Quantitative MRI of the brain in children with sickle cell disease reveals abnormalities unseen by conventional MRI

Conventional MRI (cMRI) has shown that brain abnormalities without clinical stroke can manifest in patients with sickle cell disease (SCD). We used quantitative MRI (qMRI) and psychometric testing to determine whether brain abnormalities can also be present in patients with SCD who appear normal on cMRI. Patients 4 years of age and older with no clinical evidence of stroke were stratified by cMRI as normal (n = 17) or abnormal (n = 13). Spin-lattice relaxation time (T1) of gray and white matter structures was measured by the precise and accurate inversion recovery (PAIR) qMRI method. Patient cognitive ability was assessed with a standard psychometric instrument (WISC-III or WISC-R). In all 30 patients with SCD, qMRI T1 was lower than in 24 age- and race-matched controls, in cortical gray matter (P < .0006) and caudate (P < .0009), as well as in the ratio of gray-to-white matter T1 (P < .008). In the 17 patients who were shown to be normal by cMRI, qMRI T1 was still lower than in controls, in both cortical gray matter (P < .02) and caudate (P < .004). Histograms of voxel T1 show that the proportion of voxels with T1 values intermediate between gray and white matter (ie, consistent with encephalomalacia) was 9% higher than controls in patients shown to be normal by cMRI (P < .05) and 15% higher than controls in patients shown to be abnormal by cMRI (P < .0005). The full scale intelligence quotient (FSIQ) of all patients with SCD was 75, compared to the FSIQ of 88 in a historical control group of patient siblings (P < .001). The FSIQ of patients shown to be normal by cMRI was 79, significantly lower than the FSIQ of patient siblings (P < .04). The FSIQ of 71 in patients shown to be abnormal by cMRI was significantly lower than both the patient siblings (P < .005) and the patients shown to be normal by cMRI (P < .04). Patients shown to be abnormal by cMRI scored lower than patients shown to be normal by cMRI, specifically on the subtests of vocabulary (P = .003) and information (P = .03). Cognitive impairment is thus significant, even in patients with SCD who were shown to be normal by cMRI, suggesting that cMRI may be insensitive to subtle neurologic damage that can be detected by qMRI. Because cognitive impairment can occur in children normal by cMRI, our findings imply that prophylactic therapy may be needed earlier in the course of SCD to mitigate neurologic damage.     

Clinical importance,statistical significance and the assessment of economic and quality-of-life outcomes

The assessment of economic and quality-of-life outcomes of health care interventions is moving into a new era, with such assessments increasingly being made within the context of controlled clinical trials. Traditionally the measurement of many variables in economic evaluations, particularly costs, has been deterministic. In the context of clinical trials the measurement of variables is stochastic, with the standard principles of statistical inference being applied to analyse differences between treatments in terms of effectiveness. Economists participating in clinical research are therefore being called upon to specify the sample size for the economic component of the evaluation and to undertake statistical tests for differences in cost or cost-effectiveness. This paper discusses the current methodological issues surrounding stochastic measurement in clinical trials, discusses the additional issues raised by the assessment of economic and quality-of-life outcomes and specifies the challenges facing economists if they are to answer the questions now being posed about economic analysis by statisticians and clinical researchers. It is concluded that application of the standard principles of statistical inference to economic data is not straightforward and will require value judgements to be made about statistical significance and economic importance, which may differ from those already made in purely clinical studies.     

Day 4 is better than day 3 for a single patch test reading

Readings were performed on day (D)2, D3 and D4 after application of patch tests in NN patients. 90 patch lest reactions in 49 patients were interpreted as allergic und of past or present relevance. A single D2 reading detected 58 of the allergic reactions, with 32 false-negatives and 23 false-positives. A single D3 reading detected 77 allergic reactions, with 13 false-negatives and 17 False-positives. A single D4 reading detected 85 allergic reactions, with 5 false-negatives und 4 false-positives. Therefore, if only a single reading is feasible, it is better performed on D4 than on D3.     

胚胎种植前遗传学检测助孕妊娠结局的影响因素研究

背景 育龄期女性胚胎着床失败及流产的最常见原因是胚胎异常,但移植经胚胎种植前遗传学检测(PGT)筛选后的正常胚胎后,仍出现种植失败或流产的原因目前并没有形成统一的结论。目的 分析PGT助孕后种植失败及流产的影响因素。方法 回顾性分析2018年12月至2021年2月在安徽医科大学第一附属医院生殖中心行PGT助孕的329例患者的临床资料,根据患者是否临床妊娠分为临床妊娠组(n=218)和种植失败组(n=111),并将临床妊娠组患者根据妊娠结局分为活产亚组(n=175)和流产亚组(n=43)。比较临床妊娠组和种植失败组,活产亚组和流产亚组的一般情况、促排卵及体外胚胎发育情况。采用多因素Logistic回归分析探讨PGT患者种植失败及流产的影响因素。绘制受试者工作特征(ROC)曲线分析多因素Logistic回归分析筛选出的影响因素对PGT患者发生种植失败及流产的预测价值。结果 多因素Logistic回归分析显示,既往流产次数≥2次〔OR=4.032 0,95%CI(2.423 0,6.710 0)〕、高密度脂蛋白胆固醇(HDL-C)水平低〔OR=3.890 0,95%CI(1.455 0,10...     

Die Rolle coagulasenegativer Staphylokokken in Mischinfektionen: Assoziationstestungen als in-vitro-Modell

Zusammenfassung Die Zunahme von Infektionen durch hochresistente grampositive Kokken hat in den letzten Jahren vornehmlich auf Intensivstationen zu erheblichen therapeutischen Problemen geführt. Hierbei ist eine Gruppe von Erregern in den Vordergrund getreten, die früher als harmlose Saprophyten galten: coagulasenegative Staphylokokken (CNS). In der vorliegenden Arbeit werden zunächst Daten zur Incidenz in verschiedenen Versorgungsbereichen unserer Klinik und zur Coincidenz mit anderen Erregern auf unserer Intensivstation vorgestellt. Es konnte gezeigt werden, daßS. aureus zwar der zahlenmäßig häufigste grampositive Erreger war, aber CNS sowohl aus Wundabstrichen der Intensivstation als auch aus Blutkulturen deutlich häufiger isoliert werden konnte. Ein gleichzeitiger Nachweis von CNS mitS. aureus und den neun häufigsten Enterobacteriaceae konnte in durchschnittlich 6% erbracht werden. Durch mögliche Interaktionen zwischen unterschiedlichen Erregern kann eine Veränderung der in Einzeltestung beobachteten Resistenzen auftreten. Um dies nachzuweisen, wurden sechs Erregerpaare einzeln und in Assoziation gegen Amoxicillin und Amoxicillin/Clavulansäure getestet. Unter Assoziation wurde das gemeinsame Wachstum zweier Keime unter kontrollierten Bedingungen in Boullionverdünnungsreihen oder einem Laborautomaten zur Resistenztestung (Cobas Bact) verstanden. In allen Fällen zeigte sich, daß die-Lactamasen der CNS in Assoziation die MHK der anderen Erreger deutlich erhöhte, was durch den Zusatz von Clavulansäure verhindert werden konnte. Eine Einzeltestung gibt also bei Mischinfekten mit Beteiligung von-Lactamasebildnern nur einen eingeschränkten Eindruck von der tatsächlichen Resistenzsituation.

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Role of coagulase negative staphylococci in mixed infections: associative testing as in vitro model

Summary Infections due to coagulase negative staphylococci (CNS) are of growing concern mainly in patients hospitalized in intensive care units (ICU). The ability of CNS to adhere and to grow on plastic devices and resistance to many antibiotics, including oxacillin, contributes to their pathogenicity. Using the computer assisted system of the Medical Microbiology Department, the incidences of different pathogens and the coincidence of CNS with other bacteria were evaluated in a surgical department.Staphylococcus aureus revealed to be the predominant pathogen; however, CNS showed an increasing incidence in wound specimens and blood cultures of patients on the ICU. Coincidence of CNS withS. aureus and the nine most frequent species of gram negative bacteria could be shown in 6%. To investigate the influence of-lactamases produced by CNS in mixed infections, association experiments were performed. Association means a controlled growth of two or even more bacteria in a susceptibility testing system, either a broth dilution method or an automated broth disk elution method (Cobas Bact). The association experiments showed a significant increase of amoxicillin MIC's of the pathogen associated with CNS. Addition of clavulanic acid restored activity of amoxicillin. It could be shown that in mixed infections CNS may contribute to the failure of antibiotic regimens by production of-lactamases.

     

Transdermal Dual-Controlled Delivery of Contraceptive Drugs: Formulation Development,in Vitro and in Vivo Evaluations,and Clinical Performance

Several transdermal contraceptive device (TCD) formulations were developed to provide a dual-controlled transdermal delivery of levonorgestrel (LN), a potent progestin, and 17-estradiol (E₂), a natural estrogen. Using a sensitive HPLC method, the in vitro release and skin permeation profiles of LN and E₂ from various TCD formulations were simultaneously characterized in the hydrodynamically well-calibrated Valia–Chien skin permeation cells and both were found to follow zero-order kinetics. The rates of drug release and skin permeation were observed to vary significantly depending upon some formulation parameters. Six-month stability studies were performed on seven formulations at room and elevated temperatures (37 and 45°C), and two (Formulations 4 and 5) were found to be acceptable, based on drug recovery, release rate, and skin permeation rate data. Judging from the 6-month accelerated stability studies, it is projected these two formulations will have shelf-life of at least 2 years. As a result of development of an efficient manufacturing process, Formulation 4 was selected for further evaluation. One-week primary skin irritation evaluation in 6 rabbits indicated that Formulation 4 is nonirritating, and it was thus selected for Phase I clinical bioavailability/dose proportionality studies in 12 healthy female volunteers of child-bearing age. Results of pharmacokinetic and pharmacodynamic analyses demonstrated that it is capable of achieving and maintaining a steady-state serum level of LN throughout the 3-week treatment period by weekly applications of one or two TCD patches (10 or 20 cm²). A dose proportionality was obtained in the serum drug levels, daily dose delivered, and contraception efficacy. An excellent correlation was obtained for the rates of transdermal delivery determined by the in vitro studies using human cadaver skin, the in vivo studies in rabbits, and the clinical studies in living subjects.     

Rapid diagnosis of parasitic diseases: current scenario and future needs

Background

Parasitic diseases are one of the world's most devastating and prevalent infections, causing millions of morbidities and mortalities annually. In the past, many of these infections have been linked predominantly to tropical or subtropical areas. Nowadays, however, climatic and vector ecology changes, a significant increase in international travel, armed conflicts, and migration of humans and animals have influenced the transmission of some parasitic diseases from ‘book pages’ to reality in developed countries. It has also been noted that many patients who have never travelled to endemic areas suffer from blood-borne infections caused by protozoa. In the light of existing knowledge, this new trend can be explained by the fact that in the process of migration a large number of asymptomatic carriers become a part of the blood bank donor and transplant donor populations. Accurate and rapid diagnosis represents the crucial weapon in the fight against parasitic infections.

人格测验正反向题目的时间效应

目的通过分析人格测验正反向题目的时间效应,探讨人格测验中题目陈述方式对测验效度及质量的影响,为测验编制及研究提供参考。方法1230名士兵完成计算机呈现的艾森克人格问卷,记录被试完成每个题目所需要的时间,将正反向题目平均用时进行对比分析。结果反向题目整体平均用时显著高于正向题目平均用时(P<0.01);得分的反向题目平均用时显著低于得分的正向题目(P<0.01);未得分的反向题目平均用时显著高于未得分的正向题目(P<0.01)。结论反向题目的引入可以减少人格测验的反应偏差,提高测验的效度,但也会在一定程度上影响被试作答的心理过程。因此在测验编制的过程中应平衡使用正反向题目,但反向题目的语言要尽量简洁明了,减少对被试作答的影响。