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I B Tager

Publications and source records attributed to I B Tager.

At least 19 recordsLinked to original sources

Association between self-reported leisure-time physical activity and measures of cardiorespiratory fitness in an elderly population.

Leisure-time physical activity enhances health and functioning in older populations. However, few data are available on the correlation between self-reported leisure-time physical activity and cardiorespiratory fitness in the elderly. Treadmill exercise testing results were obtained for 1,006 members (median age 67 years) of a community-based sample. Subjects completed a standardized evaluation of medical/social history and measures of physical function. Leisure-time physical activity in the 12 months and 7 days before interview and over subjects' lifetimes was summarized as total and activity-specific METs/week and [METs * (hours/week)]. Multiple linear regression was used to investigate the cross-sectional, sex-specific associations between peak oxygen consumption (VO2) and exercise duration. After adjustment for age, body mass index, smoking history, medical morbidity, direct measures of physical functioning, forced expiratory volumes, and maximum respiratory muscle pressure, leisure-time physical activity accounted for < or = 5% of the variance of VO2 and exercise duration. Results were unchanged when analyses were restricted to subjects who achieved high levels of exercise. These data indicate that measures of aerobic capacity cannot be used to "validate" self-reported leisure-time physical activity in older subjects, and they further suggest that beneficial effects of physical activity in the elderly are the result of metabolic effects that are not reflected well by maximal aerobic capacity during exercise testing.

Age Distribution

A census-based design for the recruitment of a community sample of older adults: efficacy and costs.

PURPOSE: This is a report of the scientific and cost implications of a census-based design to identify residents aged 55 and over for a community study of the effects of aging on physical function. METHODS: A census of residents in a study community was conducted by the use of a mailed questionnaire. For households that did not complete and return the mailed census questionnaire, contact was attempted first by telephone and then by home visit. A comparison was made of the unit costs and characteristics of subjects identified by the different methods. RESULTS: A total of 3509 age-eligible subjects were identified (78.3% by mailer, 19.5% by telephone, and 2.0% by home visit). Costs per enrolled age-eligible subject were lower for mailing and telephone ($7.76 and $4.72 respectively) than for home visit ($36.25). Subjects identified by home visit were significantly younger than subjects identified either by mail or telephone. After adjustment for age, subjects identified by telephone had less education and income and poorer health and functional status than subjects identified by mail. With the exception of age, there were no significant differences between subjects identified by mailer and home visit. CONCLUSIONS: A mailed questionnaire with telephone recontact is a practical strategy for community-based recruitment. Recontact of subjects by telephone can be expected to identify subjects who are not well-represented in a sample based only on a mailer. In contrast, the home visit is expensive and identifies subjects who do not differ meaningfully from those identified by mailer.

Aged

Occupation, asthma, and chronic respiratory symptoms in a community sample of older women.

We evaluated the role of occupational factors on the prevalence of self-reported asthma, chronic bronchitis, and asthma-like respiratory symptoms among women >= 55 yr. Occupational history, smoking, and respiratory conditions were collected through an interviewer-administered questionnaire from 1,226 women. Lung function data from 820 subjects were used for group "validation" of the outcome variables. Significant associations were observed between the respiratory conditions and occupational groupings based on the longest occupation held. Artists, writers, decorators, and photographers (odds ratio [OR] = 3.1), and women in service occupations (OR = 2.4) had a significantly increased risk of asthma. The odds of asthma-like symptoms was significantly elevated among nurses and other nonphysician health workers (OR = 2.9), social workers (OR = 2.9), and homemakers (OR = 2.4). Exposure to dusts, gas, vapors, fumes, or sensitizers was associated with a significantly increased odds of asthma (OR = 1.8) and with a marginally significant increased odds of asthma-like symptoms (OR = 1.4). Smoking accounted for a large proportion of asthma and asthma-like conditions in this population (population attributable risk [PAR] = 40.5% and 35.0%, respectively); employment in occupations with a high probability of exposures to dusts, gas, vapors, fumes, or sensitizers also contributed significantly to the burden of asthma (PAR = 15.1 to 20.0%) and asthma-like symptoms (PAR = 7.5 to 10.2%).

Aged

Rates and independent correlates of Pap smear testing among Korean-American women.

OBJECTIVES: This study reports population estimates of Pap smear testing among Korean-American women and evaluates correlates of testing. METHODS: Korean Americans in 2 California counties were surveyed by telephone. Frequencies were age-adjusted to the 1990 census to produce population estimates of testing. Logistic regression models were used to evaluate independent correlates of testing RESULTS: Only 50% of the Korean-American women surveyed had a Pap test in the previous 2 years. The strongest independent correlate was having had a regular check-up in the previous 2 years (odds ratio 7.2, 95% confidence interval 4.2, 12.1). CONCLUSIONS: Rates of Pap testing among Korean-American women are well below national objectives. Collaboration and community-sensitive research are essential to collect data and design programs to improve the health of ethnic minority communities.

Asian

Exposure of young infants to environmental tobacco smoke: breast-feeding among smoking mothers.

OBJECTIVES: This study examined the degree to which breast-feeding and cigarette smoking by mothers and smoking by other household members contribute to the exposure of infants to the products of tobacco smoke. METHODS: The subjects were 330 mother-infant pairs derived from a cohort of 1000 pairs enrolled in a longitudinal study of the pulmonary effects of prenatal and postnatal smoking. The main outcome measure was corrected urinary cotinine levels. RESULTS: Urinary cotinine levels were 10-fold higher in breast-fed infants of smoking mothers than among bottle-fed infants of smoking mothers. Among infants of nonsmoking mothers, urine cotinine levels were significantly increased in infants living in homes with other smokers; in this group there was no significant difference between bottle-fed and breast-fed infants. Infants whose mothers smoked in the same room as the infant had only nonsignificant increases in cotinine levels compared with infants whose mothers restricted their smoking to other rooms. CONCLUSIONS: Breast-fed infants of smoking mothers have urine cotinine levels 10-fold higher than bottle-fed infants whose mothers smoke, suggesting that breast-feeding, rather than direct inhalation of environmental tobacco smoke, is the primary determinant of cotinine levels in infants whose mothers smoke.

Bottle Feeding

Methods development for epidemiologic investigations of the health effects of prolonged ozone exposure. Part I: Variability of pulmonary function measures.

The acute and subacute effects of ambient concentrations of ozone on lung function have been studied extensively in a variety of settings. Such studies generally have focused on measures of function that reflect either lung volumes or flows that are influenced by the physiology of large and small airways (e.g., forced expiratory volume in one second [FEV1). Data from animal studies suggest that the effects of prolonged exposure to elevated ambient concentrations of ozone result in abnormalities in the centriacinar region of the lung; and dosimetry models for humans predict that long-term exposure to ozone could impact the same areas of the human lung. However, alterations in structure at this level of the lung are not well reflected by measuring FEV1 until substantial structural changes have occurred. Measures of the lung function that reflect the functional mechanics of airways smaller than 2 mm in diameter are considered to be more relevant. At least one epidemiologic study has provided evidence that small-airway functions may be relevant to effects of prolonged exposure to environments with high concentrations of oxidants. A considerable body of physiologic data has established that flow rates measured during the terminal portion of a maximum expiratory flow-volume (MEFV) curve are largely governed by airways smaller than 2 mm in diameter A similar interpretation has been given to changes in the slope of phase III (delta N2) of the single-breath nitrogen washout (SBNW) curve. Despite the attractiveness of these measures in relation to airway physiology, some data suggest that measurements of flow via the terminal portions of MEFV and SBNW curves have much greater within-subject variability than forced vital capacity (FVC and FEV1. The present study was undertaken as part of a larger feasibility study to develop methods to study the effects of prolonged exposure to elevated ambient ozone levels on lung function in adolescents. A convenience sample of 239 freshmen (ages 16-20 years) entering the University of California, Berkeley were recruited to participate in this protocol. All were lifelong residents of the San Francisco Bay Area or the Los Angeles Basin. Subjects were studied on two occasions five to seven days apart. At each test session, subjects performed up to eight forced expiratory maneuvers to produce three acceptable and reproducible MEFV curves by modified American Thoracic Society criteria. Tests of SBNW were then performed on the basis of detailed criteria for validity and reproducibility. Eight attempts to generate three curves were allowed. The delta N2 was obtained by a least-squares regression of nitrogen concentrations between the 750-mL and 1750-mL volume points. Instantaneous flow at 75% of expired volume (FEF75%), average flow between the 25% and 75% volume points (FEF25%-75%), and delta N2 were the principal outcomes. Variance components were estimated with a nested random effects model with adjustments for important covariates. The average within-subject coefficients of variation (+/-SD of distribution of means) for male subjects were: FEV1 1.2 (+/-0.8); FEF25%-75% 3.2 (+/-2.3); FEF75% 5.8 (+/-5.0); and delta N2 17.9 (+/-12.3); for female subjects they were: FEV1 1.4 (+/-0.9); FEF25%-75% 3.0 (+/-2.2); FEF75% 6.2 (+/-5.2); and delta N2 19.9 (+/-17.0). The variance attributed to test session was less than 1% for all measures. The percentages of variance due to within-subject variation for each measure (adjusted for sex, area of residence, ethnicity, and height) were: FVC 3.6%; FEV1 3.0%; FEF25%-75% 5.2%; FEF75% 8.9%; and delta N2 23.9%. Of all subjects tested, 234 (97.9%) could provide at least two acceptable MEFV curves, but only 218 (91.2%) could provide at least two acceptable SBNW curves. The results were unchanged by recent history of acute, respiratory illness.(ABSTRACT TRUNCATED)

Air Pollution

Methods development for epidemiologic investigations of the health effects of prolonged ozone exposure. Part II. An approach to retrospective estimation of lifetime ozone exposure using a questionnaire and ambient monitoring data (California sites).

An extensive body of data supports a relation between acute exposures to ambient ozone and the occurrence of various acute respiratory symptoms and changes in measures of lung function. In contrast, relatively few data are available on the human health effects that result from long-term exposure to ambient ozone, Current efforts to study long-term ozone-related health effects are limited by the methods available for ascertaining lifetime exposures to ozone. The present feasibility study was undertaken as part of the Health Effects Institute's Environmental Epidemiology Planning Project (Health Effects Institute 1994) to (1) determine whether, in the context of an epidemiologic study, reliable estimates can be obtained for lifetime exposures to ozone by combining estimates from lifetime residential histories, typical activity patterns during life, and residence-specific ambient ozone monitoring data; (2) identify the minimum data required to produce reliable estimates of lifetime exposure; and (3) analyze the relations between various estimates of lifetime ozone exposure and measures of lung function. A convenience sample of 175 first-year students at the University of California, Berkeley, who lived all of their lives in selected areas of California (the Los Angeles Basin or the San Francisco Bay Area), were studied on two occasions (test and retest or test sessions 1 and 2), five to seven days apart. Residential and lifestyle data were obtained from a questionnaire: residence-based ambient ozone exposure values were assigned by interpolation of ambient ozone monitoring data to residential locations. Estimated lifetime exposure was based on average ozone levels between 10 a.m. and 6 p.m. and hours of exposure to ozone concentrations greater than 60 parts per billion (ppb). "Effective" lifetime exposure to ozone was based on a weighted average of estimated time spent in different ambient ozone environments as determined by different combinations of activity data. Pulmonary function was evaluated with flows and volumes from maximum expiratory flow-volume curves and slope of phase III of the single-breath nitrogen washout (SBNW) curves. Although the test-retest reliability of the residential history was acceptably high only for first and second residences, most of the unreliability for other residences came from residences occupied for relatively short durations. Therefore, the test-retest reliability of estimated lifetime exposure to ozone was high, with intraclass correlations greater than 0.90 for all approaches evaluated. Multiple, linear regression analyses showed a consistently negative relation between estimates of lifetime exposure to ozone and flows that reflect the physiology of pulmonary small airways. No relation was observed between lifetime ozone exposure and forced expiratory volume or the slope of phase III, and the relation between lifetime exposure and forced expiratory volume in one second was inconsistent. The results of the flow measures were unaffected by the method used to estimate lifetime exposure and gave effect estimates that were nearly identical. The data from this study indicate that useful and reproducible estimates of lifetime ozone exposure can be obtained in epidemiologic studies by using a residential history. However, the total burden of ozone to which the subjects were exposed cannot be determined accurately from such data. Nonetheless, the estimates so obtained appear to be associated with alterations in pulmonary function that are consistent with the predicted site of maximum effect of ozone in the human lung.

Air Pollution

Maternal smoking during pregnancy and birth outcomes with weight gain adjustments via varying-coefficient models.

There is considerable interest in the impact of maternal exposures during pregnancy on birth outcomes. Clearly, exposures associated with poor birth outcomes need modification or avoidance. However, arriving at such estimates of association is made challenging by a number of features characteristic of the relevant data. First, exposures may be time varying (for example, cigarette and alcohol consumption) so that, to relate them to birth outcomes, one needs to model them and then extract derived parameters. Secondly, there are likely to be unequal numbers and spacings of exposure determinations during pregnancy. Thirdly, one needs to account for a variety of additional covariates. Finally, the variability and non-linearities inherent in birth outcomes mandate flexible modelling approaches. Here we use data from a cohort of East Boston mothers to assess the impact of smoking during pregnancy on birth weights. We emphasize modelling of, and then adjusting for, maternal weight gain during pregnancy and a proxy measure for pre-pregnancy weight, so as to obtain better estimates of the smoking effect. Throughout, our analysis is guided by appropriate graphics. The adjustment features an interesting application of varying-coefficient models. Results indicate that smoking related deficits in birth weights depend on the mode of adjustment, and that previously observed deficits of approximately 200 g are best recaptured with use of varying-coefficient models.

Adult

Association between lifetime ambient ozone exposure and pulmonary function in college freshmen--results of a pilot study.

Human health effects due to chronic exposure to ozone (O3) have not been established due to problems with exposure assignment and the use of measures of lung function which may not reflect the site of O3 toxicity in the lung. We investigated the feasibility of retrospective assessment of O3 exposure-relevant covariates and derived lifetime "effective exposure" to ozone. Mid- and end-expiratory flows (FEF25-75%, FEF75%) were regressed against effective exposure and ecological lifetime exposure. A convenience sample of 130 UC Berkeley freshmen, ages 17-21, participated twice in the same tests (residential history, questionnaire, pulmonary function), 5-7 days apart. Students had to be lifelong residents of Northern (SF) or Southern (LA) California. Monthly ambient O3 concentrations (OZ) were assigned based on the lifetime residential history. An "effective time" (T) spent in OZ environments was derived for each residence and age stratum (0-2, 3-5, 6-11, 12+) with the use of questions about "total time spent outdoors" and time spent in "moderate" and/or "heavy" activity. Effective exposure was calculated over the lifetime (OZ x T) of each subject. Ozone metrics used were 8-hr averages (10 AM-6 PM) and "hours above 60 ppb." FEF25-75% and FEF75% decreased with both effective exposure and ecologic assignment of O3 exposure. For a 20 ppb increase (interquartile range) in 8-hr O3, FEF75% decreased 334 ml/sec (95%Cl:11-657 ml/sec), which corresponds to 14% (1.0-28.3%) of the population mean FEF75%. The corresponding effect on FEF25-75% was -420 ml/sec (95%Cl: +46 to -886, P = 0.08) or 7.2% of the mean. Use of time-activity data to define exposure had no impact on estimates. Negative confounding factors were region (SF vs LA), gender, and ethnicity. Lifetime 8-hr average O3 concentrations ranged from 16 to 74 ppb with little overlap between regions. There was no evidence for different O3 effects across regions. Effects were independent of lifetime mean PM10, NO2, temperature, or humidity. Effects on FEV1 tended to be negative whereas those for FVC, although negative in some models, where inconsistent and small. The strong relationship of lifetime ambient O3 on mid- and end-expiratory flows of college freshmen and the lack of association with FEV1 and FVC are consistent with biologic models of chronic effects of O3 in the small airways. Since the present study was designed as a pilot study, these findings have to be confirmed in a larger sample that is representative of the target population.

Adolescent

Maternal smoking during pregnancy, urine cotinine concentrations, and birth outcomes. A prospective cohort study.

BACKGROUND: Most studies of the reproductive consequences of cigarette smoking base exposure on self-reported smoking habits. This study examines the relationship of birth outcomes to the timing and intensity of maternal active and passive smoking estimated both from self-reports and from cotinine concentration in maternal urine during early, middle, and late gestation. METHOD: This cohort study included 740 white and Hispanic women who obtained antenatal care at the East Boston Neighborhood Health Center between 1986 and 1992. At each antenatal visit, information on maternal active and passive smoking was obtained by a detailed questionnaire, and by measurement of urine cotinine concentrations. Infant birth outcomes were obtained from hospital records. Multiple linear regression was used to evaluate antenatal smoking variables on birth outcomes, with adjustment for maternal demographic characteristics, reproductive history, alcohol use, maternal weight and height, and infant gender. RESULTS: The percentage of mothers who ever smoked cigarettes during pregnancy was 55.5% for white and 10.2% for Hispanic women. A significant inverse exposure-response relationship between cotinine concentration in maternal urine and infant size at birth was demonstrated. However, the relationship was less clear between maternal self-reported smoking status and these outcomes. For the entire gestation, a 1000 ng increase in mean urine cotinine concentration was associated with a 59 +/- 9 g reduction in birthweight, a 0.25 +/- 0.05 cm reduction in length, and a 0.12 +/- 0.03 cm reduction in head circumference, respectively. For maternal passive smoking, the much smaller magnitude of effect precludes firm conclusions. CONCLUSIONS: These data suggest that preventing and reducing active maternal smoking during pregnancy may have a beneficial impact on infant size at birth.

Adult

Reproducibility of retrospective assessment of outdoor time-activity patterns as an individual determinant of long-term ambient ozone exposure.

BACKGROUND: Long-term effects of ambient ozone pollution are not clearly established to date. Epidemiological assessment of these effects might benefit from improved exposure measures. Tools to retrospectively assess long-term time-activity patterns as a potentially important co-predictor of true exposure have not yet been developed. METHODS: Three self-completed questionnaires for the retrospective assessment of outdoor time-activity patterns were tested in 168 lifelong residents (ages 17-21) of California. A test-retest design (within 5-7 days) was employed. (1) Based on a set of questions (AQUES) on outdoor 'heavy' and 'moderate' activity, h/day engaged in activity were derived. Definition of activity levels was based on published data regarding energy expenditure of physical activities. (2) A table format (ATAB) asked quantitative questions for each activity engaged in. (3) A 24-hour-log (A24H) had to be completed to indicate time spent outdoors in four levels of activity (heavy, moderate, light, at rest) on a 'typical day' (n = 44). Test-retest reliability was assessed. Comparison across approaches was restricted to the subgroup of 44 students that completed all three approaches. RESULTS: All approaches yielded reasonably reliable results (between-test variance 13-39% of total variance, Spearman rank correlations: 0.68-0.86 for time spent in outdoor activities). Population mean values differed across approaches, ranging from 1.0 (ATAB) to an unrealistically high estimate of 3.5 (A24H) h/day. The ATAB mean values were close to expectations when compared to published data. CONCLUSIONS: The structure of ATAB has major advantages and mean results were the most valid estimates compared to California population data. The AQUES is a less transparent 'black box' measure of exposure. For long-term retrospective time-activity assessment, we propose to use ATAB. For shorter recall periods the easier AQUES may be a reasonable alternative, yielding similar results as ATAB. The A24H was of limited value.

Adolescent

The semi-individual study in air pollution epidemiology: a valid design as compared to ecologic studies.

The assessment of long-term effects of air pollution in humans relies on epidemiologic studies. A widely used design consists of cross-sectional or cohort studies in which ecologic assignment of exposure, based on a fixed-site ambient monitor, is employed. Although health outcome and usually a large number of covariates are measured in individuals, these studies are often called ecological. We will introduce the term semi-individual design for these studies. We review the major properties and limitations with regard to causal inference of truly ecologic studies, in which outcome, exposure, and covariates are available on an aggregate level only. Misclassification problems and issues related to confounding and model specification in truly ecologic studies limit etiologic inference to individuals. In contrast, the semi-individual study shares its methodological and inferential properties with typical individual-level study designs. The major caveat relates to the case where too few study areas, e.g., two or three, are used, which render control of aggregate level confounding impossible. The issue of exposure misclassification is of general concern in epidemiology and not an exclusive problem of the semi-individual design. In a multicenter setting, the semi-individual study is a valuable tool to approach long-term effects of air pollution. Knowledge about the error structure of the ecologically assigned exposure allows consideration of the impact of ecologically assigned exposure on effect estimation. Semi-individual studies, i.e., individual level air pollution studies with ecologic exposure assignment, more readily permit valid inference to individuals and should not be labeled as ecologic studies.

Air Pollutants

Effects of ozone on normal and potentially sensitive human subjects. Part I: Airway inflammation and responsiveness to ozone in normal and asthmatic subjects.

We report here the results of a multiphase project to assess the significance of airway responsiveness and airway injury in ozone (O3)* sensitivity. In Phase I, we measured the preexposure methacholine responsiveness of 66 normal subjects and then exposed these subjects to 0.2 ppm O3 for 4 hours with moderate exercise. Preexposure methacholine responsiveness was weakly correlated with O3-induced increases in specific airway resistance (sRaw) but not O3-induced declines in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC). In addition, O3-induced lower respiratory symptoms were not well correlated with O3-induced changes in lung function. In Phase II, we exposed 23 normal subjects to O3, following an identical protocol to that of Phase I, and then performed bronchoscopy with proximal airway lavage (PAL), bronchoalveolar lavage (BAL), and bronchial biopsy at 18 hours after exposure. Ozone-induced increases in percentage of neutrophils and total protein concentration were observed in both bronchial fraction and BAL fluids; increased percentage of neutrophils also was observed in PAL fluid. These increases were correlated with O3-induced increases in sRaw, but not with O3-induced declines in FEV1 or FVC. Ozone also appeared to increase expression of intercellular adhesion molecule-1, an important mediator of neutrophil recruitment, in bronchial mucosa. In Phase III, we exposed a group of 19 asthmatic subjects to O3, following a protocol identical to that of Phase II. We then compared the lower respiratory symptom and lung function responses of the asthmatic subjects to those of the 81 normal subjects who participated in Phase I, Phase II, or both. The changes in the PAL and BAL fluids of the asthmatic subjects were compared with those of the normal subjects who participated in Phase II. Although both the asthmatic and nonasthmatic subjects showed significant O3-induced changes in lower respiratory symptoms, FEV1, FVC, and sRaw, no significant differences were found between the groups. For sRaw, however, a nonsignificant trend toward a greater O3-induced increase was noted for the asthmatic subjects. In contrast, the O3-induced increases in percentage of neutrophils and total protein concentration in BAL fluid were significantly greater for the asthmatic subjects than for the nonasthmatic subjects. These data suggest that although the lower respiratory symptom and lung function responses to O3 are not markedly greater in asthmatic subjects than in healthy subjects, the inflammatory response of the asthmatic lung may be more intense.

Adolescent

Cryptosporidiosis among patients infected with human immunodeficiency virus. Factors related to symptomatic infection and survival.

The authors reviewed the medical records of 194 human immunodeficiency virus (HIV)-positive patients newly diagnosed with cryptosporidiosis and all 3,564 patients with newly diagnosed acquired immunodeficiency syndrome (AIDS) at San Francisco General Hospital for the period 1986-1992. The study was designed to address three questions: 1) How do AIDS patients who present with cryptosporidiosis differ from other patients with AIDS? 2) What factors are associated with survival among AIDS patients with newly diagnosed cryptosporidiosis? 3) Does a diagnosis of cryptosporidiosis impact survival after AIDS diagnosis? A total of 194 cases of cryptosporidiosis among HIV-infected patients were identified during the study period. Of the 194 patients, 109 (56%) had no prior diagnosis of AIDS. These 109 patients represented 3.1% of the 3,564 newly diagnosed cases of AIDS in the same period. Among the 134 patients with CD4 T-lymphocyte counts performed within 3 months of Cryptosporidium diagnosis, 34 (25%) had CD4 counts greater than 209 cells/ml. In a multivariate conditional logistic regression model, the incidence of Cryptosporidium was related to ethnicity (for blacks vs. whites, matched odds ratio (OR) = 0.15, 95% confidence interval (CI) 0.03-0.73), CD4 count (for a CD4 count of < or = 53 cells/ml vs. > 53 cells/ml, matched OR = 12.60, 95% CI 4.01-39.61), and age (for a 10-year increase, matched OR = 0.51, 95% CI 0.27-0.98). Two factors measured at the time of Cryptosporidium diagnosis were identified as being independently associated with survival (p < 0.001) in the proportional hazards model: CD4 count < or = 53 cells/ml versus > 53 cells/ml (relative hazard = 6.18, 95% CI 2.99-12.76) and hematocrit < or 37% versus > 37% (relative hazard = 2.27, 95% CI 1.22-4.22). The median durations of survival in the four subgroups of Cryptosporidium-infected patients defined by these two variables differed significantly from each other (range, 204-1,119 days). Cryptosporidiosis as an initial AIDS-defining diagnosis was associated with an elevated relative hazard of death in comparison with other AIDS-defining diagnoses (relative hazard = 2.01, 95% CI 1.38-2.93). These data identify the groups of HIV-infected individuals at risk for presentation with symptomatic Cryptosporidium infection; the distinct survival patterns among subgroups of those patients already infected with this parasite; and the survival of AIDS patients with newly diagnosed cryptosporidiosis relative to patients with other AIDS-defining conditions. Such information is necessary for the design of prospective studies, the development of prophylactic strategies, the evaluation of candidate therapies, and the provision of prognostic information to patients.

AIDS-Related Opportunistic Infections

Application of exponential smoothing for nosocomial infection surveillance.

Detection of outbreaks of infection or increases in bacterial resistance to antimicrobial agents is an essential component of hospital infection control surveillance. The authors applied the method of exponential smoothing to microbiology data from 1987-1992 to investigate a suspected outbreak of gentamicin resistance among Pseudomonas aeruginosa bacteria at the Department of Veterans Affairs Medical Center, San Francisco, California, in 1991-1992. The years 1987-1990 were used to develop the baseline for the forecast model. Application of the model indicated that two observed prominent peaks in the annual cumulative incidence of gentamicin-resistant P. aeruginosa were within the upper bounds of their respective 95% confidence intervals as estimated by the forecast model--i.e., that no epidemic was in progress. This prediction was supported by investigations by the hospital's infection control team which indicated that the apparent increases were due to readmission of patients previously known to harbor these organisms. In contrast, application of a typically employed method that ignores the time series data structure indicated that there were 6 months in which incidence rates exceeded the upper bounds of their respective 95% confidence intervals, thereby erroneously suggesting that an epidemic was in progress. Recursive algorithms and some simplifying assumptions that do not affect the validity of inferences make the application of this method practical for nosocomial infection control programs.

Anti-Bacterial Agents

Airways responsiveness, wheeze onset, and recurrent asthma episodes in young adolescents. The East Boston Childhood Respiratory Disease Cohort.

To describe the role of airways responsiveness in predicting incidence of wheeze in early adolescence and to examine the association between airways responsiveness and active asthma symptoms, children who had been tested for airways hyperresponsiveness were assessed prospectively. Of 770 children in the East Boston Childhood Respiratory Disease Cohort who were between 5 and 9 yr of age at time of entry into the study, 281 children received airways challenges during voluntary follow-up conducted between 1980 and 1986. Each subject presented a sequence of wheeze or asthma diagnosis reports along with a sequence of time-varying covariates, including airways challenge results and symptom and exposure information. A robust "pooled repeated observations" analog of the proportional hazard regression model was used to assess associations among risk factors and the probability of incident wheeze or active asthma. In the analysis of wheeze incidence, airways responsiveness (elicited via eucapnic hyperventilation with cold air or methacholine challenge) among those free of a history of wheeze at a given visit was found to be associated with a greater tendency to develop wheezing in the next visit (odds ratio [OR] = 3.91, 95% confidence interval [CI] = 1.21, 12.66), after controlling for a constellation of known risk factors. In the analysis of recurrent asthma episodes, airways responsiveness at a given visit was associated with a greater tendency to have an asthma diagnosis reported at the subsequent visit (OR = 4.2, 95% CI = 1.92, 9.23). For subjects presenting multiple airways responsiveness challenge studies, two successive positive airways responsiveness results were independently associated with a higher likelihood of recurrent asthma episodes. These results confirm the predictive importance of airways responsiveness in the natural history of the development and persistence of asthmatic symptoms.

Adolescent