Biomedical subjects

Martin Kulldorff

Publications and source records attributed to Martin Kulldorff.

At least 37 records · Page 2Linked to original sources

PubMed2005

Dietary intake of heterocyclic amines and benzo(a)pyrene: associations with pancreatic cancer.

OBJECTIVE: Heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons, formed in temperature- and time-dependent manners during the cooking of meat, are mutagens and carcinogens. We sought to assess the association between dietary intake of HCA and benzo(a)pyrene [B(a)P] and exocrine pancreatic cancer in a population-based case-control study. METHODS: Subjects (193 cases and 674 controls) provided information on their usual meat intake and preparation method, e.g., stewed, fried, or grilled/barbecued, etc. Meat doneness preferences were measured using photographs that showed internal doneness and external brownness. We used a meat-derived HCA, B(a)P, and mutagen database with a questionnaire to estimate intake of PhIP, DiMeIQx, MeIQx, B(a)P, and mutagenic activity (revertants/g of daily meat intake). Data were analyzed with unconditional logistic regression. RESULTS: In analyses adjusted for age, sex, smoking, education, race, and diabetes, the odds ratio and 95% confidence interval for the highest compared with the lowest quintile were as follows: PhIP, 1.8 (1.0-3.1); DiMeIQx, 2.0 (1.2-3.5); MeIQx, 1.5 (0.9-2.7); B(a)P, 2.2 (1.2-4.0); and mutagenic activity, 2.4 (1.3-4.3). CONCLUSIONS: HCAs and B(a)P from well-done barbecued and pan-fried meats may be associated with increased risk for pancreatic cancer.

Aged↗

PubMed2005

Dietary benzo[a]pyrene intake and risk of colorectal adenoma.

We carried out a clinic-based case-control study specifically designed to address the hypothesis that dietary intake of polycyclic aromatic hydrocarbons (PAH) is associated with colorectal adenoma risk. We developed a food frequency questionnaire with detailed questions on meat-cooking methods and doneness levels and a benzo[a]pyrene (BaP) database (as a surrogate for total carcinogenic PAHs) based on the collection and analysis of a wide range of food samples. We estimated BaP intake derived from meat and from all foods to test its relationship with risk of colorectal adenomas. The median (10th and 90th percentiles) BaP intake in controls was 5 ng/d (0.2 and 66 ng/d) estimated from meat and 73 ng/d (35 and 140 ng/d) from all foods. In cases, median BaP intake was 17 ng/d (0.5 and 101 ng/d) from meat and 76 ng/d (44 and 163 ng/d) from all foods. Multivariate analysis was carried out on 146 cases and 228 controls. The odds ratios (95% confidence interval) for dietary BaP from meat with the first quintile as the reference group were 1.19 (0.51-2.80) for the second quintile, 1.71 (0.76-3.83) for the third quintile, 2.16 (0.96-4.86) for the fourth quintile, and 2.82 (1.24-6.43) for the fifth quintile (Ptrend=0.01). Increased risk of colorectal adenomas was more strongly associated with BaP intake estimated from all foods: 2.61 (1.08-6.29) for the second quintile, 4.21 (1.79-9.91) for the third quintile, 2.45 (0.98-6.12) for the fourth quintile, and 5.60 (2.20-14.20) for the fifth quintile (Ptrend=0.002). This study provides evidence that dietary BaP plays a role in colorectal adenoma etiology.

Adenoma↗

PubMed2005

Opportunities for health promotion education in child care.

OBJECTIVES: Comprehensive health promotion education is not feasible through pediatric office visits alone. Opportunities may exist for enhanced health promotion in child care settings. The objectives of this study were to understand the attitudes toward, barriers to, and strategies for incorporating health promotion activities in child care settings as well as topics that are deemed most useful from the perspectives of parents, child care directors, and health consultants. We also sought to understand the health consultants' (health professionals serving as consultants to child care centers) current and desired roles in leading health promotion activities in child care settings. METHODS: We conducted simultaneous surveys of all licensed child care center directors and their health consultants in Boston. A total of 240 parents in 16 randomly selected centers were also surveyed. RESULTS: A total of 97 (65%) directors in the 150 child care centers identified responded. A total of 71% (56 of 79) of consultants and 58% (138 of 240) of parents responded. Parents (89%), child care directors (88%), and health consultants (80%) believe that health promotion activities through child care centers would improve the health knowledge and behaviors of preschool children. A total of 45% of parents reported already receiving useful health information from child care staff and materials distributed in child care. Most topic areas that were suggested to parents were considered useful, with the greatest utility in the areas of behavior/discipline, child development, and emergency management. No significant barriers were identified by health professionals. Lack of funds (63%) and lack of someone to provide information (59%) were the top barriers identified by directors. An educational session on health topics by health care professionals was believed to be the best strategy to improve health promotion education for families. Among the health consultants, 83% of nurses or nurse practitioners said that they would be able to provide health education in child care compared with 53% of physicians. CONCLUSION: Parents, child care center directors, and health professionals believe that enhancing health promotion education in child care could improve child health. Collaboration between pediatricians and early care and education professionals has the potential to improve the breadth and effectiveness of health promotion education. Effective strategies are necessary to optimize access to health professionals by early educators, and effectively utilize the unique skills and preferences of physicians and nurses to promote health education in child care.

Child Care↗

PubMed2005

Simulated anthrax attacks and syndromic surveillance.

We measured sensitivity and timeliness of a syndromic surveillance system to detect bioterrorism events. A hypothetical anthrax release was modeled by using zip code population data, mall customer surveys, and membership information from HealthPartners Medical Group, which covers 9% of a metropolitan area population in Minnesota. For each infection level, 1,000 releases were simulated. Timing of increases in use of medical care was based on data from the Sverdlovsk, Russia, anthrax release. Cases from the simulated outbreak were added to actual respiratory visits recorded for those dates in HealthPartners Medical Group data. Analysis was done by using the space-time scan statistic. We evaluated the proportion of attacks detected at different attack rates and timeliness to detection. Timeliness and completeness of detection of events varied by rate of infection. First detection of events ranged from days 3 to 6. Similar modeling may be possible with other surveillance systems and should be a part of their evaluation.

Anthrax↗

PubMed2004

Meat intake, cooking-related mutagens and risk of colorectal adenoma in a sigmoidoscopy-based case-control study.

Reported habits of red meat consumption, particularly red meat that has been cooked to the degree termed 'well-done', is a positive risk factor for colorectal cancer. Under high, pyrolytic temperatures, heterocyclic amines (HCA) and benzo[a]pyrene (BP) molecules can form inside and on the surface of red meat, respectively. These compounds are precursors that are metabolically converted to compounds known to act as mutagens and carcinogens in animal models, yet their role in human colorectal carcinogenesis remains to be clarified. We investigated whether intake of these compounds is associated with risk of colorectal adenoma in the context of a polyp-screening study conducted in Southern California. Using a database of individual HCAs and BP in meats of various types and subjected to specified methods and degrees of cooking, we estimated nanogram consumption of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and benzo[a]pyrene (BP). We observed a 6% increased risk of large (>1 cm) adenoma per 10 ng/day consumption of BP [OR = 1.06 (95% CI, 1.00-1.12), P (trend) = 0.04]. A major source of BP is red meat exposed to a naked flame, as occurs during the barbecuing process. Consistent with this finding an incremental increase of 10 g of barbecued red meat per day was associated with a 29% increased risk of large adenoma [OR = 1.29 (95% CI, 1.02-1.63), P (trend) = 0.04]. Individuals in the top quintile of barbecued red meat intake were at increased risk of large adenoma [OR = 1.90 (95% CI, 1.04-3.45)], compared with never consuming barbecued red meat. The consumption of oven-broiled red meat was inversely related to adenoma risk compared with non-consumers [OR = 0.49 (95% CI, 0.28-0.85)]. We did not identify any association with consumption of individual HCAs and colorectal adenoma risk. These results support the hypothesis that BP contributes to colorectal carcinogenesis.

Adenoma↗

PubMed2004

Benchmark data and power calculations for evaluating disease outbreak detection methods.

INTRODUCTION: Early detection of disease outbreaks enables public health officials to implement immediate disease control and prevention measures. Computer-based syndromic surveillance systems are being implemented to complement reporting by physicians and other health-care professionals to improve the timeliness of disease-outbreak detection. Space-time disease-surveillance methods have been proposed as a supplement to purely temporal statistical methods for outbreak detection to detect localized outbreaks before they spread to larger regions. OBJECTIVE: The aims of this study were twofold: 1) to design and make available benchmark data sets for evaluating the statistical power of space-time early detection methods and 2) to evaluate the power of the prospective purely temporal and space-time scan statistics by applying them to the benchmark data sets at different parameter settings. METHODS: Simulated data sets based on the geography and population of New York City were created, including effects of outbreaks of varying size and location. Data sets with no outbreak effects were also created. Scan statistics were then run on these data sets, and the resulting power performances were analyzed and compared. RESULTS: The prospective space-time scan statistic performs well for a spectrum of outbreak models. By comparison, the prospective purely temporal scan statistic has higher power for detecting citywide outbreaks but lower power for detecting geographically localized outbreaks. CONCLUSIONS: The benchmark data sets created for this study can be used successfully for formal statistical power evaluations and comparisons. If an anomaly caused by an outbreak is local, purely temporal surveillance methods might be unable to detect it, in which case space-time methods would be necessary for early detection.

Benchmarking↗

PubMed2004

The geographic distribution of breast cancer incidence in Massachusetts 1988 to 1997, adjusted for covariates.

BACKGROUND: The aims of this study were to determine whether observed geographic variations in breast cancer incidence are random or statistically significant, whether statistically significant excesses are temporary or time-persistent, and whether they can be explained by covariates such as socioeconomic status (SES) or urban/rural status? RESULTS: A purely spatial analysis found fourteen geographic areas that deviated significantly from randomness: ten with higher incidence rates than expected, four lower than expected. After covariate adjustment, three of the ten high areas remained statistically significant and one new high area emerged. The space-time analysis identified eleven geographic areas as statistically significant, seven high and four low. After covariate adjustment, four of the seven high areas remained statistically significant and a fifth high area also identified in the purely spatial analysis emerged. CONCLUSIONS: These analyses identify geographic areas with invasive breast cancer incidence higher or lower than expected, the times of their excess, and whether or not their status is affected when the model is adjusted for risk factors. These surveillance findings can be a sound starting point for the epidemiologist and has the potential of monitoring time trends for cancer control activities.

Journal Article↗

PubMed2004

Fat, fiber, fruits, vegetables, and risk of colorectal adenomas.

A case-control study was conducted at the National Naval Medical Center (Maryland, USA) from 1994 to 1996 to investigate the possible association between dietary factors and colorectal adenomas. Cases (n = 239) were subjects diagnosed with adenomas (146 new and 93 recurrent) by sigmoidoscopy or colonoscopy. Those with no evidence of adenomas found by sigmoidoscopy were recruited as controls (n = 228). Dietary variables, assessed by a 100-item food frequency questionnaire, were analyzed by the logistic regression model, which was adjusted for age, gender and total energy intake. Variables of fat intake were further adjusted for red meat intake. An increased risk of 7% [odds ratio (OR): 1.07; 95% confidence interval (95% CI): 0.94-1.22] per 5% energy/day from total fat was observed. Every additional 5% unit of oleic acid intake/day significantly increased the adenoma risk by 115% (OR: 2.15; 95% CI: 1.05-4.39). Red meat fat increased the risk by 20% (OR: 1.20; 95% CI: 0.71-2.04), and white meat fat decreased the risk by 67% (OR: 0.33; 95% CI: 0.19-0.95) for every additional 5% unit of respective intake/day. Risk decreased by 41% (OR: 0.59; 95% CI: 0.41-0.86) for every additional 5% unit of fiber intake/day. Vegetable [OR per 100 g of vegetable intake/day: 0.83, 95% CI: 0.67-1.04] and fruit (OR per 100 g of fruit intake/day: 0.92, 95% CI: 0.82-1.03) intake showed an inverse association, and the results are suggestive of an association with the risk for adenomas. In conclusion, a strong positive association between oleic acid intake and colorectal adenoma risk was observed. This is likely to be an indicator of "unhealthy" food (meat, dairy, margarine, mayonnaise, sweet baked food) consumption in this population. Increased intake of dietary fiber was associated with a moderately decreased risk of adenomas.

Adenoma↗

PubMed2004

Urinary mutagenesis and fried red meat intake: influence of cooking temperature, phenotype, and genotype of metabolizing enzymes in a controlled feeding study.

Meat cooked at high temperatures contains potential carcinogenic compounds, such as heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Samples from a 2-week controlled feeding study were used to examine the relationship between the intake of mutagenicity from meat fried at different temperatures and the levels of mutagenicity subsequently detected in urine, as well as the influence of the genotype of drug metabolizing enzymes on urinary mutagenicity. Sixty subjects consumed ground beef patties fried at low temperature (100 degrees C) for 1 week, followed by ground beef patties fried at high temperature (250 degrees C) the second week. Mutagenicity in the meat was assayed in Salmonella typhimurium TA98 (+S9), and urinary mutagenicity was determined using Salmonella YG1024 (+S9). Genotypes for NAT1, NAT2, GSTM1, and UGT1A1 were analyzed using blood samples from the subjects. Meat fried at 100 degrees C was not mutagenic, whereas meat fried at 250 degrees C was mutagenic (1023 rev/g). Unhydrolyzed and hydrolyzed urine samples were 22x and 131x more mutagenic, respectively, when subjects consumed red meat fried at 250 degrees C compared with red meat fried at 100 degrees C. We found that hydrolyzed urine was approximately 8x more mutagenic than unhydrolyzed urine, likely due to the deconjugation of mutagens from glucuronide. The intake of meat cooked at high temperature correlated with the mutagenicity of unhydrolyzed urine (r = 0.32, P = 0.01) and hydrolyzed urine (r = 0.34, P = 0.008). Mutagenicity in unhydrolyzed urine was not influenced by NAT1, NAT2, or GSTM1 genotypes. However, a UGT1A1*28 polymorphism that reduced UGT1A1 expression and conjugation modified the effect of intake of meat cooked at high temperature on mutagenicity of unhydrolyzed urine (P for interaction = 0.04). These mutagenicity data were also compared with previously determined levels of HCAs (measured as MeIQx, DiMeIQx, and PhIP) and polycyclic aromatic hydrocarbons (PAHs) in the meat, levels of HCAs in the urine, and CYP1A2 and NAT2 phenotypes. The levels of mutagenicity in the meat fried at low and high temperatures correlated with levels of HCAs, but not levels of PAHs, in the meat. Also, levels of mutagenicity in unhydrolyzed urine correlated with levels of MeIQx in unhydrolyzed urine (r = 0.36; P = 0.01), and the levels of mutagenicity of hydrolyzed urine correlated with levels of MeIQx (r = 0.34; P = 0.01) and PhIP (r = 0.43; P = 0.001) of hydrolyzed urine. Mutagenicity in unhydrolyzed urine was not influenced by either the CYP1A2 or NAT2 phenotype. The data from this study indicate that urinary mutagenicity correlates with mutagenic exposure from cooked meat and can potentially be used as a marker in etiological studies on cancer.

Animals↗

PubMed2004

Geographic distribution of prostate cancer incidence in the era of PSA testing, Connecticut, 1984 to 1998.

OBJECTIVES: To evaluate the geographic variation of prostate cancer incidence in Connecticut during a 15-year period: before the introduction of prostate-specific antigen (PSA) testing (1984 to 1988), during its introduction (1989 to 1993), and after its widespread adoption (1994 to 1998). METHODS: A spatial scan statistic was used to detect and test the significance of the geographic rate variation among 29,944 incident cases. RESULTS: During 1984 to 1988, eight locations had incidence rates that differed significantly from the statewide level; for 1989 to 1993, only two locations were identified. By 1994 to 1998, a significant rate variation was noted for 10 locations around Connecticut. CONCLUSIONS: The observed geographic variation of incidence rates may reflect differing opportunities to uncover latent cases at given locales.

Adenocarcinoma↗

PubMed2004

The role of area-level influences on prostate cancer grade and stage at diagnosis.

BACKGROUND: This research explores area-level social influences on prostate cancer, to test whether area-level influences explain disparities in U.S. prostate cancer burden. METHODS: The authors geocoded 23,993 1992-1997 Maryland prostate cancer cases, and linked cases to 1990 census data. The authors examined the effect of 17 area-level social variables, measured at block group, tract, and county, modeling individual and multilevel predictors of later stage and higher tumor grade. RESULTS: Younger age, black race, higher grade or ungraded tumors, and earlier year of diagnosis were associated with later stage. Block group percentage of white-collar workers (O.R. = 0.93, 95% C.I. = 0.89, 0.98), and county resources (O.R. = 0.94, 95% C.I. = 0.89, 0.98), were protective of later stage. Older age, black race, and earlier year of diagnosis were associated with higher grade. Block group income was protective for white men (O.R. = 0.92, 95% C.I. = 0.87, 0.96), but for all men, county resources increased risk of higher grade (O.R. = 1.23, 95% C.I. = 1.16, 1.31). CONCLUSIONS: Social resources did not significantly reduce racial differences. Results suggest tumor biology is related to relative resources, with better outcomes associated with greater small-area wealth in low-resource counties, but stage at diagnosis is associated with absolute resources, with better outcomes associated with higher small-area social class in high-resource counties.

Adolescent↗

PubMed2004

The effect of different doses of micronized 17beta-estradiol on C-reactive protein, interleukin-6, and lipids in older women.

BACKGROUND: The authors evaluated the effect of 3 doses (0.25 mg/day, 0.5 mg/day, and 1 mg/day) of micronized 17beta-estradiol (E2) on C-reactive protein (CRP), interleukin-6 (IL-6), and lipids, compared with placebo, in healthy older women participating in an osteoporosis study. METHODS: This randomized, double-blind, placebo-controlled study was conducted in a University clinical research center. Participants were healthy, community-living women older than 65 years. The primary outcome measure of the study was bone metabolism as estimated by serum and urine markers of bone turnover. For this analysis, the authors measured serum markers of CRP, IL-6, lipids, intracellular adhesion molecule-1, and E-selectin at baseline, after 12 weeks of treatment, and after 12 weeks with no treatment. RESULTS: A significant dose-response effect of estrogen occurred on CRP levels. After 12 weeks of treatment, CRP decreased 59% in the 0.25 mg/day E2 group and increased 65% in the 1 mg/day E2 group, compared with placebo. The CRP level continued to be elevated (92%), compared with placebo, 12 weeks after treatment was discontinued in the 1 mg/day E2 group. High-density lipoprotein (HDL) and HDL2 cholesterol increased and low-density lipoprotein (LDL) cholesterol decreased at 12 weeks in the 1 mg/day E2 group, with a significant dose-response effect. E-selectin decreased significantly in the 1 mg/day E2 group 12 weeks after discontinuation of treatment (-7%), and there was a significant dose-response effect at this time. The 2 lower doses did not affect any of these parameters. Total and HDL3 cholesterol, triglycerides, lipoprotein(a), intracellular adhesion molecule-1, and IL-6 did not change with any dose of E2. CONCLUSIONS: C-reactive protein, an inflammation marker associated with increased risk for cardiovascular disease, decreased in women taking the lowest estrogen dose but increased in women assigned to the highest estrogen dose, suggesting decreased inflammation with lower dose E2. However, with 3 months of treatment, 0.25 or 0.5 mg/day E2 did not have the same beneficial effects on HDL or LDL cholesterol as did 1 mg/day E2. These data suggest that estradiol doses have differential short-term effects on markers of cardiovascular disease. Low-dose E2 decreased CRP, an important marker of inflammation, but did not affect lipid parameters, whereas the highest dose increased CRP and had a beneficial effect on lipid parameters. The long-term consequences of these effects are unknown, but it is possible that estradiol dose should be considered when risk:benefit ratios are evaluated for individual women before estrogen replacement therapy is initiated.

Aged↗

PubMed2004

Brain cancer mortality in the United States, 1986 to 1995: a geographic analysis.

The Atlas of Cancer Mortality in the United States, 1950-94 (Devesa et al.) published in 1999 by the National Institutes of Health suggests that there are elevated rates of brain and other nervous system cancer in the northwestern, north central, and southeastern parts of the country. Being descriptive in nature, the atlas does not evaluate whether observed patterns are simply due to random variation or if they are reflective of true geographical differences in disease risk or treatment practices. To formally test for geographical clustering of disease, we analyzed U.S. brain cancer mortality data from 1986 to 1995 with Tango's Excess Events test, the Cuzick-Edwards k-Nearest-Neighbors test, and the spatial scan statistic. All tests revealed statistically significant geographical clustering for both adult men and women. The spatial scan statistic indicated that the most likely cluster of high mortality was in parts of Arkansas, Mississippi, and Oklahoma (relative risk [RR] = 1.22, P < 0.0001) for women and in parts of Tennessee and Kentucky (RR = 1.15, P < 0.0001) for men. Several secondary clusters were detected, but there were no statistically significant clusters of a very localized nature and a high RR. For childhood brain cancer, there were no statistically significant geographical clusters. It is reassuring that no local brain cancer mortality "hot spots" with very high RRs were found. While the causes of the large geographical clusters with modest RRs are unclear, the geographical pattern of brain cancer mortality provides valuable information that can help in formulating etiological hypotheses and in targeting high-risk populations for further epidemiological and health services research.

Adolescent↗

PubMed2004

Syndromic surveillance in public health practice, New York City.

The New York City Department of Health and Mental Hygiene has established a syndromic surveillance system that monitors emergency department visits to detect disease outbreaks early. Routinely collected chief complaint information is transmitted electronically to the health department daily and analyzed for temporal and spatial aberrations. Respiratory, fever, diarrhea, and vomiting are the key syndromes analyzed. Statistically significant aberrations or "signals" are investigated to determine their public health importance. In the first year of operation (November 15, 2001, to November 14, 2002), 2.5 million visits were reported from 39 participating emergency departments, covering an estimated 75% of annual visits. Most signals for the respiratory and fever syndromes (64% and 95%, respectively) occurred during periods of peak influenza A and B activity. Eighty-three percent of the signals for diarrhea and 88% of the signals for vomiting occurred during periods of suspected norovirus and rotavirus transmission.

Adolescent↗

PubMed2003

Power evaluation of disease clustering tests.

BACKGROUND: Many different test statistics have been proposed to test for spatial clustering. Some of these statistics have been widely used in various applications. In this paper, we use an existing collection of 1,220,000 simulated benchmark data, generated under 51 different clustering models, to compare the statistical power of several disease clustering tests. These tests are Besag-Newell's R, Cuzick-Edwards' k-Nearest Neighbors (k-NN), the spatial scan statistic, Tango's Maximized Excess Events Test (MEET), Swartz' entropy test, Whittemore's test, Moran's I and a modification of Moran's I. RESULTS: Except for Moran's I and Whittemore's test, all other tests have good power for detecting some kind of clustering. The spatial scan statistic is good at detecting localized clusters. Tango's MEET is good at detecting global clustering. With appropriate choice of parameter, Besag-Newell's R and Cuzick-Edwards' k-NN also perform well. CONCLUSION: The power varies greatly for different test statistics and alternative clustering models. Consideration of the power is important before we decide which test statistic to use.

Journal Article↗

PubMed2003

Ultralow-dose micronized 17beta-estradiol and bone density and bone metabolism in older women: a randomized controlled trial.

CONTEXT: Estrogen therapy is known to prevent osteoporosis, but studies have shown that conventional doses increase adverse events. Whether lower doses, one quarter of standard treatment, prevent bone loss is not known. OBJECTIVE: To examine the effect of 3 years of treatment with 0.25 mg/d of micronized 17beta-estradiol on bone mineral density (BMD) and bone turnover in healthy older postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial conducted from July 24, 1998, through June 14, 2002, at a university general clinical research center in the United States. Healthy, community-dwelling women (N = 167) who were older than 65 years at enrollment. INTERVENTION: Dosage of 0.25 mg/d of micronized 17beta-estradiol (n = 83) or placebo (n = 84); all women who had not had a hysterectomy received 100 mg/d of oral micronized progesterone for 2-week periods every 6 months. MAIN OUTCOME MEASURES: The BMD of the hip, spine, wrist, and total body measured annually for 3 years. Serum and urine biochemical markers of bone resorption and formation and sex hormones were measured at baseline, 3 months, and during years 1 and 3 of treatment. RESULTS: Mean BMD increased at all sites for participants taking low-dose estrogen (17beta-estradiol) compared with placebo (P<.001). Compared with participants receiving placebo, participants taking low-dose estrogen had BMD increases of 2.6% for the femoral neck; 3.6%, total hip; 2.8%, spine; and 1.2%, total body. Markers of bone turnover, N-telopeptides of type 1 collagen, and bone alkaline phosphatase decreased significantly (P<.001) in participants taking low-dose estrogen compared with placebo. Estradiol, estrone, and sex hormone-binding globulin levels increased in the estrogen-treated group compared with placebo. The adverse effect profile was similar; specifically, there were no statistically significant differences in breast tenderness, changes in endometrial thickness or pathological effects, or annual mammographic results between the 2 groups. The number of abnormal mammograms over 3 years was 15 for the low-dose estrogen group and 10 for the placebo group (8 occurred at baseline) (P =.26). There were no reports of breast cancer during the study. CONCLUSIONS: In older women, a dosage of 0.25 mg/d of 17beta-estradiol increased bone density of the hip, spine, and total body, and reduced bone turnover, with minimal adverse effects. Future studies evaluating the effect of low-dose estrogen on fractures are indicated.

Absorptiometry, Photon↗

PubMed2003

Dietary fibre and colorectal adenoma in a colorectal cancer early detection programme.

BACKGROUND: Although dietary fibre has been reported to have no association with colorectal adenoma and cancer, in some studies this topic remains controversial. METHODS: We used a 137-item food frequency questionnaire to assess the relation of fibre intake and frequency of colorectal adenoma. The study was done within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomised controlled trial designed to investigate methods for early detection of cancer. In our analysis, we compared fibre intake of 33971 participants who were sigmoidoscopy-negative for polyps, with 3591 cases with at least one histologically verified adenoma in the distal large bowel (ie, descending colon, sigmoid colon, or rectum). Odds ratios were estimated by logistic regression analysis. FINDINGS: High intakes of dietary fibre were associated with a lower risk of colorectal adenoma, after adjustment for potential dietary and non-dietary risk factors. Participants in the highest quintile of dietary fibre intake had a 27% (95% CI 14-38, p(trend)=0.002) lower risk of adenoma than those in the lowest quintile. The inverse association was strongest for fibre from grains and cereals and from fruits. Risks were similar for advanced and non-advanced adenoma. Risk of rectal adenoma was not significantly associated with fibre intake. INTERPRETATION: Dietary fibre, particularly from grains, cereals, and fruits, was associated with decreased risk of distal colon adenoma.

Adenoma↗

PubMed2003

A tree-based scan statistic for database disease surveillance.

Many databases exist with which it is possible to study the relationship between health events and various potential risk factors. Among these databases, some have variables that naturally form a hierarchical tree structure, such as pharmaceutical drugs and occupations. It is of great interest to use such databases for surveillance purposes in order to detect unsuspected relationships to disease risk. We propose a tree-based scan statistic, by which the surveillance can be conducted with a minimum of prior assumptions about the group of occupations/drugs that increase risk, and which adjusts for the multiple testing inherent in the many potential combinations. The method is illustrated using data from the National Center for Health Statistics Multiple Cause of Death Database, looking at the relationship between occupation and death from silicosis.

Databases, Factual↗