Effects of ruxolitinib cream on pruritus and quality of life in atopic dermatitis: Results from a phase 2, randomized,dose-ranging,vehicle- and active-controlled study

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Diabetes diagnosis from administrative claims and estimation of the true prevalence of diabetes among 4.2 million individuals of the Veneto region (North East Italy)

Background and aimsDiabetes can often remain undiagnosed or unregistered in administrative databases long after its onset, even when laboratory test results meet diagnostic criteria. In the present work, we analyse healthcare data of the Veneto Region, North East Italy, with the aims of: (i) developing an algorithm for the identification of diabetes from administrative claims (4,236,007 citizens), (ii) assessing its reliability by comparing its performance with the gold standard clinical diagnosis from a clinical database (7525 patients), (iii) combining the algorithm and the laboratory data of the regional Health Information Exchange (rHIE) system (543,520 subjects) to identify undiagnosed diabetes, and (iv) providing a credible estimate of the true prevalence of diabetes in Veneto.Methods and resultsThe proposed algorithm for the identification of diabetes was fed by administrative data related to drug dispensations, outpatient visits, and hospitalisations. Evaluated against a clinical database, the algorithm achieved 95.7% sensitivity, 87.9% specificity, and 97.6% precision. To identify possible cases of undiagnosed diabetes, we applied standard diagnostic criteria to the laboratory test results of the subjects who, according to the algorithm, had no diabetes-related claims. Using a simplified probabilistic model, we corrected our claims-based estimate of known diabetes (6.17% prevalence; 261,303 cases) to account for undiagnosed cases, yielding an estimated total prevalence of 7.50%.ConclusionWe herein validated an algorithm for the diagnosis of diabetes using administrative claims against the clinical diagnosis. Together with rHIE laboratory data, this allowed to identify possibly undiagnosed diabetes and estimate the true prevalence of diabetes in Veneto.     

A small molecule LS-1-2F promotes the endocytosis of macromolecules into tumor cells

In the previous research, we found that anticancer agent LS-1-2F could cause the vacuolation of tumor cells. Herein we investigated the effect of compound LS-1-2F on the endocytosis of macromolecules, including fluorescence quantum dots, human serum albumin, single-stranded RNA, and monoclonal antibody, into tumor cells. We found that LS-1-2F could accelerate the endocytosis of these large molecules by laser confocal microscope and flow cytometry. The effect of LS-1-2F on the improvement of the internalization efficiency of Herceptin biosimilar was particularly significant. Promoting endocytosis will help increase the efficiency of liquid-phase drug uptake in drug-resistant cancer cells and could potentially facilitate the use of drugs in nanoparticle delivery vehicles.     

无创产前检测联合孕妇血清可溶性转铁蛋白受体、生长分化因子-15、红细胞体积分布宽度变异系数检测对胎儿β-地中海贫血的诊断价值研究

目的探讨无创产前检测(NIPT)联合孕妇血清可溶性转铁蛋白受体(sTfR)、生长分化因子(GDF)-15、红细胞体积分布宽度变异系数(RDW-CV)检测，对胎儿β-地中海贫血的诊断价值。 方法选择2017年1月至2018年6月，于自贡市妇幼保健院接受羊膜腔穿刺术确诊胎儿为β-地中海贫血的120例孕妇为研究对象。根据其妊娠胎儿的β-地中海贫血轻、中、重型，将其分别纳入轻型组(n＝48)、中型组(n＝40)与重型组(n＝32)。选取同期于本院建卡进行常规产前检查，并且妊娠胎儿发育正常的100例健康孕妇作为对照，纳入对照组。采集4组孕妇空腹肘静脉血，提取孕妇外周血浆中胎儿细胞外游离DNA(cfDNA)，采用2次PCR方法扩增后，采用反向斑点杂交方法检测胎儿β-地中海贫血基因。采用酶联免疫吸附测定法，测定4组孕妇血清sTfR、GDF-15、RDW-CV水平。对4组孕妇血清sTfR、GDF-15与RDW-CV水平分别总体比较，采用单因素方差分析，进一步两两比较，采用最小显著性差异(LSD)-t检验。与胎儿β-地中海贫血诊断"金标准"比较，计算NIPT联合孕妇血清sTfR、GDF-15、RDW-CV水平及这4项指标单独检测，对于胎儿β-地中海贫血诊断的敏感度、特异度、粗符合率、阳性预测值、阴性预测值。本研究严格按照2013年修订的《世界医学协会赫尔辛基宣言》要求进行。4组孕妇年龄及其妊娠胎儿的胎龄等一般临床资料比较，差异均无统计学意义(P>0.05)。 结果①夫妻双方β-地中海贫血基因型相同的40例孕妇中，NIPT与羊膜腔穿刺术对于胎儿β-地中海贫血诊断的符合率为90.0%(36/40)；夫妻双方β-地中海贫血基因型不同的80例孕妇中，上述2种方法对于胎儿β-地中海贫血诊断的符合率亦为90. 0%(72/80)。②4组孕妇血清sTfR、GDF-15、RDW-CV水平分别总体比较，差异均有统计学意义(F＝2 283.445、323.181、45.900，P均<0.001)，进一步两两比较，任意2组孕妇血清sTfR、GDF-15、RDW-CV水平比较，差异均有统计学意义(P<0.05)，并且孕妇血清sTfR、GDF-15、RDW-CV水平随着β-地中海贫血胎儿严重程度增加而逐渐升高。③NIPT联合孕妇血清sTfR、GDF-15、RDW-CV水平检测，对于胎儿β-地中海贫血诊断的敏感度、特异度、粗符合率、阳性预测值与阴性预测值，分别为86.7%、88.0%、87.3%、86.7%与84.6%，其特异度与阳性预测值，均显著高于单独检测孕妇血清sTfR、GDF-15、RDW-CV水平，并且差异均有统计学意义(与孕妇血清sTfR水平比较：χ²＝8.866、5.301，P＝0.003、0.021；与孕妇血清GDF-15水平比较：χ²＝9.765、5.929，P＝0.002、0.015；与孕妇血清RDW-CV水平比较：χ²＝7.167、4.327，P＝0.007、0.038)。 结论孕妇血清sTfR、GDF-15、RDW-CV可能成为诊断胎儿β-地中海贫血的生物标志物，NIPT联合这3项指标检测，可提高诊断胎儿β-地中海贫血的特异度与阳性预测值。由于本研究纳入样本量相对较小，NIPT联合孕妇血清sTfR、GDF-15、RDW-CV水平，对胎儿β-地中海贫血的诊断价值，仍然有待进一步研究、证实。     

Risk factors for complications and in-hospital mortality: An analysis of 19,834 open pelvic ring fractures

BackgroundOpen pelvic fractures are rare injuries, associated with high patient morbidity and mortality. Few studies have investigated the impact of patient demographics, comorbidities, and injury related factors on complication and mortality rates. The purpose of this study was to: (1) identify the overall incidence of complications and mortality after open pelvic fractures, (2) compare patient factors between those who did and did not develop complications, (3) identify perioperative independent risk factors for complications and mortality.MethodsA query was performed for patients with open pelvic fractures between 2007 and 2017 using the American College of Surgeons National Trauma Data Bank. Patient and injury specific variables were collected and complications were identified using International Classification of Disease Ninth and Tenth edition Codes. Patient demographic and perioperative data was compared using Fisher’s exact test and chi-square test for categorical variables, and Welch’s t-test for continuous variables. Using pooled data from multiple imputations, logistic regressions were used to calculate odds ratios and confidence intervals of independent risk factors for complications.ResultsA total of 19,834 open pelvic fracture cases were identified, with 9622 patients (48.5%) developing at least one complication. Patients who developed complications were older (35.0 vs 38.1 years), and had higher Injury Severity Scores (17.7 vs 26.5), lower Glasgow Coma Scores (14.2 vs 11.7), and a larger proportion presenting with hypotension (21% vs 6.9%). After pooled regression involving 19 factors, these were the strongest independent predictors of inpatient complication and mortality.ConclusionWe report a mortality rate of 14%, with an inclusive complication rate of 48.5%. Evaluating risk factors for morbidity and mortality for this devastating orthopaedic injury provides knowledge of an inherently sparse population.Level of EvidenceLevel II, Retrospective study.