Search PubMed⌕ Search

Biomedical subjects

R Kothari

Publications and source records attributed to R Kothari.

At least 19 recordsLinked to original sources
PubMed2006

Quality of hospital care in African American and white patients with ischemic stroke and TIA.

OBJECTIVE: To examine whether differences exist in the in-hospital diagnostic evaluation and treatment of African American and white patients with ischemic stroke (IS) and TIA. METHODS: The authors used a state-wide hospital-based stroke registry prototype designed to measure and track the quality of acute stroke care. Weighted descriptive statistics for each racial group are reported for the following variables, which were deemed to be potential confounders of the association between race and the quality of stroke care: age, gender, insurance status, emergency medical services arrival, functional status on presentation, modified Rankin score at discharge, stroke subtype, neurologist involved in care, and stroke pathway utilization. The magnitude and significance of the associations between race and each quality indicator of in-hospital acute stroke care were determined by separate multiple logistic regression models, adjusting for all potential confounding variables. RESULTS: Among patients admitted with IS and TIA who were alive at discharge (n = 1,837), 340 (18.5%) were African American and 1497 (81.5%) were white. After multivariate analysis, African Americans were less likely to have a door-to-CT time of less than 25 minutes (odds ratio [OR] 0.13 [CI 0.049 to 0.32]), obtain cardiac monitoring (OR 0.54 [CI 0.29 to 1.03]), undergo dysphagia screening (OR 0.69 [CI 0.50 to 0.95]), and receive smoking cessation counseling (OR 0.27 [CI 0.17 to 0.42]). CONCLUSIONS: Quality of hospital care for African American and white patients with acute ischemic stroke and TIA was similar in many respects. However, African Americans were less likely to receive a CT within 25 minutes of arrival, cardiac monitoring, dysphagia screening, and smoking cessation counseling.

Adolescent↗
PubMed2002

Age- and diet-related increase in transepithelial colon permeability of Fischer 344 rats.

When transepithelial permeability of rat distal colon is evaluated on the basis of transepithelial electrical resistance, age does not have an effect. Age likewise did not affect the decrease in resistance brought about by phorbol ester exposure. However, age was shown to correlate with increased transepithelial permeability when diffusion of the nonelectrolyte, D-mannitol, was used as an indicator. A phorbol ester-induced increase in transepithelial permeability to D-mannitol was observed to increase with age. Basal permeability to D-mannitol was significantly higher in older rats when the animals were allowed to age on a high-fat diet. Distance from the rectum was shown to be a potential complicating factor in these studies, since distal colon closer to the rectum was observed to have lower transepithelial permeability. The potential effect of such increased leakiness on the increased frequency of colon cancer in older individuals is discussed.

Aging↗
PubMed2001

Apolipoprotein E phenotype and the efficacy of intravenous tissue plasminogen activator in acute ischemic stroke.

We used stored plasma samples from 409 patients in the National Institute of Neurological Diseases and Stroke (NINDS) tissue plasminogen activator (t-PA) Stroke Trial to examine the relationship between an apolipoprotein (Apo) E2 or an Apo E4 phenotype and a favorable outcome 3 months after stroke, the risk of intracerebral hemorrhage, and the response to intravenous t-PA therapy. For the 27 patients with an Apo E2 phenotype who were treated with t-PA, the odds ratio (OR) of a favorable outcome at 3 months was 6.4 [95% confidence interval (CI) 2.7-15.3%] compared to the 161 patients without an Apo E2 phenotype who were treated with placebo. The 190 patients treated with t-PA who did not have an Apo E2 phenotype also had a greater, though less pronounced, likelihood of a favorable outcome (OR 2.0, 95% CI 1.2-3.2%) than patients without an Apo E2 phenotype treated with placebo. For the 31 patients with an Apo E2 phenotype treated with placebo, the OR of a favorable 3 month outcome was 0.8 (95% CI 0.4-1.7%) compared to the 161 patients without an Apo E2 phenotype treated with placebo. This interaction between treatment and Apo E2 status persisted after adjustment for baseline variables previously associated with 3 month outcome, for differences in the baseline variables in the two treatment groups and in the Apo E2-positive and -negative groups, and for a previously reported time-to-treatment x treatment interaction (p = 0.03). Apo E4 phenotype, present in 111 (27%) of the 409 patients, was not related to a favorable 3 month outcome, response to t-PA, 3 month mortality, or risk of intracerebral hemorrhage. We conclude that the efficacy of intravenous t-PA in patients with acute ischemic stroke may be enhanced in patients who have an Apo E2 phenotype, whereas the Apo E2 phenotype alone is not associated with a detectable benefit on stroke outcome at 3 months in patients not given t-PA. In contrast to prior studies of head injury and stroke, we could not detect a relationship between Apo E4 phenotype and clinical outcome.

Aged↗
PubMed2001

Greater Cincinnati/Northern Kentucky Stroke Study: volume of first-ever ischemic stroke among blacks in a population-based study.

BACKGROUND AND PURPOSE: The volume of ischemic stroke on CT scans has been studied in a standardized fashion in acute stroke therapy trials with median volumes between 10.5 to 55 cm(3). The volume of first-ever ischemic stroke in the population is not known. METHODS: The first phase of the population-based Greater Cincinnati/Northern Kentucky Stroke Study identified all ischemic strokes occurring in blacks in the greater Cincinnati region between January and June of 1993. The patients in this phase of the study who had a first-ever ischemic clinical stroke were identified, and the volume of ischemic stroke was measured. RESULTS: There were 257 verified clinical cases of ischemic stroke, of which 181 had a first-ever ischemic infarct. Imaging was available for 150 of these patients, and 79 had an infarct on the CT or MRI study that was definitely or possibly related to the clinical symptoms. For these patients, volumetric measurements were performed by means of the modified ellipsoid method. The median volume of first-ever ischemic stroke for the 79 patients was 2.5 cm(3) (interquartile range, 0.5 to 8.8 cm(3)). There was a significant relation between location of lesion and infarct size (P<0.001) and between volume and mechanism of stroke (P=0.001). CONCLUSIONS: The volume of first-ever ischemic stroke among blacks in our population-based study is smaller than has been previously reported in acute stroke therapy trials. The large proportion of small, mild strokes in blacks may be an important reason for the low percentage of patients who meet the inclusion criteria for tissue plasminogen activator. Further study is necessary to see if these results are generalizable to a multiracial population.

Acute Disease↗
PubMed2000

Finding the most powerful measures of the effectiveness of tissue plasminogen activator in the NINDS tPA stroke trial.

BACKGROUND AND PURPOSE: We sought to identify the most powerful binary measures of the treatment effect of tissue plasminogen activator (tPA) in the National Institute of Neurological Disorders and Stroke (NINDS) rTPA Stroke Trial. METHODS: Using the Classification and Regression Tree (CART) algorithm, we evaluated binary cut points and combination of binary cut points with the 4 clinical scales and head CT imaging measures in the NINDS tPA Stroke Trial at 4 times after treatment: 2 hours, 24 hours, 7 to 10 days, and 3 months. The first analysis focused on detecting evidence of "early activity" of tPA with the use of outcome measures derived from the 2-hour and 24-hour clinical and radiographic measures. The second analysis focused on longer-term outcome and "efficacy" and used outcome measures derived from 7- to 10-day and 3-month measures. After identifying the cut points with the ability to classify patients into the tPA and placebo groups using part I data from the trial, we then used data from part II of the trial to validate the results. RESULTS: Of the 5 most powerful outcome measures for early activity of tPA, 4 involved the National Institutes of Health Stroke Scale (NIHSS) score at 24 hours or changes in the NIHSS score from baseline to 24 hours. The best overall single outcome measure was an NIHSS score </=2 at 24 hours, which provided an odds ratio of 5.4 (95% CI, 2.4 to 12.1) and a projected sample size of 58 per treatment group assuming an alpha of 0.05 (2-sided test) and a power of 80% using part I data. The top 2 and 3 of the top 5 outcome measures for detecting the longer-term efficacy of tPA also involved the NIHSS score. A Rankin score of 0 or 1 at 3 months was the third most powerful outcome measure. Outcome measures identified by CART from part I data were not as sensitive in detecting the effectiveness of tPA when applied to part II data. CONCLUSIONS: Measures using the NIHSS and a Rankin score </=1 were the most sensitive discriminators of the effectiveness of tPA in the NINDS tPA Stroke Trial compared with the other clinical and radiological measures. The outcome measures identified in this exploratory analysis (eg, NIHSS score </=2 at 24 hours) would be best used as an outcome measure in future phase II trials of recanalization begun within the first 3 hours after stroke onset, with inclusion and exclusion criteria similar to those in the NINDS tPA Stroke Trial.

Algorithms↗
PubMed2000

Loss of estrogen receptor (ER) expression in endometrial tumors is not associated with de novo methylation of the 5' end of the ER gene.

Normal endometrium, an estrogen-responsive tissue, expresses the estrogen receptor (ER) alpha gene. Loss of ER expression, the basis for which is currently unknown, is often seen in advanced stage, poor prognosis endometrial tumors. The ER gene undergoes de novo methylation with high frequency in a wide variety of human tumors, including ER-negative breast cancers. In this study, we used several bisulfite-based detection methods to assess whether loss of ER positivity in endometrial tumors is associated with aberrant methylation of the ER gene. Although extensive methylation of a 600-bp region at the 5' end of the gene was seen in two endometrial carcinoma cell lines, none of the 55 CpGs in this region was methylated in 25 of 26 ER-deficient endometrial carcinomas.

Adult↗
PubMed1999

Acute stroke: delays to presentation and emergency department evaluation.

STUDY OBJECTIVE: To document prehospital and inhospital time intervals from stroke onset to emergency department evaluation and to identify factors associated with presentation to the ED within 3 hours of symptom onset, the current time window for thrombolytic therapy. METHODS: Patients admitted through the ED with a diagnosis of stroke were identified through admitting logs. Time intervals were obtained from EMS runsheets and ED records. Information regarding first medical contact, education, and income was obtained by patient interview. Baseline variables were analyzed to assess association with ED arrival within 3 hours of symptom onset; variables significant on univariate analysis were placed in a multivariable model. RESULTS: There were 151 stroke patients (59% white and 41% black). Time of stroke onset and time to ED arrival were documented for 119 patients (79%). The median time from stroke onset to ED arrival was 5.7 hours; 46 patients (30%) presenting within 3 hours. Of those with times recorded, the median time from stroke onset to EMS arrival was 1.7 hours. Multivariable logistic regression identified use of EMS (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.3 to 12.1) and white race (OR, 3.5; 95% CI, 1.3 to 10) as being independently associated with ED arrival within 3 hours of symptom onset. Median time from ED arrival to physician evaluation was 20 minutes. Median time from ED arrival to computed tomographic evaluation was 72 minutes. When patients were asked the main reason they sought medical attention, 40% (60/141) of those able to be interviewed said that they themselves did not decide to seek medical attention, but rather a friend or family member told them they should go to the hospital. CONCLUSION: The median time from stroke onset to ED evaluation was 5.7 hours, with almost a third of patients presenting within 3 hours. Use of EMS and white race were independently associated with arrival within 3 hours.

Acute Disease↗
PubMed1999

Underlying structure of the National Institutes of Health Stroke Scale: results of a factor analysis. NINDS tPA Stroke Trial Investigators.

BACKGROUND AND PURPOSE: No stroke scale has been validated as an outcome measure using data from a clinical trial demonstrating a positive therapeutic effect. Therefore, we proposed to use data from the National Institute of Neurological Disorders and Stroke (NINDS) tPA Stroke Trial to determine whether the National Institutes of Health Stroke Scale (NIHSS) was valid in patients treated with tissue plasminogen activator (tPA) and to explore the underlying clinimetric structure of the NIHSS. METHODS: We performed an exploratory factor analysis of NIHSS data from Part 1 (n=291) of the NINDS tPA Stroke Trial to derive a hypothesized underlying factor structure. We then performed a confirmatory factor analysis of this structure using NIHSS data from Part 2 of the same trial (n=333). We then tested whether this final factor structure could be found in tPA- and placebo-treated patients serially over time after stroke treatment. Using 3-month outcome data, we tested for an association between the NIHSS and other measures of stroke outcome. RESULTS: The exploratory analysis suggested that there were 2 factors underlying the NIHSS, representing left and right brain function, confirming the content validity of the scale. An alternative structure composed of 4 factors could be derived, with a better goodness of fit: the first 2 factors could represent left brain cortical and motor function, respectively, and the second 2 factors could represent right brain cortical and motor function, respectively. The same factor structures were then found in tPA and placebo patient groups studied serially over time, confirming the exploratory analysis. All 3-month clinical outcomes were associated with each other at subsequent time points, confirming predictive validity. CONCLUSIONS: This is the first study of the validity of a stroke scale in patients treated with effective stroke therapy. The NIHSS appeared to be valid in patients with acute stroke and for finding treatment-related differences. The scale was valid when used serially over time after stroke, up to 3 months, and showed good agreement with other measures of outcome.

Brain↗
PubMed1999

Incidence rates of first-ever ischemic stroke subtypes among blacks: a population-based study.

BACKGROUND AND PURPOSE: The aim of this study was to determine the incidence rates of ischemic stroke subtypes among blacks. METHODS: Hospitalized and autopsied cases of stroke and transient ischemic attack among the 187 000 blacks in the 5-county region of greater Cincinnati/northern Kentucky From January 1, 1993, through June 30, 1993, were identified. Incidence rates were age- and sex-adjusted to the 1990 US population. Subtype classification was performed after extensive review of all available imaging, laboratory data, clinical information, and past medical history. Case-control comparisons of risk factors were made with age-, race-, and sex-matched control subjects. RESULTS: Annual incidence rates per 100 000 for first-ever ischemic stroke subtypes among blacks were as follows: uncertain cause, 103 (95% confidence interval [CI], 80 to 126); cardioembolic, 56 (95% CI, 40 to 73); small-vessel infarct, 52 (95% CI, 36 to 68); large vessel, 17 (95% CI, 8 to 26); and other causes, 17 (95% CI, 9 to 26). Of the patients diagnosed with an infarct of uncertain cause, 31% underwent echocardiography, 45% underwent carotid ultrasound, and 48% had neither. Compared with age-, race-, and sex- (proportionally) matched control subjects from the greater Cincinnati/northern Kentucky region, the attributable risk of hypertension for all causes of first-ever ischemic stroke is 27% (95% CI, 7 to 43); for diabetes, 21% (95% CI, 11 to 29); and for coronary artery disease, 9% (95% CI, 2 to 16). For small-vessel ischemic stroke, the attributable risk of hypertension is 68% (95% CI, 31 to 85; odds ratio [OR], 5.0), and the attributable risk of diabetes is 30% (95% CI, 10 to 45; OR, 4.4). For cardioembolic stroke, the attributable risk of diabetes is 25% (95% CI, 4 to 41; OR, 3.1). CONCLUSIONS: Stroke of uncertain cause is the most common subtype of ischemic stroke among blacks. Cardioembolic stroke and small-vessel stroke are the most important, identifiable causes of first-ever ischemic stroke among blacks. The incidence rates of cardioembolic and large-vessel stroke are likely underestimated because noninvasive testing of the carotid arteries and echocardiography were not consistently obtained in stroke patients at the 18 regional hospitals. Most small-vessel strokes in blacks can be attributed to hypertension and diabetes.

Black or African American↗
PubMed1999

Agreement and variability in the interpretation of early CT changes in stroke patients qualifying for intravenous rtPA therapy.

BACKGROUND AND PURPOSE: Ischemic changes identified on CT scans performed in the first few hours after stroke onset, which are thought to possibly represent early cytotoxic edema and development of irreversible injury, may have important implications for subsequent treatment. However, insecurity and conflicting data exist over the ability of clinicians to correctly recognize and interpret these changes. We performed a detailed review of selected baseline CT scans from the NINDS rt-PA Stroke Trial to test agreement among experienced stroke specialists and other physicians on the presence of early CT ischemic changes. METHODS: Seventy baseline CT scans from the NINDS Stroke Trial were read and classified for the presence or absence of various early findings of ischemia by 16 individuals, including NINDS trial investigators, other neurologists, other emergency medicine physicians, and radiology or stroke fellows. CT scans included normal scans and scans from patients who later developed symptomatic intracranial hemorrhage, as well as scans on which the NINDS rt-PA Stroke Trial neuroradiologist identified clear-cut early CT changes. For each CT finding, kappa-statistics were used to assess the proportion of agreement beyond chance. RESULTS: kappa-Values (95% confidence interval [CI]) ranged from 0.20 (-0.20, 0.61) (fair agreement) to 0.41 (0.37, 0.45) (moderate agreement) among the 16 viewers, and the kappa-value was only 0.39 (0.29, 0.49) (fair) in answer to the question "do early CT changes involve more than one third of the MCA [middle cerebral artery] territory?" There was substantial variability within each specialty group and between groups. kappa-Values were only fair to moderate even among physicians experienced in selecting and treating acute stroke patients with rtPA. Observed agreement ranged from 68% to 85%. Physicians agreed on the finding of early CT changes involving >33% of the MCA territory 77% of the time, although the kappa-value of 0.39 suggested only moderate agreement beyond chance. CONCLUSIONS: There is considerable lack of agreement, even among experienced clinicians, in recognizing and quantifying early CT changes. Improved methods of recognizing and quantifying early ischemic brain damage are needed.

Cerebrovascular Disorders↗
PubMed1999

Early surgical treatment for supratentorial intracerebral hemorrhage: a randomized feasibility study.

BACKGROUND AND PURPOSE: The safety and the effectiveness of the surgical treatment of spontaneous intracerebral hemorrhage (ICH) remain controversial. To investigate the feasibility of urgent surgical evacuation of ICH, we conducted a small, randomized feasibility study of early surgical treatment versus current nonoperative management in patients with spontaneous supratentorial ICH. METHODS: Patients with spontaneous supratentorial ICH who presented to 1 university and 2 community hospitals were randomized to surgical treatment or best medical treatment. Principal eligibility criteria were ICH volume >10 cm(3) on baseline CT scan with a focal neurological deficit, Glasgow Coma Scale score >4 at the time of enrollment, randomization and therapy within 24 hours of symptom onset, surgery within 3 hours of randomization, and no evidence for ruptured aneurysm or arteriovenous malformation. The primary end point was the 3-month Glasgow Outcome Scale (GOS). A good outcome was defined as a 3-month GOS score >3. RESULTS: Twenty patients were randomized over 24 months, 9 to surgical intervention and 11 to medical treatment. The median time from onset of symptoms to presentation at the treating hospitals was 3 hours and 17 minutes, the time from randomization to surgery was 1 hour and 20 minutes, and the time from onset of symptoms to surgery was 8 hours and 35 minutes. The likelihood of a good outcome (primary outcome measure: GOS score >3) for the surgical treatment group (56%) did not differ significantly from the medical treatment group (36%). There was no significant difference in mortality at 3 months. Analysis of the secondary 3-month outcome measures showed a nonsignificant trend toward a better outcome in the surgical treatment group versus the medical treatment group for the median GOS, Barthel Index, and Rankin Scale and a significant difference in the National Institutes of Health Stroke Scale score (4 versus 14; P=0.04). CONCLUSIONS: Very early surgical treatment for acute ICH is difficult to achieve but feasible at academic medical centers and community hospitals. The trend toward less 3-month morbidity with surgical intervention in patients with spontaneous supratentorial ICH warrants further investigation of very early clot removal in larger randomized clinical trials.

Cerebellar Diseases↗
PubMed1999

Immunophenotypic diagnosis of acute leukemia by using decision tree induction.

We describe a model for decision making for bone marrow immunophenotypic analysis of acute leukemia. In this study, we used decision tree induction as an information processing system for the analysis of flow cytometry immunophenotype results of bone marrow specimens obtained for the diagnosis of acute leukemia. By using decision tree analysis, we queried which antibodies and at what percentage cut-offs led to particular diagnoses. Flow cytometry results of up to 27 monoclonal antibodies from bone marrow specimens of 175 adult and pediatric cases were used: acute lymphoblastic leukemia (n = 80), myeloid leukemia (n = 44), mixed lineage (n = 16), and reactive marrow (n = 35). The percentage of positive cells was used as input data, and the diagnoses were used as output of the information processing system. Results of the decision tree showed an easy, accurate, and intuitive algorithm that can delineate a hierarchy of antibodies relevant to diagnosis. A correct discrimination of acute myeloid and lymphoid leukemia from benign bone marrow can be inferred by using the results of four to eight from a panel of up to 27 antibodies with an accuracy of 95%. Here, we describe a computer-aided model that uses decision tree induction applied to flow cytometry immunophenotype data. If generalizable, this technique may be an alternative approach to modeling complex information like that seen in hematopathology and may complement the immunologist's interpretation, along with cytochemistry and morphology results, in the diagnosis of acute leukemia.

Acute Disease↗
PubMed1998

Retinol and retinoic acid bind to a surface cleft in bovine beta-lactoglobulin: a method of binding site determination using fluorescence resonance energy transfer.

Two potential ligand binding sites in the lipocalin beta-lactoglobulin have been postulated for small hydrophobic molecules such as retinol or retinoic acid. An agreement on one of the two alternatives, an interior cavity or a surface cleft, however, has not been achieved. In order to discriminate between these two possibilities, we measured the efficiency of fluorescence resonance energy transfer between the two intrinsic Trp-residues of beta-lactoglobulin and the ligands retinol, retinoic acid and bis-ANS. Using the crystallographic coordinates of beta-lactoglobulin, this efficiency could be accurately computed for both the interior cavity and the surface cleft as ligand binding sites. For the surface cleft, the theoretical value was found to be in excellent agreement with the measured value, whereas for the interior cavity any reasonable agreement would require a dramatic ligand-induced conformational change that can be ruled out due to the protein's known structural stability. Our conclusion that these ligands bind to the surface pocket rather than the interior cavity was further confirmed by competitive binding studies.

Animals↗
PubMed1998

State-dependent weights for neural associative memories.

In this article we study the effect of dynamically modifying the weight matrix on the performance of a neural associative memory. The dynamic modification is implemented by adding, at each step, the outer product of the current state, scaled by a suitable constant eta, to the correlation weight matrix. For single-shot synchronous dynamics, we analytically obtain the optimal value of eta. Although knowledge of the noise percentage is required for calculating the optimal value of eta, a fairly good choice of eta can be made even when the amount of noise is not known. Experimental results are provided in support of the analysis. The efficacy of the proposed modification is also experimentally verified for the case of asynchronous updating with transient length > 1.

Association Learning↗
PubMed1998

The Greater Cincinnati/Northern Kentucky Stroke Study: preliminary first-ever and total incidence rates of stroke among blacks.

BACKGROUND AND PURPOSE: The Greater Cincinnati/Northern Kentucky Stroke Study was designed to be the first large, population-based metropolitan study of temporal trends in stroke incidence rates and outcome within a biracial population. METHODS: We are identifying all hospitalized and autopsied cases of stroke and transient ischemic attack (TIA) among the 1.3 million inhabitants of a five-county region of Greater Cincinnati/Northern Kentucky for the period 7/1/93-6/30/94. We have already prospectively monitored for out-of-hospital stroke and TIAs for this same time period at 128 screening sites, including a random sample of all primary care physicians and nursing homes in the region. We have already identified all hospitalized and autopsied cases of stroke and TIA among blacks for 1/1/93-6/30/93 and report preliminary incidence rates for this 6-month period. RESULTS: The overall incidence rate for all first-ever hospitalized or autopsied stroke (excluding TIAs) among blacks in the Greater Cincinnati region was 288 per 100000 (95% CI, 250 to 325, age- and sex-adjusted to 1990 US population). The overall incidence rate for first-ever and recurrent stroke (excluding TIAs) was 411 per 100000 (95% CI, 366 to 456). By comparison, the overall incidence rate of first-ever stroke among whites in Rochester, Minn, during the period 1985-1989 was 179 per 100000 (95% CI, 164 to 194, age- and-sex adjusted to 1990 US population). The incidence rates among blacks in Greater Cincinnati were substantially greater than the rates among whites in Rochester, Minn, for all age categories except ages 75 and older, for which the rates were similar. CONCLUSIONS: We conservatively estimate that 731100 first-ever or recurrent strokes occurred in the United States during 1996. Studies of first-ever as well as total stroke among biracial and representative populations are critical for understanding temporal trends in the incidence rate and the burden of stroke in the US population.

Adult↗
PubMed1998

Hypertension and its treatment in the NINDS rt-PA Stroke Trial.

BACKGROUND AND PURPOSE: We examined the frequency, course, and treatment of hypertension in the NINDS rt-PA Stroke Trial. METHODS: Blood pressure (BP) was measured at the time of admission, at randomization, and then 36 times during the first 24 hours after randomization. Patients with a systolic BP of >185 mm Hg and a diastolic BP of >110 mm Hg at admission were defined as hypertensive before randomization, and those with a systolic BP of >180 mm Hg or a diastolic BP of >105 mm Hg within the first 24 hours after randomization were defined as hypertensive after randomization. Standardized clinical assessments were conducted at 24 hours and at 3 months. Post hoc analyses were conducted to evaluate the association of antihypertensive therapy with clinical outcomes. RESULTS: Of the 624 patients, 121(19%) had hypertension on admission and 372 (60%) had hypertension in the 24 hours after randomization. The use of antihypertensive therapy before randomization (tPA 9%, placebo 9%) and after randomization (tPA 24%, placebo 29%) was similar between placebo- and tPA-treated patients. No adverse effects of prerandomization antihypertensive therapy on 3-month favorable outcome were detected for either the placebo- or tPA-treated groups. For placebo patients with hypertension in the 24 hours after randomization, clinical outcome measures were similar for those patients who did and did not receive antihypertensive therapy after randomization (P > or = 0.26); antihypertensive therapy was not associated with declines in BP (P = 0.44) or with abrupt declines (P = 0.14). Those tPA patients who were hypertensive after randomization and received antihypertensive therapy were less likely to have a favorable outcome at 3 months (P < 0.01) than those who were hypertensive and did not receive antihypertensive therapy. CONCLUSIONS: The frequency of hypertension and the use of antihypertensive therapy were similar between the tPA and placebo groups in the NINDS rt-PA Stroke Trial. In the placebo group, antihypertensive therapy was not associated with less favorable outcomes at 3 months; postrandomization antihypertensive therapy was associated with less favorable outcomes for the tPA patients who were hypertensive. However, because of the nonrandomized use of antihypertensive therapy and the many post hoc comparisons leading to type 1 errors, the significance of this observation is unclear. Careful attention to BP and gentle management remain warranted for stroke patients treated with tPA.

Antihypertensive Agents↗