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Karen C Johnston

Publications and source records attributed to Karen C Johnston.

At least 19 recordsLinked to original sources
PubMed2006

Relationship between 3-month National Institutes of Health Stroke Scale score and dependence in ischemic stroke patients.

BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS) provides a standardized measure of stroke severity and is frequently captured to assess 3-month outcome. Other outcome measures have been assessed for the relationship to dependence; a clinically relevant outcome. The relationship between NIHSS score and functional dependence is unknown. The purpose of this study was to assess the relationship between NIHSS score and accepted measures of dependence in surviving ischemic stroke patients. METHODS: 3-month NIHSS scores were compared to residence and Glasgow Outcome Scale (GOS) scores at 3 months in the Randomized Trial of Tirilazad Mesylate in Patients with Acute Stroke (RANTTAS). For residence, patients who were in a nursing home, chronic hospital or substantially dependent on a caregiver were characterized as 'dependent'. For GOS, a score of 3 (severely disabled) or 4 (vegetative) was characterized as 'dependent'. The sensitivity, specificity and positive (PPV) and negative predictive values (NPV) for various NIHSS score cut points compared to dependence were calculated. Logistic regression analysis was used to assess the association between the NIHSS score and dependence. RESULTS: In 385 subjects from the RANTTAS, an NIHSS score cut point of > or =15 resulted in 100% of subjects identified as being dependent by residence, sensitivity = 24%, specificity = 100%, PPV = 100% and NPV = 80%. Using GOS as the measure of dependence, the results were almost identical. NIHSS was strongly related to dependence with an area under the receiver operating characteristic curve (AUC) = 0.86 for residence and an AUC = 0.94 for GOS. CONCLUSIONS: 3-month NIHSS score is strongly associated with dependence. An NIHSS score of > or =15 at 3 months may be a reasonable estimate of subjects who are highly likely to be dependent at 3 months. These data require validation in an independent data set.

Activities of Daily Living↗
PubMed2005

Applying a phase II futility study design to therapeutic stroke trials.

BACKGROUND AND PURPOSE: Most large, randomized phase III efficacy trials of therapeutic agents in ischemic stroke have failed to find treatment benefit. We determined whether some phase III studies could have been avoided if preceded by smaller single-arm phase II studies to evaluate the futility of proceeding to phase III. METHODS: To provide examples of the application of phase II methodology, we obtained primary outcome data for the active treatment group of 6 phase III ischemic stroke therapy trials. For each study, we estimated the sample size number required for a multistage single-arm study using parameters specified in the original study. We evaluated outcome data for the first number of subjects in the phase III study treatment arm ordered by enrollment dates. We compared the proportion of favorable outcomes to prespecified stopping criteria derived from a single-arm phase II futility design. If the observed proportion of favorable outcomes was less than the stopping criterion, we declared the treatment not sufficiently effective to warrant further evaluation in phase III. RESULTS: We identified 3 trials as futile in phase II; none of 3 showed treatment efficacy in phase III. In the 3 remaining phase II trials in which we did not show futility, one showed efficacy in phase III. CONCLUSIONS: Single-arm phase II futility studies have been underused in stroke research, but provide a strategy for discarding treatments likely to be ineffective in phase III trials.

Clinical Trials as Topic↗
PubMed2005

A pilot dose-escalation safety study of tenecteplase in acute ischemic stroke.

BACKGROUND AND PURPOSE: Recombinant tissue-type plasminogen activator (rtPA) is the only approved treatment in acute ischemic stroke. However, intracerebral hemorrhage (ICH) occurs in 6.4% of patients treated with rtPA and limits its use. Tenecteplase (TNK) is a modified form of rtPA, with longer half-life and greater fibrin specificity. Patients after myocardial infarction had fewer systemic hemorrhages when treated with TNK compared with rtPA. This open-label, dose-escalation safety study was conducted to develop initial experience with TNK in the treatment of ischemic stroke. METHODS: Eligible patients were treated with an intravenous bolus infusion of TNK within 3 hours of stroke onset. The dose escalation was conducted in tiers of 25 patients, starting at 0.1 mg/kg, to a planned maximum of 0.6 mg/kg. The primary endpoint was symptomatic intracranial hemorrhage within 36 hours of treatment. All patients were followed-up for 3 months. RESULTS: Eighty-eight (88) patients were treated in 4 dosing tiers. In the first 3 tiers (0.1, 0.2, 0.4 mg/kg) of 25 patients each, no symptomatic and 2 (8%), 8 (32%), and 7 (28%) asymptomatic ICHs occurred. Enrollment into the fourth tier at 0.5 mg/kg was closed after 2 of 13 patients (15%) had symptomatic and 3 (23%) had asymptomatic ICHs. Overall, modified Rankin scores at 3 months were similar to those of historical controls treated with rtPA and not significantly different between treatment groups. CONCLUSIONS: TNK doses of 0.1 to 0.4 mg/kg are safe in ischemic stroke. Future trials are needed to compare the effect of TNK on neurological outcome and safety as compared with rtPA.

Aged↗
PubMed2004

Health care resource use after acute stroke in the Glycine Antagonist in Neuroprotection (GAIN) Americas trial.

BACKGROUND AND PURPOSE: To compare 3-month stroke outcomes and stroke-related health care resource use between the US and Canada in the Glycine Antagonist in Neuroprotection (GAIN) Americas study. Delivery of medical care for stroke patients, often driven by efforts to curb costs, varies substantially between countries. Data on the potential impact of these variations on clinical outcomes are sparse. METHODS: The analysis of health care resource included total length of stay (LOS) in hospital, intensive care unit (ICU), and acute-care ward or rehabilitation unit, or both; number of outpatient rehabilitation sessions and visits to a physician; place of residence after discharge; and employment status. Cox proportional hazards models and logistic regression were used to calculate survival hazards and predictors of favorable functional outcome (Barthel Index of 95 to 100). RESULTS: One thousand six hundred four patients who were independent before stroke (mean age: 69.9+/-12.7 years, 53% men, 85% ischemic stroke, 69% in the US) were included. Three-month survival and functional outcome did not differ between the US and Canada. Survival rate was 80% in both countries. Favorable functional outcome was achieved in 43% of Canadian and 47% of US patients. Fewer Canadian patients received treatment in ICU (19% versus 63% in the US), and Canadians had longer stays in hospital or rehabilitation facility (median: 33 days versus 16 days in the US). CONCLUSIONS: Despite similar 3-month survival and functional outcome, patterns of health care resource varied substantially between the US and Canada. US patients had more intensive early care; Canadian patients had longer hospitalizations and rehabilitation care. Further research is required to determine the most cost-effective treatment and rehabilitation plan for people who have a stroke.

Acute Disease↗
PubMed2004

Risk adjustment effect on stroke clinical trials.

BACKGROUND AND PURPOSE: The ischemic stroke population is heterogeneous. Even in balanced randomized trials, patient heterogeneity biases estimates of the treatment effect toward no effect when dichotomous end points are used. Risk adjustment statistically addresses some of the heterogeneity and can reduce bias in the treatment effect estimate. The purpose of this study was to estimate the treatment effect of tissue plasminogen activator (tPA) in the National Institute of Neurological Disorders and Stroke (NINDS) tPA data set with and without adjustment for baseline differences. METHODS: Using a prespecified predictive model, we calculated unadjusted and risk-adjusted odds ratios (ORs) for favorable outcome for the Barthel Index, National Institutes of Health Stroke Scale, and Glasgow Outcome Scale for the patients in the NINDS tPA stroke trial. To assess the importance of the difference, a new sample size was calculated through the use of the risk-adjusted analysis. RESULTS: We analyzed 615 subjects. The ORs for the Barthel Index were 1.76 (unadjusted) and 2.04 (adjusted). The National Institutes of Health Stroke Scale and Glasgow Outcome Scale analyses also demonstrated increased ORs after adjustment. The estimated sample size required for the adjusted comparison was 13% smaller than the unadjusted sample. CONCLUSIONS: Risk adjustment in this data set suggests that the true treatment effect was larger than estimated by the unadjusted analysis. Stroke clinical trials should include prospective risk adjustment methodologies.

Aged↗
PubMed2003

Predicting major neurological improvement with intravenous recombinant tissue plasminogen activator treatment of stroke.

BACKGROUND AND PURPOSE: In the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study, major neurological improvement within 24 hours (MNI) occurred significantly more frequently with recombinant tissue plasminogen activator (rtPA) treatment than with placebo. We explored the relationship between MNI and 3-month favorable outcome and sought clinical predictors of MNI. METHODS: Data from 312 rtPA-treated patients from the NINDS trial were used to assess the ability of MNI to predict favorable outcome at 3 months as defined by a modified Rankin Scale score of 0 to 1. Next, a multivariable predictive model was developed for MNI within the same data set. Clinical variables examined included age, time to treatment (TTT), diabetes, pretreatment glucose, baseline National Institutes of Health Stroke Scale score, pretreatment blood pressure, history of atrial fibrillation, weight >100 kg, and a dense artery sign. Finally, this model was used to forecast into the placebo group of the NINDS trial to assess the uniqueness of the predictors in the rtPA-treated group. RESULTS: MNI had a positive predictive value and negative predictive value of 0.70 for predicting favorable 3-month outcome. Only age [odds ratio (OR), 0.68; 95% confidence interval (CI), 0.47 to 0.99] and TTT (OR, 0.56; 95% CI, 0.34 to 0.91) appear to be independently associated with MNI. The model performed only moderately well (area under the receiver-operating characteristic curve, 0.66). Age (OR, 0.67; 95% CI, 0.45 to 0.99) but not TTT was associated with MNI in the placebo group. CONCLUSIONS: MNI may be a useful surrogate for thrombolytic activity and is predictive of favorable 3-month outcome. When rates of MNI in different populations of stroke patients treated with thrombolysis are compared, adjustments for age and TTT may be necessary.

Age Factors↗
PubMed2003

Predict Resident Exam Performance (PREP) study.

Predictive relationships between Resident Inservice Training Examination (RITE) performance and first-attempt success on American Board of Psychiatry and Neurology (ABPN) neurology examinations were assessed in board-eligible residents at the University of Virginia from 1988 to 1998. Third-year RITE results were predictive of success on the written ABPN examination, but they did not adequately predict success on the oral or on combined examinations. Residency programs should consider developing training tools that predict outcome on the oral ABPN examination.

Adult↗
PubMed2003

Teleradiology Assessment of Computerized Tomographs Online Reliability Study (TRACTORS) for acute stroke evaluation.

Telemedicine has potential to increase the use of tissue plasminogen activator (t-PA) for ischemic stroke and is increasingly offered to provide stroke expertise to remote and underserved areas. The accuracy of stroke neurologists' use of telemedicine to read head computed tomography scans (CT) has not been demonstrated. We sought to determine the validity and reliability of neurologists' reading of acute stroke head CTs via teleradiology. The pilot study compared stroke neurologists' reading of CTs via teleradiology to gold standard readings of hard copies on a view box. Head CTs obtained during consecutive acute evaluations for thrombolytic therapy between February and July 2001 were used. For this study, each stroke neurologist was masked to all prior readings, clinical decisions regarding thrombolysis eligibility, and the reading of the other study neurologist. Each neurologist read one-half of the CT scans using teleradiology and the other one-half using a view box. We used the official reading by a neuroradiologist for comparison. The kappa statistic measured reliability. Validity was measured by sensitivity and specificity. Sixty scans were used for the analysis. The neurologists identified the same four hemorrhages using teleradiology that they and the neuroradiologist identified using the light board. Compared to the readings on a view box, the kappa statistic for eligibility for thrombolysis via teleradiology was 1.0. Sensitivity was 100%, 95% CI = (0.93, 1.0); specificity was 100%, 95% CI = (0.40, 0.98) in both comparisons. This pilot study provides encouraging preliminary evidence that neurologists with stroke expertise can determine radiological intravenous t-PA eligibility via teleradiology. Further analysis in a larger sample is necessary to validate these results.

Adult↗
PubMed2003

Responding to the ACGME's competency requirements: an innovative instrument from the University of Virginia's neurology residency.

The general competencies mandated by the Accreditation Council for Graduate Medical Education (ACGME) Outcome Project have resulted in new training requirements for most residency programs. To determine the training program changes necessary because of these new standards, the neurology residency program at the University of Virginia developed a simple grid-like instrument that links the objectives for residents' major rotations with the six ACGME general competencies. This instrument, created in 2002, helped the program develop specific training elements related to the general competencies that were identified as missing from the residency. The instrument was then converted to an evaluation tool that allows attending physicians to assess individual residents' competencies for each objective in all major rotations. The author describes the assessment and evaluation instruments, called Self Assessment and Vital Evaluation (SAVE), and their usefulness in the University of Virginia neurology residency program's initial response to the new standards. She also suggests that these instruments, with some modifications, may be of value to other residency programs.

Accreditation↗
PubMed2003

Predicting outcome in ischemic stroke: external validation of predictive risk models.

BACKGROUND: Six multivariable models predicting 3-month outcome of acute ischemic stroke have been developed and internally validated previously. The purpose of this study was to externally validate the previous models in an independent data set. SUMMARY OF REPORT: We predicted outcomes for 299 patients with ischemic stroke who received placebo in the National Institute of Neurological Disorders and Stroke rt-PA trial. The model equations used 6 acute clinical variables and head CT infarct volume at 1 week as independent variables and 3-month National Institutes of Health Stroke Scale, Barthel Index, and Glasgow Outcome Scale as dependent variables. Previously developed model equations were used to forecast excellent and devastating outcome for subjects in the placebo tissue plasminogen activator data set. Area under the receiver operator characteristic curve was used to measure discrimination, and calibration charts were used to measure calibration. The validation data set patients were more severely ill (National Institutes of Health Stroke Scale and infarct volume) than the model development subjects. Area under the receiver operator characteristic curves demonstrated remarkably little degradation in the validation data set and ranged from 0.75 to 0.89. Calibration curves showed fair to good calibration. CONCLUSIONS: Our models have demonstrated excellent discrimination and acceptable calibration in an external data set. Development and validation of improved models using variables that are all available acutely are necessary.

Aged↗
PubMed2002

Combined clinical and imaging information as an early stroke outcome measure.

BACKGROUND AND PURPOSE: Imaging information has been proposed as a potential surrogate outcome in stroke clinical trials. The purpose of this study was to determine whether an early outcome measure combining clinical and imaging information is better than either alone in predicting 3-month outcome in acute ischemic stroke patients. METHODS: Clinical information (National Institutes of Health Stroke Scale) and imaging information (CT infarct volume), measured at 1 week from 201 patients from the Randomized Trial of Tirilazad Mesylate in Acute Stroke (RANTTAS) study, were used in a multivariable logistic regression analysis to predict excellent and devastating 3-month outcome. The combined models were compared with the infarct volume models and the clinical models. Discrimination, calibration, and change in global model chi-square were assessed. RESULTS: The combined models and models using clinical information alone had areas under the receiver operating characteristic curves that did not differ significantly (probability value = 0.092 to 0.4), ranging from 0.83 to 0.95. The imaging alone models performed less well (P<0.005) and had areas under the receiver operating characteristic curves that ranged from 0.70 to 0.80. CONCLUSIONS: The National Institutes of Health Stroke Scale at 1 week is highly predictive of 3-month outcome in ischemic stroke patients. The addition of 1-week infarct volume does not improve the accuracy of the predictive model.

Activities of Daily Living↗