acceptability across two vaccine efficacy scenarios, and their awareness and willingness to participate in HIV vaccine research.MethodsThis secondary analysis uses data from a mHealth trial with YMSM at heightened HIV risk (N = 137; 50% racial/ethnic minority; M = 21.7 years). Most YMSM (91.2%) had tested for HIV, and 17.5% (N = 24) reported a prior STI. We used paired-samples t-test to compare differences in efficacy acceptability (50% vs 85%), followed by multivariable regressions examining whether vaccine attitudes (altruism and social concerns) were associated with vaccine acceptability and awareness and willingness to participate in HIV vaccine trials. We controlled for age, education, race/ethnicity, prior HIV testing, and STI diagnosis in our analyses.ResultsAcceptability for the HIV vaccine with 85% efficacy (M = 8.86; SD = 1.76) was greater than acceptability in the 50% efficacy scenario (M = 7.60; SD = 2.58). Altruistic attitudes were associated with greater vaccine acceptability at 50% (β = 0.62) and 85% (β = 0.59) efficacy. Higher educational attainment was negatively associated with a vaccine with 50% efficacy (β = −0.20, but not for 85% efficacy. Greater vaccine-related social concerns were negatively associated with HIV vaccine research awareness (AOR = 0.38 (95% CI: 0.22, 0.67). Willingness to participate in a HIV vaccine trial was positively associated with age (β = 0.18) and altruism (β = 0.60), and negatively associated with education (β = −0.21).ConclusionsYMSM find HIV vaccines as an acceptable prevention modality and are willing to participate in HIV vaccine trials. Findings highlight the need to consider YMSM's altruistic and social concerns attitudes in HIV vaccine research and explore how to leverage these attitudes in research campaigns.ClinicalTrials.gov Identifier: NCT02842060.     

Intranasal nanoemulsion-adjuvanted HSV-2 subunit vaccine is effective as a prophylactic and therapeutic vaccine using the guinea pig model of genital herpes

Genital herpes is a sexually transmitted disease representing a major global health concern. Currently, there is no approved vaccine and existing antiviral therapies exhibit limited efficacy. Herein, we describe an intranasal (IN) vaccine comprised of HSV-2 surface glycoproteins gD2 and gB2 formulated in a nanoemulsion adjuvant (NE01-gD2/gB2). Using the HSV-2 genital herpes guinea pig model, we demonstrate that IN NE01-gD2/gB2 induces higher levels of neutralizing antibody compared to a monovalent IN NE01-gD2 vaccine, but less than an intramuscular (IM) Alum/MPL-gD2 vaccine. Following intravaginal (IVag) challenge with HSV-2, the group immunized with IN NE01-gD2/gB2 exhibited significantly reduced acute and recurrent disease scores compared to placebo recipients. Significantly, latent virus was only detected in the dorsal root ganglia of 1 of 12 IN NE01-gD2/gB2-vaccinated animals compared to 11 of 12 placebo recipient. In the therapeutic model, IN NE01-gD2/gB2 immunized guinea pigs exhibited a significant reduction in the recurrent lesions scores (64%, p < 0.01), number of animal days with disease (64%, p < 0.01), number of animals with viral shedding (50%, p < 0.04) and reduction in virus positive vaginal swabs (56%, p < 0.04), These data suggests that the treatment may be effective in treating chronic disease and minimizing virus transmission. These results warrant advancing the development of IN NE01-gD2/gB2 as both a prophylactic and therapeutic vaccine against HSV-2.     

中国2013年18~49岁育龄妇女2型糖尿病患病率、知晓率、治疗率和控制率状况分析

目的 分析2013年中国18~49岁育龄妇女2型糖尿病患病水平及知晓、治疗和控制情况。方法 2013年在中国慢性病及其危险因素监测的302个监测点,采用多阶段分层整群随机抽样方法调查≥ 18岁居民共计176 534人,其中18~49岁女性46 674人。每名调查对象抽取静脉血测定FPG和糖化血红蛋白。自报无糖尿病病史者测定服糖后2 h血糖（OGTT-2 h）。糖尿病诊断标准依据1999年WHO糖尿病诊断标准FPG ≥ 7.0 mmol/L和/或OGTT-2 h ≥ 11.1 mmol/L。对样本经过复杂加权后,计算不同年龄、教育程度、城乡地区居民的糖尿病患病率及知晓率、治疗率和控制率。结果 中国18~49岁育龄妇女2型糖尿病患病率为5.6%,其中城市为5.7%,农村为5.4%;东、中、西部地区分别为5.8%、6.2%和4.4%,中、东部地区高于西部地区。在糖尿病人群中,患病知晓率、治疗率和控制率分别为29.3%、27.9%和29.4%;知晓自己患糖尿病的育龄妇女治疗率为95.4%,采取措施治疗的育龄妇女糖尿病控制率为38.9%;育龄妇女糖尿病知晓率呈现城市高于农村,治疗率在不同教育程度组间的差异有统计学意义,但趋势检验差异无统计学意义。结论 中国18~49岁育龄妇女2型糖尿病患病率较高,且无明显的城乡差异;而糖尿病知晓率、治疗率和控制率均处于较低水平,具有明显的城乡差异。     

1990年与2013年中国人群胃癌疾病负担分析

目的 分析1990年与2013年中国人群胃癌的疾病负担及其变化情况。方法 利用中国分省疾病负担研究结果,分析2013年中国胃癌疾病负担现状,比较1990年与2013年中国胃癌的发病、死亡、伤残调整寿命年(DALY)、过早死亡损失寿命年(YLL)和伤残损失寿命年(YLD)等,描述1990和2013年各省份胃癌发病、死亡及变化情况。结果 2013年我国胃癌发病37.11万例、死亡31.78万例,标化发病率、死亡率、DALY率分别为26.84/10万、23.55/10万、464.47/10万,有随着年龄增加而逐渐增加的趋势。1990-2013年间男性胃癌标化发病率均高于女性(2.03~2.67倍),并均呈下降趋势。1990-2013年胃癌死亡数由28.21万增加到31.78万,增加13.15%。与1990年相比,2013年我国男女性胃癌的标化死亡率、DALY率、YLL率、YLD率均下降,且女性降幅均大于男性。2013年胃癌发病率和死亡率最高的前三个省份均为青海、安徽、甘肃,下降幅度最大的三个省份均为天津、上海、浙江;所有省份胃癌死亡率下降。结论 2013年中国胃癌疾病负担仍处于较高水平;与1990年相比,2013年全国胃癌疾病负担下降,各省份胃癌死亡率均下降,但仍存在差异。     

1990年与2013年中国人群甲状腺癌疾病负担分析

目的 分析1990年与2013年中国甲状腺癌的疾病负担变化情况。方法 利用2013年中国分省疾病负担研究数据,采用发病率、死亡率、过早死亡损失寿命年(YLL)、伤残损失寿命年(YLD)及伤残调整寿命年(DALY)作为测量疾病负担的主要指标,比较1990年与2013年中国甲状腺癌的疾病负担变化情况。结果 2013年中国甲状腺癌的发病人数为33939例,与1990年相比增加21898例,标化发病率由1990年的1.25/10万升至2.07/10万,增加65.6%,其中女性发病率上升,男性发病率下降。2013年中国因为甲状腺癌死亡4974例,比1990年增加1810例,标化死亡率下降14.29%,其中女性死亡率下降而男性死亡率上升。中国女性甲状腺癌发病率随着年龄的增加而上升,50~54岁年龄组达到高峰。男性甲状腺癌发病率随着年龄增加一直呈现上升趋势。男女性甲状腺癌的死亡率均随年龄的增大而升高。2013年中国因甲状腺癌造成的DALY、YLL、YLD分别为13.35、11.42、1.93万人年,与1990年相比总体DALY标化率由10.33/10万降至8.84/10万,其中YLL标化率由9.60/10万降至7.61/10万,YLD标化率由0.72/10万升至1.23/10万。2013年中国甲状腺癌发病率前三位的省份为青海、新疆和福建,最低的为西藏;与1990年相比,除天津市外各省份发病率均上升;死亡率前三位的省份为青海、香港和福建,最低的为西藏,5个省份死亡率上升。结论 与1990年相比,2013年甲状腺癌的总体标化发病率上升,标化死亡率下降;虽然DALY下降,但由甲状腺癌伤残导致的疾病负担仍然处于上升趋势。     

Application of toxicokinetics to improve chemical risk assessment: Implications for the use of animals

While toxicokinetics has become an integral part of pharmaceutical safety assessment over the last two decades, its use in the chemical industry is relatively new. However, it is recognised as a potentially important tool in human health risk assessment and recent initiatives have advocated greater application of toxicokinetics as part of an improved assessment strategy for crop protection chemicals that could offer greater efficiency, use fewer animals and provide better data for risk assessment purposes. To explore the potential scientific and animal welfare benefits of increased use of toxicokinetic data across the chemical industry, an international workshop was held in 2008. Experts from a wide range of chemical industry sectors, including industrial chemicals, agrochemicals and consumer products, participated in the meeting as well as representatives from relevant regulatory authorities. Pharmaceutical industry experts were also invited, in order to share experiences from the extensive use of toxicokinetics in drug development. Given that increased generation of toxicokinetic data could potentially result in an increased number of animals undergoing testing, technologies and strategies to reduce and refine animal use for this purpose were also considered. This paper outlines and expands upon the key themes that emerged from the workshop.     

Surveillance for Guillain-Barré syndrome after 2015–2016 and 2016–2017 influenza vaccination of Medicare beneficiaries

BackgroundGuillain-Barré syndrome (GBS) is a serious acute demyelinating disease, an increased risk of which was found after the 1976 swine flu vaccinations. The U.S. Food and Drug Administration, in collaboration with the Centers for Medicare & Medicaid Services, has been conducting active surveillance for GBS after influenza vaccinations of Medicare Fee-For-Service beneficiaries since 2009.MethodsWe conducted active surveillance for GBS claims in the 2015–2016 and 2016–2017 influenza seasons using the Updating Sequential Probability Ratio Test (USPRT) to monitor for signals of GBS risk. We performed self-controlled risk interval (SCRI) analyses at the end of both seasons, including chart confirmation in the 2015–2016 season, to estimate the odds ratio of GBS risk. We used 1–42 and 8–21 days post-vaccination as primary and secondary risk windows, respectively, and 43–84 days post-vaccination as the control window.ResultsOver 13 million beneficiaries were vaccinated in each season. USPRT found a low magnitude signal for GBS in both seasons. SCRI analyses did not find excess GBS risk following any influenza vaccine for days 1–42 post-vaccination in either season. In the 2015–2016 season, for the 8–21 day window, our chart-confirmation showed an attributable GBS risk of 0.87 (95% CI: 0.16, 1.49) and 1.68 (95% CI: 0.69, 2.41) cases per million vaccinees after all seasonal and high dose (HD) vaccines, respectively, an elevated GBS risk for beneficiaries aged ≥75 years following all seasonal vaccines (OR: 2.25; 95% CI: 1.15, 4.39) and HD vaccine (OR: 3.67, 95% CI: 1.52, 8.85), and an elevated GBS risk for males who received seasonal vaccines (OR: 2.18; 95% CI: 1.15, 4.15) and HD vaccine (OR: 3.33; 95% CI: 1.35, 8.20). The finding of elevated GBS risk with advancing age and in males is consistent with literature; however, a distinction between HD and SD was a new finding. In the 2016–17 season, for the 8–21 day window, attributed cases showed an attributable GBS risk of 0.87 (95% CI: 0.03, 1.61) and 1.11 (95% CI: 0.00, 2.01) cases per million vaccinees after all seasonal and HD vaccines, respectively. We found no excess GBS risk for standard dose vaccines in the 8–21 day window in either season.ConclusionsOur primary analysis finding of no excess GBS risk during both seasons was reassuring. The slightly elevated GBS risk, although in the expected range, in the 8–21 day window after all seasonal and high dose vaccines, but not after standard dose vaccines is hypothesis-generating because the difference may be due to vaccine factors such as antigen amount or strains in various seasons or due to host factors.     

2013年中国25岁及以上人群身体活动不足归因死亡和对期望寿命的影响

目的 探讨中国≥ 25岁人群不同性别、不同地区身体活动不足归因死亡和对期望寿命的影响。方法 利用中国死因监测数据、慢性病危险因素调查数据以及全球疾病负担研究中身体活动相关健康结局及其相对危险度的数据,计算中国≥ 25岁人群身体活动相关不同健康结局的归因分值以及身体活动不足造成的归因死亡数和期望寿命的影响。结果 全死因死亡中,≥ 25岁人群归因于身体活动的死亡为4.24%,其中女性为4.86%,男性为3.82%。身体活动的疾病健康结局包括乳腺癌、直肠癌、缺血性心脏病、缺血性脑卒中和糖尿病,其归因分值分别为9.04%、13.96%、14.96%、17.80%和16.92%。身体活动归因死亡总数为388 954人,导致死亡最多的疾病为缺血性心脏病,其次为缺血性脑卒中。身体活动不足共造成人群的期望寿命损失0.43岁,其中女性损失0.47岁,男性损失0.39岁。结论 增加身体活动可以获得健康效益,降低慢性病疾病负担和延长期望寿命。     

2018年中国居民归因于吸烟的脑卒中死亡分析

目的了解中国居民2018年脑卒中归因于吸烟的死亡情况,为进一步采取控烟措施提供科学依据。方法利用2013年中国慢性病及其危险因素监测数据和2018年死因监测数据,计算2013年吸烟流行率和吸烟量、戒烟年数等吸烟暴露水平以及2018年我国脑卒中死亡情况,使用2017年全球疾病负担研究(GBD 2017)的最新吸烟归因疾病负担的测算方法,计算我国吸烟导致脑卒中的人群归因分值(PAF),以及吸烟导致的脑卒中死亡情况。应用SAS 9.4对数据进行统计分析。结果2013年中国30岁及以上人群总体现在吸烟率为28.4%,其中男性为53.4%,女性为2.7%。30岁及以上人群戒烟率为5.8%,其中男性为10.9%,女性为0.6%。农村吸烟率(29.2%)和戒烟率(5.9%)均高于城市(分别为26.8%、5.7%)。脑卒中死亡率总体上随着年龄的增加而上升,并且男性各年龄组死亡率均高于女性。2018年中国30岁及以上人群归因于吸烟的脑卒中死亡人数为39.0万人,其中男性死亡人数为34.4万人,远高于女性死亡人数(4.6万人)。30岁及以上人群的PAF为21.8%,男性为34.1%,高于女性(5.9%)。吸烟归因脑卒中死亡率随年龄增加而上升。男性各年龄组的PAF均高于女性。结论我国男性人群吸烟率远高于女性。吸烟导致脑卒中的死亡水平较高,亟须采取更加严格的控烟措施,降低脑卒中等疾病的疾病负担。     

Glutamic acid at position 152 and serine at position 191 are key residues required for the metallo-β-lactamase activity of NDM-7

New Delhi metallo-β-lactamase (NDM) is of significant public-health concern due to its enormous potential to hydrolyse all of the major β-lactams, including carbapenems. Previous reports indicate that amino acid substitutions affect NDM activity despite being located outside of the active site. In this study, we attempted to identify specific mutations in loops near the active site that can influence the function of NDM-7. Overall, six substitutions were performed through site-directed mutagenesis near the active-site of NDM-7 and the change in antimicrobial resistance was subsequently monitored by expressing each mutant in a suitable bacterial host. Among the six mutants, serine at position 191 (S191) and glutamic acid at position 152 (E152) were identified as the most influencing residues for NDM-7. β-Lactam resistance of NDM-7 was remarkably affected by substitution of both residues with alanine, and the results were in accordance with the changes in kinetic parameters. Purified NDM-7 ordinarily hydrolyses β-lactams efficiently, but purified NDM-7_E152A, NDM-7_S191A and the double mutant NDM-7_E152A+S191A had lost their ability to hydrolyse the β-lactams tested, especially penicillins and carbapenems. Although the substitutions did not affect the overall folding pattern of the NDM-7 enzyme, substantial differences in thermal stability were observed. Therefore, we hypothesise that the residues S191 and E152 together play a crucial role in conferring the β-lactamase character of NDM-7.