Association of metformin use and cancer incidence: a systematic review and meta-analysis.

BACKGROUND: Metformin is among the most widely used antidiabetics medications because of its minimal toxicity, favorable safety profile, availability, and low cost. In addition to its role in diabetes management, metformin may reduce cancer risk. METHODS: We conducted a comprehensive systematic review and meta-analysis to investigate the association between metformin use and cancer risk, with evaluation by specific cancer type when possible. Applicable studies were identified in PubMed/MEDLINE, Embase, Cochrane Library, Web of Science, and Scopus from inception through March 7, 2023, with metformin use categorized as "ever" or "yes" and a cancer diagnosis as the outcome. Article quality was evaluated using National Heart, Lung, and Blood Institute guidelines, and publication bias was evaluated using the Egger test, Begg test, and funnel plots. Pooled relative risk (RR) estimates were calculated using random-effects models, and sensitivity analysis was completed through leave-one-out cross-validation. RESULTS: We included 166 studies with cancer incidence information in the meta-analysis. Reduced risk for overall cancer was observed in case-control studies (RR = 0.55, 95% confidence interval [CI] = 0.30 to 0.80) and prospective cohort studies (RR = 0.65, 95% CI = 0.37 to 0.93). Metformin use was associated with reduced gastrointestinal (RR = 0.79, 95% CI = 0.73 to 0.85), urologic (RR = 0.88, 95% CI = 0.78 to 0.99), and hematologic (RR = 0.87, 95% CI = 0.75 to 0.99) cancer risk. Statistically significant publication bias was observed within the studies (Egger P < .001). CONCLUSIONS: Metformin may be associated with a decreased risk of many cancer types, but high heterogeneity and risk of publication bias limit confidence in these results. Additional studies in populations without diabetes are needed to better understand the utility of metformin in cancer prevention.

Accuracy of Cancer Registry Primary Payer Information and Implications for Policy Research.

BACKGROUND: Cancer registry-based "primary payer at diagnosis" (PPDx) data are commonly used to evaluate the effect of insurance on cancer care outcomes, yet little is known about how well they capture Medicaid or Medicare enrollment. METHODS: We linked the National Cancer Institute's Surveillance, Epidemiology, and End Results registry data to monthly Centers for Medicare and Medicaid Services (CMS) Medicaid and Medicare enrollment records, state-year Medicaid policy, and managed care enrollment. We selected adults aged 19-64 years diagnosed between 2007 and 2011. We used bivariate analyses to compare PPDx to CMS enrollment at diagnosis month and assessed underreporting rates by patient characteristics and state-year policy. RESULTS: PPDx reported 7.8% Medicare and 10.1% Medicaid, whereas CMS enrollment indicated 5.5% Medicare, 10.4% Medicaid, and 3.4% dual Medicare-Medicaid (N = 896,031). Positive predictive values for PPDx assignment to Medicaid and Medicare were 65.3% and 75.4%, with false negative rates of 52.0% and 33.8%, respectively. Medicaid underreporting was higher in low (56.5%) versus high (50.8%) poverty areas, for males (56.1%) versus females (48.9%), for Medicaid poverty expansion or waiver enrolled (63.8%) versus cash assistance-related eligibility (47.3%), and in states with large managed care enrollment (all P < 0.001). If Medicaid and Medicare enrollment data were used to edit PPDx, 12.0% of persons would switch primary payer assignment. CONCLUSIONS: Registry-reported PPDx fails to fully capture Medicaid and Medicare enrollment, which may result in biased estimates of insurance-related policy impacts. Enhancement with objective enrollment data could reduce measurement error and bias in estimates necessary to support policy assessment.

Cancer and COVID-19: US cancer incidence rates during the first year of the pandemic.

BACKGROUND: The COVID-19 pandemic has had a profound global impact on health-care systems and patient outcomes. However, the specific effects of the pandemic on cancer incidence rates in the United States during its initial year remain unknown. METHODS: In this study, we analyzed data from the Surveillance, Epidemiology, and End Results-22 registries, which encompass approximately 50% of the US population. We investigated changes in monthly incidence rates stratified by various factors, including cancer type, stage, age group, sex, race and ethnicity, socioeconomic status, rural-urban status, and registry locations. We compared the incidence rates observed during the pandemic with those from the previous year. RESULTS: Our findings revealed a decline in incidence rates for all cancer sites combined starting in March 2020, coinciding with the implementation of stay-at-home orders. This decline reached its lowest point in April 2020 and persisted at a lower level until May 2020. Notably, compared with April 2019, the incidence rates in April 2020 dropped by 48.1% and did not consistently return to prepandemic levels. The reduction in cancer rates was more pronounced in urban and affluent counties. Across all cancer types, there was a statistically significant decrease in incidence rates during the pandemic, with the largest declines observed in thyroid (71.2%), prostate (57.9%), breast (54.9%), and colon and rectum cancers (54.1%). Furthermore, these decreases were primarily observed in early stage rather than late-stage disease. CONCLUSIONS: The COVID-19 pandemic had a statistically significant impact on cancer outcomes. Monitoring long-term consequences of the pandemic on cancer incidence, stage at diagnosis, and mortality trends will be crucial.

Opportunities, challenges, and future directions for simulation modeling the effects of structural racism on cancer mortality in the United States: a scoping review.

PURPOSE: Structural racism could contribute to racial and ethnic disparities in cancer mortality via its broad effects on housing, economic opportunities, and health care. However, there has been limited focus on incorporating structural racism into simulation models designed to identify practice and policy strategies to support health equity. We reviewed studies evaluating structural racism and cancer mortality disparities to highlight opportunities, challenges, and future directions to capture this broad concept in simulation modeling research. METHODS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review Extension guidelines. Articles published between 2018 and 2023 were searched including terms related to race, ethnicity, cancer-specific and all-cause mortality, and structural racism. We included studies evaluating the effects of structural racism on racial and ethnic disparities in cancer mortality in the United States. RESULTS: A total of 8345 articles were identified, and 183 articles were included. Studies used different measures, data sources, and methods. For example, in 20 studies, racial residential segregation, one component of structural racism, was measured by indices of dissimilarity, concentration at the extremes, redlining, or isolation. Data sources included cancer registries, claims, or institutional data linked to area-level metrics from the US census or historical mortgage data. Segregation was associated with worse survival. Nine studies were location specific, and the segregation measures were developed for Black, Hispanic, and White residents. CONCLUSIONS: A range of measures and data sources are available to capture the effects of structural racism. We provide a set of recommendations for best practices for modelers to consider when incorporating the effects of structural racism into simulation models.

Community and partner engagement in dissemination and implementation research at the National Institutes of Health: an analysis of recently funded studies and opportunities to advance the field.

BACKGROUND: As the focus has grown in recent years on both engaged research and dissemination and implementation (D&I) research, so too has federal funding to support these areas. The purpose of this analysis is to provide an overall perspective about the range of practices and approaches being used to engage partners in D&I research, with special attention to disparities-relevant research, and to identify gaps and opportunities in research funded by the US National Institutes of Health (NIH) in this space. METHODS: This analysis examined a portfolio of active D&I research grants funded in fiscal years 2020 and 2021 across the NIH. Grant applications were deductively coded and summary statistics were calculated. Cross-tabulations were used to identify trends by engagement and disparities foci. RESULTS: There were 103 grants included in the portfolio, of which 87% contained some form of community or partner engagement, and 50% of engaged grants were relevant to health disparities. Engagement was planned across the research continuum with each study engaging on average 2.5 different partner types. Consultation was the most common level of engagement (56%) while partnership was the least common (3%). On average, each study used 2.2 engagement strategies. Only 16% of grants indicated formally measuring engagement. Compared to non-disparities studies, disparities-relevant studies were about twice as likely to engage partners at the higher levels of partnership or collaboration (19% vs. 11%) and were also more likely to be conducted in community settings (26% vs. 5%). CONCLUSIONS: Based on this portfolio analysis, D&I research appears to regularly integrate engagement approaches and strategies, though opportunities to deepen engagement and diversify who is engaged remain. This manuscript outlines several gaps in the portfolio and describes opportunities for increasing engagement to improve the quality of D&I research and application to advancing health equity. In addition, opportunities for leveraging the consistent and systematic application of engagement approaches and strategies to advance the science of engagement are discussed.

The Impact of Improved Treatments on Survival of Adult U.S. Leukemia Patients: 1990-2018.

INTRODUCTION: Molecularly targeted therapies such as tyrosine kinase inhibitors (TKI) are effective treatments for B-cell receptor (BCR)-ABL-bearing leukemias. We evaluated the impact of TKIs on historical chronic myeloid leukemia (CML) mortality trends compared with acute lymphoblastic leukemia (ALL) and chronic lymphoblastic leukemia (CLL). METHODS: Because mortality trends reflect combined effects of leukemia incidence and survival, we also evaluated the contribution of incidence and survival trends to mortality trends by subtypes. We used data from 13 U.S. (SEER) registries (1992-2017) among U.S. adults. We utilized histology codes to identify cases of CML, ALL, and CLL and death certificate data to calculate mortality. We used Joinpoint to characterize incidence (1992-2017) and mortality (1992-2018) trends by subtype and diagnosis year. RESULTS: For CML, mortality rates started declining in 1998 at an average rate of 12% annually. Imatinib was approved by the FDA for treating CML and ALL in 2001, leading to clear benefits for patients with CML. Five-year CML survival increased dramatically over time, especially between 1996 to 2011, 2.3% per year on average. ALL incidence increased 1.5% annually from 1992 to 2017. ALL mortality decreased 0.6% annually during 1992 to 2012 and then stopped declining. CLL incidence fluctuated during 1992 to 2017 while mortality decreased 1.1% annually during 1992 to 2011 and at a faster rate of 3.6% per year from 2011. Five-year survival increased 0.7% per year on average during 1992 to 2016. CONCLUSIONS: Survival benefit from TKIs and other novel therapies for treating leukemia subtypes has been demonstrated in clinical trials. IMPACT: Our study highlights the impact of molecularly targeted therapies at the population level.

Impact of a pre-existing diagnosis of mental illness on stage of breast cancer diagnosis among older women.

PURPOSE: Having a mental illness increases risk of mortality for women with breast cancer, partly due to barriers to accessing recommended care (e.g., cancer screening). Early detection is one important factor in breast cancer survival. To further understand this disparity in survival, we examined whether older women with mental illness are more likely to be diagnosed with later-staged breast cancers compared to women without mental illnesses. METHODS: We used 2005-2015 SEER-Medicare data to identify AJCC stage I-IV breast cancer patients with and without a history of mental illness prior to cancer diagnosis. We used generalized ordinal regression to examine associations between mental illness diagnoses and stage at diagnosis, controlling for age, race/ethnicity, income, comorbidities, primary care use, rurality, and marital status. RESULTS: Among 96,034 women with breast cancer, 1.7% have a serious mental illness (SMI), 19.9% depression or anxiety, and 7.0% other mental illness. Those with SMI have 40% higher odds of being diagnosed with AJCC Stages II, III than Stage I; women with depression/anxiety have 25% lower odds of being diagnosed with Stage IV cancer than Stage I; and women with other mental illnesses have similar odds of being diagnosed in later stages. CONCLUSION: Women with SMI have higher odds of being diagnosed at later stages, which likely contributes to higher mortality after breast cancer. Surprisingly, women with depression and anxiety have a lower risk of being diagnosed with Stage IV cancer. Earlier breast cancer diagnosis in women with SMI is an important goal for reducing disparities breast cancer survival.

Smoking reduction among homeless smokers in a randomized controlled trial targeting cessation.

INTRODUCTION: Homeless populations have high rates of smoking and unique barriers to quitting. General cessation strategies have been unsuccessful in this population. Smoking reduction may be a good intermediate goal. We conducted a secondary analysis to identify predictors of smoking reduction in a cohort of homeless smokers enrolled in a 26-week randomized clinical trial (RCT) targeting smoking cessation. METHODS: Data are from an RCT comparing motivational interviewing counseling plus nicotine replacement therapy (NRT) to brief advice to quit (standard care) plus NRT among homeless smokers. Using bivariate analyses and multinomial logistic regression, we compared demographics, health and psychosocial variables, tobacco use, substance use, and NRT adherence among those who reported: quitting; reducing smoking by 50-99%; and not reducing smoking by 50%. RESULTS: Of 324 participants who completed 26-week follow-up, 18.8% and 63.9% self-reported quitting and reducing, respectively. Compared to those who did not reduce smoking, participants reporting reducing indicated higher baseline cigarette use (OR=1.08; CI:1.04-1.12) and menthol use (OR=2.24; CI:1.05-4.77). Compared to participants who reduced, participants reporting quitting were more likely to be male (OR=1.998; CI:1.00-3.98), experience more housing instability (OR=1.97; CI:1.08-3.59), indicate higher importance of quitting (OR=1.27; CI:1.041.55), have higher NRT adherence (OR=1.75; CI:1.00-3.06), and lower odds of reported illicit drug use (OR=0.48; CI:0.24-0.95). CONCLUSIONS: Over half of participants reduced smoking by at least 50%, indicating reduction is feasible among homeless smokers. Further research is required to understand the impact of reduction on future cessation attempts in homeless smokers. This study shows that reduction is achievable and may be a valid intermediate goal.

Nativity Differences in Awareness and Knowledge About HPV Infection and Vaccination Among U.S. Adults: Findings from a National Population-Based Sample.

Foreign-born populations in the United States suffer multiple disparities related to human papillomavirus, including higher cervical cancer mortality and lower HPV vaccination. No nationally based studies have examined the relationship between nativity with HPV and HPV vaccination awareness and knowledge, especially examining acculturation, an immigration-specific process affecting health-related behaviors. We assessed nativity differences in HPV awareness and knowledge, and awareness of HPV vaccination using data from a population-based sample of adults in the U.S. (n = 2415). Among foreign-born respondents, we also assessed the association of acculturation with outcomes. Awareness of HPV and HPV vaccination were lower among foreign-born respondents compared to U.S.-born respondents. Knowledge of HPV was similar between populations. Acculturation was not associated with any of the assessed outcomes. Findings suggest HPV-related awareness deficits among foreign-born U.S. residents, highlighting a need for culturally-appropriate HPV prevention efforts.

Association of Preoperative Depression and Anxiety With Long-term Opioid Use After Hysterectomy for Benign Indications.

OBJECTIVE: To assess whether preoperative depression or anxiety is associated with increased risk of long-term, postoperative opioid use after hysterectomy among women who are opioid-naïve. METHODS: We conducted an observational cohort study of 289,233 opioid-naïve adult women (18 years or older) undergoing hysterectomy for benign indications from 2010 to 2017 using IBM MarketScan databases. Opioid use and refills in the 180 days after surgery and preoperative depression and anxiety were assessed. Secondary outcomes included 30-day incidence of emergency department visits, readmission, and 180-day incidence of opioid complications. The association of depression and anxiety were compared using inverse-probability of treatment weighted log-binomial and proportional Cox regression. RESULTS: Twenty-one percent of women had preoperative depression or anxiety, and 82% of the entire cohort had a perioperative opioid fill (16% before surgery, 66% after surgery). Although perioperative opioid fills were relatively similar across the two groups (risk ratio [RR] 1.07, 95% CI 1.06-1.07), women with depression or anxiety were significantly more likely to have a postoperative opioid fill at every studied time period (RRs 1.44-1.50). Differences were greater when restricted to persistent use (RRs 1.49-2.61). Although opioid complications were rare, women with depression were substantially more likely to be diagnosed with opioid dependence (hazard ratio [HR] 5.54, 95% CI 4.12-7.44), and opioid use disorder (HR 4.20, 95% CI 1.97-8.96). CONCLUSION: Perioperative opioid fills are common after hysterectomy. Women with preoperative anxiety and depression are more likely to experience persistent use and opioid-related complications.

Cancer survivors exercise at higher intensity in outdoor settings: The GECCOS trial.

PURPOSE: This randomized cross-over group pilot trial assessed feasibility of recruiting survivors from a long-term follow-up clinic to an exercise group and measured whether outdoor or indoor exercise sessions better supported exercise motivation and behaviors in survivors of cancer. METHODS: Sixteen adolescent and young adult survivors of any cancer completed indoor and outdoor exercise sessions in this randomized cross-over pilot trial. Measures of physical activity, motivation, and fatigue were taken 2 weeks before and 2 weeks after indoor sessions and 2 weeks before and 2 weeks after outdoor sessions. Measures of physical activity and fatigue were also taken during each exercise session. RESULTS: Initial recruiting of 19 participants met recruiting goals. Survivors who attended the most sessions lived an average of 8.7 km closer to the clinic. Objectively measured physical activity intensity was 0.63 metabolic equivalents of a task (METs) per minute greater during outdoor exercise sessions as compared to indoor exercise sessions. There were no meaningful differences in long term, habitual physical activity behavior, motivation, or fatigue in the weeks following the outdoor exercise sessions as compared to the indoor exercise sessions. CONCLUSIONS: This study shows the feasibility of recruiting survivors from a long-term follow-up clinic to community-based exercise groups. Although this brief pilot intervention did not show significant effects on habitual physical activity behavior or motivation in adolescent and young adult survivors of cancer, the greater exercise intensity during the outdoor exercise sessions indicate that holding group exercise sessions for survivors outdoors may promote greater intensity during exercise.

Community Gardening as a Way to Build Cross-Cultural Community Resilience in Intersectionally Diverse Gardeners: Community-Based Participatory Research and Campus-Community-Partnered Proposal.

BACKGROUND: Community-based agriculture has been found to decrease food insecurity and alleviate health inequities. Furthermore, it provides a sense of ownership, resources to help integrate new communities, and a space to nurture existing cultural identities for intersectionally diverse gardeners. This sense of belonging in connection with access to growing plots has been linked to psychological well-being and resilience. However, little is known about how the psychosocial benefits of plot ownership affect resilience and which aspects of this resilience are salient. OBJECTIVE: This community-based participatory research (CBPR) project will examine the role of community gardens in decreasing food insecurity and facilitating various forms of resilience in food-insecure groups in Rochester, Minnesota. Since participation in community gardens nurtures various forms of resilience along individual, group, and community dimensions, our research seeks to understand how dimensions of resilience vary along intersectional lines. In addition to mapping the psychosocial benefits linked to plot ownership, we find that examining which forms of resilience are fostered in community-based agricultural projects addresses an important gap in the academic literature. This can help us propose policy-level practices that reduce health inequities connected to food and nutrition at the local level. METHODS: Using a mixed methods approach, this ongoing community-campus partnership will examine the experiences of current and new plot owners. As a CBPR project, our data collection plan, from design to dissemination, incorporates the intellectual and creative labor of the individuals representing members of the campus community (ie, college students and faculty members engaged in other citizen science projects hosted by the garden), community growers, individuals involved in the community garden's board, and representatives of various organizational bodies. Data collection activities will consist of surveys, in-depth interviews, and photovoice. RESULTS: This project was funded in January 2020 and approved by the University of Minnesota's Institutional Review Board in March 2020. For the 2020 growing season, we will conduct evaluative interviews about the effect of COVID-19 on community gardeners, including their experiences during this growing season. For the 2021 growing season, data collection, via pre- and postsurveys, is projected to begin in March 2021 and end in November 2021. We will also conduct in-depth interviews from January to April 2021. Data analysis will commence in April 2021. Photovoice activities (ie, data collection, analysis, synthesis, and dissemination) are expected to take place during the spring and summer of 2021. CONCLUSIONS: Findings emerging from this study will provide the preliminary data to foreground community gardening projects and initiatives to improve physical and mental health outcomes in food-insecure communities. Also, the data collected will highlight the role of CBPR methods in disseminating information about the organizational practices of the community garden; this will assist others in planning and implementing similar projects. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/21218.

Beyond Diversity: Focusing on and Enhancing Inclusion in the Society for Epidemiologic Research.

Increasing diversity and inclusion among organizational membership has become a focus for many professional societies, including the Society for Epidemiologic Research (SER). In this issue of the Journal, DeVilbiss et al. (Am J Epidemiol. 2020:189(10):998-1010) assessed dimensions of diversity and inclusion within SER to provide baseline data for future evaluations of Society initiatives. In our response, we note that diversity in SER appears strong but there is lag with regard to inclusion. We also highlight some of the major weaknesses of this study that hinder efforts to accurately evaluate inclusion within SER. There is a need to more concretely define inclusion and think broadly about how measures of inclusion should be operationalized in future surveys. Additional limitations of the study include its limited generalizability to the wider SER membership and the lack of questions about barriers to inclusion in SER activities. We conclude with recommendations for SER and other professional societies based on prior literature evaluating successful diversity and inclusion efforts. We also propose a conceptual model to assist with operationalizing and directing future analyses of inclusion measures. It is essential that SER move beyond efforts around diversity to focus on measuring and enhancing inclusion.

Nativity status and genital HPV infection among adults in the U.S.

Over 43 million immigrants live in the United States (U.S.). Foreign-born populations experience multiple disparities related to human papillomavirus (HPV), including higher cervical cancer mortality rates, yet little research has examined the prevalence of genital HPV infection among this population. We used data from 1,822 women and 1,622 men ages 20-59 in the U.S. who participated in the 2013-2014 National Health and Nutrition Examination Survey (NHANES). Participants reported their nativity status (foreign- vs. U.S.-born) and provided biospecimens for HPV testing. We assessed nativity differences in the prevalence of three HPV infection outcomes (any HPV type, high-risk HPV type, and vaccine-preventable HPV type) using weighted logistic regression. Overall, 40% of women and 46% of men tested positive for any type of HPV. Compared to women born in the U.S., foreign-born women had a lower prevalence of infection with any HPV type (32% vs. 42%, p < .01). Compared to men born in the U.S., foreign-born men had a lower prevalence of all HPV infection outcomes (any type: 39% vs. 48%; high-risk: 22% vs. 34%; vaccine-preventable: 12% vs. 16%; all p < .05). Multivariable models attenuated several of these differences, though foreign-born men had lower odds of infection with a high-risk HPV type (OR = 0.75; 95% CI: 0.60-0.93, p < .01) after adjusting for covariates. Although lower than among their U.S.-born counterparts, HPV infection is prevalent among foreign-born women and men in the U.S. Findings can help inform strategic communication campaigns and targeted HPV vaccination and cervical cancer screening efforts for immigrant populations.