Matthew C. Somerville

Effect of dutasteride on the risk of prostate cancer

BACKGROUND We conducted a study to determine whether dutasteride reduces the risk of incident prostate cancer, as detected on biopsy, among men who are at increased risk for the disease. METHODS In this 4-year, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, we compared dutasteride, at a dose of 0.5 mg daily, with placebo. Men were eligible for inclusion in the study if they were 50 to 75 years of age, had a prostate-specific antigen (PSA) level of 2.5 to 10.0 ng per milliliter, and had had one negative prostate biopsy (6 to 12 cores) within 6 months before enrollment. Subjects underwent a 10-core transrectal ultrasound-guided biopsy at 2 and 4 years. RESULTS Among 6729 men who underwent a biopsy or prostate surgery, cancer was detected in 659 of the 3305 men in the dutasteride group, as compared with 858 of the 3424 men in the placebo group, representing a relative risk reduction with dutasteride of 22.8% (95% confidence interval, 15.2 to 29.8) over the 4-year study period (P<0.001). Overall, in years 1 through 4, among the 6706 men who underwent a needle biopsy, there were 220 tumors with a Gleason score of 7 to 10 among 3299 men in the dutasteride group and 233 among 3407 men in the placebo group (P=0.81). During years 3 and 4, there were 12 tumors with a Gleason score of 8 to 10 in the dutasteride group, as compared with only 1 in the placebo group (P=0.003). Dutasteride therapy, as compared with placebo, resulted in a reduction in the rate of acute urinary retention (1.6% vs. 6.7%, a 77.3% relative reduction). The incidence of adverse events was similar to that in studies of dutasteride therapy for benign prostatic hyperplasia, except that in our study, as compared with previous studies, the relative incidence of the composite category of cardiac failure was higher in the dutasteride group than in the placebo group (0.7% [30 men] vs. 0.4% [16 men], P=0.03). CONCLUSIONS Over the course of the 4-year study period, dutasteride reduced the risk of incident prostate cancer detected on biopsy and improved the outcomes related to benign prostatic hyperplasia. (ClinicalTrials.gov number, NCT00056407.)

An environmental scoping study in the Lower Rio Grande Valley of Texas — III. Residential microenvironmental monitoring for air, house dust, and soil

A principal aspect of the 1993 Lower Rio Grande Valley Environmental Scoping Study was the analysis and interpretation of residential air, household dust, and soil pollutant concentration data for exposure assessments. Measurements included respirable particulate matter (PM2.5), volatile organic compounds (VOCs), pesticides, and polycyclic aromatic hydrocarbons (PAHs) in indoor and outdoor air. Household dust, road dust, and yard soil were analyzed for elements, pesticides, and PAHs. Nine residences were monitored for three weeks in the spring of 1993. Additional monitoring was conducted at six of the nine residences for ten days the following summer. Generally good agreement was found between outdoor residential air and same-species measurements collected concurrently at a non-residential central site in Brownsville, TX (Ellenson et al. 1997) for fine particulate matter, elements, and VOCs indicating the dominance of regional influences. PM2.5 mass and element concentrations in residential indoor and outdoor air were generally higher in the summer than in the spring. Indoor air concentrations of many species were higher than outdoor air concentrations and were attributed to household activities, ventilation of residences, and track-in of dislodged soils. Evidence of agricultural activities was noted in the occurrence of crop-related pesticides (e.g., malathion and chlorpyrifos) in indoor and outdoor air. Concentrations of common household pesticides (e.g., chlordane, chlorpyrifos, diazinon, heptachlor, and propoxur) were generally higher indoors than outdoors and were also present in house dust. Seasonal comparisons of pesticides and PAHs were also presented using matched residences in spring and summer; VOCs also may have indicated seasonal effects. VOCs (notably propane and butane isomers) and PAHs were higher indoors, presumably due to cooking-related activities.

The Effect of Dutasteride on the Usefulness of Prostate Specific Antigen for the Diagnosis of High Grade and Clinically Relevant Prostate Cancer in Men With a Previous Negative Biopsy: Results From the REDUCE Study

PURPOSE We assessed whether dutasteride enhances the usefulness of total prostate specific antigen for diagnosing clinically significant prostate cancer. MATERIALS AND METHODS The 4-year REDUCE study evaluated the efficacy and safety of 0.5 mg dutasteride daily for prostate cancer risk reduction in men with a prostate specific antigen of 2.5 to 10.0 ng/ml and a negative prostate biopsy. Specificity, sensitivity, and positive and negative predictive values of prostate specific antigen for the diagnosis of prostate cancer were assessed. RESULTS Final prostate specific antigen before biopsy and change from month 6 to final prostate specific antigen performed better for the diagnosis of Gleason score 7-10 tumors in men who received dutasteride vs placebo as assessed by the area under the ROC curves (0.700 vs 0.650, p = 0.0491; and 0.699 vs 0.593, p = 0.0001, respectively). Increases in prostate specific antigen were associated with a higher likelihood of biopsy detectable, Gleason score 7-10 and clinically significant (modified Epstein criteria) prostate cancer. Percentage decreases in prostate specific antigen from baseline to month 6 in the dutasteride arm did not predict prostate cancer overall or Gleason score 7-10 cancer. CONCLUSIONS In men with a previously negative prostate biopsy, prostate specific antigen performed better during the 4-year study as a marker of prostate cancer in men who received dutasteride vs placebo. The degree of prostate specific antigen increase after 6 months was a better indicator of clinically significant cancer in the dutasteride arm than in the placebo arm. Conversely, the initial decrease in prostate specific antigen in men taking dutasteride did not predict the likelihood of prostate cancer.

Usefulness of prostate-specific antigen (PSA) rise as a marker of prostate cancer in men treated with dutasteride: Lessons from the REDUCE study

Study Type – Prognostic (RCT)

Measurements of VOCs from the TAMS network

Target volatile organic compounds (VOCs) were measured at a network of urban air monitoring locations in Boston, Chicago, Houston, and the Seattle/Tacoma area. Following a pilot-scale field evaluation of available techniques for determining concentrations of VOCs in ambient air, a technique based on evacuated stainless steel canisters was selected to collect whole air samples. Twenty-four-hour integrated samples were collected every twelfth day at ten sites over a 2-year study period. Battelle Columbus Laboratory (BCL) analyzed the samples for 25 target VOCs using cryogenic focusing, gas chromatographic separation and mass selective detection with flame ionization detection as backup. Duplicate canister samplers were operated each sampling period at one of the ten sites in the Toxic Air Monitoring System (TAMS) network to estimate overall method precision. In addition, every 10th analysis was repeated by BCL to obtain a measure of analytical precision. Finally, each sampling period a clean evacuated canis...

The characterization and comparison of ozone exposure indices used in assessing the response of loblolly pine to ozone

Abstract Using the 1988 and 1989 experimental results obtained for two loblolly pine half-sibling families (GAKR 15–23 and GAKR 15–91) at the Auburn University intensive field research site, we: (1) explored the performance of a set of exposure indices; (2) characterized the ambient air and charcoal-filtered air treatments at Auburn and compared the values of the O3 exposure indices with those values calculated for ambient O3 monitors for a select set of sites; (3) identified and characterized O3 treatments in the Auburn open-top exposure chambers where an adverse effect was noted; and (4) identified where such experimental exposure regimes occurred under ambient conditions. We found that the SUMO exposure index did not perform adequately. We were unable to distinguish among the performances of the SUM06, W126, and SUM08 exposure indices. The results of the analyses of six estimated logistic parameters for a model of diameter2 × height (d2h) vs time indicated O3 effects for both families. At pH 4.3 (near ambient conditions), a response to O3 was detected in the NF × 2.5 treatments for both families for t2, the approximate time of maximum growth during the second year. Using ln (final d2h), family 23 did not show O3 effects. A comparison of the exposures experienced in the NF × 2.5 treatments with those occurring under ambient conditions at other locations showed that in 1983 and 1986, the San Bernardino County (CA) site experienced O3 exposures similar to those values experienced at the NF × 2.5 treatments in 1989.

STATISTICAL APPROACHES IN WIND SECTOR ANALYSES FOR ASSESSING LOCAL SOURCE IMPACTS

Abstract Nonparametric statistical methods were used as part of a wind sector analysis assessment for the purpose of investigating local source impacts. Linear-angular rank correlations were employed to test for the presence of association between pollutant tracer concentrations and wind direction for a local area dominated by a single emission source (a biomedical waste combustor). Testing for the presence of these associations in ambient data from a local area likely to include multiple pollutant sources (including a resource recovery facility) was accomplished using the nonparametric Kruskal-Wallis test. Modified pollutant wind rose plots were used to qualitatively investigate the nature of the associations detected using these statistical tests, focusing on the sources of interest known to emit the pollutant tracers-of-opportunity. The statistical methods presented provide a quantitative basis for the assessment of source impacts based on observed associations between wind direction and pollutant concentrations.

Biopsy Misidentification Identified by DNA Profiling in a Large Multicenter Trial

PURPOSE The Reduction by Dutasteride of Prostate Cancer Events (REDUCE) prostate cancer risk reduction study randomly assigned 8,231 men to dutasteride or placebo for 4 years. Protocol-mandated biopsies were obtained after 2 and 4 years. After the discovery of three cases of biopsy sample misidentification in the first 2 years, all protocol-mandated biopsy samples were DNA tested to verify biopsy identity. METHODS Biopsy and blood DNA profiling was performed retrospectively for the year 2 scheduled biopsies and prospectively for the year 4 scheduled biopsies. Toward the end of year 2, multiple changes were made to improve sample handling and chain of custody. RESULTS Of the 6,458 year 2 and 4,777 year 4 biopsies, 26 biopsies reflecting 13 sample handling errors at year 2 (0.4%) and one biopsy reflecting one sample handling error at year 4 (0.02%) were confirmed to be mismatched to the patient for whom they were originally submitted. Of 6,733 reference blood samples profiled, 31 (0.5%) were found to be mismatched to the patients verified identity profile. Sample identification errors occurred at local research sites and central laboratories. CONCLUSION Biopsy misidentification is a potential problem in clinical laboratories and clinical trials. Until now, biopsy misidentification has not been studied in the setting of a large, multinational clinical trial. In the REDUCE study, process improvement initiatives halfway through the trial dramatically reduced biopsy mismatches. The potential for biopsy mismatches in clinical trials and clinical practice is an under-recognized problem that requires rigorous attention to details of chain of custody and consideration of more widespread DNA identity testing.

Techniques to assess cross-border air pollution and application to a US-Mexico border region

A year-long assessment of cross-border air pollution was conducted in the eastmost section of the US-Mexico border region, known as the Lower Rio Grande Valley, in South Texas. Measurements were conducted on the US side and included fine particle mass (PM2.5) and elemental composition, volatile organic compounds (VOCs) and meteorology. Wind sector analyses of chemical tracers and diagnostic ratios, in addition to principal component analysis (PCA), were initially applied to assess cross-border and overall air shed influences. Linear-angular correlation statistics [Biometrika, 63, (1976), 403-405] and nonparametric multiple comparisons between wind sectors were computed with the particle element data using principal component scores from PCA to determine the direction of source classes. Findings suggest crustal particles and salts carried or stirred by sea breeze winds from a southerly and southeasterly direction from the Gulf of Mexico heavily influenced the elemental composition of the particulate samples. Pair-wise comparisons of wind directions for the principal component scores suggest possible oil combustion influences from utilities or boilers coming from the south and possible coal combustion influences from the north and northwest. The techniques discussed can provide a methodology to assess future ambient levels and cross-border influences in the Valley as conditions change.

An environmental scoping study in the lower Rio Grande Valley of Texas : I. Comparative assessment of air sampling methods

Abstract The atmospheric monitoring component of the 1993 Lower Rio Grande Valley Environmental Scoping Study measured a wide range of pollutant species from different sampling and analysis methods. Extensive QA/QC activities were also conducted on the sampling and analysis techniques. This enabled a unique comparison of these methods to provide insights into air sampling for larger, long-term exposure monitoring studies. Pollutants monitored were particulate mass and elements, acidic gases, volatile organic compounds, pesticides, and polycyclic aromatic hydrocarbons. This included collocated monitoring devices which monitored same-species pollutants. Sample collection efficiencies of certain atmospheric pollutants are discussed. Finally, data from two sites located in the Lower Rio Grande Valley are also presented and compared.