Effectiveness evaluation of Contra Caries Oral Health Education Program for improving Spanish-speaking parents' preventive oral health knowledge and behaviors for their young children.

OBJECTIVES: To determine the effectiveness of the Contra Caries Oral Health Education Program (CCOHEP) for improving low-income, Spanish-speaking parents' oral health knowledge and behaviors for their young children. Mexican American children in the United States suffer disproportionately high prevalence and severity of early childhood caries, yet few evaluated, theory-based behavioral interventions exist for this population. CCOHEP is a theory-based curriculum consisting of four 2-h interactive classes designed for and by Spanish speakers and led by designated community health educators (promotoras). Topics included children's oral hygiene, caries etiology, dental procedures, nutrition, child behavior management, and parent skill-building activities. METHODS: Low-income Spanish-speaking parents/caregivers of children aged 0-5 years were recruited through community services in an agricultural city in California. Survey questions from the Oral Health Basic Research Facts Questionnaire measuring oral health-related behaviors and knowledge were verbally administered before, immediately after, and 3 months after attendance at CCOHEP. Five questions measured aspects of parental toothbrushing for their children (frequency, using fluoridated toothpaste, brushing before bed, not drinking or eating after nighttime brushing, adult assistance), three questions measured other oral health behaviors, and 16 questions measured oral health-related knowledge. Analyses of within-person changes between pre- and post-tests and again between post-test and 3-month follow-up consisted of McNemar's test for binary outcomes and sign tests for ordinal outcomes. RESULTS: Overall, 105 caregivers participated in CCOHEP (n = 105 pretest, n = 95 post-test, n = 79 second post-test). At baseline, all parents self-reported doing at least one aspect of toothbrushing correctly, but only 13% reported performing all five aspects according to professional guidelines. At post-test, 44% of parents reported completing all aspects of toothbrushing according to professional guidelines (P < .001). Statistically significant improvements were seen in 4 aspects of toothbrushing (P ≤ .008) between pretest and post-test (all but adult assistance). The second post-test showed 3 of these improvements were maintained, while adult assistance and the other reported behaviors improved (P ≤ .008). Between pretest and post-test, checking child's teeth monthly and frequency of sweet drinks consumption improved (P ≤ .008), while frequency of eating sweet foods did not change. Knowledge was high at baseline (mean 12.8 of 16), but 6 knowledge items improved significantly between pretest and post-test. Improvements were maintained at second post-test. CONCLUSIONS: Contra Caries Oral Health Education Program improved low-income Spanish-speaking parents' oral hygiene knowledge and self-reported behaviors for their young children, and change was sustained 3 months after the end of the intervention. Future, more rigorous evaluation of the intervention is recommended.

American College of Rheumatology classification criteria for Sjögren's syndrome: a data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance cohort.

OBJECTIVE: We propose new classification criteria for Sjögren's syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS. METHODS: Criteria are based on expert opinion elicited using the nominal group technique and analyses of data from the Sjögren's International Collaborative Clinical Alliance. Preliminary criteria validation included comparisons with classifications based on the American­European Consensus Group (AECG) criteria, a model-based "gold standard"obtained from latent class analysis (LCA) of data from a range of diagnostic tests, and a comparison with cases and controls collected from sources external to the population used for criteria development. RESULTS: Validation results indicate high levels of sensitivity and specificity for the criteria. Case definition requires at least 2 of the following 3: 1) positive serum anti-SSA and/or anti-SSB or (positive rheumatoid factor and antinuclear antibody titer >1:320), 2) ocular staining score >3, or 3) presence of focal lymphocytic sialadenitis with a focus score >1 focus/4 mm2 in labial salivary gland biopsy samples. Observed agreement with the AECG criteria is high when these are applied using all objective tests. However, AECG classification based on allowable substitutions of symptoms for objective tests results in poor agreement with the proposed and LCA-derived classifications. CONCLUSION: These classification criteria developed from registry data collected using standardized measures are based on objective tests. Validation indicates improved classification performance relative to existing alternatives, making them more suitable for application in situations where misclassification may present health risks.

Risks for incident human papillomavirus infection and low-grade squamous intraepithelial lesion development in young females.

CONTEXT: Low-grade squamous intraepithelial lesions (LSILs) have been described as a benign cytological consequence of active human papillomavirus (HPV) replication. Several studies have reported that certain behavioral and biological risks exist for LSIL, suggesting that HPV alone is not sufficient for the development of LSIL. However, because most of these studies have been cross-sectional, it is not known whether behavioral and biological risks are simply risks for HPV infection itself. OBJECTIVE: To prospectively examine risks of incident HPV infection in HPV-negative females and of incident LSIL development in females with HPV infection. DESIGN: Prospective cohort study conducted between 1990-2000, with a median follow-up of 50 months. SETTING AND PARTICIPANTS: Females aged 13 to 21 years who attended 2 family planning clinics in the San Francisco bay area; 496 had prevalent HPV infection and 105 were HPV-negative. MAIN OUTCOME MEASURE: Incident development of HPV infection and LSIL, analyzed by various demographic, behavioral, and clinical risk factors. RESULTS: Fifty-four incident HPV infections occurred in the 105 females who were HPV-negative at study entry (median duration of follow-up for those who remained HPV-negative was 26 months). Multivariable analysis showed that risks of HPV included sexual behavior (relative hazard [RH], 10.10; 95% confidence interval [CI], 3.24-31.50 per new partner per month), history of herpes simplex virus (RH, 3.54; 95% CI, 1.37-9.10), and history of vulvar warts (RH, 2.73; 95% CI, 1.27-5.87). Current use of oral contraceptives had a significantly protective effect (RH, 0.49; 95% CI, 0.28-0.86). Among the 496 individuals who were HPV-positive at baseline or in follow-up, there were 109 incident cases of LSIL during the follow-up interval, with a median follow-up time of 60 months for those who never developed LSIL. Human papillomavirus infection was the most significant risk factor for development of LSIL. The multivariable model showed the following risks for LSIL: HPV infection for less than 1 year (RH, 7.40; 95% CI, 4.74-11.57); HPV infection for 1 to 2 years (RH, 10.27; 95% CI, 5.64-18.69); HPV infection for 2 to 3 years (RH, 6.11; 95% CI, 1.86-20.06); and daily cigarette smoking (RH, 1.67; 95% CI, 1.12-2.48). CONCLUSION: Our results indicate distinct risks for HPV and LSIL. In addition, most women with HPV infection in our study did not develop LSIL within a median follow-up period of 60 months. These findings underscore the hypothesis that certain biological risks thought to be associated with LSIL are, in fact, risks for acquisition of HPV. Cigarette smoking was a risk specific to LSIL, supporting the role of tobacco in neoplastic development.

Predictors of cigarette smoking and smoking cessation among adults with asthma.

OBJECTIVES: This study sought to determine the predictors of smoking and time until smoking cessation in a cohort of adults with asthma. METHODS: Adults with asthma (n = 374) in northern California completed structured telephone interviews at baseline and 18-month follow-up. RESULTS: Of the 374 subjects, 156 reported ever having smoked, and 39 indicated that they currently smoked. Earlier birth cohort, lower educational attainment. White race, and presence in childhood residence of an adult who smoked were associated with a greater risk of ever smoking. Lower educational attainment, early smoking initiation, higher daily cigarette consumption, and late-childhood-onset asthma were associated with a longer interval until smoking cessation. CONCLUSIONS: Persons with asthma at high risk of cigarette smoking and delayed quitting can be identified on the basis of clinical and demographic characteristics.

Trends in oral cancer rates in the United States, 1973-1996.

OBJECTIVES: To explore changes in demographic distribution, incidence and survival rates of oral cancer in the United States from 1973 through 1996. METHODS: From the Surveillance, Epidemiology, and End Results (SEER) data, we computed the proportion of oral cancer by demographic characteristics, site, and stage at diagnosis for 1973-84 and 1985-96. We estimated incidence and 5-year relative survival rates of oral cancer by age, gender, and race/ethnicity, and compared survival rates between the two periods. The estimated annual percent change (EAPC) was used to explore trends in incidence rate from 1973 through 1996. RESULTS: Most of the tongue and floor of mouth cancers (>54%) reported during 1973-84 and 1985-96 had spread to a distant site at time of diagnosis. The age-adjusted annual incidence rates of oral cancer decreased among white men from 1973 through 1996, but increased among black men aged 65-69 years, and among young white men (aged 30-34 years) and women (aged 25-29 years). These changes in trend were all statistically significant (testing EAPC=0 at the 0.05 level). Overall, there was no improvement in the 5-year relative survival rate of either whites or blacks with oral cancer. CONCLUSION: There was little change in early detection of oral cancer or in 5-year relative survival rates between 1973-84 and 1985-96 in nine SEER regions. This suggests a deficiency in professional and public education regarding early diagnosis of oral cancer. Furthermore, the increasing trend of oral cancer among older black men and among younger whites merits further investigation.

Effect of intravaginal practices on the vaginal and cervical mucosa of Zimbabwean women.

OBJECTIVES: Lesions on the vaginal and cervical mucosa may facilitate transmission of HIV and other sexually transmitted diseases (STDs). We evaluated the relationship between intravaginal practices and the presence of colposcopic lesions in Zimbabwean women. METHODS: Users and nonusers of intravaginal practices were seen at enrollment, and at 1 and 6 months. Interviewing, counseling, and pelvic and colposcopic examinations were performed at each study visit. Specimens were collected at enrollment and 6 months. RESULTS: Colposcopic lesions were found at least once in 83% of the participants (n = 162), and in 66% of all exams (n = 430). Most lesions were classified as related to infection with human Papillomavirus (HPV) (58%) or another pathogen (20%), but 11% of lesions could have been caused by intravaginal practices (signal lesions). Intravaginal practices were not associated with an increased incidence in signal lesions (95 and 124 lesions per 100 person-years of follow-up for users and nonusers respectively; p = .290), nor with the presence of signal lesions in multivariate baseline (odds ratio [OR], 1.32; 95% confidence interval [CI], 0.37-4.72; p = .666) and six month transition models (OR, 1.67; 95% CI, 0.59-4.70; p = .333). CONCLUSIONS: No associations between intravaginal practices and colposcopic lesions were found in this study. However, the potential effect of intravaginal practices on the cervical and vaginal mucosa, and on subsequent HIV and STD transmission, warrants further study. The usefulness of colposcopy as a research tool in areas with high prevalences of HIV and HPV is questioned.

Risk factors for abnormal anal cytology in young heterosexual women.

Although anal cancers are up to four times more common in women than men, little is known about the natural history of anal human papillomavirus (HPV) infections and HPV-related anal lesions in women. This study reports on the prevalence of and risks for anal cytological abnormalities over a 1-year period in a cohort of young women participating in a study of the natural history of cervical HPV infection. In addition to their regularly scheduled sexual behavior interviews and cervical testing, consenting women received anal HPV DNA and cytological testing. Anal cytology smears were obtained from 410 women whose mean age was 22.5 +/- 2.5 years at the onset of the study. Sixteen women (3.9%) were found to have abnormal anal cytology: 4 women had low-grade squamous intraepithelial lesions (SILs) or condyloma; and 12 women had atypical cells of undetermined significance. Factors found to be significantly associated with abnormal anal cytology were a history of anal sex [odds ratio (OR), 6.90; 95% confidence interval (CI), 1.7-47.2], a history of cervical SILs (OR, 4.13; 95% CI, 1.3-14.9), and a current anal HPV infection (OR, 12.28; 95% CI, 3.9-43.5). The strong association between anal intercourse and the development of HPV-induced SILs supports the role of sexual transmission of HPV in anal SILs. Young women who had engaged in anal intercourse or had a history of cervical SILs were found to be at highest risk.

The significance of squamous metaplasia in the development of low grade squamous intraepithelial lesions in young women.

BACKGROUND: The purpose of this study was to examine, prospectively, the presence and extent of cervical epithelial immaturity as well as the rate of squamous metaplastic activity as a risk for the development of low grade squamous intraepithelial lesions (LSIL). METHODS: The study was a nested case-control design that used subjects from an ongoing cohort study of human papillomavirus infection. Fifty-four sexually active young women who developed LSIL were matched for age and number of visits with 54 women who had never developed LSIL. The percent of cervical immaturity was interpreted from colpophotography using a computer-generated pixel count of delineated immature and total cervical areas. Activity of squamous metaplasia was interpreted as the percent change in the area of immaturity over a defined time period. Conditional logistic regression analysis examined risks for the development of LSIL. RESULTS: Baseline area of biologic immaturity was not a predictor of LSIL. However, women with the a high degree of metaplastic activity near the SIL event were more likely to develop LSIL (odds ratio = 3.01 [95% confidence interval, 1.3, 6.8] for every 10% unit change in area of immaturity). CONCLUSIONS: A rapid rate of metaplastic change within the transformation zone, rather than the initial area of biologic immaturity, is a significant risk factor for the development of LSIL.

Environmental tobacco smoke and adult asthma. The impact of changing exposure status on health outcomes.

The effect of environmental tobacco smoke (ETS) exposure on adults with asthma has not been well characterized. In a prospective cohort study of 451 nonsmoking adults with asthma, we evaluated the impact of ETS exposure on asthma severity, health status, and health care utilization over 18 mo. There were 129 subjects (29%; 95% CI, 25-33%) who reported regular ETS exposure, falling into three categories: exposure at baseline but none at follow-up (n = 43, 10%), no baseline exposure and new exposure at follow-up (n = 56, 12%), and exposure at both baseline and follow-up (n = 30, 7%). In cross-sectional analyses, subjects with baseline ETS exposure had greater severity-of-asthma scores (score difference, 1.7; 95% CI, 0. 2-3.1), worse asthma-specific quality of life scores (score difference, 3.5; 95% CI, 0.03-7.0), and worse scores on the Medical Outcomes Study SF-36 physical component summary (score difference, 3. 0; 95% CI, 0-6.0) than unexposed subjects. They also had greater odds of emergency department visits (odds ratio [OR] = 2.1; 95% CI, 1.2-3.5), urgent physician visits (OR = 1.9; 95% CI, 1.1-3.3), and hospitalizations (OR = 1.9; 95% CI, 1.02-3.6). In longitudinal follow-up, subjects reporting ETS cessation showed improvement in severity-of-asthma scores (score reduction, -3.2; 95% CI, -4.4 to -2. 0) and physical component summary scores (score increase, 5.3; 95% CI, 2.6-8.1). Environmental tobacco smoke cessation decreased the odds of emergency department visits (OR = 0.4; 95% CI, 0.2-0.97) and hospitalizations (OR = 0.2; 95% CI, 0.04-0.97) after adjustment for covariates. Environmental tobacco smoke initiation was associated with greater asthma severity only in subjects with high-level (>= 3 h/wk) exposure (score increase, 1.4; 95% CI, 0.03-2.7). In conclusion, self-reported ETS exposure is associated with greater asthma severity, worse health status, and increased health care utilization in adults with asthma.

The natural history of human papillomavirus infection as measured by repeated DNA testing in adolescent and young women.

OBJECTIVES: The objectives of this study were to describe the early natural history of human papillomavirus (HPV) infection by examining a cohort of young women positive for an HPV test and to define within this cohort (1) the probability of HPV regression, (2) the risk of having a squamous intraepithelial lesion, and (3) factors that were associated with HPV regression. STUDY DESIGN: The study was a cohort analytic design. An inception cohort of 618 women positive for HPV participated. HPV testing, cytologic evaluation, and colposcopic evaluation were performed at 4-month intervals. HPV testing was characterized for two groups: low risk (five types rarely associated with cancers) and high risk (nine types most commonly associated with cancers). RESULTS: Estimates provided by Kaplan-Meier curves showed that approximately 70% of women were found to have HPV regression by 24 months. Women with low-risk HPV type infections were more likely to show HPV regression than were women with high-risk HPV type infections (log rank test p = 0.002). The relative risk for the development of high-grade squamous intraepithelial lesion (HSIL) was 14.1 (95% confidence interval: 2.3, 84.5) for women with at least three positive tests for high-risk HPV preceding the development of the HSIL compared with that for women with negative tests for high-risk HPV. However, 88% of women with persistent positive HPV tests have not had HSIL to date. No factors associated with high-risk HPV type regression were identified except for a negative association with an incident history of vulvar condyloma (relative risk = 0.5 [95% confidence interval: 0.3 to 0.8]). CONCLUSION: Most young women with a positive HPV test will become negative within a 24-month period. Persistent positive tests with oncogenic HPV types represented a significant risk for the development of HSIL. However, we found that most young women with persistent positive HPV tests did not have cytologically perceptible HSIL over a 2-year period. Factors thought to be associated with the development of HSIL were found not to be important in HPV regression.

Can preference scores for discrete states be used to derive preference scores for an entire path of events? An application to prenatal diagnosis.

The authors conducted a study exploring whether preferences for sequences of events can be approximated by preferences for component discrete states. Visual-analog-scale (VAS) and standard-gamble (SG) scores for a subset of the possible sequences of events (path states) and component temporary and chronic outcomes (discrete states) that can follow prenatal diagnostic decisions were elicited from 121 pregnant women facing a choice between chorionic villus sampling and amniocentesis. For individuals, preference scores for path states could not be predicted easily from discrete-state scores. Mean path-state VAS scores, however, were predicted reasonably accurately by multiple regression models (R2 = 0.85 and 0.82 for two different anchoring schemes), with most measured scores lying within the 95% confidence intervals of the derived scores. It is concluded that, for individual patient decision making, preferences for path states should be elicited. When mean preference values for a population are sought, however, it may be reasonable to derive regression weights from a subset of respondents and then to apply those weights to preferences for discrete states elicited from a larger group.

Risk factors for anal human papillomavirus infection and anal cytologic abnormalities in HIV-positive and HIV-negative homosexual men.

Men with advanced human immunodeficiency virus (HIV) disease have a high prevalence of anal human papillomavirus (HPV) infection and potentially precancerous anal disease. To characterize prevalence of and risk factors for anal HPV infection and anal cytologic abnormalities, 37 HIV-positive and 28 HIV-negative participants in the San Francisco General Hospital Cohort Study were studied. A questionnaire was administered, followed by an anal examination consisting of two consecutive anal swabs for cytology and HPV DNA hybridization, and anoscopy with biopsy of visible lesions. Ten of 28 (36%) HIV-negative men and 19 of 37 (51%) HIV-positive men had anal HPV infection (p = 0.32). Risk factors for anal HPV infection included HIV positivity with a CD4 count < 200/mm3 (p = 0.03) and a history of smoking (p = 0.03). Abnormal anal cytology was found in 2 of 26 (8%) HIV-negative men and 10 of 36 (28%) HIV-positive men with cytology adequate for interpretation (p = 0.09). Risk factors for abnormal anal cytology included HIV positivity with a CD4 count < 200/mm3 (p = 0.006) and current smoking (p = 0.03). We conclude that the risk of development of anal disease and HPV infection was highest among HIV-positive men with a CD4 count of < 200/mm3, and that smoking may play a role in the pathogenesis of anal disease.

Time from HIV seroconversion to oral candidiasis or hairy leukoplakia among homosexual and bisexual men enrolled in three prospective cohorts.

OBJECTIVES: We evaluated time from HIV seroconversion to diagnosis of two common oral lesions associated with HIV infection and disease progression. DESIGN: Oral examinations were performed on homosexual and bisexual men enrolled in prospective cohorts. SETTING: Homosexual and bisexual men were followed in three epidemiologic cohort studies in San Francisco, California, USA. PARTICIPANTS: Data were evaluated from 80 men with well-defined dates of HIV seroconversion from 1984 through 1991. MAIN OUTCOME MEASURES: We determined the cumulative incidence of oral candidiasis and hairy leukoplakia after HIV seroconversion. RESULTS: Four per cent of men developed oral candidiasis within 1 year after HIV seroconversion, 8% within 2, 15% within 3, 18% within 4, and 26% within 5 years. Nine per cent developed hairy leukoplakia within 1 year, 16% within 2, 25% within 3, 35% within 4, and 42% within 5 years. The median CD4+ count was 391 x 10(6)/l when oral candidiasis was first reported and 468 x 10(6)/l when hairy leukoplakia was first reported. CONCLUSIONS: Oral candidiasis or hairy leukoplakia appeared in a significant proportion of HIV-infected homosexual and bisexual men. These lesions occurred relatively soon after HIV seroconversion, typically before AIDS. Evaluation of HIV-infected individuals for these lesions has many potential clinical and research benefits, including the possible use of oral lesions as primary end-points in clinical trials.

Progression to AIDS in HIV-infected homosexual and bisexual men with hairy leukoplakia and oral candidiasis.

OBJECTIVE: This study was designed to assess the significance of HIV-related oral lesions in predicting the rate of progression to AIDS. DESIGN: Cohorts were investigated prospectively, and oral examinations were performed by clinicians trained in the diagnosis of oral lesions. SETTING: We studied three existing cohorts of homosexual and bisexual men in San Francisco, California, USA. PARTICIPANTS: Of the HIV-infected men who received standardized oral examinations (n = 791), 603 were eligible for analysis of baseline examinations and 448 for analysis of follow-up examinations. MAIN OUTCOME MEASURES: We determined time from presence of oral lesion at baseline or follow-up examination, or from participant self-reported history of the lesion, to diagnosis of AIDS. RESULTS: Using proportional hazard regression and stratifying by CD4 lymphocyte count at the time of baseline oral examination, we found that the rate of development of AIDS was increased among men with hairy leukoplakia [relative hazard, 1.8; 95% confidence interval (CI), 1.2-2.7], oral candidiasis (relative hazard, 7.3; 95% CI, 3.1-17.3), and both lesions (relative hazard, 3.1; 95% CI, 1.6-6.1) compared with men with normal findings. On follow-up examination, stratifying for CD4 count, the rate of progression to AIDS was similar for those with hairy leukoplakia compared with those with oral candidiasis. The progression rate from oral candidiasis to AIDS was faster from presence on baseline examination than from presence on follow-up examination or from self-reported history of the lesion. CONCLUSION: The presence of oral candidiasis and/or hairy leukoplakia on baseline examination confers independent prognostic information and should be incorporated into HIV-staging schemes.

Immune activation markers and AIDS prognosis.

Four assays for serum levels of cellular products of immune activation were examined as prognostic markers for AIDS in a prospective study of asymptomatic HIV-seropositive homosexual men. Baseline serum values of beta 2-microglobulin (beta 2M), neopterin, soluble CD8 (sCD8), and soluble interleukin-2 receptor (sIL-2R) for 185 men were examined univariately and multivariately as predictors of AIDS during 36 months of follow-up. Thirty-three cases of AIDS (18%) were diagnosed during the follow-up period. All four assays correlated highly with each other (r = 0.48-0.63), and all four were good univariate predictors of AIDS and comparable to CD4 lymphocyte count. beta 2M, neopterin, and sCD8 predicted AIDS independently of both CD4 count and HIV p24 antigen or p24 antibody in multivariate analysis. Within the range of CD4 count 200-499 x 10(6) cells/l, an immune activation marker used in combination with an assay for p24 antigen identifies those at 3-6% risk of AIDS over 36 months (low risk on both assays) and those at 63-86% risk (high risk on both assays). These results can be used to guide physicians and patients making decisions about treating asymptomatic HIV infection with zidovudine in individuals with CD4 lymphocyte count of 200-499 x 10(6) cells/l.

Log-linear models for cancer risk among migrants.

Epidemiological studies of migrants have played an important role in separating the environmental and genetic components of cancer aetiology. The statistical analyses of these studies have typically involved calculating age- and sex-adjusted rates by country of birth. We describe methods which permit the effect of duration of residence in the host country to be estimated after adjusting for other temporal effects such as age, and period or cohort. The methods, which are based on log-linear modelling, can also be applied in a case-control manner if appropriate denominator populations are unavailable. Examples are given in which the more traditional methods of analysis may have yielded misleading results.

A case-control study of diet and breast cancer in Argentina.

A case-control study of breast cancer was carried out in La Plata, Argentina, where the incidence of the disease is comparable to the highest rates recorded worldwide. One hundred and fifty incident cases were identified through major hospitals. For each case, a hospital control, matched by age and hospital, and a neighbourhood control, matched by residential area and age, were also chosen. Cases and controls were interviewed to obtain information on past diet, as well as demographic and socio-economic characteristics, reproductive and menstrual history and other potential breast-cancer risk factors. The dietary information was obtained from questions on the consumption of specific food items and information on portion sizes from an earlier study was used to estimate intake of calories and selected nutrients. There was a substantial excess energy intake among cases as compared to both control groups, which was present across all 3 major macronutrients which contribute to total calories. Among the food groups, the consumption of eggs was a risk factor for breast cancer, and whole-milk products and green leafy vegetables were protective. After adjusting for the calorie difference in multivariate statistical analyses of nutrients, fibre and beta-carotene consumption were weakly protective. The results are discussed with reference to possible methodological difficulties and previous studies of diet and breast cancer.

Epidemiological studies of anticancer drug carcinogenicity.

In recent years, epidemiological methods have been used increasingly to study the carcinogenicity of drugs used in the chemotherapy of cancer. Such studies are useful to clinicians in identifying therapeutic agents with particular long-term risk to patients. They can also provide information on the dose- and time-related risks of cancer in one of the few human populations intentionally exposed to known levels of carcinogens. Aspects of epidemiological studies of second cancer risk are described, including sources of cases, study design, statistical methods, and possible biases. Results from a cohort study of second cancers following ovarian cancer, testicular cancer and Hodgkin's disease and from a case-control study of leukaemia following Hodgkin's disease are also given.