This article reports upon the emergence of a novel cognitive, computer-based technology which may lead to significantly improved methods of cardiological diagnosis and a rapid and inexpensive method of cardiological screening.
The technology ‘Virtual Scanning’ illustrates how, in blood, the reaction of proteins and their reactive substrates releases light; that the colour and intensity of this bioluminescence is unique to each reaction and it's rate; and that the development of pathologies influence cognition and visual perception. This illustrates that the function of the autonomic nervous system is linked to that of the physiological systems and that the rate of biochemical reactions, and the progression of disease, can be measured by a cognitive test procedure and used as an indication of the disease(s) affecting heart function.
The article discusses the limitations of the conventional biomarker technique, and the potential value of non-invasive cognitive techniques, such as Virtual Scanning, to the medical practitioner. Finally, it discusses how the ability of Virtual Scanning to diagnose disease from its presymptomatic origins may lead to improved diagnostic accuracy and significantly reduced costs.
Computer diagnosis; autonomic nervous system; visual perception; virtual scanning; mathematical modeling; physiological systems
Fabrication of carbon microelectrode arrays, with up to 15 electrodes in total tips as small as 10 to 50 μm, is presented. The support structures of microelectrodes were obtained by pulling multiple quartz capillaries together to form hollow capillary arrays before carbon deposition. Carbon ring microelectrodes were deposited by pyrolysis of acetylene in the lumen of these quartz capillary arrays. Each carbon deposited array tip was filled with epoxy, followed by beveling of the tip of the array to form a deposited carbon-ring microelectrode array (CRMA). Both the number of the microelectrodes in the array and the tip size are independently tunable. These CRMAs have been characterized using scanning electron microscopy, energy dispersive X-ray spectroscopy, and electrogenerated chemiluminescence. Additionally, the electrochemical properties were investigated with steady-state voltammetry. In order to demonstrate the utility of these fabricated microelectrodes in neurochemistry, CRMAs containing eight microring electrodes were used for electrochemical monitoring of exocytotic events from single PC12 cells. Subcellular temporal heterogeneities in exocytosis (ie. cold spots vs. hot spots) were successfully detected with the CRMAs.
microelectrode arrays; single cell; electrochemical imaging; PC12 cells
Resolution of synaptic vesicle neurotransmitter content has mostly been limited to the study of stimulated release in cultured cell systems, and it has been controversial as to whether synaptic vesicle transmitter levels are saturated in vivo. We use electrochemical cytometry to count dopamine molecules in individual synaptic vesicles in populations directly sampled from brain tissue. Vesicles from the striatum yield an average of 33,000 dopamine molecules per vesicle, an amount considerably greater than typically measured during quantal release at cultured neurons. Vesicular content was markedly increased by L-DOPA or decreased by reserpine in a time-dependent manner in response to in vivo administration of drugs known to alter dopamine release. We investigated the effects of the psychostimulant amphetamine on vesicle content, finding that vesicular transmitter is rapidly depleted by 50% following in vivo administration, supporting the “weak base hypothesis” that amphetamine reduces synaptic vesicle transmitter and quantal size.
This Classic Article is a reprint of the original work by J. Ewing, The Bulkley Lecture: The Modern Attitude Toward Traumatic Cancer. An accompanying biographical sketch of J. Ewing is available at DOI 10.1007/s11999-011-2234-y. The Classic Article is ©1935 and is reprinted courtesy of the New York Academy of Medicine from Ewing J. The Bulkley Lecture: The Modern Attitude Toward Traumatic Cancer*. Bull N Y Acad Med. 1935;11:281–333.
This article addresses the need for age-relevant outcome measures for traumatic brain injury (TBI) research and summarizes the recommendations by the inter-agency Pediatric TBI Outcomes Workgroup. The Pediatric Workgroup's recommendations address primary clinical research objectives including characterizing course of recovery from TBI, prediction of later outcome, measurement of treatment effects, and comparison of outcomes across studies. Consistent with other Common Data Elements (CDE) Workgroups, the Pediatric TBI Outcomes Workgroup adopted the standard three-tier system in its selection of measures. In the first tier, core measures included valid, robust, and widely applicable outcome measures with proven utility in pediatric TBI from each identified domain including academics, adaptive and daily living skills, family and environment, global outcome, health-related quality of life, infant and toddler measures, language and communication, neuropsychological impairment, physical functioning, psychiatric and psychological functioning, recovery of consciousness, social role participation and social competence, social cognition, and TBI-related symptoms. In the second tier, supplemental measures were recommended for consideration in TBI research focusing on specific topics or populations. In the third tier, emerging measures included important instruments currently under development, in the process of validation, or nearing the point of published findings that have significant potential to be superior to measures in the core and supplemental lists and may eventually replace them as evidence for their utility emerges.
children; infants; outcome assessment; TBI
To investigate (1) weight maintenance among black and white participants and (2) psychosocial correlates (eg, healthy eating barriers, self-efficacy, stress) of weight maintenance 18 months after behavioral weight-loss treatment.
Linear and logistic regression examined weight change and unsuccessful weight maintenance (>5% weight gain) among 107 black and white adults.
After controlling for socio-demographics, differences in weight maintenance between ethnicities were not generally noted. Healthy eating barriers and stressful life events were associated with weight gain, P<.04.
Strategies to cope with stressful events and overcome barriers to eating healthfully are needed for weight maintenance among both ethnicities.
obesity; ethnicity; weight-loss maintenance; stress; barrier
This paper explores the association between work intensity, alcohol and/or other drug (AOD) use, and related risk factors and consequences among an at-risk youth sample that has received a first-time AOD offense. This study extends previous research focused primarily on school-based samples.
We examined the association between work intensity, AOD use, AOD-related consequences, and social environment among adolescents referred to a diversion program called Teen Court (N=193). Participants were surveyed prior to the start of the Teen Court program. Mean age was 17 (SD=1.1), 67% of the sample was male; and 45% Hispanic or Latino/a, 45.1% white; 10% other.
Greater work intensity among these youth was related to greater alcohol-related negative consequences and greater contact with co-workers who engaged in risky behaviors, but it was not significantly associated with past month AOD use.
Understanding the relationship between work intensity and AOD use among youth who are at-risk is critical to informing clinicians and public officials about the potential effects of employment in this population. Findings suggest that work intensity may be associated with negative consequences from alcohol use and increased contact with risky co-workers, all of which could contribute to the development of problems in the future.
Long INterspersed Element-1 (LINE-1) retrotransposons comprise 17% of the human genome, and move by a potentially mutagenic “copy and paste” mechanism via an RNA intermediate. Recently, the retrotransposition-mediated insertion of a new transcript was described as a novel cause of genetic disease, Duchenne muscular dystrophy, in a Japanese male. The inserted sequence was presumed to derive from a single-copy, non-coding RNA transcribed from chr. 11q22.3 that retrotransposed into the dystrophin gene. Here we demonstrate that a non-reference full-length LINE-1 is situated in the proband and maternal genome at chr. 11q22.3, directly upstream of the sequence, whose copy was inserted into the dystrophin gene. This LINE-1 is highly active in a cell culture assay. LINE-1 insertions are often associated with 3’ transduction of adjacent genomic sequences. Thus, the likely explanation for the mutagenic insertion is a LINE-1-mediated 3’ transduction with severe 5’ truncation. This is the first example of LINE-1-induced human disease caused by an “orphan” 3’ transduction.
LINE-1; retrotransposon; 3’ transduction; dystrophin; Duchenne muscular dystrophy
In previous studies on a rat model of transient cerebral ischemia, the blood and brain concentrations of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) following intravenous bolus injection were repeatedly assessed by dynamic contrast-enhanced (DCE)-MRI, and blood-to-brain influx rate constants (Ki) were calculated from Patlak plots of the data in areas with blood–brain barrier (BBB) opening. For concurrent validation of these findings, after completing the DCE-MRI study, radiolabeled sucrose or α-aminoisobutyric acid was injected intravenously, and the brain disposition and Ki values were calculated by quantitative autoradiography (QAR) assay employing the single-time equation. To overcome two of the shortcomings of this comparison, the present experiments were carried out with a radiotracer virtually identical to Gd-DTPA, Gd-[14C]DTPA, and Ki was calculated from both sets of data by the single-time equation. The protocol included 3 h of middle cerebral artery occlusion and 2.5 h of reperfusion in male Wistar rats (n = 15) preceding the DCE-MRI Gd-DTPA and QAR Gd-[14C]DTPA measurements. In addition to Ki, the tissue-to-blood concentration ratios, or volumes of distribution (VR), were calculated. The regions of BBB opening were similar on the MRI maps and autoradiograms. Within them, VR was nearly identical for Gd-DTPA and Gd-[14C]DTPA, and Ki was slightly, but not significantly, higher for Gd-DTPA than for Gd-[14C]DTPA. The Ki values were well correlated (r = 0.67; p = 0.001). When the arterial concentration–time curve of Gd-DTPA was adjusted to match that of Gd-[14C]DTPA, the two sets of Ki values were equal and statistically comparable with those obtained previously by Patlak plots (the preferred, less model-dependent, approach) of the same data (p = 0.2–0.5). These findings demonstrate that this DCE-MRI technique accurately measures the Gd-DTPA concentration in blood and brain, and that Ki estimates based on such data are good quantitative indicators of BBB injury.
arterial input function; blood–brain barrier; cerebral blood flow; cerebral ischemia; DCE-MRI; magnetic resonance contrast agents; neurovascular unit; Patlak plot
The longitudinal relaxivity on the protons of water of a Gd–chelate–albumin compound was measured at 7 T as a function of the macromolecular content of a cross-linked matrix. In agreement with previous works, the results demonstrate that the effect of gadolinium on water proton relaxivity is not constant, rising moderately with increase in the concentration of bovine serum albumin (BSA). About 35% variation in relaxivity was observed over a 0%–25% range of BSA concentrations (ℜ = 3.893 + 0.0502 × BSA [%], SE = 0.0119 and 0.1740, t = 4.215 and 22.383, p<0.014 and 0.001).
Longitudinal relaxation time; Longitudinal relaxivity; Water proton; Contrast agents
The group format is commonly used in alcohol and other drug (AOD) adolescent treatment settings, but little research exists on the use of Motivational Interviewing (MI) in groups. Further, little work has assessed the integrity of MI delivered in group settings. This study describes an approach to evaluate MI integrity using data from a group MI intervention for at-risk youth. Using the Motivational Interviewing Treatment Integrity (MITI) scale 3.1, we coded 140 group sessions, led by three different facilitators. Four trained coders assessed the group sessions. Agreement between raters was evaluated using a method based on limits of agreement, and key decisions used to monitor and calculate group MI integrity are discussed. Results indicated that there was adequate agreement between raters; we also found differences on use of MI between the MI-intervention group and a usual care group on MI global ratings and behavioral counts. This study demonstrates that it is possible to determine whether group MI is implemented with integrity in the group setting and that MI in this setting is different from what takes place in usual care.
Even though it has been suggested that antiretroviral therapy has an impact on severe hypovitaminosis D (SHD) in HIV infected patients, it could be speculated that the different levels of residual inflammation on HAART (Highly Active Anti Retroviral Therapy) could contribute to SHD and aggravate bone catabolism in these patients.
A cross-sectional study was carried out in an unselected cohort of 263 HIV infected outpatients consulting during Spring 2010. Clinical examinations were performed and medical history, food habits, sun exposure and addictions were collected. Fasting blood samples were taken for immunological, virological, inflammation, endocrine and bone markers evaluations.
Ninety-five (36%) patients had SHD. In univariate analysis, a significant and positive association was found between SHD and IL6 (p = 0.001), hsCRP (p = 0.04), increased serum C-Telopeptides X (CTX) (p = 0.005) and Parathyroid Hormon (PTH) (p < 0.0001) levels. In multivariate analysis, SHD deficiency correlated significantly with increased IL-6, high serum CTX levels, lower mean daily exposure to the sun, current or past smoking, hepatitis C, and functional status (falls), but not with the time spent on the current HAART (by specific drug or overall).
SHD is frequent and correlates with inflammation in HIV infected patients. Since SHD is also associated with falls and increased bone catabolism, it may be of interest to take into account not only the type of antiretroviral therapy but also the residual inflammation on HAART in order to assess functional and bone risks. This finding also suggests that vitamin D supplementation may be beneficial in these HIV-infected patients.
Antiretroviral therapy; Bone metabolism; HIV; Inflammation; 25-hydroxyvitamin D
Transfusion of platelets is commonly indicated in the inpatient oncology setting. These platelets are obtained either through apheresis from a single donor or pooled from the whole blood of several donors. The amount of transfused platelets, infection risk, incidence of alloimmunization, and increases in posttransfusion platelet count are similar for these two platelet products. Although single-donor platelets are preferred over pooled platelets in some instances, single-donor platelets are often given regularly, despite a higher cost and more limited donor supply. Oncology fellows at Baylor University Medical Center at Dallas initiated an education campaign regarding the indications for pooled and single-donor platelet transfusions. The quality improvement campaign included seminars led by oncology fellows for nursing personnel and resident housestaff on the two oncology floors, as well as electronic correspondence to attending physicians. The number of pooled and single-donor platelet transfusions on the two floors was recorded for the 3 months after the education campaign (July–September 2011) and compared with the corresponding data from the previous year. Over the 3-month study period after the education campaign, the average percentage of pooled platelets transfused increased to 34.1% from 13.1% for the prior year. Given this increase, the estimated cost benefit over the 3-month study period was $45,000.
Tumor interstitial fluid pressure (TIFP) has the potential to predict tumor response to nonsurgical cancer treatments, including radiation therapy. At present the only quantitative measures available are of limited use, since they are invasive and yield only point measurements. We present the mathematical framework for a quantitative, noninvasive measure of TIFP. The model describes the distribution of interstitial fluid pressure in three distinct tumor regions: vascularized tumor rim, central tumor region, and normal tissue. A relationship between the TIFP and the fluid flow velocity at the periphery of a tumor is presented. This model suggests that a measure of fluid flow rate from a tumor into normal tissue reflects TIFP. We demonstrate that the acquisition of serial images of a tumor after the injection of a contrast agent can provide a noninvasive and potentially quantitative measure of TIFP.
One of the primary challenges in translational research data management is breaking down the barriers between the multiple data silos and the integration of 'omics data with clinical information to complete the cycle from the bench to the bedside. The role of contextual metadata, also called provenance information, is a key factor ineffective data integration, reproducibility of results, correct attribution of original source, and answering research queries involving "What", "Where", "When", "Which", "Who", "How", and "Why" (also known as the W7 model). But, at present there is limited or no effective approach to managing and leveraging provenance information for integrating data across studies or projects. Hence, there is an urgent need for a paradigm shift in creating a "provenance-aware" informatics platform to address this challenge. We introduce an ontology-driven, intuitive Semantic Proteomics Dashboard (SemPoD) that uses provenance together with domain information (semantic provenance) to enable researchers to query, compare, and correlate different types of data across multiple projects, and allow integration with legacy data to support their ongoing research.
SemPoD is an intuitive and powerful provenance ontology-driven data access and query platform that uses the MIAPE and MIMIx metadata guideline to create an integrated view over large-scale systems molecular biology datasets. SemPoD leverages the SysPro ontology to create an intuitive dashboard for biologists to compose queries, explore the results, and use a query manager for storing queries for later use. SemPoD can be deployed over many existing database applications storing 'omics data, including, as illustrated here, the LabKey data-management system. The initial user feedback evaluating the usability and functionality of SemPoD has been very positive and it is being considered for wider deployment beyond the proteomics domain, and in other 'omics' centers.
We describe the systematic approach to incidental findings (IFs) used at the Mind Research Network (MRN) where all MRI scans receive neuroradiologist interpretation and participants are provided results.
From 2004 to 2011, 8,545 MRI scans were acquired by 45 researchers. As mandated by MRN′s external institutional review board, all structural sequences were evaluated by a clinical neuroradiologist who generated a report that included recommendations for referral if indicated. Investigators received a copy of their participants' reports, which were also mailed to participants unless they specifically declined. To better understand the impact of the radiology review process, a financial analysis was completed in addition to a follow-up phone survey to characterize participant perceptions regarding receiving their MRI scan results.
The radiologist identified IFs in 34% of the 4,447 participants. Of those with IFs (n = 1,518), the radiologist recommended urgent or immediate referral for 2.5% and routine referral for 17%. For 80.5%, no referral was recommended. Estimated annual cost for this approach including support for the neuroradiologist, medical director, and ancillary staff is approximately $60,000 or $24/scan. The results of the retrospective phone survey showed that 92% of participants appreciated receiving their MRI report, and the majority stated it increased their likelihood of volunteering for future studies.
Addressing IFs in a cost-effective and consistent manner is possible by adopting a policy that provides neuroradiology interpretation and offers participant assistance with clinical follow-up when necessary. Our experience suggests that an ethical, institution-wide approach to IFs can be implemented with minimal investigator burden.
To clarify effects of diet and body weight on prostate cancer development, three studies were undertaken using the TRAMP mouse model of this disease. In the first experiment, obesity was induced by injection of gold thioglucose (GTG). Age of prostate tumor detection (~33 wk) and death (~43 wk) was not significantly different among the groups. In the second study, TRAMP-C2 cells were injected into syngeneic C57BL6 mice and tumor progression was evaluated in mice fed either high-fat or low-fat diets. The high fat fed mice had larger tumors than did the low-fat fed mice. In the third study, tumor development was followed in TRAMP mice fed a high fat diet from 6 weeks of age. There were no significant effects of body weight status or diet on tumor development among the groups. When the tumors were examined for the neuroendocrine marker synaptophysin, there was no correlation with either body weight or diet. However, there was a significant correlation of the expression of synaptophysin with earlier age to tumor detection and death. In summary, TRAMP-C2 cells grew faster when the mice were fed a high-fat diet. Further synaptophysin may be a marker of poor prognosis independent of weight and diet.
Background and purpose
Sildenafil provides restorative therapeutic benefits in the treatment of experimental stroke. The majority of experimental studies on treatment of stroke have been performed in young animals; however, stroke is primarily a disease of the aged. Thus, using MRI, we evaluated the effects of sildenafil treatment of embolic stroke in aged animals.
Aged male Wistar rats (18 months) were subjected to embolic stroke and treated daily with saline (n=10) or with sildenafil (n=10) initiated at 24h and subsequently for 7 days after onset of ischemia. MRI measurements were performed at 24h and weekly to 6 weeks after embolization.
MRI and histological measurements demonstrated that sildenafil treatment of aged rats significantly enhanced angiogenesis and axonal remodeling after stroke compared to saline treated aged rats. Local CBF in the angiogenic area was elevated and expansion of the ipsilateral ventricle and consequently brain atrophy was significantly reduced in the sildenafil treated rats.
Treatment of embolic stroke in aged rats with sildenafil significantly augments angiogenesis and axonal remodeling, which increased local blood flow and reduced expansion of the ipsilateral ventricle 6 weeks after stroke, compared to control aged rats. MRI can be employed to investigate brain repair after stroke in aged rats.
aged rat; embolic stroke; magnetic resonance imaging; neurorestorative treatment; sildenafil
The basis for communication between nerve cells lies in the process of exocytosis, the fusion of neurotransmitter filled vesicles with the cell membrane resulting in release of the signaling molecules. Even though much is known about this process, the extent that the vesicles are emptied upon fusion is a topic that is being debated. We have analyzed amperometric peaks corresponding to release at PC12 cells and find stable plateau currents during the decay of peaks, indicating closing of the vesicle after incomplete release of its content. Using lipid incubations to alter the amount of transmitter released we were able to estimate the initial vesicular content, and from that, the fraction of release. We propose a process for most exocytosis events where the vesicle partially opens to release transmitter and then closes directly again, leaving the possibility for regulation of transmission within events.
Prayer is becoming more widely acknowledged as a way to cope with cancer. The goal of this study was to compare differences in use of prayer between breast cancer survivors from different ethnic groups and examine how use of prayer is related to mood and quality of life.
This study used a mixed methods design. One hundred and seventy-five breast cancer survivors participated in a longitudinal study of survivorship. Women completed in-depth qualitative interviews and a battery of measures including quality of life, spirituality, social support, and mood.
Eighty-one percent of the women prayed. There were no significant differences between the groups for any of the psychological, social support, or quality of life variables with the exception of higher benefit finding and spiritual well-being among those who prayed. The data did show that women who prayed were able to find more positive contributions from their cancer experience than women who did not pray. The interviews showed that those who prayed tended to be African American or Asian, Catholic or Protestant. The prayers were for petitioning, comfort, or praise. Some of the women stated that they had difficulty praying for themselves.
While there seems to be few differences in terms of standardized measures of quality of life, social support, and mood between those who prayed and those who did not, the interviews showed that certain ethnic minority groups seem to find more comfort in prayer, felt closer to God, and felt more compassion and forgiveness than Caucasian women.
Prayer; Spirituality; Breast cancer; Ethnic differences; Quality of life; Psychological
This paper models the behavior of the longitudinal relaxation rate of the protons of tissue water R1 (R1 = 1/T1), measured in a Look-Locker (LL) experiment at 7 Tesla after administration of a paramagnetic contrast agent (CA). It solves the Bloch-McConnell equations for the longitudinal magnetization of the protons of water in a three-site two-exchange (3S2X) model with boundary conditions appropriate to repeated sampling of magnetization. The extent to which equilibrium intercompartmental water exchange kinetics affect monoexponential estimates of R1 after administration of a CA in dynamic contrast enhanced (DCE) experiment is described.
The relation between R1 and tissue CA concentration was calculated for CA restricted to the intravascular, or to the intravascular and extracellular compartments, by varying model parameters to mimic experimental data acquired in a rat model of cerebral tumor. The model described a nearly linear relationship between R1 and tissue concentration of CA, but demonstrated that the apparent longitudinal relaxivity of CA depends upon tissue type. The practical consequence of this finding is that the extended Patlak plot linearizes the ΔR1 data in tissue with leaky microvessels, accurately determines the influx rate of the CA across these microvessels, but underestimates the volume of intravascular blood water.
Look Locker pulse sequence; relaxation rate constant; contrast mechanism; Bloch-McConnell’s equations; shutter-speed; water exchange rate
The apparent forward transfer constant,
Katrans, for albumin was measured in 9L cerebral tumors in 15 rats. An MRI study using gadolinium-labeled bovine serum albumin (Gd-BSA) was followed by terminal quantitative autoradiography (QAR) using radioiodinated serum albumin (RISA). Look-Locker MRI estimates of T1 followed Gd-BSA blood and tissue concentration. QAR and MRI maps of
Katrans were co-registered, a region of interest (ROI) that included the tumor and its surround was selected, and the two estimates of
Katrans from the ROI on QAR and MRI maps were compared by either mean per animal ROI or on pixel-by-pixel data using a generalized estimating equation (GEE).
An ROI analysis showed a moderate correlation between the two measures (r = 0.57, p = 0.026); pixel-by-pixel GEE analysis concurred (r = 0.54, p < 0.0001). The estimates of QAR with MRI of last time points (e.g., 25 minutes) showed a moderate correlation (ROI r = 0.55, p < 0.035; GEE r = 0.58, p < 0.0001). Differences between the QAR and MRI estimates of
Katrans did not differ from zero, but the MRI 25 minute estimate was significantly lower than the QAR estimate. Thus, noininvasive MRI estimates of vascular permeability can serve as a surrogate for QAR measures.
TOMROP; relaxation time; transfer constant; Patlak plot; 9L glioblastoma
Breast cancer remains one of the leading causes of morbidity and mortality for all women in the US. Current research has focused on the psychological relationship and not the sociological relationship between emotions and the experience of breast cancer survivors. This paper focuses on the emotion work involved in self-disclosing a breast cancer diagnosis in a racially or ethnically diverse population.
The participants (n=176) selected for this study were African American, Asian American, Latina, and Caucasian women who had been diagnosed with stages 0, I, or II breast cancer within the past 4 years. They completed an in-depth qualitative interview on self-disclosure and social support.
The results indicate self-disclosing was done at a time when important decisions about treatment needed to be made. Different strategies for disclosure were used, all of which entailed emotion work. Respondents talked about the various elements of emotion work in the disclosure process including: managing others' worry, protecting and soothing others, and educating and instructing others.. For many respondents, disclosure without calculating emotional management meant opening up to others which meant support and an increase in emotional resources.
The findings in this paper have implications for women with breast cancer and demonstrate the need for women to be involved in honest disclosure and less emotional management of others' feelings. There is also a need for education about the nature of the cancer experience among people who are not well educated about the treatment and consequences of cancer. This need may be even stronger among racial and ethnic minorities.
Breast cancer; Self-disclosure; Emotion work; Social support
Recruitment challenges are common in acute stroke clinical trials. In a population-based study, we determined eligibility and actual enrollment for a successful, phase II acute stroke clinical trial. We hypothesized that missed opportunities for enrollment of eligible patients occurred frequently, despite the success of the trial.
In 2005, acute ischemic stroke (AIS) cases in our region were identified at all 17 local hospitals as part of an epidemiologic study. The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA (CLEAR) trial assessed the safety of this combination in AIS patients within 3 hours of symptom onset. In 2005, we determined the proportion of AIS patients who were eligible for CLEAR and the proportion that were actually enrolled.
At 8 participating hospitals, 33 (2.8%) of 1175 AIS patients were eligible for CLEAR. Of 33 eligible patients, 18 (54.5%) were approached for enrollment, 4 (12.1%) refused, 1 (3.0%) was not consentable, and 13 (39.4%) were enrolled. Of the 15 not approached for enrollment in the trial, 10 were evaluated by the stroke team; 7 received rt-PA. Enrollment was not associated with night or weekend presentation.
Although the CLEAR trial was successful in meeting its delineated recruitment goals, our findings suggest enrollment could have been more efficient. Three out of 4 patients approached for enrollment participated in the trial. Eligible patients who were not approached and those treated with rt-PA but not enrolled represent targets for improving enrollment rates.
clinical trials; emergency medicine; acute stroke; thrombolysis