Oxygen for relief of dyspnoea in mildly- or non-hypoxaemic patients with cancer: a systematic review and meta-analysis.

The aim of this study was to determine the efficacy of palliative oxygen for relief of dyspnoea in cancer patients. MEDLINE and EMBASE were searched for randomised controlled trials, comparing oxygen and medical air in cancer patients not qualifying for home oxygen therapy. Abstracts were reviewed and studies were selected using Cochrane methodology. The included studies provided oxygen at rest or during a 6-min walk. The primary outcome was dyspnoea. Standardised mean differences (SMDs) were used to combine scores. Five studies were identified; one was excluded from meta-analysis due to data presentation. Individual patient data were obtained from the authors of the three of the four remaining studies (one each from England, Australia, and the United States). A total of 134 patients were included in the meta-analysis. Oxygen failed to improve dyspnoea in mildly- or non-hypoxaemic cancer patients (SMD=-0.09, 95% confidence interval -0.22 to 0.04; P=0.16). Results were stable to a sensitivity analysis, excluding studies requiring the use of imputed quantities. In this small meta-analysis, oxygen did not provide symptomatic benefit for cancer patients with refractory dyspnoea, who would not normally qualify for home oxygen therapy. Further study of the use of oxygen in this population is warranted given its widespread use.

Cost of multiple sclerosis by level of disability: a review of literature.

We performed a review of the economic literature to identify what is known about the relationship between Expanded Disability Status Scale (EDSS) categories and cost of multiple sclerosis (MS). We sought cohort studies of patients with multiple sclerosis that described the costs attributed to each EDSS score and utilized specific inclusion criteria for the selection of 10 studies. We found that both direct and indirect costs rise continuously with increasing EDSS category, and this rise is qualitatively exponential. The rise in indirect costs appears at lower EDSS scores. The cost of a relapse occurring in any given EDSS category exceeds that associated with that particular EDSS category. Few studies comprehensively assessed the entire spectrum of the costs, and much of the literature is based on EDSS categories in coarse groupings. In spite of several variations between studies, one important conclusion that we can draw is that rise in cost is positively correlated to scores on the EDSS categories, and therefore agents with a capacity to prevent or arrest the rate of MS progression may affect the overall cost of MS.

VA Stroke Study: neurologist care is associated with increased testing but improved outcomes.

OBJECTIVE: VA Stroke Study (VASt) data were analyzed to determine whether neurologist management affected the process and outcome of care of patients with ischemic stroke. METHODS: VASt prospectively identified patients with stroke admitted to nine VA hospitals (April 1995 to March 1997). Demographics, stroke severity (Canadian Neurologic Score), stroke subtype (Trial of ORG 10172 in Acute Stroke Treatment [TOAST] classification), tests/procedures, and discharge status (independent, Rankin < or = 2, vs dead or dependent, Rankin 3 through 5) were compared between patients who were or were not cared for by a neurologist. RESULTS: Of 1,073 enrolled patients, 775 (neurologist care, n = 614; non-neurologist, n = 161) with ischemic stroke were admitted from home. Stroke severity (Canadian Neurologic Score 8.7 +/- 0.1 vs 8.4 +/- 0.2; p = 0.44), TOAST subtype (p = 0.55), and patient age (71.4 +/- 0.4 vs 72.4 +/- 0.7; p = 0.23) were similar for neurologists and non-neurologists. Neurologists more frequently obtained MRI (44% vs 16%; p < 0.001), transesophageal echocardiograms (12% vs 2%; p < 0.001), carotid ultrasounds (65% vs 57%; p = 0.05), cerebral angiography (8% vs 1%; p = 0.001), speech (35% vs 18%; p < 0.001), and occupational therapy (46% vs 33%; p = 0.005) evaluations. Brain CT, transthoracic echocardiogram, 24-hour ambulatory ECG use, and hospitalization durations (18.2 +/- 0.8 vs 19.7 +/- 4.1 days; p = 0.725) were similar. Neurologists' patients were less likely to be dead (5.6% vs 13.5%; OR = 0.38; 95% CI 0.22, 0.68; p = 0.001) and less likely to be dead or dependent (46.1% vs 57.1%; OR = 0.64; 95% CI 0.45, 0.92; p = 0.019) at the time of discharge. The benefit remained after controlling for stroke severity and comorbidity (OR = 0.63; 95% CI 0.42, 0.94; p = 0.025). CONCLUSION: Neurologist care was associated with more extensive testing, but similar lengths of hospitalization and improved outcomes.

Racial differences in survival post cerebral infarction among the elderly.

OBJECTIVE: To investigate whether there are differences in poststroke survival between African American and white patients, aged 65 and over, in the United States. METHODS: A biracial cohort of patients was selected from a random 20% national sample of Medicare patients (age 65 and over) hospitalized with cerebral infarction in 1991, and was followed up to a period of 3 years. The Cox regression model was used for covariate adjustment. RESULTS: A total of 47,045 patients (including 5,324 African Americans) were identified for our analysis. Compared to white patients, African American patients on average were 6% more likely to die post cerebral infarction. The subpopulation analyses further suggest that African Americans age 65 to 74 had much lower 3-year survival probabilities (15 to 20%) than their white counterparts. CONCLUSIONS: The authors find evidence of racial disparities in survival post cerebral infarction among the elderly, although the differences by race are not as great as reported elsewhere for stroke incidence and mortality. Future analyses, using more clinically detailed data, should focus especially on whether survival differences by race persist in the young-old (age 65 to 74) population.

Studies of a targeted risk reduction intervention through defined exercise (STRRIDE).

PURPOSE: The Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) trial is a randomized controlled clinical trial designed to study the effects of exercise training regimens differing in dose (kcal.wk-1) and/or intensity (relative to peak VO2) on established cardiovascular risk factors and to investigate the peripheral biologic mechanisms through which chronic physical activity alters carbohydrate and lipid metabolism to result in improvements in these parameters of cardiovascular risk in humans. METHODS: We will recruit 384 subjects and randomly assign them to one of three exercise training regimens or to a sedentary control group. The recruiting goal is to attain a subject population that is 50% female and 30% ethnic minority. The overall strategy is to use graded exercise training regimens in moderately overweight subjects with impairments in insulin action and mild to moderate lipid abnormalities to investigate whether there are dose or intensity effects and whether adaptations in skeletal muscle (fiber type, metabolic capacity, and/or capillary surface area) account for improvements in insulin action and parameters of lipoprotein metabolism. We will study these variables before and after exercise training, and over the course of a 2-wk detraining period. The study sample size is chosen to power the study to examine differences in responses between subjects of different gender and ethnicity to exercise training with respect to the least sensitive parameter-skeletal muscle capillary density. RESULTS: The driving hypothesis is that improvements in cardiovascular risk parameters derived from habitual exercise are primarily mediated through adaptations occurring in skeletal muscle. CONCLUSION: Identification that amount and intensity of exercise matter for achieving general and specific health benefits and a better understanding of the peripheral mechanisms mediating the responses in carbohydrate and lipid metabolism to chronic physical activity will lead to better informed recommendations for those undertaking an exercise program to improve cardiovascular risk.

Effect of moderate weight loss on health-related quality of life: an analysis of combined data from 4 randomized trials of sibutramine vs placebo.

OBJECTIVES: To determine whether (1) patients who experience greater weight loss also experience correspondingly greater improvements in health-related quality of life (HRQOL); (2) the improvement in HRQOL is noticeable for patients achieving moderate (5%-10%) weight reduction; and (3) the relationship between weight reduction and HRQOL is similar for patients receiving sibutramine hydrochloride vs placebo. STUDY DESIGN: We combined data from 4 double-blind, randomized, controlled trials of administration of sibutramine (20 mg/d) vs placebo. PATIENTS AND METHODS: Patients (n = 555) were mildly to moderately obese and had type 2 diabetes mellitus, dyslipidemia, or hypertension that was well controlled with an angiotensin-converting enzyme inhibitor or calcium channel blocker. The HRQOL was operationalized using the Impact of Weight on Quality of Life (IWQOL) and the Medical Outcomes Study 36-Question Short-Form (SF-36) instruments. The main statistical technique was a patient-level analysis of variance predicting change in HRQOL from study, treatment, and weight change. RESULTS: Moderate weight loss was associated with a statistically significant improvement in HRQOL for approximately half of the subscales evaluated (P < .05). The greatest sensitivity to change was shown by the SF-36 general health perception and change in health since last year subscales and the IWQOL overall health, mobility, and total subscales. Greater weight loss was associated with the most improvement in HRQOL. Weight losses of 5.01% to 10.00% were associated with 2-unit changes in the SF-36 general health perception subscale and 10-unit changes in the IWQOL total subscale. Results were similar across study and treatment. CONCLUSIONS: Moderate weight loss is associated with noticeably improved HRQOL. Improvements in HRQOL are achievable by patients receiving sibutramine.

Reasons for quitting smoking among low-income African American smokers.

The psychometric characteristics of the Reasons For Quitting scale (RFQ) were assessed among a sample of African American smokers with low income (N=487). The intrinsic and extrinsic scales and their respective subscales were replicated. As hypothesized, higher levels of motivation were associated significantly, in patterns that supported the measure's construct validity, with advanced stage of readiness to quit smoking, greater perceived vulnerability to health effects of smoking, and greater social support for cessation. On the basis of the present study, the RFQ might best predict short-term cessation among older and female smokers. Refinement of the RFQ is needed to assess intrinsic motivators other than health concerns and to identify salient motivators for young and male smokers.

Relationship between self-reported disability and caregiver hours.

OBJECTIVE: In a large, population-based cohort of patients with spinal cord dysfunction, we assessed the relationship between self-reported physical function and hours of care received. DESIGN: Data were obtained by a cross-sectional, self-administered survey used to help establish a national registry of veterans with spinal cord dysfunction. Participants were originally identified from Department of Veterans Affairs databases as having a high probability of spinal cord dysfunction. All 13,542 respondents reporting spinal cord dysfunction and also having complete data on physical function and caregiver hours (CGHs) were included. Physical function was measured using the Self-Reported Functional Measure, and CGHs were obtained from a self-report of hours of caregiving received during the last 2 wk. RESULTS: The relationship between self-reported disability and CGHs was strong (Spearman correlation = -0.70). Subjects with moderate levels of disability had the most variability in CGHs. After stratifying by total Self-Reported Functional Measure score, the strongest predictors of CGHs were instrumental activities of daily living and individual Self-Reported Functional Measure items, explaining a moderate amount of variation in CGHs. CONCLUSION: These data support the construct validity of the Self-Reported Functional Measure and suggest that self-reported disability measures can be of use in describing the clinical epidemiology of patients with spinal cord dysfunction.

The short-term impact of tailored mammography decision-making interventions.

BACKGROUND: We assessed the short-term impact of decision-making interventions on knowledge about mammography, accuracy of women's breast cancer risk perceptions, attitudes toward mammography, satisfaction with decisions, and mammography use since the intervention. METHODS: The study was conducted among women who were members of Blue Cross Blue Shield of North Carolina and were in their 40s or 50s at the time the study began in 1997. Women were randomly assigned to usual care (UC), tailored print booklets (TP) alone, or TP plus telephone counseling (TP+TC ). RESULTS: 12-month interviews were completed by 1127 women to assess short-term intervention effects. Generally, women who received TP+TC were significantly more knowledgeable about mammography and breast cancer risk and were more accurate in their breast cancer risk perceptions than women in the TP and UC groups. They also were more likely to have had a mammogram since the baseline interview. In multivariable analyses, we found significant benefits of the combination of TP+TC compared to TP and to UC for knowledge, accuracy of risk perceptions, and mammography use. DISCUSSION: For complex decision-making tasks, such as women's decisions about mammography in the face of controversy, the combination of TP and TC may be more effective than TP alone, and certainly more effective than UC. It is critical that investigators determine the topics for which TP is appropriate and the situations that require additional supportive interventions.

Hormone replacement therapy and ischemic stroke severity in women: a case-control study.

OBJECTIVE: To investigate whether ischemic stroke severity differed among women who were receiving hormone replacement therapy (HRT) as compared with those who were not receiving these drugs. BACKGROUND: Estrogen has a neuroprotective effect in animal models of ischemic stroke, but data reflecting the impact of HRT on ischemic stroke severity in humans are lacking. METHODS: All women receiving HRT at the time of admission for acute ischemic stroke to an academic medical center over 3 years were identified by medical record review (n = 58). HRT users were matched with 116 HRT nonusers by age and number of stroke risk factors. Stroke severity was assessed retrospectively with the Canadian Neurological SCALE: Data were analyzed with nonparametric univariate tests (Spearman rank and chi(2) tests) and linear regression modeling using nonparametric matched-pair analysis. RESULTS: History of congestive heart failure or coronary artery disease (p = 0.01), atrial fibrillation (p = 0.02), and African American race (p = 0.04), were significantly associated with greater stroke severity in the univariate analysis. There was a nonsignificant trend toward lesser stroke severity in HRT users (median Canadian Neurological Scale score, 10, vs 9.5 in non-HRT users, p = 0.08). Multivariate analysis showed no independent effect of HRT use on stroke severity (F = 1.24, p = 0.17). CONCLUSIONS: There was no significant effect of HRT status on stroke severity. Because this was a retrospective analysis, prospective studies are also needed to further elucidate any potential neuroprotective effect of hormone replacement.

Have randomized controlled trials of neuroprotective drugs been underpowered? An illustration of three statistical principles.

BACKGROUND AND PURPOSE: The results of phase III trials of neuroprotective drugs for acute ischemic stroke have been disappointing. We examine the question of whether these trials may have been underpowered. METHODS: Computer simulations were based on the binomial distribution. RESULTS: We illustrate that even small overestimates of the efficacy of an intervention can lead to a serious reduction in statistical power, that the use of data from phase II studies tends to lead to such overestimation, and that a minimum clinically important difference derived with cost-effectiveness modeling techniques is considerably smaller than might be suggested by intuition. CONCLUSIONS: We recommend placing more emphasis on minimum clinically important differences when planning stroke trials, with these differences being derived from an assessment of the public health impact obtained in conjunction with the use of epidemiological and cost-effectiveness models. Even small benefits, when averaged over a sufficiently large number of cases, will, in total, accrue to a large positive impact on the public health.

Differences in skeletal muscle between men and women with chronic heart failure.

Men with chronic heart failure (CHF) have alterations in their skeletal muscle that are partially responsible for a decreased exercise tolerance. The purpose of this study was to investigate whether skeletal muscle alterations in women with CHF are similar to those observed in men and if these alterations are related to exercise intolerance. Twenty-five men and thirteen women with CHF performed a maximal exercise test for evaluation of peak oxygen consumption (VO(2)) and resting left ventricular ejection fraction, after which a biopsy of the vastus lateralis was performed. Twenty-one normal subjects (11 women, 10 men) were also studied. The relationship between muscle markers and peak VO(2) was consistent for CHF men and women. When controlling for gender, analysis showed that oxidative enzymes and capillary density are the best predictors of peak VO(2.) These results indicate that aerobically matched CHF men and women have no differences in skeletal muscle biochemistry and histology. However, when CHF groups were separated by peak exercise capacity of 4.5 metabolic equivalents (METs), CHF men with peak VO(2) >4.5 METs had increased citrate synthase and 3-hydroxyacyl-CoA dehydrogenase compared with CHF men with peak VO(2) <4.5 METs. CHF men with a lower peak VO(2) had increased capillary density compared with men with higher peak VO(2). These observations were not reproduced in CHF women. This suggests that differences may exist in how skeletal muscle adapts to decreasing peak VO(2) in patients with CHF.

Factors associated with repeat mammography screening.

BACKGROUND: Even organizations with differing mammography recommendations agree that regular repeat screening is required for mortality reduction. However, most studies have focused on one-time screening rather than repeat adherence. We compare trends in beliefs and health-related behaviors among women screened and adherent to the National Cancer Institute's screening mammography recommendations (on schedule), those screened at least once and nonadherent (off schedule), and those never screened. METHODS: Our data are from a baseline telephone interview conducted among 1,287 female members of Blue Cross Blue Shield of North Carolina who were aged either 40 to 44 years or 50 to 54 years. RESULTS: The 3 groups differed significantly on beliefs and health-related behaviors, with the off-schedule group almost consistently falling between the on-schedule and never screened groups. Off-schedule women were more likely than on-schedule women, but less likely than those never screened, to not have a clinical breast examination within 12 months, to be ambivalent about screening mammography, to be confused about screening guidelines, and to not be advised by a physician to get a mammogram in the past 2 years. Off-schedule women perceived their breast cancer risk as lower and were less likely to be up to date with other cancer screening tests. CONCLUSIONS: Our findings suggest that women who are off schedule are in need of mammography-promoting interventions, including recommendations from and discussion with their health care providers. Because they are more positive and knowledgeable about mammography than women who have never been screened, they may benefit from brief interventions from health care providers that highlight the importance of repeat screening.

New transient ischemic attack and stroke: outpatient management by primary care physicians.

BACKGROUND: Patients with transient ischemic attack (TIA) or stroke frequently first contact their primary care physician rather than seeking care at a hospital emergency department. The purpose of the present study was to identify a group of patients seen by primary care physicians in an office setting for a first-ever TIA or stroke and characterize their evaluation and management. METHODS: Practice audit based on retrospective, structured medical record abstraction from 27 primary care medical practices in 2 geographically separate communities in the eastern United States. RESULTS: Ninety-five patients with a first-ever TIA and 81 with stroke were identified. Seventy-nine percent of those with TIA vs 88% with stroke were evaluated on the day their symptoms occurred (P =.12). Only 6% were admitted to a hospital for evaluation and treatment on the day of the index visit (2% TIA; 10% stroke; P =.03); only an additional 3% were admitted during the subsequent 30 days. Specialists were consulted for 45% of patients. A brain imaging study (computed tomography or magnetic resonance imaging) was ordered on the day of the index visit in 30% (23% TIA, 37% stroke; P =.04), regardless of whether the patient was referred to a specialist. Carotid ultrasound studies were obtained in 28% (40% TIA, 14% stroke; P<.001), electrocardiograms in 19% (18% TIA, 21% stroke; P =.60), and echocardiograms in 16% (19% TIA, 14% stroke; P =.34). Fewer than half of patients with a prior history of atrial fibrillation (n = 24) underwent anticoagulation when evaluated at the index visit. Thirty-two percent of patients (31% TIA, 33% stroke; P =.70) were not hospitalized and had no evaluations performed during the first month after presenting to a primary care physician with a first TIA or stroke. Of these patients, 59% had a change in antiplatelet therapy on the day of the index visit. CONCLUSIONS: Further primary care physician education regarding the importance of promptly and fully evaluating patients with TIA or stroke may be warranted, and barriers to implementation of established secondary stroke prevention strategies need to be carefully explored. Arch Intern Med. 2000;160:2941-2946

Community impact of anticoagulation services: rationale and design of the Managing Anticoagulation Services Trial (MAST).

We describe the design of the Managing Anti-coagulation Services Trial (MAST), a practice-improvement trial testing whether anticoagulation services are a preferred method of managing anticoagulation for stroke prevention among patients with atrial fibrillation. Most randomized trials within the health care environment are designed as efficacy studies to determine what works under ideal conditions or ideal clinical practice. In contrast, effectiveness trials seek to generalize the results of efficacy studies by determining what works under more typical practice conditions. Practice-improvement trials are effectiveness trials that examine the management of a clinical problem in the context in which care is usually given. Noteworthy features of the MAST include defining the intervention in functional terms and collaboration with managed care organizations.

Quality of anticoagulation management among patients with atrial fibrillation: results of a review of medical records from 2 communities.

BACKGROUND: Most treatment of patients at risk for stroke is provided in the ambulatory setting. Although many studies have addressed the proportion of eligible patients with atrial fibrillation (AF) receiving warfarin sodium, few have addressed the quality of their anticoagulation management. OBJECTIVE: As a comprehensive assessment of quality, we analyzed the proportion of eligible patients receiving warfarin, the proportion of time their international normalized ratios (INRs) were within the target range, and, when an out-of-target range INR value occurred, the time until the next INR measurement was made. METHODS: Retrospective review of the medical records of 660 patients with AF managed by general internists and family practitioners in Rochester, NY, and the Research Triangle area of North Carolina. RESULTS: Only 34.7% of eligible patients with AF received warfarin. The INR values were out of the target range approximately half the time, and the response to these values was not always timely. For all the measures considered, both Rochester practices with access to an anticoagulation service had higher (albeit not ideal) quality of warfarin management than the remaining practices. CONCLUSIONS: We found significant deficiencies in the practice of warfarin management and suggestive evidence that anticoagulation services can partially ameliorate these deficiencies. More research is needed to describe the quality of anticoagulation management in typical practice and how this management can be improved.

Relationship between test frequency and outcomes of anticoagulation: a literature review and commentary with implications for the design of randomized trials of patient self-management.

BACKGROUND: Patient self-management (PSM) of anticoagulation, which is primarily based upon the premise that more frequent testing will lead to tighter anticoagulation control and thus to improved clinical outcomes, is a promising model of care. The goals of this paper are (1) to describe the strength of evidence correlating more frequent testing with improved outcomes; and (2) to discuss implications of these findings for the design of randomized controlled trials (RCTs) assessing the effectiveness and cost-effectiveness of PSM. METHODS: We performed two literature reviews: one examining the strength of the relationship between time in target range (TTR) and the clinical outcomes of major bleeding and thromboembolism; and the second examining the strength of the relationship between frequency of testing and TTR. RESULTS: We found that (1) the relationship between TTR and clinical outcomes is strong, thus supporting use of TTR as a primary outcome variable; and (2) more frequent testing seems to increase TTR, although the studies supporting this latter conclusion were relatively few and not definitive. Statistical analysis suggested that a study which uses clinical event rates as its primary outcome would need to be much larger than a comparable study which is based upon TTR. CONCLUSIONS: When designing randomized trials of PSM, the design should (1) use as its control group high quality anticoagulation management rather than usual care; (2) include the maximum possible amount of self-management in the intervention group; (3) include different testing intervals in the intervention group; (4) use TTR as the primary outcome variable and event rates as a secondary outcome; and (5) base the sample size calculations upon a 5-10% absolute improvement in TTR. Additional RCTs are needed in order to determine how the promise of PSM can best be fulfilled.

Racial variation in treatment for transient ischemic attacks: impact of participation by neurologists.

OBJECTIVE: This study evaluates the role of neurologists in explaining African American-white differences in the use of diagnostic and therapeutic services for cerebrovascular disease. DATA SOURCES/STUDY SETTING: Medicare inpatient hospital records were used to identify a random 20 percent sample of patients age 65 and over hospitalized with a principal diagnosis of TIA between January 1, 1991 and November 30, 1991 (n = 17,437). STUDY DESIGN: Medicare administrative data were used to identify five outcome measures: noninvasive cerebrovascular tests, cerebral angiography, carotid endarterectomy, anticoagulant therapy (as proxied by outpatient prothrombin time tests), and the specialty of the attending physician (neurologist versus other specialist). DATA COLLECTION/EXTRACTION METHODS: All Medicare claims were extracted for a 30-day period beginning with the date of admission. PRINCIPAL FINDINGS: Even after adjusting for patient demographics, comorbidity, ability to pay, and provider characteristics, African American patients were significantly less likely to receive noninvasive cerebrovascular testing, cerebral angiography, or carotid endarterectomy, compared with white patients, and to have a neurologist as their attending physician. At the same time, patients treated by neurologists were more likely to undergo diagnostic testing and less likely to undergo carotid endarterectomy. CONCLUSIONS: The findings suggest that African American patients with TIA may have less access to services for cerebrovascular disease and that at least some of this may be attributed to less access to neurologists. More research is needed on how patients at risk for stroke are referred to specialists.

Incidence and occurrence of total (first-ever and recurrent) stroke.

BACKGROUND AND PURPOSE: It has recently been hypothesized that the figure of approximately half a million strokes substantially underestimates the actual annual stroke burden for the United States. The majority of previously reported studies on the epidemiology of stroke used relatively small and homogeneous population-based stroke registries. This study was designed to estimate the occurrence, incidence, and characteristics of total (first-ever and recurrent) stroke by using a large administrative claims database representative of all 1995 US inpatient discharges. METHODS: We used the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project, release 4, which contains approximately 20% of all 1995 US inpatient discharges. Because the accuracy of International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) coding is suboptimal, we performed a literature review of ICD-9-CM 430 to 438 validation studies. The pooled results from the literature review were used to make appropriate adjustments in the analysis to correct for some of the inaccuracies of the diagnostic codes. RESULTS: There were 682 000 occurrences of stroke with hospitalization (95% CI 660 000 to 704 000) and an estimated 68 000 occurrences of stroke without hospitalization. The overall incidence rate for occurrence of total stroke (first-ever and recurrent) was 259 per 100 000 population (age- and sex-adjusted to 1995 US population). Incidence rates increased exponentially with age and were consistently higher for males than for females. CONCLUSIONS: We conservatively estimate that there were 750 000 first-ever or recurrent strokes in the United States during 1995. This new figure emphasizes the importance of preventive measures for a disease that has identifiable and modifiable risk factors and for the development of new and improved treatment strategies and infrastructures that can reduce the consequences of stroke.