Sex and gender differences in Alzheimer’s disease: current challenges and implications for clinical practice

Alzheimer’s disease (AD) is characterized by high heterogeneity in disease manifestation, progression and risk factors. High phenotypic variability is currently regarded as one of the largest hurdles in early diagnosis and in the design of clinical trials; there is therefore great interest in identifying factors driving variability that can be used for patient stratification. In addition to genetic and lifestyle factors, the individual’s sex and gender are emerging as crucial drivers of phenotypic variability. Evidence exists on sex and gender differences in the rate of cognitive deterioration and brain atrophy, and in the effect of risk factors as well as in the patterns of diagnostic biomarkers. Such evidence might be of high relevance and requires attention in clinical practice and clinical trials. However, sex and gender differences are currently seldom appreciated; importantly, consideration of sex and gender differences is not currently a focus in the design and analysis of clinical trials for AD. The objective of this position paper is (i) to provide an overview of known sex and gender differences that might have implications for clinical practice, (ii) to identify the most important knowledge gaps in the field (with a special regard to clinical trials) and (iii) to provide conclusions for future studies. This scientific statement is endorsed by the European Academy of Neurology.     

Risk Factors for Chronic Opioid Use Following Hip and Knee Arthroplasty: Evidence from New Zealand Population Data

BackgroundPatients awaiting total joint arthroplasty (TJA) have high rates of opioid use, and many continue to use opioid medications long term after surgery. The objective of this study is to estimate the risk factors associated with chronic opioid use after TJA in a comprehensive population-based cohort.MethodsAll patients undergoing TJA in the New Zealand public healthcare system were identified from Ministry of Health records. Dispensing of opioid medications up to 3 years postsurgery and potential risk factors, including demographic, socioeconomic, and surgery-related characteristics, pre-existing medical comorbidities, and use of other analgesic medications prior to surgery, were identified from linked population databases. Logistic regression analysis was used to identify factors associated with chronic postoperative opioid use.ResultsThe strongest risk factor for chronic postoperative opioid use was preoperative opioid use. Other significant risk factors included perioperative opioid use, history of alcohol or drug abuse, younger age, female gender, knee arthroplasty, several comorbid health conditions, and preoperative use of some analgesic medications. Protective factors included higher education levels and preoperative use of nonsteroidal anti-inflammatory drugs. Most risk factors had similar effects on chronic postoperative opioid use irrespective of the length of follow-up considered (1, 2, or 3 years).ConclusionThis study of a comprehensive nationwide population-based cohort of TJA patients with 3 years of follow-up identified several modifiable risk factors and other easily measured patient characteristics associated with higher risk of long-term postoperative opioid use.     

Endothelial function,regulation of angiogenesis and embryonic central hemodynamics in ART-conceived pregnancies

Abstract

This study was undertaken to compare the concentrations of pro- and anti-angiogenic growth factors, nitric oxide (NO) stable metabolites in maternal serum and embryonic left ventricular (LV) isovolumic relaxation time (IRT, ms) during the first trimester in two groups of women: with pregnancy conceived by assisted reproductive technologies (ART, n?=?39) and normally conceived (control group, n?=?68) pregnancy. The concentration of vasoconstrictor endothelin 1 was 45.5 times more in ART than in control group. On the contrary, the concentrations of NO stable metabolites in ART were 1.9 times less than in control women. The assessment of angiogenic suppressors in ART women demonstrates the decrease in s-endoglin concentration was 1.6 times and in soluble receptor to vascular endothelial growth factor concentration was 2.0 times in comparison with control group. There was a significant increase in LV IRT in ART embryos in comparison to control ones. These data suggest significant changes in pro- anti-angiogenic factors balance and increase in vascular impedance in ART-conceived embryos.     

新生儿重症监护病房中重症肺炎多种菌感染相关因素分析

目的分析新生儿重症监护病房(NICU)中重症肺炎新生儿多种菌感染危险因素。方法回顾分析2014年1月至2019年5月收入NICU的1 057例重症细菌肺炎新生儿的临床资料,分析其多种菌感染的危险因素。结果单因素分析显示,胎龄(37周)、出生体质量(2 500 g)、发病日龄(7 d)、羊水污染(Ⅱ、Ⅲ度)、感染类型(医院感染)、住院时间(≥14天)、机械通气、Apagar评分(7分)、胎膜早破、抗菌药物使用天数(≥10天)、更换抗菌药物(≥3种)、联合使用抗菌药物(≥3种)12个因素是NICU中重症肺炎新生儿多种菌感染的危险因素,差异有统计学意义(P均0.05)。多因素分析显示,更换抗菌药物(≥3种)、Apagar评分(7分)、感染类型(医院感染)、机械通气、羊水污染(Ⅱ、Ⅲ度)是NICU中重症肺炎新生儿多种菌感染的独立危险因素(P0.05)。结论临床应针对主要危险因素采取综合防控措施,减少NICU新生儿重症肺炎多种菌感染。     

稽留流产孕早期预测模型的构建与验证

目的构建稽留流产(missed abortion,MA)患者在孕早期流产危险因素列线图。方法纳入2017年2月至2019年10月因稽留流产于中国建筑第二工程局职工医院治疗的孕妇125例为研究组,随机纳入同时期正常孕妇126例为对照组,分析两组患者临床基本资料:年龄、环境因素、动物接触史、叶酸使用、文化程度、流产情况、疾病史、激素水平等。采用Logistic回归分析对孕早期发生稽留流产的危险因素进行分析,应用R软件建立孕早期稽留流产预测列线图,并进行验证。结果研究组孕妇年龄、睾酮(testosterone,T)水平高于对照组,而催乳素(prolactin,PRL)、雌二醇(estradiol,E2)、孕酮(progesterone,P)水平低于对照组,差异均有统计学意义(P<0.05);Logistic回归分析提示孕妇年龄(OR=1.809,P=0.003)、吸烟饮酒(OR=78.120、P=0.044)、职业暴露(OR=61.238,P=0.021)、T水平(OR=5.432,P=0.001)是孕早期发生MA的危险因素。PRL(OR=0.376,P=0.003)、E2(OR=0.258,P=0.016)、P(OR=0.396,P=0.005)是孕早期发生MA的保护因素。预测孕早期MA发生的相关危险因素的C-index为0.912(95%CI:0.874-0.943)。结论列线图中孕妇年龄、环境因素、激素水平能较准确的预测孕早期发生MA的风险。     

Patients Are Knowledge Workers in the Clinical Information Space

Background  Limited research exists on patient knowledge/cognition or “getting inside patients'' heads.” Because patients possess unique and privileged knowledge, clinicians need this information to make patient-centered and coordinated treatment planning decisions. To achieve patient-centered care, we characterize patient knowledge and contributions to the clinical information space. Methods and Objectives  In a theoretical overview, we explore the relevance of patient knowledge to care provision, apply historical perspectives of knowledge acquisition to patient knowledge, propose a representation of patient knowledge types across the continuum of care, and include illustrative vignettes about Mr. Jones. We highlight how the field of human factors (a core competency of health informatics) provides a perspective and methods for eliciting and characterizing patient knowledge. Conclusion  Patients play a vital role in the clinical information space by possessing and sharing unique knowledge relevant to the clinical picture. Without a patient''s contributions, the clinical picture of the patient is incomplete. A human factors perspective informs patient-centered care and health information technology solutions to support clinical information sharing.     

赤芝FPS基因酵母单杂交文库构建及其上游转录因子的筛选

目的筛选赤芝三萜合成途径中法尼基焦磷酸合酶(farnesyl diphosphate synthase,FPS)基因的上游调控转录因子。方法首先克隆了FPS基因启动子,并连接至pAbAi质粒构建诱饵载体pAbAi-FPS。将pAbAi-FPS转化Y1H酵母感受态细胞构建诱饵菌。采用SMART技术构建赤芝酵母单杂交cDNA文库,再将纯化的双链cDNA、pGADT7-Rec共转化诱饵菌株,筛选FPS上游的转录调控因子。结果构建了含pAbAi-FPS的诱饵载体并筛选出诱饵菌株,构建了cDNA文库并转化诱饵菌株,筛选出阳性克隆37个,得到作用FPS基因上游的转录调控因子18个,包括转录因子3个、核糖体蛋白5个及其他家族蛋白10个。结论筛选出转录因子GlSNF2、GlMHR和GlZn2Cys6为调控FPS表达的候选基因,为深入研究FPS基因的表达调控机制奠定了研究基础。     

持续性特发性耳鸣严重程度的相关因素分析

目的 探讨导致持续性特发性耳鸣严重程度的相关因素。 方法 分析870例持续性特发性主观性耳鸣患者的一般资料、病史、听力学结果、耳鸣匹配实验、耳鸣残疾量表、匹兹堡睡眠质量指数量表和焦虑自评量表,应用多因素Logistic回归分析研究与患者耳鸣严重程度相关的因素。 结果 (1)性别(P<0.001)、年龄(P=0.010)、耳鸣主调声频率(P=0.005)、听力损失(P=0.037)、焦虑程度(P<0.001)、睡眠状况(P<0.001)在THI分级上差异有统计学意义(P<0.05);(2)病程(P=0.053)、侧别(P=0.437)、主调声响度(P=0.120)在THI分级上差异均无统计学意义(P>0.05)。 结论 女性患者特发性耳鸣的程度较男性更为严重;低频较高频更扰人;焦虑程度和睡眠状况是影响耳鸣严重程度的因素,而病程、侧别、耳鸣主调声响度不是影响患者特发性耳鸣严重程度的因素。