Results of the performance verification of the CoaguChek XS system

Background

This is the first paper reporting a performance verification study of a point-of-care (POC) monitor for prothrombin time (PT) testing according to the requirements given in chapter 8 of the International Organization for Standardization (ISO) 17593:2007 standard “Clinical laboratory testing and in vitro medical devices — Requirements for in vitro monitoring systems for self-testing of oral anticoagulant therapy”. The monitor under investigation was the new CoaguChek XS system which is designed for use in patient self testing. Its detection principle is based on the amperometric measurement of the thrombin activity generated by starting the coagulation cascade using a recombinant human thromboplastin.

Methods

The system performance verification study was performed at four study centers using venous and capillary blood samples on two test strip lots. Laboratory testing was performed from corresponding frozen plasma samples with six commercial thromboplastins. Samples from 73 normal donors and 297 patients on oral anticoagulation therapy were collected. Results were assessed using a refined data set of 260 subjects according to the ISO 17593:2007 standard.

Results

Each of the two test strip lots met the acceptance criteria of ISO 17593:2007 versus all thromboplastins (bias − 0.19 to 0.18 INR; > 97% of data within accuracy limits). The coefficient of variation for imprecision of the PT determinations in INR ranged from 2.0% to 3.2% in venous, and from 2.9% to 4.0% in capillary blood testing. Capillary versus venous INR data showed agreement of results with regression lines equal to the line of identity.

Conclusion

The new system demonstrated a high level of trueness and accuracy, and low imprecision in INR testing. It can be concluded that the CoaguChek XS system complies with the requirements in chapter 8 of the ISO standard 17593:2007.     

Fulminant myasthenia gravis and polymyositis after thymectomy for thymoma

Two days after thymectomy for thymoma a patient developed myasthenia gravis and polymyositis; these rapidly progressed to a near total paralysis.     

Prediction of maximal oxygen uptake from the ratings of perceived exertion and heart rate during a perceptually-regulated sub-maximal exercise test in active and sedentary participants

This study assessed whether the accuracy of predicting maximal oxygen uptake (VO2max) from sub-maximal heart rate (HR) and ratings of perceived exertion (RPE) values was moderated by gender and habitual activity. In total, 27 men and 18 women completed two GXTs to determine VO2max and three perceptually-regulated GXTs, incremented by RPE 9, 11, 13, 15 and 17. The RPE and HR were individually regressed against VO2max (approximately 0.96) to enable predictions of VO2max. The VO2max was predicted from three RPE ranges (9-17, 9-15, 9-13). The RPE ranges were extrapolated to RPE(19), RPE(20) and age-predicted maximal HR (HRmax(pred)). ANOVA revealed no differences between measured and predicted VO2max (P > 0.05) when the RPE range 9-17 was extrapolated to RPE(19) and HRmax(pred). Extrapolation of RPE 9-17 to RPE(20) overestimated VO2max (P < 0.05), but no differences were observed when predicted from the RPE ranges 9-15 and 9-13. The prediction of VO2max was not moderated by gender or activity status. Hierarchical regression analysis revealed that HR explained additional variance in VO2max when added to the RPE (2%). Hierarchical multiple regression analysis also indicated that VO2max was significantly correlated with power output at sub-maximal RPE values of 13 and 15 (P < 0.01) in men and women. The addition of HRmax(pred) improved the accuracy of the prediction equation for men (P = 0.05) but not for women. The study confirmed the validity of estimating VO2max from perceptually-regulated, sub-maximal GXT and indicated the potential utility of regression analysis to gauge appropriate sub-maximal exercise intensities.     

Personalized medicine approach for optimizing the dose of tafamidis to potentially ameliorate wild-type transthyretin amyloidosis (cardiomyopathy)

Placebo-controlled clinical trials are useful for identifying the dose of a drug candidate that produces a meaningful clinical response in a patient population. Currently, Pfizer, Inc. is enrolling a 400-person clinical trial to test the efficacy of 20 or 80?mg of tafamidis to ameliorate transthyretin (TTR)-associated cardiomyopathy using clinical endpoints. Herein, we provide guidance for how to optimize the dose of tafamidis for each WT TTR cardiomyopathy patient using its mechanism of action as the key readout, i.e. we identify the dose of tafamidis that maximally kinetically stabilizes TTR in the blood. Tetramer dissociation is rate limiting for TTR aggregation, which appears to drive the pathology of the TTR amyloidoses. Hence, we measure the TTR tetramer dissociation rate (kinetic stability) in the patient's plasma as a function of tafamidis dose to optimize the dose employed to maximize kinetic stability. Historical data tell us that a subset of patients exhibiting higher tafamidis plasma concentrations are maximally kinetically stabilized at the 20-mg tafamidis dose, whereas the patient studied herein required a 60?mg once daily dose to achieve maximum kinetic stabilization. We anticipate that establishing the dose of tafamidis that achieves maximal TTR kinetic stabilization will translate into a maximal clinical effect, but that remains to be demonstrated.

Trial registration: ClinicalTrials.gov identifier: NCT01994889.     

糖尿病对慢性肾脏病患者血清RBP4水平的影响和临床意义

目的：探讨糖尿病对CKD患者血清RBP4水平的影响和临床意义。方法：选取212例CKD1～5期患者及健康体检者24例,采用ELISA方法检测血清RBP4及甲状腺转运蛋白（TTR）的水平。结果：糖尿病对CKD患者血清RBP4水平影响的研究结果显示：CKD合并糖尿病组以及CKD不伴糖尿病组间eGFR、RBP4、RBP4/TTR水平差异无统计学意义;根据eGFR对患者进行分层研究,发现各组内糖尿病组与非糖尿病组的RBP4水平差异无统计学意义（CKD1～4,P＆gt;0.05）。而随着eGFR的下降,无论在糖尿病或非糖尿病患者中RBP4水平均明显升高。结论：随着eGFR的下降血清RBP4逐步升高,而RBP4水平与糖尿病之间差异无统计学意义相关。     

Finding of vascular amyloid TTR in inferior nasal concha in a patient with FAP TTRVal30Met

We report the case of a female patient with familial amyloid polyneuropathy (FAP) who demonstrated TTR amyloid deposition in the inferior nasal conchal vessels.

To our knowledge this location has not been described previously in FAP; in addition, it was detected in a patient who had undergone successful liver transplantation (LTX) 4 years earlier.

The amyloid deposition was found incidentally during examination of a right nasal obstruction caused by a nonspecific inflammatory polyp. Small focal deposits of amyloid TTR were observed on deep thick walled vessels, contrasting with the massive deposition reported in neoformed vessels in amyloidomas. This amyloid was clearly deposited between the onset of FAP and LTX and had probably decreased since the graft.

If amyloid deposition is frequent in inferior nasal concha in FAP, this location could be a suitable biopsy site.     

Meta-Analysis to Assess the Quality of International Normalized Ratio Control and Associated Outcomes in Venous Thromboembolism Patients

Introduction

Patients with venous thromboembolism (VTE) frequently require vitamin K antagonists (VKAs) to prevent recurrent events, but their use increases hemorrhage risk. We performed a meta-analysis to assess the quality of international normalized ratio (INR) control, identify study-level predictors of poor control and to examine the relationship between INR control and adverse outcomes in VTE patients.

Materials and Methods

We searched bibliographic databases (1990-June 2013) for studies of VTE patients receiving adjusted-dose VKAs that reported time in range (2.0-3.0) or proportion of INRs in range and/or reported INR measurements coinciding with thromboembolic or hemorrhagic events. Meta-analysis and meta-regression analysis was performed.

Results

Upon meta-analysis, studies found 59% (95%CI: 54-64%) of INRs measured and 61% (95%CI: 59-63%) of the time patients were treated were spent outside the target range of 2.0-3.0; with a tendency for under- versus over-anticoagulation. Moreover, this poor INR control resulted in a greater chance of recurrent VTE (beta-coefficient = -0.46, p = 0.01) and major bleeding (beta-coefficient = -0.30, p = 0.02). Patients with an INR < 2.0 made up 58% (95%CI: 39-77%) of VTE cases, while those with an INR > 3.0 made up 48% (95%CI: 34-61%) of major hemorrhage cases. Upon meta-regression, being VKA-naïve (-14%, p = 0.04) and treated in the community (-7%, p < 0.001) were associated with less time in range, while being treated in Europe/United Kingdom (compared to North America) was associated with (11%, p = 0.003) greater time.

Conclusions

Strategies to improve INR control or alternative anticoagulants, including the newer oral agents, should be widely implemented in VTE patients to reduce the rate of recurrent events and bleeding.     

Advanced practice nurses transitional care promotes anti- coagulation therapy of warfarin in atrial fibrillation patients in South China

Background Advanced practice chronic conditions. However, nurse transitional care has been proofed to be important for older adults with such effectiveness has never been studied in the management of appropriate Warfarin use in clinical practice. Methods A total of 97 patients were randomly distributed into control group who received usual care, and interventional group who received transitional care provided by APNs. A 12-month observation of both groups were recorded by physicians and APNs and the impact of APNs on the managing of Warfarin therapy was also evaluated based on time in the therapeutic range （TTR）. Results APNs transitional care significantly （P 〈 0.01） improved patients＇ adherence, increased TTR and high TTR ratio compared with control group. Re-admission due to stroke was significantly （P 〈 0.01） reduced by APNs transitional care. Conclusion APNs transitional care improves patients＇ knowledge on AF and reduces stroke risk. The current research strongly suggest the necessity of APNs transitional interventional in managing anticoagulation therapy in AF patients in China.     

宫颈癌患者血清相关蛋白的初步分离及鉴定

目的寻找宫颈癌患者和对照组血清之间的蛋白差异,并以质谱技术进行鉴定。方法表面增强激光解析电离化飞行时间质谱(SELDI-TOF-MS)分析两组血清得到差异蛋白(或肽段),进一步分离纯化差异蛋白,最后以液相色谱-电喷雾-串联质谱(LC-ESI-MS/MS)进行鉴定。结果宫颈癌患者和对照组血清之间差异蛋白12个(P<0.05),其中质荷比M/Z 15.96 ku的差异蛋白进行分离纯化鉴定,转甲状腺素蛋白前体(TTR)的分子质量最为接近,转录中介因子1-β(TIF1-β)的蛋白生物学行为与肿瘤最相关,它的表达可能引起肿瘤相关基因的失活或活化,导致肿瘤发生发展。结论 SELDI-TOF-MS寻找差异蛋白并辅助蛋白分离纯化,LC-ESI-MS/MS鉴定蛋白为可行技术路线。鉴定M/Z 15.96 ku的差异蛋白,TTR分子质量与之最接近,而TIF1-β与肿瘤发生发展更相关。