Surrogate end points for overall survival in breast cancer trials: A review

Our aim was to review the studies which assessed potential surrogate endpoints for overall survival (OS) in breast cancer trials. A Literature search in PubMed database of studies which assessed potential surrogate endpoints for OS in breast cancer trials was conducted. The surrogacy was assessed with the German institute of Quality and efficiency in Health Care’s (IWQiG) framework and the Fleming hierarchy. Thirteen studies were identified. At the neoadjuvant setting, two individual patient data (IPD) meta-analyses and one aggregate data meta-analysis assessing surrogacy of pathological complete response (PCR) were identified. Trial-level association was calculated in one study and the squared correlation was 0.24. Therefore PCR was not judged to be valid surrogate for OS at the neoadjuvant setting according to the IWQiG framework and Fleming hierarchy. At the adjuvant setting, one meta-analysis on aggregate data was identified. 2-year DFS was not judged to be valid surrogate for OS at the neoadjuvant setting according to the IWQiG framework and Fleming hierarchy. At the metastatic setting, six meta-analyses based on aggregate data, three IPD meta-analyses and one retrospective study were identified. Within the IPD meta-analyses, at the trial-level association the squared correlation between the potential surrogates and OS ranged from 0.10 to 0.57 and no endpoint was judged to be valid surrogate for OS at the metastatic setting. The level of evidence available supporting a relationship between OS and potential surrogate endpoints in breast cancer trials is low.     

自拟舒郁汤联合镇静六穴治疗产后抑郁症的临床研究

目的:探讨自拟舒郁汤联合镇静六穴治疗产后抑郁症的临床效果。方法:选择2019年5月—2020年3月产后抑郁症患者60例,按照投掷硬币法分为对照组和观察组,每组30例。对照组给予盐酸帕罗西汀片治疗,观察组给予自拟舒郁汤联合“镇静六穴”治疗。比较两组患者近期疗效以及治疗前后抑郁症状、产后生活自理能力、照料婴儿能力与生活质量变化情况。结果:观察组治疗总有效率高于对照组,差异有统计学意义(P<0.05);观察组治疗2,4,6,8周末汉密尔顿抑郁量表(HAMD-24)评分均低于对照组,差异有统计学意义(P<0.05);观察组治疗8周末产后生活自理能力评分、照料婴儿能力评分及36条简明健康状况调查表(SF-36)评分均高于对照组,差异有统计学意义(P<0.05)。结论:自拟舒郁汤联合镇静六穴治疗产后抑郁症疗效显著,可有效改善患者抑郁症状,提升产后生活自理能力、照料婴儿能力和生活质量。     

美国妇产科医师学会“妊娠期恶心呕吐指南2015版”要点解读

正妊娠期恶心、呕吐是一种影响孕妇及其胎儿健康的常见疾病。早孕期轻度的恶心、呕吐是一种生理性反应;中度(和)或重度或病情迁延(和)或加重的妊娠期恶心、呕吐,会严重影响孕妇的生活质量,乃至危及母胎生命安全,需及时诊治。美国妇产科医师学会(ACOG)近年来针对妊娠期呕吐,颁布了一系列指南,并提出一些与妊娠期恶心、呕吐诊治有关的新观念及循证医学证据。本文对2015年颁布的第153号《妊娠期恶心     

Study of anomalies in the circle of Willis using magnetic resonance angiography in north eastern India

IntroductionThe circle of Willis is a large arterial anastomotic ring present at the basal cistern of the brain, uniting the internal carotid and the vertebrobasilar system. Branches from this arterial ring are distributed to supply the brain. In the year 1664, Sir Thomas Willis was the first to describe the importance of the circle in maintaining collateral flow. It was observed that there is very little mixing of blood between the collateral branches of the circle. These collaterals may however open up during occlusive episodes of the proximal feeding vessels. The anatomy of the circle is known to vary considerably and functionally a complete circle is a rare finding. This type of incomplete or variant forms off the circle may diminish its role as a collateral route.MethodsThe morphological pattern of circle of Willis of 70 healthy individuals from northeast India was studied retrospectively using Time of Flight-Magnetic resonance angiography (TOF-MRA).ResultsOnly 17 (24.28%) MRA's presented with a complete (classic) circle of Willis. Most common variant observed in our study was unilateral hypoplastic posterior communicating artery (20%). Most common variant observed in the anterior circulation was unilateral hypoplastic A1 segment of anterior cerebral artery (11.42%).DiscussionMost of the variant forms observed were comparable with earlier established findings. This variability (rare patterns) can be distinguished from an anomalous architecture if correlated phylogenically and embryologically.     

Collateral augmentation treatment with a combination of acetazolamide and head-down tilt in a rat ischemic stroke model

Cerebral collaterals is crucially important in the pathophysiology of acute ischemic stroke and associated with outcome after reperfusion therapy. We explored the effectiveness of collateral augmentation treatment with a combination of acetazolamide (ACZ) and head-down tilt (HDT) in the transient middle cerebral artery occlusion (MCAO) rat model. Transient MCAO was induced in all animals for 1.5 h, followed by reperfusion for 22.5 h. Seventy-two male Wistar rats were divided into four treatment groups: control, ACZ, HDT, and combination. Twenty sham rats, which underwent surgery, were randomly allocated to these groups. Twenty-four hours after MCAO or sham surgery, we measured the infarction volume, brain edema (aquaporin-4 [AQP4], and brain water content), and neurological deficits (Garcia and Longa tests). Collateral augmentation treatments were associated with reduced infarction volume, less brain edema, and better neurological outcomes compared with untreated animals. More specifically, ACZ and HDT treatments resulted in small infarction volumes, and HDT was associated with a low AQP4 expression and improved neurological score, while the combination of ACZ and HDT improved neurological scores and reduced brain water content. This study shows that collateral augmentation treatments are associated with a better stroke prognosis compared with untreated animals after transient MCAO. The combination of ACZ and HDT seems to have some synergistic effect, but was not proven to be superior to HDT treatment alone.     

Is the present cut-point to define type 2 diabetes appropriate in Latin-Americans?

The diagnosis of diabetes mellitus type 2 (DM2) is based either on increased plasma glucose or Glycated hemoglobin levels. Since these measures are the only means for diagnosis of DM2, they must be well adapted to each population according to their metabolic characteristics, given that these may vary in each population. The World Health Organization (WHO) determined the cut-points of plasma glucose levels for the diagnosis of DM2 by associating hyperglycemia with the risk of a specific microvascular complication-retinopathy. Cardiovascular diseases are however the principal causes of mortality in patients with DM2 and we reported that in the Colombo-Ecuadorian population impaired fasting glucose and impaired glucose tolerance are both risk markers for myocardial infarction. We propose that the current cut-points accepted by the WHO need to be revaluated in populations such as Latin America and that there should be lower cut points for glycaemia in this population, to reduce the prevalence of cardiovascular complications associated with DM2.