Demographic variation in cancer in relation to industrial and environmental influence. (1/797)

Mortality data (183,064 deaths in a 30-year period, 1940-1969) by sex and three ethnic groups (white excluding Spanish-surnamed, nonwhite, and Spanish-surnamed) in 15 regions within the city (Houston), grouped around the air pollution sample collection stations have been analyzed. Valid contrast studies were possible in only one region within the city for all three groups and in six regions for white excluding Spanish-surnamed and nonwhite. There is evidence that the environmental factors of exposure over time to air and industrial pollutants in Houston has had a demonstrable effect in increasing regional mortality from cancer of the respiratory tract as well as from all other diseases and conditions of the respiratory tract and heart disease. This study points out the need for mutually sustained collaboration of effort of the scientific and industrial communities to redirect their attention and research efforts to the exploration of the carcinogenic potential of the microchemical environment.  (+info)

Risk of malformations and other outcomes in children exposed to fluconazole in utero. (2/797)

AIM: Fluconazole is an active drug systematically used in the oral treatment of vaginal candidiasis and other fungal diseases. We examined the risk of malformations and other birth outcomes following pregnancy related exposures. METHOD: From 1 January 1991 to 31 December 1996 we identified 165 women who had taken fluconazole just before or during pregnancy in the Pregnancy Outcome Section of the North Jutland Pharmacoepidemiological Prescription Database, Denmark, which is linked to the Danish Medical Birth Registry. We compared their birth outcomes (malformation, low birth weight and preterm delivery) with the outcomes among 13 327 women who did not receive any prescriptions during their pregnancies. RESULTS: The prevalence of malformation was 3.3% (four cases) among the 121 women, who had used fluconazole in the first trimester, and 5.2% (697 cases) in offspring to controls (odds ratio: 0.65, 95% confidence limits: 0.24-1.77). Furthermore, we did not find any significantly elevated risk of preterm delivery (odds ratio: 1.17, 95% confidence limits: 0.63-2.17) and low birth weight (odds ratio: 1.19, 95% confidence limits: 0.37-3.79). CONCLUSION: The study showed no increased risk of congenital malformations, low birth weight or preterm birth in offspring to women who had used single dose fluconazole before conception or during pregnancy.  (+info)

World's population to reach six billion. (3/797)

The United Nations (UN) estimates that the world's population will reach six billion on October 12, 1999. The world's population reached one billion in 1804; subsequently, one billion increases came at intervals of 123, 33, 14, 13, and 12 years. Population growth rates increased over time because of high fertility rates and declines in mortality rates, especially since the early to mid-1900s. The UN projects that it will take 14 years for the world's population to reach 7 billion and another 15 years to reach 8 billion.  (+info)

Trends in world population: how will the millenium compare with the past? (4/797)

This paper reviews historical and projected trends in world population numbers, and the underlying determinants of those trends. Whereas the world's population has shown little change over most of its one million-year history, the past 200 years have witnessed dramatic changes in fertility, mortality and population growth rates. Recent decades, in particular, have seen unprecedented demographic events, with more people added to the world's population in the past 50 years than in the preceding million. The demographic impact of HIV/AIDS, selective as it is to young adults and infants, is also unprecedented, with life expectancy among some populations reduced by almost 20 years. As we approach the end of the 20th century, further demographic changes are underway with, for the first time in recent human history, a slowing down of world population growth. Nonetheless, world population is projected to grow from 6 billion currently to about 9.4 billion by 2050 (medium fertility assumption), with ageing emerging as the most pressing demographic issue facing humanity in the millenium.  (+info)

Population pharmacokinetics of lamivudine in adult human immunodeficiency virus-infected patients enrolled in two phase III clinical trials. (5/797)

Lamivudine population pharmacokinetics were investigated by using nonlinear mixed-effect modelling (NONMEM) analysis of data from 394 human immunodeficiency virus (HIV)-infected patients treated with lamivudine (150 to 300 mg every 12 h) in two large, phase III clinical efficacy-safety trials, NUCA3001 and NUCA3002. Analyses of 1,477 serum lamivudine concentration determinations showed that population estimates for lamivudine oral clearance (CL/F; 25.1 liters/h) and volume of distribution (V/F; 128 liters) were similar to values previously reported for HIV-infected patients in phase I pharmacokinetic studies. Lamivudine CL/F was significantly influenced by the covariates creatinine clearance and weight and not affected by age, Centers for Disease Control and Prevention (CDC) classification, CD4(+) cell count, HIV type 1 (HIV-1) RNA PCR, or gender and race when CL/F was corrected for differences in patient weight. The population estimate for lamivudine V/F was not significantly influenced by the covariates gender, race, age, weight, renal function, HIV-1 RNA PCR, or CDC classification and CD4(+) cell count when creatinine clearance was included with CL/F in the model. Lamivudine disposition was significantly influenced by renal function. However, as only three patients had an estimated creatinine clearance of <60 ml/min, dosage adjustments for patients with impaired renal function should not be determined based on the population parameters derived in this analysis.  (+info)

Population pharmacokinetics of enterally administered cisapride in young infants with gastro-oesophageal reflux disease. (6/797)

AIMS: To investigate the pharmacokinetics of enterally administered cisapride suspension in young infants being treated for gastro-oesophageal reflux disease. METHODS: Plasma cisapride concentrations in 49 subjects (weight: 825-5010 g; n=108 samples, median two per patient; concentration: 14.8-170 ng ml-1 ) were fitted to a one-compartment model with first-order absorption and elimination in the NONMEM program using a logarithmic transformation of the observed and predicted concentrations. Fitting was achieved using the first order conditional estimation (FOCE) method with interaction between the interpatient and intrapatient variabilities. The interpatient variance of clearance (CL/F ) and volume of distribution (V /F ) and their covariance were estimated using an exponential error model. Intrapatient (residual) variance was estimated using an additive model. RESULTS: The clearance of cisapride was shown to be linearly related to current body weight, slope: 0.538. The typical population values of CL/F, V /F and Ka (absorption rate constant) were 0.538 l h-1 kg-1, 21.9 l, and 2.58 h-1, respectively. The population coefficients of variation (CV%) for CL/F and V/F were 34.4% and 84.3%, respectively. The squared coefficient of correlation between random effects for CL/F and V /F was 0.45. The intrapatient variance was 0.15. V /F and Ka were not influenced significantly by any patient characteristic. CONCLUSIONS: Cisapride pharmacokinetics in infants with reflux disease were satisfactorily described by a one-compartment model. Current weight should be taken into account when calculating maintenance cisapride doses in these infants.  (+info)

Population pharmacokinetics of tolcapone in parkinsonian patients in dose finding studies. (7/797)

AIMS: To use pharmacostatistical models to characterize tolcapone's pharmacokinetics in parkinsonian patients, and to identify any demographic subpopulations which may be at risk of either under- or over-exposure to this catechol-O-methyltransferase (COMT) inhibitor. METHODS: Four hundred and twelve patients participated in three multicentre, parallel, double-blind, placebo-controlled, dose-finding studies and received either placebo or tolcapone (50, 200 or 400 mg three times daily) in addition to levodopa/decarboxylase inhibitor therapy. Sparse blood samples were obtained from 275 patients for tolcapone assay and the concentrations (1414 in total) were analysed using the NONMEM program. RESULTS: The pharmacokinetic model which best described the data was a two-compartment open model with first-order absorption and possibly a lag-time. Tolcapone pharmacokinetics were shown to be stable, with no systematic trend between 2 and 6 weeks of treatment. The absorption of the drug was shown to be rapid and concomitant food intake had only a minor effect on the relative bioavailability (10-20% reduction compared with fasting). The overall clearance of tolcapone could be estimated with good precision (approximately 4. 5-5 l h-1 ), and none of the investigated covariates (e.g. sex, age, body weight) had any clinically significant influence on this parameter. The volume of distribution showed relatively high variability and was calculated to be approximately 30 l, leading to an estimated half-life in patients of approximately 5-8 h. CONCLUSIONS: Using sparse concentrations and mixed effect-effects modelling analysis it is possible to describe the pharmacokinetics of tolcapone in parkinsonian populations. The parameter estimates obtained agreed with those obtained from conventional pharmacokinetic studies and no subpopulation was shown to be at risk of either under- or over-exposure to tolcapone.  (+info)

Patterns of neuroleptic drug prescription: a national cross-sectional survey of a random sample of French psychiatrists. (8/797)

AIMS: To describe the psychiatric indications of neuroleptics (especially the relative share of schizophrenic and other psychotic disorders) and the usage patterns of these drugs (dose, duration, coprescriptions). METHODS: A one-day national cross-sectional survey in a random sample of 723 French psychiatrists was carried out in 1996. Each psychiatrist was asked to complete a standardized questionnaire for the first three patients seen the day of the survey to whom at least one neuroleptic was prescribed (initiated or renewed). RESULTS: One thousand seven hundred and fifty-four questionnaires were returned. Three quarters of the patients (74%) were psychotic (664 with schizophrenia, and 636 other psychosis), 19. 3% were depressive and 6.7% had other psychiatric disorders. Phenothiazines were the most often prescribed (40.8%), followed by butyrophenones (22.5%), benzamides (15.8%), other neuroleptics (14. 8%) and thioxanthenes (6.1%). Among schizophrenic subjects, an average number of 1.54 (95% CI: 1.50-1.60) neuroleptics were prescribed per patient, compared with 1.4 (95% CI: 1.32-1.41) and 1. 2 (95% CI: 1.14-1.23) in other psychotic and depressive subjects, respectively. Regardless of the indication, non-neuroleptic psychotropic drugs were coprescribed in 75.4%, mainly benzodiazepines (75.7%). Adjuvant drugs used in prevention or treatment of side-effects were coprescribed in 46.7%, mostly anticholinergic antiparkinsonians (86.1%). CONCLUSIONS: Neuroleptics are mainly prescribed for psychotic disorders and especially schizophrenia. However, current recommendations are not always followed.  (+info)