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Biomedical subjects

Martin Kulldorff

Publications and source records attributed to Martin Kulldorff.

45 records · Page 3Linked to original sources

Dead bird clusters as an early warning system for West Nile virus activity.

An early warning system for West Nile virus (WNV) outbreaks could provide a basis for targeted public education and surveillance activities as well as more timely larval and adult mosquito control. We adapted the spatial scan statistic for prospective detection of infectious disease outbreaks, applied the results to data on dead birds reported from New York City in 2000, and reviewed its utility in providing an early warning of WNV activity in 2001. Prospective geographic cluster analysis of dead bird reports may provide early warning of increasing viral activity in birds and mosquitoes, allowing jurisdictions to triage limited mosquito-collection and laboratory resources and more effectively prevent human disease caused by the virus. This adaptation of the scan statistic could also be useful in other infectious disease surveillance systems, including those for bioterrorism.

Animals↗

[Spatial analysis on the distribution of hemorrhagic fever with renal syndrome by geographic information system in Haidian district, Beijing].

OBJECTIVE: To analyze the spatial distribution of hemorrhagic fever with renal syndrome (HFRS) in Haidian district, Beijing and to explore the geographical characteristics of HFRS in highly endemic areas. METHODS: Administration boundary layer was established under the background of 1:100,000 map in the ArcInfo 8.1 software. The HFRS cases from 1997 to 2002 were positioned on the map. Highly endemic areas were identified by spatial cluster analysis using SaTScan 3.0 software. Distribution of HFRS cases was shown in different colors and contours by spatial analysis of geographic information system (GIS). RESULTS: Spatial Cluster Analysis of confirmed cases of HFRS identified in 1997 - 2002 in Haidian district showed that HFRS patients were not randomly distributed. The highly endemic areas were founded in Sujiatuo township, Yongfeng township, Shangzhuang township, Wenquan town and Bei'anhe township (relative risk = 4.43, P = 0.001). A thematic map of HFRS in haidian district was set up. CONCLUSION: HFRS infections were not randomly distributed, since the distribution was related to geographic-environmental factors.

China↗

Meat intake and cooking techniques: associations with pancreatic cancer.

Heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs), formed in temperature and time-dependent manners during cooking of meat, may increase the risk of certain cancers. As these compounds could be carcinogenic for the pancreas, we assessed meat intake, preparation methods, and doneness preferences as risk factors for exocrine pancreatic cancer. In a case-control study (cases=193, controls=674), subjects provided information on their usual meat intake and how it was cooked, e.g. fried, grilled or barbecued (BBQ), etc. Meat doneness preferences were measured using photographs that showed internal doneness and external brownness with a numerical scale. Data were analyzed with unconditional logistic regression. Odds ratios (ORs) increased with increased intake of grilled/BBQ red meat in an analysis adjusted for age, sex, smoking, education, race, and diabetes. Based on amount of BBQ meat consumed, the OR and 95% confidence interval (CI) for the fifth quintile relative to the reference group (quintiles 1 and 2) was 2.19 (1.4, 3.4). Findings were not substantively changed by further adjustment for calories, total fat, fruit and vegetables, or alcohol consumption (from a food frequency questionnaire (FFQ)). Other meat variables did not show statistically significant associations with risk nor did they substantively alter the findings for BBQ. These included total meat, processed meat, total red meat, total white meat, total broiled meat, total fried meat, or total meat cooked by means other than grilling. We conclude that grilled red meat intake is a risk factor for pancreatic cancer and that method of meat preparation in addition to total intake is important in assessing the effects of meat consumption in epidemiologic studies.

Adult↗

A geographic analysis of prostate cancer mortality in the United States, 1970-89.

The recently published atlas of cancer mortality in the United States revealed that prostate cancer mortality rates were elevated among white men in the Northwest, the Rocky Mountain states, the north-central area, New England and the South Atlantic area, and among black men in the South Atlantic area. Here we determine whether the elevated regional rates were statistically different from rates in the rest of the country and whether the pattern can be explained by selected regional characteristics. A spatial scan statistic was applied to county-based mortality data from 1970 through 1989 to identify geographic clusters of the elevated rates for prostate cancer. Five clusters of elevated mortality were detected in white men (p < 0.005) and 3 in black men (p = 0.0001-0.056). For white men, the primary cluster was in the northwestern quadrant, followed by clusters in New England, the eastern part of the north-central area, the mid-Atlantic states and the South Atlantic area, whereas for black men the primary cluster was in the South Atlantic area, followed by clusters in Alabama and the eastern part of the north-central area. Further analyses of these clusters revealed several significant subclusters (p < 0.05). None of the selected demographic and socioeconomic factors, separately or collectively, accounted for the primary clusters in the U.S. white and black populations. The patterns observed could not be attributed to selected demographic or socioeconomic characteristics but should provide leads for further study into the risk factors and the medical or reporting practices that may contribute to geographic variation in mortality from prostate cancer.

Age Factors↗

Geographic differences in invasive and in situ breast cancer incidence according to precise geographic coordinates, Connecticut, 1991-95.

To evaluate geographical variation of invasive and in situ breast cancer incidence rates using precise geographical coordinates for place of residence at diagnosis, latitude-longitude coordinates pertaining to 10,601 invasive and 1,814 in situ breast cancers for Connecticut women, 1991-95, were linked to US Census information on the 2,905 State census block groups. A spatial scan statistic was used to detect geographic excess or deficits in incidence and test the statistical significance of results, without prior assumptions about the size or location of such areas. The age adjusted invasive cancer incidence rate was 165.3/100,000 women/year. The spatial scan statistic identified 3 places with significantly low incidence rates and 4 places where rates were significantly high. The most probable location of low incidence was rural northeastern Connecticut where risk of disease, relative to elsewhere around the state, was 0.70 (p = 0.0001); the most probable place of elevated incidence was north central Connecticut where a relative risk of 1.34 (p = 0.002) was observed. Incidence of in situ disease was estimated to be significantly high for north central Connecticut (RR = 1.84; p = 0.0001). Geographic differences of invasive and in situ breast cancer incidence were observed. Examining cancer events at the lowest available level of data aggregation is beneficial in highlighting localized rate variations. Such information may enable public health officials to target additional resources for promoting breast cancer screening to specific locations.

Adult↗

Effects of smoking cessation or reduction on hormone profiles and bone turnover in postmenopausal women.

The purpose of this study was to prospectively evaluate the impact of smoking cessation on hormonal concentrations, sex hormone-binding globulin (SHBG) and markers of bone turnover in postmenopausal women. Sixty-six women who were either users or non-users of estrogen replacement therapy (ERT) were randomly assigned, using a weighted randomization scheme, to smoking cessation (SC) or to smoking cessation after 6 weeks of monitoring (wait-list control group, WLC). We measured hormones [estrone, estradiol, testosterone, parathyroid hormone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS) and androstenedione] and SHBG, markers of bone turnover [procollagen peptide (PINP), bone alkaline phosphatase (BAP), and osteocalcin (OC), N- and C-terminal collagen cross-links (NTx and CTx)], and cotinine, at baseline and again at 6 weeks in women who reported smoking cessation and in women randomized to the WLC group. Analyses included 20 subjects who quit or significantly reduced their smoking and 18 subjects in the WLC group. After controlling for differences in age and ERT use between groups, we found a significant change in SHBG in the SC vs. the WLC group (-8% vs. +5%, respectively; p = 0.01), and in DHEA (-18% vs. -5%, respectively; p = 0.04), but not in other hormonal concentrations. We also noted a significant change in NTx in the SC vs. WLC group (-5% vs. +56%, respectively, p = 0.01), but not in other markers of bone turnover. Percentage changes in SHBG and NTx were correlated with changes in plasma cotinine (r = 0.48; p = 0.004 and r = 0.36; p = 0.04, respectively). Six weeks of smoking abstinence produces reductions in SHBG and NTx. This may partly explain how smoking contributes to osteoporosis in postmenopausal women.

Dehydroepiandrosterone↗

Genetic polymorphisms in heterocyclic amine metabolism and risk of colorectal adenomas.

High red meat intake has been linked with an increased risk of colorectal cancer and adenomas. During high temperature cooking of red meats, heterocyclic amines (HCAs) are generated; however, to be carcinogenic, they must be metabolized by enzymes including cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 1 (NAT1) and/or N-acetyltransferase 2 (NAT2). We have conducted a clinic-based case-control study of colorectal adenomas that focused on assessment of exposure to HCAs (estimated by use of a HCA database and meat cooking module) and modification of these exposures by genetic factors. We have previously reported that intake of MeIQx was associated with an increased risk of colorectal adenomas [overall association at 80th percentile, > 27.00 ng/day: odds ratio (OR) = 2.68, 95% confidence interval (CI) 1.58-4.55]. Here, we report our evaluation of whether variation in CYP1A2, NAT1 and/or NAT2 modify the association between HCAs and colorectal adenoma formation in 146 cases and 228 frequency-matched controls. The NAT1*10 allele was associated with a nonsignificant increased risk of colorectal adenomas (OR = 1.43; 95% CI 0.86-2.36). Further, when we analysed 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) intake as a categorical variable, we observed a six-fold increase in adenoma risk among rapid NAT1 acetylators who consumed more than 27 ng a day (OR = 6.50; 95% CI 2.16-19.7), whereas among slow NAT1 acetylators, the increase in risk was two-fold (OR = 2.32; 95% CI 1.12-4.81). While suggestive, the results were not significantly different from each other on either an additive or multiplicative scale. In contrast, NAT2 genotype and CYP1A2 and NAT2 hepatic activity measured by caffeine urinary metabolites were not associated with adenoma risk, although an increase in risk with rapid CYP1A2 activity could not be ruled out (OR = 1.46; 95% CI 0.76-2.81). Moreover, there was no evidence that the effect of MeIQx was enhanced among subjects in any subgroup defined by variation in these measures. These results are compatible with the hypothesis that high HCA exposure is associated with an increased risk of colorectal adenomas, particularly in genetically susceptible subgroups. Further study of larger populations is needed to confirm and extend these observations.

Adenoma↗

Retrospective evaluation and adjustment of dual energy X-ray absorptiometry measurements for bone mineral density research studies.

Dual-energy X-ray absorptiometry (DXA) is widely used for bone mineral density (BMD) measurements. Prospective daily quality control procedures such as cumulative sum (CUSUM) plots and Shewhart charts are very important and commonly used for routine monitoring of DXA measurements. These procedures are less suitable for post hoc adjustment of DXA measurements for clinical research studies, if and when that is needed. Extending previous methods, we propose and illustrate a simple statistical method for retrospective quality evaluation that may be used to adjust BMD measurements before they are analyzed in clinical research studies. Using multivariate regression, this method allows for simultaneous adjustment of different types of temporal variation such as sudden jumps, simple linear trends, changes in the slope of these trends, quadratic terms, and seasonal fluctuations. Adjusting the measurements to account for different types of temporal trends decreases the variance of bone mass density measurements and is an inexpensive way to increase the power of a study without increasing the sample size. The method is illustrated with measurements of two different phantoms used on the same DXA, with 2 and 3 yr of data, respectively. Results were consistent for both phantoms, with a gradual trend and a sudden jump, as well as a seasonal fluctuation term.

Absorptiometry, Photon↗