Higher early recurrence risk and potential benefit of dual antiplatelet therapy for minor stroke with watershed infarction: subgroup analysis of CHANCE.

BACKGROUND AND PURPOSE: The aim was to explore the risk of early stroke recurrence within 3 months after watershed infarction and to investigate whether early dual antiplatelet therapy is more effective in decreasing such risk. METHODS: Patients enrolled in the Clopidogrel in High-risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial and who had acute infarction on diffusion-weighted imaging were included in this subgroup analysis. All magnetic resonance images were read centrally by two neurologists who were blinded to the patients' baseline and outcome information. The primary outcome was any stroke recurrence within 3 months. The hazard ratios were adjusted by known predictors of stroke recurrence. RESULTS: Of the 1089 patients with magnetic resonance imaging data enrolled in CHANCE, 834 (76.58%) patients had acute infarcts on diffusion-weighted imaging. The median and range of duration from randomization to stroke recurrence was 1.5 (1-6) days. Patients with watershed infarction had higher risk of stroke recurrence than those without (17.20% vs. 6.34%) within the first week after initial stroke; the hazard ratio (95% confidence interval) was 2.799 (1.536-5.101) adjusted by age, sex, smoking, body mass index, medical history, time to randomization, open-label aspirin dose at first day, single or dual antiplatelet therapy, National Institutes of Health Stroke Scale score at randomization, in-hospital treatment and white matter lesions, P < 0.001. There was no interaction between antiplatelet therapy and the presence of watershed infarction (P = 0.544). CONCLUSIONS: Minor stroke with watershed infarction has high recurrent risk in the first week. Dual antiplatelet therapy may be safely implemented, yet watershed infarction mechanisms of hypoperfusion and emboli may not be addressed.

Health-related quality of life in patients with myalgic encephalomyelitis/chronic fatigue syndrome: an Australian cross-sectional study.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and debilitating disorder associated with significant disruptions in daily life including. This study aimed to examine the impact of sociodemographic and patient symptom characteristics on health-related quality of life (HRQoL) of Australians with ME/CFS. METHODS: Self-reported data collected from 480 individuals diagnosed with ME/CFS were obtained between August 2014 and August 2018. This cross-sectional survey analysed sociodemographic, symptom characteristics and HRQoL according to the 36-Item Health Survey (SF-36). Multivariate linear regression models were used to determine ME/CFS symptoms associated with eight domains of HRQoL. RESULTS: Reported HRQoL was significantly impaired in ME/CFS patients across all domains compared with the general population. Scores were the lowest for physical role (4.11 ± 15.07) and energy/fatigue (13.54 ± 13.94). Associations with females, higher body mass index (BMI), employment status, cognitive difficulties, sensory disturbances and cardiovascular symptoms were observed in the physical functioning domain. Impaired pain domain scores were associated with high BMI, annual visits to their general practitioner, flu-like symptoms and fluctuations in body temperature. Reduced well-being scores were associated with smoking status, psychiatric comorbidity, cognitive difficulties, sleep disturbances and gastrointestinal difficulties. CONCLUSION: This study provides evidence that ME/CFS has a profound and negative impact on HRQoL in an Australian cohort.

Influence of smoking on CYP2C19 genetic variants and clopidogrel efficacy in patients with minor stroke or transient ischaemic attack.

BACKGROUND AND PURPOSE: Studies suggest that smoking affects clopidogrel efficacy. However, whether it influences the association between CYP2C19 genetic variants and clopidogrel efficacy is not clear. METHODS: In total, 2961 patients from the CHANCE trial were involved in this substudy and were successfully genotyped for two single-nucleotide polymorphisms of CYP2C19 (*2 and *3). The Cox proportional risk regression model was used to evaluate the interactions between CYP2C19*2 and CYP2C19*3 carrier status and clopidogrel efficacy stratified by smoking status. RESULTS: There were marginal significant interactions between CYP2C19*2 and CYP2C19*3 allele carrier status and antiplatelet treatment regimen for the risk of recurrent stroke and composite events (P = 0.054, P = 0.051, respectively) amongst smokers, but not in non-smokers. Amongst smokers, clopidogrel plus aspirin decreased the recurrence rate of stroke compared with aspirin alone in non-carriers (3.8% vs. 11.8%, hazard ratio 0.32, 95% confidence interval 0.15-0.65, P = 0.002), but not in carriers. Similar results were also found for the recurrence rate of composite events in smokers. No significant difference was found for hemorrhage events in any group. CONCLUSIONS: Amongst patients with minor stroke or transient ischaemic attack, marginal significant interactions between CYP2C19*2 and CYP2C19*3 allele carrier status and clopidogrel efficacy were found in smokers but not in non-smokers. Amongst smokers, clopidogrel plus aspirin might decrease the recurrence rate of stroke in non-carriers of *2 and *3 alleles of CYP2C19 compared with aspirin alone. However, caution should be taken to interpret our findings in view of several limitations in our study.

Oxidative lipoprotein markers predict poor functional outcome in patients with minor stroke or transient ischaemic attack.

BACKGROUND AND PURPOSE: Oxidative stress plays an important role in acute ischaemic stroke. However, the association of oxidative lipoprotein markers, including oxidized low-density lipoprotein (oxLDL), oxLDL:high-density lipoprotein (HDL) and oxLDL:low-density lipoprotein (LDL), with functional outcome of minor stroke or transient ischaemic attack (TIA) remains unclear. We aimed to investigate the association between oxidative lipoprotein markers and poor functional outcome in patients with minor stroke or TIA. METHODS: All patients with minor stroke or TIA were recruited from the Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) trial. The poor functional outcome included modified Rankin Scale (mRS) score 2-6 and 3-6 at 90-day and 12-month follow-up. Multivariate logistic regression was used to investigate the associations of oxLDL, oxLDL:HDL and oxLDL:LDL with poor functional outcome. RESULTS: Among 3019 patients included in this study, the median (interquartile range) oxLDL, oxLDL:HDL and oxLDL:LDL were 13.96 (6.65-28.81), 4.52 (2.08-9.32) and 11.73 (5.27-24.85) µg/dL, respectively. After adjusted for confounding factors, patients in the highest oxLDL quartile had a higher proportion of mRS score 2-6 at 90 days [hazard ratio (HR), 1.78; 95% confidence interval (CI), 1.26-2.52] and 12 months (HR, 1.42; 95% CI, 1.01-1.99), and mRS score 3-6 at 90 days (HR, 1.98; 95% CI, 1.29-3.04) and 12 months (HR, 1.77; 95% CI, 1.09-2.89) when compared with the lowest oxLDL quartile (P < 0.05). Similar results were found for oxLDL:HDL and oxLDL:LDL. CONCLUSIONS: Higher levels of oxidative lipoprotein markers are independent predictors of poor functional outcome in patients with minor stroke or TIA at 90 days and 12 months.

Experimental aerosolized guinea pig-adapted Zaire ebolavirus (variant: Mayinga) causes lethal pneumonia in guinea pigs.

Eight guinea pigs were aerosolized with guinea pig-adapted Zaire ebolavirus (variant: Mayinga) and developed lethal interstitial pneumonia that was distinct from lesions described in guinea pigs challenged subcutaneously, nonhuman primates challenged by the aerosol route, and natural infection in humans. Guinea pigs succumbed with significant pathologic changes primarily restricted to the lungs. Intracytoplasmic inclusion bodies were observed in many alveolar macrophages. Perivasculitis was noted within the lungs. These changes are unlike those of documented subcutaneously challenged guinea pigs and aerosolized filoviral infections in nonhuman primates and human cases. Similar to findings in subcutaneously challenged guinea pigs, there were only mild lesions in the liver and spleen. To our knowledge, this is the first report of aerosol challenge of guinea pigs with guinea pig-adapted Zaire ebolavirus (variant: Mayinga). Before choosing this model for use in aerosolized ebolavirus studies, scientists and pathologists should be aware that aerosolized guinea pig-adapted Zaire ebolavirus (variant: Mayinga) causes lethal pneumonia in guinea pigs.

Unruptured intracranial aneurysms: their illusive natural history and why subgroup statistics cannot provide normative criteria for clinical decisions or selection criteria for a randomized trial.

There is currently no evidence that treatment of unruptured aneurysms is beneficial. Confronted with the uncertainty, many clinicians are attracted by an individual calculus of risks using numbers extracted from subgroup statistics of observational studies or natural history data. The so-called natural history of unruptured aneurysms refers to a purely man-made ratio of events divided by the number of untreated patients identified by imaging, a ratio heavily influenced by referral patterns and arbitrary clinical decisions. Available studies lacked prespecified hypotheses, exposing all analyses to sampling error and bias, and sample sizes were too small to provide reliable subgroup statistics. Far from being "natural kinds" of aneurysms, subgroups were post-hoc creations. Resulting data-driven statistics can only be exploratory, the error too uncontrollable to serve for clinical decisions. A randomized trial is in order, but selection according to fixed size criteria is ill-advised, given the imprecision of imaging, the influence of other factors such as location, previous history, multiplicity of lesions, risks of treatment, age and the danger of arbitrarily excluding from a long trial a large segment of the population with aneurysms for whom the research question is most pertinent.

Trial on endovascular treatment of unruptured aneurysms (TEAM): study monitoring and rationale for trial interruption or continuation.

Preventive treatment of unruptured intracranial aneurysms is often performed but has never been proved beneficial as compared to conservative management. In a context of uncertainty, the 'best treatment' that can be offered to each individual is a chance to be treated and thus to be protected from rupture of the aneurysm, and an equal chance not to be treated, and hence to be exempted from possible immediate complications, using randomization. Such action is optimal unless or until an independent committee with privileged access to data judges that, given the comparative outcome of the 2 groups, preventive treatment or conservative management, is generally warranted. Potential reasons to interrupt such a study are reviewed, including insufficient recruitment, poor compliance, excessive cross-overs, unacceptable iatrogenia, and treatments being convincingly different or equivalent. We conclude that insufficient recruitment is the sole realistic event that could lead to premature interruption. This review may provide a deeper understanding of the principles justifying the necessity of the study.

Geographic Differences in Endovascular Treatment and Retreatment of Cerebral Aneurysms.

BACKGROUND AND PURPOSE: Comparing outcomes between endovascular aneurysm coiling trials can be difficult because of heterogeneity in patients and end points. We sought to understand the impact of geography on aneurysm retreatment in patients enrolled in the Matrix and Platinum Science Trial. MATERIALS AND METHODS: Post hoc analysis was performed on data from the Matrix and Platinum Science trial. Patients were stratified as either North American or international. Baseline patient demographics, comorbidities, aneurysm characteristics, procedural complications, and clinical and angiographic outcomes were compared. RESULTS: We evaluated 407 patients from 28 North American sites and 219 patients from 15 international sites. Patient demographics differed significantly between North American and international sites. Aneurysms were well occluded postprocedure more often at international than North American sites (P < .001). Stents were used significantly more often at North American sites (32.7% [133 of 407]) compared with international sites (10.0% [22 of 219]; P < .001). At 455 days, there was no difference in the proportion of patients alive and free of disability (P = .56) or with residual aneurysm filling (P = .10). Ruptured aneurysms were significantly more likely to have been retreated at North American sites within the first year (P < .001) and at 2 years (P < .001). Among all patients for whom the treating physician believed there to be Raymond 3 aneurysm filling at follow-up, absolute rates of retreatment at international and North American sites were similar by 2-year follow-up. CONCLUSIONS: Data from the Matrix and Platinum Science Trial demonstrate that aneurysm retreatment occurs with different frequency and at different times in different regions of the world. This trend has critical value when interpreting trials reporting short-term outcomes, especially when judgment-based metrics such as retreatment are primary end points that may or may not take place within the defined study follow-up period. Though these variations can be controlled for and balanced within a given randomized trial, such differences in practice patterns must be accounted for in any attempt to compare outcomes between different trials. Despite these differences, endovascular-treated intracranial aneurysms around the world have similar clinical outcomes.

Hormone therapy and the risk of stroke after acute myocardial infarction in postmenopausal women.

OBJECTIVES: We examined the association of hormone therapy (HRT) with hemorrhagic and ischemic stroke among postmenopausal women with acute myocardial infarction (AMI). BACKGROUND: Hemorrhagic and ischemic strokes are common complications of AMI, and women are at increased risk for hemorrhagic stroke after thrombolytic therapy. This risk may be related to female hormones. METHODS: Using data from the National Registry of Myocardial Infarction-3, we studied 114,724 women age 55 years or older admitted to the hospital for AMI, of whom 7,353 reported HRT use on admission. We determined rates of in-hospital hemorrhagic and ischemic stroke stratified by HRT use and estimated the independent association of HRT with each stroke type using multivariable logistic regression. RESULTS: The HRT users were younger than non-users, had fewer risk factors for stroke including diabetes and prior stroke, and received more pharmacologic and invasive therapy including cardiac catheterization. A total of 2,152 (1.9%) in-hospital strokes occurred, with 442 (0.4%) hemorrhagic, 1,017 (0.9%) ischemic and 693 (0.6%) unspecified. Among HRT users and non-users, the rates of hemorrhagic stroke (0.40% vs. 0.42%, p = 1.00) and ischemic stroke (0.80% vs. 0.96%, p = 0.11) were similar. Among 13,328 women who received thrombolytic therapy, the rate of hemorrhagic stroke was not significantly different for users and non-users (1.6% vs. 2.1%, p = 0.22). After adjustment for baseline and treatment differences, HRT was not associated with hemorrhagic (odds ratio [OR], 0.88; 95% confidence intervals [CI], 0.58 to 1.35) or ischemic stroke (OR, 0.89; CI, 0.66 to 1.18). CONCLUSIONS: Acute myocardial infarction is a high-risk setting for stroke among postmenopausal women, but HRT does not appear to modify that risk. Clinicians should not alter their approach to thrombolytic therapy based on HRT use.

The discussion about advance directives. Patient and physician opinions regarding when and how it should be conducted. End of Life Study Group.

BACKGROUND: Widely publicized court cases have focused national attention on the importance of advance directives. In spite of initiatives such as the Patient Self-Determination Act of 1991, fewer than 10% of Americans have prepared advance directives. One way to increase the preparation of advance directives may be to increase the frequency and quality of discussions about them between individual patients and their physicians. We performed a multicenter observational study to assess the opinions of primary care patients and physicians regarding these discussions. METHODS: This was a cross-sectional descriptive survey of randomly selected primary care patients and physicians in eight primary care internal medicine clinics in the eastern and midwestern United States. Quantitative questionnaires were used to elicit subjects' demographic characteristics, and their opinions regarding the timing, content, and location of discussions about advance directives. RESULTS: The 883 subjects included 329 adult outpatients, 282 resident physicians, and 272 practicing physicians. Physician and patient response rates were 75% and 76%, respectively. Patients felt that the discussion should occur earlier than did the physicians: at an earlier age, earlier in the natural history of disease, and earlier in the patient-physician relationship. Most subjects agreed it was the physician's responsibility to initiate the discussion. CONCLUSION: We defined a discrepancy between the preferences of primary care patients and physicians regarding the timing of the discussion about advance directives. We propose physician education regarding patient preferences as the most effective way to accomplish the goal of improving the frequency and quality of discussions about advance directives.

Evaluation of equilibrium constants for antigen-antibody interactions by solid-phase immunoassay: the binding of paraquat to its elicited mouse monoclonal antibody.

A procedure is devised for simple graphical evaluation of the association constant for antibody-antigen interactions from data obtained by conventional solid-phase immunoassay for antigen. Application of the method to situations involving a univalent antigen is illustrated by means of ELISA data for the interactions of paraquat with its elicited murine monoclonal antibody, and the Fab fragment derived therefrom. Although the completely general situation with both antibody and antigen multivalent is not amenable to study by the present procedure, the quantitative expression is readily modified to accommodate antigen multivalency provided that the univalent Fab fragment may be substituted for the multivalent antibody (IgG or IgM) as partitioning species in the solid-phase immunoassay.

The proteasome 11S regulator subunit REG alpha (PA28 alpha) is a heptamer.

Activity of the 20S proteasome, which performs much of the cytosolic and nuclear proteolysis in eukaryotic cells, is controlled by regulatory complexes that bind to one or both ends of the cylindrical proteasome. One of these complexes, the 11S regulator (REG), is a complex of 28 kDa subunits that is thought to activate proteasomes toward the production of antigenic peptides. REG, purified from red blood cells, is a complex of REG alpha and REG beta subunits. We have crystallized recombinant REG alpha (rREG alpha) and collected diffraction data to 3.0 A resolution. The self-rotation function indicates that rREG alpha forms a heptameric ring in the crystal. Equilibrium sedimentation demonstrates that rREG alpha is a heptamer in solution also.

Characteristics of academic medical centers and ischemic stroke outcomes.

BACKGROUND AND PURPOSE: Data supporting the efficacy of stroke center characteristics are limited. METHODS: A questionnaire detailing stroke treatment practices was sent to 42 academic medical centers in the University Health Systems Consortium. In-hospital mortality of all emergency department admissions for ischemic stroke at these institutions was evaluated in a database of discharge abstracts during 1997-1999. Institutional characteristics were evaluated as predictors of in-hospital mortality after adjustment for age, sex, race, hospital treatment volume of ischemic stroke, and admission status (emergent, urgent, elective). Length of stay (LOS), total hospital charges, and frequency of tissue plasminogen activator (tPA) administration were evaluated as secondary outcomes. We used a multivariable method called generalized estimating equations, which broadens confidence intervals to adjust for clustering of variables at institutions. RESULTS: Thirty-two institutions completed the questionnaire, and 29 of these were included in the database of discharge abstracts. In-hospital deaths occurred in 758 (7.0%) of the 10 880 ischemic stroke patients admitted through the emergency department. In-hospital deaths were less frequent at hospitals with a vascular neurologist (odds ratio [OR] 0.51; 95% CI, 0.36 to 0.74; P<0.0001) and at those with guidelines stating that only neurologists could administer tPA (OR, 0.65; 95% CI, 0.49 to 0.88; P=0.004). There was a trend toward fewer deaths at hospitals with a dedicated stroke team available by pager (OR, 0.76; 95% CI, 0.56 to 1.04; P=0.09). The presence of a dedicated neurological intensive care unit, stroke unit, and written clinical pathway for stroke were not significantly associated with in-hospital death. LOS was shorter at hospitals with a vascular neurologist (P=0.01). CONCLUSIONS: Academic medical centers with a vascular neurologist and those with written guidelines limiting tPA administration to neurologists had lower rates of in-hospital mortality for ischemic stroke patients.

The ICH score: a simple, reliable grading scale for intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) constitutes 10% to 15% of all strokes and remains without a treatment of proven benefit. Despite several existing outcome prediction models for ICH, there is no standard clinical grading scale for ICH analogous to those for traumatic brain injury, subarachnoid hemorrhage, or ischemic stroke. METHODS: Records of all patients with acute ICH presenting to the University of California, San Francisco during 1997-1998 were reviewed. Independent predictors of 30-day mortality were identified by logistic regression. A risk stratification scale (the ICH Score) was developed with weighting of independent predictors based on strength of association. RESULTS: Factors independently associated with 30-day mortality were Glasgow Coma Scale score (P<0.001), age >/=80 years (P=0.001), infratentorial origin of ICH (P=0.03), ICH volume (P=0.047), and presence of intraventricular hemorrhage (P=0.052). The ICH Score was the sum of individual points assigned as follows: GCS score 3 to 4 (=2 points), 5 to 12 (=1), 13 to 15 (=0); age >/=80 years yes (=1), no (=0); infratentorial origin yes (=1), no (=0); ICH volume >/=30 cm(3) (=1), <30 cm(3) (=0); and intraventricular hemorrhage yes (=1), no (=0). All 26 patients with an ICH Score of 0 survived, and all 6 patients with an ICH Score of 5 died. Thirty-day mortality increased steadily with ICH Score (P<0.005). CONCLUSIONS: The ICH Score is a simple clinical grading scale that allows risk stratification on presentation with ICH. The use of a scale such as the ICH Score could improve standardization of clinical treatment protocols and clinical research studies in ICH.

Treatment of unruptured cerebral aneurysms in California.

BACKGROUND AND PURPOSE: The impact of endovascular therapy on treatment outcomes of unruptured cerebral aneurysms has not been studied in a defined geographic area. METHODS: All primary diagnoses of unruptured aneurysms were retrieved from a statewide database of hospital discharges in California from January 1990 through December 1998. Admissions for initial treatment and all follow-up care were combined to reflect the entire course of therapy. An adverse outcome was defined as an in-hospital death or discharge to nursing home or rehabilitation hospital at any point during the treatment course. Multivariable analyses were performed with generalized estimating equations with adjustment for age, sex, ethnicity, source of admission, year of treatment, hospital volume, and clustering of observations at institutions. RESULTS: A total of 2069 patients were treated for unruptured aneurysms. Adverse outcomes were more frequent in the 1699 patients treated with surgery (25%) than in those treated with endovascular therapy (10%; P:<0.001). The difference persisted after multivariable adjustment (surgery versus endovascular therapy: odds ratio for adverse outcomes, 3.1; 95% CI, 2.5 to 4.0; P:<0.001). Adverse outcomes declined from 1991 to 1998 in patients treated with endovascular therapy (P:<0.005) but not for surgery. In-hospital deaths occurred in 3.5% of surgical cases and 0.5% of endovascular cases (P:=0.003), and the difference remained significant after adjustment (odds ratio, 6.3; 95% CI, 3.5 to 11.4; P:<0.001). Total length of stay and hospital charges were greater in surgical cases (both P:<0.001). Results were similar in a confirmatory analysis focusing on treatment differences between institutions. Institutional treatment volume was also associated with outcome but did not account for the differences between surgery and endovascular therapy. CONCLUSIONS: In California, endovascular therapy of unruptured aneurysms is associated with less risk of adverse outcomes and in-hospital death, lower hospital charges, and shorter hospital stays compared with surgery. Differences between therapies became more distinct through the years. Uncontrolled differences in prognosis of patients receiving endovascular therapy and surgery cannot be ruled out in this study of discharge abstracts.

C-reactive protein levels and viable Chlamydia pneumoniae in carotid artery atherosclerosis.

BACKGROUND AND PURPOSE: An elevated serum level of C-reactive protein, an inflammatory marker, is an independent predictor of stroke and coronary artery disease. To determine whether chronic infection with Chlamydia pneumoniae, which has been identified in atherosclerotic plaques, is responsible for systemic inflammation, we studied the association between serum C-reactive protein levels and infection of carotid artery atherosclerotic plaque with viable C pneumoniae. METHODS: Serum C-reactive protein levels were obtained before endarterectomy for carotid artery stenosis. Plaques were tested for C pneumoniae mRNA, an indicator of viability, and DNA by polymerase chain reaction of DNA and cDNA, respectively. RESULTS: Forty-eight samples were studied, of which 18 (38%; 95% CI, 23 to 50) were infected with viable C pneumoniae as evidenced by isolated chlamydial mRNA. All 18 of these samples, plus 1 additional sample, were positive for chlamydial DNA. Serum C-reactive protein levels were higher in those with viable C pneumoniae compared with those without infection (median, 8 mg/L versus undetectable; P=0.045 by Wilcoxon rank-sum test). In multivariable models, the only independent predictor of the presence of viable C pneumoniae was a detectable C-reactive protein level (odds ratio, 4.2; 95% CI, 1.1 to 17; P=0.04). CONCLUSIONS: Viable C pneumoniae are present in a substantial portion of carotid artery atherosclerotic plaques and are associated with increased serum C-reactive protein levels. These findings may explain the link between elevated C-reactive protein levels and the risk of cardiovascular disease and stroke but should be reproduced in a larger cohort.

Utilization of intravenous tissue-type plasminogen activator for ischemic stroke at academic medical centers: the influence of ethnicity.

BACKGROUND AND PURPOSE: We sought to measure the overall rate of usage of tissue-type plasminogen activator (tPA) for ischemic stroke at academic medical centers, and to determine whether ethnicity was associated with usage. METHODS: Between June and December 1999, 42 academic medical centers in the United States each identified 30 consecutive ischemic stroke cases. Medical records were reviewed and information on demographics, medical history, and treatment were abstracted. Rates of tPA use were compared for African Americans and whites in univariate analysis and after adjustment for age, gender, stroke severity, and type of medical insurance with multivariable logistic regression. RESULTS: Complete information was available for 1195 ischemic stroke patients; 788 were whites and 285 were African Americans: Overall, 49 patients (4.1%) received tPA. In the subgroup of 189 patients without a documented contraindication to therapy, 39 (20.6%) received tPA. Ten (20%) of those receiving tPA had documented contraindication. African Americans were one fifth as likely to receive tPA as whites (1.1% African Americans versus 5.3%; P=0.001), and the difference persisted after adjustment (OR 0.21, 95% CI 0.06 to 0.68; P=0.01). When comparison was restricted to those without a documented contraindication to tPA, the difference remained significant (OR 0.24, 95% CI 0.06 to 0.93; P=0.04). Medical insurance type was independently associated with tPA treatment. After adjustment for ethnicity and other demographic characteristics, those with Medicaid or no insurance were one ninth as likely to receive tPA as those with private medical insurance (OR 0.11, 95% CI 0.02 to 0.17; P=0.003). CONCLUSIONS: tPA is used infrequently for ischemic stroke at US academic medical centers, even among qualifying candidates. African Americans are significantly less likely to receive tPA for ischemic stroke. Contraindications to treatment do not appear to account for the difference.

Enhanced hepatotoxicity of acetaminophen in the alcoholic patient. Two case reports and a review of the literature.

We report 2 fatal cases of the acetaminophen-alcohol syndrome and review 51 reported cases in the medical literature. The MEDLINE database from January 1966 to December 1995 and bibliographies of selected articles were used to obtain the case reports. Inclusion criteria were a clear history of alcohol use, a history of acetaminophen use and/or an elevated serum acetaminophen level, peak aspartate aminotransferase (AST) greater than 800 U/L, and exclusion of other causes of hepatotoxicity by negative hepatitis serologies and/or a liver biopsy showing typical findings of acetaminophen toxicity. Demographic characteristics, clinical features, treatment, and outcome were extracted from reports meeting inclusion criteria and our own 2 cases. This syndrome affected relatively young, frequently healthy patients. Acetaminophen was invariably taken for nonsuicidal intent. The mortality rate was 32%. A typical laboratory picture was defined, characterized by an extraordinarily high AST level. Treatment with N-acetylcysteine was not effective due to delayed presentation and diagnosis. Patients who use alcohol and health care providers should be educated about this potentially fatal syndrome. Prevention is the key to reducing its occurrence.

The burden, trends, and demographics of mortality from subarachnoid hemorrhage.

OBJECTIVE: The objective of this study was to describe the recent epidemiology of mortality from subarachnoid hemorrhage in the United States. BACKGROUND: Subarachnoid hemorrhage is distinct from other forms of stroke in its risk factors, demographics, and treatment. However, it is often clustered with other stroke subtypes, obscuring its unique epidemiology. METHODS: We analyzed subarachnoid hemorrhage mortality data from the National Center for Health Statistics of the United States for the years 1979 to 1994 and compared it with other stroke subtypes. RESULTS: Age-adjusted mortality rates of subarachnoid hemorrhage were 62% greater in females than in males and 57% greater in blacks than in whites. The median age of death from subarachnoid hemorrhage was 59 years compared with 73 years for intracerebral hemorrhage and 81 years for ischemic stroke. Mortality rates of subarachnoid hemorrhage have decreased by approximately 1% per year since 1979, and the mean age of death has steadily increased from 57 years in 1979 to 60 years in 1994. Subarachnoid hemorrhage accounted for 4.4% of stroke mortality but 27.3% of all stroke-related years of potential life lost before age 65, a measure of premature mortality. The proportion of years of potential life lost due to subarachnoid hemorrhage was comparable with ischemic stroke (38.5%) and intracranial hemorrhage (34.2%). CONCLUSIONS: Subarachnoid hemorrhage is an uncommon cause of stroke mortality but occurs at a young age, producing a relatively large burden of premature mortality, comparable with ischemic stroke.

Surgical and endovascular treatment of unruptured cerebral aneurysms at university hospitals.

OBJECTIVE: To compare complications of surgical clipping and coil embolization in the treatment of unruptured aneurysms. BACKGROUND: Surgical clipping has been the preferred treatment for unruptured cerebral aneurysms but endovascular coil embolization is an increasingly employed alternative. No direct comparisons of the techniques are available to guide clinical decision making. METHODS: We performed a cohort study of patients treated for unruptured cerebral aneurysms at 60 university hospitals from January 1994 through June 1997 using the University HealthSystem Consortium database. The database was validated by chart review from one of the participant universities. The main outcome measures were in-hospital mortality and adverse outcomes, defined as in-hospital deaths and discharges to nursing homes or rehabilitation hospitals. RESULTS: The primary treatment modality was surgical in 2,357 cases and endovascular in 255 cases. Adverse outcomes were significantly more common in surgical cases (18.5%) compared to endovascular cases (10.6%) (p = 0.002), and the difference was not altered after adjusting for age, sex, race, transfer admissions, emergency room admissions, and year of treatment (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.4 to 3.3; p = 0.001). In-hospital mortality was also increased in surgical cases (2.3% versus 0.4%; p = 0.039), but the difference was not significant in the multivariable model (OR 6.3, 95% CI 0.9 to 46.1; p = 0.07). Length of stay and hospital charges were significantly greater for surgical cases (p < 0.0001 for each), and these differences were not affected by risk adjustment. CONCLUSION: Endovascular coil embolization resulted in fewer adverse outcomes than surgery for unruptured cerebral aneurysms treated at the university hospitals studied. Although these results should be seen as preliminary, the magnitude of difference and current predominance of surgery appear to justify a randomized trial.