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Biomedical subjects

S C Johnston

Publications and source records attributed to S C Johnston.

At least 19 recordsLinked to original sources
PubMed2003

Spinal manipulative therapy is an independent risk factor for vertebral artery dissection.

OBJECTIVE: To determine whether spinal manipulative therapy (SMT) is an independent risk factor for cervical artery dissection. METHODS: Using a nested case-control design, the authors reviewed all patients under age 60 with cervical arterial dissection (n = 151) and ischemic stroke or TIA from between 1995 and 2000 at two academic stroke centers. Controls (n = 306) were selected to match cases by sex and within age strata. Cases and controls were solicited by mail, and respondents were interviewed using a structured questionnaire. The medical records of interviewed patients were reviewed by two blinded neurologists to confirm that the patient had stroke or TIA and to determine whether there was evidence of arterial dissection. RESULTS: After interview and blinded chart review, 51 patients with dissection (mean age 41 +/- 10 years; 59% female) and 100 control patients (44 +/- 9 years; 58% female) were studied. In univariate analysis, patients with dissection were more likely to have had SMT within 30 days (14% vs 3%, p = 0.032), to have had neck or head pain preceding stroke or TIA (76% vs 40%, p < 0.001), and to be current consumers of alcohol (76% vs 57%, p = 0.021). In multivariate analysis, vertebral artery dissections were independently associated with SMT within 30 days (OR 6.62, 95% CI 1.4 to 30) and pain before stroke/TIA (OR 3.76, 95% CI 1.3 to 11). CONCLUSIONS: This case-controlled study of the influence of SMT and cervical arterial dissection shows that SMT is independently associated with vertebral arterial dissection, even after controlling for neck pain. Patients undergoing SMT should be consented for risk of stroke or vascular injury from the procedure. A significant increase in neck pain following spinal manipulative therapy warrants immediate medical evaluation.

Adult↗
PubMed2003

Prevalence and knowledge of transient ischemic attack among US adults.

BACKGROUND: Little information is available about public knowledge of TIA and prevalence of a TIA diagnosis. METHODS: The National Stroke Association sponsored a telephone survey by single-stage random-digit dialing of noninstitutionalized US residents > or =18 years old, which was conducted in 1999. Demographic characteristics of participants were compared to the US population to produce weights for projections. Independent predictors of knowledge and diagnosis of TIA were determined by including all demographic characteristics in logistic regression models. RESULTS: Among 10,112 participants, 2.3% reported having been told by a physician that they had a TIA. Older age, lower income, and fewer years of education were independently associated with a diagnosis of TIA. Of those with TIA, only 64% saw a physician within 24 hours of the event. A physician diagnosis of stroke was reported by 2.3% of participants, of whom 19% recalled having had a TIA before the stroke. An additional 3.2% of participants recalled symptoms consistent with TIA but did not seek medical attention. Only 8.2% correctly related the definition of TIA and 8.6% could identify a typical symptom. Men, nonwhites, and those with lower income and fewer years of education were less likely to be knowledgeable about TIA. CONCLUSIONS: An estimated 4.9 million people in the US report a diagnosis of TIA, and many more recall symptoms consistent with TIA but do not seek medical attention. Reducing stroke risk after TIA could have substantial impact on public health but will require public education about the importance of having stroke symptoms evaluated, even if they resolve.

Adolescent↗
PubMed2003

Distinguishing intracerebral hemorrhages caused by arteriovenous malformations.

BACKGROUND: There is a shortage of data addressing the clinical characteristics of patients with arteriovenous malformations (AVMs) who present with intracerebral hemorrhages (ICH). METHODS: A retrospective cohort study of members of a large, pre-paid health care program was conducted to identify factors that distinguish ICH secondary to cerebral AVMs from all other causes. Univariate and multivariate analysis was performed using Student's t test, Wilcoxon rank-sum test, and logistic regression. RESULTS: Patients with an underlying AVM were younger and more likely to be female, non-smokers with lower blood pressures, lower cholesterol, and lower white blood cell counts on presentation. CONCLUSIONS: These clinical characteristics may be useful in defining potential risk factors in future prospective studies as well as targeting candidates for additional imaging studies after ICH with no apparent etiology.

Adult↗
PubMed2002

Deaths from stroke in US children, 1979 to 1998.

BACKGROUND: Studies have documented declining mortality from stroke in adults over the past two decades, with black adults at greater risk of death from stroke than whites in all years. As these findings have been attributed to control of stroke risk factors that are less important in children, trends and demographics of childhood stroke mortality are of interest, but have not been explored. METHODS: The authors analyzed death certificate data for ischemic and hemorrhagic stroke (subarachnoid hemorrhage [SAH] and intracerebral hemorrhage [ICH]) in children under 20 years of age in the United States for the years 1979 through 1998, covering approximately 1.5 billion person-years. RESULTS: Childhood mortality from stroke declined by 58% overall, with reductions in all major subtypes (ischemic stroke decreased by 19%; SAH, by 79%; ICH, by 54%). Black ethnicity was a risk factor for mortality from all stroke types (relative risk 1.74 for ischemic stroke; 1.76 for SAH; 2.06 for ICH; p < 0.0001 for all types). Male sex was a risk factor for mortality from SAH (relative risk 1.30, p < 0.0001) and ICH (relative risk 1.21, p < 0.0001), but not from ischemic stroke (relative risk 1.02, p = 0.76). CONCLUSIONS: Mortality from stroke in US children has decreased dramatically over the last 20 years. Black children are at greater risk of death from all stroke types than are white children. As control of known stroke risk factors is unlikely to account for declining stroke mortality and ethnic differences in children, unrecognized stroke risk factors may be important.

Adolescent↗
PubMed2002

Incidence and mortality of generalized convulsive status epilepticus in California.

BACKGROUND: Few population-based studies of status epilepticus have been performed in the United States. OBJECTIVE: To determine the incidence, case fatality, and demographics of generalized convulsive status epilepticus (GCSE) in the state of California. METHODS: Using a state-wide hospital discharge database, the authors identified all hospitalizations from 1991 through 1998 with a discharge diagnosis of convulsive status epilepticus. They identified the first admission for each individual to estimate the incidence of GCSE. In-hospital case fatality rates were calculated, and multivariate analysis was performed to determine predictors of death during hospitalization. Secondary diagnoses were analyzed by retrieving all discharge diagnoses accompanying the diagnosis of GCSE. RESULTS: The incidence rate of GCSE was 6.2/100,000 population and fell by 42% between the years 1991 and 1998 from 8.5 to 4.9/100,000. The rate of GCSE was highest among children under the age of 5 (7.5/100,000) and among the elderly (22.3/100,000). Blacks also demonstrated a relatively high incidence of GCSE (13.4/100,000). The case fatality for incident admissions was 10.7%, with increasing age being the only significant predictor in multivariate analysis. Case fatality was highest in patients who also carried a diagnosis of anoxia, CNS infection, or stroke. CONCLUSIONS: The incidence of GCSE requiring hospitalization has fallen over the last decade and is lower than that reported in previous studies. The case fatality is also lower than that reported previously. Further studies are needed to determine the cause of this decline in incidence and mortality of GCSE.

Adolescent↗
PubMed2001

Chronic dyspnea and hyperventilation in an awake patient with small subcortical infarcts.

A 79-year-old woman presented with chronic dyspnea and hyperventilation. There was no evidence of pulmonary disease. Hyperventilation persisted during sleep and after high-dose administration of a narcotic. A head MRI revealed bilateral medial thalamic infarctions. Central neurogenic hyperventilation was diagnosed in this alert patient. The case may illustrate a role for the thalamus in regulating ventilation, but another small infarct not visible on MRI also could be responsible.

Aged↗
PubMed2001

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.

Aged↗
PubMed2001

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.

Age Distribution↗
PubMed2001

Arterial dissection and stroke in children.

OBJECTIVE: To describe the clinical characteristics of dissections of cerebral arteries in children. METHODS: Searches of MEDLINE (1966-2000) and bibliographies were systematically performed for English-language publications that described patients <18 years old with anterior circulation arterial dissections (ACAD) or posterior circulation arterial dissections (PCAD). RESULTS: A total of 2,027 studies were reviewed; 118 patients were identified in 79 studies. Seventy-four percent of patients with ACAD (n = 73) and 87% with PCAD (n = 47) were male (p < 0.0001). When patients with preceding trauma were excluded, this male predominance persisted. All patients had evidence of cerebral ischemia at the time of diagnosis. Headache was reported in approximately half of patients. Sixty percent of ACAD were intracranial. ACAD with no preceding trauma were more commonly intracranial than those preceded by significant trauma (86 vs 25%, p = 0.002). The most common location for PCAD was the vertebral artery at the level of the C1-C2 vertebral bodies (53%). Recurrent ischemic events after the diagnosis of dissection were reported in 15% of PCAD and 5% of ACAD cases. None of the PCAD group and 10% of the ACAD group had recurrent dissections. CONCLUSIONS: There is a marked male predominance among children with cerebral arterial dissections that is not explained by trauma. Unlike adult ACAD, childhood ACAD are most commonly intracranial. Spontaneous ACAD, in particular, tend to be intracranial, while post-traumatic ACAD are more often extracranial. The vertebral artery segment most susceptible to dissection is similar between children and adults.

Aortic Dissection↗
PubMed2001

Identifying confounding by indication through blinded prospective review.

Confounding by indication is a relentless threat to validity in observational studies of treatment effects. Multivariable models allow adjustment for known and readily measurable prognostic factors, but they may incompletely or inaccurately represent the underlying overall perceived risk of treatment. To incorporate practitioners' judgments about treatment indication and preprocedural prognosis into an observational study of cerebral aneurysm treatments, the author and colleagues presented patient characteristics and radiographic images from 179 aneurysm cases (University of California, San Francisco, 1990--1997) to panels of practitioners who were blinded as to actual treatment selection and outcome. In this way, the review process was designed to recreate the presentation of information in a prospective study. Judgments about inclusion and prognosis were reproducible. Perceived prognosis correlated with complication rates and provided information not present in a multivariable model including all available clinical characteristics. The association between treatment modality and outcome was examined while stratifying and adjusting for differences in perceived prognosis. Blinded prospective review may provide an unbiased observational study design with which to define a cohort that could have received any of the treatments being compared and to measure and adjust for overall perceived procedural risk.

Cohort Studies↗
PubMed2001

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.

Aneurysm, Ruptured↗
PubMed2001

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.

Adult↗
PubMed2001

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.

Academic Medical Centers↗
PubMed2001

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.

Academic Medical Centers↗
PubMed2000

Short-term prognosis after emergency department diagnosis of TIA.

CONTEXT: Management of patients with acute transient ischemic attack (TIA) varies widely, with some institutions admitting all patients and others proceeding with outpatient evaluations. Defining the short-term prognosis and risk factors for stroke after TIA may provide guidance in determining which patients need rapid evaluation. OBJECTIVE: To determine the short-term risk of stroke and other adverse events after emergency department (ED) diagnosis of TIA. DESIGN AND SETTING: Cohort study conducted from March 1997 through February 1998 in 16 hospitals in a health maintenance organization in northern California. Patients A total of 1707 patients (mean age, 72 years) identified by ED physicians as having presented with TIA. MAIN OUTCOME MEASURES: Risk of stroke during the 90 days after index TIA; other events, including death, recurrent TIA, and hospitalization for cardiovascular events. RESULTS: During the 90 days after index TIA, 180 patients (10.5%) returned to the ED with a stroke, 91 of which occurred in the first 2 days. Five factors were independently associated with stroke: age greater than 60 years (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.7; P=.01), diabetes mellitus (OR, 2.0; 95% CI, 1.4-2.9; P<.001), symptom duration longer than 10 minutes (OR, 2.3; 95% CI, 1.3-4.2; P=.005), weakness (OR, 1.9; 95% CI, 1.4-2.6; P<.001), and speech impairment (OR, 1.5; 95% CI, 1.1-2.1; P=.01). Stroke or other adverse events occurred in 428 patients (25.1%) in the 90 days after the TIA and included 44 hospitalizations for cardiovascular events (2.6%), 45 deaths (2.6%), and 216 recurrent TIAs (12.7%). CONCLUSIONS: Our results indicate that the short-term risk of stroke and other adverse events among patients who present to an ED with a TIA is substantial. Characteristics of the patient and the TIA may be useful for identifying patients who may benefit from expeditious evaluation and treatment.

Aged↗
PubMed2000

Charged residues dominate a unique interlocking topography in the heterodimeric cytokine interleukin-12.

Human interleukin-12 (IL-12, p70) is an early pro-inflammatory cytokine, comprising two disulfide-linked subunits, p35 and p40. We solved the crystal structures of monomeric human p40 at 2.5 A and the human p70 complex at 2.8 A resolution, which reveals that IL-12 is similar to class 1 cytokine-receptor complexes. They also include the first description of an N-terminal immunoglobulin-like domain, found on the p40 subunit. Several charged residues from p35 and p40 intercalate to form a unique interlocking topography, shown by mutagenesis to be critical for p70 formation. A central arginine residue from p35 projects into a deep pocket on p40, which may be an ideal target for a small molecule antagonist of IL-12 formation.

Arginine↗
PubMed2000

Ischemic stroke risk with oral contraceptives: A meta-analysis.

CONTEXT: The relationship between ischemic stroke and oral contraceptive (OC) use has been studied for 40 years, but disagreement about an association persists. OBJECTIVE: To review available literature to determine whether OC use is associated with increased stroke risk. DATA SOURCES: Studies published from January 1960 through November 1999 were identified from electronic databases (MEDLINE, BIOSIS, and Dissertation Abstracts Online), Index Medicus, bibliographies of pertinent review articles and pertinent original articles, textbooks, and expert consultation. STUDY SELECTION: From 804 potentially relevant references retrieved, 73 were studies investigating risk of ischemic stroke with OC use. Two reviewers independently applied the following inclusion criteria: more than 10 stroke cases sampled, clear stroke subtype differentiation, concurrent controls included, adequate data included to determine relative risks (RRs) and confidence intervals (CIs), analysis controlled for age, and no later publication of identical data. A third investigator adjudicated disagreements. Sixteen studies met all inclusion criteria and were included in the meta-analysis. DATA EXTRACTION: Two investigators independently extracted data, with disagreements resolved through discussion. DATA SYNTHESIS: The 16 studies were analyzed using random effects modeling. Current OC use was associated with increased risk of ischemic stroke (RR, 2.75; 95% CI, 2.24-3.38). Smaller estrogen dosages were associated with lower risk (P=.01 for trend), but risk was significantly elevated for all dosages. Studies that did not control for smoking (P=.01) and those using hospital-based controls (P<.001) found higher RRs, but no other patient characteristics or elements of study design were important. The summary RR was 1.93 (95% CI, 1.35-2.74) for low-estrogen preparations in population-based studies that controlled for smoking and hypertension. This translates to an additional 4.1 ischemic strokes per 100,000 nonsmoking, normotensive women using low-estrogen OCs, or 1 additional ischemic stroke per year per 24,000 such women. The RR of stroke due to OC use was not different in women who smoked, had migraines, or had hypertension. CONCLUSIONS: Summary results indicate that risk of ischemic stroke is increased in current OC users, even with newer low-estrogen preparations. However, the absolute increase in stroke risk is expected to be small since incidence is very low in this population. JAMA. 2000;284:72-78

Adult↗