Fine particulate matter and incidence of metabolic syndrome in non-CVD patients: A nationwide population-based cohort study

Background

It has been reported that particulate matter (PM) is associated with cardiovascular diseases (CVD) while metabolic syndrome is also an important risk factor for CVD. However, few studies have investigated the epidemiological association between PM and metabolic syndrome.

Innovative Thinking on Endpoint Selection in Clinical Trials

ABSTRACT

In clinical trials, selection of appropriate study endpoints is critical for an accurate and reliable evaluation of safety and effectiveness of a test treatment under investigation. In practice, however, there are usually multiple endpoints available for measurement of disease status and/or therapeutic effect of the test treatment under study. For example, in cancer clinical trials, overall survival, response rate, and/or time to disease progression are usually considered as primary clinical endpoints for evaluation of safety and effectiveness of the test treatment under investigation. Once the study endpoints have been selected, sample size required for achieving a desired power is then determined. It, however, should be noted that different study endpoints may result in different sample sizes. In practice, it is usually not clear which study endpoint can best inform the disease status and measure the treatment effect. Moreover, different study endpoints may not translate one another although they may be highly correlated one another. In this article, we intend to develop an innovative endpoint namely therapeutic index based on a utility function to combine and utilize information collected from all study endpoints. Statistical properties and performances of the proposed therapeutic index are evaluated theoretically. A numerical example concerning a cancer clinical trial is given to illustrate the use of the proposed therapeutic index.     

不伴红细胞增多的慢性阻塞性肺疾病患者并发肺栓塞的影响因素研究

背景　慢性阻塞性肺疾病（COPD）患者肺栓塞（PE）发生率显著高于常人，但目前不伴红细胞增多的COPD患者并发PE的机制尚不明确。目的　探讨不伴红细胞增多的COPD患者并发PE的影响因素。方法　本研究为回顾性病例对照研究。收集2017年1-12月在新疆医科大学第一附属医院呼吸与呼吸危重症中心住院治疗的血红蛋白（Hb）≤140 g/L的COPD患者。依据肺多层螺旋CT肺血管成像（CTPA）检查结果将患者分为并发PE组和单纯COPD组。记录患者的年龄、性别、合并症、服用抗血小板或抗凝药物史。采用倾向性评分匹配（PSM）方法，通过二元Logistic回归分析估计倾向性评分值，采用1∶1最邻近原则匹配，卡钳值为0.05，筛选出基线相同的两组病例。记录患者的D-二聚体、血常规检查结果，比较两组间差异；分析不伴红细胞增多的COPD患者并发PE的影响因素，红细胞分布宽度（RDW）与中性粒细胞/淋巴细胞比值（NLR）的相关性。结果　共纳入病例339例，其中单纯COPD组289例，并发PE组50例。采用PSM方法筛选两组患者，最终得到单纯COPD组、并发PE组各50例进行后续研究。并发PE组患者D-二聚体、中性粒细胞计数（N）、RDW、NLR高于单纯COPD组，淋巴细胞计数（L）低于单纯COPD组（P<0.05）。二元Logistic回归分析结果显示，RDW是不伴红细胞增多的COPD患者并发PE的影响因素〔OR=1.561，95%CI（1.096，2.225），P<0.05〕。Spearman秩相关分析结果显示，不伴红细胞增多的COPD患者RDW与NLR呈正相关（rs=0.225，P<0.05）。结论　RDW升高是Hb≤140 g/L的COPD患者并发PE的危险因素，且RDW与NLR呈正相关。     

Rare patients in routine care: Treatment and outcome in advanced papillary renal cell carcinoma in the prospective German clinical RCC-Registry

Non-clear cell renal cell carcinoma is a very rare malignancy that includes several histological subtypes. Each subtype may need to be addressed separately regarding prognosis and treatment; however, no Phase III clinical trial data exist. Thus, treatment recommendations for patients with non-clear cell metastatic RCC (mRCC) remain unclear. We present first prospective data on choice of first- and second-line treatment in routine practice and outcome of patients with papillary mRCC. From the prospective German clinical cohort study (RCC-Registry), 99 patients with papillary mRCC treated with systemic first-line therapy between December 2007 and May 2017 were included. Prospectively enrolled patients who had started first-line treatment until May 15, 2016, were included into the outcome analyses (n = 82). Treatment was similar to therapies used for clear cell mRCC and consisted of tyrosine kinase inhibitors, mechanistic target of rapamycin inhibitors and recently checkpoint inhibitors. Median progression-free survival from start of first-line treatment was 5.4 months (95% confidence interval [CI], 4.1–9.2) and median overall survival was 12.0 months (95% CI, 8.1–20.0). At data cutoff, 73% of the patients died, 6% were still observed, 12% were lost to follow-up, and 9% were alive at the end of the individual 3-year observation period. Despite the lack of prospective Phase III evidence in patients with papillary mRCC, our real-world data reveal effectiveness of systemic clear cell mRCC therapy in papillary mRCC. The prognosis seems to be inferior for papillary compared to clear cell mRCC. Further studies are needed to identify drivers of effectiveness of systemic therapy for papillary mRCC.     

Management of Valvular Heart Disease in Adults: Implications for Nurse Practitioner Practice

Valvular heart disease affects patients of all ages, with the highest incidence in patients older than 75 years. The nurse practitioner, whether in the primary or acute care setting, plays a vital role in the detection, monitoring, and shared decisions in treatment options. Assessment skills in conjunction with appropriate testing can identify patients early in the trajectory of the disease. The purpose of this article is to provide tips for history-taking and physical exam techniques, identify appropriate diagnostic testing, and review treatment options for adults with valvular heart disease.     

Toxic tau: structural origins of tau aggregation in Alzheimer's disease

Alzheimer’s disease is characterized by the extracellular accumulation of the amyloidβin the form of amyloid plaques and the intracellular deposition of the microtubule-associated protein tau in the form of neurofibrillary tangles.Most of the Alzheimer’s drugs targeting amyloidβhave been failed in clinical trials.Particularly,tau pathology connects greatly in the pathogenesis of Alzheimer’s disease.Tau protein enhances the stabilization of microtubules that leads to the appropriate function of the neuron.Changes in the quantity or the conformation of tau protein could affect its function as a microtubules stabilizer and some of the processes wherein it is involved.The molecular mechanisms leading to the accumulation of tau are principally signified by numerous posttranslational modifications that change its conformation and structural state.Therefore,aberrant phosphorylation,as well as truncation of tau protein,has come into focus as significant mechanisms that make tau protein in a pathological entity.Furthermore,the shape-shifting nature of tau advocates to comprehend the progression of Alzheimer’s disease precisely.In this review,we emphasize the recent studies about the toxic and shape-shifting nature of tau in the pathogenesis of Alzheimer’s disease.