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PubMed1989

Breast cancer before age 45 and oral contraceptive use: new findings.

The relation between the risk of breast cancer before 45 years of age and oral contraceptive use was examined in a case-control study conducted in New York, Philadelphia, Baltimore, and Boston from 1983 to 1986 of 407 patients with breast cancer and 424 controls. With allowance for confounding, for ever use, the multivariate relative risk estimate was 2.0 (95% confidence interval (CI), 1.4-2.9). For less than 10 years of use, the estimate approximated 2.0 in all categories of duration, including less than three months; for 10 or more years of use it was 4.1 (95% CI, 1.8-9.3). The association was apparent in virtually all subgroups examined, including younger and older women, and women at low and high underlying risk of breast cancer. Contrary to some previous reports, the association was not stronger for use before a first term pregnancy or at an early age. The results suggest that oral contraceptive users, particularly those with very long durations of use, may be at increased risk of breast cancer. However, information bias, particularly for short-term use, could not be ruled out. There may also have been selection bias if oral contraceptive users were under more intensive medical surveillance. It has not been possible to reconcile the findings of the various studies to date, including the authors' earlier results showing no association. The latter results were derived from data collected using methods almost identical to those used in the present study.

Adult↗
PubMed1990

Breast feeding and the risk of severe cholera in rural Bangladeshi children.

The association between breast feeding and the risk of severe cholera was examined in a case-control study of rural Bangladeshi children under 36 months of age who were studied in 1985-1986 during a field trial of killed oral cholera vaccines. A total of 116 cases who were treated for severe cholera were compared with 464 age-matched community controls without severe cholera. Overall, the odds ratio relating breast feeding to severe cholera (0.30, p less than 0.0001) reflected a 70% reduction in the risk of severe cholera among breast-fed children. The estimated reduction of risk declined with age, but was clearly evident in children up to 30 months of age. Although the association between breast feeding and a reduced risk of severe cholera was not significantly greater in children of mothers who had received cholera vaccine than in children whose mothers had received placebo during the trial, maternal vaccination per se was suggestively associated with a reduced risk of severe cholera in their nonvaccinated children (odds ratio = 0.53, p = 0.05). These results indicate that breast feeding was associated with a substantial reduction of the risk of severe cholera and raise the possibility that vaccination of mothers may provide protection to their young children in endemic settings.

Bangladesh↗
PubMed1990

Detecting disease clusters: the importance of statistical power.

A variety of methods and models have been proposed for the statistical analysis of disease excesses, yet rarely are these methods compared with respect to their ability to detect possible clusters. Evaluation of statistical power is one approach for comparing different methods. In this paper, the authors study the probability that a test will reject the null hypothesis, given that the null hypothesis is indeed false. They present a discussion of some considerations involved in power studies of cluster methods and review two methods for detecting space-time clusters of disease, one based on cell occupancy models and the other based on interevent distance comparisons. The authors compare these approaches with respect to: 1) the sensitivity to detect disease excesses (false negatives); 2) the likelihood of detecting clusters that do not exist (false positives); and 3) the structure of a cluster in a given investigation (the alternative hypothesis). The methods chosen, which are two of the most commonly used, are specific to different hypotheses. They both show low power for the small number of cases which are typical of citizen reports to health departments.

Clinical Protocols↗
PubMed1991

The prevalence of selected physical activities and their relation with coronary heart disease risk factors in elderly men: the Zutphen Study, 1985.

Physical activity patterns and their relation with coronary heart disease risk factors are described for a representative sample of 863 Dutch men, 65-84 years old, who participated in the 1985 survey of the Zutphen cohort of the Seven Countries Study. Cross-sectional results revealed a median total of reported physical activity of about 1 hour and 20 minutes per day; only 5.8% reported no physical activity. The percentage of participation and total weekly time spent in physical activity decreased as age increased; the decrease was less pronounced for walking, bicycling, gardening, and doing odd jobs than for sports, hobbies, and work. Statistically significant mean differences were found among quartiles of total weekly physical activity for both total cholesterol and high-density lipoprotein cholesterol (HDL cholesterol); however, only the differences for HDL cholesterol remained significant (p = 0.045) after adjusting for potential confounders. Statistically significant regression coefficients (p less than 0.05) were found for the independent association between walking and total cholesterol and between gardening and total cholesterol, HDL cholesterol, and systolic blood pressure, after adjusting for confounders. Total weekly physical activity and specific activities, e.g., gardening and walking, demonstrated generally favorable associations with cholesterol and systolic blood pressure.

Aged↗
PubMed1992

Nonlinear modeling of alcohol consumption for analysis of beverage type effects and beverage preference effects.

In a previous report (Kimball and Friedman, Am J Epidemiol, 1992;135:1279-86), linear models for relating health outcomes to alcohol consumption were proposed for differentiating between beverage type effects and beverage preference effects. The models were applied to data relating serum high density lipoprotein cholesterol to alcohol consumption. In this report, those models are extended to the nonlinear case and are applied to data from the 1982 Maryland Hypertension Survey relating systolic blood pressure to alcohol consumption.

Adolescent↗
PubMed1992

The complementary effect of latrines and increased water usage on the growth of infants in rural Lesotho.

The effects of water quantity and sanitation, alone and in combination with each other, on infant weight gain and length gain were examined. Data on 119 infants were collected from 20 villages in rural Lesotho between July 1984 and January 1985. The interactions between sanitation and increased water usage for weight gain (p = 0.007) and length gain (p = 0.006) were significant after potential confounding was controlled. The biggest growth effects were dependent on families possessing a latrine and increasing their use of water during the warm, wet season. Infants gained 1.031 kg (95% confidence interval (CI) 0.420 to 1.642) and 2.028 cm (95% CI 0.523 to 3.533) more when both positive factors were present, as compared with only having a latrine. Increasing water usage compared with not increasing water usage resulted in only 0.105 kg (95% CI -0.175 to 0.385) more weight gain and -0.309 cm (95% CI -1.005 to 0.387) more length in the absence of a latrine. Similarly, infants gained 1.106 kg (95% CI 0.484 to 1.728) and 2.076 cm (95% CI 0.559 to 3.593) more if both factors were operating than did infants whose families only increased their water usage. In the nonincreased water group, the difference in growth between having and not having a latrine was 0.180 kg (95% CI -0.093 to 0.453) and -0.261 cm (95% CI -0.951 to 0.429). Water supply programs should emphasize use of more water for personal hygiene, and sanitation programs should install toilet facilities where water usage is high or has been increased because of an educational program.

Bias↗
PubMed1994

Invited commentary: ecologic studies--biases, misconceptions, and counterexamples.

Many authors have pointed out that relative-risk estimates derived from ecologic data are vulnerable to biases not found in estimates derived from individual-level data. Nevertheless, biases in ecologic studies still are often dealt with in the same manner as biases in other observational studies, and so are not given adequate treatment. This commentary reviews and illustrates some of the more recent findings about bias in ecologic estimates. Special attention is given to problems of ecologic confounder control when individual risks follow a nonlinear model, and to misconceptions about ecologic bias that have appeared in the literature.

Bias↗
PubMed1994

Limited sampling models for topotecan pharmacokinetics.

BACKGROUND: Limited sampling models for the estimation of the topotecan Area Under the concentration versus time Curve (AUC) and its lactone ring opened form (AUC Tm), from one or more plasma concentration determinations, are desired for further population-kinetic studies. PATIENTS AND METHODS: The models were developed and validated using 34 pharmacokinetic curves in 19 patients who participated in a phase I study. RESULTS: A single point model was selected as optimal: AUC (mumol/L.min) = 499 (min).C2h (mumol/L) +0.85 (m2/mg.mumol/L.min).dose(mg/m2), and for topotecan-metabolite (Tm), AUC Tm (mumol/L.min) = 55.1 (min).CTm2h (mumol/L) -0.011 (m2/mg.mg.mumol/L.min).dose (mg/m2), where C2h is the plasma concentration (mumol/L) of topotecan at 2 h after the end of a 30-min infusion, and CTm2h the concentration of the opened form at the same time point. The models are valid for dosages ranging from 0.5 to 1.5 mg/m2/day and proved to be unbiased (MPE% = -1.8% and -9.3%, respectively) and precise (RMSE% = 17.9% and 22.7%, respectively). From the predicted AUCs, the clearance (Cl = dose (mumol)/AUC(mumol/L.min)) could also reliably be predicted, as well as the total AUC (AUC+AUC Tm) RMSE% = 17.1% and MPE% = -0.02%). Half-life values could not be predicted with acceptable precision and accuracy. CONCLUSION: The limited sampling models presented may useful for future studies focused on pharmacokinetic/pharmacodynamic relationships of topotecan in large populations.

Adolescent↗
PubMed1998

The effect of environmental temperature and body weight on growth rate and feed:gain of male broilers.

High environmental temperatures are detrimental to the growth and feed:gain of broilers. The objective of this research was to determine the effects of incremental differences in environmental temperature on growth and feed:gain. The data are needed for decisions about the profitability of energy inputs when managing the housing environment. In Trial 1, broiler chicks were reared as a group to 21 d on litter with constant lighting and with water and feed available for ad libitum consumption. They were then moved to 10 environmental chambers. Each chamber was set at a different temperature ranging from 21.1 C to 31.1 C in 1.11 C increments. Weight gain and feed:gain were determined when the broilers were 28, 35, and 42 d old. In Trials 2 and 3, broilers were placed in the environmental chambers, and weight gain and feed:gain were determined for the 42 to 49 d period. The data were analyzed statistically, and regression equations were obtained for growth and feed:gain. Equations were based on body weight and temperature, and the body weight equation was plotted as grams gain per bird per day. Feed:gain was plotted for that body weight and temperature. Body weight gain per day increased to a maximum with increasing weight and then declined. The body weight at the maximum rate of gain was inversely related to temperature. Feed:gain increased as body weight increased. Feed:gain was directly related to temperature at weights above 800 g and the effect of temperature increased as body weight increased. The data will be useful for the evaluation of various management scenarios to determine the inputs that are profitable.

Adaptation, Physiological↗
PubMed2001

Relating weight gain and feed:gain of male and female broilers to rearing temperature.

The effects of environmental temperature on growth and feed:gain were studied in three trials each for male and female broilers. Chicks were reared in a common environment to 21 d of age. At 21 d, they were randomly allocated to 10 environmental chambers. Each chamber was maintained at a constant temperature; the chambers ranged from 12 to 30 C in two-degree increments. The dewpoint was maintained at 18 C, except that relative humidity was not permitted to exceed 82.9%. Body weight was determined at 21 d. Weight gain and feed:gain were determined at 28, 35, 42, and 49 d. The data were analyzed statistically, and regression equations were obtained for weight gain and feed:gain for each sex. Equations were based on body weight and temperature, and the body weight equations were plotted as grams gained per bird per day. Feed:gain increased with increasing weight. The temperature that resulted in the most favorable feed:gain decreased with increasing weight. These results support lower rearing temperatures for optimum growth and feed:gain by large broilers than those of other reports in the literature.

Adaptation, Physiological↗
PubMed2002

Dietary polyunsaturated fatty acids decrease fat deposition in separable fat depots but not in the remainder carcass.

Two experiments were conducted in order to determine the effect of dietary fatty acid profile on deposition of body fat, carcass fat, and separable fat depots. Diets with four types of fat (tallow, olive, sunflower, and linseed oils) at an inclusion level of 10% were administered to female broiler chickens. In Experiment 1, total body fat, carcass fat (total body fat minus abdominal fat), and abdominal fat (AF) were determined. In Experiment 2, several separable fat depots (abdominal, neck, sartorial, and mesenteric fat) were removed and weighed. In general, the analyzed separable fat depots were reduced in broilers fed sunflower or linseed oils with respect to those fed tallow or olive oil (P < 0.05). Percentages of body and carcass fat were also slightly reduced in birds fed sunflower or linseed oil, with respect to those fed tallow; however, the differences were not statistically significant. Regression analysis showed that body fat, carcass fat, and fat depots variability were closely correlated with AF (R2 = 0.69, 0.56, and 0.81, respectively), except for birds fed tallow, in which abdominal and mesenteric fat showed a different growth pattern with respect to the other treatments and to the other fat depots. These results suggest that polyunsaturated fatty acids reduce fat deposition in separable fat depots with respect to monounsaturated and saturated fats but not in the rest of the body fat depots. The growth pattern of fat depots can be modified by dietary fatty acid profile. Broilers fed saturated fat tend to deposit more fat in abdominal and mesenteric depots.

Abdomen↗
PubMed1994

Morphometric analysis of melanocytic tumors. A study of nuclear area and density.

Because the differential diagnosis of melanocytic tumors is sometimes difficult, we performed a morphometric analysis of 20 benign nevi, 20 malignant melanomas, and 10 Spitz's nevi. The nuclear pleomorphism and the maturation to the depth of the tumor were quantified by measuring nuclear area and nuclear density at serial levels of the tumor (every 220 microns of thickness). Data obtained were analyzed statistically. Linear regression was used to represent the variation of nuclear area to the depth, and the standard deviation of nuclear areas reflected nuclear pleomorphism. We attempted to separate different tumors from each other using the Jacknife procedure and morphometric data. Using the Jacknife procedure rather than the usual histological procedures, we were able to distinguish benign nevi from Spitz's nevi and malignant melanoma in as many as 92% of cases, but we distinguished Spitz's nevi from malignant melanoma in only up to 60% of cases. In conclusion, we found it difficult to distinguish between Spitz nevi and melanoma using nuclear morphometric parameters. Other studies using new morphometric parameters are needed in order to improve our ability to make this discrimination.

Adolescent↗
PubMed2006

Flexible interaction model for complex interactions of multiple anesthetics.

BACKGROUND: Minto et al. (Anesthesiology 2000) described a mathematical approach based on response surface methods for characterizing drug-drug interactions between several intravenous anesthetic drugs. To extend this effort, the authors developed a flexible interaction model based on the general Hill dose-response relation that includes a set of parameters that can be statistically assessed for interaction significance. METHODS: This new model was developed to identify pharmacologically meaningful interaction-related parameters and address mathematical limitations in previous models. The flexible interaction model and the model of Minto et al. were compared in their assessment of additivity using simulated sample data sets. The flexible interaction model was also compared with the Minto model in describing drug interactions using data from several other clinical studies of propofol, opioids, and benzodiazepines from Short et al. (Anesthesiology 2002) and Kern et al. (Anesthesiology 2004). RESULTS: The flexible interaction model was able to accurately classify an additive interaction based on the classic definition proposed by Loewe, with at most an 8% difference between the two surfaces. Also, the proposed model fit the clinical interaction data as well or slightly better than that of Minto et al. CONCLUSIONS: The new model can accurately classify additive and synergistic drug interactions. It also can classify antagonistic interactions with biologically rational surfaces. This has been a problem for other interaction models in the past. The statistically assessable interaction parameters provide a quantitative manner to assess the interaction significance.

Algorithms↗
PubMed1991

Breast cancer risk and oral contraceptive use: results from a large case-control study.

The association between oral contraceptive use and breast cancer risk was examined using data from a case-control study of breast cancer in Long Island, New York. Cases were defined as female residents of Nassau and Suffolk Counties between the ages of 20 and 79, diagnosed with breast cancer between January 1, 1984 and December 31, 1986. Age- and county-matched controls were selected from driver's license files. Among all women under age 70 at diagnosis, there was no association between oral contraceptive use and breast cancer; there was, however, a positive association in the subgroup ages 20-49 (adjusted odds ratio = 1.68, 95% CI: 1.16-2.42). Risk increased with increasing duration of use, but did not differ between women who first used oral contraceptives before the first pregnancy and those who first used them later, or between women who first used oral contraceptives before age 25 and those who first used them at a later age. Risk also appeared to increase with number of years of use before the first pregnancy or before age 25, although numbers were small. History of benign breast disease did not influence risk. The association of breast cancer risk with oral contraceptive use appeared stronger in women from Suffolk County than Nassau County.

Adult↗
PubMed1993

Methods for pooled analyses of epidemiologic studies.

This paper presents a systematic methodology for the pooling and analysis of previously conducted epidemiologic studies. It discusses the methodologic issues to consider and the procedures to follow when conducting a pooled analysis of individual subject level data. I review random and fixed effects models to estimate pooled risks and the methods to examine whether heterogeneity in study-specific effect estimates exists. Analytic strategies presented here can be used to assess sources of heterogeneity, particularly those originating from different study designs and methods. I describe methods for incorporating a qualitative assessment of the study design and data collection methods into the quantitative estimation of the overall effect. Finally, I make recommendations for future pooled analyses of epidemiologic studies.

Epidemiologic Methods↗
PubMed2001

Diminished use of osteopathic manipulative treatment and its impact on the uniqueness of the osteopathic profession.

PURPOSE: To determine whether osteopathic manipulative treatment (OMT), a key identifiable feature of osteopathic medicine, is becoming a "lost art" in the profession, and whether the long-term evolution of osteopathic medicine into mainstream medicine and particularly specialization has had a similar impact on the use of OMT by family practitioners and specialists. METHOD: In April 1998, a two-page questionnaire was mailed to 3,000 randomly selected osteopathic physicians in the United States to assess factors affecting their use of OMT. Descriptive statistics, linear regression analyses, and analysis of variance techniques were used to test for differences. RESULTS: The response rate was 33.2%. Over 50% of the responding osteopathic physicians used OMT on less than 5% of their patients, and analysis of variance revealed OMT use was significantly affected by practice type, graduation date, and family physicians versus specialists. For specialists, 58% of the variance regression was attributed to barriers to use, practice protocol, attitudes, and training, whereas for family physicians, 43% of the variance regression was attributed to barriers to use, practice protocol, and attitudes. More important, the eventual level of OMT use was related to whether postgraduate training had been undertaken in osteopathic, allopathic, or mixed staff facilities, particularly for osteopathic specialists. CONCLUSIONS: The evidence supports the assertion that OMT is becoming a lost art among osteopathic practitioners. Osteopathic as well as allopathic medical educators and policymakers should address the impact of the diminished use of OMT on both U.S. health care and the unique identifying practices associated with the osteopathic profession.

Adult↗
PubMed1990

Heterosexual transmission of HIV-1 among employees and their spouses at two large businesses in Zaire.

To better understand the reasons why up to 80% of all HIV-1 infections in Zaire, but less than 5% in North America and Europe, are acquired through heterosexual transmission, and to assess the impact of HIV-1 infection on a large urban African workforce, we enrolled 7068 male employees, 416 female employees and 4548 female spouses of employees at two large Kinshasa businesses (a textile factory and a commercial bank) in a prospective study of HIV-1 infection. The HIV-1 seroprevalence rate was higher in male employees (5.8%) and their spouses (5.7%) at the bank than among male employees (2.8%) and their spouses (3.3%) at the textile factory. At both businesses HIV-1 seroprevalence was higher among employees in managerial positions (5.0%) than among workers in lower-level positions (3.0%; P less than 0.0001). In a multivariate analysis of male employees, receipt of a transfusion, a history of genital ulcer disease, working at the bank, urethritis, or being divorced or separated were independently associated with HIV-1 infection. During 1987 and 1988, AIDS was the most common cause of death among recently employed workers, accounting for 20 and 24% of all deaths at the textile factory and the commercial bank, respectively. The HIV-1 seroprevalence rate was higher among female workers (7.7%) than among the spouses of male workers (3.9%; P = 0.001). In multivariate analysis of the wives of workers, having an HIV-1-seropositive spouse, receipt of a blood transfusion, or a history of genital ulcer disease were independently associated with HIV-1 infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗