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Item 10 Tips for Maintaining a Healthy Lifestyle and Body Weight(Fairbanks School of Public Health, 2020-03-18) Song, Yiqing; Epidemiology, School of Public HealthAt this extreme moment, we began working from home, away from campus, and keeping social distance for as many people as possible. As we stay home and are stuck with the foods that have been in our fridge or pantry for a while, we are temporarily living a sedentary lifestyle with increased odds of physical inactivity, excessive eating and sitting, stress, anxiety, and depression. In particular, many of us will gain some weight during the pandemic and may keep the extra weight permanently, which may carry considerable health risks for type 2 diabetes, hypertension, heart attack, stroke, and other health problems. Here, I’d like to share some basic tips and resources for how to maintain your healthy lifestyle, body weight, and overall well-being while staying home and engaging in social distancing.Item A Review of Research on Disparities in the Care of Black and White Patients With Cancer in Detroit(Frontiers Media, 2021-07-07) Simon, Michael S.; Raychaudhuri, Sreejata; Hamel, Lauren M.; Penner, Louis A.; Schwartz, Kendra L.; Harper, Felicity W. K.; Thompson, Hayley S.; Booza, Jason C.; Cote, Michele; Schwartz, Ann G.; Eggly, Susan; Epidemiology, Richard M. Fairbanks School of Public HealthRacial disparities in cancer incidence and outcomes are well-documented in the US, with Black people having higher incidence rates and worse outcomes than White people. In this review, we present a summary of almost 30 years of research conducted by investigators at the Karmanos Cancer Institute's (KCI's) Population Studies and Disparities Research (PSDR) Program focusing on Black-White disparities in cancer incidence, care, and outcomes. The studies in the review focus on individuals diagnosed with cancer from the Detroit Metropolitan area, but also includes individuals included in national databases. Using an organizational framework of three generations of studies on racial disparities, this review describes racial disparities by primary cancer site, disparities associated with the presence or absence of comorbid medical conditions, disparities in treatment, and disparities in physician-patient communication, all of which contribute to poorer outcomes for Black cancer patients. While socio-demographic and clinical differences account for some of the noted disparities, further work is needed to unravel the influence of systemic effects of racism against Black people, which is argued to be the major contributor to disparate outcomes between Black and White patients with cancer. This review highlights evidence-based strategies that have the potential to help mitigate disparities, improve care for vulnerable populations, and build an equitable healthcare system. Lessons learned can also inform a more equitable response to other health conditions and crises.Item A risk prediction tool for individuals with a family history of breast, ovarian, or pancreatic cancer: BRCAPANCPRO(Springer Nature, 2021) Blackford, Amanda L.; Childs, Erica J.; Porter, Nancy; Petersen, Gloria M.; Rabe, Kari G.; Gallinger, Steven; Borgida, Ayelet; Syngal, Sapna; Cote, Michele L.; Schwartz, Ann G.; Goggins, Michael G.; Hruban, Ralph H.; Parmigiani, Giovanni; Klein, Alison P.; Epidemiology, Richard M. Fairbanks School of Public HealthIntroduction: Identifying families with an underlying inherited cancer predisposition is a major goal of cancer prevention efforts. Mendelian risk models have been developed to better predict the risk associated with a pathogenic variant of developing breast/ovarian cancer (with BRCAPRO) and the risk of developing pancreatic cancer (PANCPRO). Given that pathogenic variants involving BRCA2 and BRCA1 predispose to all three of these cancers, we developed a joint risk model to capture shared susceptibility. Methods: We expanded the existing framework for PANCPRO and BRCAPRO to jointly model risk of pancreatic, breast, and ovarian cancer and validated this new model, BRCAPANCPRO on three data sets each reflecting the common target populations. Results: BRCAPANCPRO outperformed the prior BRCAPRO and PANCPRO models and yielded good discrimination for differentiating BRCA1 and BRCA2 carriers from non-carriers (AUCs 0.79, 95% CI: 0.73-0.84 and 0.70, 95% CI: 0.60-0.80) in families seen in high-risk clinics and pancreatic cancer family registries, respectively. In addition, BRCAPANCPRO was reasonably well calibrated for predicting future risk of pancreatic cancer (observed-to-expected (O/E) ratio = 0.81 [0.69, 0.94]). Discussion: The BRCAPANCPRO model provides improved risk assessment over our previous risk models, particularly for pedigrees with a co-occurrence of pancreatic cancer and breast and/or ovarian cancer.Item A Systematic Review and Meta-Analysis on the Prognostic Value of BRCA Mutations, Homologous Recombination Gene Mutations, and Homologous Recombination Deficiencies in Cancer(Hindawi, 2022-07-20) Shao, Changxia; Chang, Michael S.; Lam, Fred C.; Marley, Andrew R.; Tang, Huilin; Song, Yiqing; Miller, Chelsey; Brown, Madeline; Wan, Isabella; Han, Jiali; Adeboyeje, Gboyega; Epidemiology, Richard M. Fairbanks School of Public HealthPatients with BRCA1/2 mutations (BRCAm), loss-of-function mutations in other homologous recombination repair (HRRm) genes, or tumors that are homologous recombination deficiency positivity (HRD+) demonstrate a robust response to PARPi therapy. We conducted a systematic literature review and meta-analysis to evaluate the prognostic value of BRCAm, HRRm, and HRD+ on overall survival (OS) among those treated by chemotherapy or targeted therapy other than PARPi across tumor types. A total of 135 eligible studies were included. Breast cancer (BC) patients with BRCA1/2m had a similar overall survival (OS) to those with wild-type BRCA1/2 (BRCA1/2 wt) across 18 studies. Ovarian cancer (OC) patients with BRCA1/2m had a significantly longer OS than those with BRCA1/2 wt across 24 studies reporting BRCA1m and BRCA2m, with an HR of 0.7 (0.6-0.8). Less OS data were reported for other tumors: 6 studies for BRCA2m compared with BRCA2 wt in prostate cancer with an HR of 1.9 (1.1-3.2) and 2 studies for BRCA1/2m compared with BRCA1/2 wt in pancreatic cancer with an HR of 1.5 (0.8-3.1). Only 4 studies reported HRD+ by either BRCA m or genomic instability score (GIS) ≥ 42 and OS by HRD status. The HR was 0.67 (0.43-1.02) for OS with HRD+ vs. HRD-. A total of 15 studies reported the association between HRRm and OS of cancers in which one or more HRR genes were examined. The HR was 1.0 (0.7-1.4) comparing patients with HRRm to those with HRR wild-type across tumors. Our findings are useful in improving the precision and efficacy of treatment selection in clinical oncology.Item Adapting ethical guidelines for adolescent health research to street-connected children and youth in low- and middle-income countries: a case study from western Kenya(Springer (Biomed Central Ltd.), 2015-12-18) Embleton, L.; Ott, Mary A.; Wachira, J.; Naanyu, V.; Kamanda, A.; Makori, D.; Ayuku, D.; Braitstein, P.; Department of Epidemiology, Richard M. Fairbanks School of Public HealthBACKGROUND: Street-connected children and youth (SCCY) in low- and middle-income countries (LMIC) have multiple vulnerabilities in relation to participation in research. These require additional considerations that are responsive to their needs and the social, cultural, and economic context, while upholding core ethical principles of respect for persons, beneficence, and justice. The objective of this paper is to describe processes and outcomes of adapting ethical guidelines for SCCY's specific vulnerabilities in LMIC. METHODS: As part of three interrelated research projects in western Kenya, we created procedures to address SCCY's vulnerabilities related to research participation within the local context. These consisted of identifying ethical considerations and solutions in relation to community engagement, equitable recruitment, informed consent, vulnerability to coercion, and responsibility to report. RESULTS: Substantial community engagement provided input on SCCY's participation in research, recruitment, and consent processes. We designed an assent process to support SCCY to make an informed decision regarding their participation in the research that respected their autonomy and their right to dissent, while safeguarding them in situations where their capacity to make an informed decision was diminished. To address issues related to coercion and access to care, we worked to reduce the unequal power dynamic through street outreach, and provided access to care regardless of research participation. CONCLUSIONS: Although a vulnerable population, the specific vulnerabilities of SCCY can to some extent be managed using innovative procedures. Engaging SCCY in ethical research is a matter of justice and will assist in reducing inequities and advancing their health and human dignity.Item Adult BMI change and risk of Breast Cancer: National Health and Nutrition Examination Survey (NHANES) 2005-2010(Springer-Verlag, 2015-11) Gathirua-Mwangi, Wambui G.; Zollinger, Terrell W.; Murage, Mwangi J.; Pradhan, Kamnesh R.; Champion, Victoria L.; Department of Epidemiology, Richard M. Fairbanks School of Public HealthOBJECTIVE: Breast cancer is the second leading cause of cancer mortality among women in the developed world. This study assessed the association between occurrence of breast cancer and body mass index (BMI) change from age 25 to age closest to breast cancer diagnosis while exploring the modifying effects of demographic variables. METHODS: The National Health and Nutrition Examination Survey data were used. Women included were ≥50 years, not pregnant and without a diagnosis of any cancer but breast. The total sample included 2895 women (172 with breast cancer and 2723 controls with no breast cancer diagnosis). Multivariate logistic regression was used to estimate the OR and 95 % CIs and interaction evaluated by including an interaction term in the model. RESULTS: Women whose BMI increased from normal or overweight to obese compared to those who remained at a normal BMI were found to have a 2 times higher odds (OR = 2.1; 95 % CI 1.11-3.79) of developing breast cancer. No significant association was observed for women who increased to overweight. However, a more pronounced association was observed in non-Hispanic black women (OR = 6.6; 95 % CI 1.68-25.86) and a significant association observed when they increased from normal to overweight (OR = 4.2; 95 % CI 1.02-17.75). CONCLUSIONS: Becoming obese after age 25 is associated with increased risk of breast cancer in women over 50 years old, with non-Hispanic black women being at greatest risk.Item Adverse effects of incretin-based therapies on major cardiovascular and arrhythmia events: meta-analysis of randomized trials(Wiley, 2016-11) Wang, Tiansheng; Wang, Fei; Zhou, Junwen; Tang, Huilin; Giovenale, Sharon; Department of Epidemiology, Richard M. Fairbanks School of Public HealthRecent cardiovascular outcome trials of incretin-based therapies (IBT) in type 2 diabetes have not demonstrated either benefit or harm in terms of major adverse cardiovascular events (MACE). Earlier meta-analyses showed conflicting results but were limited in methodology. We aimed to perform an updated meta-analysis of all available incretin therapies on the incidence of MACE plus arrhythmia and heart failure. Methods We identified studies published through November 2014 by searching electronic databases and reference lists. We included RCTs in which the intervention group received incretin-based therapies and the control group received placebo or standard treatment; enrolled >100 participants in each group; interventions lasted >24 weeks; and reported data on one or more primary major adverse cardiovascular events endpoints plus terms for arrhythmia and heart failure. We used the Peto method for each CV event for individual IBT treatment. Results In this meta-analysis of 100 RCTs involving 54,758 incretin-based therapies users and 48,175 controls, exenatide was associated with increased risk of arrhythmia (OR 2.83; 95% CI, 1.06–7.57); saxagliptin was associated with an increased risk of heart failure (OR 1.23; 95% CI, 1.03–1.46), and sitagliptin was associated with a significantly decreased risk of all cause death compared to active controls (OR 0.39, 95% CI 0.18–0.82). Conclusions In type 2 diabetes, exenatide may increase the risk of arrhythmia, and sitagliptin may reduce the risk of all cause death; however, the subgroup of patients most likely to experience harm or benefit is unclear.Item An Adversorial Approach to Enable Re-Use of Machine Learning Models and Collaborative Research Efforts Using Synthetic Unstructured Free-Text Medical Data(IOS, 2019) Kasthurirathne, Suranga N.; Dexter, Gregory; Grannis, Shaun J.; Epidemiology, School of Public HealthWe leverage Generative Adversarial Networks (GAN) to produce synthetic free-text medical data with low re-identification risk, and apply these to replicate machine learning solutions. We trained GAN models to generate free-text cancer pathology reports. Decision models were trained using synthetic datasets reported performance metrics that were statistically similar to models trained using original test data. Our results further the use of GANs to generate synthetic data for collaborative research and re-use of machine learning models.Item Age at Menarche and Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study Among 27,482 Women(American Diabetes Association, 2016-03) Chen, Liwei; Li, Shanshan; He, Chunyan; Zhu, Yeyi; Buck Louis, Germaine M.; Yeung, Edwina; Hu, Frank B.; Zhang, Cuilin; Department of Epidemiology, Richard M. Fairbanks School of Public HealthOBJECTIVE: To examine the association between age at menarche and risk of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: A prospective cohort study of 42,109 eligible pregnancies from 27,482 women in the Nurses' Health Study II. RESULTS: The adjusted risk ratios for GDM across the age at menarche categories (≤11, 12, 13, and ≥14 years) were 1.34 (95% CI 1.14-1.58), 1.13 (0.97-1.31), 1.11 (0.95-1.29), and 1.00 (referent; P for trend = 0.0005), respectively. Analysis of the mediating effect indicated that 42.1% (P = 0.0007) of the association was mediated through prepregnancy BMI. CONCLUSIONS: These findings suggested that earlier menarche was significantly associated with an increased risk of GDM. This association was largely mediated through prepregnancy excessive body adiposity.Item Alcohol intake is associated with increased risk of squamous cell carcinoma of the skin: three US prospective cohort studies(Taylor & Francis, 2016-05) Siiskonen, Satu; Han, Jiali; Li, Tricia; Cho, Eunyoung; Nijsten, Tamar; Qureshi, Abrar; Department of Epidemiology, School of Public HealthThe association between alcohol intake and cutaneous squamous cell carcinoma (cSCC) is unclear. We studied the association between alcohol intake and incident invasive cSCC in three cohorts of women and men with repeated assessments of alcohol intake in the US. Information on alcohol intake was collected repeatedly during follow-up. Cumulative average of alcohol intakes was used. Multivariable Cox proportional hazards models with time-dependent exposure were used to estimate relative risks (RRs) and 95% confidence intervals, followed by a meta-analysis. During a follow-up of 4,234,416 person-years, 2,938 cSCC were identified. Alcohol intake was associated with an increased risk of cSCC with a dose-response relationship. Each additional drink (12.8 gram of alcohol) per day was associated with a 22% increased risk of cSCC (RR 1.22, 95% confidence interval: 1.13-1.31). White wine consumption of ≥5 times/wk was associated with an increased risk of cSCC (RR 1.31, 95% confidence interval: 1.09-1.59). We found no increased risk of cSCC with other alcoholic beverages. The population-attributable risk associated with alcohol intake of ≥20 grams/d was 3% of cSCCs. In conclusion, alcohol intake was associated with an elevated risk of cSCC. Among alcoholic beverages, white wine was associated with cSCC.