Standardizing diagnostic markers to evaluate and compare their performance

BACKGROUND: Markers that purport to distinguish subjects with a condition from those without a condition must be evaluated rigorously for their classification accuracy. A single approach for statistical evaluation and comparison of markers is not yet established. METHODS: We suggest a standardization that uses the marker distribution in unaffected subjects as a reference. For an affected subject with marker value Y, the standardized placement value is the proportion of unaffected subjects with marker values that exceed Y. RESULTS: We applied the standardization to 2 illustrative datasets. As a marker for pancreatic cancer, the CA-19-9 marker had smaller placement values than the CA-125 marker, indicating that CA-19-9 was the better marker. For detecting hearing impairment, the placement values for the test output (the marker) were smaller when the input sound stimulus was of lower intensity, which indicates that the test better distinguishes hearing-impaired from unimpaired ears when a lower intensity sound stimulus is used. Explicit connections are drawn between the distribution of standardized marker values and the receiver operating characteristic curve, one established statistical technique for evaluating classifiers. CONCLUSION: The standardization is an intuitive procedure for evaluating markers. It facilitates direct and meaningful comparisons between markers. It also provides a new view of receiver operating characteristic analysis that may render it more accessible to those as yet unfamiliar with it. The general approach provides a statistical tool to address important questions that are typically not addressed in current marker research, such as quantifying and controlling for covariate effects.     

Elevated blood acetate as indicator of fast ethanol elimination in chronic alcoholics

The concentration of acetate was determined in the hepatic and peripheral blood of 10 chronic alcoholics and six healthy non-alcoholic controls after a peroral dose of ethanol (0.8 g/kg b.wt.). The blood acetate concentration was significantly higher in the hepatic vein than peripherally and remained at a rather constant level both in alcoholics and controls during the course of ethanol elimination. However, the level of acetate was significantly (p less than 0.005) higher in alcoholics than in controls both in the hepatic vein (1.79 and 1.15 mM) and peripherally (0.91 and 0.52 mM) (alcoholics and controls respectively). The alcoholics also eliminated ethanol 54% faster than the controls (159 mg/kg b.wt./hr and 103 mg/kg b.wt./hr; alcoholics and controls respectively). Furthermore a highly significant correlation was found between the rate of ethanol elimination and blood acetate level both in the hepatic (r = 0.877, p less than 0.001) and in the peripheral vein (r = 0.799, p less than 0.001). Our results suggest that an increased level of blood acetate during ethanol oxidation may be used as an indicator of enhanced ethanol elimination.     

血清降钙素原对脓毒症早期诊断价值及预后意义

目的 探讨血清降钙素原(PCT)对脓毒症早期诊断价值及预后意义.方法 将2008年12月至2009年4月收治的67例系统性炎症反应综合征(SIRS)患者,根据脓毒症诊断标准分为脓毒症组50例、SIRS组(非细菌性)17例,同时收集非SIRS患者23例作为对照组,根据28 d预后将脓毒症组分为生存组和死亡组两个亚组.于入院第1天、第4天晨时取血,动态观察PCT、C反应蛋白(CRP)、红细胞沉降率(ESR)、白细胞(WBC)、中性粒细胞百分率(N)等炎性指标变化,同时记录当日最高体温.结果 脓毒症组患者入院第1天血清PeT高于SIRS组及对照组[6.68μg/L(1.16~12.46μg/L)比0.22μg/L(0.05～0.54μg/L)比0.05 μg/L(0.05~0.27 μg/L),P<0.05];死亡组15例患者血清PCT高于生存组35例患者[11.89μg/L(10.00~28.67μg/L)比2.44μg/L(1.11~10.00μg/L),P<0.05];脓毒症组患者血清PCT与急性生理和慢性健康状况(APACHE)Ⅱ评分呈正相关(r=0.511,P=0.000);PCT的受试者特征操作曲线下面积高于CRP、WBC、N、ESR;生存组血清PCT呈下降趋势直至正常,死亡组无明显下降趋势.结论 血清PCT是脓毒症早期诊断的一个较好指标,其灵敏度和特异度高于其他炎性指标,与疾病严重程度相关,能够反映疾病预后.     

Kinetics of ethanol and methanol in alcoholics during detoxification.

We investigated the kinetics of ethanol and methanol in 20 dependent alcoholics (16 men and four women) during the first 24 hr after admission to hospital for detoxification. The blood-ethanol concentration (BEC) on admission ranged from 238 to 489 mg/dl (mean 386 mg/dl). The mean rate of ethanol disappearance from the blood was 23 mg/dl/hr with a spread from 13 to 36 mg/dl/hr. The concentrations of methanol in blood at the start of detoxification ranged from 0.16 to 2.8 mg/dl (mean 1.15 mg/dl) and these levels remained more or less unchanged until the BEC had dropped below 30 mg/dl. The concentrations of ethanol and methanol in blood at the start of detoxification were not correlated (r = 0.032, P > 0.05). The results of this study do not support the notion that the metabolism of methanol in chronic alcoholics proceeds independently of the prevailing BEC. We found a three-fold difference in the rate of disappearance of ethanol from blood in alcohol-dependent subjects.     

Lack of differences in blood and tissue concentrations of endogenous ethanol in conventional and germfree rats

Headspace gas chromatography was used to determine the concentrations of endogenous ethanol in blood and tissue of conventional and germfree rats. In all biological specimens analysed, the four principal volatile endogenous substances were identified as methanol, acetaldehyde, ethanol and acetone. No statistically significant differences in the concentrations of endogenous ethanol were noted between conventional and germfree animals. In whole blood, liver, kidney, and brain of germfree rats the concentrations of endogenous ethanol were 4.2 +/- 0.19 microM, 5.1 +/- 0.55 microM, 8.2 +/- 0.59 microM and 4.4 +/- 0.17 microM (means +/- SE), respectively. The higher concentration in kidney was also observed in conventional rats. Our results suggest that ethanol is a normal metabolic intermediate in rats and does not exclusively arise from microbial fermentation reactions in the gastrointestinal tract.     

Examination of hepatitis c virus antibody seropositive blood donors and their relatives

INTRODUCTION: 239 anti-HCV seropositive blood donors (132 male, 107 female, age: 19-61, mean: 40.59 y.) and 174 family members of them (74 male, 100 female, age: 4-65, mean: 23.67 y.) were studied for chronic hepatitis C virus infection and chronic liver disease. Detailed virus serology, ultrasonography, and 6 months follow-up and--in patients with HCV RNA--liver biopsy were made. RESULTS: HCV RNA was determined in 165 patients. 70% of them were HCV RNA positive. The ALT level was normal in 95 cases (57%), and lower, than twice of the normal was in 34 cases (20%) among them. Liver biopsy was made in 79 patients; chronic C hepatitis was proven in 75 cases (steatosis in 3 cases, alcoholic liver disease in 1 case was observed). Inflammatory activity was minimal (HAI < 3) in 17, mild (HAI: 3-6) in 41, moderate (HAI: 7-9) in 7, and severe (HAI > 9) in 10 cases. There was no correlation between the serum ALT levels and the severity of the histological activity of chronic C hepatitis. Authors stress the importance of the fact, that 2 patients had normal ALT and 5 patients ALT levels were lower, than the twice of the normal of the 17 patients with significant inflammatory activity (HAI < 6). Chronic C hepatitis need for antiviral therapy was occurred in 45% of patients who known themselves previously healthy. CONCLUSIONS: The necessity of the systematic examination of anti-HCV seropositive patients and of the importance of the liver biopsy in patients with HCV RNA positivity is stressed. 3 anti-HCV seropositive cases of 174 family members of the blood donors were observed, but none of them was HCV RNA positive. It seems to be, family members of the HCV infected patients have no increased risk for HCV infection.     

Benign pleuropathies due to asbestos: their clinical prognostic significance and the medicolegal aspects]

Benign pleural disease due to asbestos, which at present is frequently the sole lesion in asbestos-exposed subjects due to the fall in full-blown asbestosis, consists of a series of phenomena of increasing severity, from minor manifestations without functional impairment, to manifestations associated with proven functional damage due directly to or as a consequence of as yet undiagnosed parenchymal asbestosis. In assessing individual cases from a medico-legal viewpoint, benign pleural disease must always be considered as a morbid manifestation of asbestos exposure. The implications for prognosis and insurance purposes must, however, take account of various factors such as internal dose, whenever detectable, time elapsed since beginning of exposure, presence and extent of functional damage. The tendency of assessing pleural disease merely as an indicator of past asbestos exposure should in any case be abandoned.     

Rates of ethanol metabolism decrease in sons of alcoholics following a priming dose of ethanol.

Rapid changes in rates of ethanol metabolism in response to acute ethanol administration have been observed in animals and humans. To examine whether this phenomenon might vary by risk for alcoholism, 23 young men with a positive family history of alcoholism (family history positive [FHP]) were compared to 15 young men without a family history of alcoholism (family history negative [FHN]). Rates of ethanol metabolism were measured in all subjects first after an initial ethanol dose (0.85 g/kg) and then, several hours later, a second dose (0.3 g/kg), and the two rates were compared. The two groups of subjects were similar in their histories of ethanol consumption. FHP subjects demonstrated faster initial rates of ethanol metabolism, 148+/-36 mg/kg/h, compared to FHN subjects, 124+/-18 mg/kg/h, P=.01. However, FHN subjects increased their rate of metabolism by 10+/-27% compared to a decrease of -15+/-24% in FHP subjects, P=.007. Fifty-two percent of the FHP and none of the FHN subjects exhibited a decline in metabolic rate of 20% or more, P=.0008. Since a significant proportion of FHP subjects exhibited a decrease in the second rate of ethanol metabolism, these preliminary data might help to partly explain why FHP individuals differ in their sensitivity to ethanol and are more likely to develop alcohol dependence.     

探究巨大儿血糖及血脂水平的变化及临床意义

目的探讨妊娠期糖尿病母亲巨大儿与非妊娠期糖尿病巨大儿血糖及血脂水平的异同。方法选择日照市中医医院妇产科2012年12月至2014年12月收治的64例妊娠期糖尿病巨大儿产妇、62例健康巨大儿产妇及63例健康足月儿产妇为研究对象,将妊娠期糖尿病巨大儿组(试验组)、健康巨大儿组(对照组A)、健康足月儿组(对照组B)采用回顾性分析的方法,研究三组患者的病历资料,分析各组患者相关指标。结果试验组与对照组A相比,血糖和HDL、Apo A、Apo B降低,新生儿低血糖发生率升高,且差异在组间均有统计学意义(t值分别为2.89、2.32、2.43、2.38、3.54,均P<0.05);试验组的甘油三酯(TG)比对照组A升高,且差异在组间有统计学意义(t=2.02,P<0.05)。试验组与对照组B相比,血糖和HDL、Apo A、Apo B降低,且差异在组间均有统计学意义(t值分别为3.15、2.21、2.32、2.64,均P<0.05);试验组的TG比对照组B升高,新生儿低血糖发生率也升高,且差异在组间均有统计学意义(t值分别为2.53、3.68,均P<0.05)。结论妊娠期糖尿病母亲生出的巨大儿,生后常表现为低血糖和/或脂质代谢异常,因此临床医生对孕妇要进行宣传和孕前及孕期的健康教育,通过干预减少巨大儿出生的比率。     

An original approach was used to better evaluate the capacity of a prognostic marker using published survival curves

ObjectivesPredicting chronic disease evolution from a prognostic marker is a key field of research in clinical epidemiology. However, the prognostic capacity of a marker is not systematically evaluated using the appropriate methodology. We proposed the use of simple equations to calculate time-dependent sensitivity and specificity based on published survival curves and other time-dependent indicators as predictive values, likelihood ratios, and posttest probability ratios to reappraise prognostic marker accuracy.Study Design and SettingThe methodology is illustrated by back calculating time-dependent indicators from published articles presenting a marker as highly correlated with the time to event, concluding on the high prognostic capacity of the marker, and presenting the Kaplan–Meier survival curves. The tools necessary to run these direct and simple computations are available online at http://www.divat.fr/en/online-calculators/evalbiom.ResultsOur examples illustrate that published conclusions about prognostic marker accuracy may be overoptimistic, thus giving potential for major mistakes in therapeutic decisions.ConclusionOur approach should help readers better evaluate clinical articles reporting on prognostic markers. Time-dependent sensitivity and specificity inform on the inherent prognostic capacity of a marker for a defined prognostic time. Time-dependent predictive values, likelihood ratios, and posttest probability ratios may additionally contribute to interpret the marker's prognostic capacity.     

An extension of affected-pedigree-member analyses to triads of relatives

The affected third-degree relatives method (“cousins method” - CM) shares key features with the affected-sibling method, but it groups first cousins in triads, with the hope of requiring fewer individuals to be typed. The aim is to provide an efficient and computationally convenient method of genome screening, capitalizing on the vast number of highly informative markers mapped in recent years. The nonparametric CM statistic measures increased marker similarity, making no assumptions concerning how the disease is inherited; this can be advantageous when dealing with complex diseases for which the mode of inheritance is difficult to determine. This article presents a brief statistical development of the CM method and describes the results of applying the method to one replicate of the simulated extended family data set. © 1997 Wiley-Liss, Inc.     

转诊中风险告知患者及家属的艺术及注意事项

在危重孕产妇确定需要转诊时,医务人员应充分评估转诊风险并做好沟通及告知工作,让患者及家属充分了解病情及转诊风险的同时能做到积极配合医务人员,共同面对可能存在的风险,积极做好转诊准备,保障母婴安全。本文就转诊风险告知的相关内容进行讲述,包括告知转诊的目的,风险告知应遵循的原则,告知的内容,告知时机的选择,告知的技巧以及应追求的效果。     

Concepts of mental health and care according to mentally-ill patients and their relatives

This study aimed at 1) identifying social, demographic and clinical characteristics of mentally-ill patients and their relatives and 2) analyzing their conceptions concerning mental illness and psychiatric care. The Attitude Measurement Scale (AMS) was used. Quantitative and qualitative analyses of the data were carried out. The 104 study subjects comprised 35 patients and 69 relatives (n=104). The Mann-Whitney Test was used for comparing the opinions of patients X relatives and the Wilcoxon Test for comparing Concept and Care. There was homogeneity in the distribution of the subjects' scores for both Concept and Care. No questions stood out or were concentrated in either group. The subjects' profile shows the transition from asylum care to innovative experiences, although there is still a concentration of drug treatments and dependence on the psychiatric institution.