Toxic substance exposure and multiple myeloma: a case-control study.

By means of a population-based, multicenter case-control investigation, certain toxic substances were evaluated as risk factors for multiple myeloma. Interviews were completed on 698 subjects with newly diagnosed multiple myeloma, and 1,683 controls were selected from the same geographic areas as those of the cases. Respondents were asked if they had ever been "highly" exposed" to one or more of a list of toxic substances or to other substances not on the list. With the aid of a toxicologist, responses were then categorized into 20 exposure groups. Those who reported past exposure to pesticides had an estimated relative risk of 2.6 for multiple myeloma [95% confidence interval (CI) = 1.5-4.6]. Subjects exposed to a variety of compounds commonly used by painters had an estimated relative risk of 1.6 (95% CI = 1.1-2.4). An increased risk also was found for those who were exposed to sources of carbon monoxide (relative risk = 1.8, 95% CI = 1.0-3.2). Associations of borderline statistical significance were found for metals and organically high polymers (plastics and elastomers). No statistically significant associations were seen for exposure to fertilizers; dyes and inks; alkalies; acids; other caustic substances; chemical asphyxiants; aliphatic, chlorinated, or aromatic hydrocarbons; aldehydes and ketones; ethers; esters; oils; dusts; or asbestos.

Infectious and noninfectious exposures in the etiology of light chain myeloma: a case-control study.

Sixty-nine subjects with light chain myeloma were interviewed in a multicenter case-control study, and their responses were compared to those of 1683 controls selected from the general population of the same geographic areas. The interview was directed at the subject's history of exposure to a variety of chemical and infectious agents. Persons with a history of a medical implant had 2.2 times the risk of other persons (95% confidence interval = 0.9-5.8), a relative risk that increased with increasing time that the implant had been present. Alkali exposure that was deemed by the subject to be unusually heavy was associated with a relative risk of light chain myeloma of 7.8 (95% confidence interval = 1.7-35.3), while similarly defined exposure to carbon monoxide increased the risk by 6.1 times (95% confidence interval = 2.0-18.2). These findings differ from those obtained in our study of the more common forms of multiple myeloma and, while the differences are plausibly due only to chance given the large number of exposures investigated, they could be an indication that light chain myeloma is an etiologically distinct entity.

Health outcomes associated with beta-blocker and diltiazem treatment of unstable angina.

OBJECTIVE: We compared long-term health outcomes associated with beta-adrenergic blocking agents and diltiazem treatment for unstable angina. BACKGROUND: No long-term data have been published comparing these two antianginal treatments in this setting. METHODS: Eligible veterans were discharged from the Veterans Affairs Puget Sound Health Care System (VAPSHCS), Seattle Division, between October 1989 and September 1995 with an unstable angina diagnosis and were prescribed monotherapy beta-blocker or diltiazem treatment at discharge. Medication data were collected from medical records and computerized VAPSHCS outpatient pharmacy files. Follow-up death and coronary artery disease rehospitalization data were collected through 1996. Proportional hazards regression compared survival among diltiazem and beta-blocker users, controlling for patient characteristics with propensity scores. RESULTS: Two hundred forty-seven veterans (24% on beta-blockers, 76% on diltiazem) were included in this study. There were 54 (22%) deaths during an average follow-up of 51 months. After propensity score adjustment, there was no difference in risk of death comparing diltiazem to beta-blocker treatment (hazards ratios [HR] 1.1; 95% confidence interval [CI] 0.49 to 2.4). Among Washington residents (n=207), there were 146 (71%) coronary artery disease rehospitalizations or deaths during follow-up. After adjustment, there was a nonsignificant increase in risk of rehospitalization or death associated with diltiazem use (HR 1.4; 95% CI 0.80 to 2.4). For both analyses, similar risks were found among veterans without relative contraindications to beta-blockers. CONCLUSIONS: We found no survival benefit of diltiazem over beta-blocker treatment for unstable angina in this cohort of veterans.

Hypothesis: a motor neuron toxin produced by a clostridial species residing in gut causes ALS.

We hypothesize that a yet-to-be-identified motor neuron toxin produced by a clostridial species causes sporadic amyotrophic lateral sclerosis (ALS) in susceptible individuals. This clostridial species would reside undetected in the gut and chronically produce a toxin that targets the motor system, like the tetanus and botulinum toxins. After gaining access to the lower motor neuron, the toxin would be transported back to the cell body, as occurs with the tetanus toxin, and destroy the lower motor neuron - the essential feature of ALS. Again like the tetanus toxin, some of the toxin would cross to neighboring cells and to the upper motor neuron and similarly destroy these motor neurons. Weakness would relentlessly progress until not enough motor neurons remained to sustain life. If this hypothesis were correct, treatment with appropriate antibiotics or antitoxins might slow or halt progression of disease, and immunization might prevent disease.

Patient-physician racial concordance and the perceived quality and use of health care.

BACKGROUND: Patients from racial and ethnic minority groups use fewer health care services and are less satisfied with their care than patients from the majority white population. These disparities may be attributable in part to racial or cultural differences between patients and their physicians. OBJECTIVE: To determine whether racial concordance between patients and physicians affects patients' satisfaction with and use of health care. METHODS: We analyzed data from the 1994 Commonwealth Fund's Minority Health Survey, a nationwide, telephone survey of noninstitutionalized adults. For the 2201 white, black, and Hispanic respondents who reported having a regular physician, we examined the association between patient-physician racial concordance and patients' ratings of their physicians, satisfaction with health care, reported receipt of preventive care, and reported receipt of needed medical care. RESULTS: Black respondents with black physicians were more likely than those with nonblack physicians to rate their physicians as excellent (adjusted odds ratio [OR], 2.40; 95% confidence interval [CI], 1.55-3.72) and to report receiving preventive care (adjusted OR, 1.74; 95% CI, 1.01-2.98) and all needed medical care (adjusted OR, 2.94; 95% CI, 1.10-7.87) during the previous year. Hispanics with Hispanic physicians were more likely than those with non-Hispanic physicians to be very satisfied with their health care overall (adjusted OR, 1.74; 95% CI, 1.01-2.99). CONCLUSIONS: Our findings confirm the importance of racial and cultural factors in the patient-physician relationship and reaffirm the role of black and Hispanic physicians in caring for black and Hispanic patients. Improving cultural competence among physicians may enhance the quality of health care for minority populations. In the meantime, by reducing the number of underrepresented minorities entering the US physician workforce, the reversal of affirmative action policies may adversely affect the delivery of health care to black and Hispanic Americans.

Risk factors for acquiring pneumococcal infections.

To identify risk factors for developing pneumococcal infections, we carried out a case-controlled study on a retrospectively constituted cohort of 3074 clinic patients in a presumed high-risk population. Culture-proved pneumococcal infections were identified in 63 men over a period of 5.5 years, yielding an estimated incidence of 6.3 cases per 1000 person-years. By comparing these patients with 130 uninfected control patients, the relative risk of pneumococcal infections related to various exposures was calculated by logistic regression analysis. Statistically significant independent risk factors (and their relative risks) were as follows: dementia (5.82), seizure disorders (4.38), current cigarette smoking (4.00), congestive heart failure (3.83), cerebrovascular disease (3.82), institutionalization (3.13), and chronic obstructive pulmonary disease (2.38). Risk was increased with age and previous hospitalizations, and, to a nonsignificant degree, by hotel residence (3.93), lung cancer (2.24), previous smoking (2.14), corticosteroid use (1.81), and alcoholism (1.35); but not by diabetes mellitus (0.99), nonlung malignancies (0.93), nonwhite race (0.89), or ischemic heart disease (0.58).

Level of blood pressure and risk of myocardial infarction among treated hypertensive patients.

To examine the association between the level of treated blood pressure and the incidence of myocardial infarction, we conducted a population-based case-control study of 912 members of a health maintenance organization who were receiving standard clinical treatment for hypertension. We found a J-shaped relationship between the most recently measured diastolic blood pressure and the risk of myocardial infarction, the lowest risk occurring at 84 mm Hg. The relative risk of myocardial infarction at 60 mm Hg was 2.07 (95% confidence interval, 0.86 to 5.01), and at 100 mm Hg, 1.45 (95% confidence interval, 1.02 to 2.06). Treated systolic pressure bore a linear relationship to the risk of infarction. We conclude that the optimum target range for diastolic blood pressure in hypertensive patients may be 84 to 90 mm Hg. Levels outside this range may be associated with increased risk of myocardial infarction.

Use of calcium channel blockers and risk of hospitalized gastrointestinal tract bleeding.

BACKGROUND: We conducted a case-control study of the association between calcium channel blocker use and gastrointestinal (GI) tract bleeding in hypertensive members of a health maintenance organization. METHODS: Case patients (n=174) were treated hypertensive health maintenance organization members hospitalized for GI tract bleeding between January 1992 and December 1994. Case patients were identified using computerized diagnosis codes and were confirmed by medical record review. Control subjects (n=771) were treated hypertensive members selected from ongoing studies at the health maintenance organization. Computerized pharmacy data and medical records were used to assess medication use and other risk factors for GI tract bleeding. RESULTS: Compared with beta-blocker users, calcium channel blocker users had an age-, sex- and calendar year-adjusted relative risk (RR) of GI tract bleeding of 2.60 (95% confidence interval [CI], 1.71-3.96). The RR associated with calcium channel blocker use was 2.05 (95% CI, 1.33-3.17) after further adjustment for number of recent visits, diastolic blood pressure, chronic congestive heart failure, and duration of hypertension. No significant dose-response relationship was observed. Compared with beta-blocker users, angiotensin-converting enzyme inhibitor users had an RR of 1.22 (95% CI, 0.75-1.97). Calcium channel blocker use tended to be more strongly associated with risk of lower GI tract bleeding (RR, 2.56; 95% CI, 1.08-6.05) than with risk of upper GI tract bleeding (RR, 1.54; 95% CI, 0.91-2.59) or peptic ulcer-related bleeding (RR, 1.17; 95% CI, 0.62-2.21), although these results were compatible with chance. CONCLUSIONS: Calcium channel blocker use might be associated with an elevated risk of GI tract bleeding. These findings require confirmation in randomized studies.

Physicians' responses to patients' requests for physician-assisted suicide.

BACKGROUND: Studies show that patient requests for physician-assisted suicide (PAS) are a relatively common clinical occurrence. The purpose of this study was to describe how experienced physicians assess and respond to requests for assisted suicide. METHODS: Focused ethnography in the offices of 11 acquired immunodeficiency syndrome physicians, 8 oncologists, and 1 hospice physician who had received requests for assisted suicide in their practice. Ten had facilitated PAS. RESULTS: Informants had a similar approach to evaluating patients who requested assisted suicide, often asking, "Why do you want to die now?" Reasons for requests fell into 3 broad categories: physical symptoms, psychological issues, and existential suffering. Physicians thought they competently addressed patients' physical symptoms, and this obviated most requests. They treated depression empirically and believed they did not assist depressed patients with assisted suicide. Physicians had difficulty addressing patients' existential suffering, which led to most facilitated requests. Informants rarely talked to colleagues about requests for assisted suicide, suggesting a "professional code of silence." CONCLUSIONS: Regardless of divergent attitudes about PAS, physicians respond similarly to requests for assisted suicide from their patients, creating a common ground for professional dialogue. Our sample addressed physical suffering aggressively, treated depression empirically, but struggled with requests arising from existential suffering. A professional code of silence regarding PAS creates professional isolation. Clinicians do not share knowledge or receive social support from peers about their decisions regarding assisted suicide. Educational strategies drawing on approaches used by experienced clinicians may create an atmosphere that enables physicians with divergent beliefs to discuss this difficult subject.

The risk of myocardial infarction associated with the combined use of estrogens and progestins in postmenopausal women.

BACKGROUND: While observational studies have suggested that unopposed estrogens reduce the incidence of coronary disease in postmenopausal women, there are few data on the effect of combined therapy with estrogens and progestins--a regimen adopted in recent years to minimize the risk of endometrial hyperplasia and cancer. In clinical trials, the addition of progestins has an adverse effect on serum lipid levels, and these lipid effects have raised the question of whether combined estrogen-progestin therapy increases the risk of coronary disease compared with the use of estrogen alone. METHODS: We conducted a population-based, case-control study among enrollees of Group Health Cooperative of Puget Sound. Cases were postmenopausal women who sustained an incident fatal or nonfatal myocardial infarction in 1986 through 1990. Controls were a stratified random sample of female Group Health Cooperative enrollees frequency matched to the cases by age and calendar year. We reviewed the medical records of the 502 cases and 1193 controls and conducted brief telephone interviews with consenting survivors. The health maintenance organization's computerized pharmacy database was used to ascertain the use of postmenopausal hormones. For the primary analysis of current use, we classified women into one of three groups: (1) nonusers of hormones; (2) users of estrogens alone; or (3) users of combined therapy including both estrogens and progestins. Each group of hormone users was compared with nonusers. RESULTS: After adjustment for potential confounding factors, the risk ratio of myocardial infarction associated with current use of estrogens alone was 0.69 (95% confidence interval, 0.47 to 1.02); and the risk ratio of myocardial infarction associated with current use of combined therapy was 0.68 (95% confidence interval, 0.38 to 1.22). Duration of combined-therapy use was relatively short, averaging less than 2 years in cases and controls. CONCLUSIONS: In this case-control study, the reduced risk of myocardial infarction associated with the use of estrogens alone was consistent with previous observational studies. Although the 95% confidence interval only excluded a risk above 1.22, the current use of combined therapy was not associated with an adverse effect on the incidence of myocardial infarction in postmenopausal women.

Duration of estrogen replacement therapy in relation to the risk of incident myocardial infarction in postmenopausal women.

BACKGROUND: There is little information about whether an increasing duration of estrogen replacement therapy is associated with a declining risk for myocardial infarction in postmenopausal women. OBJECTIVE: To conduct a population-based, case-control study among enrollees of the Group Health Cooperative (GHC) of Puget Sound, Seattle, Wash. SUBJECTS AND METHODS: Case subjects were all post-menopausal women who were enrolled in the GHC with an incident fatal or nonfatal myocardial infarction from July 1986 through December 1993. Control subjects were a stratified random sample of postmenopausal women who were enrolled in the GHC without myocardial infarction and matched to case subjects by age and calendar year. We reviewed the medical records of the 850 case subjects and 1974 control subjects and conducted telephone interviews with consenting survivors. Use of estrogen or estrogen and progestin was assessed using GHC's computerized pharmacy database. RESULTS: Among women who were currently using estrogen, a longer duration of use was inversely associated with a risk for myocardial infarction after adjustment for age, year of identification, diabetes mellitus, angina, and smoking. For categories of increasing duration of estrogen use (never, > 0-< 1.8 years, 1.8-< 4.2 years, 4.2-< 8.2 years, and > or = 8.2 years), the odds ratios for myocardial infarction were 1.00 (reference), 0.91, 0.70, 0.65, and 0.55 (for trend among the current users, P = .05). Among women who had used estrogen in the past, there was no evidence of decreasing risk with increasing duration of estrogen use. CONCLUSION: In this study, a long duration of hormone replacement therapy among women currently using estrogen was associated with a reduced risk for first myocardial infarction.

A review of the association of estrogens and progestins with cardiovascular disease in postmenopausal women.

The purpose of this article was to review, with special attention to the hypothesized mechanisms of atherosclerosis and thrombosis, the literature on the association of estrogens and progestins with cardiovascular disease. The data sources included recent reviews and their citations as well as literature searches of Medline. For coronary heart disease, we relied on a recent meta-analysis; for the lipid effects of estrogens and progestins, we refer to recent reviews and studies; for stroke, we identified all cohort and case-control studies; and for the effects of hormones on coagulation factors, we identified all relevant studies. The lipid effects of estrogens in postmenopausal women probably prevent atherosclerosis, and we would expect long duration of use rather than current use to provide the greatest benefit. Few epidemiologic studies have, however, assessed duration of estrogen use. High doses of estrogens are likely to be thrombogenic during current use, and it is possible that even moderate doses may increase the risk of clotting among women who smoke or who have existing coronary atherosclerosis. Compared with the lipid effects of estrogens alone, the lipid effects of combined therapy with progestins may increase atherosclerosis. The effect of progestins on coagulation factors is largely unknown, and no epidemiologic study has assessed the risk of cardiovascular disease associated with the use of combined hormone therapy in postmenopausal women. Cardiovascular risk or benefit associated with the use of postmenopausal hormones may involve several competing mechanisms, including effects on prostaglandins and vascular tone as well as atherosclerosis and thrombosis.

How does provider and patient awareness of high-risk status for lower-extremity amputation influence foot-care practice?

OBJECTIVE: To assess whether patients with diabetes at high risk for lower extremity amputation received more intensive medical care or self-care instruction and to determine the association between foot care and risk of lower-extremity amputation. RESEARCH DESIGN AND METHODS: Patients with diabetes were seen at he Seattle Veterans Affairs Medical Center (VAMC) between October 1984 and April 1987; 67 patients were seen for initial non-traumatic amputation, and 236 consecutive control subjects were seen for non-traumatic but medically necessary surgery unrelated to diabetes. Data collection included patient interview and medical record review. High-risk status, defined as presence of peripheral neuropathy, peripheral vascular disease, or or prior foot ulcer, was temporally fixed at 2 years before study enrollment. RESULTS: Peripheral neuropathy, peripheral vascular disease, and prior foot ulcer were independently associated with risk of lower-extremity amputation: peripheral neuropathy odds ratio (OR) = 1.4 (95% confidence interval (CI) 0.7-2.7), peripheral vascular disease OR = 2.6 (95% CI 1.5-4.5), and prior foot ulcer OR = 10.9 (95% CI 4.6-25.5). Patients with a prior foot ulcer were significantly more likely to have seen a podiatrist and to have received outpatient diabetes education at the Seattle VAMC; their providers were more likely to prescribe clipping toenails, regular foot washing, and elevating feet during the day (chi 1(2) for proportions P < 0.05). However, for patients with a history of peripheral neuropathy or peripheral vascular disease, there was no statistically significant increase in medical care (podiatry visits, outpatient diabetes education) or self-care instruction (clip nails, elevate feet, or self-monitor blood glucose) compared with patients without either of these two conditions (chi 1(2) for proportions P > 0.20). CONCLUSIONS: When clinicians were aware of a patient's very elevated risk for lower-extremity amputation (evidenced by prior history of foot ulcer), they were more likely to prescribe preventive foot-care behaviors, but awareness of other risk factors (peripheral neuropathy or peripheral vascular disease) did not necessarily increase preventive care. Physicians and patients should receive periodic education and reinforcement of diabetes management skills to modify care delivered to individuals at highest risk for lower-extremity amputation.

Factors affecting staphylococcal colonization among NIDDM outpatients.

Because colonization with Staphylococcus aureus probably predisposes to staphylococcal infections, we examined several factors that may be associated with staphylococcal carriage in outpatients with non-insulin-dependent diabetes mellitus and in nondiabetic controls. Nose and skin carrier rates for 59 diabetic patients were significantly greater (30.5%) than for 44 controls (11.4%) (P = .02), but rates did not differ significantly between diabetic patients who injected insulin (31.0%) and those who did not (30.0%). Among the diabetic patients, staphylococcal colonization was not significantly correlated (P greater than .05) with recent antibiotic treatment, age, race, or clinical duration of diabetes but was inversely correlated (P less than .03) with glycemic control, as measured by fasting plasma glucose and glycosylated hemoglobin levels. Hospitalization in the previous year was also associated with staphylococcal colonization, and it was significantly more common among the diabetic patients than the controls; however, this did not account for the increased colonization rates observed. Our results in a well-characterized population confirm an increased rate of staphylococcal colonization among diabetic as compared with nondiabetic outpatients but demonstrate that neither injections of insulin nor various pertinent demographic factors explain this finding.

Comparative clinical reliability of fasting plasma glucose and glycosylated hemoglobin in non-insulin-dependent diabetes mellitus.

Because accurate determination of glycosylated hemoglobin (GHb) is difficult and relatively expensive in comparison with the modest cost and ready availability for tests of fasting plasma glucose (FPG), we examined the reliability of repeated measurements of FPG and GHb in typical diabetic outpatients taken in the usual clinical setting. We determined FPG and GHb concurrently on three separate occasions spanning 4 wk in 41 patients with non-insulin-dependent diabetes mellitus (NIDDM) and, for contrast, 5 with insulin-dependent diabetes mellitus (IDDM). Most of the NIDDM subjects were obese, with initial FPG levels ranging from 93 to 355 mg/dl. The reliability of each test was estimated by calculating two measures: the intraclass correlation coefficient (rho I) and the coefficient of variation (CV) for the repeated test values. For NIDDM patients treated with diet or oral hypoglycemic agents (OHA), rho I for FPG, log(FPG), and GHb were very similar. For insulin-treated NIDDM patients, rho I for FPG was somewhat lower than the coefficient in other treatment groups, and the reliability of FPG by this measure did not match the reliability of GHb within the limits of statistical significance. By analyzing the CV of test values repeated within subject, the reliability of FPG did not differ from GHb in any of the NIDDM treatment groups. Although patients were recruited sequentially to minimize sample selection bias, caution must be exercised in the interpretation of the statistical analyses of reliability with either rho I or CV due to limitations imposed by small sample size.(ABSTRACT TRUNCATED AT 250 WORDS)

Subarachnoid hemorrhage and family history. A population-based case-control study.

OBJECTIVE: To evaluate family history as a risk factor for subarachnoid hemorrhage. DESIGN AND SETTING: A population-based case-control study in King County, Washington. SUBJECTS: Cases consisted of 149 patients with spontaneous subarachnoid hemorrhage. Two control subjects who were matched to cases by gender and age within 5 years were identified for each case using random digit telephone dialing. MAIN MEASURE: Detailed information on family history was obtained through an in-person interview. RESULTS: Some 11.4% of cases had a first-degree relative with a history of subarachnoid hemorrhage, compared with 6.4% of controls, yielding an odds ratio of 1.8 (95% CI, 0.92 to 3.7). The odds ratio for a positive family history among other relatives was 2.4 (95% CI, 1.1 to 5.2), likely reflecting family information bias. Findings were similar after adjustment was made for potential confounding variables, including cigarette smoking, a history of hypertension, and number of siblings and children. CONCLUSION: Although familial factors may be important in some families, overall they account for few cases of subarachnoid hemorrhage.

Risk of amyotrophic lateral sclerosis and history of physical activity: a population-based case-control study.

OBJECTIVE: To assess in greater detail than previous studies the purported association between a history of physical activity and amyotrophic lateral sclerosis (ALS). METHODS: A population-based case-control study was used to identify risk factors for ALS. Case patients were from 3 counties of western Washington State who were newly diagnosed as having ALS by a neurologist. Two control subjects matched with each case patient for sex and age within 5 years were identified by random digit telephone dialing or random selection from Medicare eligibility lists. All subjects underwent an in-person structured interview including detailed information about physical activity before a reference date, which was the month and year the case patient was diagnosed as having ALS. Various measures of physical activity both at work and leisure time were evaluated using conditional logistic regression taking into account the matching for sex and age. RESULTS: One hundred seventy-four case patients and 348 control subjects participated in the study. Physical activity was not significantly different between case patients and controls--whether at work, leisure time or both combined, and whether during a person's lifetime (from 10 years before reference date back to age 15 years) or during specific decades before reference date. An exception was that case patients reported having participated in organized sports in high school slightly more frequently than control subjects (odds ratio, 1.52; 95% confidence interval, 1.03-2.25). CONCLUSION: A history of physical activity has little, if any, effect on the risk of ALS.

Incidence of amyotrophic lateral sclerosis in three counties in western Washington state.

We conducted a population-based study of amyotrophic lateral sclerosis (ALS) in King, Pierce, and Snohomish counties in western Washington state. Between April 1, 1990 and March 31, 1995, neurologists diagnosed 235 patients with ALS, including 127 men (54%) and 108 women (46%). The incidence rate, age-adjusted to the 1990 total U.S. population, was higher for men at 2.1 per 100,000 per year (95% CI, 1.3 to 2.9) than for women at 1.9 (95% CI, 1.1, 2.7) and increased with age for both men and women. These incidence rates are consistent with other studies from northern latitudes.

Clinical course of spontaneous subarachnoid hemorrhage: a population-based study in King County, Washington.

Over 2 years, we identified 171 patients in King County, Washington, experiencing an incident subarachnoid hemorrhage and characterized their clinical course and outcome. Most (65%) were women and most (68%) were under age sixty-five. Only five died without medical attention. The remaining 166 patients were hospitalized and had CTs of the head. Of these, 103 underwent aneurysm surgery, 40 developed acute hydrocephalus, 32 had symptomatic vasospasm, and 30 re-bled. Sixty-eight percent (68%) survived to 1 month after the bleed and 62% to 1 year. Independent predictors of good recovery by 1 month after the bleed included youth, a high score on the admission Glasgow Coma Scale, and absence of blood on the first CT. In this population-based series, at 1 month after the bleed, approximately one-third of patients were dead, one-third had neurologic deficits, and one-third were doing well.

Aspartame ingestion and headaches: a randomized crossover trial.

To examine whether ingestion of aspartame is associated with headaches, we conducted a double-blind crossover study using volunteers with self-identified headaches after using aspartame. Of the 32 subjects randomized to receive aspartame (approximately 30 mg/kg/d) and placebo in a two-treatment, four-period crossover design, 18 completed the full protocol, seven completed part of the protocol before withdrawing due to adverse effects, three withdrew for other reasons, two were lost to follow-up, one was withdrawn due to noncompliance, and one withdrew and gave no reason. Each experimental period was 7 days long. Subjects reported headaches on 33% of the days during aspartame treatment, compared with 24% on placebo treatment (p = 0.04). Subjects who were "very sure" prior to the study that aspartame triggered some of their headaches reported larger treatment differences (aspartame = 0.37 headache-days, placebo = 0.18 headache-days; p < 0.001) than subjects who were "somewhat sure" (aspartame = 0.29 headache-days, placebo = 0.22 headache-days; p = 0.51) or "not sure" (aspartame = 0.33 headache-days, placebo = 0.39 headache-days; p = 0.51). There was no significant treatment difference in the length or intensity of headaches or in the occurrence of side effects associated with the headaches. This experiment provides evidence that, among individuals with self-reported headaches after ingestion of aspartame, a subset of this group report more headaches when tested under controlled conditions. It appears that some people are particularly susceptible to headaches caused by aspartame and may want to limit their consumption.