横断面研究能否进行因果推断

基于变量调查(或测量)的共时性、统计学关联及幸存者偏倚等原因,横断面研究被认为不能进行因果推断,这是当前的"共识"。本文基于因果思维,借助因果图,首先明确定义真实截面和测量截面,并识别截面概念仅存在于理论的特性。实际横断面研究中,测量变量的共时性并不存在,而是无一例外地表现为非共时性时序,其实质上相当于测量变量间互为独立性假设,或不存在有差别错分偏倚。类似于累积病例对照研究和历史性队列研究,横断面研究均为暴露和结局已存在或发生后进行的测量,这种测量相当于对变量值的历史重建或"考古"。这类研究进行因果推断的共性前提条件之一是,测量变量与其历史变量间必须存在着因果律。测量变量均为真实变量的替代者,测量变量间的时序在因果推断上并不重要。应加强对横断面研究分析性角色的认识。     

A multivalent Kaposi sarcoma-associated herpesvirus-like particle vaccine capable of eliciting high titers of neutralizing antibodies in immunized rabbits

Kaposi sarcoma-associated herpesvirus (KSHV) is an emerging pathogen and the causative agent of multiple cancers in immunocompromised patients. To date, there is no licensed prophylactic KSHV vaccine. In this study, we generated a novel subunit vaccine that incorporates four key KSHV envelope glycoproteins required for viral entry in diverse cell types (gpK8.1, gB, and gH/gL) into a single multivalent KSHV-like particle (KSHV-LP). Purified KSHV-LPs were similar in size, shape, and morphology to KSHV virions. Vaccination of rabbits with adjuvanted KSHV-LPs generated strong glycoprotein-specific antibody responses, and purified immunoglobulins from KSHV-LP-immunized rabbits neutralized KSHV infection in epithelial, endothelial, fibroblast, and B cell lines (60–90% at the highest concentration tested). These findings suggest that KSHV-LPs may be an ideal platform for developing a safe and effective prophylactic KSHV vaccine. We envision performing future studies in animal models that are susceptible to KSHV infection, to determine correlates of immune protection in vivo.     

Trends of self-reported non-adherence among type 2 diabetes medication users in the United States across three years using the self-reported Medication Adherence Reasons Scale

Background & aimsTo determine the trends of self-reported non-adherence rates among adults taking Type 2 medicines (T2D) medicines between 2017 and 2019 and to identify the patterns for the frequently reported reasons for non-adherence in the United States.Methods & resultsData from the National Health and Wellness Survey, a self-administered, internet-based cross-sectional survey of US adults from 2017 to 2019 was used. Non-adherence was measured using the self-reported Medication Adherence Reasons Scale (MAR-Scale). Frequencies were used to identify the reasons for non-adherence for insulin and non-insulin therapies for T2D.Data were obtained from 2983 respondents in 2017, 5416 in 2018, and 5268 in 2019. Based on the MAR-Scale, the self-reported medication non-adherence rate was 25% in 2017, 21% in 2018, and 27% in 2019. The most common reason for non-adherence across all the three years was simple forgetfulness, yet patients reported the lowest mean number of days missing medication for that reason. Though less frequently reported, non-adherence lasted longer when patient did not know how to take their medicines, cost was a reason, or had concerns about the long term effects of the medicines.ConclusionsWith no significant improvement in adherence with T2D medicines over time, regardless of better awareness and extensive diabetes education, focus should be on individualized non-adherence reasons-based interventions.     

基于大自然时间轴的测量时序分类法

因果推断中，时序（或方向性）的概念尚未完全明确。本文从因果思维出发，以真实因和真实果的发生时间将大自然时间轴划分为3个时域和2个时点，从而锚定了因果推断只能实现于第3时域。测量时序可分为5种类型：跨第1和3时域纵向时序（实验性时序）、跨第2和3时域纵向时序、同时域纵向时序、同时域逆纵向时序和同时域横向时序（观察性时序）。这种分类法适用于首次或多次测量、及时和延后测量等所有测量策略。除了实验中真实因的测量（或干预措施）在其发生之前（第1时域）或观察和实验中真实因的测量在真实果发生之前（第2时域）的情形外，所有其他测量策略类似于历史重建或"考古"，测量时序的重要性次于测量的准确性。从研究设计应整合偏倚设计的观点来看，本文提出基于大自然时间轴的测量时序五分类法，概念清楚并将有助于判断研究过程中可能出现的偏倚，为正确进行因果推断研究奠定基础。     

Adverse family experiences and obesity in children and adolescents in the United States

While exposure to adverse family experiences (AFEs), subset of adverse childhood experiences (ACEs), has been associated with childhood obesity, less is known about the impact of exposures to each type of AFE. Using 2011–2012 National Survey of Children's Health data, we evaluated associations between exposure to individual AFEs and overweight/obesity status in children 10 years or older, adjusting for socio-demographic factors. Caregivers reported their child's height, weight, and exposure to nine AFEs; body mass index (BMI) was classified by Center for Disease Control and Prevention's (CDC) guidelines.At Mayo Clinic, we calculated frequencies and weighted estimates of socio-demographic factors and AFEs. Unadjusted and adjusted weighted multinomial logistic regression models were employed to assess the independent associations of each AFE and the different AFE composite scores with BMI category. Exposure to two or more AFEs was independently associated with increased odds of overweight (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.13, 1.56) and obese (OR, 1.45; 95% CI, 1.21, 1.73) status after adjustment for age, household income, parents' education-level, race and sex. Death of parent (OR, 1.59; 95% CI, 1.18, 2.15) and hardship due to family income (OR, 1.26; 95% CI, 1.06, 1.50) were independently associated with obesity status with adjustment for other AFEs and socio-demographic factors.Our results suggest that, in addition to cumulative exposure to AFEs, exposure to certain childhood experiences are more strongly associated with childhood obesity than others. Death of parent and hardship due to family income are individual AFEs, which are strongly predictive of obesity.     

不同诊断情景下结核病负担预测的动力学模型研究

目的 通过建立考虑不同诊断情景的结核病动力学模型,预测不同延迟诊断时间和及时就诊率下发病负担,为控制结核病的传播提供建议。方法 建立系统动力学模型拟合中国CDC 2005-2018年结核病年发病例数,计算结核病基本再生数(R0),通过诊断情景相关参数的数值变化探究其对结核病发病负担影响。结果 模型符合程度的χ²检验结果:χ²=1.102,P=1.000。通过本模型计算得到的结核病R₀=0.063<1,说明在中国结核病会逐渐走向消亡。减少延迟诊断时间和提高及时就诊率短期内引起感染后到医院诊断治疗者人数波动,长期可使感染后未到医院就诊人数持续减少。结论 本研究模型是对2005-2018年结核病发病趋势的良好拟合。在减少延迟诊断时间和提高及时就诊率的诊断情景下,对于结核病长期负担的减少有重要意义,并进一步探讨模型有待改进的地方。