The predictive characteristics of D-dimer testing in outpatients with suspected venous thromboembolism: a Bayesian approach

BACKGROUND: Despite the widespread use of quantitative methods to measure D-dimer, clinical decisions commonly are based only on binary test information (positive/negative). This study aimed to determine the significance of quantitative D-dimer results in the evaluation of venous thromboembolism (VTE) by means of a differentiated Bayesian approach. METHODS: Prospective study in 118 outpatients referred for workup of suspected pulmonary embolism (n = 75) or deep vein thrombosis (n = 43). The sensitivity and specificity of D-dimer results obtained by DD VIDAS (Biomerieux, France), STA Liatest (Diagnostica Stago, France), and D-dimer plus (Dade, US) were assessed for five different cut-offs. Further, predictive values and multilevel likelihood ratios were calculated in order to assess the operative test characteristics in excluding or confirming VTE. RESULTS: At a cut-off of 500 ng/ml and pretest probabilities < 47%, the VIDAS provides a negative predictive value (NPV) > 95%, whereas a positive predictive value (PPV) > 95% is obtained in patients with a D-dimer > 10,000 ng/ml and pretest probabilities > 50%. At a cut-off of 500 ng/ml and pretest probabilities < 33%, the Liatest exhibits a NPV > 95%, whereas a PPV > 95% is obtained in patients with a D-dimer >10,000 ng/ml and pretest probabilities > 37%. Finally, with the D-dimer plus, a NPV > 95% is seen at a cut-off of 150 ng/ml and pretest probabilities < 30%, whereas a PPV > 95% is obtained at a cut-off > 1000 ng/ml and pretest probabilities > 67%. CONCLUSIONS: D-dimer measurements in outpatients cannot only allow for exclusion but, in some situations, also for confirmation of venous thromboembolism. It is therefore advisable to conduct a quantitative interpretation of D-dimer results.     

Effects of female sex hormones on responses to CGRP, acetylcholine, and 5-HT in rat isolated arteries

BACKGROUND: Female sex hormones are implicated in the modulation of reactivity of a wide range of blood vessels under physiological as well as pathological conditions. Migraine, a neurovascular syndrome, is 3 times more prevalent in women during their reproductive period than in men. OBJECTIVE: This study sets out to investigate the effects of the female sex steroids, 17beta-estradiol and progesterone (separately and in combination) on vasoactive responses to calcitonin gene-related peptide (CGRP), acetylcholine, and 5-hydroxytryptamine (5-HT) in rat isolated mesenteric, caudal, and basilar arteries. METHODS: Female Sprague-Dawley rats were ovariectomized (Day 0) and 7 days later subcutaneously implanted with pellets releasing over a 21-day period 17beta-estradiol (0.25 mg), progesterone (50 mg), their combination, or placebo. On days 25-28, the animals were killed, arteries isolated and mounted in Mulvany myographs, and cumulative concentration response curves to CGRP, acetylcholine, and 5-HT were constructed. RESULTS: The relaxant responses to CGRP were significantly potentiated in mesenteric and caudal arteries from rats treated with 17beta-estradiol as compared to the placebo-treated rats. Acetylcholine-induced relaxations were potentiated in the caudal artery from rats treated with the combination of 17beta-estradiol and progesterone, as compared to that from placebo-treated rats. The 5-HT-induced contractions in the 3 arteries were not significantly different in efficacy or potency. CONCLUSION: Our results show that 17beta-estradiol potentiates CGRP-induced relaxations in the mesenteric and caudal arteries, while the combination treatment enhances acetylcholine-induced relaxations in the caudal artery. Although these in vitro experiments have been carried out in rats and a direct extrapolation to migraine in humans is not possible, our results may provide a new avenue to study the effects of sex steroids on vascular reactivity.     

The effects of powered ankle-foot orthoses on joint kinematics and muscle activation during walking in individuals with incomplete spinal cord injury

Background  

Powered lower limb orthoses could reduce therapist labor during gait rehabilitation after neurological injury. However, it is not clear how patients respond to powered assistance during stepping. Patients might allow the orthoses to drive the movement pattern and reduce their muscle activation. The goal of this study was to test the effects of robotic assistance in subjects with incomplete spinal cord injury using pneumatically powered ankle-foot orthoses.     

An RCT of the effect of motivational interviewing on medication adherence in hypertensive African Americans: rationale and design

BACKGROUND: Hypertension disproportionately affects African Americans compared to whites, and it is the single most common explanation for the disparity in mortality between African Americans and whites. Adherence with antihypertensive medications can help reduce risk of negative hypertension-related outcomes. Motivational interviewing is a promising patient-centered approach for improving adherence in patients with chronic diseases. In this paper we describe the rationale and design of an ongoing randomized controlled trial testing the effectiveness of motivational interviewing versus usual care in improving medication adherence among 190 African American uncontrolled hypertensive patients, who receive care in a primary care setting. METHODS: The usual care group receives standard medical care, while those in the intervention group receive standard care plus four sessions of motivational interviewing at 3-month intervals for a period of 1 year. This technique consists of brief, patient-driven counseling sessions to facilitate initiation and maintenance of behavior change. The primary outcome is adherence to prescribed antihypertensive medication, assessed with the electronic medication events monitoring system (MEMS) and the Morisky self-report adherence questionnaire. Secondary outcomes are within-patient changes in blood pressure, self-efficacy, and intrinsic motivation between baseline and 12 months. We report the baseline sociodemographic and clinical characteristics of the participants. CONCLUSIONS: Despite the potential utility of motivational interviewing, little is known about its effectiveness in improving medication adherence among hypertensive patients, especially African Americans. In addition to the baseline data this study has generated, this trial should provide data with which we can assess the effectiveness of this approach as a behavioral intervention.     

The role of secreted frizzled-related protein 2 expression in prostate cancer

O’Hurley G, Perry A S, O’Grady A, Loftus B, Smyth P, O’Leary J J, Sheils O, Fitzpatrick J M, Hewitt S M, Lawler M & Kay E W
(2011) Histopathology  59 , 1240–1248
The role of secreted frizzled‐related protein 2 expression in prostate cancer Aims: Improved prostate cancer (PCa)‐specific biomarkers are urgently required to distinguish between indolent and aggressive disease, in order to avoid overtreatment. In this study, we investigated the prostatic tissue expression of secreted frizzled‐related protein (SFRP)‐2. Methods and results: Following immunohistochemical analysis on PCa tissue microarrays with samples from 216 patients, strong/moderate SFRP‐2 expression was observed in epithelial cells of benign prostatic hyperplasia, and negative/weak SFRP‐2 expression was observed in the majority of tumour epithelia. However, among Gleason grade 5 carcinomas, 40% showed strong/moderate SFRP‐2 expression and 60% showed negative SFRP‐2 expression in epithelial cells. Further microscopic evaluation of Gleason grade 5 tumours revealed different morphological patterns, corresponding with differential SFRP‐2 expression. The first subgroup (referred to as Type A) appeared to have a morphologically solid growth pattern, whereas the second subgroup (referred to as Type B) appeared to have a more diffuse pattern. Furthermore, 100% (4/4) of Type A patients experienced biochemical recurrence, as compared with 0% (0/6) of Type B patients. Conclusions: These results imply: (i) that there is a loss of SFRP‐2 expression from benign to malignant prostate glands; and (ii) differential SFRP‐2 expression among two possible subgroups of Gleason grade 5 tumours.