ADAMTS‐13 activity and autoantibodies classes and subclasses as prognostic predictors in acquired thrombotic thrombocytopenic purpura

Summary. Background: Thrombotic thrombocytopenic purpura (TTP) is a rare life‐threatening disease. Of surviving patients, 45% develops an exacerbation or a late recurrence. Severe ADAMTS‐13 deficiency, both during the acute episode and remission, is a well‐established predictor of recurrence. The predictive value of anti‐ADAMTS‐13 antibodies, their inhibitory activity and Ig class subtype for disease recurrence is still to be established. Objectives: To analyze ADAMTS‐13‐related biomarkers (ADAMTS‐13 and anti‐ADAMTS‐13 immunoglobulins, classes and subclasses) and their potential relationship with prognosis. Patients/Methods: In 115 patients with TTP, we assessed the association between levels of these biomarkers and the severity of acute episodes; we analysed also the hazard ratio (HR) and 95% confidence interval (CI) of recurrence in association with biomarkers levels retrieved at the previous acute episode or during remission, using Cox regression models. Results: During the acute phase, higher IgA, IgG1 and IgG3 titers showed the strongest association with acute episode severity. In the survival analyzes, the only biomarker significantly associated with a high hazard of recurrence after an acute episode was the presence of IgG. Conversly, low ADAMTS‐13 activity or antigen levels (< 10%), the presence of ADAMTS‐13 inhibitor or IgG during remission were all significantly associated with a higher hazard of recurrence. Conclusions: Both the Ig class and subclass are of predictive value for acute episode severity in patients with TTP. Although markers that could predict the risk of recurrence in the acute phase are limited, a thorough assessment of ADAMTS‐13‐related parameters during remission is warranted.     

手术获得性压力性损伤风险评估量表对手术患者压力性损伤预测效果的研究

目的 比较并评价手术获得性压力性损伤风险评估量表、Braden性压力性损伤风险评估量表、Munro围术期成人压力性损伤风险评估量表对外科择期手术患者手术获得性压力损伤的预测效果,为临床选择使用适宜量表提供依据。方法 选取2所三级甲等医院2019年12月—2020年6月外科择期手术患者237例,应用3种量表于术前、术中、术后对患者进行压力性损伤风险评估和皮肤检查。比较3种量表的预测效果和操作便利性。结果 手术获得性压力性损伤风险评估量表、Braden压力性损伤风险评估量表、Munro围术期成人压力性损伤风险评估量表,术前ROC曲线下面积AUC分别为0.695、0.619、0.684;术中ROC曲线下面积AUC分别为0.848、0.633、0.882;术后ROC曲线下面积AUC分别为0.861、0.757、0.870;3种量表的评估用时比较,手术获得性压力性损伤风险评估量表评估用时最短。结论 手术获得性压力性损伤风险评估量表对手术获得性压力性损伤患者预测能力较好,方便使用,值得临床推广应用。     

Validity of pressure ulcer risk assessment scales; Cubbin and Jackson, Braden, and Douglas scale

This study was to compare the validity of three pressure ulcer risk tools: Cubbin and Jackson, Braden, and Douglas scales. Data were collected three times per week from 48 to 72 h after admission based on the three pressure ulcer risk assessment scales and skin assessment tool developed by the Panel for the Prediction and Prevention of Pressure Ulcers (1994) from 112 intensive care unit (ICU) patients in a educational hospital Ulsan, Korea during December 11, 2000 to February 10, 2001. When a patient developed a pressure ulcer at the time of assessment, the patient was classified into 'pressure ulcer group', and when patients did not have a pressure ulcer until they died, moved to other wards or were discharged from the hospital, they were classified into 'not pressure ulcer group'. Four indices of validity and area under the curves (AUC) of receiver operating characteristic (ROC) were calculated. Based on the cut-off point presented by the developer, sensitivity, specificity, positive predictive value, negative predictive value were as follows: Cubbin and Jackson scale: 89%, 61%, 51%, 92%, respectively, Braden scale: 97%, 26%, 37%, 95%, respectively, and Douglas scale: 100%, 18%, 34%, 100%, respectively. AUCs of ROC curve were 0.826 for Cubbin and Jackson, 0.707 for Braden, and 0.791 for Douglas. Overall, the Cubbin and Jackson scale showed the best validity among scales tested and we recommended it for this ICU.     

SAS macros for point and interval estimation of area under the receiver operating characteristic curve for non‐proportional and proportional hazards Weibull models

Aims and objectives For prediction of risk of cardiovascular end points using survival models the proportional hazards assumption is often not met. Thus, non‐proportional hazards models are more appropriate for developing risk prediction equations in such situations. However, computer program for evaluating the prediction performance of such models has been rarely addressed. We therefore developed SAS macro programs for evaluating the discriminative ability of a non‐proportional hazards Weibull model developed by Anderson (1991) and that of a proportional hazards Weibull model using the area under receiver operating characteristic (ROC) curve. Method Two SAS macro programs for non‐proportional hazards Weibull model using Proc NLIN and Proc NLP respectively and model validation using area under ROC curve (with its confidence limits) were written with SAS IML language. A similar SAS macro for proportional hazards Weibull model was also written. Results The computer program was applied to data on coronary heart disease incidence for a Framingham population cohort. The five risk factors considered were current smoking, age, blood pressure, cholesterol and obesity. The predictive ability of the non‐proportional hazard Weibull model was slightly higher than that of its proportional hazard counterpart. An advantage of SAS Proc NLP in terms of the example provided here is that it provides significance level for the parameter estimates whereas Proc NLIN does not. Conclusion The program is very useful for evaluating the predictive performance of non‐proportional and proportional hazards Weibull models.     

Clinician predictions of intensive care unit mortality

OBJECTIVE: Predicting outcomes for critically ill patients is an important aspect of discussions with families in the intensive care unit. Our objective was to evaluate clinical intensive care unit survival predictions and their consequences for mechanically ventilated patients. DESIGN: Prospective cohort study. SETTING: Fifteen tertiary care centers. PATIENTS: Consecutive mechanically ventilated patients > or = 18 yrs of age with expected intensive care unit stay > or = 72 hrs. INTERVENTIONS: We recorded baseline characteristics at intensive care unit admission. Daily we measured multiple organ dysfunction score (MODS), use of advanced life support, patient preferences for life support, and intensivist and bedside intensive care unit nurse estimated probability of intensive care unit survival. MEASUREMENTS AND MAIN RESULTS: The 851 patients were aged 61.2 (+/- 17.6, mean + SD) yrs with an Acute Physiology and Chronic Health Evaluation (APACHE) II score of 21.7 (+/- 8.6). Three hundred and four patients (35.7%) died in the intensive care unit, and 341 (40.1%) were assessed by a physician at least once to have a < 10% intensive care unit survival probability. Independent predictors of intensive care unit mortality were baseline APACHE II score (hazard ratio, 1.16; 95% confidence interval, 1.08-1.24, for a 5-point increase) and daily factors such as MODS (hazard ratio, 2.50; 95% confidence interval, 2.06-3.04, for a 5-point increase), use of inotropes or vasopressors (hazard ratio, 2.14; 95% confidence interval, 1.66-2.77), dialysis (hazard ratio, 0.51; 95% confidence interval, 0.35-0.75), patient preference to limit life support (hazard ratio, 10.22; 95% confidence interval, 7.38-14.16), and physician but not nurse prediction of < 10% survival. The impact of physician estimates of < 10% intensive care unit survival was greater for patients without vs. those with preferences to limit life support (p < .001) and for patients with less vs. more severe organ dysfunction (p < .001). Mechanical ventilation, inotropes or vasopressors, and dialysis were withdrawn more often when physicians predicted < 10% probability of intensive care unit survival (all ps < .001). CONCLUSIONS: Physician estimates of intensive care unit survival < 10% are associated with subsequent life support limitation and more powerfully predict intensive care unit mortality than illness severity, evolving or resolving organ dysfunction, and use of inotropes or vasopressors.     

Measurement of shoulder disability in the athlete: a systematic review]

OBJECTIVES: To identify all available shoulder disability questionnaires and to examine those that could be used for athlete. METHODS: We systematically reviewed the literature in Medline using the keywords shoulder, function, scale, index, score, questionnaire, disability, quality of life, assessment, and evaluation. We searched for scales used for athletes with the keywords scale name AND (sport OR athlete). Data were completed by using the "Guide des Outils de Mesure et d'Evaluation en Médecine Physique et de Réadaptation" textbook. Analysis took into account the clinimetric quality of the instruments and the number of items specifically related to sports. RESULTS: A total of 37 instruments have been developed to measure disease-, shoulder-specific or upper extremity specific outcome. Older instruments were developed before the advent of modern measurement methods. They usually combined objective and subjective measures. Recent instruments were designed with use of more advanced methods. Most are self-administered questionnaires. Fourteen scales included items assessing sport activity. Four of these scales have been used to assess shoulder disability in athlete. Six scales have been used to assess such disability but do not have specific items related to sports. CONCLUSION: There is no gold standard for assessing shoulder outcome in the general population and no validated outcome instruments specifically for athletes. We suggest the use of ASES, WOSI and WORC scales for evaluating shoulder function in the recreational athletes. The DASH scale should be evaluated in this population. The principal criterion in evaluating shoulder function in the high level athlete is a return to the same level of sport performance. Further studies are required to identify measurement tools for shoulder disability that have a high predictive value for return to sport.     

An Independent Evaluation of Four Quantitative Emergency Department Crowding Scales

Background Emergency department (ED) overcrowding has become a frequent topic of investigation. Despite a significant body of research, there is no standard definition or measurement of ED crowding. Four quantitative scales for ED crowding have been proposed in the literature: the Real‐time Emergency Analysis of Demand Indicators (READI), the Emergency Department Work Index (EDWIN), the National Emergency Department Overcrowding Study (NEDOCS) scale, and the Emergency Department Crowding Scale (EDCS). These four scales have yet to be independently evaluated and compared. Objectives The goals of this study were to formally compare four existing quantitative ED crowding scales by measuring their ability to detect instances of perceived ED crowding and to determine whether any of these scales provide a generalizable solution for measuring ED crowding. Methods Data were collected at two‐hour intervals over 135 consecutive sampling instances. Physician and nurse agreement was assessed using weighted κ statistics. The crowding scales were compared via correlation statistics and their ability to predict perceived instances of ED crowding. Sensitivity, specificity, and positive predictive values were calculated at site‐specific cut points and at the recommended thresholds. Results All four of the crowding scales were significantly correlated, but their predictive abilities varied widely. NEDOCS had the highest area under the receiver operating characteristic curve (AROC) (0.92), while EDCS had the lowest (0.64). The recommended thresholds for the crowding scales were rarely exceeded; therefore, the scales were adjusted to site‐specific cut points. At a site‐specific cut point of 37.19, NEDOCS had the highest sensitivity (0.81), specificity (0.87), and positive predictive value (0.62). Conclusions At the study site, the suggested thresholds of the published crowding scales did not agree with providers' perceptions of ED crowding. Even after adjusting the scales to site‐specific thresholds, a relatively low prevalence of ED crowding resulted in unacceptably low positive predictive values for each scale. These results indicate that these crowding scales lack scalability and do not perform as designed in EDs where crowding is not the norm. However, two of the crowding scales, EDWIN and NEDOCS, and one of the READI subscales, bed ratio, yielded good predictive power (AROC >0.80) of perceived ED crowding, suggesting that they could be used effectively after a period of site‐specific calibration at EDs where crowding is a frequent occurrence.     

Comparison of different clinical development plans for confirmatory subpopulation selection

Given ever increasing costs to develop a new drug and intense competition, adaptive enrichment designs are an attractive option for a development program that allows selecting a potential subgroup defined by a binary biomarker. Such designs explicitly factor in the possibility that the new drug might differentially benefit distinct biomarker subgroups. We have compared three clinical development plans for a time-to-event endpoint, such as overall survival, that all lead to a decision in a pivotal trial either in all comers only, in allcomers and biomarker positive, in the biomarker positive only, or to declare the drug futile. The decision about which hypothesis to test at the final analysis is made based on a fast time-to-event endpoint, such as progression-free survival, at an interim analysis. We quantify the time gain when using an adaptive enrichment Phase II/III design versus alternative development approaches and we outline what type of biomarker needs to be available prior to Phase II in each scenario. We conclude with a discussion of further features of each of the considered development plans.     

Estimating the survival functions for right-censored and interval-censored data with piecewise constant hazard functions

The exponential distribution is frequently used to model the survival time of a patient population, which assumes the hazard rate to be a constant over time. This assumption is often violated as the hazard function may vary over time and exhibit one or more change points in its values. Several methods exist in the literature for detecting a single change point in a piecewise constant hazard function for right-censored data. A sequential testing approach to detecting multiple change points in the hazard function using likelihood ratio statistics and resampling is proposed, which is applicable to both right-censored and interval-censored data. Numerical results based on simulated survival data and a real example show that the proposed approach can accurately detect the change points in the hazard function for both right-censored and interval-censored data.     

Noninvasive Voice Biomarker Is Associated With Incident Coronary Artery Disease Events at Follow-up

ObjectiveTo evaluate the association between a preidentified voice biomarker and incident coronary artery disease (CAD) events.MethodsPatients referred for clinically indicated coronary angiography underwent a total of three 30-second voice recordings using the Vocalis Health smartphone application between January 1, 2015, and February 28, 2017. A pre-established voice biomarker was derived from each individual recording, and the mean biomarker value was calculated for each patient. Individuals were clinically observed through December 31, 2019. The prespecified primary outcome was a composite of presenting to the emergency department with chest pain, being admitted to the hospital with chest pain, or having an acute coronary syndrome; the prespecified secondary outcome was a composite of a positive stress test result at follow-up or the presence of CAD at follow-up coronary angiography.ResultsIn the final analysis, 108 patients were included (mean age, 59.47±11.44 years; male, 59 [54.6%]). The median follow-up time was 24 months (range, 1 to 60 months). In multivariable Cox proportional hazards models adjusting for CAD grade on baseline angiography, a high baseline mean voice biomarker was significantly associated with both the primary (hazard ratio, 2.61; 95% CI, 1.42 to 4.80; P=.002) and secondary (hazard ratio, 3.13; 95% CI, 1.13 to 8.68; P=.03) composite outcomes.ConclusionThis study found a significant association between a noninvasive voice biomarker and incident CAD events at follow-up. These results may have important clinical implications for the remote and noninvasive screening of patients to identify those at risk of coronary disease and its complications.     

疼痛的测量和评估方法

测量疼痛的方法包括词语和数字的自我评定量表、行为观察量表和生理学方法。视觉模拟量表(VAS)和McGill疼痛问卷表(MPQ)可能是进行疼痛测量时最常用的自我评估手段。MPQ是用来评估疼痛过程中具有多方向性的,而且已被证实是一种可靠的、有效的、有一致性的测量手段;描述语的区分量表(DDS)运用了复杂的精神物理学技术,是用来分别测量疼痛的感觉和不愉快的情绪,已证实DDS具有比率量表性质,是有效的,可靠的疼痛测量方法,被广泛应用于临床。     

Evaluating Correlation and Interrater Reliability for Four Performance Scales in the Palliative Care Setting

Performance scales are used by clinicians to objectively represent a patient's level of function and have been shown to be important predictors of response to therapy and survival. Four different scales are commonly used in the palliative care setting, two of which were specifically developed to more accurately represent this population. It remains unclear which scale is best suited for this setting. The objectives of this study were to determine the correlations among the four scales and concurrently compare interrater reliability for each. Patients were each assessed at the same point in time by three different health care professionals, and all four scales were used to rate each patient. Spearman correlation coefficient values and both weighted and unweighted kappa values were calculated to determine correlation and interrater reliability. The results confirmed highly significant linear correlation among and between all four scales. Whether using a reliability measure that incorporates the concept of “partial credit” for “near misses” or a measure reflecting exact rater agreement, no one scale emerged as having a significantly higher likelihood of agreement among raters. We propose that what may be more important than clinical experience or rater profession is the level of training an individual health care professional rater receives on the administration of any particular performance scale. In addition, given that low levels of exact rater agreement could have substantial clinical implications for patients, we suggest that this parameter be considered in the design of future comparative studies.     

Serum alpha 2-HS glycoprotein predicts survival in patients with glioblastoma

BACKGROUND: Glioblastoma, the most common primary brain tumor, has variable prognosis. We aimed to identify serum biomarkers that predict survival of patients with glioblastoma. METHODS: In phase 1 (biomarker discovery), SELDI-TOF mass spectra were studied in 200 serum samples from 58 control subjects and 36 patients with grade II astrocytoma, 15 with anaplastic astrocytoma, and 91 with glioblastoma. To identify potential biomarkers, we searched for peptide peaks that changed progressively in size with increasing malignancy. One peak, identified as the B-chain of alpha 2-Heremans-Schmid glycoprotein (AHSG), was less prominent with increasing tumor grade. We therefore investigated AHSG as a survival predictor in glioblastoma. We measured serum AHSG by turbidimetry and determined indices of malignancy, including tumor proliferation (Ki67 immunolabel) and necrosis (tumor lipids on magnetic resonance spectroscopy). In phase 2 (biomarker validation), the prognostic power of AHSG was validated in an independent group of 72 glioblastoma patients. RESULTS: Median survival was longer (51 vs 29 weeks) in glioblastoma patients with normal vs low serum AHSG concentrations (hazard ratio 2.7, 95% CI 1.5-5.0, P <0.001), independent of age and Karnofsky score. Serum AHSG inversely correlated with Ki-67 immunolabeling and tumor lipids. A prognostic index combining serum AHSG with patient age and Karnofsky score separated glioblastoma patients with short (<3 months) and long (>2 years) median survival. The prognostic value of serum AHSG was validated in a different cohort of glioblastoma patients. CONCLUSIONS: We conclude that serum AHSG concentration, measured before starting treatment, predicts survival in patients with glioblastoma.     

Beta-Blocker Exposure and Survival in Patients With Transthyretin Amyloid Cardiomyopathy

ObjectiveTo investigate a potential association between beta-blocker exposure and survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).MethodsIn this real-world prospective registry of 128 consecutive patients with ATTR-CM recruited in 7 institutions in Galicia (Spain), survival of 65 patients who received beta blockers on registry enrollment was compared with that of 63 untreated controls by means of both unweighted Cox regression and Cox regression with inverse probability of treatment weighting. Tolerance to and adverse effects of beta blockers were recorded. Median study follow-up was 520 days.ResultsPatients with ATTR-CM who received beta blockers showed statistically significant lower all-cause mortality than untreated controls as evaluated by either unweighted Cox regression (hazard ratio, 0.31; 95% CI, 0.12 to 0.79) or Cox regression with inverse probability of treatment weighting (hazard ratio, 0.18; 95% CI, 0.08 to 0.41; P<.001). Several sensitivity analyses confirmed the internal validity of these results. The overall frequency of beta-blocker suspension due to adverse effects was 25% (95% CI, 15.5% to 34.5%).ConclusionIn this real-world, prospective, multi-institutional registry, patients with ATTR-CM who received beta blockers had lower all-cause mortality than untreated controls.     

Critical analysis of a systematic review of the literature and a meta-analysis on exercise therapy and chronic low back pain]

OBJECTIVES: To determine wether the type of quality assessment scale used for evaluating the role of the physical training in chronic low back pain affects the conclusions of meta-analytic studies. DESIGN AND SETTING: Analysis of 20 trials assessing exercise therapy in chronic low back pain using 16 different scales to identify high-quality trials. Correlations between the scale scores were assessed using the Spearmans rank correlation coefficient. Inter-reader reliability was assessed with the intraclass correlation coefficient (ICC) and with the Bland and Altman technique. For the quality assessment scales allowing the classification in high quality or low quality trials, the degree of agreement between the two readers was calculated using the kappa coefficient. RESULTS: The range of the Spearman rank correlation coefficients between the different quality scales was wide (from 0.94 to 0.49). The quality scales inter-reader reliability were heterogeneous, ICC ranging from 0.86 to 0.39. The Bland and Altman analysis showed that with two scales the differences were not centered and that with 3 scales there was a systematic effect (r=0.32, 0.41, and 0.50). Finally, inter-reader agreement was low most of the time, the K coefficient being less than or equal to 0.60 for 8 of the 12 quality scales tested. CONCLUSIONS: Our data suggest that the use of summary scores to identify trials of high quality is problematic. Relevant methodological aspects should be assessed more specifically based on treatment strategies than on the own disease. A large reflexion on the elaboration and validation of specific quality scales is needed.     

Can the aspiration detected by videofluoroscopic swallowing studies predict long-term survival in stroke patients with dysphagia?

PURPOSE: This study aimed to evaluate whether the aspiration detected by videofluoroscopic swallowing study (VSS) could predict the long-term survival in stroke patients with dysphagia in the post-acute phase of stroke. METHODS: A cohort of 182 consecutive patients with stroke-related dysphagia referred for VSS from July 1994 to April 1999 was retrospectively constructed. VSS findings and clinical features in the post-acute phase of stroke were recorded. The records thus obtained were then linked to the National Death Register to track the occurrence of patient deaths until December 31, 2000. RESULTS: Of the 182 patients, 91 (50%) showed aspiration during VSS performed for a median duration of 8.4 weeks after stroke, and 76 (42%) had silent aspiration. In the post-acute phase of stroke (14.7 +/- 8.7 weeks after stroke, mean + standard deviation), 56 (31%) were tube-fed, and 88 (48%) were wheelchair-confined. A total of 65 patients died in a median follow-up duration of 30.8 months after VSS. Patients were classified into three groups based on the findings of VSS-detected aspiration or penetration, but no difference was noted in their survival curves. In the Cox stepwise regression analysis, only advanced age, recurrent stroke (hazard ratio 1.74, 95% CI 1.06-2.85), the need of tube-feeding (hazard ratio 2.07, 95% CI 1.19-3.59), and being wheelchair-confined (hazard ratio 2.83, 95% CI 1.54-5.19) during follow-up were independent predictors of long-term survival. CONCLUSIONS: VSS-detected aspiration during the post-acute phase of stroke was not predictive for the long-term survival in stroke patients with dysphagia.     

Predictive models for post-operative nausea and vomiting in patients using patient-controlled analgesia

This study identified predictive factors for post-operative nausea and vomiting (PONV) in patients using patient-controlled analgesia (PCA) and developed five predictive model pathways to calculate the probability of PONV using decision tree analysis. The sample consisted of 1181 patients using PCA. Data were collected using: a specifically designed check-off form to collect patient-, surgery-, anaesthesia- and post-operation-related data; the Beck Anxiety Inventory to measure pre-operative anxiety; and a visual analogue scale, to measure post-operative pain. The incidence of PONV was 27.7%. Nine factors were highly predictive of PONV in our five model pathways: gender, obesity, anxiety, history of previous PONV, history of motion sickness, inhalation of nitrous oxide during operation, use of inhalational agents, starting oral fluid/food intake after operation, and post-operative pain. With these five predictive model pathways, we can predict the probability of PONV in an individual patient according to their individual characteristics.     

A risk assessment scale for the prediction of pressure sore development: reliability and validity

BACKGROUND: The ability to assess the risk of a patient developing pressure sores is a major issue in pressure sore prevention. Risk assessment scales should be valid, reliable and easy to use in clinical practice. AIM: To develop further a risk assessment scale, for predicting pressure sore development and, in addition, to present the validity and reliability of this scale. METHODS: The risk assessment pressure sore (RAPS) scale, includes 12 variables, five from the re-modified Norton scale, three from the Braden scale and three from other research results. Five hundred and thirty patients without pressure sores on admission were included in the study and assessed over a maximum period of 12 weeks. Internal consistency was examined by item analysis and equivalence by interrater reliability. To estimate equivalence, 10 pairs of nurses assessed a total of 116 patients. The underlying dimensions of the scale were examined by factor analysis. The predictive validity was examined by determination of sensitivity, specificity and predictive value. RESULTS: Two variables were excluded as a result of low item-item and item-total correlations. The average percentage of agreement and the intraclass correlation between raters were 70% and 0.83, respectively. The factor analysis gave three factors, with a total variance explained of 65.1%. Sensitivity, specificity and predictive value were high among patients at medical and infection wards. CONCLUSION: The RAPS scale is a reliable scale for predicting pressure sore development. The validity is especially good for patients undergoing treatment in medical wards and wards for infectious diseases. This indicates that the RAPS scale may be useful in clinical practice for these groups of patients. For patients undergoing surgical treatment, further analysis will be performed.     

3种压疮危险评估量表在老年患者中应用的信效度研究

目的 比较和评价Norton、Braden和Waterlow 3种压疮危险评估量表在老年患者中应用的信效度.方法 选取某三级甲等医院老年患者271例,运用3种量表连续评估患者的压疮危险,以Cronbach's α系数、内容效度指数、因子分析、ROC曲线等方法评价和比较各量表的信效度.结果Norton、Braden、Watedow量表的内部一致性信度分别为0.71、0.79、0.32;内容效度指数分别为0.85、0.91、0.87;因子分析得到的方差累计贡献率分别为71.73%、70.34%、65.76%;灵敏度和特异度分别为(0.75、0.62)、(0.74、0.59)、(0.86、0.59).结论 Waterlow量表的内部一致性信度低,但预测能力最好;Braden量表的信效度均高,但预测能力偏低.     

The designs of exploratory biomarker study

With the progress of molecular biology and other disciplines, biomarkers are becoming increasingly important in both drug discovery and development. Several critical issues, including scientific rationale, study design, marker assessment, cost and feasibility should be carefully considered in the validation of biomarkers through clinical research. Here, we highlight several important aspects related to the design for clinical researches which incorporate biomarkers. First, we define the term "biomarker" and illustrate the difference between prognostic and predictive markers. Second, in exploratory clinical studies, we focus on issues related to study design for screening and evaluating biomarkers. Finally, we review the design of confirmatory clinical trials for new treatments and companion biomarker diagnostic tests.