Screening Beyond the Evidence: Patterns of Age and Comorbidity for Breast, Cervical, and Colorectal Cancer Screening.

BACKGROUND: Little evidence exists to guide continuation of screening beyond the recommended ages of national guidelines for breast, cervical, and colorectal cancers, although increasing age and comorbidity burden is likely to reduce the screening benefit of lower mortality. OBJECTIVE: Characterize screening after recommended stopping ages, by age and comorbidities in a large, diverse sample. DESIGN: Serial cross-sectional. PARTICIPANTS: All individuals in the PROSPR-I consortium cohorts from 75 to 89 years of age for breast cancer screening, 66-89 years of age for cervical cancer screening, and 76-89 years of age for colorectal cancer screening from 2011 to 2013. The lower age thresholds were based on the guidelines for each respective cancer type. MAIN MEASURES: Proportion of annual screening by cancer type in relation to age and Charlson comorbidity score and median years of screening past guideline age. We estimated the likelihood of screening past the guideline-based age as a function of age and comorbidity using logistic regression. KEY RESULTS: The study cohorts included individuals screening for breast (n = 33,475); cervical (n = 459,318); and colorectal (n = 556,356) cancers. In the year following aging out, approximately 30% of the population was screened for breast cancer, 2% of the population was screened for cervical, and almost 5% for colorectal cancer. The median number of years screened past the guideline-based recommendation was 5, 3, and 4 for breast, cervical, and colorectal cancer, respectively. Of those screening > 10 years past the guideline-based age,15%, 46%, and 25% had ≥ 3 comorbidities respectively. Colorectal cancer screening had the smallest decline in the likelihood of screening beyond the age-based recommendation. CONCLUSIONS: The odds of screening past guideline-based age decreased with comorbidity burden for breast and cervical cancer screening but not for colorectal. These findings suggest the need to evaluate shared decision tools to help patients understand whether screening is appropriate and to generate more evidence in older populations.

Bundling Colorectal Cancer Screening Outreach with Screening for Social Risk in Federally Qualified Health Centers: A Stepped-Wedge Implementation-Effectiveness Study.

BACKGROUND: Bundling is combining individual interventions to meet quality metrics. Bundling offers of cancer screening with screening for social determinants of health (SDOH) may enable health centers to assist patients with social risks and yield efficiencies. OBJECTIVE: To measure effects of bundling fecal immunochemical testing (FIT) and SDOH screening in federally qualified health centers (FQHCs). DESIGN: Clustered stepped-wedge trial. PARTICIPANTS: Four Massachusetts FQHCs randomized to implement bundled FIT-SDOH over 8-week "steps." INTERVENTION: Outreach to 50-75-year-olds overdue for CRC screening to offer FIT with SDOH screening. The implementation strategy used facilitation and training for data monitoring and reporting. MAIN MEASURES: Implementation process descriptions, data from facilitation meetings, and CRC and SDOH screening rates. Rates were compared between implementation and control FQHCs in each "step" by fitting generalized linear mixed-effects models with random intercepts for FQHCs, patients, and "step" by FQHC. KEY RESULTS: FQHCs tailored implementation processes to their infrastructure, workflows, and staffing and prioritized different groups for outreach. Two FQHCs used population health outreach, and two integrated FIT-SDOH within established programs, such as pre-visit planning. Of 34,588 patients overdue for CRC screening, 54% were female; 20% Black, 11% Latino, 10% Asian, and 47% white; 32% had Medicaid, 16% Medicare, 32% private insurance, and 11% uninsured. Odds of CRC screening completion in implementation "steps" compared to controls were higher overall and among groups prioritized for outreach (overall: adjusted odds ratio (aOR) 2.41, p = 0.005; prioritized: aOR 2.88, p = 0.002). Odds of SDOH screening did not differ across "steps." CONCLUSIONS: As healthcare systems are required to conduct more screenings, it is notable that outreach for a long-standing cancer screening requirement increased screening, even when bundled with a newer screening requirement. This outreach was feasible in a real-world safety-net clinical population and may conserve resources, especially compared to more complex or intensive outreach strategies. CLINICAL TRIALS REGISTRATION: NCT04585919.

Multilevel barriers and facilitators to widespread use of preconception carrier screening in the United States.

PURPOSE: Although preconception reproductive genetic carrier screening (RGCS) is preferred to screening during pregnancy, population-wide preconception screening is not routinely performed in the United States. We explored the multilevel barriers to the widespread adoption of preconception RGCS in the United States via key informant interviews. METHODS: Semi-structured virtual video interviews were conducted with 29 informants with a breadth of professional expertise between May and October 2022. Data collection and qualitative analyses were guided by the Consolidated Framework for Implementation Research and socioecological model. Analysis focused on identifying barriers to delivering preconception RGCS at and across different levels of health care and exploring potential facilitators of preconception RGCS delivery. RESULTS: Barriers to preconception RGCS were identified at the levels of test characteristics, patients and couples, clinicians and care teams, and the external health care and policy environments. Across the different levels of care delivery, 3 themes of barriers emerged: (1) fragmentation and inconsistencies hinder care delivery, (2) gaps in knowledge, misconceptions, and uncertainties about RGCS are pervasive, and (3) expanding preconception RGCS in the diverse US population presents unique implementation challenges. Potential solutions were detailed by informants. CONCLUSION: Identifying individual and thematic barriers to preconception RGCS delivery may help to define strategies to alleviate obstacles.

Evaluation of Harms Reporting in U.S. Cancer Screening Guidelines.

BACKGROUND: Cancer screening should be recommended only when the balance between benefits and harms is favorable. This review evaluated how U.S. cancer screening guidelines reported harms, within and across organ-specific processes to screen for cancer. OBJECTIVE: To describe current reporting practices and identify opportunities for improvement. DESIGN: Review of guidelines. SETTING: United States. PATIENTS: Patients eligible for screening for breast, cervical, colorectal, lung, or prostate cancer according to U.S. guidelines. MEASUREMENTS: Information was abstracted on reporting of patient-level harms associated with screening, diagnostic follow-up, and treatment. The authors classified harms reporting as not mentioned, conceptual, qualitative, or quantitative and noted whether literature was cited when harms were described. Frequency of harms reporting was summarized by organ type. RESULTS: Harms reporting was inconsistent across organ types and at each step of the cancer screening process. Guidelines did not report all harms for any specific organ type or for any category of harm across organ types. The most complete harms reporting was for prostate cancer screening guidelines and the least complete for colorectal cancer screening guidelines. Conceptualization of harms and use of quantitative evidence also differed by organ type. LIMITATIONS: This review considers only patient-level harms. The authors did not verify accuracy of harms information presented in the guidelines. CONCLUSION: The review identified opportunities for improving conceptualization, assessment, and reporting of screening process-related harms in guidelines. Future work should consider nuances associated with each organ-specific process to screen for cancer, including which harms are most salient and where evidence gaps exist, and explicitly explore how to optimally weigh available evidence in determining net screening benefit. Improved harms reporting could aid informed decision making, ultimately improving cancer screening delivery. PRIMARY FUNDING SOURCE: National Cancer Institute.

A Multilevel Primary Care Intervention to Improve Follow-Up of Overdue Abnormal Cancer Screening Test Results: A Cluster Randomized Clinical Trial.

Importance: Realizing the benefits of cancer screening requires testing of eligible individuals and processes to ensure follow-up of abnormal results. Objective: To test interventions to improve timely follow-up of overdue abnormal breast, cervical, colorectal, and lung cancer screening results. Design, Setting, and Participants: Pragmatic, cluster randomized clinical trial conducted at 44 primary care practices within 3 health networks in the US enrolling patients with at least 1 abnormal cancer screening test result not yet followed up between August 24, 2020, and December 13, 2021. Intervention: Automated algorithms developed using data from electronic health records (EHRs) recommended follow-up actions and times for abnormal screening results. Primary care practices were randomized in a 1:1:1:1 ratio to (1) usual care, (2) EHR reminders, (3) EHR reminders and outreach (a patient letter was sent at week 2 and a phone call at week 4), or (4) EHR reminders, outreach, and navigation (a patient letter was sent at week 2 and a navigator outreach phone call at week 4). Patients, physicians, and practices were unblinded to treatment assignment. Main Outcomes and Measures: The primary outcome was completion of recommended follow-up within 120 days of study enrollment. The secondary outcomes included completion of recommended follow-up within 240 days of enrollment and completion of recommended follow-up within 120 days and 240 days for specific cancer types and levels of risk. Results: Among 11 980 patients (median age, 60 years [IQR, 52-69 years]; 64.8% were women; 83.3% were White; and 15.4% were insured through Medicaid) with an abnormal cancer screening test result for colorectal cancer (8245 patients [69%]), cervical cancer (2596 patients [22%]), breast cancer (1005 patients [8%]), or lung cancer (134 patients [1%]) and abnormal test results categorized as low risk (6082 patients [51%]), medium risk (3712 patients [31%]), or high risk (2186 patients [18%]), the adjusted proportion who completed recommended follow-up within 120 days was 31.4% in the EHR reminders, outreach, and navigation group (n = 3455), 31.0% in the EHR reminders and outreach group (n = 2569), 22.7% in the EHR reminders group (n = 3254), and 22.9% in the usual care group (n = 2702) (adjusted absolute difference for comparison of EHR reminders, outreach, and navigation group vs usual care, 8.5% [95% CI, 4.8%-12.0%], P < .001). The secondary outcomes showed similar results for completion of recommended follow-up within 240 days and by subgroups for cancer type and level of risk for the abnormal screening result. Conclusions and Relevance: A multilevel primary care intervention that included EHR reminders and patient outreach with or without patient navigation improved timely follow-up of overdue abnormal cancer screening test results for breast, cervical, colorectal, and lung cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03979495.

Real-world treatment persistence in patients with rheumatoid arthritis initiating DMARDs in Germany-a health insurance claims data analysis.

OBJECTIVE: To investigate treatment patterns in patients with rheumatoid arthritis (RA) in Germany who had previously received conventional synthetic (cs) or biologic (b) disease-modifying antirheumatic drugs (DMARDs). METHODS: Patients with RA who initiated treatment with a csDMARD, bDMARD, or Janus kinase (JAK) inhibitor between 2017 and 2018 and who had previously received csDMARD or bDMARD therapy were retrospectively selected from the Institute for Applied Health Research Berlin GmbH (InGef). Time on treatment and discontinuation risk were assessed using the Kaplan-Meier method. Cox regression identified variables associated with an increased discontinuation risk. RESULTS: A total of 990 patients had received prior csDMARD therapy; 375 had received prior bDMARD therapy. Tumor necrosis factor (TNF)-α inhibitors and JAK inhibitors were the most commonly prescribed DMARD class in those previously treated with a csDMARD or bDMARD, respectively. In both cohorts, more patients received DMARD monotherapy than combination therapy. In the prior csDMARD cohort, median time on treatment was 276, 252, and 148 days with JAK inhibitors, TNF­α inhibitors, and csDMARDs, respectively, and those treated with JAK or TNF­α inhibitors were less likely to discontinue treatment than those on csDMARDs (log-rank test p-value < 0.01 for both comparisons); no significant differences were found within the prior bDMARD cohort. CONCLUSION: This is among the first detailed analyses of RA treatment patterns in a real-world setting in Germany since the introduction of JAK inhibitors. TNF­α inhibitors were the most commonly prescribed DMARD after failure of an initial csDMARD, while JAK inhibitors were the most common among patients previously treated with a bDMARD. In both groups, monotherapy with bDMARD or targeted synthetic DMARD was common. In the prior csDMARD cohort, treatment duration was significantly longer with JAK or TNF­α inhibitors than with csDMARDs.

Development of a workflow process mapping protocol to inform the implementation of regional patient navigation programs in breast oncology.

BACKGROUND: Implementing city-wide patient navigation processes that support patients across the continuum of cancer care is impeded by a lack of standardized tools to integrate workflows and reduce gaps in care. The authors present an actionable workflow process mapping protocol for navigation process planning and improvement based on methods developed for the Translating Research Into Practice study. METHODS: Key stakeholders at each study site were identified through existing community partnerships, and data on each site's navigation processes were collected using mixed methods through a series of team meetings. The authors used Health Quality Ontario's Quality Improvement Guide, service design principles, and key stakeholder input to map the collected data onto a template structured according to the case-management model. RESULTS: Data collection and process mapping exercises resulted in a 10-step protocol that includes: 1) workflow mapping procedures to guide data collection on the series of activities performed by health care personnel that comprise a patient's navigation experience, 2) a site survey to assess program characteristics, 3) a semistructured interview guide to assess care coordination workflows, 4) a site-level swim lane workflow process mapping template, and 5) a regional high-level process mapping template to aggregate data from multiple site-level process maps. CONCLUSIONS: This iterative, participatory approach to data collection and process mapping can be used by improvement teams to streamline care coordination, ultimately improving the design and delivery of an evidence-based navigation model that spans multiple treatment modalities and multiple health systems in a metropolitan area. This protocol is presented as an actionable toolkit so the work may be replicated to support other quality-improvement initiatives and efforts to design truly patient-centered breast cancer treatment experiences. LAY SUMMARY: Evidence-based patient navigation in breast cancer care requires the integration of services through each phase of cancer treatment. The Translating Research Into Practice study aims to implement patient navigation for patients with breast cancer who are at risk for delays and are seeking care across 6 health systems in Boston, Massachusetts. The authors designed a 10-step protocol outlining procedures and tools that support a systematic assessment for health systems that want to implement breast cancer patient navigation services for patients who are at risk for treatment delays.

Factors associated with timely colposcopy following an abnormal cervical cancer test result.

Successful cervical cancer prevention requires screening and appropriate management of abnormal test results. Management includes diagnostic evaluation and treatment, if indicated, based on cervical cancer risk after most abnormal test results. There is little guidance on the optimal timing of diagnostic evaluation, and few data exist on factors associated with timely management. We quantified time-to-colposcopy within 12 months of an abnormal cervical cancer screening or surveillance test result from 2010 to 2018 across three diverse healthcare systems and described factors associated with timely colposcopy. Among 21-65 year-old patients with an abnormal test result for which colposcopy was indicated (n = 28,706), we calculated the proportion who received a colposcopy within 12 months of the abnormal test and used Kaplan-Meier methods to estimate the probability of colposcopy within 12 months. Across all systems, 75.3% of patients received a colposcopy within 12 months, with site-specific estimates ranging from 70.0 to 83.0%. We fit mixed-effects multivariable logistic regression models to identify factors associated with receipt of colposcopy within 12 months. The healthcare system and cytology result severity were the most important factors associated with of timely colposcopy. We observed that sites with more centralized processes had higher proportions of colposcopy completion, and patients with high-grade results were more consistently evaluated earlier than patients with low-grade results. Patient age also affected receipt of timely colposcopy, though this association differed by healthcare system and result severity. These data suggest opportunities for system-level interventions to improve management of abnormal cervical cancer test results.

Variation in the receipt of human papilloma virus co-testing for cervical screening: Individual, provider, facility and healthcare system characteristics.

Since 2012, cervical cancer screening guidelines allow for choice of screening test for women age 30-65 years (i.e., Pap every 3 years or Pap with human papillomavirus co-testing every 5 years). Intended to give patients and providers options, this flexibility reflects a trend in the growing complexity of screening guidelines. Our objective was to characterize variation in cervical screening at the individual, provider, clinic/facility, and healthcare system levels. The analysis included 296,924 individuals receiving screening from 3626 providers at 136 clinics/facilities in three healthcare systems, 2010 to 2017. Main outcome was receipt of co-testing vs. Pap alone. Co-testing was more common in one healthcare system before the 2012 guidelines (adjusted odds ratio (AOR) of co-testing at the other systems relative to this system 0.00 and 0.50) but was increasingly implemented over time in a second with declining uptake in the third (2017: AORs shifted to 7.32 and 0.01). Despite system-level differences, there was greater heterogeneity in receipt of co-testing associated with providers than clinics/facilities. In the three healthcare systems, providers in the highest quartile of co-testing use had an 8.35, 8.81, and 25.05-times greater odds of providing a co-test to women with the same characteristics relative to the lowest quartile. Similarly, clinics/ facilities in the highest quartile of co-testing use had a 4.20, 3.14, and 6.56-times greater odds of providing a co-test relative to the lowest quartile. Variation in screening test use is associated with health system, provider, and clinic/facility levels even after accounting for patient characteristics.

A comparative assessment of neutropenia events, healthcare resource use, and costs among cancer patients treated with lipegfilgrastim compared with pegfilgrastim in Germany.

PURPOSE: We assessed the occurrence of neutropenia and febrile neutropenia (FN) and the associated healthcare resource in cancer patients receiving myelosuppressive chemotherapy in combination with pegfilgrastim versus lipegfilgrastim. METHODS: This is a retrospective analysis using a German health insurance claims database. Adults receiving chemotherapy with a prescription code for pegfilgrastim (n = 734) or lipegfilgrastim (n = 346) were observed over a 1-year follow-up period. Patient subgroups were analyzed according to cancer type and FN risk. FN risk was based on the chemotherapy regimen and any additional neutropenia risk factors. Outcomes were adjusted via regression analysis. RESULTS: Most patients were classified as high FN risk (70.0% pegfilgrastim; 65.6% lipegfilgrastim cohort). The mean age was 58.2 years in the pegfilgrastim cohort and 58.0 years in the lipegfilgrastim cohort, with more female patients than male patients (77.3% vs 79.8%, respectively), and the majority had breast cancer (64.9% and 68.8%, respectively). Overall, 10.0% and 10.4% of patients receiving pegfilgrastim or lipegfilgrastim experienced a neutropenia event (p = 0.82), with 4.4% and 3.5% of patients experiencing a FN event (p = 0.49). The mean neutropenia event-related healthcare costs were €604 and €441 for the pegfilgrastim and lipegfilgrastim cohorts; among patients with lymphoma, these costs were significantly greater (p = 0.03) with pegfilgrastim (€1,612) versus lipegfilgrastim (€382). The mean all-cause hospitalizations were significantly (p < 0.01) higher for lymphoma patients receiving pegfilgrastim (2.76) versus lipegfilgrastim (1.60). CONCLUSION: Overall, patients treated with pegfilgrastim and lipegfilgrastim were comparable in terms of neutropenia occurrences in the 1-year follow-up. In patients with lymphoma, neutropenia event-related healthcare costs and all-cause hospitalizations were significantly higher with pegfilgrastim compared with lipegfilgrastim in this study; however, this should be interpreted with caution in light of the limited sample size and the absence of clinical information.

Assessment of patient navigation programs for breast cancer patients across the city of Boston.

PURPOSE: Healthcare systems contribute to disparities in breast cancer outcomes. Patient navigation is a widely cited system-based approach to improve outcomes among populations at risk for delays in care. Patient navigation programs exist in all major Boston hospitals, yet disparities in outcomes persist. The objective of this study was to conduct a baseline assessment of navigation processes at six Boston hospitals that provide breast cancer care in preparation for an implementation trial of standardized navigation across the city. METHODS: We conducted a mixed methods study in six hospitals that provide treatment to breast cancer patients in Boston. We administered a web-based survey to clinical champions (n = 7) across six sites to collect information about the structure of navigation programs. We then conducted in-person workflow assessments at each site using a semi-structured interview guide to understand site-specific implementation processes for patient navigation programs. The target population included administrators, supervisors, and patient navigators who provided breast cancer treatment-focused care. RESULTS: All sites offered patient navigation services to their patients undergoing treatment for breast cancer. We identified wide heterogeneity in terms of how programs were funded/resourced, which patients were targeted for navigation, the type of services provided, and the continuity of those services relative to the patient's cancer treatment. CONCLUSIONS: The operationalization of patient navigation varies widely across hospitals especially in relation to three core principles in patient navigation: providing patient support across the care continuum, targeting services to those patients most likely to experience delays in care, and systematically screening for and addressing patients' health-related social needs. Gaps in navigation across the care continuum present opportunities for intervention. TRIAL REGISTRATION: Clinical Trial Registration Number NCT03514433, 5/2/2018.

Using community-engaged methods to develop a study protocol for a cost analysis of a multi-site patient navigation intervention for breast cancer care.

BACKGROUND: Patient navigation is an evidence-based intervention for reducing delays in oncology care among underserved populations. In order to address the financial sustainability of this intervention, information is needed on the cost of implementing patient navigation in diverse healthcare settings. Because patient navigation programs and care settings are highly variable, this paucity of cost data creates difficulties in identifying best practices and decisions about the feasibility of implementing navigation programs within a health care system. One barrier to collecting these cost data is the lack of assessment tools available to support patient navigation programs. These tools must be relevant to the wide variety of navigation activities that exist in health care settings, and be flexible enough to collect cost data important to stakeholders in fee-for-service and value-based care environments. METHODS AND RESULTS: We present a novel approach and methods for assessing the cost of a patient navigation program implemented across six hospital systems to enhance timely entry and uptake of breast cancer care and treatment. These methods and tools were developed in partnership with breast oncology patient navigators and supervisors using principles of stakeholder engagement, with the goal of increasing usability and feasibility in the field. CONCLUSIONS: This methodology can be used to strengthen cost analysis and assessment tools for other navigation programs for improving care and treatment for patients with chronic conditions. TRIAL REGISTRATION: NCT03514433.

Peer sexual harassment, affect, and substance use: Daily level associations among adolescents.

INTRODUCTION: Peer sexual harassment is associated with adolescent substance use at the global level; however, it is unknown whether substance use occurs proximal in time to the sexual harassment experience. This study used daily reports to examine the proximal relations between sexual harassment victimization and affect and substance use. Based on theories of self-medication, we hypothesized that negative affect and substance use (cigarettes, electronic cigarettes, alcohol, and marijuana) would be higher than typical on days when sexual harassment occurred relative to nonvictimization days. METHOD: A community sample of 13-16-year-old adolescents (N = 204, 55.4% female) from a metropolitan area in the northeastern United States completed 56 days of online reports assessing experiences with peer sexual harassment, substance use (cigarettes, electronic cigarettes, alcohol, and marijuana), and positive and negative affect. RESULTS: Multilevel modeling revealed that experiencing sexual harassment on a given day was associated with higher than typical negative affect on that day, relative to nonvictimization days. The likelihood of cigarette and alcohol use (but not electronic cigarettes, marijuana, or positive affect) was greater on days when sexual harassment occurred. CONCLUSION: Sexual harassment victimization is proximally associated with negative affect and alcohol and cigarette use, suggesting that adolescents may be using substances to cope with sexual harassment victimization. The co-occurrence of sexual harassment with negative affect and substance use points to the need for prevention efforts that conjointly address sexual harassment victimization, coping, and substance use.

Noncatalytic Bruton's tyrosine kinase activates PLCγ2 variants mediating ibrutinib resistance in human chronic lymphocytic leukemia cells.

Treatment of patients with chronic lymphocytic leukemia (CLL) with inhibitors of Bruton's tyrosine kinase (BTK), such as ibrutinib, is limited by primary or secondary resistance to this drug. Examinations of CLL patients with late relapses while on ibrutinib, which inhibits BTK's catalytic activity, revealed several mutations in BTK, most frequently resulting in the C481S substitution, and disclosed many mutations in PLCG2, encoding phospholipase C-γ2 (PLCγ2). The PLCγ2 variants typically do not exhibit constitutive activity in cell-free systems, leading to the suggestion that in intact cells they are hypersensitive to Rac family small GTPases or to the upstream kinases spleen-associated tyrosine kinase (SYK) and Lck/Yes-related novel tyrosine kinase (LYN). The sensitivity of the PLCγ2 variants to BTK itself has remained unknown. Here, using genetically-modified DT40 B lymphocytes, along with various biochemical assays, including analysis of PLCγ2-mediated inositol phosphate formation, inositol phospholipid assessments, fluorescence recovery after photobleaching (FRAP) static laser microscopy, and determination of intracellular calcium ([Ca2+] i ), we show that various CLL-specific PLCγ2 variants such as PLCγ2S707Y are hyper-responsive to activated BTK, even in the absence of BTK's catalytic activity and independently of enhanced PLCγ2 phospholipid substrate supply. At high levels of B-cell receptor (BCR) activation, which may occur in individual CLL patients, catalytically-inactive BTK restored the ability of the BCR to mediate increases in [Ca2+] i Because catalytically-inactive BTK is insensitive to active-site BTK inhibitors, the mechanism involving the noncatalytic BTK uncovered here may contribute to preexisting reduced sensitivity or even primary resistance of CLL to these drugs.

Predicting Self-Rated Health Across the Life Course: Health Equity Insights from Machine Learning Models.

BACKGROUND: Self-rated health is a strong predictor of mortality and morbidity. Machine learning techniques may provide insights into which of the multifaceted contributors to self-rated health are key drivers in diverse groups. OBJECTIVE: We used machine learning algorithms to predict self-rated health in diverse groups in the Behavioral Risk Factor Surveillance System (BRFSS), to understand how machine learning algorithms might be used explicitly to examine drivers of self-rated health in diverse populations. DESIGN: We applied three common machine learning algorithms to predict self-rated health in the 2017 BRFSS survey, stratified by age, race/ethnicity, and sex. We replicated our process in the 2016 BRFSS survey. PARTICIPANTS: We analyzed data from 449,492 adult participants of the 2017 BRFSS survey. MAIN MEASURES: We examined area under the curve (AUC) statistics to examine model fit within each group. We used traditional logistic regression to predict self-rated health associated with features identified by machine learning models. KEY RESULTS: Each algorithm, regularized logistic regression (AUC: 0.81), random forest (AUC: 0.80), and support vector machine (AUC: 0.81), provided good model fit in the BRFSS. Predictors of self-rated health were similar by sex and race/ethnicity but differed by age. Socioeconomic features were prominent predictors of self-rated health in mid-life age groups. Income [OR: 1.70 (95% CI: 1.62-1.80)], education [OR: 2.02 (95% CI: 1.89, 2.16)], physical activity [OR: 1.52 (95% CI: 1.46-1.58)], depression [OR: 0.66 (95% CI: 0.63-0.68)], difficulty concentrating [OR: 0.62 (95% CI: 0.58-0.66)], and hypertension [OR: 0.59 (95% CI: 0.57-0.61)] all predicted the odds of excellent or very good self-rated health. CONCLUSIONS: Our analysis of BRFSS data show social determinants of health are prominent predictors of self-rated health in mid-life. Our work may demonstrate promising practices for using machine learning to advance health equity.

The trajectory of racial/ethnic disparities in the use of cancer screening before and during the COVID-19 pandemic: A large U.S. academic center analysis.

Cancer screening rates declined sharply early in the COVID-19 pandemic. The impact of the pandemic may have exacerbated existing disparities in cancer screening due to the disproportionate burden of illness and job loss among racial/ ethnic minorities, and potentially, uneven resumption of care between different racial/ ethnic groups. Using electronic health record data from Mass General Brigham (MGB), we assessed changes in rates of breast, cervical, colorectal and lung cancer screening before and during the pandemic. Among patients who received primary care in an MGB-affiliated primary care practice, cancer screening rates were calculated as the number of individuals who received a screening test for each cancer type over the number of individuals due for each test, during each month between April 2019-November 2020. We conducted an interrupted time-series analysis to test for changes in screening rates by race/ethnicity before and during the pandemic. Prior to the pandemic, relative to White individuals, Asian women were less likely to receive breast cancer screening (p < 0.001), and Latinx and Black individuals were less likely to screen for lung cancer (p < 0.001 and p = 0.02). Our results did not show significant improvement or worsening of racial/ethnic disparities for any cancer screening type as screening resumed. However, as of November 2020 rates of screening for breast cancer were lower than pre-pandemic levels for Latinx individuals, and lung cancer screening rates were higher than baseline for Latinx, Black or White individuals. Further monitoring of disparities in cancer screening is warranted as the pandemic evolves.

Cancer screening in the U.S. through the COVID-19 pandemic, recovery, and beyond.

COVID-19 has proved enormously disruptive to the provision of cancer screening, which does not just represent an initial test but an entire process, including risk detection, diagnostic follow-up, and treatment. Successful delivery of services at all points in the process has been negatively affected by the pandemic. There is a void in empirical high-quality evidence to support a specific strategy for administering cancer screening during a pandemic and its resolution phase, but several pragmatic considerations can help guide prioritization efforts. Targeting guideline-eligible people who have never been screened, or those who are significantly out of date with screening, has the potential to maximize benefits now and into the future. Disruptions to care due to the pandemic could represent an unparalleled opportunity to reassess early detection programs towards an explicit, thoughtful, and just prioritization of populations historically experiencing cancer disparities. By focusing screening services on populations that have the most to gain, and by careful and deliberate planning for the period following the pandemic, we can positively affect cancer outcomes for all.

De-implementation of cervical cancer screening before age 21.

In 2012, United States consensus guidelines were modified to recommend that cervical cancer screening not begin before age 21 and, since 2014, the Health Effectiveness Data and Information Set (HEDIS), a health plan quality measurement too, has included a measure for non-recommended cervical cancer screening among females ages 16-20. Our goal was to describe prevalence over time of cervical cancer screening before age 21 following the 2012 guideline change, and provide information to help understand how rapidly new guidelines may be disseminated and implemented into clinical practice. We used longitudinal clinical and administrative data from three diverse healthcare systems in the Population-based Research to Optimize the Screening Process (PROSPR II) consortium to examine annual trends in screening before age 21. We identified 55,316 average-risk, screening-eligible females ages 18-20 between 2011 and 2017. For each calendar year, we estimated the proportion of females who received a Papanicolaou (Pap) test. We observed a steady decline in the proportion of females under age 21 who received a Pap test, from an average of 8.3% in 2011 to <1% in 2017 across the sites. The observed steady decline suggests growing adherence to the 2012 consensus guidelines. This trend was consistent across diverse geographic regions, healthcare systems, and patient populations, strengthening the generalizability of the results; however, since we only had 1-2 years of study data prior to the consensus guidelines, we cannot discern whether screening under age 21 was already in decline. Nonetheless, these results provide data to compare with other guideline changes to de-implement non-recommended screening practices.

Predictors of Enrollment of Older Smokers in Six Smoking Cessation Trials in the Lung Cancer Screening Setting: The Smoking Cessation at Lung Examination (SCALE) Collaboration.

SIGNIFICANCE: Increased rates of smoking cessation will be essential to maximize the population benefit of low-dose CT screening for lung cancer. The NCI's Smoking Cessation at Lung Examination (SCALE) Collaboration includes eight randomized trials, each assessing evidence-based interventions among smokers undergoing lung cancer screening (LCS). We examined predictors of trial enrollment to improve future outreach efforts for cessation interventions offered to older smokers in this and other clinical settings. METHODS: We included the six SCALE trials that randomized individual participants. We assessed demographics, intervention modalities, LCS site and trial administration characteristics, and reasons for declining. RESULTS: Of 6285 trial- and LCS-eligible individuals, 3897 (62%) declined and 2388 (38%) enrolled. In multivariable logistic regression analyses, Blacks had higher enrollment rates (OR 1.5, 95% CI 1.2,1.8) compared to Whites. Compared to "NRT Only" trials, those approached for "NRT + prescription medication" trials had higher odds of enrollment (OR 6.1, 95% CI 4.7,7.9). Regarding enrollment methods, trials using "Phone + In Person" methods had higher odds of enrollment (OR 1.6, 95% CI 1.2,1.9) compared to trials using "Phone Only" methods. Some of the reasons for declining enrollment included "too busy" (36.6%), "not ready to quit" (8.2%), "not interested in research" (7.7%), and "not interested in the intervention offered" (6.2%). CONCLUSION: Enrolling smokers in cessation interventions in the LCS setting is a major priority that requires multiple enrollment and intervention modalities. Barriers to enrollment provide insights that can be addressed and applied to future cessation interventions to improve implementation in LCS and other clinical settings with older smokers. IMPLICATIONS: We explored enrollment rates and reasons for declining across six smoking cessation trials in the lung cancer screening setting. Offering multiple accrual methods and pharmacotherapy options predicted increased enrollment across trials. Enrollment rates were also greater among Blacks compared to Whites. The findings offer practical information for the implementation of cessation trials and interventions in the lung cancer screening context and other clinical settings, regarding intervention modalities that may be most appealing to older, long-term smokers.

Safety and Persistence of Nalmefene Treatment for Alcohol Dependence. Results from Two Post-authorisation Safety Studies.

AIMS: Two post-authorisation studies assessed the safety and persistence of patients' use of nalmefene. METHODS: The START study (EUPAS5678) was a non-interventional, multi-country, prospective, 18-month (8 follow-up visits) cohort study including outpatients initiating nalmefene for the first time. The multi-database retrospective cohort study (MDRC, EUPAS14083) included baseline and follow-up data from German, Swedish and UK healthcare databases. Both studies permitted 'all comers' without explicit exclusion criteria; predefined subgroups of interest included the elderly (≥65 years) as well as patients with significant psychiatric and/or somatic comorbidities. RESULTS: START study: Overall, the mean duration of nalmefene treatment was 10.3 ± 7.3 months (N = 1348), with 49.0% of patients treated for ≥1 year; frequent reasons for treatment discontinuation were 'goal reached' and 'drug cost'. The most frequently reported adverse drug reactions (ADRs) were nausea (4.7%), dizziness (3.2%) and insomnia (2.0%). ADR rates appeared higher in the elderly subpopulation (18.6% reported ≥1 ADR vs. 12.0% in the total population) but were not higher in the other predefined subgroups.MDRC study: The database follow-up analysis followed 2892 patients over 18 months for whom the duration of nalmefene treatment was between 2 and 3 months and <5% of patients used nalmefene for ≥1 year. CONCLUSIONS: Despite the inclusion of a wider patient population (e.g. elderly patients and those with relevant co-morbidities), the safety and tolerability profile of nalmefene given in routine practice was consistent with previous clinical studies. The differing rates of persistence beyond 1 year likely reflect the different methodologies and highlight the relevance of psychosocial support at follow-up visits.