Age at lung cancer diagnosis in females versus males who never smoke by race and ethnicity.

BACKGROUND: We characterized age at diagnosis and estimated sex differences for lung cancer and its histological subtypes among individuals who never smoke. METHODS: We analyzed the distribution of age at lung cancer diagnosis in 33,793 individuals across 8 cohort studies and two national registries from East Asia, the United States (US) and the United Kingdom (UK). Student's t-tests were used to assess the study population differences (Δ years) in age at diagnosis comparing females and males who never smoke across subgroups defined by race/ethnicity, geographic location, and histological subtypes. RESULTS: We found that among Chinese individuals diagnosed with lung cancer who never smoke, females were diagnosed with lung cancer younger than males in the Taiwan Cancer Registry (n = 29,832) (Δ years = -2.2 (95% confidence interval (CI):-2.5, -1.9), in Shanghai (n = 1049) (Δ years = -1.6 (95% CI:-2.9, -0.3), and in Sutter Health and Kaiser Permanente Hawai'i in the US (n = 82) (Δ years = -11.3 (95% CI: -17.7, -4.9). While there was a suggestion of similar patterns in African American and non-Hispanic White individuals. the estimated differences were not consistent across studies and were not statistically significant. CONCLUSIONS: We found evidence of sex differences for age at lung cancer diagnosis among individuals who never smoke.

Mammographic Screening in Routine Practice: Multisite Study of Digital Breast Tomosynthesis and Digital Mammography Screenings.

Background The use of digital breast tomosynthesis (DBT) is increasing over digital mammography (DM) following studies demonstrating lower recall rates (RRs) and higher cancer detection rates (CDRs). However, inconsistent interpretation of evidence on the risks and benefits of mammography has resulted in varying screening mammography recommendations. Purpose To evaluate screening outcomes among women in the United States who underwent routine DM or DBT mammographic screening. Materials and Methods This retrospective cohort study included women aged 40-79 years who underwent DM or DBT screening mammograms between January 2014 and December 2020. Outcomes of RR, CDR, positive predictive value of recall (PPV1), biopsy rate, and positive predictive value of biopsy (PPV3) were compared between DM and DBT with use of adjusted multivariable logistic regression models. Results A total of 2 528 063 screening mammograms from 1 100 447 women (mean age, 57 years ± 10 [SD]) were included. In crude analyses, DBT (1 693 727 screening mammograms vs 834 336 DM screening mammograms) demonstrated lower RR (10.3% [95% CI: 10.3, 10.4] for DM vs 8.9% [95% CI: 8.9, 9.0] for DBT; P < .001) and higher CDR (4.5 of 1000 screening mammograms [95% CI: 4.3, 4.6] vs 5.3 of 1000 [95% CI: 5.2, 5.5]; P < .001), PPV1 (4.3% [95% CI: 4.2, 4.5] vs 5.9% [95% CI: 5.7, 6.0]; P < .001), and biopsy rates (14.5 of 1000 screening mammograms [95% CI: 14.2, 14.7] vs 17.6 of 1000 [95% CI: 17.4, 17.8]; P < .001). PPV3 was similar between cohorts (30.0% [95% CI: 29.2, 30.9] for DM vs 29.3% [95% CI: 28.7, 29.9] for DBT; P = .16). After adjustment for age, breast density, site, and index year, associations remained stable with respect to statistical significance. Conclusion Women undergoing digital breast tomosynthesis had improved screening mammography outcomes compared with women who underwent digital mammography. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Bae and Seo in this issue.

Factors associated with adherence to provider referrals for lung cancer screening with low dose computed tomography before and during COVID-19 pandemic.

BACKGROUND: Lung cancer has been the leading cause of American deaths from cancer. Although Medicare started covering lung cancer screening (LCS) with low-dose computed tomography (LDCT) in 2015, the uptake of LDCT-LCS remains low. This study examines the changes in adherence to provider referrals for LDCT-LCS and the factors at patient, provider, and health system levels that influence the completion rate of LDCT-LCS orders before and during the COVID-19 pandemic. METHODS: Our study examined electronic health record data (December 2013 - December 2020) from a large, community-based clinical healthcare delivery system in California. We plotted monthly trends in the frequency of LDCT-LCS orders and completion rate and compared the annual LDCT-LCS completion rate between LCS-eligible, LCS-ineligible, and unknown eligibility groups. We then explored multilevel factors associated with the completion of LDCT-LCS orders using hierarchical generalized linear models. RESULTS: There was an increase in LDCT-LCS orders (N = 12,469) from 2013 to 2019, followed by a sharp decline in March 2020 due to the onset of the COVID-19 pandemic. Thereafter, LDCT-LCS orders slowly increased again in June 2020. The completion rate of LDCT-LCS increased from 0% in December 2013 to approximately 70% in 2018-2019 but declined to 50-60% in 2020 during the pandemic. Ineligible patients had lower completion rates of LDCT-LCS. Patients who were new to the healthcare system, Black, received the LDCT-LCS order in the first few years after Medicare coverage (2016 or 2017), during the pandemic, had major comorbidities, and smoked less than 30 pack-years were less likely to complete an order. Patients were more likely to complete LDCT-LCS orders if they were younger, received the LDCT-LCS order from a physician (vs. nonphysician provider), from family medicine or other specialties (vs. internal medicine), or saw a provider with more experience in LDCT-LCS. CONCLUSIONS: The beginning of the COVID-19 pandemic largely decreased the volume of LDCT-LCS orders, but rates have since been slowing recovering. Future interventions to improve lung cancer screening should consider doing more targeted outreach to new patients and Black patients as well as providing additional education to nonphysician practitioners and those providers with lower rates of LDCT-LCS referral orders.

Sequential Targeted Therapy for Advanced, Metastatic, and Recurrent Cervical Cancer: A Cost-Effectiveness Analysis of the Patient Journey.

OBJECTIVES: To evaluate outcomes and cost-effectiveness of targeted therapy sequencing for metastatic and recurrent cervical cancer. METHOD: Models were simulated based on phase II and III trials on bevacizumab (bev) from GOG-240, cemiplimab (cemi) from GOG 3016, pembrolizumab (pembro) from KEYNOTE-826, and tisotumab vedotin (tiso) from GOG 3023. Costs were based on IBM Micromedex RED BOOK™ and company listed costs. RESULTS: For [chemo + bev → chemo], total cost was $125,918.04, with median overall survival (mOS) of 21.8 months, and cost-effectiveness ratio (CER) of $119,835.79. For [chemo + bev → cemi], total cost was $187,562.99 with mOS of 28.5 months and CER of $162,039.16. For [chemo + bev + pembro → chemo], total cost was $319,963.78 with mOS 32.9 months and CER of $249,930.10. For [chemo + bev + pembro → tiso], total cost was $455,204.45, with mOS 36.5 months and CER of $320,072.99. CONCLUSION: The combination of immunotherapies and biologics have significantly increased overall survival, but with associated higher costs, primarily related to drug costs.

"Go ahead and screen" - advice to healthcare systems for routine lynch syndrome screening from interviews with newly diagnosed colorectal cancer patients.

BACKGROUND: Lynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC). Universal tumor screening (UTS) of newly diagnosed CRC cases is recommended to aid in diagnosis of LS and reduce cancer-related morbidity and mortality. However, not all health systems have adopted UTS processes and implementation may be inconsistent due to system and patient-level complexities. METHODS: To identify barriers, facilitators, and suggestions for improvements of the UTS process from the patient perspective, we conducted in-depth, semi-structured interviews with patients recently diagnosed with CRC, but not screened for or aware of LS. Patients were recruited from eight regionally diverse US health systems. Interviews were conducted by telephone, 60-minutes, audio-recorded, and transcribed. An inductive, constant comparative analysis approach was employed.  RESULTS: We completed 75 interviews across the eight systems. Most participants were white (79%), about half (52%) were men, and the mean age was 60 years. Most self-reported either no (60%) or minimal (40%) prior awareness of LS. Overall, 96% of patients stated UTS should be a routine standard of care for CRC tumors, consistently citing four primary motivations for wanting to know their LS status and engage in the process for LS identification: "knowledge is power"; "family knowledge"; "prevention and detection"; and "treatment and surveillance." Common concerns pertaining to the process of screening for and identifying LS included: creating anticipatory worry for patients, the potential cost and the accuracy of the genetic test, and possibly having one's health insurance coverage impacted by the LS diagnosis. Patients suggested health systems communicate LS results in-person or by phone from a trained expert in LS; offer proactive verbal and written education about LS, the screening steps, and any follow-up surveillance recommendations; and support patients in communicating their LS screening to any of their blood relatives. CONCLUSION: Our qualitative findings demonstrate patients with CRC have a strong desire for healthcare systems to regularly implement and offer UTS. Patients offer key insights for health systems to guide future implementation and optimization of UTS and other LS screening programs and maximize diagnosis of individuals with LS and improve cancer-related surveillance and outcomes. TRIAL REGISTRATION: Not available: not a clinical trial.

Road to Better Work-Life Balance? Lean Redesigns and Daily Work Time among Primary Care Physicians.

PURPOSE: To assess the impact of Lean primary care redesigns on the amount of time that physicians spent working each day. METHODS: This observational study was based on 92 million time-stamped Epic® EHR access logs captured among 317 primary care physicians in a large ambulatory care delivery system. Seventeen clinic facilities housing 46 primary care departments were included for study. We conducted interrupted time series analysis to monitor changes in physician work patterns over 6 years. Key measures included total daily work time; time spent on "desktop medicine" outside the exam room; time spent with patients during office visits; time still working after clinic, i.e., after seeing the last patient each day; and remote work time. RESULTS: The amount of time that physicians spent on desktop EHR activities throughout the day, including after clinic hours, decreased by 10.9% (95% CI: -22.2, -2.03) and 8.3% (95% CI: -13.8, -2.12), respectively, during the first year of Lean implementation. Total daily work hours among physicians, which included both desktop activity and time in office visits, decreased by 20% (95% CI: -29.2, -9.60) by the third year of Lean implementation. CONCLUSIONS: These findings suggest that Lean redesign may be associated with time savings for primary care physicians. However, since this was an observational analysis, further study is warranted (e.g., randomized trial) -to determine the impact of Lean interventions on physician work experiences.

Genetic counselors' experience with reimbursement and patient out-of-pocket cost for multi-cancer gene panel testing for hereditary cancer syndromes.

Multi-cancer gene panels for hereditary cancer syndromes (hereditary cancer panels, HCPs) are widely available, and some laboratories have programs that limit patients' out-of-pocket (OOP) cost share. However, little is known about practices by cancer genetic counselors for discussing and ordering an HCP and how insurance reimbursement and patient out-of-pocket share impact these practices. We conducted a survey of cancer genetic counselors based in the United States through the National Society of Genetic Counselors to assess the impact of reimbursement and patient OOP share on ordering of an HCP and hereditary cancer genetic counseling. Data analyses were conducted using chi-square and t tests. We received 135 responses (16% response rate). We found that the vast majority of respondents (94%, 127/135) ordered an HCP for patients rather than single-gene tests to assess hereditary cancer predisposition. Two-thirds of respondents reported that their institution had no protocol related to discussing HCPs with patients. Most respondents (84%, 114/135) indicated clinical indications and patients' requests as important in selecting and ordering HCPs, while 42%, 57/135, considered reimbursement and patient OOP share factors important. We found statistically significant differences in reporting of insurance as a frequently used payment method for HCPs and in-person genetic counseling (84% versus 59%, respectively, p < 0.0001). Perceived patient willingness to pay more than $100 was significantly higher for HCPs than for genetic counseling(41% versus 22%, respectively, p < 0.01). In sum, genetic counselors' widespread selection and ordering of HCPs is driven more by clinical indications and patient preferences than payment considerations. Respondents perceived that testing is more often reimbursed by insurance than genetic counseling, and patients are more willing to pay for an HCP than for genetic counseling. Policy efforts should address this incongruence in reimbursement and patient OOP share. Patient-centered communication should educate patients on the benefit of genetic counseling.

Implementing Lean Quality Improvement in Primary Care: Impact on Efficiency in Performing Common Clinical Tasks.

BACKGROUND: Many primary care practices have adopted Lean techniques to reduce the amount of time spent completing routine tasks. Few studies have evaluated both immediate and sustained impacts of Lean to improve this aspect of primary care work efficiency. OBJECTIVE: To examine 3-year impacts of Lean implementation on the amount of time taken for physicians to complete common clinical tasks. DESIGN: Non-randomized stepped wedge with segmented regression and interrupted time series analysis (January 2011-December 2016). PARTICIPANTS: A total of 317 physician-led teams in 46 primary care departments in a large ambulatory care delivery system. INTERVENTION: Lean redesign was initiated in one pilot site followed by system-wide spread across all primary care departments. Redesigns included standardization of exam room equipment and supplies, streamlining of call management processes, care team co-location, and team management of the electronic inbox. MEASURES: Time-stamped EHR tracking of physicians' completion time for 4 common tasks: (1) office visit documentation and closure of patient charts; (2) telephone call resolution; (3) prescription refill renewal; and (4) response to electronic patient messages. RESULTS: After Lean implementation, we found decreases in the amount of time to complete: office visit documentation (- 29.2% [95% CI: - 44.2, - 10.1]), telephone resolution (- 22.2% [95% CI: - 38.1, - 2.27]), and renewal of prescription refills (- 2.96% per month [95% CI: - 4.21, - 1.78]). These decreases were sustained over several years. Response time to electronic patient messages did not change significantly. CONCLUSIONS: Lean redesigns led to improvements in timely completion of 3 out of 4 common clinical tasks. Our findings support the use of Lean techniques to engage teams in routine aspects of patient care. More research is warranted to understand the mechanisms by which Lean promotes quality improvement and effectiveness of care team workflows.

How, when, and why individuals with stage IV cancer seen in an outpatient setting are referred to palliative care: a mixed methods study.

PURPOSE: Early palliative care (PC) for individuals with advanced cancer improves patient and family outcomes and experience. However, it is unknown when, why, and how in an outpatient setting individuals with stage IV cancer are referred to PC. METHODS: At a large multi-specialty group in the USA with outpatient PC implemented beginning in 2011, clinical records were used to identify adults diagnosed with stage IV cancer after January 1, 2012 and deceased by December 31, 2017 and their PC referrals and hospice use. In-depth interviews were also conducted with 25 members of medical oncology, gynecological oncology, and PC teams and thematically analyzed. RESULTS: A total of 705 individuals were diagnosed and died between 2012 and 2017: of these, 332 (47%) were referred to PC, with 48.5% referred early (within 60 days of diagnosis). Among referred patients, 79% received hospice care, versus 55% among patients not referred. Oncologists varied dramatically in their rates of referral to PC. Interviews revealed four referral pathways: early referrals, referrals without active anti-cancer treatment, problem-based referrals, and late referrals (when stopping treatment). Participants described PC's benefits as enhancing pain/symptom management, advance care planning, transitions to hospice, end-of-life experiences, a larger team, and more flexible patient care. Challenges reported included variation in oncologist practices, patient fears and misconceptions, and access to PC teams. CONCLUSION: We found high rates of use and appreciation of PC. However, interviews revealed that exclusively focusing on rates of referrals may obscure how referrals vary in timing, reason for referral, and usefulness to patients, families, and clinical teams.

Insights From a Temporal Assessment of Increases in US Private Payer Coverage of Tumor Sequencing From 2015 to 2019.

OBJECTIVES: To examine the temporal trajectory of insurance coverage for next-generation tumor sequencing (sequencing) by private US payers, describe the characteristics of coverage adopters and nonadopters, and explore adoption trends relative to the Centers for Medicare and Medicaid Services' National Coverage Determination (CMS NCD) for sequencing. METHODS: We identified payers with positive coverage (adopters) or negative coverage (nonadopters) of sequencing on or before April 1, 2019, and abstracted their characteristics including size, membership in the BlueCross BlueShield Association, and whether they used a third-party policy. Using descriptive statistics, payer characteristics were compared between adopters and nonadopters and between pre-NCD and post-NCD adopters. An adoption timeline was constructed. RESULTS: Sixty-nine payers had a sequencing policy. Positive coverage started November 30, 2015, with 1 payer and increased to 33 (48%) as of April 1, 2019. Adopters were less likely to be BlueCross BlueShield members (P < .05) and more likely to use a third-party policy (P < .001). Fifty-eight percent of adopters were small payers. Among adopters, 52% initiated coverage pre-NCD over a 25-month period and 48% post-NCD over 17 months. CONCLUSIONS: We found an increase, but continued variability, in coverage over 3.5 years. Temporal analyses revealed important trends: the possible contribution of the CMS NCD to a faster pace of coverage adoption, the interdependence in coverage timing among BlueCross BlueShield members, the impact of using a third-party policy on coverage timing, and the importance of small payers in early adoption. Our study is a step toward systematic temporal research of coverage for precision medicine, which will inform policy and affordability assessments.

Implementing universal Lynch syndrome screening (IMPULSS): protocol for a multi-site study to identify strategies to implement, adapt, and sustain genomic medicine programs in different organizational contexts.

BACKGROUND: Systematic screening of all colorectal tumors for Lynch Syndrome (LS) has been recommended since 2009. Currently, implementation of LS screening in healthcare systems remains variable, likely because LS screening involves the complex coordination of multiple departments and individuals across the healthcare system. Our specific aims are to (1) describe variation in LS screening implementation across multiple healthcare systems; (2) identify conditions associated with both practice variation and optimal implementation; (3) determine the relative effectiveness, efficiency, and costs of different LS screening protocols by healthcare system; and (4) develop and test in a real-world setting an organizational toolkit for LS screening program implementation and improvement. This toolkit will promote effective implementation of LS screening in various complex health systems. METHODS: This study includes eight healthcare systems with 22 clinical sites at varied stages of implementing LS screening programs. Guided by the Consolidated Framework for Implementation Research (CFIR), we will conduct in-depth semi-structured interviews with patients and organizational stakeholders and perform economic evaluation of site-specific implementation costs. These processes will result in a comprehensive cross-case analysis of different organizational contexts. We will utilize qualitative data analysis and configurational comparative methodology to identify facilitators and barriers at the organizational level that are minimally sufficient and necessary for optimal LS screening implementation. DISCUSSION: The overarching goal of this project is to combine our data with theories and tools from implementation science to create an organizational toolkit to facilitate implementation of LS screening in various real-world settings. Our organizational toolkit will account for issues of complex coordination of care involving multiple stakeholders to enhance implementation, sustainability, and ongoing improvement of evidence-based LS screening programs. Successful implementation of such programs will ultimately reduce suffering of patients and their family members from preventable cancers, decrease waste in healthcare system costs, and inform strategies to facilitate the promise of precision medicine. TRIAL REGISTRATION: N/A.

The economic value of personalized medicine tests: what we know and what we need to know.

PURPOSE: There is uncertainty about when personalized medicine tests provide economic value. We assessed evidence on the economic value of personalized medicine tests and gaps in the evidence base. METHODS: We created a unique evidence base by linking data on published cost-utility analyses from the Tufts Cost-Effectiveness Analysis Registry with data measuring test characteristics and reflecting where value analyses may be most needed: (i) tests currently available or in advanced development, (ii) tests for drugs with Food and Drug Administration labels with genetic information, (iii) tests with demonstrated or likely clinical utility, (iv) tests for conditions with high mortality, and (v) tests for conditions with high expenditures. RESULTS: We identified 59 cost-utility analyses studies that examined personalized medicine tests (1998-2011). A majority (72%) of the cost/quality-adjusted life year ratios indicate that testing provides better health although at higher cost, with almost half of the ratios falling below $50,000 per quality-adjusted life year gained. One-fifth of the results indicate that tests may save money. CONCLUSION: Many personalized medicine tests have been found to be relatively cost-effective, although fewer have been found to be cost saving, and many available or emerging medicine tests have not been evaluated. More evidence on value will be needed to inform decision making and assessment of genomic priorities.

Amblyopia Care Trends Following Widespread Photoscreener Adoption.

Importance: Amblyopia can result in permanent vision loss if not properly treated before age 7 years. In 2017, the US Preventive Services Task Force recommended that vision screening should occur at least once in all children aged 3 to 5 years to detect amblyopia. Objective: To understand trends and factors associated with screening, referral, or diagnosis of amblyopia before and after photoscreening expansion across a relatively large health care system in late 2017. Design, Setting, and Participants: This is a retrospective cohort study of electronic health record data from patients with a well child care visit at approximately age 3 years (ages 2.75-3.25 years) in a relatively large, multispecialty group practice in Northern California and linked census data between 2015 and 2022. Data were extracted and analyzed from October 2022 through August 2023. Exposures: Patient sex, race and ethnicity, immunization records, previous well child care visits, and census-level median household income. Main Outcomes and Measures: Vision screening, pediatric ophthalmology referral, or amblyopia diagnosis, compared using adjusted odds ratios (AORs). Results: The study included 2015-2017 data from 23 246 patients aged 3 years with at least 1 well child care visit (11 206 [48.2%] female) compared with 2018-2022 postexpansion data from 34 281 patients (16 517 [48.2%] female). The screening rate increased from 5.7% (424 of 7505) in 2015 to 72.1% (4578 of 6354) in 2022. The referral rate increased from 17.0% (1279 of 7505) in 2015 to 23.6% (1836 of 7792) in 2018. The diagnosis rate was 2.7% (200 of 7505) in 2015, peaked at 3.4% (263 of 7792) in 2018, and decreased to 1.4% (88 of 6354) in 2022. Compared with White patients, patients who were Asian, Black, or Hispanic were less likely to be screened (Asian: AOR, 0.80; 95% CI, 0.72-0.88; Black: AOR, 0.71; 95% CI, 0.53-0.96; Hispanic: AOR, 0.88; 95% CI, 0.80-0.97). Compared with White patients, patients who were Asian or Hispanic were more likely to be referred (Asian: AOR, 1.49; 95% CI, 1.36-1.62; Hispanic: AOR, 1.32; 95% CI, 1.18-1.48) and were more likely to be diagnosed (Asian: AOR, 1.29; 95% CI, 1.07-1.56; Hispanic: AOR, 1.67; 95% CI, 1.33-2.11). Conclusions and Relevance: In this study, increased availability of photoscreeners was associated with an increase in overall rates of vision screening for children aged 3 years in a relatively large health care system. Given that US rates of visual impairment are predicted to increase, additional targeted interventions would be needed to address remaining disparities in amblyopia care along patient- and clinician-level factors.

Trends in Detection of Adenoma and Sessile Serrated Lesions Over a Decade in a Community-Based Healthcare System.

INTRODUCTION: Adenoma detection rate (ADR) is an accepted benchmark for screening colonoscopy. Factors driving ADR and its relationship with sessile serrated lesions detection rate (SSLDR) over time remain unclear. We aim to explore patient, physician, and procedural influences on ADR and SSLDR trends. METHODS: Using a large healthcare system in northern California from January 2010 to December 2020, a total of 146,818 screening colonoscopies performed by 33 endoscopists were included. ADR and SSLDR were calculated over time using natural language processing. Logistic regression was used to calculate the odd ratios of patient demographics, physician attributes, and procedural details over time. RESULTS: Between 2010 and 2020, ADR rose from 19.4% to 44.4%, whereas SSLDR increased from 1.6% to 11.6%. ADR increased by 2.7% per year (95% confidence interval 1.9%-3.4%), and SSLDR increased by 1.0% per year (95% confidence interval 0.8%-1.2%). Higher ADR was associated with older age, male sex, higher body mass index, current smoker, higher comorbidities, and high-risk colonoscopy. By contrast, SSLDR was associated with younger age, female sex, white race, and fewer comorbidities. Patient and procedure characteristics did not significantly change over time ( P -interaction >0.05). Longer years in practice and male physician were associated with lower ADR and SSLDR in 2010, but significantly attenuated over time ( P -interaction <0.05). DISCUSSION: Both ADR and SSLDR have increased over time. Patient and procedure factors did not significantly change over time. Male endoscopist and longer years in practice had lower initial ADR and SSLDR, but significantly lessened over time.

Risk of Gastric Adenocarcinoma in a Multiethnic Population Undergoing Routine Care: An Electronic Health Records Cohort Study.

BACKGROUND: Gastric adenocarcinoma (GAC) is often diagnosed at advanced stages and portends a poor prognosis. We hypothesized that electronic health records (EHR) could be leveraged to identify individuals at highest risk for GAC from the population seeking routine care. METHODS: This was a retrospective cohort study, with endpoint of GAC incidence as ascertained through linkage to an institutional tumor registry. We utilized 2010 to 2020 data from the Palo Alto Medical Foundation, a large multispecialty practice serving Northern California. The analytic cohort comprised individuals ages 40-75 receiving regular ambulatory care. Variables collected included demographic, medical, pharmaceutical, social, and familial data. Electronic phenotyping was based on rule-based methods. RESULTS: The cohort comprised 316,044 individuals and approximately 2 million person-years (p-y) of observation. 157 incident GACs occurred (incidence 7.9 per 100,000 p-y), of which 102 were non-cardia GACs (incidence 5.1 per 100,000 p-y). In multivariable analysis, male sex [HR: 2.2, 95% confidence interval (CI): 1.6-3.1], older age, Asian race (HR: 2.5, 95% CI: 1.7-3.7), Hispanic ethnicity (HR: 1.9, 95% CI: 1.1-3.3), atrophic gastritis (HR: 4.6, 95% CI: 2.2-9.3), and anemia (HR: 1.9, 95% CI: 1.3-2.6) were associated with GAC risk; use of NSAID was inversely associated (HR: 0.3, 95% CI: 0.2-0.5). Older age, Asian race, Hispanic ethnicity, atrophic gastritis, and anemia were associated with non-cardia GAC. CONCLUSIONS: Routine EHR data can stratify the general population for GAC risk. IMPACT: Such methods may help triage populations for targeted screening efforts, such as upper endoscopy.

Software Application Profile: dynamicLM-a tool for performing dynamic risk prediction using a landmark supermodel for survival data under competing risks.

MOTIVATION: Providing a dynamic assessment of prognosis is essential for improved personalized medicine. The landmark model for survival data provides a potentially powerful solution to the dynamic prediction of disease progression. However, a general framework and a flexible implementation of the model that incorporates various outcomes, such as competing events, have been lacking. We present an R package, dynamicLM, a user-friendly tool for the landmark model for the dynamic prediction of survival data under competing risks, which includes various functions for data preparation, model development, prediction and evaluation of predictive performance. IMPLEMENTATION: dynamicLM as an R package. GENERAL FEATURES: The package includes options for incorporating time-varying covariates, capturing time-dependent effects of predictors and fitting a cause-specific landmark model for time-to-event data with or without competing risks. Tools for evaluating the prediction performance include time-dependent area under the ROC curve, Brier Score and calibration. AVAILABILITY: Available on GitHub [https://github.com/thehanlab/dynamicLM].

Antimicrobial exposure is associated with decreased survival in triple-negative breast cancer.

Antimicrobial exposure during curative-intent treatment of triple-negative breast cancer (TNBC) may lead to gut microbiome dysbiosis, decreased circulating and tumor-infiltrating lymphocytes, and inferior outcomes. Here, we investigate the association of antimicrobial exposure and peripheral lymphocyte count during TNBC treatment with survival, using integrated electronic medical record and California Cancer Registry data in the Oncoshare database. Of 772 women with stage I-III TNBC treated with and without standard cytotoxic chemotherapy - prior to the immune checkpoint inhibitor era - most (654, 85%) used antimicrobials. Applying multivariate analyses, we show that each additional total or unique monthly antimicrobial prescription is associated with inferior overall and breast cancer-specific survival. This antimicrobial-mortality association is independent of changes in neutrophil count, is unrelated to disease severity, and is sustained through year three following diagnosis, suggesting antimicrobial exposure negatively impacts TNBC survival. These results may inform mechanistic studies and antimicrobial prescribing decisions in TNBC and other hormone receptor-independent cancers.

A picture is worth a thousand words: advancing the use of visualization tools in implementation science through process mapping and matrix heat mapping.

BACKGROUND: Identifying key determinants is crucial for improving program implementation and achieving long-term sustainment within healthcare organizations. Organizational-level complexity and heterogeneity across multiple stakeholders can complicate our understanding of program implementation. We describe two data visualization methods used to operationalize implementation success and to consolidate and select implementation factors for further analysis. METHODS: We used a combination of process mapping and matrix heat mapping to systematically synthesize and visualize qualitative data from 66 stakeholder interviews across nine healthcare organizations, to characterize universal tumor screening programs of all newly diagnosed colorectal and endometrial cancers and understand the influence of contextual factors on implementation. We constructed visual representations of protocols to compare processes and score process optimization components. We also used color-coded matrices to systematically code, summarize, and consolidate contextual data using factors from the Consolidated Framework for Implementation Research (CFIR). Combined scores were visualized in a final data matrix heat map. RESULTS: Nineteen process maps were created to visually represent each protocol. Process maps identified the following gaps and inefficiencies: inconsistent execution of the protocol, no routine reflex testing, inconsistent referrals after a positive screen, no evidence of data tracking, and a lack of quality assurance measures. These barriers in patient care helped us define five process optimization components and used these to quantify program optimization on a scale from 0 (no program) to 5 (optimized), representing the degree to which a program is implemented and optimally maintained. Combined scores within the final data matrix heat map revealed patterns of contextual factors across optimized programs, non-optimized programs, and organizations with no program. CONCLUSIONS: Process mapping provided an efficient method to visually compare processes including patient flow, provider interactions, and process gaps and inefficiencies across sites, thereby measuring implementation success via optimization scores. Matrix heat mapping proved useful for data visualization and consolidation, resulting in a summary matrix for cross-site comparisons and selection of relevant CFIR factors. Combining these tools enabled a systematic and transparent approach to understanding complex organizational heterogeneity prior to formal coincidence analysis, introducing a stepwise approach to data consolidation and factor selection.

Second Primary Lung Cancer Among Lung Cancer Survivors Who Never Smoked.

Importance: Lung cancer among never-smokers accounts for 25% of all lung cancers in the US; recent therapeutic advances have improved survival among patients with initial primary lung cancer (IPLC), who are now at high risk of developing second primary lung cancer (SPLC). As smoking rates continue to decline in the US, it is critical to examine more closely the epidemiology of lung cancer among patients who never smoked, including their risk for SPLC. Objective: To estimate and compare the cumulative SPLC incidence among lung cancer survivors who have never smoked vs those who have ever smoked. Design, Setting, and Participants: This population-based prospective cohort study used data from the Multiethnic Cohort Study (MEC), which enrolled participants between April 18, 1993, and December 31, 1996, with follow-up through July 1, 2017. Eligible individuals for this study were aged 45 to 75 years and had complete smoking data at baseline. These participants were followed up for IPLC and further SPLC development through the Surveillance, Epidemiology, and End Results registry. The data were analyzed from July 1, 2022, to January 31, 2023. Exposures: Never-smoking vs ever-smoking exposure at MEC enrollment. Main Outcomes and Measures: The study had 2 primary outcomes: (1) 10-year cumulative incidence of IPLC in the entire study cohort and 10-year cumulative incidence of SPLC among patients with IPLC and (2) standardized incidence ratio (SIR) (calculated as the SPLC incidence divided by the IPLC incidence) by smoking history. Results: Among 211 414 MEC participants, 7161 (3.96%) developed IPLC over 4 038 007 person-years, and 163 (2.28%) developed SPLC over 16 470 person-years. Of the participants with IPLC, the mean (SD) age at cohort enrollment was 63.6 (7.7) years, 4031 (56.3%) were male, and 3131 (43.7%) were female. The 10-year cumulative IPLC incidence was 2.40% (95% CI, 2.31%-2.49%) among ever-smokers, which was 7 times higher than never-smokers (0.34%; 95% CI, 0.30%-0.37%). However, the 10-year cumulative SPLC incidence following IPLC was as high among never-smokers (2.84%; 95% CI, 1.50%-4.18%) as ever-smokers (2.72%; 95% CI, 2.24%-3.20%), which led to a substantially higher SIR for never-smokers (14.50; 95% CI, 8.73-22.65) vs ever-smokers (3.50; 95% CI, 2.95-4.12). Conclusions and Relevance: The findings indicate that SPLC risk among lung cancer survivors who never smoked is as high as among those with IPLC who ever-smoked, highlighting the need to identify risk factors for SPLC among patients who never smoked and to develop a targeted surveillance strategy.