Estimation,Testing and Adjustment of Transient Healthy Entrant Effects

At recruitment, cohorts often selectively exclude non-healthy individuals with symtoms prodromal to the response. After a certain time from study entry, the health status of participants regresses towards the underlying population. Methods developed here estimate, test and adjust out this transient healthy entrant effect from survival function estimation. In the simplest case, each participant's time is divided into: Ω₁ - immediately after study entry while these transient healthy entrant effects are strong, and Ω₂ - later, after they have vanished or greatly diminished. Truncated Kaplan-Meier models fit separately to risk sets in Ω₁ and Ω₂ quantify and remove the bias from transient healthy entrant effects and test for statistical significance. If sufficient data are available, these methods can be expanded to dividing the subjects' time into multiple subperiods or fitting specific models of attenuation for the transient healthy entrant effect. Examination of nickel refinery workers and an HIV-1 infected cohort suggest that, without the adjustments proposed here, transient healthy entrant effects cause moderate overestimations of survival probability.     

Surgical aortic valve replacement in patients older than 75 years: is there really a quality of life benefit?

BackgroundTo evaluate the results of elective isolated surgical aortic valve replacement (SAVR) on quality of life (QoL) in patients > 75 years.Methods138 patients operated between January 2008 and December 2011 were included. The EuroQOL questionnaire (EQ-5D, EQ-VAS) was completed preoperatively, and 1- and 2-years postoperatively. The logistic EuroSCORE was used for risk stratification, the Corpus Christi Heart project criteria to assess physical activity.ResultsMean age was 79.5 ± 2.8 years, mean risk 9.7 ± 5.4, hospital mortality 2.8 %. For 115 patients (83.3 %) the preoperative QoL information was complete. Fifty patients were classified as sedentary. In the first postoperative year 13 patients died, mostly sedentary patients (p = 0.046) with a low EQ-5D (p = 0.017). There was no QoL information on 32 survivors, mostly sedentary patients (p = 0.001). The 70 patients with QoL information showed an increased QoL (NS). Two years postoperatively, 16 patients died, significantly more sedentary patients (p = 0.015) with a low EQ-5D (p = 0.006). For 42 survivors, there was no QoL information; these were mostly sedentary patients (p = 0.021). The 57 patients with 2-year QoL information had an increased EQ-5D (NS) and EQ-VAS (p = 0.024).ConclusionsQoL increases after SAVR. However, the patients lost to follow-up were mostly sedentary or had a low preoperative QoL, which can lead to biased results.     

Anxiety and depression disorders in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

Background

The objective of this prospective study was to assess the prevalence of anxiety and depression disorders and their association with quality of life (QoL), clinical parameters and survival in patients with pulmonary hypertension (PH).

Methods

We prospectively assessed 158 patients invasively diagnosed with pulmonary arterial hypertension (n = 138) and inoperable chronic thromboembolic PH (n = 20) by clinical measures including quality of life (QoL, SF-36 questionnaire), cardiopulmonary exercise testing and six minute walking distance and by questionnaires for depression (PHQ-9) and anxiety (GAD-7). According to the results of the clinical examination and the questionnaires for mental disorders (MD) patients were classified into two groups, 1) with moderate to severe MD (n = 36, 22,8%), and 2) with mild or no MD (n = 122). Patients were followed for a median of 2.7 years. Investigators of QoL, SF-36 were blinded to the clinical data.

Results

At baseline the 2 groups did not differ in their severity of PH or exercise capacity. Patients with moderate to severe MD (group 1) had a significantly lower QoL shown in all subscales of SF-36 (p < 0.002). QoL impairment significantly correlated with the severity of depression (p < 0.001) and anxiety (p < 0.05). During follow-up period 32 patients died and 3 were lost to follow-up. There was no significant difference between groups regarding survival. Only 8% of the patients with MD received psychopharmacological treatment.

Conclusion

Anxiety and depression were frequently diagnosed in our patients and significantly correlated with quality of life, but not with long term survival. Further prospective studies are needed to confirm the results.     

Regression analysis of mean quality-adjusted lifetime with censored data

In clinical trials of chronic diseases such as acquired immunodeficiency syndrome, cancer, or cardiovascular diseases, the concept of quality-adjusted lifetime (QAL) has received more and more attention. In this paper, we consider the problem of how the covariates affect the mean QAL when the data are subject to right censoring. We allow a very general form for the mean model as a function of covariates. Using the idea of inverse probability weighting, we first construct a simple weighted estimating equation for the parameters in our mean model. We then find the form of the most efficient estimating equation, which yields the most efficient estimator for the regression parameters. Since the most efficient estimator depends on the distribution of the health history processes, and thus cannot be estimated nonparametrically, we consider different approaches for improving the efficiency of the simple weighted estimating equation using observed data. The applicability of these methods is demonstrated by both simulation experiments and a data example from a breast cancer clinical trial study.     

Flexible hazard regression modeling for medical cost data

The modeling of lifetime (i.e. cumulative) medical cost data in the presence of censored follow-up is complicated by induced informative censoring, rendering standard survival analysis tools invalid. With few exceptions, recently proposed nonparametric estimators for such data do not extend easily to handle covariate information. We propose to model the hazard function for lifetime cost endpoints using an adaptation of the HARE methodology (Kooperberg, Stone, and Truong, Journal of the American Statistical Association, 1995, 90, 78-94). Linear splines and their tensor products are used to adaptively build a model that incorporates covariates and covariate-by-cost interactions without restrictive parametric assumptions. The informative censoring problem is handled using inverse probability of censoring weighted estimating equations. The proposed method is illustrated using simulation and also with data on the cost of dialysis for patients with end-stage renal disease.     

Quality control of microbiota metagenomics by k-mer analysis

Background

The biological and clinical consequences of the tight interactions between host and microbiota are rapidly being unraveled by next generation sequencing technologies and sophisticated bioinformatics, also referred to as microbiota metagenomics. The recent success of metagenomics has created a demand to rapidly apply the technology to large case–control cohort studies and to studies of microbiota from various habitats, including habitats relatively poor in microbes. It is therefore of foremost importance to enable a robust and rapid quality assessment of metagenomic data from samples that challenge present technological limits (sample numbers and size). Here we demonstrate that the distribution of overlapping k-mers of metagenome sequence data predicts sequence quality as defined by gene distribution and efficiency of sequence mapping to a reference gene catalogue.

Results

We used serial dilutions of gut microbiota metagenomic datasets to generate well-defined high to low quality metagenomes. We also analyzed a collection of 52 microbiota-derived metagenomes. We demonstrate that k-mer distributions of metagenomic sequence data identify sequence contaminations, such as sequences derived from “empty” ligation products. Of note, k-mer distributions were also able to predict the frequency of sequences mapping to a reference gene catalogue not only for the well-defined serial dilution datasets, but also for 52 human gut microbiota derived metagenomic datasets.

Conclusions

We propose that k-mer analysis of raw metagenome sequence reads should be implemented as a first quality assessment prior to more extensive bioinformatics analysis, such as sequence filtering and gene mapping. With the rising demand for metagenomic analysis of microbiota it is crucial to provide tools for rapid and efficient decision making. This will eventually lead to a faster turn-around time, improved analytical quality including sample quality metrics and a significant cost reduction. Finally, improved quality assessment will have a major impact on the robustness of biological and clinical conclusions drawn from metagenomic studies.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1406-7) contains supplementary material, which is available to authorized users.     

85例多系统萎缩患者预后影响因素的分析

目的:探讨多系统萎缩(multiple system atrophy,MSA)患者预后的影响因素。方法:连续收集2016年1月到2019年1月空军军医大学第一附属医院神经内科住院及门诊收治的85名临床确诊MSA患者的临床资料,每隔6月对患者进行随访记录,直至需辅助行走时间,研究时限3.5年,筛选10个可能影响MSA独立行走的危险因素,应用Cox比例风险回归模型进行单因素及多因素回归分析。结果:85例MSA患者中,很可能MSA38例(44.7%),可能MSA47例(55.3%),以帕金森表现(MSA-P)43例(50.6%),以小脑性共济失调表现(MSA-C)42例(49.4%),男性46例(54.1%),女性39例(45.9%),起病年龄54.7±8.8岁,首发运动症状30例(35.3%),首发非运动症状55例(64.7%)。起病至非运动症状合并运动症状中位时程27.9(11.5, 40.5)月。截至本研究终止,28例(32.9%)患者独立行走,57例(67.1%)患者不能独立行走,起病至辅助行走中位时程36.0(22.5, 54.0)月。Cox比例风险回归模型显示起病年龄大(HR=1.041, 95%CI 1.000-1.083, P=0.049)、HY高分期(HR=2.015,95%CI 1.031-3.938,P=0.040)、起病至非运动症状合并运动症状短时程(HR=0.980,95%CI 0.967-0.993, P=0.003)是MSA患者发展至辅助行走状态的危险因素。结论:起病年龄大、HY高分期、起病至非运动症状合并运动症状短时程是MSA患者辅助行走的不良预后因素。     

基于Logistic回归模型分析维持性血液透析患者肌少症的危险因素及其对患者生活质量、负性情绪及生存状况的影响

摘要 目的：基于Logistic回归模型分析维持性血液透析（MHD）患者肌少症的危险因素及其对患者生活质量、负性情绪及生存状况的影响。方法：选取江苏省人民医院肾内科肾脏病重症病房于2019年2月-2021年2月期间收治的MHD患者289例,收集所有患者的一般资料,根据是否患有肌少症将患者分为肌少症组（n=71）及非肌少症组（n=218）。采用单因素和多因素Logistic回归模型分析MHD患者肌少症的危险因素,并观察两组生活质量、负性情绪及生存状况。结果：肌少症组、非肌少症组在年龄、透析时间、规律运动、体质量指数（BMI）、人体蛋白质含量（PM）、去脂体质量（FFM）、改良定量主观评估表（MQSGA）评分、血磷、超敏C反应蛋白（hs-CRP）、血肌酐、前白蛋白、白蛋白组间对比差异有统计学意义（P<0.05）。多因素Logistic回归分析,结果显示年龄偏大、透析时间偏长、BMI下降、MQSGA评分偏高、hs-CRP偏高、血肌酐偏高是MHD患者发生肌少症的危险因素,高血磷、规律运动则是其保护因素（P<0.05）。肌少症组患者的精神健康、生理职能、总体健康、生理功能、社会功能、活力、躯体疼痛、情感职能评分均低于非肌少症组（P<0.05）。肌少症组患者的抑郁自评量表（SDS）、焦虑自评量表（SAS）评分高于非肌少症组（P<0.05）。随访1年后,肌少症组的死亡率明显高于非肌少症组（P<0.05）。结论：MHD患者并发肌少症受到年龄、透析时间、BMI、MQSGA评分、hs-CRP、血肌酐、血磷、规律运动等因素的影响,且并发肌少症的患者其抑郁焦虑程度更重,生活质量更差,生存期缩短。     

透析充分性、微炎症、营养状态对血液透析患者生存质量及长期生存率的影响

目的:探讨透析充分性、微炎症、营养状态对血液透析患者生存质量及长期生存率的影响。方法:随机选择我院血液透析中心维持透析每周3次,治疗6月以上的患者89例,观察并评估其入组时、入组后第3、6、12、18、24月的生存质量(KDTA、SF-36)、营养状况(MQSGA、MAMC)、微炎症(hCRP、IL-6)及透析充分性(iPTH、Kt/V、β2-MG),并分析透析充分性、营养状况、微炎症与生存质量、生存率的相关性。结果:89例患者有9例死亡,死亡率为10.1%;iPHT、MQSGA与KDTA、SF-36呈负相关(P0.05),Kt/V与KDTA、SF-36呈正相关(P0.05),β2-MG、胆固醇与KDTA、SF-36无明显相关(P0.05);hCRP、IL-6分别与KDTA、SF-36呈负相关(P0.05);HGS与KDTA呈正相关(P0.05),与SF-36无明显相关(P0.05),ALB、MAMC与KDTA、SF-36呈正相关(P0.05);Kt/V、MQSGA、IL-6、iPTH均与KDAT及SF-36存回归关系(P0.05);Cox回归模型发现Kt/V、ALB及开始透析年龄是导致血透患者死亡的危险因素(P0.05)。结论:透析充分性、微炎症及营养状况均影响透析患者的生存质量及长期生存率;iPTH、Kt/V、MQSGA、IL-6是其生存质量的独立影响因素,Kt/V、ALB及开始透析年龄是血透患者的死亡独立危险因素。