A phase 2 study of the bivalent VLP norovirus vaccine candidate in older adults; impact of MPL adjuvant or a second dose

IntroductionAcute norovirus gastroenteritis causes significant morbidity and in uncommon cases fatality in older adults. We investigated the safety and immunogenicity of bivalent virus-like particle (VLP) vaccine candidate formulations with and without monophosphoryl lipid A (adjuvant MPL) in this population.MethodsIn this phase II, double-blind, controlled trial 294 healthy adults, ≥ 60 years of age, were randomized (1:1:1:1) to four groups to receive one or two intramuscular immunizations 28 days apart, with 26 18–49 year-old controls who received one MPL-free dose. One-dose groups received placebo on Day 1. Vaccine formulations contained 15 μg GI.1 and 50 μg GII.4c VLP antigens and 500 μg Al(OH)₃, with or without 15 μg MPL. We measured histo-blood group antigen blocking (HBGA) antibodies and ELISA Ig at Days 1, 8, 29, 57, 211 and 393, and avidity indices and cell-mediated immunity (CMI). Solicited local and systemic adverse events (AE) were assessed for 7 days and unsolicited AEs for 28 days after each injection.ResultsAfter one dose HBGA antibodies to both VLP antigens increased with similar kinetics and magnitude in all groups; geometric mean titres (GMTs) persisted above baseline through Day 393. GMTs were similar across age strata (18–49, 60–74, 75–84 and ≥ 85 years of age) and unaffected by a second vaccination or MPL. Total Ig showed similar responses. No clinically relevant differences or changes in avidity or CMI were observed between formulations. Both formulations were well tolerated with no vaccine-related SAEs, the most frequent AEs being mild injection site pain and fatigue.ConclusionsAdults over 60 years of age displayed no safety concerns and had similar immune responses to the norovirus VLP vaccine candidate as younger adults, unaffected by increasing age, a second dose or inclusion of MPL. This data supports the further development of the MPL-free vaccine candidate for older adults.     

老年难治性胃食管反流病患者食管动力学特征和反流特点分析

目的 分析老年难治性胃食管反流病（rGERD）患者食管动力学特征和反流特点。方法 以我院2017 年2 月～2019 年12 月收治的100 例rGERD 患者为观察对象。按照年龄分为老年组（年龄≥60 岁）42 例和非老年组（年龄＜60 岁）58 例。比较两组基线资料、临床表现特征、食管动力学特征、反流特点。结果 老年组与非老年组在性别、BMI 指数、吸烟及饮酒方面比较，差异均无统计学意义（P＞0.05）。老年组胸痛、上腹部不适及慢性咳嗽发生率均高于非老年组，差异均有统计学意义（P＜0.05）。老年组LESP 及LEPP 水平均低于非老年组，差异均有统计学意义（P＜0.05）。老年组酸反流、弱酸反流、非酸反流、气体反流、气液混合反流次数均高于非老年组，差异均有统计学意义（P＜0.05）。结论 老年rGERD 患者存在明显的食管动力学异常，且该类患者的反流主要是弱酸反流、非酸反流、气体反流、气液混合反流。     

Survival Outcomes After Initial Treatment for Anal Adenocarcinoma: A Population-Based Cohort Study

BackgroundAnal adenocarcinoma (AA) is reported to represent 5% to 10% of all anal cancer. Currently there is no evidence-based treatment of AA. We investigated clinical outcomes after treatment regimens in patients with AA and used the Surveillance, Epidemiology, and End Results (SEER) registry to examine the outcome.Patients and MethodsWe searched for patients diagnosed with histologically confirmed adenocarcinoma of the anal canal with stage I to III disease between 2010 and 2016 using SEER1Stat software.ResultsA total of 393 patients treated from 2010 to 2016 for AA were identified. Patients were divided into 5 groups according to treatment: 68 patients (17.3%) receiving radiotherapy (RT) and chemotherapy (CTx), 16 patients (4.1%) receiving RT or CTx, 108 patients (27.5%) receiving surgery alone, 137 patients (34.8%) receiving preoperative RT or CTx with surgery, and 64 patients (16.3%) receiving postoperative RT or CTx with surgery. The 3-year cause-specific survival (CSS) rates were 63.9% in the RT and CTx group, 35.7% in the RT or CTx group, 77.7% in the surgery-alone group, 80.3% in the preoperative RT or CTx group, and 65.8% in the postoperative group (P < .001). Preoperative RT or CTx was associated with improved CSS on multivariate analysis (P = .024). The 3-year CSS rates for those who received surgery and those who did not receive surgery were 81.5% and 87.5% for stage I disease, and 74.4% and 57.3% for stage II/III disease.ConclusionPreoperative treatment with surgical resection may maximize the survival outcome. Although chemoradiotherapy alone may be sufficient for early stages of disease, patients with advanced disease should be treated with a combination of surgical resection and chemoradiotherapy. Future studies are required to determine the appropriate treatment strategies in AA.     

高龄产妇妊娠分娩结局的临床现状研究

介绍高龄产妇妊娠分娩结局的临床现状研究，探讨其可研究的方向。本文通过横向比较多篇研究高龄产妇妊娠分娩结局的文献进行综述。近年来，高龄产妇数量不断增加，并已成为全球的趋势。高龄产妇不良妊娠分娩结局较多，包括妊娠高血压、妊娠糖尿病、胎盘早剥、围产期死亡、早产、胎儿巨体症和胎儿生长受限等；与产妇高龄无关的妊娠分娩结局有冠心病、子女的长期发病率等；医学界普遍鼓励妇女早育。     

右美托咪定对老年机械通气患者睡眠与认知的影响

目的 探讨老年机械通气患者使用右美托咪定对睡眠和认知功能的影响。方法 自2018年1月～2019年12月,将我院ICU老年呼吸机患者随机分为右美托咪定组和咪达唑仑组,每组30例。用脑电双频指数监测镇静深度,以多导睡眠检测仪记录睡眠脑电图。记录两组呼吸机使用期间不良反应的发生次数。通过ICU模糊评估方法(CAM-ICU)评估两组患者在7 d内出现谵妄的病例数。使用PSQI和MMSE量表追踪患者3个月的睡眠质量和认知功能状态。结果 右美托咪定组的睡眠效率显著更高(P0.05)。7 d内谵妄发生率右美托咪定组较咪达唑仑组患者显著减少(P0.05)。两组患者在ICU期间发生呼吸抑制不良事件发生率有显著差异(P0.05),但意外脱管和心血管事件的不良事件发生率无显著差异(P0.05)。两组在3个月时的MMSE评分有显着差异(P0.05),但PSQI检查无统计学差异(P0.05)。结论 对于有短期机械通气的老年患者,右美托咪定的镇静作用是理想的。     

老年人股骨粗隆间骨折手术时机对预后影响的临床研究

目的：探讨老年股骨粗隆间骨折手术时机对临床预后结局的影响。方法整群选取2015年1月—2016年1月该院收治的老年股骨粗隆间骨折患者68例为研究对象。根据患者手术时间将其分为A组与B组, A组32例,B组36例,观察两组患者不同年龄术后30 d、1年的死亡情况。结果两组患者术后30d、1年死亡率比较差异无统计学意义,P>0.05；但A组、B组患者中超过80岁的患者术后1年死亡率明显低于80岁以下年龄患者,P<0.05,差异具有统计学意义。结论年龄超过80岁的老年股骨粗隆间骨折患者术后1年死亡率相对较高。