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Background: Nonalcoholic fatty liver disease (NAFLD) has become a major contributor to the rising incidence of hepatocellular carcinoma (HCC) in the United States and other developed countries. Iron, an essential metal primarily stored in hepatocytes, may play a role in the development of NAFLD-related HCC. Epidemiologic data on iron overload without hemochromatosis in relation to HCC are sparse. This study aimed to examine the associations between serum biomarkers of iron and the risk of HCC in patients with NAFLD., Methods: We identified 18,569 patients with NAFLD using the University of Pittsburgh Medical Center electronic health records from 2004 through 2018. After an average 4.34 years of follow-up, 244 patients developed HCC. Cox proportional hazard regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) of HCC incidence associated with elevated levels of iron biomarkers with adjustment for age, sex, race, body mass index, history of diabetes, and tobacco smoking., Results: The HRs (95% CIs) of HCC for clinically defined elevation of serum iron and transferrin saturation were 2.91 (1.34-6.30) and 2.02 (1.22-3.32), respectively, compared with their respective normal range. No statistically significant association was observed for total iron-binding capacity or serum ferritin with HCC risk., Conclusions: Elevated levels of serum iron and transferrin saturation were significantly associated with increased risk of HCC among patients with NAFLD without hemochromatosis or other major underlying causes of chronic liver diseases., Impact: Clinical surveillance of serum iron level may be a potential strategy to identify patients with NAFLD who are at high risk for HCC., (©2021 American Association for Cancer Research.)

Objective: This prospective, longitudinal study explored the impact of a continuing education class on librarians' knowledge levels about and professional involvement with systematic reviews. Barriers to systematic review participation and the presence of formal systematic review services in libraries were also measured., Methods: Participants completed web-based surveys at three points in time: pre-class, post-class, and six-months' follow-up. Descriptive statistics were calculated for demographics and survey questions. Linear mixed effects models assessed knowledge score changes over time., Results: Of 160 class attendees, 140 (88%) completed the pre-class survey. Of those 140, 123 (88%) completed the post-class survey, and 103 (74%) completed the follow-up survey. There was a significant increase ( p <0.00001) from pre-class to post-class in knowledge test scores, and this increase was maintained at follow-up. At post-class, 69% or more of participants intended to promote peer review of searches, seek peer review of their searches, search for grey literature, read or follow published guidelines on conduct and documentation of systematic reviews, and ask for authorship on a systematic review. Among librarians who completed a systematic review between post-class and follow-up, 73% consulted published guidelines, 52% searched grey literature, 48% sought peer review, 57% asked for authorship, and 70% received authorship., Conclusions: Attendance at this continuing education class was associated with positive changes in knowledge about systematic reviews and in librarians' systematic review-related professional practices. This suggests that in-depth professional development classes can help librarians develop skills that are needed to meet library patrons' changing service needs., (Copyright: © 2020, Authors.)

Background: Previous studies examining associations between use of fertility drugs and ovarian cancer risk have provided conflicting results. We used data from a large case-control study to determine whether fertility drug use significantly impacts ovarian cancer risk when taking into account parity, gravidity, and cause of infertility., Methods: Data from the Hormones and Ovarian Cancer Prediction (HOPE) study were used (902 cases, 1,802 controls). Medical and reproductive histories were collected via in-person interviews. Logistic regression was used to calculate ORs and 95% confidence intervals (CI). Models were adjusted for age, race, education, age at menarche, parity, oral contraceptive use, breastfeeding, talc use, tubal ligation, and family history of breast/ovarian cancer., Results: Ever use of fertility drugs was not significantly associated with ovarian cancer within the total HOPE population (OR, 0.93; 95% CI, 0.65-1.35) or among women who reported seeking medical attention for infertility (OR, 0.87; 95% CI, 0.54-1.40). We did observe a statistically significant increased risk of ovarian cancer for ever use of fertility drugs among women who, despite seeking medical attention for problems getting pregnant, remained nulligravid (OR, 3.13; 95% CI, 1.01-9.67)., Conclusions: These results provide further evidence that fertility drug use does not significantly contribute to ovarian cancer risk among the majority of women; however, women who despite infertility evaluation and fertility drug use remain nulligravid, may have an elevated risk for ovarian cancer., Impact: Our results suggest that fertility drug use does not significantly contribute to overall risk of ovarian cancer when adjusting for known confounding factors., (©2012 AACR.)

Background: The Pennsylvania Department of Health established a registry of the Three Mile Island (TMI) nuclear power plant accident in 1979. Over 93% of the population present on the day of the accident within a 5-mile radius was enrolled and interviewed. We used the registry to investigate the potential cancer risk from low-dose radiation exposure among the TMI population., Methods: Cancer incidence data among the TMI cohort were available from 1982 to 1995. Because more than 97% of the population were white and few cancer cases were reported for those younger than 18 years of age, we included whites of age 18 years and older (10,446 men and 11,048 women) for further analyses. Cox regression models were used to estimate the relative risk (RR) per 0.1 mSv and 95% confident interval (CI) of cancer by radiation-related exposures. The cancers of interest were all malignant neoplasms, cancer of bronchus, trachea, and lung, cancer of lymphatic and hematopoietic tissues, leukemia, and female breast., Results: Among men and women, there was no evidence of an increased risk for all malignant neoplasms among the TMI cohort exposed to higher maximum and likely γ radiation (RR=1.00, 95% CI=0.97, 1.01 and RR=0.99, 95% CI=0.94, 1.03, respectively) after adjusting for age, gender, education, smoking, and background radiation. Elevation in risk was noted for cancer of the bronchus, trachea, and lung in relation to higher background radiation exposure (RR=1.45, 95% CI=1.02-2.05 at 8.0-8.8 μR/h compared to 5.2-7.2 μR/h). An increased risk of leukemia was found among men exposed to higher maximum and likely γ radiation related to TMI exposure during the ten days following the accident (RR=1.15, 95% CI=1.04, 1.29 and RR=1.36, 95% CI=1.08, 1.71, respectively). This relationship was not found in women., Conclusion: Increased cancer risks from low-level radiation exposure within the TMI cohort were small and mostly statistically non-significant. However, additional follow-up on this population is warranted, especially to explore the increased risk of leukemia found in men., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder associated with infertility, cardiovascular disease and type 2 diabetes. Despite anecdotal evidence that lesbians may have higher PCOS rates than heterosexuals, little empirically based evidence supports this theory. To address this gap, we examined PCOS prevalence and associated factors among a community sample of lesbian and heterosexual women., Methods: Lesbian (n = 114) and heterosexual (n = 97) women aged 35 to 45 who participated in The Epidemiologic STudy of HEalth Risk (ESTHER) Project (Pittsburgh, PA) were recruited into our PCOS exploratory study between April and October 2008. A reproductive endocrinologist, "blinded" to participant sexual orientation, identified women with PCOS using a modified version of the 2003 Rotterdam Diagnostic Criteria for PCOS. Sexual orientation was defined by self-reported sexual identity, behavior, and attraction. Fisher's exact, chi-square, and Wilcoxon rank-sum tests were used for analysis., Results: Approximately 6.2% (n = 13) of the total sample (n = 211) had PCOS. PCOS rates did not significantly differ between lesbian and heterosexual women ([7.9%, n = 9] vs. [4.1%, n = 4]; p = .256). No significant differences in PCOS-related factors were found between lesbian and heterosexual women: polycystic ovaries ([10.5%, n = 12] vs. [6.2%, n = 6]; p = 0.261), hirsutism ([24.6%, n = 28] vs. [15.5%, n = 15]; p = 0.102), oligomenorrhea ([3.6%, n = 4] vs. [5.4%, n = 5]; p = 0.735), adult acne ([21.1%, n = 24] vs. [24.7%, n = 24], p = 0.524), and median testosterone ([1.69 ng/mL, n = 114] vs. [1.52 ng/mL, n = 97]; p = 0.069) and androstenedione ([1.63 ng/mL, n = 114] vs. [1.51 ng/mL, n = 97]; p = 0.079) concentrations, respectively., Conclusion: PCOS and related factors did not differ by sexual orientation. Despite this, our observed rates warrant the need for additional studies to examine the relationship between PCOS diagnoses, PCOS-related factors, and sexual orientation., (Copyright © 2011 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess the temporal and spatial relationship of risk for total leukemia and AML (acute myelogenous leukemia) among community residents of an area in northeastern (NE) Pennsylvania (PA) affected by the Tranguch Gasoline Spill which occurred in the early 1990s., Methods: Standardized incidence ratios (SIR) were calculated for total leukemia and AML among 625 residents affected by the gasoline spill in relation to both PA and local county cancer incidence rates. The risk of total leukemia and AML among the gasoline exposed population was evaluated for the period prior to the spill, 1985-1989; during the time surrounding the spill, 1990-1994; and for a period subsequent to the spill, 1995-2001., Results: The incidence of total leukemia and AML was significantly elevated subsequent to the spill for the entire period 1990-2001 and was highest for the period 1995-2001, whether comparison was made to PA or local county leukemia rates. Based on comparison to PA rates, the SIRs for total leukemia and AML were 7.69 (95% CI=1.58-22.46) and 11.54 (95% CI=2.38-33.69) for the 1995-2001 period, respectively. Prior to the spill, 1985-1989, and during the period of the spill, 1990-1994, no cases of leukemia were identified among the affected residents., Conclusions: These results suggest a possible association between chronic low level benzene exposure and increased risk of leukemia among residents of the Tranguch Spill Site in NE PA. Our study provides additional support to the growing body of evidence implicating low level benzene exposure and cancer risk. We recommend that other communities contaminated with gasoline vapor through leaking underground storage vessels be monitored for elevated risk of leukemia., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: In a cohort in which racial data are unknown for some persons, race-specific persons and person-years are imputed using a model-based iterative allocation algorithm (IAA)., Methods: An EM algorithm-based approach to address misclassification in a censored data regression setting can be adapted to estimate the probability that a person of unknown race is white. The corresponding race-specific person-years are obtained as a by-product of the estimation procedure. Variance estimates are computed using the bootstrap. The proposed approach is compared with the proportional allocation method (PAM)., Results: In an occupational cohort where racial data were missing for 41% of the workers, the age-time-race-specific person-years were estimated within a relative variation of approximately 20%, using the IAA. The deaths were less reliably estimated. The standardized mortality ratios (SMRs) for all-cause mortality estimated using the IAA and the PAM were more similar for the non-white workers than for a smaller subgroup of white workers., Conclusions: The IAA provides a method to reliably estimate race-specific person-year denominators in cohort studies with missing racial data. This method is applicable to other incompletely observed non-time-dependent categorical covariates. Internal cohort rates or SMRs can be computed and modeled, with bootstrap confidence intervals that account for the uncertainty in the determination of race.

Objective: To examine the cause-specific mortality experience of an occupational cohort with probable past exposure to beta-naphythylamine (BNA)., Methods: Subjects were 374 male and 26 female workers employed at a Pennsylvania chemical plant that produced or used beta-naphthylamine (BNA) between 1940 and 1981. Vital status through 1998 was determined for 97.5% of the cohort and cause of death for 100% of 79 deaths. Limited industrial hygiene data and reports from former employees were used to categorize workers as high, medium, or low risk for BNA exposure. Statistical analyses included US and local county-based standardized mortality ratios (SMRs)., Results: We observed statistically significantly elevated county rate-based SMRs for all causes combined (SMR = 1.98, 95% confidence interval (CI) = 1.56-2.49), all malignant neoplasms combined (28 deaths, SMR = 3.08, 95% CI = 2.05-4.46), respiratory system cancer (12 deaths, SMR = 3.91, 95% CI = 2.02-6.83), and bladder cancer (four deaths, SMR = 16.83, 95% CI = 4.59-43.1). Three bladder cancer cases were classified as high risk (SMR = 26.79, 95% CI = 5.53-78.29). Mortality risks were also elevated for most other malignant and non-malignant cause of death categories examined., Conclusions: Bladder cancer risk remains highly elevated among Drake/Kilsdonk workers and appears to be causally related to past BNA exposure. While lifestyle and behavioral risk factors may explain some of the mortality excesses for non-urological cancers, the possibility remains that BNA exposure may have also played a role in these and other observed cancer excesses., (Copyright 2003 Wiley-Liss, Inc.)

The Three Mile Island (TMI) nuclear power plant accident (1979) prompted the Pennsylvania Department of Health to initiate a cohort mortality study in the TMI accident area. This study is significant because of the long follow-up (1979-1998), large cohort size (32,135), and evidence from earlier reports indicating increased cancer risks. Standardized mortality ratios (SMRs) were calculated to assess the mortality experience of the cohort compared with a local population. Relative risk (RR) regression modeling was performed to assess cause-specific mortality associated with radiation-related exposure variables after adjustment for individual smoking and lifestyle factors. Overall cancer mortality in this cohort was similar to the local population [SMRs = 103.7 (male); 99.8 (female)]. RR modeling showed neither maximum gamma nor likely gamma exposure was a significant predictor of all malignant neoplasms; bronchus, trachea, and lung; or heart disease mortality after adjusting for known confounders. The RR estimates for maximum gamma exposure (less than or equal to 8, 8-19, 20-34, greater than or equal to 35 mrem) in relation to all lymphatic and hematopoietic tissue (LHT) are significantly elevated (RRs = 1.00, 1.16, 2.54, 2.45, respectively) for males and are suggestive of a potential dose-response relationship, although the test for trend was not significant. An upward trend of RRs and SMRs for levels of maximum gamma exposure in relation to breast cancer in females (RRs = 1.00, 1.08, 1.13, 1.31; SMRs = 104.2, 113.2, 117.9) was also noted. Although the surveillance within the TMI cohort provides no consistent evidence that radioactivity released during the nuclear accident has had a significant impact on the overall mortality experience of these residents, several elevations persist, and certain potential dose-response relationships cannot be definitively excluded.

The largest U.S. population exposed to low-level radioactivity released by an accident at a nuclear power plant is composed of residents near the Three Mile Island (TMI) Plant on 28 March 1979. This paper (a collaboration of The University of Pittsburgh and the Pennsylvania Department of Health) reports on the mortality experience of the 32,135 members in this cohort for 1979-1992. We analyzed standardized mortality ratios (SMRs) using a local comparison population and performed relative risk regression modeling to assess overall mortality and specific cancer risks by confounding factors and radiation-related exposure variables. Total mortality was significantly elevated for both men and women (SMRs = 109 and 118, respectively). All heart disease accounted for 43.3% of total deaths and demonstrated elevated SMRs for heart disease of 113 and 130 for men and women, respectively; however, when controlling for confounders and natural background radiation, these elevations in heart disease were no longer evident. Overall cancer mortality was similar in this cohort as compared to the local population (male SMR = 100; female SMR = 101). In the relative risk modeling, there was a significant effect for all lymphatic and hematopoietic tissue in males in relation to natural background exposure (p = 0.04). However, no trend was noted. We found a significant linear trend for female breast cancer risk in relation to increasing levels of TMI-related likely [gamma]-exposure (p = 0.02). Although such a relationship has been noted in other investigations, emissions from the TMI incident were significantly lower than in other documented studies. Therefore, it is unlikely that this observed increase is related to radiation exposure on the day of the accident. The mortality surveillance of this cohort does not provide consistent evidence that radioactivity released during the TMI accident has a significant impact on the mortality experience of this cohort to date. However, continued follow-up of these individuals will provide a more comprehensive description of the morbidity and mortality experience of the cohort.