A broad anticancer effect of aspirin?
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Biomedical subjects
Publications and source records attributed to J A Baron.
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BACKGROUND: Epidemiological studies have indicated that aspirin consumption can lower the risk of large-bowel cancer. These studies are not entirely consistent, however, and their interpretation has been complicated by the possibility that cancer symptoms may have led patients to avoid aspirin or that aspirin may have influenced cancer diagnosis and treatment. PURPOSE: Our purpose was to determine the effect of aspirin on risk of large-bowel neoplasms in a study in which aspirin use would not be expected to affect tumor detection and tumor-related symptoms would not likely influence aspirin use. A less complicated assessment of the relationship between aspirin and large-bowel tumors should thus be possible. METHODS: We studied 793 patients enrolled in a clinical trial of nutrient supplements to prevent large-bowel adenomas. Unlike invasive cancers, adenomas usually do not cause symptoms or detectable gastrointestinal bleeding; thus, adenomas are unlikely to influence aspirin use. Each patient had at least one large-bowel adenoma diagnosed and removed shortly before study entry and had been judged to be free of further tumors by colonoscopy. Use of aspirin was assessed by responses on questionnaires administered 6 and 12 months after enrollment. We performed complete colonoscopies on all patients 1 year after they entered the study and removed all polyps. RESULTS: Patients who reported taking aspirin on both questionnaires (consistent users) had a lower risk of new adenomas at their 1-year follow-up colonoscopy (odds ratio = 0.52; 95% confidence interval = 0.31-0.89) compared with patients who did not report using aspirin on either of the questionnaires. The apparent protective effect of consistent aspirin use was present among both men and women and did not appear to be influenced by the number of prior adenomas. CONCLUSIONS: These data further support the hypothesis that aspirin has an antineoplastic effect in the large bowel. Nevertheless, the question of whether aspirin should be used to prevent large-bowel tumors would be best answered by a randomized controlled clinical trial specifically designed to address this issue.
It has been proposed that differences in diet between smokers and nonsmokers may partially explain the positive association between cigarette smoking and diseases such as cancer and coronary heart disease. To investigate the potential for this confounding, the authors studied the relation between cigarette smoking and nutrient intake in a population-based sample of 451 Australian women between 1982 and 1984. Dietary intake was determined by a quantitative food frequency questionnaire. Relations with smoking were assessed by use of analysis of covariance. The mean daily intake of total dietary fiber in current smokers was 4.1 g lower than in never smokers, with a 95% confidence interval for the difference of 1.4-6.8 g. The mean intake of total calories, cholesterol, sucrose, linoleic acid, total fat, and monounsaturated and polyunsaturated fat did not vary significantly by smoking status. However, former smokers were found to have a higher ratio of polyunsaturated to saturated fat as compared with current or never smokers and a lower intake of saturated fat as compared with current smokers. These associations persisted when the effects of total energy intake, age, years of education, and alcohol consumption were considered. The decreased ingestion of fiber by cigarette smokers could contribute to their increased risks of coronary heart disease and cancer compared with those in nonsmokers. The increased ratio of polyunsaturated to saturated fat and decreased ingestion of saturated fat in the diet of former smokers may help to reduce their risks.
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OBJECTIVE: To test whether a patient's perception of benefit is influenced by whether the benefit is presented in relative or absolute terms. DESIGN: Questionnaire-based study. SETTING: A general medicine outpatient clinic at a rural tertiary care center associated with a medical school. PATIENTS: 470 of 511 consecutive patients who agreed to answer a questionnaire while waiting for their clinic visit. Mean age was 49.1 years, 62.1% were female, and 51.9% had at least one year of education beyond high school. MAIN OUTCOME MEASURES: Patient response to the choice of two equally efficacious medications for the management of a hypothetical serious disease. The benefit of one medication was stated in relative terms, the other in absolute terms. Patients could choose either medication alone, indicate indifference to the choice of medication, or choose not to answer. MAIN RESULTS: 56.8% of the patients chose the medication whose benefit was in relative terms. 14.7% chose the medication whose benefit was in absolute terms. Only 15.5% were indifferent to the choice of medication. The patients preferred the medication whose benefit was in relative terms across a wide range of ages and educational levels. Further questioning suggested that the patients thought benefit was greater when expressed in relative terms because they ignored the underlying risk of disease and assumed it was one. CONCLUSIONS: The "framing" of benefit (or risk) in relative versus absolute terms may have a major influence on patient preference.
OBJECTIVE: The primary aims of this study were to assess risk of subsequent basal and squamous cell skin cancer among patients with a prior history of these tumors and to examine these risks in relation to patient characteristics and life-style factors. DESIGN: Follow-up of participants in a randomized trial of betacarotene as a possible skin cancer preventive agent. SETTING: Clinical centers in Los Angeles, Calif, San Francisco, Calif, Minneapolis, Minn, and Hanover, NH. PARTICIPANTS: Patients (n = 1805) who were diagnosed as having a basal or squamous cell skin cancer between January 1980 and February 1986 and were free of skin cancer at study entry. MAIN OUTCOME MEASURE: Time from study entry to first new occurrence of basal and squamous cell skin cancer. RESULTS: The estimated risk of developing one or more new skin cancers was 35% at 3 years and 50% at 5 years. New skin cancers tended to be of the same cell type as the previous skin cancers. For both basal and squamous cell skin cancer, risk was higher among patients who were male, were over the age of 60 years, had more prior skin cancers, had severe actinic skin damage, or who burned easily with sun exposure. Compared with those who had never smoked, the rate of subsequent squamous cell skin cancer was higher among current smokers (rate ratio, 2.01; 95% confidence interval, 1.21 to 3.34) and former smokers (rate ratio, 1.62; 95% confidence interval, 1.07 to 2.47) and increased with both duration and amount smoked. There was no clear relationship between smoking and basal cell skin cancer; the rate appeared lower among heavy smokers but was unrelated to duration of smoking. CONCLUSIONS: Persons with a prior nonmelanoma skin cancer had a substantial 5-year risk of developing another tumor of the same histologic type. Number of previous skin cancers, solar damage, and skin sensitivity to sun exposure were particularly related to this risk. The increased risk of squamous cell skin cancer associated with cigarette smoking merits further study.
OBJECTIVE: To determine if the association between smoking and osteoporotic fractures is related to the quantity of cigarettes smoked and to determine if smoking modifies the protection by estrogens. DESIGN: Cohort study. SETTING: A population-based cohort study, the Framingham Study. PARTICIPANTS: A total of 2873 women in the Framingham Study followed through examination 19 (1985-1987). MEASUREMENTS: All fractures of the proximal femur sustained by women in the Framingham Study from 1948 to 1987 were ascertained. At almost all examinations, available information on cigarette smoking was used to classify women as "ever smokers" compared with "never smokers," and, among "ever smokers," "current" compared with "former smokers." A similar classification for estrogen use was created. Information on potentially confounding variables was taken from each examination, including age, adiposity (weight/height2), alcohol consumption (ounces per week), and caffeine intake (coffee and tea). RESULTS: Overall, 207 hip fractures occurred among 34,700 woman-examinations of observation. In the entire cohort, current smoking did not appear to increase hip fracture risk (adjusted odds ratio [AOR], 1.22; 95% CI, 0.76 to 1.95; P greater than 0.2). Also overall, current estrogen use appeared to be protective (AOR, 0.38; CI, 0.12 to 1.21, P = 0.10). Among current smokers, however, estrogen use did not protect against fracture (AOR for current use, 1.26; CI, 0.29 to 5.45), whereas estrogen was protective in nonsmokers (AOR for current or past use, 0.37; CI, 0.19 to 0.75; P = 0.005). CONCLUSIONS: Overall, smoking does not appear to increase the risk for hip fracture in women. Although estrogen replacement protects nonsmokers from fracture, smoking may negate the protective skeletal effects of estrogen replacement therapy.
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BACKGROUND: Health care databases provide a widely used source of data for health care research, but their accuracy remains uncertain. We analyzed data from the 1985 National DRG Validation Study, which carefully reabstracted and reassigned ICD-9-CM diagnosis and procedure codes from a national sample of 7050 medical records, to determine whether coding accuracy had improved since the Institute of Medicine studies of the 1970s and to assess the current coding accuracy of specific diagnoses and procedures. METHODS: We defined agreement as the proportion of all reabstracted records that had the same principal diagnosis or procedure coded on both the original (hospital) record and on the reabstracted record. We also evaluated coding accuracy in 1985 using the concepts of diagnostic test evaluation. RESULTS: Overall, the percentage of agreement between the principal diagnosis on the reabstracted record and the original hospital record, when analyzed at the third digit, improved from 73.2% in 1977 to 78.2% in 1985. However, analysis of the 1985 data demonstrated that the accuracy of diagnosis and procedure coding varies substantially across conditions. CONCLUSIONS: Although some diagnoses and all major surgical procedures that we examined were accurately coded, the variability in the accuracy of diagnosis coding poses a problem that must be overcome if claims-based research is to achieve its full potential.
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Female registered nurses in the United States who responded to a questionnaire in 1976 that inquired about height, weight, and smoking history were followed for the development of colon or rectal cancers through May of 1984. Among the 118,404 respondents free of cancer in 1976, 191 colon cancers and 49 rectal cancers were observed during 916,170 person-years of follow-up. After omitting cases diagnosed within two years of weight report, we found little overall relation of body mass (Quetelet's) index to colon cancer risk; however there was a suggestion of elevated risk for the heaviest category of body mass index (greater than or equal to 29 kg/m2, relative risk (RR) = 1.5; 95 percent confidence interval = 0.8 - 2.7) relative to the lowest category (less than 21 kg/m2). Self-reported body mass index from adolescence had a slightly more pronounced, although not significant, association with risk of colon cancer. Increasing height was significantly associated with colon cancer (RR = 1.6, 95 percent confidence interval = 1.1 - 2.5 for the tallest category [greater than or equal to 168 cm] versus the shortest (less than 160 cm], trend, P = 0.04). Measures of current or past smoking failed to demonstrate any consistent relationship with colon cancer.
We investigated differences in lung cancer care and outcome between academic and community settings for all lung cancer patients diagnosed during 1973-1976 in New Hampshire and Vermont. Trained abstracters reviewed hospital charts to record personal, diagnostic, and clinical information, and survival was determined for all patients through the end of 1979. Patients diagnosed in university hospital cancer centers underwent more staging procedures and tended to be assigned to a higher stage than similar patients diagnosed in community hospitals. When tumor stage was considered as a covariable in a survival analysis, these patients appeared to have a lower mortality rate both for non-small cell tumors (mortality rate ratio, 95% confidence interval = 0.81, 0.71-0.91) and for small cell tumors (0.71, 0.55-0.91). When functional status rather than tumor stage was used to adjust for disease severity, there was no apparent survival advantage for university patients with non-small cell cancer (0.96, 0.85-1.09) and the lower mortality for small cell cancers (0.76, 0.59-0.97) was attenuated, although still statistically significant. We conclude that inconsistently-collected data on clinical stage can complicate comparisons of prognosis between cancer patients from different types of hospitals and that measures of performance status may be more useful indicators of disease severity in population based studies.
Epidemiological evidence has suggested that cigarette smoking has an anti-oestrogenic effect in women, but the effects of smoking on steroid hormone metabolism are not fully understood. We compared serum concentrations of oestradiol, progesterone (luteal phase) and dehydroepiandrosterone sulphate (DHEA-S), and urinary excretion rates of six steroids of predominantly adrenal origin, in healthy premenopausal and postmenopausal female smokers and non-smokers. Serum concentrations of oestradiol, progesterone and DHEA-S did not differ between smokers and non-smokers by greater than 5%, and none of these differences was statistically significant. Mean urinary excretion rates of androsterone, aetiocholanolone, DHEA, 11-keto-aetiocholanolone, 11-hydroxyandrosterone and 11-hydroxyaetiocholanolone were very similar in smokers and non-smokers in premenopausal women, but were from 2-44% higher in smokers than non-smokers in postmenopausal women. The difference was statistically significant only for 11-hydroxyandrosterone. These results confirm previous reports that cigarette smoking does not affect serum oestradiol in premenopausal or postmenopausal women, but provide only weak evidence to support previous findings of increased levels of some adrenal steroids in postmenopausal women smokers. The mechanism for the apparent anti-oestrogenic effect of cigarette smoking remains unclear.
One of the goals of our medical school is to teach our students how to learn. In theory, this is a noble goal, but, in practice, our style is often to "impart" our knowledge to the students without allowing them to question it, to practice with it, and to really understand it. To address this problem, we are developing a vertically integrated four-year program in medical decision making funded by the Culpeper Foundation. The curriculum begins with classic epidemiology in year one. In year-two courses, principles of clinical epidemiology (diagnosis, variability, etc) and the elements of quantitative decision making are woven into our organ system courses. In year three, these skills are practiced in clerkships, and critical thinking sessions occur in several clerkships. The curriculum culminates in year four with sessions on expected value decision analysis in one of our required courses. Built into this experience are computer interactive programs, faculty and housestaff development sessions, and availability of consultation from a medical decision making team. We are developing competency-based exams in which students will have to demonstrate skills in medical decision making, critical thinking, and problem solving. We hope this will help teach our students "how to" make decisions and understand such things as critical thinking, probability, uncertainty, and variability. Through this, we hope the decisions they will help their patients make will lead to the "best" outcomes for these patients.
We studied the relationship between eight variables, including age, sex, baseline plasma beta-carotene (BC) concentration, and smoking status and the increase in plasma BC in 582 subjects receiving oral supplementation with 50 mg BC/d. Median plasma BC concentrations after 1 y of supplementation increased from 335 nmol/L at entry to 3163 nmol/L. Changes in plasma BC concentrations ranged widely from -313 to 16,090 nmol/L (median 2721 nmol/L). Multivariate analysis revealed that the subject's plasma BC concentration before supplementation was the most important indicator of the amount of increase after supplementation. Nonsmokers, women, and leaner subjects all had larger increases in plasma concentrations although the statistical model could account for relatively little of the variability in subjects' plasma response to BC supplementation (R2 = 0.14). We conclude that between-subject variability in response to daily supplementation with oral BC is very large and that the best predictor of this response is the initial plasma BC concentration.
The relationship between smoking habits and the risk of benign breast disease (BBD) was analyzed using data from a case-control study conducted between 1981 and 1983 in the greater Milan area, Northern Italy. Cases (n = 288) were women with histologically confirmed BBD (203 dysplasia, 85 benign tumours) referred to the National Cancer Institute of Milan for biopsies. Controls were women (n = 291) seen on selected days for a cytological smear for cervical cancer in outpatient clinics of the same Institute. No consistent association emerged between various indicators of smoking habits (smoking status, number of cigarettes smoked per day, duration of smoking) and the risk of BBD. Compared with never smokers the relative risk (RR) of all BBD combined was 0.7 (95% confidence interval, Cl: 0.4-1.3) in exsmokers, 1.4 (95% Cl: 0.8-2.5) in smokers of less than 10 cigarettes per day, and 1.1 (95% Cl: 0.7-1.7) in smokers of 10 or more cigarettes per day. There was some suggestion that the risk may be below unity post-menopause, but the relative risks for smokers were not statistically different in pre- (RR = 1.2; 95% Cl: 0.8-1.8) and post-menopausal (RR = 0.6; 95% Cl: 0.2-1.7) women. The risk of benign tumours (chiefly fibradenoma) was higher in current smokers, but this finding was not statistically significant (RR = 1.5; 95% Cl: 0.9-2.6) and the highest risks were observed in the strata of lighter smokers and those with shorter duration of smoking. Overall these results fail to support a negative association between smoking habits and benign breast disease.