Showing papers in "American Journal of Epidemiology in 2000"

5, 10-Methylenetetrahydrofolate Reductase Gene Variants and Congenital Anomalies: A HuGE Review

Abstract: The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism. The MTHFR gene is located on chromosome 1 (1p36.3), and two common alleles, the C677T (thermolabile) allele and the A1298C allele, have been described. The population frequency of C677T homozygosity ranges from 1% or less among Blacks from Africa and the United States to 20% or more among Italians and US Hispanics. C677T homozygosity in infants is associated with a moderately increased risk for spina bifida (pooled odds ratio = 1.8; 95% confidence interval: 1.4, 2.2). Maternal C677T homozygosity also appears to be a moderate risk factor (pooled odds ratio = 2.0; 95% confidence interval: 1.5, 2.8). The A 1298C allele combined with the C677T allele also could be associated with an increased risk for spina bifida. Some data suggest that the risk for spina bifida associated with C677T homozygosity may depend on nutritional status (e.g., blood folate levels, intake of vitamins) or on the genotype of other folate-related genes (e.g., cystathionine-beta-synthase and methionine synthase reductase). Studies of the C677T allele in relation to oral clefts, Down syndrome, and fetal anticonvulsant syndrome either have yielded conflicting results or have not been yet replicated.

Pooled Analysis of Prospective Cohort Studies on Height, Weight, and Breast Cancer Risk

Abstract: The association between anthropometric indices and the risk of breast cancer was analyzed using pooled data from seven prospective cohort studies. Together, these cohorts comprise 337,819 women and 4,385 incident invasive breast cancer cases. In multivariate analyses controlling for reproductive, dietary, and other risk factors, the pooled relative risk (RR) of breast cancer per height increment of 5 cm was 1.02 (95% confidence interval (Cl): 0.96, 1.10) in premenopausal women and 1.07 (95% Cl: 1.03, 1.12) in postmenopausal women. Body mass index (BMI) showed significant inverse and positive associations with breast cancer among pre- and postmenopausal women, respectively; these associations were nonlinear. Compared with premenopausal women with a BMI of less than 21 kg/m2, women with a BMI exceeding 31 kg/m2 had an RR of 0.54 (95% Cl: 0.34, 0.85). In postmenopausal women, the RRs did not increase further when BMI exceeded 28 kg/m2; the RR for these women was 1.26 (95% Cl: 1.09, 1.46). The authors found little evidence for interaction with other breast cancer risk factors. Their data indicate that height is an independent risk factor for postmenopausal breast cancer; in premenopausal women, this relation is less clear. The association between BMI and breast cancer varies by menopausal status. Weight control may reduce the risk among postmenopausal women.

A Multiethnic Cohort in Hawaii and Los Angeles: Baseline Characteristics

Abstract: The authors describe the design and implementation of a large multiethnic cohort established to study diet and cancer in the United States. They detail the source of the subjects, sample size, questionnaire development, pilot work, and approaches to future analyses. The cohort consists of 215,251 adult men and women (age 45-75 years at baseline) living in Hawaii and in California (primarily Los Angeles County) with the following ethnic distribution: African-American (16.3%), Latino (22.0%), Japanese-American (26.4%), Native Hawaiian (6.5%), White (22.9%), and other ancestry (5.8%). From 1993 to 1996, participants entered the cohort by completing a 26-page, self-administered mail questionnaire that elicited a quantitative food frequency history, along with demographic and other information. Response rates ranged from 20% in Latinos to 49% in Japanese-Americans. As expected, both within and among ethnic groups, the questionnaire data show substantial variations in dietary intakes (nutrients as well as foods) and in the distributions of non-dietary risk factors (including smoking, alcohol consumption, obesity, and physical activity). When compared with corresponding ethnic-specific cancer incidence rates, the findings provide tentative support for several current dietary hypotheses. As sufficient numbers of cancer cases are identified through surveillance of the cohort, dietary and other hypotheses will be tested in prospective analyses.

Relation of Demographic and Lifestyle Factors to Symptoms in a Multi-Racial/Ethnic Population of Women 40–55 Years of Age

Abstract: A community-based survey was conducted during 1995-1997 of factors related to menopausal and other symptoms in a multi-racial/ethnic sample of 16,065 women aged 40-55 years. Each of seven sites comprising the Study of Women's Health across the Nation (SWAN) surveyed one of four minority populations and a Caucasian population. The largest adjusted prevalence odds ratios for all symptoms, particularly hot flashes or night sweats (odds ratios = 2.06-4.32), were for women who were peri- or postmenopausal. Most symptoms were reported least frequently by Japanese and Chinese (odds ratios = 0.47-0.67 compared with Caucasian) women. African-American women reported vasomotor symptoms and vaginal dryness more (odds ratios = 1.17-1.63) but urine leakage and difficulty sleeping less (odds ratios = 0.64-0.72) than Caucasians. Hispanic women reported urine leakage, vaginal dryness, heart pounding, and forgetfulness more (odds ratios = 1.22-1.85). Hot flashes or night sweats, urine leakage, and stiffness or soreness were associated with a high body mass index (odds ratios = 1.15-2.18 for women with a body mass index > or =27 vs. 19-26.9 kg/m2). Most symptoms were reported most frequently among women who had difficulty paying for basics (odds ratios = 1.15-2.05), who smoked (odds ratios = 1.21-1.78), and who rated themselves less physically active than other women their age (odds ratios = 1.24-2.33). These results suggest that lifestyle, menstrual status, race/ethnicity, and socioeconomic status affect symptoms in this age group.

Carotid Wall Thickness is Predictive of Incident Clinical Stroke: The Atherosclerosis Risk in Communities (ARIC) Study

Abstract: Few studies have determined whether carotid artery intima-media thickness (IMT) is associated prospectively with risk of first ischemic stroke In the Atherosclerosis Risk in Communities Study, carotid IMT, an index of generalized atherosclerosis, was defined as the mean of IMT measured by B-mode ultrasonography at six sites of the carotid arteries The authors assessed the relation of mean IMT to stroke incidence over 6-9 years' follow-up (1987-1995) among 7,865 women and 6,349 men aged 45-64 years without prior stroke at baseline in four US communities There were 90 incident ischemic stroke events for women and 109 for men In sex-specific Cox proportional hazards models adjusting only for age, race, and community, the hazard rate ratios comparing extreme mean IMT values (> or =1 mm) to values less than 06 mm were 85 for women (95% confidence interval: 35, 207) and 36 for men (95% confidence interval: 15, 92) The relation was graded, and models with cubic splines indicated significant nonlinearity, with hazards increasing more rapidly at lower IMTs than at higher IMTs Thus, models using linear IMT values substantially underestimate the strength of the association at lower IMTs The strength of the association was reduced by the inclusion of putative stroke risk factors, but it remained elevated at higher IMTs Hence, mean carotid IMT is a noninvasive predictor of future ischemic stroke incidence

Associations of Light, Moderate, and Vigorous Intensity Physical Activity with Longevity The Harvard Alumni Health Study

Abstract: Physical activity is associated with better health; however, the optimal intensity of activity remains unclear. A total of 13,485 men (mean age, 57.5 years) from the Harvard Alumni Health Study reported their walking, stair climbing, and sports/recreation in 1977. Between 1977 and 1992, 2,539 died. After adjusting for the different activity components, distance walked and storeys climbed independently predicted longevity (p, trend = 0.004 and or =6 METs) clearly predicted lower mortality rates (p, trend = 0.72, 0.07, and <0.001, respectively). These data provide some support for current recommendations that emphasize moderate intensity activity; they also clearly indicate a benefit of vigorous activity.

Survival, Functional Limitations, and Self-rated Health in the NHANES I Epidemiologic Follow-up Study, 1992

Abstract: This study examined relative hazards for mortality and functional limitations according to poor self-ratings of health using prospective data from the NHANES I Epidemiologic Follow-up Study, a representative sample of US adults aged 25-74 years that has been followed since the First National Health and Nutrition Examination Survey (NHANES I) was conducted in 1971-1975. Follow-up data were taken from death records and from the 1982 and 1992 reinterviews. Respondents (n = 6,913) provided extensive baseline data through physician examinations, laboratory testing, and self-reports of conditions, symptoms, and risk behaviors. Functional limitations were assessed among survivors in 1982 and 1992. Cox regression models accounting for sample design indicated that baseline self-rated health was associated with a significantly reduced hazard of mortality for males but not for females through 1992; adjusted hazards ratios for excellent health as compared with poor health were 0.52 for males (95% confidence interval: 0.36, 0.73) and 0.80 for females (95% confidence interval: 0.51, 1.23). Self-rated health also predicted 1982 and 1992 functional limitation for both men and women and 1992 function net of 1982 function for men only. Self-rated health contributes unique information to epidemiologic studies that is not captured by standard clinical assessments or self-reported histories, but evidence suggests that the effect may be stronger for men than for women.

Sickle Hemoglobin (Hb S) Allele and Sickle Cell Disease: A HuGE Review

Abstract: Sickle cell disease is caused by a variant of the beta-globin gene called sickle hemoglobin (Hb S). Inherited autosomal recessively, either two copies of Hb S or one copy of Hb S plus another beta-globin variant (such as Hb C) are required for disease expression. Hb S carriers are protected from malaria infection, and this protection probably led to the high frequency of Hb S in individuals of African and Mediterranean ancestry. Despite this advantage, individuals with sickle cell disease exhibit significant morbidity and mortality. Symptoms include chronic anemia, acute chest syndrome, stroke, splenic and renal dysfunction, pain crises, and susceptibility to bacterial infections. Pediatric mortality is primarily due to bacterial infection and stroke. In adults, specific causes of mortality are more varied, but individuals with more symptomatic disease may exhibit early mortality. Disease expression is variable and is modified by several factors, the most influential being genotype. Other factors include beta-globin cluster haplotypes, alpha-globin gene number, and fetal hemoglobin expression. In recent years, newborn screening, better medical care, parent education, and penicillin prophylaxis have successfully reduced morbidity and mortality due to Hb S.

Evaluation of Simple Indices of Insulin Sensitivity and Insulin Secretion for Use in Epidemioiogic Studies

Abstract: The metabolic characteristics of type 2 diabetes, insulin resistance, and diminished insulin secretion are costly to measure directly. To evaluate the utility of several simple indices derived from insulin and glucose measurements, the indices were examined from 1982 to 1997 with respect to correlation with more sophisticated measures of insulin sensitivity and secretion in Pima Indians in the Gila River Indian Community of Arizona. Ability to predict the incidence of diabetes in 1,731 persons was also examined. Indices were calculated from fasting and 2-hour glucose (G0, G120) and insulin (I0, I120) concentrations obtained during an oral glucose tolerance test. Fasting serum insulin concentration and the insulin sensitivity index (10(4)/(I0 x G0)) each showed a moderate correlation with the estimate of insulin sensitivity derived from the hyperinsulinemic-euglycemic clamp (absolute value r approximately 0.60). They also strongly predicted the incidence of diabetes (incidence rate ratio comparing the most and least insulin-resistant tertile groups approximately 3.0). Corrected insulin response (I120/(G120 x (G120 - 70))) was modestly correlated with insulin secretion as measured by an intravenous glucose tolerance test (r = 0.35). Impaired insulin secretion assessed by this index predicted incidence of diabetes, particularly after control for insulin sensitivity index (incidence rate ratio = 1.6). Thus, simple indices of insulin sensitivity and secretion may be reasonable surrogates for more sophisticated measures in epidemiologic studies.

Weight Gain Continues in the 1990s: 10-year Trends in Weight and Overweight from the CARDIA Study

Abstract: The prevalence of obesity increased in the United States through the 1980s. The authors examined 10-year aging and secular (time-related) trends in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort for indications of whether these trends are continuing and for ages of peak weight gain in young adults. CARDIA is a population-based, prospective study of 5,115 African-American and White men and women aged 18-30 years at baseline. Body weight and overweight prevalence were measured at five time points from 1985-1986 to 1995-1996. Linear, mixed-model regression was used to partition weight gain into that due to secular trends and that due to aging. Prevalence of overweight (body mass index (BMI) > or = 25.0 kg/m2) increased markedly, and prevalence of severe obesity (BMI > or = 40.0 kg/m2) doubled in all race-sex groups. Each race-sex group experienced significant secular weight gains, ranging from 0.96 kg/year (95% confidence interval: 79, 1.13) in African-American women to 0.55 kg/year (95% confidence interval: 0.41, 0.69) in White women. Significant secular gains were present during each follow-up period. Each race-sex group also experienced significant weight increases related to aging during their early to midtwenties. Secular trends for weight gain are continuing in CARDIA, but the magnitude of weight gain differed among the four race-sex groups.

Mathematical Model for the Natural History of Human Papillomavirus Infection and Cervical Carcinogenesis

Abstract: The authors constructed a Markov model as part of a systematic review of cervical cytology conducted at the Duke University Evidence-based Practice Center (Durham, North Carolina) between October 1997 and September 1998. The model incorporated states for human papillomavirus infection (HPV), low- and high-grade squamous intraepithelial lesions, and cervical cancer stages I-IV to simulate the natural history of HPV infection in a cohort of women from ages 15 to 85 years. The age-specific incidence rate of HPV, and regression and progression rates of HPV and squamous intraepithelial lesions, were obtained from the literature. The effects of varying natural history parameters on cervical cancer incidence were evaluated by using sensitivity analysis. The base-case model resulted in a lifetime cervical cancer risk of 3.67% and a lifetime cervical cancer mortality risk of 1.26%, with a peak incidence of 81/100,000 at age 50 years. Age-specific distributions of precursors were similar to reported data. Lifetime risk of cancer was most sensitive to the incidence of HPV and the probability of rapid HPV progression to high-grade lesions (two- to threefold variations in risk). The model approximates the age-specific incidence of cervical cancer and provides a tool for evaluating the natural history of HPV infection and cervical cancer carcinogenesis as well as the effectiveness and cost-effectiveness of primary and secondary prevention strategies.

Prevalence and Patterns of Gulf War Illness in Kansas Veterans: Association of Symptoms with Characteristics of Person, Place, and Time of Military Service

Abstract: Gulf War veterans have reported health problems that they attribute to their military service, but little is understood about the nature or extent of these conditions. To determine whether Kansas Gulf War veterans are affected by excess health problems, a population-based survey of 1,548 veterans who served in the Persian Gulf War (PGW) and 482 veterans who served elsewhere (non-PGW) was conducted in 1998. Gulf War illness, defined as having chronic symptoms in three of six domains, occurred in 34% of PGW veterans, 12% of non-PGW veterans who reported receiving vaccines during the war, and 4% of non-PGW veterans who did not receive vaccines. The prevalence of Gulf War illness was lowest among PGW veterans who served on board ship (21%) and highest among those who were in Iraq and/or Kuwait (42%). Among PGW veterans who served away from battlefield areas, Gulf War illness was least prevalent among those who departed the region prior to the war (9%) and most prevalent among those who departed in June or July of 1991 (41%). Observed patterns suggest that excess morbidity among Gulf War veterans is associated with characteristics of their wartime service, and that vaccines used during the war may be a contributing factor.

Cumulative Risk of Breast Cancer to Age 70 Years According to Risk Factor Status: Data from the Nurses' Health Study

Abstract: Because of the temporal relations between reproductive risk factors and incidence of breast cancer, the authors developed a nonlinear Poisson regression that accounts for time and summarizes risk to age 70 years. Reproductive risk factors, benign breast disease, use of postmenopausal hormones, weight, and alcohol intake were evaluated as risk factors. Among 58,520 women aged 30-55 years in 1980, followed through June 1, 1994, 1,761 incident invasive breast cancer cases were identified. All risks are multivariate adjusted. History of benign breast disease is associated with a 57% increase (95% confidence interval (CI): 43%, 73%) in cumulative risk of breast cancer by age 70 years. Use of unopposed postmenopausal estrogen from ages 50-60 years increases risk of breast cancer to age 70 by 23% (95% CI: 6%, 42%) compared with a woman who never uses hormones. Ten years of use of estrogen plus progestin increases risk to age 70 years by 67% (95% CI: 18%, 136%). Compared with never drinking alcohol, one drink per day from age 18 years increases risk to age 70 by 7% (95% CI: 0%, 13%). Use of unopposed postmenopausal hormones for 10 years significantly increases the risk of breast cancer, and the addition of progestin further increases the risk.

Randomized Controlled Trial of Audio Computer-assisted Self-Interviewing: Utility and Acceptability in Longitudinal Studies

Abstract: Recent studies have reported on the utility of audio computer-assisted self-interviewing (ACASI) in surveys of human immunodeficiency virus (HIV) risk behaviors that involve a single assessment. This paper reports the results of a test of ACASI within a longitudinal study of HIV risk behavior and infection. Study participants (gay men (n = 1,974) and injection drug users (n = 903)) were randomly assigned to either ACASI or interviewer-administered assessment at their second follow-up visit 12 months after baseline. Significantly more of the sexually active gay men assessed via ACASI reported having sexual partners who were HIV antibody positive (odds ratio = 1.36, 95% confidence interval: 1.08, 1.72), and a higher proportion reported unprotected receptive anal intercourse. Among injection drug users (IDUs), our hypothesis was partially supported. Significantly more IDUs assessed via ACASI reported using a needle after another person without cleaning it (odds ratio = 2.40, 95% confidence interval: 1.34, 4.30). ACASI-assessed IDUs reported similar rates of needle sharing and needle exchange use but a lower frequency of injection. Participants reported few problems using ACASI, and it was well accepted among members of both risk groups. Sixty percent of the participants felt that the ACASI elicited more honest responses than did interviewer-administered questionnaires. Together, these data are consistent with prior research findings and suggest that ACASI can enhance the quality of behavioral assessment and provide an acceptable method for collecting self-reports of HIV risk behavior in longitudinal studies and clinical trials of prevention interventions.

Clustering of Procoagulation, Inflammation, and Fibrinolysis Variables with Metabolic Factors in Insulin Resistance Syndrome

Abstract: The known metabolic cardiovascular disease risk factors associated with insulin resistance syndrome (IRS) do not adequately explain the excess cardiovascular disease risk attributed to this syndrome, and abnormalities in hemostatic variables may contribute to this excess risk. Using data from 322 nondiabetic elderly men and women (aged 65-100 years) participating in the Cardiovascular Health Study during 1989-1990, the authors performed factor analysis on 10 metabolic risk factors associated with IRS and 11 procoagulation, inflammation, and fibrinolysis variables to examine the clustering of the metabolic and hemostatic risk markers. Factor analysis of the metabolic variables confirmed four uncorrelated factors: body mass, insulin/glucose, lipids, and blood pressure. Adding the hemostatic variables yielded three new factors interpreted as inflammation, vitamin K-dependent proteins, and procoagulant activity. Plasminogen activator inhibitor-1 clustered with the body mass factor, supporting the hypothesis that obesity is related to impaired fibrinolysis. Fibrinogen clustered with the inflammation summary factor rather than procoagulant activity, supporting the position that fibrinogen principally reflects underlying inflammation rather than procoagulant potential. The authors conclude that should hemostatic variables be shown to contribute to IRS-related cardiovascular disease, apart from plasminogen activator inhibitor-1, they may do so independently of the established metabolic abnormalities. Am J Epidemiol 2000;152:897-907.

Relation between Psychiatric Syndromes and Behaviorally Defined Sexual Orientation in a Sample of the US Population

Abstract: Most surveys of the prevalence of psychiatric disorders among lesbians and gay men find no increased risk in comparison with heterosexuals. However, the majority of this work has relied on convenience samples drawn from the visible lesbian and gay community. The authors examined differences in 1-year prevalence of six psychiatric syndromes among sexually active individuals in the 1996 National Household Survey of Drug Abuse who reported either exclusive heterosexuality (n = 9,714) or having any same-gender sex partners (n = 194) in the prior year. Although nearly three quarters of homosexually active individuals did not meet criteria for any of the six syndromes assessed, in multivariate logistic regression analyses, homosexually active men were more likely than other men to evidence major depression and panic attack syndromes. In contrast, homosexually active women were more likely than other women to be classified with alcohol or drug dependency syndromes. Both men and women reporting any same-gender sex partners were more likely than others to have used mental health services in the year prior to interview. These findings suggest a small increased risk among homosexually active populations in 1-year psychiatric morbidity and use of mental health care services.

Are the Obese at Greater Risk for Depression

Abstract: Two waves of data from a community-based study (Alameda County Study, 1994-1995) were used to investigate the association between obesity and depression. Depression was measured with 12 items covering Diagnostic and Statistical Manual of Mental Disorders: DSM-IV diagnostic criteria for major depressive episode. Following US Public Health Service criteria, obese subjects were defined as those with body mass index scores at the 85th percentile or higher. Covariates were age, sex, education, marital status, social isolation and social support, chronic medical conditions, functional impairment, life events, and financial strain. Results were mixed. In cross-sectional analyses, greater odds for depression in 1994 were observed for the obese, with and without adjustment for covariates. When obesity and depression were examined prospectively, controlling for other variables, obesity in 1994 predicted depression in 1995 (odds ratio (OR) = 1.73, 95% confidence interval (CI): 1.04, 2.87). When the data were analyzed with obesity defined as a body mass index of > or = 30, cross-sectional results were the same. However, the prospective multivariate analyses were not significant (OR = 1.43, 95% CI: 0.85, 2.43). Although these data do not resolve the role of obesity as a risk factor for depression, overall the results suggest an association between obesity and depression. The authors found no support for the "jolly fat" hypothesis (obesity reduces risk of depression). However, there has been sufficient disparity of results thus far to justify continued research.

Invited Commentary: Insulin Resistance Syndrome? Syndrome X? Multiple Metabolic Syndrome? A Syndrome At All? Factor Analysis Reveals Patterns in the Fabric of Correlated Metabolic Risk Factors

Abstract: Factor analysis has emerged as a useful method for understanding patterns underlying the co-occurrence of metabolic risk factors for both type 2 diabetes and atherosclerosis--often referred to as "insulin resistance syndrome." In factor analysis of data on 322 healthy elderly people from the Cardiovascular Health Study, Sakkinen et al. (Am J Epidemiol 2000;152:897-907) confirmed findings from a dozen prior studies that as many as four distinct physiologic domains comprise the syndrome, with a unifying role for markers of insulin resistance. With the addition of markers of hemostasis and inflammation, they also found that impaired fibrinolysis and endothelial dysfunction are central features of the syndrome, while inflammation is only weakly linked to insulin resistance through associations with obesity.

Self-reported Life Satisfaction and 20-Year Mortality in Healthy Finnish Adults

Abstract: The authors investigated the role of self-reported life satisfaction in mortality with a prospective cohort study (1976-1995). A nationwide sample of healthy adults (18-64 years, n = 22,461) from the Finnish Twin Cohort responded to a questionnaire about life satisfaction and known predictors of mortality in 1975. A summary score for life satisfaction (LS), defined as interest in life, happiness, loneliness, and general ease of living (scale range, 4-20), was determined and used as a three-category variable: the satisfied (LS, 4-6) (21%), the intermediate group (LS, 7-11) (65%), and the dissatisfied (LS, 12-20) (14%). Mortality data were analyzed with Cox regression. Dissatisfaction was linearly associated with increased mortality. The age-adjusted hazard ratios of all-cause, disease, or injury mortality among dissatisfied versus satisfied men were 2.11 (95% confidence interval (CI): 1.68, 2.64), 1.83 (95% CI: 1.40, 2.39), and 3.01 (95% CI: 1.94, 4.69), respectively. Adjusting for marital status, social class, smoking, alcohol use, and physical activity diminished these risks to 1.49 (95% CI: 1.16, 1.92), 1.35 (95% CI: 1.01, 1.82), and 1.93 (95% CI: 1.19, 3.12), respectively. Dissatisfaction was associated with increased disease mortality, particularly in men with heavy alcohol use (hazard ratio = 3.76, 95% CI: 1.61, 8.80). Women did not show similar associations between life satisfaction and mortality. Life dissatisfaction may predict mortality and serve as a general health risk indicator. This effect seems to be partially mediated through adverse health behavior.

Associations of Substance Use, Abuse, and Dependence with Subsequent Suicidal Behavior

Abstract: General population survey data are used to disaggregate the associations of substance use disorders with suicide attempts in order to evaluate a number of hypotheses about the processes leading to these associations. Data are from the US National Comorbidity Survey (1990-1992). Discrete-time survival analysis is used to study the effects of retrospectively reported temporally prior substance use, abuse, and dependence in predicting first onset of suicidal behavior. Alcohol and drug use predict subsequent suicide attempts after controlling for sociodemographics and comorbid mental disorders. Previous use is not a significant predictor among current nonusers. Abuse and dependence are significant predictors among users for three of the 10 substances considered (alcohol, inhalants, and heroin). The number of substances used is more important than the types of substances used in predicting suicidal behavior. Disaggregation shows that the effects of use are largely on suicidal ideation and nonplanned attempts among ideators. In comparison, the effects of use on suicide plans and planned attempts among ideators are not significant. Clinicians need to be aware that current substance use, even in the absence of abuse or dependence, is a significant risk factor for unplanned suicide attempts among ideators.

Psychiatric and Sociodemographic Predictors of Attrition in a Longitudinal Study The Netherlands Mental Health Survey and Incidence Study (NEMESIS)

Abstract: This article discusses the effects of sociodemographics and the presence of psychiatric disorders diagnosed in the 12 months before the first interview by using the Diagnostic and Statistical Manual of Mental Disorders: DSM-III-R, third edition, revised, on three types of attrition (failure to locate, refusal to participate, morbidity/mortality) in the second wave (1997-1998) of the Netherlands Mental Health Survey and Incidence Study, a longitudinal, general population survey of psychopathology among 7,076 subjects aged 18-64 years. Compared with those reinterviewed successfully, persons not located at the 1-year follow-up (n = 219) were more often younger, poorly educated, urban, not cohabiting with a steady partner, and born outside the Netherlands. Refusers (n = 923) had a lower educational level. Morbidity/mortality (n = 72) was associated with higher age, lower educational level, not being employed, and somatic disorders. After adjustment for sociodemographics, none of the disorders was positively associated with refusal. Failure to locate was linked to agoraphobia, alcohol abuse, and the categories of mood, substance use, and eating disorders. Morbidity/mortality was linked to dysthymia, agoraphobia, simple phobia, obsessive-compulsive disorder, and the category of anxiety disorders. Overall attrition was only slightly higher among respondents with one or more disorders (odds ratio = 1.20, 95% confidence interval: 1.04, 1.38). Thus, psychopathology has only weak-to-moderate effects on attrition and is mainly related to failure to locate and morbidity/mortality but not to refusal.

Calibration of the Dietary Questionnaire for a Multiethnic Cohort in Hawaii and Los Angeles

Abstract: The performance of the dietary questionnaire used in a multiethnic cohort study in Hawaii and Los Angeles was assessed in a calibration substudy that compared diet reported from the questionnaire with three 24-hour dietary recalls. For the calibration substudy, subjects from each of eight subgroups defined by sex and ethnic group (African-American, Japanese-American, Latino, and White) were chosen randomly from among the cohort members, and each participant's previous day's diet was assessed by telephone recall on three occasions over approximately 2 months. After completing the three 24-hour recalls, each calibration subject was sent a second questionnaire; 1,606 persons completed three recalls and a second questionnaire (127 to 267 per ethnic-sex group). This report describes correlation coefficients and calibration slopes for the relation between the 24-hour recalls and second questionnaire values for a selected set of macro- and micronutrients, as absolute intakes, nutrient densities, and calorie-adjusted nutrients. In all subgroups, estimates of the correlation between the questionnaire and 24-hour recalls were greater after energy adjustment (average correlations ranged from 0.57-0.74 for nutrient densities and from 0.55-0.74 for calorie-adjusted nutrients) than when absolute nutrient values were used (average range 0.26-0.57). For absolute nutrient intakes, the correlations were greatest for Whites, somewhat lower for Japanese-Americans and Latinos, and lowest for African-Americans. After energy adjustment, the difference between subgroups were diminished, and the correlations were generally highly satisfactory.

Harvesting and Long Term Exposure Effects in the Relation between Air Pollution and Mortality

Abstract: While time series analyses have demonstrated that airborne particles are associated with early death, they have not clarified how much the deaths are advanced. If all of the pollution-related deaths were advanced by only a few days, one would expect little association between weekly averages of air pollution and daily deaths. The author used the STL algorithm to classify data on air pollution, daily deaths, and weather from Boston, Massachusetts (1979-1986) into three time series: one reflecting seasonal and longer fluctuations, one reflecting short term fluctuations, and one reflecting intermediate patterns. By varying the cutoff point between short term and intermediate term, it was possible to examine harvesting on different time scales. For chronic obstructive pulmonary disease, there was evidence that most of the mortality was displaced by only a few months. For pneumonia, heart attacks, and all-cause mortality, the effect size increased with longer time scales. The percentage increase in all deaths associated with a 10-microg/m3 increase in PM2.5 rose from 2.1% (95% confidence interval: 1.5, 4.3) to 3.75% (95% confidence interval: 3.2, 4.3) as the focus moved from daily patterns to monthly patterns. This is consistent with the larger effect seen in prospective cohort studies, rather than harvesting's playing a major role.

Relations among Chronic Medical Conditions, Medications, and Automobile Crashes in the Elderly: A Population-based Case-Control Study

Abstract: Older drivers have elevated crash rates and are more likely to be injured or die if they have a crash. Medical conditions and medications have been hypothesized as determinants of crash involvement. This population-based case-control study sought to identify medical conditions and medications associated with risk of at-fault crashes among older drivers. A total of 901 drivers aged 65 years and older were selected in 1996 from Alabama Department of Public Safety driving records: 244 at-fault drivers involved in crashes; 182 not at-fault drivers involved in crashes; and 475 drivers not involved in crashes were enrolled. Information on demographic factors, chronic medical conditions, medications, driving habits, visual function, and cognitive status was collected. Older drivers with heart disease (odds ratio (OR) = 1.5, 95% confidence interval (CI): 1.0, 2.2) or stroke (OR = 1.9, 95% CI: 0.9, 3.9) were more likely to be involved in at-fault automobile crashes. Arthritis was also associated with an increased risk among females (OR =1.8, 95% CI: 1.1, 2.9). Use of nonsteroidal antiinflammatory drugs (OR = 1.7, 95% CI 1.0, 2.6), angiotensin converting enzyme inhibitors (OR = 1.6, 95 CI: 1.0, 2.7), and anticoagulants (OR = 2.6, 95% CI: 1.0, 73) was associated with an increased risk of at-fault involvement in crashes. Benzodiazepine use (OR = 5.2, 95% CI: 0.9, 30.0) was also associated with an increased risk. Calcium channel blockers (OR = 0.5, 95% CI: 0.2, 0.9) and vasodilators (OR = 0.3, 95% CI: 0.1, 1.0) were associated with a reduced risk of crash involvement. The identification of medical conditions and medications associated with risk of crashes is important for enhancing the safety and mobility of older drivers.

NF1 Gene and Neurofibromatosis 1

Abstract: Neurofibromatosis 1 (NF1), also known as von Recklinghausen disease, is an autosomal dominant condition caused by mutations of the NF1 gene, which is located at chromosome 17q11.2. NF1 is believed to be completely penetrant, but substantial variability in expression of features occurs. Diagnosis of NF1 is based on established clinical criteria. The presentation of many of the clinical features is age dependent. The average life expectancy of patients with NF1 is probably reduced by 10-15 years, and malignancy is the most common cause of death. The prevalence of clinically diagnosed NF1 ranges from 1/2,000 to 1/5,000 in most population-based studies. A wide variety of NF1 mutations has been found in patients with NF1, but no frequently recurring mutation has been identified. Most studies have not found an obvious relation between particular NF1 mutations and the resulting clinical manifestations. The variability of the NF1 phenotype, even in individuals with the same NF1 gene mutation, suggests that other factors are involved in determining the clinical manifestations, but the nature of these factors has not yet been determined. Laboratory testing for NF1 mutations is difficult. A protein truncation test is commercially available, but its sensitivity, specificity, and predictive value have not been established. No general, population-based molecular studies of NF1 mutations have been performed. At this time, it appears that the benefits of population-based screening for clinical features of NF1 would not outweigh the costs of screening.

Body Mass Index and Colon Cancer Mortality in a Large Prospective Study

Abstract: Obesity has been reported to increase the risk of colon cancer, especially in men. The authors examined this relation in the American Cancer Society's Cancer Prevention Study II, a nationwide mortality study of US adults. After 12 years of follow-up, 1,616 deaths from colon cancer in women and 1,792 in men were observed among 496,239 women and 379,167 men who were cancer free at enrollment in 1982. The authors used Cox proportional hazards analyses to control for effects of age, race, education, smoking, exercise, alcohol, parental history of colon cancer, fat intake, vegetable and grain intake, aspirin use and, in women, estrogen replacement therapy. In men, death rates from colon cancer increased across the entire range of body mass index (BMI). The rate ratio was highest for men with BMI > or =32.5 (rate ratio (RR) = 1.90, 95% confidence interval (CI): 1.46, 2.47) compared with men with BMI between 22.00 and 23.49. In women, a weaker association was seen in the three BMI categories of 27.5-29.9 (RR = 1.26, 95% CI: 1.03, 1.53), 30.0-32.4 (RR = 1.37, 95% CI: 1.09, 1.72), and > or =32.5 (RR = 1.23, 95% CI: 0.96, 1.59). These prospective data support the hypothesis that obesity increases the risk of colon cancer death and that the relation is stronger and more linear in men than in women.

Problems due to small samples and sparse data in conditional logistic regression analysis.

Abstract: Conditional logistic regression was developed to avoid "sparse-data" biases that can arise in ordinary logistic regression analysis. Nonetheless, it is a large-sample method that can exhibit considerable bias when certain types of matched sets are infrequent or when the model contains too many parameters. Sparse-data bias can cause misleading inferences about confounding, effect modification, dose response, and induction periods, and can interact with other biases. In this paper, the authors describe these problems in the context of matched case-control analysis and provide examples from a study of electrical wiring and childhood leukemia and a study of diet and glioma. The same problems can arise in any likelihood-based analysis, including ordinary logistic regression. The problems can be detected by careful inspection of data and by examining the sensitivity of estimates to category boundaries, variables in the model, and transformations of those variables. One can also apply various bias corrections or turn to methods less sensitive to sparse data than conditional likelihood, such as Bayesian and empirical-Bayes (hierarchical regression) methods.

Occupational and Environmental Risk Factors for Idiopathic Pulmonary Fibrosis: A Multicenter Case-Control Study

Abstract: Occupational exposures were investigated in a multicenter case-control study of clinically and histologically diagnosed idiopathic pulmonary fibrosis (IPF), a chronic diffuse interstitial lung disease of unknown etiology. Results are based on 248 cases, aged 20-75 years, diagnosed at 16 referral centers between January 1989 and July 1993. There were 491 controls ascertained by random digit dialing and matched to cases on sex, age, and geographic region. Data were collected using a standard telephone questionnaire. Occupational factors were based on a detailed history of jobs lasting 6 months or more and job activity, hobby, and specific substance checklists. Several occupational factors, adjusted for age and smoking in conditional multivariate logistic regression analyses, were significantly associated with IPF: farming (odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.5); livestock (OR = 2.7, 95% CI: 1.3, 5.5); hairdressing (OR = 4.4, 95% CI: 1.2, 16.3); metal dust (OR = 2.0, 95% CI: 1.0, 4.0); raising birds (OR = 4.7, 95% CI: 1.6, 14.1); stone cutting/polishing (OR = 3.9, 95% CI: 1.2, 12.7); and vegetable dust/animal dust (OR = 4.7, 95% CI: 2.1, 10.4). Interaction was detected between smoking and exposure to livestock (p = 0.06) and farming (p = 0.08). Results confirm previous studies showing increased risk associated with dusty environments.

Estimating Particulate Matter-Mortality Dose-Response Curves and Threshold Levels: An Analysis of Daily Time-Series for the 20 Largest US Cities

Abstract: Numerous studies have shown a positive association between daily mortality and particulate air pollution, even at concentrations below regulatory limits. These findings have motivated interest in the shape of the exposure-response relation. The authors have developed flexible modeling strategies for time-series data that include spline and threshold exposure-response models; they apply these models to daily time-series data for the 20 largest US cities for 1987-1994, using the concentration of particulate matter <10 microm in aerodynamic diameter (PM10) as the exposure measure. The spline model showed a linear relation without indication of threshold for PM10 and relative risk of death for all causes and cardiorespiratory causes; by contrast, for other causes, the risk did not increase until approximately 50 microg/m3 PM10. For all-cause mortality, a linear model without threshold was preferred to the threshold model and to the spline model, using the Akaike information criterion (AIC). The findings were similar for cardiovascular and respiratory deaths combined. By contrast, for causes other than cardiovascular and respiratory, a threshold model was more competitive with a threshold value estimated at 65 microg/m3. These findings indicate that linear models without a threshold are appropriate for assessing the effect of particulate air pollution on daily mortality even at current levels.

Relation between Aluminum Concentrations in Drinking Water and Alzheimer's Disease: An 8-year Follow-up Study

Abstract: To investigate the effect of aluminum and silica in drinking water on the risk of dementia and Alzheimer's disease, the authors analyzed data from a large prospective cohort (Paquid), including 3,777 subjects aged 65 years and over living at home in 75 civil parishes in Gironde and Dordogne in southwestern France in 1988-1989. The subjects were followed for up for 8 years with an active search for incident cases of dementia or Alzheimer's disease. Mean exposure to aluminum and silica in drinking water was estimated in each area. The sample studied included 2,698 nondemented subjects at baseline, for whom components of drinking water and covariates were available. A total of 253 incident cases of dementia (with 17 exposed to high levels of aluminum), including 182 Alzheimer's disease (with 13 exposed to high aluminum levels), were identified. The relative risk of dementia adjusted for age, gender, educational level, place of residence, and wine consumption was 1.99 (95 percent CI: 1.20, 3.28) for subjects exposed to an aluminum concentration greater than 0.1 mg/liter. This result was confirmed for Alzheimer's disease (adjusted relative risk = 2.14, 95 percent CI: 1.21, 3.80). However, no dose-response relation was found. Inversely, the adjusted relative risk of dementia for subjects exposed to silica (> or = 11.25 mg/liter) was 0.74 (95 percent CI: 0.58, 0.96). These findings support the hypothesis that a high concentration of aluminum in drinking water may be a risk factor for Alzheimer's disease.