Perfluorooctanoate and changes in anthropometric parameters with age in young girls in the Greater Cincinnati and San Francisco Bay Area.

METHODS: We conducted a study of per- and polyfluoroalkyl substance biomarkers, including PFOA, in girls from Greater Cincinnati (CIN, N = 353) and the San Francisco Bay Area (SFBA, N = 351). PFOA was measured in the baseline serum sample collected in 2004-2007 of 704 girls at age 6-8 years. Mixed effects models were used to derive the effect of PFOA on BMI, waist-to-height and waist-to-hip ratios over increasing age in this longitudinal cohort. RESULTS: Median PFOA serum concentrations were 7.3 (CIN) and 5.8 (SFBA) ng/mL, above the U.S. population median for children 12-19 years in 2005-2006 (3.8 ng/mL). Log-transformed serum PFOA had a strong inverse association with BMIz in the CIN girls (p = 0.0002) and the combined two-site data (p = 0.0008); the joint inverse effect of PFOA and Age*PFOA weakened at age at 10-11 years. However, in the SFBA group alone, the relationship was not significant (p = 0.1641) with no evidence of changing effect with age. The effect of PFOA on waist:height ratio was similar to BMIz at both sites, but we did not find a significant effect of PFOA on waist:hip ratio in either the CIN or SFBA girls. CONCLUSIONS: PFOA is associated with decreased BMI and waist:height ratio in young girls, but the strength of the relationship decreases with age. Site heterogeneity may be due to greater early life exposure in Cincinnati. DISCLAIMER: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the CDC, the Public Health Service, or the US Department of Health and Human Services.

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.

Cancer screening in public health clinics: the importance of clinic utilization.

OBJECTIVES: To determine how screening for breast and cervical cancer in public health clinics was associated with overall clinic utilization. METHODS: Evidence of screening and clinic visits between June 1989 and May 1992 was obtained by medical record audit for a random sample of 1825 women aged 40 to 75 attending eight public health clinics in the San Francisco Bay Area. RESULTS: With an average number of visits (4 per year), women who did not receive a physical examination were much less likely than those who did to obtain a clinical breast examination (OR = 0.03), mammography referral (OR = 0.1), or a mammogram (OR = 0.4) within 2 years, or a Papanicolaou smear (OR = 0.1) within 3 years. Without a physical examination, the odds of screening or referral increased with the first visit (OR = 1.2 for referral, breast examination, and Pap; 1.3 for mammography), but with a decreasing marginal effect of each additional visit (ratio of successive one-visit OR values = 0.992 for referral and breast examination; 0.995 for Pap; 0.98 for mammography). With a physical exam, visits were associated with mammography only (first visit OR = 1.2; OR ratio = 0.992). CONCLUSIONS: In public health clinics, screening is associated either with receipt of routine care or repeated visits for treatment. Women who fall through the cracks are those who come to the clinic with a medical problem but otherwise receive few services. Interventions in public health clinics need to facilitate the provider's ability to use medically related visits as opportunities to increase adherence to screening recommendations.

Abnormal Pap smear follow-up in a high-risk population.

Low-income women are at high risk of developing cervical cancer attributable not only to the higher prevalence of risk factors in this population but also to the lack of timely follow-up of abnormal Pap smears. This study evaluates the efficacy of an aggressive follow-up strategy. Women with abnormal Pap smear results after screening in a public hospital emergency department were randomly assigned to follow-up either by a case-managed approach using computerized tracking and universal colposcopy or by traditional care. The main outcome was the proportion of women receiving follow-up in 6 months. A secondary outcome was the proportion of women receiving follow-up by 6 months and diagnostic resolution in 18 months. Of 54 women in the intervention group, 65% kept at least one follow-up appointment in 6 months compared with 41% of the 54 women in the control group (P = 0.012). Half the women in the intervention group versus 19% of women in the control group had follow-up in 6 months and diagnostic resolution in 18 months (P = 0.001). After adjusting for age, initial Pap smear result, and race/ethnicity, the odds of having follow-up in 6 months were four times greater for women in the intervention group (odds ratio = 4.0; 95% confidence interval, 1.6-9.7), and the odds of having both follow-up in 6 months and diagnostic resolution in 18 months were more than six times greater (odds ratio = 6.5; 95% confidence interval, 2.4-17.8). This study demonstrates that an aggressive follow-up strategy significantly improves the rate of both initial follow-up and diagnostic resolution of abnormal Pap smears among low-income women with atypical squamous cells of undetermined significance and atypical glandular cells of undetermined significance when compared with traditional care.

Community-based cancer screening for underserved women: design and baseline findings from the Breast and Cervical Cancer Intervention Study.

BACKGROUND: Underutilization of breast and cervical cancer screening has been observed in many ethnic groups and underserved populations. Effective community-based interventions are needed to eliminate disparities in screening rates and thus to improve prospects for survival. METHODS: The Breast and Cervical Cancer Intervention Study was a controlled trial of three interventions in the San Francisco Bay Area from 1993 to 1996: (1) community-based lay health worker outreach; (2) clinic-based provider training and reminder system; and (3) patient navigator for follow-up of abnormal screening results. Study design and a description of the interventions are reported along with baseline results of a household survey conducted in four languages among 1599 women, aged 40-75. RESULTS: Seventy-six percent of women ages 40 and over had had at least one mammogram, and most had had a clinical breast examination (88%) and Pap smear (89%). Rates were significantly lower for non-English-speaking Latinas and Chinese women (56 and 32%, respectively, for mammography), and maintenance screening (three mammograms in the past 5 years) varied from 7% (non-English-speaking Chinese) to 53% (Blacks). Pap smear screening in the past 3 years was low among non-English-speaking Latinas (72%) and markedly lower among non-English-speaking Chinese women (24%). The strongest predictors of screening behavior were having private health insurance and frequent use of medical services. Having a regular clinic and speaking English were also important. Race/ethnicity, education, household income, and employment status were, overall, not significant predictors of screening behavior. CONCLUSIONS: These baseline results support the importance of cancer screening interventions targeted to persons of foreign origin, particularly those less acculturated.

Advancing age and cervical cancer screening and prognosis.

OBJECTIVES: To determine associations between advancing age and screening behavior and prognosis in long-term members of a prepaid health plan diagnosed with invasive cervical cancer (ICC). DESIGN: Case series. SETTING: Prepaid health plan. PARTICIPANTS: All women diagnosed with ICC at Kaiser Permanente Medical Care Program-Northern California health plan from 1988 to 1994. MEASUREMENTS: From medical records, we recorded participants' age, stage at diagnosis, tumor histology, and results of and reasons for all previous cervical smears. We limited our analysis to women who had been members of the health plan for at least 30 of the 36 months preceding diagnosis (n = 455). RESULTS: Women in older age groups were less likely than younger women to have been screened within the 3 years before diagnosis (P = .005 for trend). Nonadherence to follow-up of abnormal cervical smears was uncommon (17/455, 3.7%) and not age related (P = .932 for trend). The proportions of ICC that were interval cancers, defined as ICC diagnosed within 3 years of a negative screening smear, were highest in women under age 30 (P = .004 for trend). In multivariate analyses controlling for stage at diagnosis, women age 60 and older were not more likely to die of ICC within 3 years of diagnosis than were women younger than age 60 (odds ratio 1.30, 95% confidence interval 0.75-2.28). CONCLUSION: The disproportionate burden of cervical cancer observed in older women appears to be largely attributable to lack of screening within the 3 years before diagnosis.

The use of electric bed heaters and the risk of clinically recognized spontaneous abortion.

We conducted a prospective cohort study to evaluate the relation of spontaneous abortion and electric bed heater use during the first trimester of pregnancy. Compared with non-users, rates of spontaneous abortion were lower for women who used electric bed heaters. The adjusted odds ratio and 95% confidence interval (CI) for the two major devices used, electric blankets (N = 524) and waterbeds (N = 796), were, respectively, 0.8 (95% CI = 0.5-1.1) and 0.9 (95% CI = 0.7-1.2). An increase of risk with increasing intensity (setting-duration combination) of use was not observed. Users of electric blankets at low settings for most of the night (N = 171) had lower risks of spontaneous abortion than non-users (adjusted odds ratio = 0.5; 95% CI = 0.3-1.0). Twenty women who used electric blankets at a high setting for 1 hour or less had an adjusted odds ratio of 3.0 (95% CI = 1.1-8.3), but we found no spontaneous abortions among the few women (N = 13) who used a high setting for 2 or more hours. We found that exposure rankings of the magnetic field time-weighted average and a rate of change metric did not correspond monotonically to the pattern of spontaneous abortion risks and that electric blankets contribute less to overnight time-weighted average magnetic fields than has been thought.

Papanicolaou smear history and diagnosis of invasive cervical carcinoma among members of a large prepaid health plan.

BACKGROUND: Despite the widespread use of Papanicolaou (Pap) smear screening, substantial morbidity and mortality from cervical carcinoma continue in the U.S. Although access to screening is a major barrier to use of the Pap smear, invasive cervical carcinoma (ICC) still is observed in health plan members who have comprehensive preventive care coverage. METHODS: For all women diagnosed with ICC between 1988 and 1994 in a large prepaid health plan, the authors retrospectively reviewed the medical records for prediagnosis Pap smear history to identify antecedents to ICC. RESULTS: Of 642 women diagnosed as having ICC, 455 (71%) had been plan members for > or = 30 of the 36 months before diagnosis. Of these 455 women, 240 (53%) had no Pap smear during the 6-36 months prior to diagnosis (i.e., were nonadherent to screening), 127 (28%) had only "normal" Pap smear results, 42 (9%) had at least 1 abnormal Pap smear and were adequately followed, 17 (4%) had at least 1 abnormal result without adequate follow-up, and 29 (6%) were classified as "other." Compared with adherent women, more nonadherent women presented with later stage disease, were symptomatic at the time of diagnosis, were older, and were of a race/ethnicity other than non-Hispanic white. CONCLUSIONS: Nonadherence to screening recommendations was found to be the most important modifiable antecedent to ICC in this population. The rate of incidence of ICC could be reduced by interventions to increase screening in women who do not have Pap smears regularly and by the use of newer screening technologies to reduce the false-negative rate of Pap smears.

Identifying women with cervical neoplasia: using human papillomavirus DNA testing for equivocal Papanicolaou results.

CONTEXT: A Papanicolaou (Pap) test result of atypical squamous cells of undetermined significance (ASCUS) presents a clinical challenge. Only 5% to 10% of women with ASCUS harbor serious cervical disease, but more than one third of the high-grade squamous intraepithelial lesions (HSILs) in screening populations are identified from ASCUS Pap test results. OBJECTIVE: To determine whether human papillomavirus (HPV) DNA testing of residual material from liquid-based Pap tests and referral of cases found to be HPV-positive directly to colposcopy could provide sensitive detection of underlying HSILs in women with ASCUS Pap results, compared with repeat Pap testing. DESIGN AND SETTING: Natural history of women with ASCUS Pap smear results, all of whom had liquid-based cytology, HPV testing, and subsequent repeat Pap tests and colposcopy with histologic evaluation, conducted at 12 gynecology clinics in a large managed care organization between October 1995 and June 1996. PARTICIPANTS: From a cohort of 46009 women who had routine cervical examinations, 995 women with Pap test results of ASCUS who consented to participate were identified. MAIN OUTCOME MEASURES: Cervical histology, HPV test results, and repeat Pap smear results, and sensitivity of HPV testing to identify patients found to have HSIL+ histology. RESULTS: Of 995 participants with ASCUS Pap test results, 973 had both a definitive histologic diagnosis and HPV result. Sixty-five (6.7%) had histologic HSIL or cancer. For women with histologic HSIL+, the HPV test was positive in 89.2% (95% confidence interval [CI], 78.4%-95.2%), and the specificity was 64.1 % (95% CI, 60.9%-67.2%). The repeat Pap smear result was abnormal in 76.2% (95% CI, 63.5%-85.7%). Triage based on HPV testing only or on repeat Pap testing only would refer similar proportions (approximately 39%) to colposcopy. The sensitivity of HPV DNA testing for HSIL was equivalent to, if not greater than, that of the repeat Pap test. We further estimated that an HPV-based algorithm including the immediate colposcopy of HPV-positive women, and then repeat Pap testing of all others, would provide an overall sensitivity of 96.9% (95% CI, 88.3%-99.5%). CONCLUSIONS: For women with ASCUS Pap tests, HPV DNA testing of residual specimens collected for routine cervical cytology can help identify those who have underlying HSIL. By testing the specimen collected at initial screening, the majority of high-risk cases can be identified and referred for colposcopy based on a single screening.

Association between high-density lipoprotein cholesterol and breast cancer varies by menopausal status.

A nested case-control study was conducted to investigate the hypothesis that women with high levels of high-density lipoprotein cholesterol (HDL-C) are at an increased risk of breast cancer. The source population was a cohort of 95,000 women enrolled in the Kaiser Permanente Medical Care Program who underwent a routine multiphasic health examination between 1964 and 1971. From the more than 2,000 breast cancer cases diagnosed in this cohort, 200 cases were randomly selected for this study. For each case, one control who matched on age and date of examination was chosen. Lipid and lipoprotein levels were measured in archived serum samples collected at the time of the women's examinations. Breast cancer risk factor information was obtained from questionnaires completed by the women when their blood was drawn and was supplemented with information from medical records. HDL-C levels were not significantly different between the cases and controls overall; however, a statistically significant interaction between the HDL-C level and menopausal status at diagnosis was detected. Premenopausal cases had mean HDL-C levels 3.48 mg/dl lower than matched controls [95% confidence interval (CI), -7.05, 0.09], whereas postmenopausal cases had levels 2.05 mg/dl higher than controls (95% CI, -0.94, 5.03). In multivariate conditional logistic regression analyses, the odds ratio associated with each 1 mg/dl increase in HDL-C was 0.96 (95% Cl, 0.93-1.0) for premenopausal women and 1.02 (95% CI, 0.99-1.05) for postmenopausal women. Although many breast cancer risk factors are associated with high HDL-C, the relationship between breast cancer and HDL-C was independent of other factors evaluated.

Rate of caffeine metabolism and risk of spontaneous abortion.

In a case-control study of 73 women with and 141 women without spontaneous abortion, the authors determined the activity of the three principal caffeine-metabolizing enzymes--cytochrome P-4501A2 (CYP1A2), xanthine oxidase, and N-acetyltransferase 2--by measuring levels of caffeine metabolites in urine. After examining the effect of enzyme activity and different levels of caffeine intake, they concluded that there was no evidence that an interaction between enzyme activity and caffeine intake during pregnancy resulted in risk of spontaneous abortion. In a subsample comparing 24 cases with recurrent (two or more) spontaneous abortions and 21 controls with two or more livebirths and no previous spontaneous abortions, the unadjusted odds ratio for low CYP1A2 enzyme activity (below the median) was 0.92 (95% confidence interval (CI) 0.28-3.04) compared with higher CYP1A2 activity. The odds ratio for risk of recurrent spontaneous abortion and low xanthine oxidase activity (below the median) versus higher activity was 0.37 (95% CI 0.10-1.29). Phenotypically slow acetylators (N-acetyltransferase 2 index <0.37) had an odds ratio of 1.58 (95% CI 0.48-5.13) for recurrent loss compared with rapid acetylators. Thus, some association of the latter two caffeine-metabolizing enzymes with recurrent spontaneous abortion is suggested but may also be due to chance.

Helicobacter pylori infection and urinary excretion of 8-hydroxy-2-deoxyguanosine, an oxidative DNA adduct.

To assess whether Helicobacter pylori-related inflammation increases oxidative DNA damage, we evaluated the association between H. pylori infection and urinary excretion of an adduct of oxidative DNA damage, 8-hydroxy-2-deoxyguanosine (8ohdG). Subjects included 555 healthy persons, ages 20-39, within the Kaiser Permanente Medical Care Program in Northern California. We tested sera for antibodies to H. pylori by ELISA; collected demographic, dietary, smoking, and alcohol data by questionnaire; and assayed 24-h urine samples for 8ohdG with a newly developed ELISA kit. Two hundred eighty-one subjects provided adequate 24-h urine samples for 8ohdG and creatinine assays and had detectable levels of 8ohdG. After adjusting for 24-h urinary creatinine (Ucr) and demographic factors, persons without H. pylori infection had significantly higher amounts of 24-h urinary 8ohdG than infected persons (geometric mean, 18.04 microg 8ohdG/Ucr g versus 14.36 microg 8ohdG/Ucr g, respectively; P = 0.008). Excretion of 8ohdG was higher in whites and Hispanics (17.44 and 18.09 microl/Ucr g) than in blacks (13.21 microg/Ucr g; P < 0.001). Gender was not significantly associated with 8ohdG excretion (16.18 microg/Ucr g for males versus 16.01 microg/Ucr g for females; P = 0.883). Of the dietary factors evaluated, vitamin C negatively correlated (P < 0.001) and carbohydrate intake positively correlated with 8ohdG excretion (P = 0.003). Infection with H. pylori was strongly associated with decreased 8ohdG excretion in the urine. This unexpected finding suggests either that DNA repair is deficient in infected subjects, that inflammation destroys the adduct, or that urinary 8ohdG is not an accurate measure of gastric damage.

Missed opportunities for cervical cancer screening of HMO members developing invasive cervical cancer (ICC).

OBJECTIVE: To identify potential missed opportunities and to suggest interventions for cervical cancer screening in members of a prepaid health plan by examining the membership histories and medical records of women who had no Pap smear performed in the 3 years prior to the diagnosis of ICC. METHODS: Medical records of all 642 members of a prepaid health plan developing ICC during the period from 1988 to 1994 were reviewed and details of patient interaction with the health care system were abstracted. Assessment of screening history and history of clinic visits was limited to the period 36 months prior to diagnosis, but excluded the last 6 months prior to diagnosis, so as to avoid including smears or visits which were part of the evaluation that led to the recognition of ICC. RESULTS: Of women developing ICC, 384/642 (60%) had not had a smear in the period from 36 months to 6 months preceding the diagnosis. Of these 384 unscreened women, 241 (63%) had been insured by our HMO for at least 30 of the 36 months prior to diagnosis. Contact with the medical system in one of the primary care outpatient clinics was documented in 180/241 (75%) of these long-standing members during the specified period. Considering only Internal Medicine and Family Practice clinic visits, 169/241 (70%) had been seen at least once and 101/241 (42%) had been seen 3 or more times. CONCLUSION: Most long-standing HMO members developing ICC without benefit of recent Pap smear screening were seen in primary care outpatient clinics in the 3 years preceding their diagnosis.

Screening mammography in an integrated health care system: the Kaiser permanente experience.

In this paper, we describe the attributes of a comprehensive approach to breast cancer screening possible in an integrated health care system. We define an integrated health care system as one in which comprehensive preventive and medical care is provided to a defined population, by a defined panel of providers, and in which this care can be tracked using automated electronic data systems. Guided by the Pathways Conceptual Framework, it is possible to identify and systematically address (through research and interventions) the multiple predisposing, enabling, and reinforcing factors at the individual and organizational level associated with each step along the screening process. This framework is helpful as both a planning and an evaluation tool, in identifying places in the screening and follow-up process that could benefit from concerted quality improvement efforts and in guiding an evaluation of those efforts. We describe examples from research and organizational programmatic efforts, and use the framework to point to additional areas for further investigation and potential organizational intervention. These examples use a variety of research methods, impact the breast cancer screening pathway in different places, and therefore show how it is possible to approach the broad issue of reduction of breast cancer mortality from multiple perspectives. Integrated health care systems, unlike more traditional academic settings, are well suited to supporting this full spectrum of research while also providing the context for its application.

Behavioral research contributions and needs in cancer prevention and control: adherence to cancer screening advice.

BACKGROUND: Research has been critical in understanding human behavior related to the early detection of cancer. METHODS: Based on the literature and the author's experience, this paper reviews behavioral research accomplishments in the past decade and needs for the future. RESULTS: Accomplishments have included an improved understanding of the barriers to screening, methods to improve the provision of tests by practitioners, and progress in the development and application of community interventions. Outstanding needs are summarized in 12 areas that include a continued focus on underserved populations and an examination of the use of screening tests in the presence of incomplete evidence of efficacy, translational research that explores the behavioral consequences of genetic susceptibility testing, continued development and use of computer-based technologies in the delivery of preventive services, and studies of the potential negative consequences of screening. Critical changes in the delivery of health care in the era of managed care call for increased behavioral research in health services and health care policy. CONCLUSION: Although this review of research needs is not exhaustive, it is clear that the challenges and opportunities for behavioral research are substantial, and this effort will be a critical part of the overall national research agenda for cancer control.

Caffeinated beverages, decaffeinated coffee, and spontaneous abortion.

We examined the relations between spontaneous abortion and the consumption of caffeine, individual caffeine-containing beverages (coffee, tea, and soda), and decaffeinated coffee in a prospective study of 5,144 pregnant women. We collected information about potential risk factors for spontaneous abortion, including consumption of caffeinated beverages and decaffeinated coffee before and during pregnancy, by interview in the first trimester. Neither total estimated caffeine nor individual caffeinated beverage consumption during the first trimester was associated with an appreciable increase in risk for spontaneous abortion. The adjusted odds ratio for consumption of greater than 300 mg per day of caffeine was 1.3 [95% confidence interval (CI) = 0.8-2.1] after adjustment for maternal age, pregnancy history, cigarette and alcohol consumption, employment, race, gestational age at interview, and marital and socioeconomic status. The adjusted odds ratio for spontaneous abortion related to consumption of three or more cups of decaffeinated coffee during the first trimester was 2.4 (95% CI = 1.3-4.7) in the same model. Although we could not demonstrate this with available data, we suspect that this association was due to bias resulting from the relations among fetal viability, symptoms of pregnancy such as nausea, and consumption patterns during pregnancy.

The effect of patient and provider reminders on mammography and Papanicolaou smear screening in a large health maintenance organization.

BACKGROUND: We evaluated the effectiveness of 2 reminder interventions to increase the use of screening mammograms and Papanicolaou (Pap) smears among female members of a large health maintenance organization. METHODS: Seven thousand seventy-seven female health maintenance organization members (aged 50-74 years with no prior mammogram in the previous 30 months or aged 20-64 years with no prior Pap smear in the previous 36 months) were randomized to receive one of the following: a letter inviting them to make an appointment for a mammogram or a Pap smear; in addition to the letter, a reminder manually placed in the patient's medical chart alerting providers of that member's need for screening; or their usual care. RESULTS: Compared with women who did not receive the reminder letter, women who did receive the letter were more likely to obtain mammograms (16.0% vs 25.5%, respectively; P < .001) or Pap smears (9.1% vs 19.5%, respectively; P < .001) in the 6 months following their entry into the study. Compared with women who received only the reminder letter, women who received a reminder letter and had a reminder placed in their medical chart were more likely to obtain mammograms (26.5% vs 30.9%, respectively; P = .02) and marginally more likely to receive Pap smears (19.5% vs 22.8%, respectively; P = .04). CONCLUSIONS: We recommend the use of patient reminder letters as a first step in a mammography or Pap smear screening outreach program. Further research is needed to evaluate a cost-effective provider reminder system and additional outreach strategies directed to women who do not use health care services.

'Spontaneous' genetic damage in man: evaluation of interindividual variability, relationship among markers of damage, and influence of nutritional status.

The 'spontaneous' frequency of genetic damage (normal background) and the possible relationship of this damage to nutritional variables in humans were investigated in 22 subjects using several indices of genetic damage. The subjects were chosen, out of 122 initially analyzed, for being at the extremes of the highest and lowest values of one index of genetic damage, the frequency of micronucleated erythrocytes in peripheral blood. This index reflects chromosomal damage and loss in bone marrow erythropoietic cells. The assay for micronuclei is convenient but is restricted to splenectomized individuals because the human spleen removes micronucleated cells. The initial 122 subjects were splenectomized, but all were normal and healthy at the time of this study and none had a previous history of neoplastic disease. Factors investigated were stability of micronucleus frequency as a function of time, correlations among multiple markers of genetic damage, and influence on damage indices of nutritional variables, including blood levels of folate, B12 and antioxidant vitamins. Among different individuals, the range of values was 10-fold or more in the erythrocyte micronucleus, glycophorin A, plasma ascorbate and urinary 8-hydroxydeoxyguanosine (oxo8dG) assays, was approximately 6-fold in the lymphocyte micronucleus assay, and was 2-fold in the lymphocyte sister chromatid exchange (SCE) assay. Red blood cell folate and plasma folate, B12 and alpha-tocopherol values varied by up to 10-fold among individuals. Micronucleus frequencies in erythrocytes and peripheral blood lymphocytes ranged from < 0.3 to 16.9/1000 in mature red blood cells, < 1 to 33/1000 in reticulocytes, and 2.5 to 15/1000 in binucleate lymphocytes. Frequencies of glycophorin A variant erythrocytes ranged from 5.6 to 77.3 x 10(6) N/0 cells and 3.2 to 16.2 x 10(6) N/N cells, and oxo8dG excretion varied from 32 to 397 pmol/kg/day. Although a wide range of values was observed in each genetic endpoint, the extreme values for various endpoints of genetic damage were not observed in the same individuals. The frequency of micronucleated erythrocytes varied over time within individuals and indicated that individuals with the highest levels of damage exhibit greater variability than those with lower levels. In some subjects, frequencies of micronucleated erythrocytes changed dramatically over an interval of 2-3 years: four subjects with initial micronucleated reticulocyte frequencies of 20.4, 5.9, 6.4 and 33/1000 changed to 2.5, 20.5, 18.5 and 12/1000, respectively. Among more than 150 individuals we have studied, including the 64 individuals studied by Everson et al. [(1988) J. Natl. Cancer Inst., 80, 525-529] and Smith et al. [(1990) Cancer Res., 50, 5049-5054], the seven individuals with the highest observed frequencies of micronucleated erythrocytes all had exceptionally low values of plasma folate, red cell folate, or plasma B12, suggesting that folate and B12 status are the major determinants of the types of damage that lead to spontaneous micronucleus formation in erythrocytic cells.