Marguerite Stevens

A clinical trial of antioxidant vitamins to prevent colorectal adenoma

BACKGROUND People who consume a diet high in vegetables and fruits have a lower risk of cancer of the large bowel. Antioxidant vitamins, which are present in vegetables and fruits, have been associated with a diminished risk of cancers at various anatomical sites. We conducted a randomized, controlled clinical trial to test the efficacy of beta carotene and vitamins C and E in preventing colorectal adenoma, a precursor of invasive cancer. METHODS We randomly assigned 864 patients, using a two-by-two factorial design, to four treatment groups, which received placebo; beta carotene (25 mg daily); vitamin C (1 g daily) and vitamin E (400 mg daily); or the beta carotene plus vitamins C and E. In order to identify new adenomas, we performed complete colonoscopic examinations in the patients one year and four years after they entered the study. The primary end points for analyses were new adenomas identified after the first of these two follow-up examinations. RESULTS Patients adhered well to the prescribed regimen, and 751 completed the four-year clinical trial. There was no evidence that either beta carotene or vitamins C and E reduced the incidence of adenomas; the relative risk for beta carotene was 1.01 (95 percent confidence interval, 0.85 to 1.20); for vitamins C and E, it was 1.08 (95 percent confidence interval, 0.91 to 1.29). Neither treatment appeared to be effective in any subgroup of patients or in the prevention of any subtype of polyp defined by size or location. CONCLUSIONS The lack of efficacy of these vitamins argues against the use of supplemental beta carotene and vitamins C and E to prevent colorectal cancer. Although our data do not prove definitively that these antioxidants have no anticancer effect, other dietary factors may make more important contributions to the reduction in the risk of cancer associated with a diet high in vegetables and fruits.

A clinical trial of beta carotene to prevent basal-cell and squamous-cell cancers of the skin

BACKGROUND Beta carotene has been associated with a decreased risk of human cancer in many studies employing dietary questionnaires or blood measurements, and it has had protective effects in some animal models of carcinogenesis. METHODS We tested the possible cancer-preventing effects of beta carotene by randomly assigning 1805 patients who had had a recent nonmelanoma skin cancer to receive either 50 mg of beta carotene or placebo per day and by conducting annual skin examinations to determine the occurrence of new nonmelanoma skin cancer. RESULTS Adherence to the prescribed treatment was good, and after one year the actively treated groups median plasma beta carotene level (3021 nmol per liter) was much higher than that of the control group (354 nmol per liter). After five years of follow-up, however, there was no difference between the groups in the rate of occurrence of the first new nonmelanoma skin cancer (relative rate, 1.05; 95 percent confidence interval, 0.91 to 1.22). In subgroup analyses, active treatment showed no efficacy either in the patients whose initial plasma beta carotene level was in the lowest quartile or in those who currently smoked. There was also no significant difference between treated and control groups in the mean number of new nonmelanoma skin cancers per patient-year. CONCLUSIONS In persons with a previous nonmelanoma skin cancer, treatment with beta carotene does not reduce the occurrence of new skin cancers over a five-year period of treatment and observation.

Role of Written Advance Directives in Decision Making

OBJECTIVE: To understand the role of written advance directives (ADs) in medical decision making through examination of qualitative and quantitative data sources. We specifically wanted to address whether physicians unilaterally disregard advance directives.DESIGN: Block randomized controlled trial to improve decision making and outcomes of seriously ill patients.SETTING: Five academic medical centers.PATIENTS: Fourteen hospitalized, seriously ill adults were randomized to receive an intervention of patient-specific information on prognoses and specially trained nurse to facilitate decision making. To be included in this analysis, patients reported having an AD and also met one of these criteria of severity; were comatose, had objective estimate of prognosis for surviving 2 months of 40% or less, or died during this hospital admission.MEASUREMENTS AND MAIN RESULTS: Quantitative data sources consisted of medical record review and interviews with the patient (when possible), surrogate, and responsible physician about prognosis, symptoms, preferences, and decision making. Qualitative data consisted of narratives by the nurse responsible for counseling and facilitating decision making. Each element of the quantitative database was reviewed, and a timeline of communication and decision making was constructed. Qualitative data were analyzed using grounded theory and narrative summary analysis. We compared and contrasted qualitative and quantitative data to better understand the role of ADs in decision making. In each case, the patient had a period of diminished capacity in which ADs should have been invoked. Advance directives played an important role in decision making of 5 of 14 cases, but even in those cases, life-sustaining treatment was stopped only when the patient was “absolutely, hopelessly ill.” In two of these cases, the family member wrongly reported that the patient had an AD, and in the remaining seven cases, ADs had a limited role. The limited role could not be traced to a single explanation. Rather, a complex interaction of several factors was identified: patients were not considered hopelessly ill, so the directive was never seen as applicable and a transition in the goals of care did not occur; family members or the designated surrogate were not available, were ineffectual, or were overwhelmed; or the content of the AD was vague, or not applicable to the clinical situation, and the intent in completing the AD was never clarified. A physician did not unilaterally disregard a patient’s preference in any of the cases. Two factors that enhanced the role of the AD were an available surrogate who was able to advocate for the patient and open communication between the physician and the surrogate in which the patient’s prognosis was reconsidered.CONCLUSIONS: Our findings indicate that physicians are not unilaterally disregarding patients’ ADs. Despite the patients’ serious illnesses, family members and physicians did not see them as “absolutely, hopelessly ill.” Hence, ADs were not considered applicable to the majority of these cases. Cases in which Ads had an impact evidenced open negotiation with a surrogate that yielded a transition in the goals of care.

Rethinking fundamental assumptions : SUPPORT's implications for future reform

BACKGROUND: The intervention in SUPPORT, the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments, was ineffective in changing communication, decision‐making, and treatment patterns despite evidence that counseling and information were delivered as planned. The previous paper in this volume shows that modest alterations in the intervention design probably did not explain the lack of substantial effects.

Ineffectiveness of the SUPPORT intervention: review of explanations.

BACKGROUND: The aim of the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments — SUPPORT — was to improve the care of seriously ill patients by improving decision‐making for patients with life‐threatening illnesses. Several theories have been proposed to explain why the SUPPORT intervention was unsuccessful at improving outcomes.

Description of the SUPPORT Intervention

BACKGROUND: The purpose of Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) was to improve outcomes for seriously ill hospitalized adults by improving information and decisionmaking. The SUPPORT intervention has been characterized only briefly in previous publications.

The Skin Cancer Prevention Study: design of a clinical trial of beta-carotene among persons at high risk for nonmelanoma skin cancer.

We describe a randomized clinical trial of oral beta-carotene (50 mg/day) for preventing nonmelanoma skin cancer. It is a multicenter study conducted at sites in California, Minnesota, and New Hampshire. This report describes the design of the study, baseline characteristics of the 1805 randomized patients, changes in their plasma beta-carotene and retinol levels after 1 year of treatment, and plans for statistical analyses. Important features of this study are (1) a high proportion of potential subjects were found to be ineligible or chose not to enter the study, (2) the study agent is readily available over the counter and in common foods, and (3) nonmelanoma skin cancer is a relatively minor health concern for most patients. These considerations necessitated intensive efforts to encourage compliance with the study regimen. There are also some unusual statistical features of the study. One is that the study outcome is routinely assessed only at annual examinations, so the precise time of failure cannot be identified. Also, a secondary goal of the study is to determine whether beta-carotene decreases the average number of new skin cancers per patient per year, and there are no established statistical methods for analysis of data in this situation. Alternative approaches to the analysis are discussed.

Three-year results of prevention programs on marijuana use : The New Hampshire study

The effects on marijuana use of 1) a drug prevention curriculum, or 2) this curriculum with added parent and other adult community activities in comparison with 3) a control community were investigated. Baseline information on drug-related behaviors from a sample of fourth, fifth, and sixth graders aged nine to fourteen years in rural New Hampshire (N = 1200) were obtained. The children completed these initial questionnaires in classrooms in 1987. In the comprehensive community intervention regular marijuana use was reduced by over 50 percent. No program had a significant effect on the initiation of marijuana use. The predictors of initiation were being in a higher grade, low school satisfaction, poor academic achievement, feeling unloved by ones family, feeling unpopular, and being part of a drug-using peer group. The baseline predictors of subsequent regular marijuana use were poor academic achievement, feeling unpopular, and being part of a drug-using peer group. In interviews the cultural and social contexts of marijuana use were explored. Strategies to prevent marijuana use need to take into account the profile of the marijuana-using child, the adult communitys attitudes and beliefs about drugs, and the access of drug sellers and users to children.

Prevalence and Correlates of Alcohol Use in a Survey of Rural Elementary School Students: The New Hampshire Study

Alcohol use by 1190 fourth, fifth and sixth grade students was assessed in a survey of four rural New Hampshire school districts. Half the students surveyed (596) drank, but not regularly; 5 percent (59) were regular drinkers, and an additional 2 percent (19) were regular drinkers and had been drunk at least once. Reported alcohol use increased with both grade and age, and males drank more than females. The childs attitude towards drinking, perceived family attitudes towards drinking, the number of drinking friends, and self-perceived wrongdoing by the child were four factors strongly related to alcohol use. Increased alcohol use was also associated with experimental and current use of cigarettes, marijuana, and smokeless tobacco.

MAMMOGRAPHY IN NEW HAMPSHIRE: CHARACTERISTICS OF THE WOMEN AND THE EXAMS THEY RECEIVE

New Hampshire (NH) is one of two states that has developed a population-based mammography registry. The purpose of this paper is to describe what we have learned about mammography use in New Hampshire. After collecting data for 20 months, the database contains almost 110,000 mammographic encounters representing 101,679 NH women, who range in age from 18 to 97 with a mean of 56.7 years (SD=10.91). Education levels are high with 92% having a high school education and 59% with some college. Forty-six percent report their primary insurance is private, 29% report HMO/PPO coverage, and 25% receive federal health care assistance. Risk factors represented in the database include (categories not mutually exclusive) advancing age (60% over age 50), hormone replacement therapy use by menopausal women (40.6%), and a family history of breast cancer (29%). Penetration of mammography relative to the NH population is higher for younger age groups (40–48% for those aged 44–64) than older age groups (34–39% for those aged 65–84). The majority of mammographic encounters are routine screening exams (86%), often interpreted as negative or normal with benign findings (88%). Use of comparison films to interpret either diagnostic or screening mammography occurred in 86% of encounters. We have matched 3,877 breast pathology records to these mammographic encounters. The distribution of pathology outcomes for diagnostic exams was very similar to that for screening exams (approximately 65% benign, 17% invasive breast cancer, and 6% noninvasive breast cancer). Overall, we have designed a system that is well accepted by the NH community. Challenges include careful monitoring of data for coding errors, and a limitation of linking variables in mammography and pathology data. Data represented in this registry are a critical resource for research in mammographic screening and breast cancer early detection.