Person:

Rosner, Bernard

Background: A recent randomized controlled trial in critical-care units revealed that the elimination of extended-duration work shifts (≥24 h) reduces the rates of significant medical errors and polysomnographically recorded attentional failures. This raised the concern that the extended-duration shifts commonly worked by interns may contribute to the risk of medical errors being made, and perhaps to the risk of adverse events more generally. Our current study assessed whether extended-duration shifts worked by interns are associated with significant medical errors, adverse events, and attentional failures in a diverse population of interns across the United States. Methods and Findings: We conducted a Web-based survey, across the United States, in which 2,737 residents in their first postgraduate year (interns) completed 17,003 monthly reports. The association between the number of extended-duration shifts worked in the month and the reporting of significant medical errors, preventable adverse events, and attentional failures was assessed using a case-crossover analysis in which each intern acted as his/her own control. Compared to months in which no extended-duration shifts were worked, during months in which between one and four extended-duration shifts and five or more extended-duration shifts were worked, the odds ratios of reporting at least one fatigue-related significant medical error were 3.5 (95% confidence interval [CI], 3.3–3.7) and 7.5 (95% CI, 7.2–7.8), respectively. The respective odds ratios for fatigue-related preventable adverse events, 8.7 (95% CI, 3.4–22) and 7.0 (95% CI, 4.3–11), were also increased. Interns working five or more extended-duration shifts per month reported more attentional failures during lectures, rounds, and clinical activities, including surgery and reported 300% more fatigue-related preventable adverse events resulting in a fatality. Conclusions: In our survey, extended-duration work shifts were associated with an increased risk of significant medical errors, adverse events, and attentional failures in interns across the United States. These results have important public policy implications for postgraduate medical education.

Introduction: A number of breast cancer risk prediction models have been developed to provide insight into a woman's individual breast cancer risk. Although circulating levels of estradiol in postmenopausal women predict subsequent breast cancer risk, whether the addition of estradiol levels adds significantly to a model's predictive power has not previously been evaluated. Methods: Using linear regression, the authors developed an imputed estradiol score using measured estradiol levels (the outcome) and both case status and risk factor data (for example, body mass index) from a nested case-control study conducted within a large prospective cohort study and used multiple imputation methods to develop an overall risk model including both risk factor data from the main cohort and estradiol levels from the nested case-control study. Results: The authors evaluated the addition of imputed estradiol level to the previously published Rosner and Colditz log-incidence model for breast cancer risk prediction within the larger Nurses' Health Study cohort. The follow-up was from 1980 to 2000; during this time, 1,559 invasive estrogen receptor-positive breast cancer cases were confirmed. The addition of imputed estradiol levels significantly improved risk prediction; the age-specific concordance statistic increased from 0.635 ± 0.007 to 0.645 ± 0.007 (P < 0.001) after the addition of imputed estradiol. Conclusion: Circulating estradiol levels in postmenopausal women appear to add to other lifestyle factors in predicting a woman's individual risk of breast cancer.

Introduction: Body mass index (BMI) during adulthood is inversely related to the incidence of premenopausal breast cancer, but the role of body fatness earlier in life is less clear. We examined prospectively the relation between body fatness during childhood and adolescence and the incidence of breast cancer in premenopausal women. Methods: Participants were 109,267 premenopausal women in the Nurses' Health Study II who recalled their body fatness at ages 5, 10 and 20 years using a validated 9-level figure drawing. Over 12 years of follow up, 1318 incident cases of breast cancer were identified. Cox proportional hazards regression was used to compute relative risks (RRs) and 95% confidence intervals (CIs) for body fatness at each age and for average childhood (ages 5–10 years) and adolescent (ages 10–20 years) fatness.Results Body fatness at each age was inversely associated with premenopausal breast cancer incidence; the multivariate RRs were 0.48 (95% CI 0.35–0.55) and 0.57 (95% CI 0.39–0.83) for the most overweight compared with the most lean in childhood and adolescence, respectively (P for trend < 0.0001). The association for childhood body fatness was only slightly attenuated after adjustment for later BMI, with a multivariate RR of 0.52 (95% CI 0.38–0.71) for the most overweight compared with the most lean (P for trend = 0.001). Adjustment for menstrual cycle characteristics had little impact on the association. Conclusion: Greater body fatness during childhood and adolescence is associated with reduced incidence of premenopausal breast cancer, independent of adult BMI and menstrual cycle characteristics.

OBJECTIVE: Individuals with type 2 diabetes have high risk of late-life cognitive impairment, yet little is known about strategies to modify risk. Targeting insulin resistance and vascular complications—both associated with cognitive decline—may be a productive approach. We investigated whether dietary fat, which modulates glucose and lipid metabolism, might influence cognitive decline in older adults with diabetes. RESEARCH DESIGN AND METHODS: Beginning in 1995–1999, we evaluated cognitive function in 1,486 Nurses' Health Study participants, aged ≥70 years, with type 2 diabetes; second evaluations were conducted 2 years later. Dietary fat intake was assessed regularly beginning in 1980; we considered average intake from 1980 (at midlife) through initial cognitive interview and also after diabetes diagnosis. We used multivariate-adjusted linear regression models to obtain mean differences in cognitive decline across tertiles of fat intake. RESULTS: Higher intakes of saturated and trans fat since midlife, and lower polyunsaturated to saturated fat ratio, were each highly associated with worse cognitive decline in these women. On a global score averaging all six cognitive tests, mean decline among women in the highest trans fat tertile was 0.15 standard units worse than that among women in the lowest tertile (95% CI −0.24 to −0.06, P = 0.002); this mean difference was comparable with the difference we find in women 7 years apart in age. Results were similar when we analyzed diet after diabetes diagnosis. CONCLUSIONS: These findings suggest that lower intakes of saturated and trans fat and higher intake of polyunsaturated fat relative to saturated fat may reduce cognitive decline in individuals with type 2 diabetes.

Models of breast cancer incidence have evolved from the observation by Armitage and Doll in the 1950s that the pattern of incidence by age differs for reproductive cancers from those of other major malignancies. Both two-stage and multistage models have been applied to breast cancer incidence. Consistent across modeling approaches, risk accumulation or the rate of increase in breast cancer incidence is most rapid from menarche to first birth. Models that account for the change in risk after menopause and the temporal sequence of reproductive events summarize risk efficiently and give added insights to potentially important mechanistic features. First pregnancy has an adverse impact on progesterone receptor negative tumors, while increasing parity reduces the risk of estrogen/progesterone receptor positive tumors but not estrogen/progesterone receptor negative tumors. Integrated prediction models that incorporate prediction of carrier status for highly penetrant genes and also account for lifestyle factors, mammographic density, and endogenous hormone levels remain to be efficiently implemented. Models that both inform and reflect the emerging understanding of the molecular and cell biology of carcinogenesis are still a long way off.

Diesel exhaust has been suspected to be a lung carcinogen. The assessment of this lung cancer risk has been limited by lack of studies of exposed workers followed for many years. In this study, we assessed lung cancer mortality in 54,973 U.S. railroad workers between 1959 and 1996 (38 years). By 1959, the U.S. railroad industry had largely converted from coal-fired to diesel-powered locomotives. We obtained work histories from the U.S. Railroad Retirement Board, and ascertained mortality using Railroad Retirement Board, Social Security, and Health Care Financing Administration records. Cause of death was obtained from the National Death Index and death certificates. There were 43,593 total deaths including 4,351 lung cancer deaths. Adjusting for a healthy worker survivor effect and age, railroad workers in jobs associated with operating trains had a relative risk of lung cancer mortality of 1.40 (95% confidence interval, 1.30–1.51). Lung cancer mortality did not increase with increasing years of work in these jobs. Lung cancer mortality was elevated in jobs associated with work on trains powered by diesel locomotives. Although a contribution from exposure to coal combustion products before 1959 cannot be excluded, these results suggest that exposure to diesel exhaust contributed to lung cancer mortality in this cohort.

Background: An elevated risk of lung cancer in truck drivers has been attributed to diesel exhaust exposure. Interpretation of these studies specifically implicating diesel exhaust as a carcinogen has been limited because of limited exposure measurements and lack of work records relating job title to exposure-related job duties. Objectives: We established a large retrospective cohort of trucking company workers to assess the association of lung cancer mortality and measures of vehicle exhaust exposure.Methods Work records were obtained for 31,135 male workers employed in the unionized U.S. trucking industry in 1985. We assessed lung cancer mortality through 2000 using the National Death Index, and we used an industrial hygiene review and current exposure measurements to identify jobs associated with current and historical use of diesel-, gas-, and propane-powered vehicles. We indirectly adjusted for cigarette smoking based on an industry survey.Results Adjusting for age and a healthy-worker survivor effect, lung cancer hazard ratios were elevated in workers with jobs associated with regular exposure to vehicle exhaust. Mortality risk increased linearly with years of employment and was similar across job categories despite different current and historical patterns of exhaust-related particulate matter from diesel trucks, city and highway traffic, and loading dock operations. Smoking behavior did not explain variations in lung cancer risk. Conclusions: Trucking industry workers who have had regular exposure to vehicle exhaust from diesel and other types of vehicles on highways, city streets, and loading docks have an elevated risk of lung cancer with increasing years of work.

Epidemiologic evidence suggests a possible association between genital use of talcum powder and risk of epithelial ovarian cancer; however, the biological basis for this association is not clear. We analyzed interactions between talc use and genes in detoxification pathways [glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), and N-acetyltransferase 2 (NAT2)] to assess whether the talc/ovarian cancer association is modified by variants of genes potentially involved in the response to talc. Our analysis included 1,175 cases and 1,202 controls from a New England-based case-control study and 210 cases and 600 controls from the prospective Nurses' Health Study. We genotyped participants for the GSTM1 and GSTT1 gene deletions and three NAT2 polymorphisms. We used logistic regression to analyze the main effect of talc use, genotype, and gene-talc interactions in each population and pooled the estimates using a random-effects model. Regular talc use was associated with increased ovarian cancer risk in the combined study population (RR, 1.36; 95% CI, 1.14-1.63; P(trend) < 0.001). Independent of talc, the genes examined were not clearly associated with risk. However, the talc/ovarian cancer association varied by GSTT1 genotype and combined GSTM1/GSTT1 genotype. In the pooled analysis, the association with talc was stronger among women with the GSTT1-null genotype (P(interaction) = 0.03), particularly in combination with the GSTM1-present genotype (P(interaction) = 0.03). There was no clear evidence of an interaction with GSTM1 alone or NAT2. These results suggest that women with certain genetic variants may have a higher risk of ovarian cancer associated with genital talc use. Additional research is needed on these interactions and the underlying biological mechanisms.

Several recent studies have evaluated the association between dietary flavonoid intake and ovarian cancer risk, and all reported significant or suggestive inverse associations with certain flavonoids or flavonoid subclasses; however, most of these studies were small to moderate in size. We therefore examined this association in a large, population-based case-control study. We calculated intake of five common dietary flavonoids (myricetin, kaempferol, quercetin, luteolin, and apigenin), as well as total intake of these flavonoids, for 1,141 cases and 1,183 frequency-matched controls. We used unconditional logistic regression to estimate the relative risk (RR) of ovarian cancer for each quintile of flavonoid intake, compared to the lowest quintile. We did not observe an association between total flavonoid intake and ovarian cancer risk. The multivariable-adjusted RR for the highest versus lowest quintile of total flavonoid intake was 1.06 (95% confidence interval [CI]=0.78–1.45). In analyses of each individual flavonoid, only intake of apigenin was associated with a borderline significant decrease in risk (RR, highest versus lowest quintile=0.79, 95% CI=0.59–1.06; p-trend=0.26), and this association was significant after adjustment for intake of the other four individual flavonoids (comparable RR=0.72, 95% CI=0.53–0.98; p-trend=0.09). These results provide limited support for an association between flavonoid intake and ovarian cancer risk. However, given the findings of previous studies and the biologic plausibility of this association, additional studies are warranted.