Xin Qun Wang

A Predictive Risk Model for Outcomes of Ischemic Stroke

BACKGROUND AND PURPOSE The great variability of outcome seen in stroke patients has led to an interest in identifying predictors of outcome. The combination of clinical and imaging variables as predictors of stroke outcome in a multivariable risk adjustment model may be more powerful than either alone. The purpose of this study was to determine the multivariable relationship between infarct volume, 6 clinical variables, and 3-month outcomes in ischemic stroke patients. METHODS Included in the study were 256 eligible patients from the Randomized Trial of Tirilazad Mesylate in Acute Stroke (RANTTAS). Six clinical variables and 1-week infarct volume were the prespecified predictor variables. The National Institutes of Health Stroke Scale, Barthel Index, and Glasgow Outcome Scale were the outcomes. Multivariable logistic regression techniques were used to develop the model equations, and bootstrap techniques were used for internal validation. Predictive performance of the models was assessed for discrimination with receiver operator characteristic (ROC) curves and for calibration with calibration curves. RESULTS The predictive models had areas under the ROC curve of 0.79 to 0.88 and demonstrated nearly ideal calibration curves. The areas under the ROC curves were statistically greater (P<0.001) with both clinical and imaging information combined than with either alone for predicting excellent recovery and death or severe disability. CONCLUSIONS Combined clinical and imaging variables are predictive of 3-month outcome in ischemic stroke patients. Demonstration of this relationship with acute clinical variables and 1-week infarct information supports future attempts to predict 3-month outcome with all acute variables.

Validation of an acute ischemic stroke model: does diffusion-weighted imaging lesion volume offer a clinically significant improvement in prediction of outcome?

Background and Purpose— Prediction models for ischemic stroke outcome have the potential to contribute prognostic information in the clinical and/or research setting. The importance of diffusion-weighted magnetic resonance imaging (DWI) in the prediction of clinical outcome, however, is unclear. The purpose of this study was to combine acute clinical data and DWI lesion volume for ischemic stroke patients to determine whether DWI improves the prediction of clinical outcome. Methods— Patients (N=382) with baseline DWI data from the Glycine Antagonist In Neuroprotection and citicoline (010 and 018) trials were used to develop the prediction models by multivariable logistic regression. Data from prospectively collected patients (N=266) from the Acute Stroke Accurate Prediction Study were used to externally validate the model equations. The models predicted either full recovery or nursing home–level disability/death, as defined by the National Institutes of Health Stroke Scale, Barthel Index, or modified Rankin Scale. Results— The full-recovery models with DWI lesion volume had areas under the receiver operating characteristic curves (AUCs) of 0.799 to 0.821, and those without DWI lesion volume had AUCs of 0.758 to 0.798. The nursing home–level disability/death models with DWI had AUCs of 0.832 to 0.882, and those without DWI had AUCs of 0.827 to 0.867. All models had mean absolute errors ≤0.4 for calibration. Conclusions— All 12 models had excellent discrimination and calibration, with 8 of 12 meeting prespecified performance criteria (AUC ≥0.8, mean absolute error ≤0.4). Although DWI lesion volume significantly increased model explanatory power, the magnitude of increase was not large enough to be clinically important.

Topiramate for the Treatment of Cocaine Addiction: A Randomized Clinical Trial

IMPORTANCE No medication has been established as an efficacious treatment for cocaine dependence. We hypothesized that dual modulation of the mesocorticolimbic dopamine system by topiramate-a glutamate receptor antagonist and γ-aminobutyric acid receptor agonist-would result in efficacious treatment for cocaine dependence compared with placebo. OBJECTIVE To determine the efficacy of topiramate vs placebo as a treatment for cocaine dependence. DESIGN, SETTING, AND PARTICIPANTS Double-blind, randomized, placebo-controlled, 12-week trial of 142 cocaine-dependent adults in clinical research facilities at the University of Virginia between November 22, 2005, and July 25, 2011. INTERVENTIONS Topiramate (n = 71) or placebo (n = 71) in escalating doses from 50 mg/d to the target maintenance dose of 300 mg/d in weeks 6 to 12, combined with weekly cognitive-behavioral treatment. MAIN OUTCOMES AND MEASURES For the efficacy period, weeks 6 to 12, the primary outcome was the weekly difference from baseline in the proportion of cocaine nonuse days; the secondary outcome was urinary cocaine-free weeks, and exploratory outcomes included craving and self- and observer-rated global functioning on the Clinical Global Impression scales. RESULTS Using an intent-to-treat analysis, topiramate was more efficacious than placebo at increasing the weekly proportion of cocaine nonuse days, irrespective of whether missing data were not or were imputed conservatively to the baseline value (13.3% vs 5.3%, 95% CI for the estimated mean difference, 1.4%-14.6%, P = .02 or 8.9% vs 3.7%, 95% CI for the estimated mean difference, 0.2%-10.1%, P = .04, respectively). Topiramate also was associated, significantly more than placebo, with increasing the likelihood of urinary cocaine-free weeks (16.6% vs 5.8%; odds ratio, 3.21; 95% CI, 1.24-8.32; P = .02), as well as decreasing craving and improving observer-rated global functioning (all P < .05). CONCLUSIONS AND RELEVANCE Topiramate is more efficacious than placebo at increasing the mean weekly proportion of cocaine nonuse days and associated measures of clinical improvement among cocaine-dependent individuals.

Effects of acute topiramate dosing on methamphetamine-induced subjective mood

Clinical studies have shown that topiramate, a sulphamate-substituted fructopyranose derivative, might be an efficacious treatment for alcohol dependence, smoking cessation within an alcohol-dependent population, and cocaine dependence. Mechanistically, topiramates therapeutic effects have been hypothesized to be due to inhibition of cortico-mesolimbic dopamine function, the primary substrate that governs the acquisition, maintenance, and reinstatement of goal-directed behaviour towards seeking abused drugs. Predicated on this hypothesis, we tested in 10 methamphetamine-dependent individuals (three females) whether low- or high-dose (15 or 30 mg i.v.) methamphetamine-induced positive subjective effects and reinforcement can be antagonized by low- or high-dose (100 or 200 mg orally) topiramate using a placebo-controlled, cross-over, factorial design. Methamphetamine administration was associated with orderly, prototypical, and significant increases on measures of stimulation, euphoria, craving, and reinforcement; however, some dysphoric symptoms also emerged. Topiramate alone showed a non-significant trend towards mild reductions in positive mood and reinforcement; yet topiramate appeared to accentuate the appreciation of methamphetamine-induced stimulation and euphoria significantly, but not craving or reinforcement. The experimental combination of topiramate and methamphetamine appeared to be safe and well tolerated, with few adverse events. Acute dosing with up to 200 mg topiramate appears to enhance, rather than attenuate, the positive subjective effects of methamphetamine. Perhaps this indicates a partial inhibition of methamphetamines reinforcing effects. Thus, testing chronically administered or higher doses, or both, of topiramate would be necessary to determine conclusively whether or not it can attenuate the positive subjective and reinforcing effects of methamphetamine.

Effects of Adjunctive Swedish Massage and Vibration Therapy on Short-Term Postoperative Outcomes: A Randomized, Controlled Trial

OBJECTIVE To examine the effects of adjunctive postoperative massage and vibration therapy on short-term postsurgical pain, negative affect, and physiologic stress reactivity. DESIGN Prospective, randomized controlled trial. The treatment groups were: (1) usual postoperative care (UC); (2) UC plus massage therapy; or (3) UC plus vibration therapy. SETTING The University of Virginia Hospital Surgical Units, Gynecology-Oncology Clinic, and General Clinical Research Center. SUBJECTS One hundred and five (N = 105) women who underwent an abdominal laparotomy for removal of suspected cancerous lesions. INTERVENTIONS All patients received UC with analgesic medication. Additionally, the massage group received standardized 45-minute sessions of gentle Swedish massage on the 3 consecutive evenings after surgery and the vibration group received 20-minute sessions of inaudible vibration therapy (physiotones) on the 3 consecutive evenings after surgery, as well as additional sessions as desired. OUTCOME MEASURES Sensory pain, affective pain, anxiety, distress, analgesic use, systolic blood pressure, 24-hour urine free cortisol, number of postoperative complications, and days of hospitalization. RESULTS On the day of surgery, massage was more effective than UC for affective (p = 0.0244) and sensory pain (p = 0.0428), and better than vibration for affective pain (p = 0.0015). On postoperative day 2, massage was more effective than UC for distress (p = 0.0085), and better than vibration for sensory pain (p = 0.0085). Vibration was also more effective than UC for sensory pain (p = 0.0090) and distress (p = .0090). However, after controlling for multiple comparisons and multiple outcomes, no significant differences were found. CONCLUSIONS Gentle Swedish massage applied postoperatively may have minor effects on short-term sensory pain, affective pain, and distress among women undergoing an abdominal laparotomy for removal of suspected malignant tissues.

Characteristics of adult primary care patients as predictors of future health services charges.

Background.Utilization risk assessment is potentially useful for allocation of health care resources, but precise measurement is difficult. Objective.Test the hypotheses that health-related quality of life (HRQOL), severity of illness, and diagnoses at a single primary care visit are comparable case-mix predictors of future 1-year charges in all clinical settings within a large health system, and that these predictors are more accurate in combination than alone. Research Design. Longitudinal observational study in which subjects’ characteristics were measured at baseline, and their outpatient clinic visits and charges and their inpatient hospital days and charges were tracked for 1 year. Subjects.Adult primary care patients. Measures.Duke Health Profile for HRQOL, Duke Severity of Illness Checklist for severity of illness, and Johns Hopkins Ambulatory Care Groups for diagnostic groups classification. Results.Of 1,202 patients, 84.4% had follow up in the primary care clinic, 63.2% in subspecialty clinics, 14.8% in the emergency room, and 9.6% in the hospital. Of

Detection of Coronary Stenoses at Rest With Myocardial Contrast Echocardiography

6,290,775 total charges,

Outcome of patients with acute coronary syndromes and moderate coronary lesions undergoing deferral of revascularization based on fractional flow reserve assessment.

779,037 (12.2%) was for follow-up primary care. The highest accuracy was found for predicting primary care charges, where R2 for predictors ranged from 0.083 for medical record auditor-reported severity of illness to 0.107 for HRQOL. When predictors were combined, the highest R2 of 0.125 was found for the combination of HRQOL and diagnostic groups. Conclusions.Baseline HRQOL, severity of illness, and diagnoses were comparable predictors of 1-year health services charges in all clinical sites but most predictive for primary care charges, and were more accurate in combination than alone.

Unobserved versus observed office buprenorphine/naloxone induction: A pilot randomized clinical trial

Background—We hypothesized that autoregulatory changes in arteriolar blood volume (aBV) that develop distal to a stenosis can be measured with myocardial contrast echocardiography, allowing coronary stenosis detection at rest without recourse to stress. Methods and Results—Patients with varying degrees of coronary artery stenosis on quantitative angiography underwent high-mechanical-index myocardial contrast echocardiography at 15 Hz to allow measurement of phasic changes in aBV in large intramyocardial vessels using either Definity (group 1; n=22) or Imagent (group 2; n=22). Progressive increases in the background-subtracted systolic/diastolic aBV signal ratio were noted between each level (none, mild [<50%], moderate [50% to 75%], and severe [>75%]) of stenosis severity for both group 1 (0.09±0.13, 0.13±0.08, 0.58±0.22, and 0.77±0.40; P<0.001) and group 2 (0.10±0.05, 0.27±0.18, 0.39±0.28, and 0.74±0.37; P<0.0001) patients. A systolic/diastolic aBV signal ratio of >0.34 provided a sensitivity and specificity of 80% and 71%, respectively, for the detection of >75% coronary stenosis in group 1 patients, whereas a ratio of >0.43 provided a sensitivity and specificity of 89% and 74%, respectively, for the detection of >75% stenosis in group 2 patients. Conclusions—Both the presence and severity of a physiologically significant coronary stenosis can be detected at rest by measuring the increase in aBV on myocardial contrast echocardiography that occurs distally to the stenosis without recourse to any form of stress.

Effects of topiramate on methamphetamine-induced changes in attentional and perceptual-motor skills of cognition in recently abstinent methamphetamine-dependent individuals

Objectives: To determine the outcome of consecutive patients with and without acute coronary syndromes (ACS) in whom revascularization was deferred on the basis of fractional flow reserve (FFR). Background: FFR < 0.75 correlates with ischemia on noninvasive tests and deferral of treatment on the basis of FFR is associated with low event rates in selected populations. Whether these low event rates apply to patients undergoing assessment of moderate stenoses in association with an ACS is not known and is an important clinical question. Methods: Retrospective analysis and 12 month follow‐up of consecutive, moderate (50–70%) de novo coronary lesions assessed with FFR. Results: Revascularization was deferred in 120 lesions (111 patients) with FFR ≥ 0.75. ACS was present in 35 patients (40 lesions). The clinical, angiographic and coronary hemodynamic characteristics of patients with and without ACS were similar. Among the 35 patients with ACS, there were 3 deaths, 1 MI, and 6 target vessel revascularizations (TVRs) (15% of lesions). Among the 76 patients without ACS, there were 5 deaths, 1 MI, and 7 TVRs (9% of lesions). Conclusions: Deferral of revascularization based on FFR in patients with ACS and moderate coronary stenoses is associated with acceptable and low event rates at 1 year.