Issues in the design of a clinical trial with a behavioral intervention--the Zambia exclusive breast-feeding study

PURPOSE: We present the rationale and design of the Zambian Exclusive Breast-feeding Study (ZEBS), a randomized trial evaluating the efficacy of short-duration exclusive breast-feeding (EBF) as a strategy to reduce postnatal human immunodeficiency virus (HIV) transmission while preserving the other health benefits of this important mode of infant feeding. METHODS: One thousand two hundred HIV-positive pregnant women were recruited in Lusaka, Zambia, and followed with their infants for 24 months. In addition to Nevirapine (NVP), all women received intensive and frequent clinic- and home-based counseling to support exclusive breast-feeding. When the infant was 1 week of age, half of the women were randomly assigned to a group encouraged to abruptly (<24 h) cease all breast-feeding at 4 months. The primary outcome of the experimental (randomized) comparison is HIV-free survival at 24 months. The design is also observational and will compare HIV transmission rates between those who do and do not adhere to the counseling intervention promoting exclusive breast-feeding. CONCLUSION: Our study aims to quantify the benefit-risk ratio of early cessation of exclusive breast-feeding to interrupt mother-to-child transmission of HIV with an intensive behavioral intervention and has both observational and experimental analytic approaches. Our study design assesses efficacy and also has a prominent applied component that if the intervention is effective, it will permit rapid and sustainable adoption within low-resource communities.     

Effect of occupational exposure to rayon manufacturing chemicals on skin barrier to evaporative water loss

To evaluate the effects of the occupational exposure to rayon manufacturing chemicals (RMC, containing predominantly carbon disulfide (CS(2)) and minor sulfuric acid) in a rayon factory on the basal transepidermal water loss (TEWL), barrier integrity (BI), and sequential increasing TEWL profiles. Six Thais and five Chinese workers in the spinning department of a rayon manufacturing plant and five healthy unexposed controls were recruited as the test subjects. An area of 4.5 x 5.5 cm on the mid-side of the volar forearm on the right hand was stripped by means of moderate pressure with commercially available adhesive tape by the same technician throughout the experiment. The skin was progressively stripped until glistening. TEWL was measured at every three and five tape strips on the right hand. The corresponding site on the left hand was measured parallel as the self-control. We found significant differences in basal TEWL and in BI between Chinese workers and Chinese controls, and between Thai workers and Chinese workers, respectively. Two-stage patterns of progressive TEWL profiles were found in such a chronic and repeated occupational exposure to RMC containing CS(2). The occupational exposure to RMC could result in the perturbation of the skin barrier function. Basal TEWL might be more sensitive to chronic skin irritant exposure. The TEWL profile achieved to the glistening stage might be necessary to avoid erroneous pattern estimation. Due to the lack of Thais control in this study, the racial difference in response to the RMC warrants further study.     

Mortality patterns among residents in Louisiana's industrial corridor, USA, 1970-99

Background: Because of the high concentration of oil refining and petrochemical facilities, the industrial area of the lower Mississippi River of South Louisiana has been termed the Industrial Corridor and has frequently been referred to as the "Cancer Corridor".

Aims: To quantitatively assess the "Cancer Corridor" controversy based on mortality data available in the public domain, and to identify potential contributing factors to the observed differences in mortality.

Methods: Age adjusted mortality rates were calculated for white and non-white males and females in the Industrial Corridor, Louisiana, and the United States for the time periods 1970–79, 1980–89, and 1990–99.

Results: All-cause mortality and all cancer combined for white males in the Industrial Corridor were significantly lower than the corresponding Louisiana population while Louisiana had significantly higher rates than the US population for all three time periods. Cancer of the lung was consistently higher in the Industrial Corridor region relative to national rates but lower than or similar to Louisiana. Non-respiratory disease and cerebrovascular disease mortality for white males in the Industrial Corridor were consistently lower than either Louisiana or the USA. However, mortality due to diabetes and heart disease, particularly during the 1990s, was significantly higher in the Industrial Corridor and Louisiana when compared to the USA. Similar mortality patterns were observed for white females. The mortality for non-white males and females in the Industrial Corridor was generally similar to the corresponding populations in Louisiana. There were no consistent patterns for all cancer mortality combined. Stomach cancer was increased among non-whites in both the Industrial Corridor and Louisiana when compared to the corresponding US data. Mortality from diabetes and heart disease among non-whites was significantly higher in the Industrial Corridor and Louisiana than in the USA.

Conclusions: Mortality rates in the Industrial Corridor area were generally similar to or lower than the State of Louisiana, which were increased compared to the United States. Contrary to prior public perceptions, mortality due to cancer in the Industrial Corridor does not exceed that for the State of Louisiana.

     

Organ-Specific Toxicokinetics and Dose–Response of Arsenic in Tilapia <Emphasis Type="Italic">Oreochromis mossambicus</Emphasis>

We appraised organ-specific toxicokinetics and dose responses of arsenic burdens in tilapia Oreochromis mossambicus. We kinetically linked an Area-under-the-curve (AUC)–based acute toxicity model and a pharmacodynamic model to derive dose–response relationships between equilibrium organ-specific arsenic concentrations and mortality effects. The AUC-based acute toxicity model was also used to derive organ-specific internal effect concentration (IEC)–time-response relationships, which can also be applied to predict a time–mortality profile. We conducted a 7-day exposure experiment to obtain toxicokinetic parameters, whereas the AUC-based acute toxicity model was verified with LC₅₀(t) data obtained from a 7-day acute toxicity bioassay. Our results demonstrated that 96-hour LC₅₀ and incipient LC₅₀ for tilapia exposed to arsenic are 28.68 (95% confidence interval to 24.92 to 32.44) and 25.55 mg L^–1, respectively. Dose–response relationships followed the Hill equation, which could be expressed as organ-specific bioconcentration factors and incipient LC₅₀. Organ-specific dose-response relationships showed that muscle, gill, and liver have a relatively steep sigmoid dose-response profile in that IEC₅₀ were 26.6, 62.5, and 78.5 g g^–1 dry wt (dw), respectively. Organ-specific arsenic internal lethal burdens were the highest in the gill and the lowest in the muscle in waterborne-exposed tilapia. The IEC and target-organ concentrations derived in this study can be used in site-specific risk assessment.     

A prospective cohort study of nut consumption and the risk of gallstone disease in men

Gallstone disease is a major source of morbidity in Western countries. Nuts are rich in several compounds that may be protective against gallstones. The objective of the study was to examine the relation between nut consumption and gallstone disease in the Health Professionals Follow-up Study. The consumption of nuts was assessed starting in 1986 as part of a 131-item semiquantitative food frequency questionnaire. The main outcome measure was newly diagnosed symptomatic gallstones. During 457,305 person-years of follow-up, 1,833 participants reported gallstone disease. After adjustment for age and other known or suspected risk factors, men consuming 5 or more units of nuts per week (frequent consumption) had a significantly lower risk of gallstone disease (relative risk = 0.70, 95% confidence interval: 0.60, 0.86; p(trend) < 0.001) than did men who never ate or who ate less than 1 unit per month (rare consumption) (1 unit = 1 ounce (0.028 kg) of nuts). Further adjustment for fat consumption (saturated fat, trans-fat, polyunsaturated fat, and monounsaturated fat) did not materially alter the relation. In analyses examining consumption of peanuts and other nuts separately, both were significantly associated with a lower risk of gallstone disease in the age-adjusted and multivariate models. Our findings suggest that frequent nut consumption is associated with a reduced risk of gallstone disease in men.