The added value of ordinal analysis in clinical trials: an example in traumatic brain injury

Introduction  

In clinical trials, ordinal outcome measures are often dichotomized into two categories. In traumatic brain injury (TBI) the 5-point Glasgow outcome scale (GOS) is collapsed into unfavourable versus favourable outcome. Simulation studies have shown that exploiting the ordinal nature of the GOS increases chances of detecting treatment effects. The objective of this study is to quantify the benefits of ordinal analysis in the real-life situation of a large TBI trial.     

The fragile X syndrome: implications of molecular genetics for the clinical syndrome

Abstract. The fragile X syndrome of mental retardation is one of the most common genetic diseases. Characterization of the mutations involved has greatly improved our knowledge of the transmission of fragile X syndrome and new DNA-based diagnostics tools significantly outperform cytogenetic testing both for establishing the diagnosis and for determining carrier status. Fragile X mutations consist of an expansion of a CGG trinucleotide repeat localized in a gene (FMR-1) that is abnormally methylated in all affected individuals. They are classified as premutations (asymptomatic) and full mutations (associated with the disease). Several different DNA analysis protocols are used for fragile X genotyping but only a few have been tested on large samples of individuals. There are several clinical indications for direct DNA genotyping for fragile X including mental retardation, learning disability or hyperactivity in children with or without a family history of mental retardation, the establishment of carrier diagnosis in fragile X families and prenatal screening of children from carrier women.     

黑斑息肉病临床诊断和影像检查意义

目的:黑斑息肉病(PJS)是常染色体显性遗传病,属少见病,通过临床表现及影像学分析,加深对此少见病的认识。方法:收集我院1994年10月~2004年6月入院诊治的PJS患者26例,男12例,女14例。22例行结肠镜检查;23例行全消化道造影检查;4例患者行腹部CT及CT三维结肠重建和仿真内窥镜检查。结果:①临床以口唇粘膜、肢端色素沉着为体征,腹痛、腹胀及消化道出血为症状。②结肠镜检查19例发现结肠多发息肉;全消化道造影21例发现小肠多发息肉;CT结肠仿真内镜均发现多发息肉;2例随诊病例确诊结肠腺癌。结论:PJS恶变率远高于正常人群,内窥镜活检及染色体检查是诊断关键,影像学检查对发现息肉,特别是小肠息肉有重要诊断意义,而且为无创的定期复查提供了平台。     

Metabolic syndrome: clinical concept and molecular basis

The metabolic syndrome is a cluster of insulin resistance, elevated blood pressure, and atherogenic dyslipidemia and is a common basis of cardiovascular diseases (CVD). Although the precise mechanism remains to be elucidated, a practical definition is needed. A worldwide definition that considers increased waist circumference as an essential component has been settled. Visceral fat locates upstream of the liver. Free fatty acids and glycerol derived from visceral fat reach the liver and stimulate lipoprotein synthesis and gluconeogenesis, respectively. The adipose tissue produces a variety of bioactive substances conceptualized as 'adipocytokines'. Overproduction of plasminogen activator inhibitor-1 and tumor necrosis factor- seems to relate to the thrombotic and inflammatory tendency. On the other hand, adiponectin, which has antiatherogenic and antidiabetic activities, is reduced in subjects with metabolic syndrome. In Japan, the waist circumference criterion based on visceral fat accumulation has been adopted. The concept of this syndrome has been widely publicized, and health promotion programs based on the concept have commenced in various areas of the country. Such 'Adipo-Do-It' movement is an incentive to encourage physical exercise to reduce visceral fat and is a big challenge to prevent life-style-related diseases and CVD.     

Meta-analysis of heterogeneous clinical trials: an empirical example

Meta-analysis of heterogeneous clinical trials is currently sub-optimal. This is because there has been no improvement in the method of weighted averaging for such studies since the DL method in 1986. This article presents the argument for the use of situation specific weights to integrate results from such trials. An empirical example is given with data from a meta-analysis done 10 years earlier. Previously reported data on 21 studies that looked at the effect of working conditions on preterm births were re-analyzed. Several methods were used to estimate the overall effect sizes. Study specific scores were included in the weighting process when combining studies and it was shown that this model not only was more conservative than the model of DL but also retains the legitimacy of the pooled effect size. The inclusion of appropriate study specific scores in an appropriate meta-analysis model permits the quantification of the variation between studies based on something tangible as opposed to the random adjustments made by the random effects model to the pooled effect size. It is important that such differences are recognized by the wider research community so that meta-analyses remain a valid tool for synthesizing research.     

Insights from integrating clinical and preclinical studies advance understanding of graft-versus-host disease

As a result of impressive increases in our knowledge of rodent and human immunology, the understanding of the pathophysiologic mechanisms underlying graft-versus-host disease (GVHD) has dramatically improved in the past 15 years. Despite improved knowledge, translation to clinical care has not proceeded rapidly, and results from experimental models have been inconsistent in their ability to predict the clinical utility of new therapeutic agents. In parallel, new tools in immunology have allowed in-depth analyses of the human system and have recently been applied in the field of clinical GVHD. Notwithstanding these advances, there is a relative paucity of mechanistic insights into human translational research, and this remains an area of high unmet need. Here we review selected recent advances in both preclinical experimental transplantation and translational human studies, including new insights into human immunology, the microbiome, and regenerative medicine. We focus on the fact that both approaches can interactively improve our understanding of both acute and chronic GVHD biology and open the door to improved therapeutics and successes.     

肾病综合征患者凝血分子标志物测定的临床价值

目的:观察45例原发性肾病综合征(N S)患者血浆止凝血分子标志物的变化,探讨其临床价值。方法:对照组25人,年龄(25.6±6.50)岁。患者组45人,年龄(29.87±10.87)岁。分别检测血浆血管性血友病因子(vW F)、D二聚体(D-D im er)、抗凝血酶Ⅲ(A TⅢ)、凝血酶原时间(PT)、活化部分凝血活酶时间(A PTT)及纤维蛋白原(FIB)含量。结果:(1)两组观察对象PT、A PTT无明显改变(P>0.05)。N S患者vW F、D-D im er、FIB均高于正常对照组(P<0.01),而A TⅢ明显低于正常对照(P<0.01)。(2)以血白蛋白(A IB)、24h尿蛋白(24H PR)、血胆固醇(C H)、血甘油三酯(TG)、血小板(PLT)为对象,观察止凝血指标与上述因素的相关性。结果显示vW F分别与C H、TG呈显著正相关(P<0.01及P<0.05)。A TⅢ与A IB呈显著正相关(P<0.01)而与24H PR呈显著负相关(P<0.01)。D二聚体与所有单因素之间无明确相关性。结论:vW F、A TⅢ、D二聚体分别从血管内皮细胞、抗凝、纤溶系统等不同角度反映了患者血液流变...     

The value of clinical examination in the diagnosis of carpal tunnel syndrome

Carpal tunnel syndrome is the most common neuropathy of the peripheral nerves. In diagnosing carpal tunnel syndrome, the case history and physical examination are of primary importance. The goal of our research was to examine the dependencies between particular clinical parameters in the diagnosis of carpal tunnel syndrome. For this purpose 80 cases of carpal tunnel syndrome were analyzed, involving 51 patients ranging in age to 81 (average 50). When the patient history was taken, the major complaints were noted: numbness, swelling, stiffness of the fingers, pain in the region of the wrist and fingers. As part of the clinical testing Lovett's method was used to evaluate muscle strength in the short abductor muscles of the thumb and the antagonist muscle of the thumb in both hands; surface and bifocal sensation were tested on the tips of the first, second, and third fingers; and the Tinel and Phalen Tests performed. In the clinical interviews most often complained of nocturnal pain in the wrist region (98,75%). On the Lovett scale the muscle strength of the short abductor muscle of the thumb was 5 in 85% of the cases, and 4 in the other 15%. Similarly, when the antagonist muscle of the thumb was tested, the result was 5 in 77,5% of the cases, 4 in 17,5% and 3 in 5%. Reduced surface sensation within the innervation zone of the medial nerve was found in 70% of the examined cases. Weakened bifocal sensation occurred in the first finger of the affected hand in 21,25% of the cases, in the second finger in 20% and in the third finger in 22,5% of the cases. On physical examination 54% of the cases showed a positive Tinel symptom, and 87,5% a Phalen symptom. The Tinel test results showed positive correlation with weakened bifocal sensation in the first and second fingers, which was confirmed statistically. The lack of statistical correlation between the results of case history and physical examination render it impossible to diagnosis carpal tunnel syndrome exclusively on the basis of either case history or physical examination.     

Dubin-J0hnson综合征4例临床病理分析

目的：探讨Dubin-Johnson综合征的临床病理特征、诊断和及鉴别诊断。方法：收集4例临床病理资料，切片作常规HE染色及特殊染色，镜下观察。结果：肝细胞内见大量棕黄色色素存在，脂褐素染色阳性，黑色素染色阴性，含铁血黄素染色阴性，部分病例胆色素染色阳性。结论：Dubin-Johnson综合征是一种良性病变过程，肝细胞内的色素可合并胆色素存在，这种色素与其他黄疸性疾病的胆汁淤积不同。     

First example of anti-Kx in a person with the McLeod phenotype and without chronic granulomatous disease

BACKGROUND: Kx is lacking in the RBCs of patients with the McLeod syndrome. This condition is sometimes associated with chronic granulomatous disease (CGD). If given allogeneic RBCs, CGD patients with the McLeod phenotype may produce anti-Kx and anti-Km, and only phenotypically matched McLeod blood would be compatible. McLeod phenotype persons without CGD have made anti-Km but not anti-Kx (2 examples), and thus both McLeod and K(O) blood would be compatible. CASE REPORT: RBCs from a transfused patient with the McLeod phenotype but not with CGD (non-CGD McLeod) were typed for the Kell blood group antigens, and the plasma was analyzed for the presence of antibody by agglutination. The molecular basis was determined by analyzing for XK protein on RBC membranes by Western immunoblotting, by sequencing the XK gene, and by RFLP. RESULTS: The RBCs did not react with anti-Kx + anti-Km and showed weakening of Kell system antigens. The patient's plasma reacted moderately (2+) with RBCs of common Kell type and strongly (4+) with K(O) RBCs and RBCs of common Kell type treated with dithiothreitol, and did not react with McLeod RBCs. XK protein was absent from the RBC membranes. The XK gene had a point mutation in the donor splice site of intron 1 (G>C). CONCLUSION: This is the first report describing the molecular alteration in a non-CGD McLeod patient who has made anti-Kx. The immune response of people with the McLeod phenotype can vary, and K(O) blood may not always be compatible.     

Primary Whipple's disease of the brain: characterization of the clinical syndrome and molecular diagnosis

BACKGROUND: Whipple's disease (WD) of the brain without evidence of systemic involvement is a rare illness that is difficult to recognize and potentially life-threatening. AIM: To elucidate the clinical features and diagnosis of primary WD of the brain. DESIGN: A single case study, with review of published data. METHODS: We linked the information about our patient with 956 citations to published WD material. We were able to identify 19 other patients with primary WD of the brain. RESULTS: Our patient was a 48-year-old woman who presented 2 years ago with generalized tonic/clonic seizures. WD of the brain was diagnosed after a life-threatening subacute deterioration leading to reduced consciousness and eye movement abnormalities. She had atrophy and gliosis of the right hippocampal formation, and nodular enhanc-ing lesions. She developed the syndrome of inappropriate ADH secretion, blepharospasm with a complete paralysis of vertical gaze, a severe amnesic syndrome, obstructive sleep apnoea, altered sleep physiology and CSF oligoclonal bands. Primary WD of the brain was diagnosed after PCR confirmed Tropheryma whipplei DNA in CSF and blood. She recovered after intravenous methylprednisolone, meropenem and cotrimoxazole. She has now survived for 24 months, lives independently and drives. Comparing our patient with the 19 others, two clinical syndromes were apparent, in both adults and children: (i) multifarious neurological symptoms and signs with a CT or MRI showing multiple nodular enhancing lesions; (ii) focal neurology secondary to solitary mass lesions. DISCUSSION: Primary WD of the brain may be diagnosed by recognition of these two clinical syndromes, and confirmed by the application of molecular biological techniques such as PCR.     

Endotracheal suctioning: an example of the problems of relevance and rigour in clinical research

• ? Endotracheal suctioning is a routine but potentially dangerous procedure. The literature documenting approaches to minimizing the cardiopulmonary complications of endotracheal suctioning is reviewed. Hyperoxygenation, hyperventilation, hyperinflation and the use of adaptors are all evaluated. The effects of endotracheal suctioning on haemodynamics and oxygen transport are also examined. The traditional dualist approach to the respiratory and cardiovascular systems is contrasted with the recent emphasis on oxygen transport by the cardiopulmonary system.
• ? The trade-off between the rigour of laboratory studies (which can be well controlled but are difficult to generalize) and the relevance of clinical research (which is more easily generalized but which often lacks internal validity) is discussed. Although research studies have become both more methodologically and conceptually sophisticated, definitive recommendations for a safe and effective suctioning procedure still remain elusive.

     

The clinical value of determination of natriuretic peptides in acute coronary syndrome

The production and release of natriuretic peptides (NPs) into the bloodstream are stimulated by increased left ventricular wall tension during volume overload. In ischemia, NPs are secreted by myocardial cells in response to stress or overload, particularly in the development of myocardial systolic dysfunction. The review details the time course of changes in amino acid N-terminal proBNP in acute coronary syndrome (ACS) with and without ST-segment elevation and discusses the role of the index in defining the tactics of treatment and prognosis in patients with ACS.     

经颅彩色编码超声诊断帕金森综合征的临床价值

目的 探讨经颅彩色编码超声(TCCS)诊断帕金森综合征(PD)的价值。方法 选择52例PD患者(PD组)和50例健康人群(对照组),经颞窗探查中脑区黑质(SN)的回声强度,对其进行分级,并测量SN强回声的面积及双侧黑质强回声/中脑面积(S/M)值。结果 TCCS显示SN出现强回声41 (/52, 78.8%)例,而对照组出现SN强回声为19 (24.0%)例,两组差异有统计学意义(X 2 = 4.766, P = 0.000)。PD组单侧SN强回声面积0.34±0.10 cm2,S/M为11±4%;对照组单侧SN强回声面积0.17±0.05 cm2,S/M为5±1%。PD组与对照组SN强回声面积及S/M均有明显统计学差异(t = 9.859, p = 0.000; t = 10.394, p = 0.000)。依据受试者工作特征曲线,以S/M为6.5%作为诊断PD临界值,其曲线下面积为0.964,敏感性为98.1%,特异性为84.6%;以单侧SN强回声面积0.215作为诊断PD的临界值,其曲线下面积为0.929,敏感性为88.5%,特异性为75.0%。结论 TCCS对于预测正常人群中罹患PD的风险及早期诊断PD具有重要临床应用价值。     

胱抑素C诊断急性冠脉综合征的价值评价

目的采用循证检验医学方法评价血清CysC水平变化是否可作为急性冠脉综合征诊断指标。方法检测ACS患者、ACS疑似患者、健康对照者血清中CysC的水平,同步检测ACS患者组、疑似组患者的CK-MB、hs-CRP,绘制此三种标志物用于诊断ACS的受试者特征曲线（ROC）曲线,并对标志物诊断准确度进行比较。结果ACS病人组的CysC浓度较对照组和疑似病人组低,其差异有统计学意义（P〈0．05）。绘制ROC曲线得出AUC（CysC）为0．659（95％CI：0．522—0．795）,AUC（hs-CRP）为0．622（95％CI：0．478—0．765）,AUC（CK-MB）为0．674（95％CI：0．544—0．804）,三者AUC差异无统计学意义。结论ACS患者存在CysC水平下降,但不适合作为ACS的诊断指标。