In vitro drug causality assessment in Stevens-Johnson syndrome - alternatives for lymphocyte transformation test

BACKGROUND Patients with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) are often exposed simultaneously to a few potentially culprit drugs. However, both the standard lymphocyte transformation tests (LTT) with proliferation as the assay end-point as well as skin tests, if done, are often negative. OBJECTIVE As provocation tests are considered too dangerous, there is an urgent need to identify the relevant drug in SJS/TEN and to improve sensitivity of tests able to identify the causative drug. METHODS Fifteen patients with SJS/TEN with the ALDEN score ≥ 6 and 18 drug-exposed controls were included. Peripheral blood mononuclear cells (PBMC) were isolated and cultured under defined conditions with drugs. LTT was compared to the following end-points: cytokine levels in cell culture supernatant, number of granzyme B secreting cells by ELISpot and intracellular staining for granulysin and IFNγ in CD3(+) CD4(+), CD3(+) CD8(+) and NKp46(+) cells. To further enhance sensitivity, the effect of IL-7/IL-15 pre-incubation of PBMC was evaluated. RESULTS Lymphocyte transformation tests was positive in only 4/15 patients (sensitivity 27%, CI: 8-55%). Similarly, with granzyme B-ELISpot culprit drugs were positive in 5/15 patients (sensitivity 33%, CI: 12-62%). The expression of granulysin was significantly induced in NKp46(+) and CD3(+) CD4(+) cells (sensitivity 40%, CI: 16-68% and 53%, CI: 27-79% respectively). Cytokine production could be demonstrated in 38%, CI: 14-68% and 43%, CI: 18-71% of patients for IL-2 and IL-5, respectively, and in 55%, CI: 23-83% for IFNγ. Pre-incubation with IL-7/IL-15 enhanced drug-specific response only in a few patients. Specificities of tested assays were in the range of 95 (CI: 80-99%)-100% (CI: 90-100%). CONCLUSIONS AND CLINICAL RELEVANCE Granulysin expression in CD3(+) CD4(+) , Granzyme B-ELISpot and IFNγ production considered together provided a sensitivity of 80% (CI: 52-96%) and specificity of 95% (80-99%). Thus, this study demonstrated that combining different assays may be a feasible approach to identify the causative drug of SJS/TEN reactions; however, confirmation on another group of patients is necessary.

Children's performance estimation in mathematics and science tests over a school year: A pilot study

The metacognitve ability to accurately estimate ones performance in a test, is assumed to be of central importance for initializing task-oriented effort. In addition activating adequate problem-solving strategies, and engaging in efficient error detection and correction. Although school children's' ability to estimate their own performance has been widely investigated, this was mostly done under highly-controlled, experimental set-ups including only one single test occasion. Method: The aim of this study was to investigate this metacognitive ability in the context of real achievement tests in mathematics. Developed and applied by a teacher of a 5th grade class over the course of a school year these tests allowed the exploration of the variability of performance estimation accuracy as a function of test difficulty. Results: Mean performance estimations were generally close to actual performance with somewhat less variability compared to test performance. When grouping the children into three achievement levels, results revealed higher accuracy of performance estimations in the high achievers compared to the low and average achievers. In order to explore the generalization of these findings, analyses were also conducted for the same children's tests in their science classes revealing a very similar pattern of results compared to the domain of mathematics. Discussion and Conclusion: By and large, the present study, in a natural environment, confirmed previous laboratory findings but also offered additional insights into the generalisation and the test dependency of students' performances estimations.

Self-Assessment in a Competency-Based Curriculum: Preliminary Findings

Introduction: The introduction of the ACGME core competency framework brought challenges of developing appropriate evaluation tools (i.e. self assessment) to provide evidence of competency. Baylor College of Medicine has 43 competency goals organized within the 6 ACGME domains, each domain having 4-10 goals. [See PDF for complete abstract]

Understanding the underlying mechanisms of recent Jatropha curcas L. adoption by smallholders in Kenya: A rural livelihood assessment in Bondo, Kibwezi, and Kwale districts

Between 2004 and 2007, NGOs, community based organisations and private investors promoted jatropha in Kenya with the aim of generating additional income and producing biofuel for rural development. By 2008 it became gradually evident that jatropha plantations (both mono- and intercropping) are uneconomical and risky due to competition for land and labour with food crops. Cultivation of jatropha hedges was found to have better chances of economic success and to present only little risks for the adopting farmers. Still, after 2008 a number of farmers went on adopting jatropha in plots rather than as hedges. It is hypothesised that lack of awareness about the low economic prospects of jatropha plantations was the main reason for continued adoption, and that smallholder farmers with higher resource endowments mainly ventured into its cultivation. In this study we provide an empirical basis for understanding the role of households' capital assets in taking up new livelihood strategies by smallholder farmers in three rural districts in Kenya. For that purpose, we assess the motivation and enabling factors that led to the adoption of jatropha as a new livelihood strategy, as well as the context in which promotion and adoption took place. A household survey was conducted in 2010, using a structured questionnaire, to collect information on household characteristics and capital asset endowment. Data were analysed using descriptive statistics and non-parametric statistical tests. We established that access to additional income and own energy supply were the main motivation for adoption of jatropha, and that financial capital assets do not necessarily have a positive influence on adoption as hypothesised. Further, we found that the main challenges that adopting farmers faced were lack of access to information on good management practices and lack of a reliable market. We conclude that continued adoption of on-farm jatropha after 2008 is a result of lacking awareness about the low economic value of this production type. We recommend abandoning on-farm production of jatropha until improved seed material and locally adapted agronomic knowledge about jatropha cultivation becomes available and its production becomes economically competitive.

Cardiopulmonary performance testing using a robotics-assisted tilt table: Feasibility assessment in able-bodied subjects

BACKGROUND: Robotics-assisted tilt table technology was introduced for early rehabilitation of neurological patients. It provides cyclical stepping movement and physiological loading of the legs. The aim of the present study was to assess the feasibility of this type of device for peak cardiopulmonary performance testing using able-bodied subjects. METHODS: A robotics-assisted tilt table was augmented with force sensors in the thigh cuffs and a work rate estimation algorithm. A custom visual feedback system was employed to guide the subjects' work rate and to provide real time feedback of actual work rate. Feasibility assessment focused on: (i) implementation (technical feasibility), and (ii) responsiveness (was there a measurable, high-level cardiopulmonary reaction?). For responsiveness testing, each subject carried out an incremental exercise test to the limit of functional capacity with a work rate increment of 5 W/min in female subjects and 8 W/min in males. RESULTS: 11 able-bodied subjects were included (9 male, 2 female; age 29.6 ± 7.1 years: mean ± SD). Resting oxygen uptake (O_{2}) was 4.6 ± 0.7 mL/min/kg and O_{2}peak was 32.4 ± 5.1 mL/min/kg; this mean O_{2}peak was 81.1% of the predicted peak value for cycle ergometry. Peak heart rate (HRpeak) was 177.5 ± 9.7 beats/min; all subjects reached at least 85% of their predicted HRpeak value. Respiratory exchange ratio (RER) at O_{2}peak was 1.02 ± 0.07. Peak work rate) was 61.3 ± 15.1 W. All subjects reported a Borg CR10 value for exertion and leg fatigue of 7 or more. CONCLUSIONS: The robotics-assisted tilt table is deemed feasible for peak cardiopulmonary performance testing: the approach was found to be technically implementable and substantial cardiopulmonary responses were observed. Further testing in neurologically-impaired subjects is warranted.

Incidence and Imaging Outcomes of Acute Scaffold Disruption and Late Structural Discontinuity After Implantation of the Absorb Everolimus-Eluting Fully Bioresorbable Vascular Scaffold: Optical Coherence Tomography Assessment in the ABSORB Cohort B Trial (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions).

OBJECTIVES This study sought to describe the frequency and clinical impact of acute scaffold disruption and late strut discontinuity of the second-generation Absorb bioresorbable polymeric vascular scaffolds (Absorb BVS, Abbott Vascular, Santa Clara, California) in the ABSORB (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) cohort B study by optical coherence tomography (OCT) post-procedure and at 6, 12, 24, and 36 months. BACKGROUND Fully bioresorbable scaffolds are a novel approach to treatment for coronary narrowing that provides transient vessel support with drug delivery capability without the long-term limitations of metallic drug-eluting stents. However, a potential drawback of the bioresorbable scaffold is the potential for disruption of the strut network when overexpanded. Conversely, the structural discontinuity of the polymeric struts at a late stage is a biologically programmed fate of the scaffold during the course of bioresorption. METHODS The ABSORB cohort B trial is a multicenter single-arm trial assessing the safety and performance of the Absorb BVS in the treatment of 101 patients with de novo native coronary artery lesions. The current analysis included 51 patients with 143 OCT pullbacks who underwent OCT at baseline and follow-up. The presence of acute disruption or late discontinuities was diagnosed by the presence on OCT of stacked, overhung struts or isolated intraluminal struts disconnected from the expected circularity of the device. RESULTS Of 51 patients with OCT imaging post-procedure, acute scaffold disruption was observed in 2 patients (3.9%), which could be related to overexpansion of the scaffold at the time of implantation. One patient had a target lesion revascularization that was presumably related to the disruption. Of 49 patients without acute disruption, late discontinuities were observed in 21 patients. There were no major adverse cardiac events associated with this finding except for 1 patient who had a non-ischemia-driven target lesion revascularization. CONCLUSIONS Acute scaffold disruption is a rare iatrogenic phenomenon that has been anecdotally associated with anginal symptoms, whereas late strut discontinuity is observed in approximately 40% of patients and could be viewed as a serendipitous OCT finding of a normal bioresorption process without clinical implications. (ABSORB Clinical Investigation, Cohort B [ABSORB B]; NCT00856856).

Comprehensive geriatric assessment in patients undergoing transcatheter aortic valve implantation–rationale and design of the European CGA-TAVI registry

Abstract Purpose Aortic stenosis (AS) is the most common valvular abnormality in the elderly population. For inoperable patients or those at high-risk for surgery, transcatheter aortic valve implantation (TAVI) has become an alternative therapeutic option. The aim of the “Comprehensive geriatric assessment for transcatheter aortic valve implantation” (CGA-TAVI) registry is to evaluate the effectiveness of TAVI from the perspective of the geriatrician and to identify patient characteristics and indicators related to complications and clinical benefits for patients with symptomatic severe calcified degenerative AS undergoing TAVI. Materials and methods The CGA-TAVI registry is an international, multi-center, prospective, observational registry across Europe with consecutive patient enrolment. The registry will enrol up to 200 patients with AS undergoing TAVI, starting August 2013. CGA-TAVI has two co-primary objectives: (1) Establish predictive value of Comprehensive geriatric assessment (CGA) for mortality and/or hospitalization in TAVI patients. (2) Demonstrate CGA changes within 3 months after TAVI. Secondary objectives are: (1) Establish predictive value of CGA in TAVI patients for all-cause hospitalization, TAVI-related hospitalization, and nursing home admission. (2) Develop a comprehensive score for the assessment of TAVI patient prognosis. Conclusions The data obtained from the CGA-TAVI registry will supplement previous results to document the potential value of the effectiveness of TAVI from the perspective of geriatricians and will allow the assessment of the predictive value of CGA for mortality and/or hospitalization in elderly TAVI patients. Keywords Aortic stenosis; Transcatheter aortic valve implantation (TAVI); Comprehensive geriatric assessment (CGA); Registry; Predictor

Motivation and Learning in Mathematics Pre-service Teachers

Based on a review of literature of conceptual and procedural knowledge in relation to intrinsic and extrinsic motivation, the purpose of this study was to test the relationship between conceptual and procedural knowledge and intrinsic and extrinsic motivation. Thirty-eight education students with a mathematics focus (elementary or secondary) in their junior, senior, or fifth year completed a survey with a Likert scale measuring their preference to learning (conceptual or procedural) and their motivation type (intrinsic or extrinsic). Findings showed that secondary mathematics focused students were more likely to prefer learning mathematics conceptually than elementary mathematics focused students. However, secondary and elementary mathematics focused students showed an equal preference for learning mathematics procedurally and sequentially. Elementary and secondary students reported similar intrinsic and extrinsic motivation. Extrinsically motivated students preferred procedural learning more than conceptual learning. While there was no statistically significant preference with intrinsically motivated students, there was a trend favoring preference of conceptual learning over procedural learning. These results tend to support the hypothesis that mathematics focused students who prefer conceptual learning are more intrinsically motivated, and mathematics focused students who prefer procedural learning are more extrinsically motivated.

South Asian immigrant cardiovascular risk assessment in Houston, Texas 2005

Background. Heart disease is the leading cause of death and stroke is the third leading cause of deaths for all people in the United States. South Asian Americans have a higher risk of developing cardiovascular diseases than native United States residents. ^ Purpose. This study examines the cardiovascular risk factors in the South Asian immigrant community residing in Southwest Houston. This study also explores the level of health insurance available to the South Asian in Houston. ^ Methods. One hundred sixty-two South Asian patients aged 18 years and older received cardiovascular screening from January 1 st, 2005 to March 31st, 2005 at Ibn Sina Community Clinic; blood pressure was measured twice in both arms after resting five minutes. Height and weight were also recorded. Demographic data was collected through personal interview (questionnaire) and blood samples were drawn to collect laboratory data. ^ Results. There were 162 eligible South Asian patients, among whom 127 (78%) participated in the study. There were no significant differences between the responders and the non-responders in terms of demographics and clinical characteristics. Laboratory data revealed a mean total cholesterol of 201 ± 34 mg/dl, 54 percent had high total cholesterol above 200 mg/dl. The mean fasting glucose was 108 ± 43 mg/dl, and body mass index (BMI) was 28 ± 4 kg/m2. The prevalence of hypertension was comparable with the general U.S. population; 38 percent of the South Asian males and 29 percent of females had hypertension. The prevalence of diabetes was also compared; 21 percent of SA males (3% for white American males) and 7 percent of SA females (2% for white American females) were found to have undiagnosed diabetes. Of the sample 12 percent had both hypertension and diabetes; 21 percent had both hypertension and high BMI, and 19 percent had hypertension and high total cholesterol levels. ^ Conclusion. The present study shows that the South Asians in this sample are at greater risk of developing cardiovascular diseases than other ethnicities. The high prevalence of hypertension, type 2 diabetes, higher total cholesterol levels with overweight and obesity, and less leisure time physical activity are important cardiovascular risk factors for South Asians population. ^

Emergency health care assessment in the Houston-Galveston region 2002--2006

Background. Previous studies show emergency rooms to be over crowded nation wide. With growing attention to this problem, the Houston-Galveston Area Council (H-GAC) initiated a study in 2005 to assess their region's emergency health care system, and continued this effort in 2007. The purpose of this study was to examine recent changes in volume, capacity and performance in the Houston-Galveston region's emergency health care system and determine whether the system has been able to effectively respond to the residents' demands. Methods. Data were collected by the Houston-Galveston Area Council and The Abaris Group using a self-administered 2002-2006 survey completed by administrators of the region's hospitals, EMS providers, and select fire departments that provide EMS services. Data from both studies were combined and matched to examine trends. Results. Volume increased among the reporting hospitals within the Houston-Galveston region from 2002 to 2006; however, capacity remained relatively unchanged. EMS providers reported higher average off load times in 2007 compared to 2005, but the increases were not statistically significant. Hospitals reported transferring a statistically significant greater percentage of patients in 2006 than 2004. There was no statistically significant change in any of the other measures. Conclusion. These findings indicate an increase in demand for the Houston-Galveston region's emergency healthcare services with no change in supply. Additional studies within the area are needed to fully assess and evaluate the impact of these changes on system performance. ^