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Objective: To describe the enrollment rates and characteristics of Hispanics and non-Hispanics from Kaiser Permanente Colorado invited to participate in a web-based intervention promoting increased fruit and vegetable consumption.Design: Hispanics were identified by the Passel-Word Spanish surname list. Characteristics associated with the likelihood of enrollment overall and by ethnicity were examined by logistic regression.Results: A total of 174 (6.1%) probable Hispanics and 340 probable non-Hispanics (11.8%) enrolled. Hispanics were 48% less likely to enroll than non-Hispanics, females were almost four times as likely to enroll as males, and those living in a census tract associated with higher income levels were 41% more likely to enroll than other income groups. Among Hispanics, females were 87% more likely to enroll than males and those living in a census tract associated with higher income levels were 62% more likely to enroll than other income groups. Among non-Hispanics, the odds for enrolling increased 14% for each decade increase of age, females were 43% more likely to enroll than males and those living in a census tract associated with higher income levels were 68% more likely to enroll than those in other income groups.Conclusion: Identifying Hispanics through surname for oversampling can be successful in terms of sampling yield and accuracy. However, our results suggest that Hispanics are less likely to enroll in a web-based nutritional intervention. Additional research is needed to identify methods of attracting more Hispanic subjects to these kinds of interventions. [ABSTRACT FROM AUTHOR]

Objective: This study sought to determine whether a computerized tool that alerted pharmacists when pregnant patients were prescribed U.S. Food and Drug Administration pregnancy risk category D or X medications was effective in decreasing dispensings of these medications.Design: Randomized trial. Pharmacy, diagnostic, and laboratory data were linked to identify pregnant patients prescribed targeted medications. Women (n = 11,100) were randomized to intervention or usual care. Physicians and pharmacists collaborated on the intervention.Measurements: The primary outcome was the proportion of pregnant women dispensed a category D or X medication. The secondary outcome was the total number of first dispensings of targeted medications.Results: A total of 2.9% of intervention (n = 177) and 5.5% of usual care (n = 276) patients were dispensed targeted medications (p < 0.001): 1.8% of intervention (n = 108) and 3.9% of usual care (n = 198) patients were dispensed only category D medication(s); 0.9% of intervention (n = 54) and 1.2% of usual care (n = 58) patients were dispensed only category X medication(s); 0.2% of intervention (n = 15) and 0.4% of usual care (n = 20) patients were dispensed both category D and X medications (p = 0.05). This resulted in intervention patients receiving 238 dispensings of unique targeted medications and usual care patients receiving 361 dispensings of unique targeted medications (p = 0.03). The study was stopped primarily due to 2 false-positive alert types: Misidentification of medications as contraindicated in pregnancy by the pharmacy information system and misidentification of pregnancy related to delayed transfer of diagnosis information.Conclusion: Coupling data from information systems with knowledge and skills of physicians and pharmacists resulted in improved prescribing safety. Systems limitations contributed to project discontinuation. Linking ambulatory clinical, laboratory, and pharmacy information to provide safety alerts is not sufficient to ensure project success and sustainability. [ABSTRACT FROM AUTHOR]

Background: Patients from ethnic and racial minority groups with primary hyperparathyroidism may have greater time delays to curative parathyroidectomy. Contributing factors are unclear., Methods: This was a sequential mixed-methods study. The quantitative phase was a retrospective chart review of adults with primary hyperparathyroidism who underwent parathyroidectomy between 2015 and 2020, collecting demographic and clinical data. Social vulnerability of the patients' residential area, measured with the Social Vulnerability Index, and relevant clinical time intervals were calculated. A multivariable analysis of factors associated with greater time intervals was performed. The qualitative phase involved semistructured interviews with endocrinologists, analyzed inductively for themes., Results: On chart review of 1,083 patients, the median age was determined to be 61 years and 856 (79%) were female. Six hundred twenty-eight (57.9%) were non-Hispanic White and 456 (42.1%) were Hispanic ethnicity or Asian, Pacific Islander, Black, Native American, Other or Unknown race. Patients of Hispanic ethnicity, or Asian or Pacific Islander, Black, Native American, Other or Unknown race were more likely than non-Hispanic White patients to live in the most socially vulnerable areas (19.3% vs 5.9%, P < .01) and had greater time intervals than non-Hispanic White patients between index hypercalcemia and first parathyroid hormone level, surgical referral, or parathyroidectomy (all P < .05). On multivariable analysis, age (coefficient 7.9, 95% CI 2.8-13.0) and living in the most socially vulnerable areas (coefficient 297.9, 95% CI 87-508.7) were associated with greater days between index hypercalcemia and parathyroidectomy. In the study's qualitative phase, identified themes for reasons for care delays included socioeconomic, nonsocioeconomic patient, and nonsocioeconomic nonpatient factors., Conclusion: Care delays are driven by a combination of socioeconomic and nonsocioeconomic factors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

TOETVA's adoption has been slow in the Western hemisphere. Our study aimed to evaluate how endocrine patients in the United States perceive the risks and benefits of TOETVA. This was a cross-sectional study where a de novo survey was sent via email to patients seen from 2018 to 2020. The survey asked how each of TOETVA's risks and benefits affect their choice between traditional thyroidectomy (TT) and TOETVA on a scale from 1 (favors TT) to 10 (favors TOETVA). Statistical significance was determined at p  < 0.05. Of 422 patients (3.2% response rate), 76.0% were female, 28.9% were non-Whites, 58.3% possessing graduate/professional degrees, and 34.1% were diagnosed with thyroid cancer. Significant differences were found between groups of age, race, educational attainment, thyroid cancer diagnosis, and history of thyroid or parathyroid surgery with respect to their preference for thyroidectomy between TT and TOETVA. In multivariate analysis, attitudes towards longer operative time (estimate 0.130, 95% CI 0.026-0.235, p  = 0.002), limited outcome data (estimate 0.142, 95% CI 0.029-0.254, p  = 0.024), having less pain (estimate 0.108, 95% CI 0.004-0.212, p  = 0.042), travel to seek care (estimate 0.166, 95% CI 0.042-0.290, p  = 0.009), as well as African American race (estimate 0.714, 95% CI 0.093-1.334, p  = 0.024), and history of surgery (estimate - 0.843, 95% CI - 1.364- - 0.323, p  = 0.002) were independently predictive of overall preferences. TOETVA's risks and benefits may carry varying degrees of significance in patients' decision-making process, which helps tailor the discussion to choose the right procedure for patients., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Indian Association of Surgical Oncology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: In 2015, the Centers for Medicare & Medicaid Services and commercial insurance plans began covering lung cancer screening (LCS) without patient cost-sharing for all plans. We explore the impact of enrolling into a deductible plan on the utilization of LCS services despite having no out-of-pocket cost requirement., Methods: This retrospective study analyzed data from the Population-based Research to Optimize the Screening Process Lung Consortium. Our cohort included non-Medicare LCS-eligible individuals enrolled in managed care organizations between February 5, 2015, and February 28, 2019. We estimate a series of sequential logistic regression models examining utilization across the sequence of events required for baseline LCS. We report the marginal effects of enrollment into deductible plans compared with enrollment in no-deductible plans., Results: The total effect of deductible plan enrollment was a 1.8 percentage-point (PP) decrease in baseline LCS. Sequential logistic regression results that explore each transition separately indicate deductible plan enrollment was associated with a 4.3 PP decrease in receipt of clinician visit, a 1.7 PP decrease in receipt of LCS order, and a 7.0 PP decrease in receipt of baseline LCS. Reductions persisted across all observable races and ethnicities., Conclusions: These findings suggest individuals enrolled in deductible plans are more likely to forgo preventive LCS services despite requiring no out-of-pocket costs. This result may indicate that increased cost-sharing is associated with suboptimal choices to forgo recommended LCS. Alternatively, this effect may indicate individuals enrolling into deductible plans prefer less health care utilization. Patient outreach interventions at the health plan level may improve LCS., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Lung cancer screening (LCS) guidelines in the United States recommend LCS for those age 50-80 years with at least 20 pack-years smoking history who currently smoke or quit within the last 15 years. We tested the performance of simple smoking-related criteria derived from electronic health record (EHR) data and developed and tested the performance of a multivariable model in predicting LCS eligibility., Methods: Analyses were completed within the Population-based Research to Optimize the Screening Process Lung Consortium (PROSPR-Lung). In our primary validity analyses, the reference standard LCS eligibility was based on self-reported smoking data collected via survey. Within one PROSPR-Lung health system, we used a training data set and penalized multivariable logistic regression using the Least Absolute Shrinkage and Selection Operator to select EHR-based variables into the prediction model including demographics, smoking history, diagnoses, and prescription medications. A separate test data set assessed model performance. We also conducted external validation analysis in a separate health system and reported AUC, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy metrics associated with the Youden Index., Results: There were 14,214 individuals with survey data to assess LCS eligibility in primary analyses. The overall performance for assigning LCS eligibility status as measured by the AUC values at the two health systems was 0.940 and 0.938. At the Youden Index cutoff value, performance metrics were as follows: accuracy, 0.855 and 0.895; sensitivity, 0.886 and 0.920; specificity, 0.896 and 0.850; PPV, 0.357 and 0.444; and NPV, 0.988 and 0.992., Conclusion: Our results suggest that health systems can use an EHR-derived multivariable prediction model to aid in the identification of those who may be eligible for LCS.

Background: Declines in the prevalence of cigarette smoking, advances in targeted therapies, and implementation of lung cancer screening have changed the clinical landscape for lung cancer. The proportion of lung cancer deaths is increasing in those who have never smoked cigarettes. To better understand contemporary patterns in survival among patients with lung cancer, a comprehensive evaluation of factors associated with survival, including differential associations by smoking status, is needed., Methods: Patients diagnosed with lung cancer between January 1, 2010, and September 30, 2019, were identified. We estimated all-cause and lung cancer-specific median, 5-year, and multivariable restricted mean survival time (RMST) to identify demographic, socioeconomic, and clinical factors associated with survival, overall and stratified by smoking status (never, former, and current)., Results: Analyses included 6813 patients with lung cancer: 13.9% never smoked, 54.2% formerly smoked, and 31.9% currently smoked. All-cause RMST through 5 years for those who never, formerly, and currently smoked was 32.1, 25.9, and 23.3 months, respectively. Lung cancer-specific RMST was 36.3 months, 30.3 months, and 26.0 months, respectively. Across most models, female sex, younger age, higher socioeconomic measures, first-course surgery, histology, and body mass index were positively associated, and higher stage was inversely associated with survival. Relative to White patients, Black patients had increased survival among those who formerly smoked., Conclusions: We identify actionable factors associated with survival between those who never, formerly, and currently smoked cigarettes. These findings illuminate opportunities to address underlying mechanisms driving lung cancer progression, including use of first-course treatment, and enhanced implementation of tailored smoking cessation interventions for individuals diagnosed with cancer., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Authors aimed to calculate the percentage up-to-date with testing in the context of lung cancer screening across 5 healthcare systems and evaluate differences according to patient and health system characteristics., Methods: Lung cancer screening‒eligible individuals receiving care within the five systems in the Population-based Research to Optimize the Screening Process Lung consortium from October 1, 2018 to September 30, 2019 were included in analyses. Data collection was completed on June 15, 2021; final analyses were completed on April 1, 2022. Chest computed tomography scans and patient characteristics were obtained through electronic health records and used to calculate the percentage completing a chest computed tomography scan in the previous 12 months (considered up-to-date). The association of patient and healthcare system factors with being up-to-date was evaluated with adjusted prevalence ratios and 95% CIs using log-binomial regression models., Results: There were 29,417 individuals eligible for lung cancer screening as of September 30, 2019; 8,333 (28.3%) were up-to-date with testing. Those aged 65-74 years (prevalence ratio=1.19; CI=1.15, 1.24, versus ages 55-64), those with chronic obstructive pulmonary disease (prevalence ratio=2.05; CI=1.98, 2.13), and those in higher SES census tracts (prevalence ratio=1.22; CI=1.16, 1.30, highest quintile versus lowest) were more likely to be up-to-date. Currently smoking (prevalence ratio=0.91; CI=0.88, 0.95), having a BMI ≥30 kg/m 2 (prevalence ratio=0.83; CI=0.77, 0.88), identifying as Native Hawaiian or other Pacific Islander (prevalence ratio=0.79; CI=0.68, 0.92), and having a decentralized lung cancer screening program (prevalence ratio=0.77; CI=0.74, 0.80) were inversely associated with being up-to-date., Conclusions: The percentage up-to-date with testing among those eligible for lung cancer screening is well below up-to-date estimates for other types of cancer screening, and disparities in lung cancer screening participation remain., (Copyright © 2023 American Journal of Preventive Medicine. All rights reserved.)

Research is increasingly conducted through multi-institutional consortia, and best practices for establishing multi-site research collaborations must be employed to ensure efficient, effective, and productive translational research teams. In this manuscript, we describe how the Population-based Research to Optimize the Screening Process Lung Research Center (PROSPR-Lung) utilized evidence-based Science of Team Science (SciTS) best practices to establish the consortium's infrastructure and processes to promote translational research in lung cancer screening. We provide specific, actionable examples of how we: (1) developed and reinforced a shared mission, vision, and goals; (2) maintained a transparent and representative leadership structure; (3) employed strong research support systems; (4) provided efficient and effective data management; (5) promoted interdisciplinary conversations; and (6) built a culture of trust. We offer guidance for managing a multi-site research center and data repository that may be applied to a variety of settings. Finally, we detail specific project management tools and processes used to drive collaboration, efficiency, and scientific productivity., Competing Interests: KR discloses research grants paid to her institution with funding from Pfizer and AstraZeneca and personal fees as a scientific consultant for Merck and American Journal of Managed Care, all outside of the submitted work. DPR and NMC report grant funding from Pfizer, outside of this work, paid to their institution. AV reports grants from the Moore Foundation, PCORI, Lungevity, the National Comprehensive Cancer Network, Precyte Inc., Optellum, Ltd, and MagArray Inc. outside of the submitted work and personal fees as scientific advisor for the Lung Cancer Initiative at Johnson and Johnson., (© The Author(s) 2023.)

Introduction: Quality of life (QoL) of endocrine surgery patients is an important patient outcome but the role of social determinants of health (SDH) on preoperative QoL is understudied., Methods: This study used preoperative data of 233 endocrine surgery patients participating in a longitudinal QoL study to examine the influence of SDH (patient-level and environmental) on preoperative QoL. Patient-level SDH was assessed with structured survey questions and environmental SDH with the Social Vulnerability Index. Multiple domains of QoL were assessed with the Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29)., Results: The average age of the sample was 52.9 y and 76.8% were female, 10% were Hispanic, 55.8% were White, 32.6% were Black, 6.9% were Other, and 4.7% were Asian. Patients with patient-level SDH were more likely to have worse preoperative QoL in multiple PROMIS domains. Patients who lived in the most socially vulnerable areas had the same or better QoL scores in the PROMIS-29 domains than those living in less vulnerable areas. Minority race patients were more likely to have patient-level SDH and to live in the most vulnerable areas., Conclusions: This study is the first to our knowledge to examine the role of patient-level and environmental SDH on preoperative QoL among endocrine surgery patients. The results identified specific patient-level factors that could be used as the basis for interventions aimed to improve patients' QoL. Future studies that evaluate the role of preoperative SDH on long-term QoL and clinical outcomes would further enhance our understanding of the impact of SDH on patient wellbeing., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction/background: Systemic treatment for advanced non-small cell lung cancer (NSCLC) is shifting from platinum-based chemotherapy to immunotherapy and targeted therapies associated with improved survival in clinical trials. As new therapies are approved for use, examining variations in use for treating patients in community practice can generate additional evidence as to the magnitude of their benefit., Patients and Methods: We identified 1,442 patients diagnosed with de novo stage IV NSCLC between 3/1/2012 and 12/31/2020. Patient characteristics and treatment patterns are described overall and by type of first- and second-line systemic therapy received. Prevalence ratios estimate the association of patient and tumor characteristics with receipt of first-line therapy., Results: Within 180 days of diagnosis, 949 (66%) patients received first-line systemic therapy, increasing from 53% in 2012 to 71% in 2020 (p = 0.0004). The proportion of patients receiving first-line immunotherapy+/-chemotherapy (IMO) increased from 14%-66% (p<0.0001). Overall, 380 (26%) patients received both first- and second-line treatment, varying by year between 16%-36% (p = 0.18). The proportion of patients receiving second-line IMO increased from 13%-37% (p<0.0001). Older age and current smoking status were inversely associated with receipt of first-line therapy. Higher BMI, receipt of radiation, and diagnosis year were positively associated with receipt of first-line therapy. No association was found for race, ethnicity, or socioeconomic status., Conclusion: The proportion of advanced NSCLC patients receiving first- and second-line treatment increased over time, particularly for IMO treatments. Additional research is needed to better understand the impact of these therapies on patient outcomes, including short-term, long-term, and financial toxicities., Microabstract: Systemic treatment for non-small cell lung cancer (NSCLC) is shifting from platinum-based therapies to immunotherapy and targeted therapies. Using de novo stage IV NSCLC patients identified from 4 healthcare systems, we examine trends in systemic therapy. We saw an increase in the portion of patients receiving any systemic therapy and a sharp increase in the proportion of patients receiving immunotherapy., Competing Interests: Declaration of Competing Interest NMC and DPR report research support from Pfizer paid to their institution, outside of the submitted work. KAR reports research support from Pfizer and AstraZeneca paid to her institution and personal fees as a scientific advisor to Merck, all outside of the submitted work. ABH reports research support from Biodesix, paid to her institution outside of the submitted work. AV reports personal fees as a scientific advisor to the Lung Cancer Initiative at Johnson & Johnson and grants to his institution from MagArray, Inc., Broncus Medical, Inc., and Precyte, Inc. outside of the submitted work. AV is an advisory board member of the Lungevity Foundation (unpaid). CND reports research support from Genentech paid to her institution, outside of the submitted work. All other authors reported no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Despite evidence from clinical trials of favorable shifts in cancer stage and improvements in lung cancer-specific mortality, the effectiveness of lung cancer screening (LCS) in clinical practice has not been clearly revealed., Methods: We performed a multicenter cohort study of patients diagnosed with a primary lung cancer between January 1, 2014, and September 30, 2019, at one of four U.S. health care systems. The primary outcome variables were cancer stage distribution and annual age-adjusted lung cancer incidence. The primary exposure variable was receipt of at least one low-dose computed tomography for LCS before cancer diagnosis., Results: A total of 3678 individuals were diagnosed with an incident lung cancer during the study period; 404 (11%) of these patients were diagnosed after initiation of LCS. As screening volume increased, the proportion of patients diagnosed with lung cancer after LCS initiation also rose from 0% in the first quartile of 2014 to 20% in the third quartile of 2019. LCS did not result in a significant change in the overall incidence of lung cancer (average annual percentage change [AAPC]: -0.8 [95% confidence interval (CI): -4.7 to 3.2]) between 2014 and 2018. Stage-specific incidence rates increased for stage I cancer (AAPC = 8.0 [95% CI: 0.8-15.7]) and declined for stage IV disease (AAPC = -6.0 [95% CI: -11.2 to -0.5])., Conclusions: Implementation of LCS at four diverse health care systems has resulted in a favorable shift to a higher incidence of stage I cancer with an associated decline in stage IV disease. Overall lung cancer incidence did not increase, suggesting a limited impact of overdiagnosis., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Few studies have compared the features of thyroid cancer among races and ethnicities. We hypothesized that race and ethnicity may influence the frequency and features of thyroid malignancy in thyroid nodules., Method: This was a retrospective chart review of patients between 2013 and 2020 who underwent thyroidectomy., Results: In the analysis of 2737 patients, thyroid cancer was less prevalent among Blacks (24.0% vs Whites 52.1%, Hispanics 58.7%, Asians 71.7%, and Others 57.9%, p < 0.001). Thyroid cancer in Blacks was less likely to have extrathyroidal extension (9.7% vs Whites 18.6%, Hispanics 25.8%, Asians 18.2%, and Others 17.8%, p = 0.01), overall nodal involvement (12.4% vs Whites 31.1%, Hispanics 37.5%, Asians 36.3%, and Others 30.1%, p < 0.01), and lateral neck metastasis (4.4% vs Whites 10.8%, Hispanics 6.3%, Asians 13.2%, and Others 9.6%, p = 0.02)., Conclusions: Race and ethnicity may play important roles in the risk of malignancy as well as in the extent of thyroid cancer., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Rationale: Lung-RADS classification was developed to standardize reporting and management of lung cancer screening using low-dose computed tomographic (LDCT) imaging. Although variation in Lung-RADS distribution between healthcare systems has been reported, it is unclear if this is explained by patient characteristics, radiologist experience with lung cancer screening, or other factors. Objectives: Our objective was to determine if patient or radiologist factors are associated with Lung-RADS score. Methods: In the Population-based Research to Optimize the Screening Process (PROSPR) Lung consortium, we conducted a study of patients who received their first screening LDCT imaging at one of the five healthcare systems in the PROSPR Lung Research Center from May 1, 2014, through December 31, 2017. Data on LDCT scans, patient factors, and radiologist characteristics were obtained via electronic health records. LDCT scan findings were categorized using Lung-RADS (negative [1], benign [2], probably benign [3], or suspicious [4]). We used generalized estimating equations with a multinomial distribution to compare the odds of Lung-RADS 3, and separately Lung-RADS 4, versus Lung-RADS 1 or 2 and estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between Lung-RADS assignment and patient and radiologist characteristics. Results: Analyses included 8,556 patients; 24% were assigned Lung-RADS 1, 60% Lung-RADS 2, 10% Lung-RADS 3, and 5% Lung-RADS 4. Age was positively associated with Lung-RADS 3 (OR, 1.02; 95% CI, 1.01-1.03) and 4 (OR, 1.03; 95% CI, 1.01-1.05); chronic obstructive pulmonary disease (COPD) was positively associated with Lung-RADS 4 (OR, 1.78; 95% CI, 1.45-2.20); obesity was inversely associated with Lung-RADS 3 (OR, 0.70; 95% CI, 0.58-0.84) and 4 (OR, 0.58; 95% CI, 0.45-0.75). There was no association between sex, race, ethnicity, education, or smoking status and Lung-RADS assignment. Radiologist volume of interpreting screening LDCT scans, years in practice, and thoracic specialty were also not associated with Lung-RADS assignment. Conclusions: Healthcare systems that are comprised of patients with an older age distribution or higher levels of COPD will have a greater proportion of screening LDCT scans with Lung-RADS 3 or 4 findings and should plan for additional resources to support appropriate and timely management of noted positive findings.

Objectives: There is limited knowledge about the cost patterns of patients who receive a diagnosis of de novo and recurrent advanced cancers in the United States., Methods: Data on patients who received a diagnosis of de novo stage IV or recurrent breast, colorectal, or lung cancer between 2000 and 2012 from 3 integrated health systems were used to estimate average annual costs for total, ambulatory, inpatient, medication, and other services during (1) 12 months preceding de novo or recurrent diagnosis (preindex) and (2) diagnosis month through 11 months after (postindex), from the payer perspective. Generalized linear regression models estimated costs adjusting for patient and clinical factors., Results: Patients who developed a recurrence <1 year after their initial cancer diagnosis had significantly higher total costs in the preindex period than those with recurrence ≥1 year after initial diagnosis and those with de novo stage IV disease across all cancers (all P < .05). Patients with de novo stage IV breast and colorectal cancer had significantly higher total costs in the postindex period than patients with cancer recurrent in <1 year and ≥1 year (all P < .05), respectively. Patients in de novo stage IV and those with recurrence in ≥1 year experienced significantly higher postindex costs than the preindex period (all P < .001)., Conclusions: Our findings reveal distinct cost patterns between patients with de novo stage IV, recurrent <1-year, and recurrent ≥1-year cancer, suggesting unique care trajectories that may influence resource use and planning. Future cost studies among patients with advanced cancer should account for de novo versus recurrent diagnoses and timing of recurrence to obtain estimates that accurately reflect these care pattern complexities., (Copyright © 2021 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. Published by Elsevier Inc. All rights reserved.)

Importance: The US Preventive Services Task Force (USPSTF) released updated lung cancer screening recommendations in 2021, lowering the screening age from 55 to 50 years and smoking history from 30 to 20 pack-years. These changes are expected to expand screening access to women and racial and ethnic minority groups., Objective: To estimate the population-level changes associated with the 2021 USPSTF expansion of lung cancer screening eligibility by sex, race and ethnicity, sociodemographic factors, and comorbidities in 5 community-based health care systems., Design, Setting, and Participants: This cohort study analyzed data of patients who received care from any of 5 community-based health care systems (which are members of the Population-based Research to Optimize the Screening Process Lung Consortium, a collaboration that conducts research to better understand how to improve the cancer screening processes in community health care settings) from January 1, 2010, through September 30, 2019. Individuals who had complete smoking history and were engaged with the health care system for 12 or more continuous months were included. Those who had never smoked or who had unknown smoking history were excluded., Exposures: Electronic health record-derived age, sex, race and ethnicity, socioeconomic status (SES), comorbidities, and smoking history., Main Outcomes and Measures: Differences in the proportion of the newly eligible population by age, sex, race and ethnicity, Charlson Comorbidity Index, chronic obstructive pulmonary disease diagnosis, and SES as well as lung cancer diagnoses under the 2013 recommendations vs the expected cases under the 2021 recommendations were evaluated using χ2 tests., Results: As of September 2019, there were 341 163 individuals aged 50 to 80 years who currently or previously smoked. Among these, 34 528 had electronic health record data that captured pack-year and quit-date information and were eligible for lung cancer screening according to the 2013 USPSTF recommendations. The 2021 USPSTF recommendations expanded screening eligibility to 18 533 individuals, representing a 53.7% increase. Compared with the 2013 cohort, the newly eligible 2021 population included 5833 individuals (31.5%) aged 50 to 54 years, a larger proportion of women (52.0% [n = 9631]), and more racial or ethnic minority groups. The relative increases in the proportion of newly eligible individuals were 60.6% for Asian, Native Hawaiian, or Pacific Islander; 67.4% for Hispanic; 69.7% for non-Hispanic Black; and 49.0% for non-Hispanic White groups. The relative increase for women was 13.8% higher than for men (61.2% vs 47.4%), and those with a lower comorbidity burden and lower SES had higher relative increases (eg, 68.7% for a Charlson Comorbidity Index score of 0; 61.1% for lowest SES). The 2021 recommendations were associated with an estimated 30% increase in incident lung cancer diagnoses compared with the 2013 recommendations., Conclusions and Relevance: This cohort study suggests that, in diverse health care systems, adopting the 2021 USPSTF recommendations will increase the number of women, racial and ethnic minority groups, and individuals with lower SES who are eligible for lung cancer screening, thus helping to minimize the barriers to screening access for individuals with high risk for lung cancer.

Genetic testing has increased over the last decade due to growth in the number of clinical and direct-to-consumer (DTC) tests. However, there is uncertainty about how increased DTC genetic testing affects disparities. Between November 2017 and February 2018, a nationwide electronic survey on experiences with genetic testing was conducted among adult Kaiser Permanente members. Logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals comparing receipt of clinical and DTC genetic testing between groups by race and ethnicity. Invitations were sent to 57,331 members, and 10,369 surveys were completed. 22% of respondents had received genetic testing (17% DTC and 5% provider-ordered). Non-Hispanic Whites were more likely than other groups to have clinical genetic testing but were similar to Hispanics and non-Hispanic Blacks in rates of DTC genetic testing. Among those who received any health-related genetic test, 10% reported abnormal results. Of these, non-Hispanic Whites were more likely than other racial/ethnic groups to speak to a medical professional about abnormal results. Results suggest that racial/ethnic disparities in the use of clinical genetic services persist. Additional research is needed to identify lessons learned from DTC genetic testing that may increase equity in the use of clinical genetic services., (© 2019 National Society of Genetic Counselors.)

Background: Lung cancer screening (LCS) requires complex processes to identify eligible patients, provide appropriate follow-up, and manage findings. It is unclear whether LCS in real-world clinical settings will realize the same benefits as the National Lung Screening Trial (NLST)., Objective: To evaluate the impact of process modifications on compliance with LCS guidelines during LCS program implementation, and to compare patient characteristics and outcomes with those in NLST., Design: Retrospective cohort study., Setting: Kaiser Permanente Colorado (KPCO), a non-profit integrated healthcare system., Patients: A total of 3375 patients who underwent a baseline lung cancer screening low-dose computed tomography (S-LDCT) scan between May 2014 and June 2017., Measurements: Among those receiving an S-LDCT, proportion who met guidelines-based LCS eligibility criteria before and after LCS process modifications, differences in patient characteristics and outcomes between KPCO LCS patients and the NLST cohort, and factors associated with a positive screen., Results: After modifying LCS eligibility confirmation processes, patients receiving S-LDCT who met guidelines-based LCS eligibility criteria increased from 45.6 to 92.7% (P < 0.001). Prior to changes, patients were older (68 vs. 67 years; P = 0.001), less likely to be current smokers (51.3% vs. 52.5%; P < 0.001), and less likely to have a ≥ 30-pack-year smoking history (50.0% vs. 95.3%; P < 0.001). Compared with NLST participants, KPCO LCS patients were older (67 vs. 60 years; P < 0.001), more likely to currently smoke (52.3% vs. 48.1%; P < 0.001), and more likely to have pulmonary disease. Among those with a positive baseline S-LDCT, the lung cancer detection rate was higher at KPCO (9.4% vs. 3.8%; P < 0.001) and was positively associated with prior pulmonary disease., Conclusion: Adherence to LCS guidelines requires eligibility confirmation procedures. Among those with a positive baseline S-LDCT, comorbidity burden and lung cancer detection rates were notably higher than in NLST, suggesting that the study of long-term outcomes in patients undergoing LCS in real-world clinical settings is warranted.

Background: Most genetics studies lack the diversity necessary to ensure that all groups benefit from genetic research., Objectives: To explore facilitators and barriers to genetic research participation., Methods: We conducted a survey on genetics in research and healthcare from November 15, 2017 to February 28, 2018 among adult Kaiser Permanente (KP) members who had been invited to participate in the KP biobank (KP Research Bank). We used logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing the willingness to participate in genetic research under different return of results scenarios and genetic discrimination concerns between groups, according to their demographic characteristics., Results: A total of 57,331 KP members were invited to participate, and 10,369 completed the survey (18% response rate). Respondents were 65% female, 44% non-Hispanic White (NH White), 22% Asian/Native Hawaiian or other Pacific Islander (Asian/PI), 19% non-Hispanic Black (NH Black), and 16% Hispanic. Respondents willing to participate in genetic research ranged from 22% with no results returned to 87% if health-related genetic results were returned. We also found variation by race/ethnicity; when no results were to be returned, Asian/PIs, Hispanics, and NH Blacks were less likely to want to participate than NH Whites (p < 0.05). However, when results were returned, disparities in the willingness to participate disappeared for NH Blacks and Hispanics. Genetic discrimination concerns were more prevalent in Asian/PIs, Hispanics, and NH Blacks than in NH Whites (p < 0.05)., Conclusions: Policies that prohibit the return of results and do not address genetic discrimination concerns may contribute to a greater underrepresentation of diverse groups in genetic research., (© 2020 S. Karger AG, Basel.)

Background: Oral tyrosine kinase inhibitors (TKIs) have been the standard of care for chronic myeloid leukemia (CML) since 2001. However, few studies have evaluated changes in the treatment landscape of CML over time. This study assessed the long-term treatment patterns of oral anticancer therapies among patients with CML., Methods: This retrospective cohort study included patients newly diagnosed with CML between January 1, 2000, and December 31, 2016, from 10 integrated healthcare systems. The proportion of patients treated with 5 FDA-approved oral TKI agents-bosutinib, dasatinib, imatinib, nilotinib, and ponatinib-in the 12 months after diagnosis were measured, overall and by year, between 2000 and 2017. We assessed the use of each oral agent through the fourth-line setting. Multivariable logistic regression estimated the odds of receiving any oral agent, adjusting for sociodemographic and clinical characteristics., Results: Among 853 patients with CML, 81% received an oral agent between 2000 and 2017. Use of non-oral therapies decreased from 100% in 2000 to 5% in 2005, coinciding with imatinib uptake from 65% in 2001 to 98% in 2005. Approximately 28% of patients switched to a second-line agent, 9% switched to a third-line agent, and 2% switched to a fourth-line agent. Adjusted analysis showed that age at diagnosis, year of diagnosis, and comorbidity burden were statistically significantly associated with odds of receiving an oral agent., Conclusions: A dramatic shift was seen in CML treatments away from traditional, nonoral chemotherapy toward use of novel oral TKIs between 2000 and 2017. As the costs of oral anticancer agents reach new highs, studies assessing the long-term health and financial outcomes among patients with CML are warranted.

Background: Thyroid surgery is becoming more common in the elderly as elderly population continues to grow. We aim to evaluate the relative risk of morbidity from thyroidectomy in patients greater than 75 y of age., Methods: A retrospective analysis was performed for patients who were undergoing thyroidectomy between 2001 and 2018 in a multihospital network. A matched control group was selected with use of a propensity score, which was based on gender, ethnicity, type of surgery, insurance status, and comorbidities. The Charlson Comorbidity Index was used to quantify comorbidities. Total complications included both thyroid-specific and systemic complications., Results: We identified 313 patients over the age of 75 y with a propensity score matched group of 313 patients. There was no difference between the percent female (73% versus 73%, P = 0.92), race composition (P = 0.91), insurance status (P = 0.99), percent undergoing total thyroidectomy (84% versus 84%, P = 0.91), and Charlson Index (2.6 versus 2.69, P = 0.70) of the two groups. Overall complications (4.8% versus 1.9%, P = 0.05) and thrombotic events (1.2 versus 0%, P = 0.04) were significantly higher but there was no statistically significant difference between postoperative emergency room visits (7% versus 6%, P = 0.61), readmissions (11.5% versus 8.6%, P = 0.18), cardiovascular (1.3 versus 0.6%, P = 0.61), pulmonary (3.2 versus 0.9%, P = 0.07), or neurologic complications (1.0 versus 0.3%, P = 0.34). No reoperations were noted in either group. Elder patients did have a longer length of stay (2.64 versus 1.29 d, P < 0.01)., Conclusions: Elderly patients did have a longer length of stay when compared to a matched younger population. Although there was a trend with higher complication rates in the elderly, those differences did not reach statistical significance., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Numerous studies have examined melanoma incidence and survival, but studies on melanoma recurrence are limited. We examined melanoma incidence, recurrence, and mortality among members of Kaiser Permanente Colorado (KPCO) between January 1, 2000 and December 31, 2015., Methods: Age-adjusted incidence rates were computed to examine trends among KPCO members aged 21 years and older. Cox proportional hazards models were used to examine factors associated with recurrence and mortality., Results: Our cohort included 1931 cases of invasive melanoma. Incidence rates increased over time and were higher than SEER rates; however, the increase was limited to early stage disease. In multivariable models, stage at initial diagnosis, gender, and age were associated with melanoma recurrence. Men were more likely to have a recurrence than women (adjusted hazard ratio [HR]: 1.70, 95% confidence interval [CI]: 1.19-2.43), and for each decade of increasing age, the adjusted HR = 1.20 (95% CI: 1.06-1.37). Factors associated with all-cause mortality included stage (HR = 12.87, 95% CI: 6.63-24.99, for stage IV vs stage I), male gender (HR = 1.42, 95% CI: 1.12-1.79), older age at diagnosis, lower socioeconomic status, and comorbidity index. For melanoma-specific mortality, results were similar, with one exception: age was not associated with melanoma-specific death (HR = 1.09, 95% CI: 0.94-1.25, P = 0.253)., Conclusions: Data derived from an insured patient population, such as KPCO, have the potential to enhance our understanding of emerging trends in melanoma. This is the first population-based study in the United States to examine patient characteristics associated with risk of recurrence. Men have an increased risk of both recurrence and death, and thus may benefit from more intensive follow-up than women., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Spending for patients with advanced cancer is substantial. Past efforts to characterize this spending usually have not included patients with recurrence (who may differ from those with de novo stage IV disease) or described which services drive spending., Methods: Using SEER-Medicare data from 2008 to 2013, we identified patients with breast, colorectal, and lung cancer with either de novo stage IV or recurrent advanced cancer. Mean spending/patient/month (2012 US dollars) was estimated from 12 months before to 11 months after diagnosis for all services and by the type of service. We describe the absolute difference in mean monthly spending for de novo versus recurrent patients, and we estimate differences after controlling for type of advanced cancer, year of diagnosis, age, sex, comorbidity, and other factors., Results: We identified 54,982 patients with advanced cancer. Before diagnosis, mean monthly spending was higher for recurrent patients (absolute difference: breast, $1,412; colorectal, $3,002; lung, $2,805; all P < .001), whereas after the diagnosis, it was higher for de novo patients (absolute difference: breast, $2,443; colorectal, $4,844; lung, $2,356; all P < .001). Spending differences were driven by inpatient, physician, and hospice services. Across the 2-year period around the advanced cancer diagnosis, adjusted mean monthly spending was higher for de novo versus recurrent patients (spending ratio: breast, 2.39 [95% CI, 2.05 to 2.77]; colorectal, 2.64 [95% CI, 2.31 to 3.01]; lung, 1.46 [95% CI, 1.30 to 1.65])., Conclusion: Spending for de novo cancer was greater than spending for recurrent advanced cancer. Understanding the patterns and drivers of spending is necessary to design alternative payment models and to improve value.

Purpose: We previously developed and validated informatic algorithms that used International Classification of Diseases 9th revision (ICD9)-based diagnostic and procedure codes to detect the presence and timing of cancer recurrence (the RECUR Algorithms). In 2015, ICD10 replaced ICD9 as the worldwide coding standard. To understand the impact of this transition, we evaluated the performance of the RECUR Algorithms after incorporating ICD10 codes., Methods: Using publicly available translation tables along with clinician and other expertise, we updated the algorithms to include ICD10 codes as additional input variables. We evaluated the performance of the algorithms using gold standard recurrence measures associated with a contemporary cohort of patients with stage I to III breast, colorectal, and lung (excluding IIIB) cancer and derived performance measures, including the area under the receiver operating curve, average absolute prediction error, and correct classification rate. These values were compared with the performance measures derived from the validation of the original algorithms., Results: A total of 659 colorectal, 280 lung, and 2,053 breast cancer cases were identified. Area under the receiver operating curve derived from the updated algorithms was 89.0% (95% CI, 82.3% to 95.7%), 88.9% (95% CI, 79.3% to 98.2%), and 80.5% (95% CI, 72.8% to 88.2%) for the colorectal, lung, and breast cancer algorithms, respectively. Average absolute prediction errors for recurrence timing were 2.7 (SE, 11.3%), 2.4 (SE, 10.4%), and 5.6 months (SE, 21.8%), respectively, and timing estimates were within 6 months of actual recurrence for more than 80% of colorectal, more than 90% of lung, and more than 50% of breast cancer cases using the updated algorithm., Conclusion: Performance measures derived from the updated and original algorithms had overlapping confidence intervals, suggesting that the ICD9 to ICD10 transition did not affect the RECUR Algorithm performance.

Background: Medical comorbidity may influence treatment initiation and engagement for alcohol and other drug (AOD) use disorders. We examined the association between medical comorbidity and Healthcare Effectiveness Data and Information Set (HEDIS) treatment initiation and engagement measures. Methods: We used electronic health record and insurance claims data from 7 US health care systems to identify patients with AOD use disorders between October 1, 2014, and August 15, 2015 ( N  = 86,565). Among patients identified with AOD use disorders in outpatient and emergency department (ED) settings, we examined how Charlson/Deyo comorbidity index scores and medical complications of AOD use were associated with treatment initiation. Among those who initiated treatment in inpatient and outpatient/ED settings, we also examined how comorbidity and AOD use-related medical complications were associated with treatment engagement. Analyses were conducted using generalized estimating equation logistic regression modeling. Results: Among patients identified as having an AOD diagnosis in outpatient and ED settings ( n  = 69,965), Charlson/Deyo comorbidity index scores of 2 or more were independently associated with reduced likelihood of initiation (risk ratio [RR] = 0.80, 95% confidence interval [CI] = 0.74, 0.86; reference score = 0), whereas prior-year diagnoses of cirrhosis (RR = 1.25, 95% CI = 1.12, 1.35) and pancreatic disease (RR = 1.34, 95% CI = 1.15, 1.56) were associated with greater likelihood of initiation. Among those who were identified in outpatient/ED settings and initiated, higher comorbidity scores were associated with lower likelihood of engagement (score 1: RR = 0.85, 95% CI = 0.76, 0.94; score 2+: RR = 0.61, 95% CI = 0.53, 0.71). Conclusion: Medical comorbidity was associated with lower likelihood of initiating or engaging in AOD treatment, but cirrhosis and pancreatic disease were associated with greater likelihood of initiation. Interventions to improve AOD treatment initiation and engagement for patients with comorbidities are needed, such as integrating medical and AOD treatment.

Purpose: Data from claims and electronic medical records (EMRs) are frequently used to identify clinical events (eg, cancer diagnosis, stroke). However, accurately determining the time of clinical events can be challenging, and the methods used to generate time estimates are underdeveloped. We sought to develop an approach to determine the time of a clinical event-cancer recurrence-using high-dimensional longitudinal structured data., Methods: Manual chart abstraction provided information regarding the actual time of cancer recurrence. These data were linked to claims from Medicare or structured EMR data from the Cancer Research Network, which were used to determine time of recurrence for patients with lung or colorectal cancer. We analyzed the longitudinal profile of codes that could help determine the time of recurrence, adjusted for systematic differences between code dates and recurrence dates, and integrated time estimates from different codes to empirically derive an optimal algorithm., Results: We identified twelve code groups that could help determine the time of recurrence. Using claims data for patients with lung cancer, the optimal algorithm consisted of three code groups and provided an average prediction error of 4.8 months. Using EMR data or applying this approach to patients with colorectal cancer yielded similar results., Conclusion: Time estimates were improved by selecting codes not necessarily the same as those used to identify recurrence, combining time estimates from multiple code groups, and adjusting for systematic bias between code dates and recurrence dates. Improving the accuracy of time estimates for clinical events can facilitate research, quality measurement, and process improvement.

Objective: To address the knowledge gap regarding medical care costs for advanced cancer patients, we compared costs for recurrent versus de novo stage IV breast, colorectal, and lung cancer patients., Data Sources/study Setting: Virtual Data Warehouse (VDW) information from three Kaiser Permanente regions: Colorado, Northwest, and Washington., Study Design: We identified patients aged ≥21 with de novo or recurrent breast (n de novo  = 352; n recurrent  = 765), colorectal (n de novo  = 1,072; n recurrent  = 542), and lung (n de novo  = 4,041; n recurrent  = 340) cancers diagnosed 2000-2012. We estimated average total monthly and annual costs in the 12 months preceding, month of, and 12 months following the index de novo/recurrence date, stratified by age at diagnosis (<65, ≥65). Generalized linear repeated-measures models controlled for demographics and comorbidity., Principal Findings: In the pre-index period, monthly costs were higher for recurrent than for de novo breast (<65: +$2,431; ≥65: +$1,360), colorectal (<65: +$3,219; ≥65: +$2,247), and lung cancer (<65: +$3,086; ≥65: +$2,260) patients. Conversely, during the index and post-index periods, costs were higher for de novo patients. Average total annual pre-index costs were five- to ninefold higher for recurrent versus de novo patients <65., Conclusions: Cost differences by type of advanced cancer and by age suggest heterogeneous patterns of care that merit further investigation., (© Health Research and Educational Trust.)

The treatments provided to and survival of patients with recurrent vs de novo stage IV advanced breast, lung, and colorectal cancer may differ but have not been well studied. Using population-based data from the Cancer Research Network for 4510 patients with advanced breast, lung, or colorectal cancer, we matched recurrent/de novo patients on demographic factors. We found longer survival for recurrent vs de novo lung cancer (182 matched pairs); no significant difference for colorectal cancer (332 matched pairs); and shorter survival for recurrent vs de novo breast cancer (219 matched pairs). Compared with recurrent cases, chemotherapy use and radiation therapy use were more common among de novo cases. Differences in treatment and survival between recurrent and de novo advanced cancer patients could inform prognostic estimates and clinical trial design.

Background: This study developed, validated, and disseminated a generalizable informatics algorithm for detecting breast cancer recurrence and timing using a gold standard measure of recurrence coupled with data derived from a readily available common data model that pools health insurance claims and electronic health records data., Methods: The algorithm has two parts: to detect the presence of recurrence and to estimate the timing of recurrence. The primary data source was the Cancer Research Network Virtual Data Warehouse (VDW). Sixteen potential indicators of recurrence were considered for model development. The final recurrence detection and timing models were determined, respectively, by maximizing the area under the ROC curve (AUROC) and minimizing average absolute error. Detection and timing algorithms were validated using VDW data in comparison with a gold standard recurrence capture from a third site in which recurrences were validated through chart review. Performance of this algorithm, stratified by stage at diagnosis, was compared with other published algorithms. All statistical tests were two-sided., Results: Detection model AUROCs were 0.939 (95% confidence interval [CI] = 0.917 to 0.955) in the training data set (n = 3370) and 0.956 (95% CI = 0.944 to 0.971) and 0.900 (95% CI = 0.872 to 0.928), respectively, in the two validation data sets (n = 3370 and 3961, respectively). Timing models yielded average absolute prediction errors of 12.6% (95% CI = 10.5% to 14.5%) in the training data and 11.7% (95% CI = 9.9% to 13.5%) and 10.8% (95% CI = 9.6% to 12.2%) in the validation data sets, respectively, and were statistically significantly lower by 12.6% (95% CI = 8.8% to 16.5%, P < .001) than those estimated using previously reported timing algorithms. Similar covariates were included in both detection and timing algorithms but differed substantially from previous studies., Conclusions: Valid and reliable detection of recurrence using data derived from electronic medical records and insurance claims is feasible. These tools will enable extensive, novel research on quality, effectiveness, and outcomes for breast cancer patients and those who develop recurrence.

Introduction: Recurrent cancer is common, costly, and lethal, yet we know little about it in community-based populations. Electronic health records and tumor registries contain vast amounts of data regarding community-based patients, but usually lack recurrence status. Existing algorithms that use structured data to detect recurrence have limitations., Methods: We developed algorithms to detect the presence and timing of recurrence after definitive therapy for stages I-III lung and colorectal cancer using 2 data sources that contain a widely available type of structured data (claims or electronic health record encounters) linked to gold-standard recurrence status: Medicare claims linked to the Cancer Care Outcomes Research and Surveillance study, and the Cancer Research Network Virtual Data Warehouse linked to registry data. Twelve potential indicators of recurrence were used to develop separate models for each cancer in each data source. Detection models maximized area under the ROC curve (AUC); timing models minimized average absolute error. Algorithms were compared by cancer type/data source, and contrasted with an existing binary detection rule., Results: Detection model AUCs (>0.92) exceeded existing prediction rules. Timing models yielded absolute prediction errors that were small relative to follow-up time (<15%). Similar covariates were included in all detection and timing algorithms, though differences by cancer type and dataset challenged efforts to create 1 common algorithm for all scenarios., Conclusions: Valid and reliable detection of recurrence using big data is feasible. These tools will enable extensive, novel research on quality, effectiveness, and outcomes for lung and colorectal cancer patients and those who develop recurrence.

Purpose: With the shift in the majority of oncology clinical care in the United States from paper records to electronic health records, researchers need efficient and validated processes to obtain accurate data about the entire treatment history of patients diagnosed with cancer. The objective of this study was to develop and validate an algorithm that is agnostic to the source of data but that can identify specific regimens in the entire course of systemic therapy treatment for patients diagnosed with breast, colorectal, or lung cancer., Methods: A cohort of patients with incident breast, colorectal, and lung cancer were randomly distributed into six groups. The algorithm was iteratively modified, and the performance was assessed until no additional modifications could be identified in the first three groups. The performance of the algorithm was confirmed in the three groups that remained., Results: The final model produced ranges of sensitivity between 97.2% and 100% for first-course systemic therapy across all cancers, with a false-positive rate of 0%. The algorithm matched the exact number of courses and the exact regimens of systemic therapy agents as captured by infusion, pharmacy, and procedure electronic medical record data for all courses of therapy 88% to 100% of the time., Conclusion: Use of our validated algorithm that characterizes entire courses of systemic therapy treatment in patients diagnosed with breast, colorectal, and lung cancer will allow researchers in a variety of settings to conduct comparative effectiveness studies related to the uptake, safety, outcomes, and costs associated with the use of both novel and standard regimens.

Background: The experiences of patients with recurrent cancer are assumed to reflect those of patients with de novo stage IV disease; yet, little is truly known because most registries lack recurrence status. Using two databases with excellent recurrence and death information, we examined determinants of survival duration after recurrence of breast (BC), colorectal (CRC), and lung cancers (LC)., Methods: Recurrence status was abstracted from the medical records of patients who participated in the Cancer Care Outcomes Research and Surveillance study and who received care at two Cancer Research Network sites-the Colorado and Northwest regions of Kaiser Permanente. The analysis included 1653 patients who developed recurrence after completing definitive therapy for stages I-III cancer. Multivariable modeling identified independent determinants of survival duration after recurrence, controlling for other factors., Results: Through 60 months' average follow-up, survival after recurrence for BC, CRC, and LC were 28.4, 23.1 and 16.1 months, respectively. Several factors were independently associated with shorter survival for all three cancers, including higher initial stage (III vs. I: BC -9.9 months; CRC -6.9 months; LC -7.4 months; P≤0.01). Factors associated with shorter survival for selected cancers included: distant/regional recurrence for BC and CRC; current/former smoker for LC; high grade for CRC; and <4-year time-to-recurrence for BC., Conclusions: Initial stage predicts survival duration after recurrence, whereas time-to-recurrence usually does not. The impact of biologic characteristics (e.g., grade, hormone-receptor status) on survival duration after recurrence needs further study. Predictors of survival duration after recurrence may help facilitate patient decision-making., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Preclinical studies suggest that angiotensin system inhibitors (ASI) and bevacizumab improve tumor perfusion and chemotherapy efficacy. We performed a retrospective study to examine whether concomitant ASI use during carboplatin and paclitaxel (CP) without or with bevacizumab (CPB) was associated with improved overall survival (OS) in patients with advanced nonsquamous, non-small-cell lung cancer (NS-NSCLC)., Patients and Methods: In a retrospective cohort study, adult patients diagnosed with stage IIIB or IV NS-NSCLC between 2005 and 2011 were identified from tumor registries at 1 of 4 Kaiser Permanente regions. Survival differences between those who did and did not receive ASIs concomitant with chemotherapy (CP or CPB) were assessed using propensity score-matched proportional hazard models. OS was measured from the initiation of chemotherapy until death, disenrollment, or December 31, 2012., Results: Of the 1465 CP and 348 CPB patients included, 273 (19%) and 78 (22%), respectively, received concomitant ASI. For CP patients with and without concomitant ASI exposure, median OS was 12.0 and 8.4 months, respectively (crude hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.63-0.84). For CPB patients, the comparable median OS was 14.9 and 11.9 months, respectively (crude HR, 0.77; 95% CI, 0.57-1.02). Using propensity score-matched cohorts, the HR for concomitant ASI use was 0.73 (95% CI, 0.61-0.88) for CP patients and 0.79 (95% CI, 0.51-1.21) for CPB patients., Conclusion: Concomitant ASI receipt during CP or CPB therapy for NS-NSCLC was associated with improved survival, although the association was only statistically significant in the CP group., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Controversy exists about breast cancer risk associated with long-term use of calcium channel blockers (CCBs) or angiotensin-converting enzyme inhibitors (ACEis), respectively. Our objective in this study was to separately evaluate associations between duration of CCB or ACEi use and breast cancer in hypertensive women aged ≥55 years at 3 sites in the Kaiser Permanente health-care system (1997–2012). Exposures included CCB or ACEi use of 1–12 years’ duration, determined from pharmacy dispensings. Outcomes included invasive lobular or ductal carcinoma. Statistical methods included discrete-time survival analyses. The cohort included 19,674 (17.9%) CCB users and 90,078 (82.1%) ACEi users. Two percent (n = 397) of CCB users and 1.9% (n = 1,733) of ACEi users developed breast cancer. Compared with 1–<2 years of use, in adjusted analysis, there was no association between CCB use for 2–<12 years and breast cancer: All 95% confidence intervals included 1. Increasing duration of ACEi use was associated with reduced breast cancer risk: Compared with 1–<2 years of use, the adjusted hazard ratio was 0.76 (95% confidence interval: 0.63, 0.92) for 5–<6 years of use and 0.63 (95% confidence interval: 0.43, 0.93) for 9–<10 years of use. We conclude that among older women with hypertension, long-term CCB use does not increase breast cancer risk and long-term treatment with ACEis may confer protection against breast cancer.

Purpose: Little is known regarding toxicities and hospitalizations in community-based settings for patients with advanced non-small-cell lung cancer (NSCLC) who received commonly prescribed carboplatin-paclitaxel (CP) or carboplatin-paclitaxel-bevacizumab (CPB) chemotherapy., Methods: Patients with stages IIIB-IV NSCLC age ≥ 21 years diagnosed between 2005 and 2010 who received first-line CP or CPB were identified at four health maintenance organizations (N = 1,109). Using patient and tumor characteristics and hospital and ambulatory encounters from automated data in the 180 days after chemotherapy initiation, the association between CP and CPB and toxicities and hospitalizations were evaluated with χ(2) tests and propensity score-adjusted regression models., Results: Patients who received CPB were significantly younger and had significantly more bleeding, proteinuria, and GI perforation events (all P < .05). For these patients, the unadjusted odds ratio associated with the likelihood of having a hospitalization was 0.46 (95% CI, 0.32 to 0.67). As shown by multivariable and propensity score-adjusted models, patients who received CPB were less likely to have been hospitalized (odds ratio, 0.48; 95% CI, 0.32 to 0.71) and had fewer total hospitalizations (rate ratio, 0.62; 95% CI, 0.47 to 0.82) and hospital days (rate ratio, 0.53; 95% CI, 0.47 to 0.60) than patients who received CP., Conclusion: Consistent with earlier randomized clinical trials, significantly more toxicity events were identified in patients treated with CPB. However, both unadjusted and adjusted models showed that patients who received CPB were less likely than patients who received CP to experience a hospital-related event after the initiation of chemotherapy. Findings here confirm the need for adherence to clinical recommendations for judicious use of CPB, but provide reassurance regarding the relative risk for hospitalizations., (Copyright © 2015 by American Society of Clinical Oncology.)

Considerable debate exists about the optimal treatment of ductal carcinoma in situ (DCIS). Using electronic data sources, we examined first course treatment patterns among women aged 18 years and older diagnosed with DCIS between 2000-2010 from six Kaiser Permanente (KP) regions. We calculated the proportion of patients receiving breast conserving surgery (BCS), BCS plus radiation therapy, unilateral mastectomy, bilateral mastectomy, and hormone therapy. Multinomial logistic regression was used to assess the association between patient characteristics and treatment. We included 9,437 women: 1,086 (11.5%) African-American; 1,455 (15.4%) Asian; 918 (9.7%) Hispanic; and 5,978 (63.3%) non-Hispanic white. Most cases (42.2%) received BCS plus radiation as their initial treatment. Nearly equal numbers of women received BCS without radiation (28.5%) or unilateral mastectomy (24.6%). Use of bilateral mastectomy was uncommon (4.7%), and most women (72.2%) did not receive hormone therapy has part of their first course treatment. We observed statistically significant differences in treatment patterns for DCIS by KP region and patient age. Predictably, nuclear grade and the presence of comorbidities were associated with first course treatment for DCIS. We observed statistically significant increases in BCS plus radiation therapy and bilateral mastectomy over time. Although still uncommon, the frequency of bilateral mastectomy increased from 2.7% in 2000 to 7.0% in 2010. We also observed differences in treatment by race/ethnicity. Our findings help illustrate the complex nature of DCIS treatment in the United States, and highlight the need for evidence based guidelines for DCIS care.

Background: Spinal metastases (SMs) due to thyroid cancer (TC) are associated with significantly reduced quality of life. The goal of this study is to analyze the clinical manifestations, presentation, and treatments of TC SMs, and to describe specific features of SMs associated with different TC types., Patients and Methods: A retrospective analysis of 202 TC SM patients treated at Medstar Washington Hospital Center (37) and collected from the literature (165) was performed., Results: The mean age of patients with SMs was 56.9±14.7 years, and the female-to-male ratio was 2.1:1. Of all patients, 29% (28% of follicular thyroid cancer [FTC] and 37% of papillary thyroid cancer [PTC]) had SMs only. Twenty-nine percent of all patients and 54% of patients with single-site SMs had neither bone non-SMs nor solid organ metastases at the time of presentation. Thirty-five percent of patients had SMs as an initial presentation of TC. TC patients presenting with SMs had a lower rate of other bone and visceral involvement compared with patients whose SMs were diagnosed at the time of thyroid surgery or during follow-up (p<0.05). SMs were more often the initial manifestation of FTC (41% vs. 24%), while PTC SMs were more commonly diagnosed after TC diagnosis (76% vs. 59%; p<0.05). PTC SMs were more frequently diagnosed as synchronous (63% vs. 36% in FTC) versus FTC SMs that developed as metachronous metastases (64% vs. 37% in PTC; p<0.01). All FTC SMs developed within 82 (0-372) months and all PTC SMs within 35 (0-144) months (p<0.01). In FTC SMs as TC manifestation, solid organ metastases involvement was less common than in FTC SMs that were found after TC diagnosis (34% vs. 67%; p<0.01); multisite FTC SMs compared to solitary FTC SMs were associated with the development of other bone nonspinal metastases (82% vs. 30%; p<0.01) and solitary organ metastases (65% vs. 41%; p<0.01). These correlations were not observed in PTC SMs. FTC patients often had neural structure compression (myelopathy/radiculopathy; 72% vs. 36% in PTC), while PTC patients frequently were asymptomatic (38% vs. 5% in FTC; p<0.01). FTC SMs more commonly were (131)I-avid (p<0.01). FTC patients required surgery more frequently (72% vs. 55% in PTC; p<0.05)., Conclusions: Our study reveals that a significant part of TC SMs patients have solitary spinal involvement at the time of presentation and may be considered for aggressive treatment with the intention to improve quality of life and survival. FTC SMs and PTC SMs appear to have distinct presentations, behavior, and treatment modalities, and should be categorized separately for treatment and follow-up planning.

Background: The spine is the most common site of bone metastases due to thyroid cancer, which develop in more than 3% of patients with well-differentiated thyroid cancer. Nearly half of patients with bone metastases from thyroid cancer develop vertebral metastases. Spinal metastases are associated with significantly reduced quality of life due to pain, neurological deficit, and increased mortality., Summary: Treatment options for patients with thyroid spinal metastases include radioiodine therapy, pharmacologic therapy, and surgical treatments, with recent advances in radiosurgery and minimally invasive spinal surgery as well. Therapeutic interventions require a multidisciplinary approach and aim to control pain, preserve or improve neurologic function, optimize local tumor control, and improve quality of life. We have proposed a three-tiered approach to the management and practical algorithms for patients with spinal metastases from thyroid carcinoma., Conclusions: The introduction of novel and improved techniques for the treatment of spinal metastases has created the opportunity to significantly improve control of metastatic tumor growth and the quality of life for the patients with spinal metastases from thyroid cancer. In order for these options to be effectively used, a multidisciplinary approach must be applied in the management of the patients with thyroid spinal metastases.

Introduction: Bevacizumab plus carboplatin-paclitaxel (BCP) chemotherapy has Food and Drug Administration approval for advanced nonsquamous, non-small-cell lung cancer based upon improved survival in a clinical trial. However, subgroup analyses of this and other studies have suggested variable results by age and gender., Methods: Using data from four health maintenance organizations (HMOs) belonging to the Cancer Research Network, 1605 HMO nonsquamous, non-small-cell lung cancer patients aged younger than 21 years, diagnosed 2002-2010, who received carboplatin-paclitaxel (CP), with and without bevacizumab for first-line treatment of stage IIIB/IV disease were identified. Patients were categorized into three groups based on year of diagnosis and regimen during 120 days postdiagnosis: (1) diagnosed 2005-2010 and received BCP; (2) 2005-2010, CP (CP2005), and (3) 2002-2004, CP (CP2002). Survival differences between groups were estimated using Cox proportional hazard models with several propensity score adjustments for demographic, comorbidity, and tumor characteristics. Multivariable subanalyses were also estimated., Results: Median survival was 12.3 months (interquartile range [IQR], 6.0-29.1) for BCP patients versus 8.8 months (IQR, 3.7-21.3) for CP2005 patients and 7.5 months (IQR, 3.8-15.6) for CP2002 patients. In the propensity score-adjusted models, BCP demonstrated a significant survival benefit with a hazard ratio of BCP relative to CP2005 and CP2002 patients of 0.79 (95% confidence interval [CI], 0.66-0.94) and 0.63 (95% CI, 0.52-0.75), respectively. In the multivariable-adjusted subanalyses, relative to the CP2005 cohort, the BCP hazard ratios for patients age less than 65 years, age 65 years old or older, and females were 0.78 (95% CI, 0.62-1.00), 0.74 (95% CI, 0.54-1.00), and 0.77 (95% CI, 0.58-1.00)., Conclusions: In this community-based, comparative effectiveness analysis, we found an overall survival benefit for adults receiving BCP compared with CP., Competing Interests: There is no conflict of interest by any of the authors of this paper.

Purpose: To evaluate whether enrollment in deductible health plans (DHP) with higher patient cost-sharing requirements than traditional health maintenance organization plans (HMP) decreased initiation and completion of the human papillomavirus (HPV) vaccine series recommended for prevention of cervical cancer., Methods: This was a retrospective observational study of 9- to 26-year-old females at Kaiser Permanente Georgia and Kaiser Permanente Colorado who were HPV vaccine naive at time of enrollment in a self-pay DHP or HMP in 2007. Estimates of rates of initiation and completion of the HPV vaccine series from plan enrollment in 2007 through December 2009 were obtained using Cox proportional hazards regressions (accounting for censoring) on samples matched on the propensity to enroll in a DHP versus HMP., Results: Initiation of the HPV vaccine series was 22.2% and 24.4% in the DHP and HMP groups, respectively, at Kaiser Permanente Georgia; completion was 12.3% and 14.4% in the DHP and HMP groups, respectively. Human papillomavirus vaccine series initiation was higher at Kaiser Permanente Colorado, but completion was lower. In the Cox proportional hazards regressions, rates of initiation and completion of the HPV vaccine series did not differ significantly (p ≤ .05) by plan type (DHP vs. HMP) at both sites. The primary care visit rate included in these regressions had a significant, positive association with initiation and completion of the HPV vaccine series., Conclusions: Enrollment in a DHP versus an HMP did not directly affect initiation or completion of the HPV vaccine series among age-eligible females. Independent of plan type, more frequent primary care visits increased initiation and completion rates., (Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Population-based biobanks are a critical resource for genetic research. It is important to know what potential participants understand about the risks and benefits of providing samples in order to ensure adequate informed consent. Kaiser Permanente Colorado (KPCO) is currently planning a biobank where adult members would be asked to contribute an additional tube of blood during a routine blood draw. Adult KPCO members in clinic waiting rooms were asked to read an informational brochure and informed consent form. Respondents then completed a survey to evaluate their understanding of the materials, willingness to provide a blood sample to a biobank, and facilitators and barriers to participation. Two hundred three members participated in the survey, of whom 69 % indicated willingness to contribute to a biobank. Nearly all understood that they would not be paid for any products resulting from the use of their blood and would not receive results from their samples (91 and 84 %, respectively). Seventy-four percent would donate a sample because, "it is important to contribute to research," and over half the participants (56 %) said they had no concerns about contributing to a biobank. Of those with concerns, 35 % said information security was a reason. In multivariate models, older age and trust in KPCO were significant predictors of willingness to participate (p = 0.03 and p < 0.0001, respectively). Data from this survey indicate an overall willingness to participate in a biobank, provide possible barriers to participation, and identify ways to improve informational materials to ensure adequate informed consent.

Background: Relatively low rates of chemotherapy receipt have been observed in older patients diagnosed with advanced non-small cell lung cancer (NSCLC) in SEER-Medicare-based studies. However, little is known about variation in first-line NSCLC chemotherapy use in younger patients, health maintenance organization (HMO)-based settings, and for high-cost, novel agents, such as bevacizumab and erlotinib., Methods: A cohort of 6614 stage IIIB/IV NSCLC patients aged ≥ 21 years diagnosed between 2000 and 2007 was identified at four HMOs that participate in the Cancer Research Network (CRN). Demographic, comorbidity, tumor characteristics, and chemotherapy treatment data were included in logistic regression models to identify factors associated with chemotherapy receipt and tests of association examined secular and age-specific variation in first-line chemotherapy regimens., Results: Within 120 days of diagnosis, 3612 (55%) patients received chemotherapy; increasing from 52% of patients diagnosed in 2000 to 59% in 2007 (p<0.001). Receipt was significantly higher for patients aged <65 years (64% versus 46% in ≥ 65) and was inversely related to stage and comorbidites (all p<0.001). Carboplatin and paclitaxel were received most frequently. Erlotinib and bevacizumab use in the later years of the study was associated with a significant change in distributions of first-line chemotherapies (p<0.001)., Conclusions: For patients alive 30 days post diagnosis, chemotherapy use was higher in the aged population (>65 years) than previously published estimates, and higher still among younger patients. Chemotherapy use increased over the observation period, and the mix of first-line therapies used changed substantially over time. Of note, novel, high cost treatments were used in first-line therapy prior to FDA approval, increasing significantly throughout the study period. These findings demonstrate the utility of HMO CRN data to augment SEER-Medicare to conduct comparative effectiveness research related to chemotherapy use and the use of specific agents, especially among younger patients., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Information comparing characteristics of patients who do and do not pick up their prescriptions is sparse, in part because adherence measured using pharmacy claims databases does not include information on patients who never pick up their first prescription, that is, patients with primary non-adherence. Electronic health record medication order entry enhances the potential to identify patients with primary non-adherence, and in organizations with medication order entry and pharmacy information systems, orders can be linked to dispensings to identify primarily non-adherent patients., Objective: This study aims to use database information from an integrated system to compare patient, prescriber, and payment characteristics of patients with primary non-adherence and patients with ongoing dispensings of newly initiated medications for hypertension, diabetes, and/or hyperlipidemia., Design: This is a retrospective observational cohort study. PARTICIPANTS (OR PATIENTS OR SUBJECTS): Participants of this study include patients with a newly initiated order for an antihypertensive, antidiabetic, and/or antihyperlipidemic within an 18-month period., Main Measures: Proportion of patients with primary non-adherence overall and by therapeutic class subgroup. Multivariable logistic regression modeling was used to investigate characteristics associated with primary non-adherence relative to ongoing dispensings., Key Results: The proportion of primarily non-adherent patients varied by therapeutic class, including 7% of patients ordered an antihypertensive, 11% ordered an antidiabetic, 13% ordered an antihyperlipidemic, and 5% ordered medications from more than one of these therapeutic classes within the study period. Characteristics of patients with primary non-adherence varied across therapeutic classes, but these characteristics had poor ability to explain or predict primary non-adherence (models c-statistics = 0.61-0.63)., Conclusions: Primary non-adherence varies by therapeutic class. Healthcare delivery systems should pursue linking medication orders with dispensings to identify primarily non-adherent patients. We encourage conduct of research to determine interventions successful at decreasing primary non-adherence, as characteristics available from databases provide little assistance in predicting primary non-adherence.

Background: Many medication adherence metrics are based on refill rates determined from pharmacy claims databases. However, these methods do not incorporate assessment of nonadherence to new prescriptions when those prescriptions are never dispensed (primary nonadherence), or dispensed only once (early nonpersistence). As a result, published studies may overestimate adherence, but the extent of overestimation posed by not considering patients with primary nonadherence and early nonpersistence has not been assessed., Objective: To estimate the magnitude of misestimation in adherence estimates that results from not including patients with primary nonadherence and early nonpersistence., Methods: We conducted a retrospective cohort study of 15,417 patients enrolled in an integrated health care delivery system who were newly prescribed an antihypertensive, antidiabetic, or antihyperlipidemic medication. We linked prescription orders to medication dispensings. Based on dispensing and refill rates, we stratified patients into primary nonadherent, early nonpersistent, and ongoing dispensings groups. Adherence was estimated using the proportion of days covered (PDC). Standardized observation periods were applied across all groups., Results: A total of 1142 (7.4%) patients were primarily nonadherent, 3356 (21.8%) demonstrated early nonpersistence, and 10,919 (70.8%) patients received ongoing dispensings, with a mean PDC of 84%. Not including primarily nonadherent and early nonpersistent patients in calculations resulted in adherence estimates overestimated by 9-18%., Conclusions: When medication adherence is estimated from pharmacy claims databases, adherence estimates are substantially inflated because primarily nonadherent and early nonpersistent patients are not included in the estimations. An implication of this incorrect estimation is potential distortion of the true relationship between medication adherence and clinical outcomes.

We developed an accurate and valid medication order algorithm to identify from electronic health records the definitive medication order intended for dispensing and applied this process to identify a cohort of patients and to stratify them into one of three medication adherence groups: early non-persistence, primary non-adherence, or ongoing adherence. We identified medication order data from electronic health record tables, obtained the orders, and linked the orders to dispensings. These steps were then used to identify patients newly prescribed antihypertensive, antidiabetic, or antihyperlipidemic medications and to determine the adherence group of each patient. Record review validated each process step, thus increasing the accuracy of group assignment as well as the criteria used to select patients. This work is an important first step to accurately identify study-specific patient adherence cohorts and allow more comprehensive estimates of population medication adherence.

Study Objective: To determine whether a computerized Drug Renal Alert Pharmacy (DRAP) program could decrease the rate of medication errors in drug selection or dosing for 15 target drugs in patients with renal insufficiency., Design: Randomized, controlled, population-based effectiveness trial., Setting: A large integrated health care delivery system., Patients: A total of 32,917 health plan members who were at least 18 years old, had an estimated creatinine clearance of 50 ml/minute or lower, and were not receiving dialysis between December 1, 2003, and February 28, 2005, were randomly assigned to either the intervention group (16,577 patients) or usual care (control) group (16,340 patients). Of the 32,917 patients, 6125 patients (3025 in the intervention group and 3100 in the usual care group) were prescribed at least one target drug and were included in the analysis., Intervention: A computerized tool--the DRAP program--was used to alert pharmacists at the time of dispensing to possible errors in target drug selection and dosing for patients with renal insufficiency. The 15 target drugs were previously identified based on frequency of use in our health care system and risk of serious adverse events., Measurements and Main Results: The primary outcome was the proportion of medication errors, defined as target drugs that should be avoided or were dosed inappropriately, in the intervention and usual care groups. The Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework was used to evaluate the intervention's potential for translation and generalizability. Among the 6125 patients who received a target drug, no significant differences were noted in age, sex, creatinine clearance, comorbid conditions, and number of target drugs between groups at baseline. Over the 15-month intervention period, the proportion of medication errors was significantly lower in the intervention group than the usual care group (33% vs 49%, p<0.001). After the study period, when the intervention was expanded to both groups, a 20% reduction in errors was sustained in the combined groups over the subsequent 7 months., Conclusion: The DRAP program was successful in reducing medication errors for patients with renal insufficiency in an ambulatory setting and was demonstrated to have sustainability after study completion.

Background: Thymic hyperplasia is associated with Graves' disease, particularly in young patients. The degree of thymic transformation is minimal in most but not all patients. In the latter group radiological measurements of thyroid size and their change with treatment have rarely been reported. We present two patients with Graves' disease and relatively rapid resolution of thymic enlargement after successful treatment of their hyperthyroidism., Summary: Three patients with thyrotoxicosis secondary to Graves' disease and marked thymic enlargement were seen at our institution during a 2-year period. On computed tomography (CT) studies their volumes were 67, 81, and 54 cm(3). Thymic hyperplasia in the setting of Graves' disease was the diagnosis of exclusion. Two of the patients returned for follow-up after successful treatment of thyrotoxicosis as requested. On repeat CT their thymic volumes had decreased by 72% and 78%, respectively. Two types of histological modifications of the thymus have been described in association with Graves' disease, namely, thymic parenchyma hyperplasia and medullary lymphoid hyperplasia. The mechanisms underlying thymic transformation in patients with Graves' hyperthyroidism are not completely elucidated, but autoimmune processes underlying Graves' disease are presumed to play a role. The clinical course of our patients is consistent with earlier literature, indicating that thymic enlargement may occur in conjunction with Graves' hyperthyroidism, and that it usually resolves as hyperthyroidism is treated, but there is little quantitative pre- and posttreatment of hyperthyroidism data., Conclusion: Although every patient must be individually considered, it appears that thymic hyperplasia can be diagnosed in most Graves' hyperthyroid patients by considering the clinical context and appropriate radiologic studies such as CT. Raising awareness of the association of thymic hyperplasia in patients with Graves' hyperthyroidism and its resolution with the reversibility of the hyperthyroid state should prevent unnecessary thymic evaluation and surgery with its attendant risks.

Background: Studies suggest that extended clopidogrel use after drug-eluting stent (DES) implantation may decrease the risk of myocardial infarction (MI) and death. Little is known about the competing risk of bleeding from clopidogrel in "real world" clinical practice., Methods and Results: We studied 7689 patients undergoing drug-eluting stent implantation enrolled in the HMO Research Network-Stent Registry between 2004 and 2007. Patients were analyzed in 6-month intervals for the occurrence of major bleeding, MI, and death. Clopidogrel use was determined by pharmacy dispensing data. Regression models assessed the association between clopidogrel use and outcomes. Overall, 3603 patients (49.1%) received clopidogrel for >6 months. During a mean follow-up of 418 days (SD, +/-168 days), 217 (2.9%) patients died, 279 (3.7%) had a MI, and 271 (3.6%) had major bleeding. After adjustment, patients on clopidogrel therapy were associated with increased major bleeding in all time intervals (0 to 6 months: relative risk (RR)=2.70, 95% CI=1.41 to 5.19; 7 to 12 months: RR=1.71, 95% CI=1.05 to 2.79; 13 to 18 months: RR=2.34, 95% CI=1.26 to 4.34), compared with patients off clopidogrel. Clopidogrel use was also associated with decreased risk of MI for all time intervals (0 to 6 months: RR=0.52, 95% CI=0.36 to 0.77; 7 to 12 months: RR=0.46, 95% CI=0.30 to 0.70; 13 to 18 months: RR=0.53, 95% CI=0.29 to 0.99) and decreased death in the 7 to 12 month interval (RR=0.50, 95% CI=0.30 to 0.83)., Conclusions: Clopidogrel use was associated with increased major bleeding and decreased MI persisting to 18 months. Bleeding risks on clopidogrel therapy deserve consideration in the ongoing debate regarding optimal clopidogrel duration after PCI.