What Goes into Patient Selection for Lung Cancer Screening? Factors Associated with Clinician Judgments of Suitability for Screening.

Rationale: Achieving the net benefit of lung cancer screening (LCS) depends on optimizing patient selection. Objective: To identify factors associated with clinician assessments that a patient was unlikely to benefit from LCS ("LCS-inappropriate") because of comorbidities or limited life expectancy. Methods: Retrospective analysis of patients assessed for LCS at 30 Veterans Health Administration facilities from January 1, 2015 to February 1, 2021. We conducted hierarchical mixed-effects logistic regression analyses to determine factors associated with clinicians' designations of LCS inappropriateness (primary outcome), accounting for 3-year predicted probability (i.e., competing risk) of non-lung cancer death. Measurements and Main Results: Among 38,487 LCS-eligible patients, 1,671 (4.3%) were deemed LCS-inappropriate by clinicians, whereas 4,383 (11.4%) had an estimated 3-year competing risk of non-lung cancer death greater than 20%. Patients with higher competing risks of non-lung cancer death were more likely to be deemed LCS-inappropriate (odds ratio [OR], 2.66; 95% confidence interval [CI], 2.32-3.05). Older patients (ages 75-80; OR, 1.45; 95% CI, 1.18-1.78) and those with interstitial lung disease (OR, 1.98; 95% CI, 1.51-2.59) were more likely to be deemed LCS-inappropriate than would be explained by competing risk of non-lung cancer death, whereas patients currently smoking (OR, 0.65; 95% CI, 0.58-0.73) were less likely to be deemed LCS-inappropriate, suggesting that clinicians over- or underweighted these factors. The probability of being deemed LCS-inappropriate varied from 0.4% to 74%, depending on the clinician making the assessment (median OR, 3.07; 95% CI, 2.89-3.25). Conclusion: Concerningly, the likelihood that a patient is deemed LCS-inappropriate is more strongly associated with the clinician making the assessment than with patient characteristics. Patient selection may be optimized by providing decision support to help clinicians assess net LCS benefit.

Factors Associated With Declining Lung Cancer Screening After Discussion With a Physician in a Cohort of US Veterans.

Importance: Lung cancer screening (LCS) is underused in the US, particularly in underserved populations, and little is known about factors associated with declining LCS. Guidelines call for shared decision-making when LCS is offered to ensure informed, patient-centered decisions. Objective: To assess how frequently veterans decline LCS and examine factors associated with declining LCS. Design, Setting, and Participants: This retrospective cohort study included LCS-eligible US veterans who were offered LCS between January 1, 2013, and February 1, 2021, by a physician at 1 of 30 Veterans Health Administration (VHA) facilities that routinely used electronic health record clinical reminders documenting LCS eligibility and veterans' decisions to accept or decline LCS. Data were obtained from the Veterans Affairs (VA) Corporate Data Warehouse or Medicare claims files from the VA Information Resource Center. Main Outcomes and Measures: The main outcome was documentation, in clinical reminders, that veterans declined LCS after a discussion with a physician. Logistic regression analyses with physicians and facilities as random effects were used to assess factors associated with declining LCS compared with agreeing to LCS. Results: Of 43 257 LCS-eligible veterans who were offered LCS (mean [SD] age, 64.7 [5.8] years), 95.9% were male, 84.2% were White, and 37.1% lived in a rural zip code; 32.0% declined screening. Veterans were less likely to decline LCS if they were younger (age 55-59 years: odds ratio [OR], 0.69; 95% CI, 0.64-0.74; age 60-64 years: OR, 0.80; 95% CI, 0.75-0.85), were Black (OR, 0.80; 95% CI, 0.73-0.87), were Hispanic (OR, 0.62; 95% CI, 0.49-0.78), did not have to make co-payments (OR, 0.92; 95% CI, 0.85-0.99), or had more frequent VHA health care utilization (outpatient: OR, 0.70; 95% CI, 0.67-0.72; emergency department: OR, 0.86; 95% CI, 0.80-0.92). Veterans were more likely to decline LCS if they were older (age 70-74 years: OR, 1.27; 95% CI, 1.19-1.37; age 75-80 years: OR, 1.93; 95% CI, 1.73-2.17), lived farther from a VHA screening facility (OR, 1.06; 95% CI, 1.03-1.08), had spent more days in long-term care (OR, 1.13; 95% CI, 1.07-1.19), had a higher Elixhauser Comorbidity Index score (OR, 1.04; 95% CI, 1.03-1.05), or had specific cardiovascular or mental health conditions (congestive heart failure: OR, 1.25; 95% CI, 1.12-1.39; stroke: OR, 1.14; 95% CI, 1.01-1.28; schizophrenia: OR, 1.87; 95% CI, 1.60-2.19). The physician and facility offering LCS accounted for 19% and 36% of the variation in declining LCS, respectively. Conclusions and Relevance: In this cohort study, older veterans with serious comorbidities were more likely to decline LCS and Black and Hispanic veterans were more likely to accept it. Variation in LCS decisions was accounted for more by the facility and physician offering LCS than by patient factors. These findings suggest that shared decision-making conversations in which patients play a central role in guiding care may enhance patient-centered care and address disparities in LCS.

Invasive Procedures and Associated Complications After Initial Lung Cancer Screening in a National Cohort of Veterans.

BACKGROUND: Little is known about rates of invasive procedures and associated complications after lung cancer screening (LCS) in nontrial settings. RESEARCH QUESTION: What are the frequency of invasive procedures, complication rates, and factors associated with complications in a national sample of veterans screened for lung cancer? STUDY DESIGN AND METHODS: We conducted a retrospective cohort analysis of veterans who underwent LCS in any Veterans Health Administration (VA) facility between 2013 and 2019 and identified veterans who underwent invasive procedures within 10 months of initial LCS. The primary outcome was presence of a complication within 10 days after an invasive procedure. We conducted hierarchical mixed-effects logistic regression analyses to determine patient- and facility-level factors associated with complications resulting from an invasive procedure. RESULTS: Our cohort of 82,641 veterans who underwent LCS was older, more racially diverse, and had more comorbidities than National Lung Screening Trial (NLST) participants. Overall, 1,741 veterans (2.1%) underwent an invasive procedure after initial screening, including 856 (42.3%) bronchoscopies, 490 (24.2%) transthoracic needle biopsies, and 423 (20.9%) thoracic surgeries. Among veterans who underwent procedures, 151 (8.7%) experienced a major complication (eg, respiratory failure, prolonged hospitalization) and an additional 203 (11.7%) experienced an intermediate complication (eg, pneumothorax, pleural effusion). Veterans who underwent thoracic surgery (OR, 7.70; 95% CI, 5.48-10.81), underwent multiple nonsurgical procedures (OR, 1.49; 95% CI, 1.15-1.92), or carried a dementia diagnosis (OR, 3.91; 95% CI, 1.79-8.52) were more likely to experience complications. Invasive procedures were performed less often than in the NLST (2.1% vs 4.2%), but veterans were more likely to experience complications after each type of procedure. INTERPRETATION: These findings may reflect a higher threshold to perform procedures in veteran populations with multiple comorbidities and higher risks of complications. Future work should focus on optimizing the identification of patients whose chance of benefit likely outweighs the complication risks.

Adherence to Follow-up Testing Recommendations in US Veterans Screened for Lung Cancer, 2015-2019.

Importance: Lung cancer screening (LCS) can reduce lung cancer mortality with close follow-up and adherence to management recommendations. Little is known about factors associated with adherence to LCS in real-world practice, with data limited to case series from selected LCS programs. Objective: To analyze adherence to follow-up based on standardized follow-up recommendations in a national cohort and to identify factors associated with delayed or absent follow-up. Design, Setting, and Participants: This retrospective cohort study was conducted in Veterans Health Administration (VHA) facilities across the US. Veterans were screened for lung cancer between 2015 to 2019 with sufficient follow-up time to receive recommended evaluation. Patient- and facility-level logistic regression analyses were performed. Data were analyzed from November 26, 2019, to December 16, 2020. Main Outcomes and Measures: Receipt of the recommended next step after initial LCS according to Lung CT Screening Reporting & Data System (Lung-RADS) category, as captured in VHA or Medicare claims. Results: Of 28 294 veterans (26 835 [94.8%] men; 21 969 individuals [77.6%] were White; mean [SD] age, 65.2 [5.5] years) who had an initial LCS examination, 17 863 veterans (63.1%) underwent recommended follow-up within the expected timeframe, whereas 3696 veterans (13.1%) underwent late evaluation, and 4439 veterans (15.7%) had no apparent evaluation. Facility-level differences were associated with 9.2% of the observed variation in rates of late or absent evaluation. In multivariable-adjusted models, Black veterans (odds ratio [OR], 1.19 [95% CI, 1.10-1.29]), veterans with posttraumatic stress disorder (OR, 1.13 [95% CI, 1.03-1.23]), veterans with substance use disorders (OR, 1.11 [95% CI, 1.01-1.22]), veterans with lower income (OR, 0.88 [95% CI, 0.79-0.98]), and those living at a greater distance from a VHA facility (OR, 1.06 [95% CI, 1.02-1.10]) were more likely to experience delayed or no follow-up; veterans with higher risk findings (Lung-RADS category 4 vs Lung-RADS category 1: OR, 0.35 [95% CI, 0.28-0.43]) and those screened in high LCS volume facilities (OR, 0.38 [95% CI, 0.21-0.67]) or academic facilities (OR, 0.86 [95% CI, 0.80-0.92]) were less likely to experience delayed or no follow-up. In sensitivity analyses, varying how stringently adherence was defined, expected evaluation ranged from 14 486 veterans (49.7%) under stringent definitions to 20 578 veterans (78.8%) under liberal definitions. Conclusions and Relevance: In this cohort study that captured follow-up care from the integrated VHA health care system and Medicare, less than two-thirds of patients received timely recommended follow-up after initial LCS, with higher risk of delayed or absent follow-up among marginalized populations, such as Black individuals, individuals with mental health disorders, and individuals with low income, that have long experienced disparities in lung cancer outcomes. Future work should focus on identifying facilities that promote high adherence and disseminating successful strategies to promote equity in LCS among marginalized populations.

Global, regional, and national levels and trends in maternal mortality between 1990 and 2015, with scenario-based projections to 2030: a systematic analysis by the UN Maternal Mortality Estimation Inter-Agency Group.

BACKGROUND: Millennium Development Goal 5 calls for a 75% reduction in the maternal mortality ratio (MMR) between 1990 and 2015. We estimated levels and trends in maternal mortality for 183 countries to assess progress made. Based on MMR estimates for 2015, we constructed projections to show the requirements for the Sustainable Development Goal (SDG) of less than 70 maternal deaths per 100,000 livebirths globally by 2030. METHODS: We updated the UN Maternal Mortality Estimation Inter-Agency Group (MMEIG) database with more than 200 additional records (vital statistics from civil registration systems, surveys, studies, or reports). We generated estimates of maternal mortality and related indicators with 80% uncertainty intervals (UIs) using a Bayesian model. The model combines the rate of change implied by a multilevel regression model with a time-series model to capture data-driven changes in country-specific MMRs, and includes a data model to adjust for systematic and random errors associated with different data sources. RESULTS: We had data for 171 of 183 countries. The global MMR fell from 385 deaths per 100,000 livebirths (80% UI 359-427) in 1990, to 216 (207-249) in 2015, corresponding to a relative decline of 43·9% (34·0-48·7), with 303,000 (291,000-349,000) maternal deaths worldwide in 2015. Regional progress in reducing the MMR since 1990 ranged from an annual rate of reduction of 1·8% (0·0-3·1) in the Caribbean to 5·0% (4·0-6·0) in eastern Asia. Regional MMRs for 2015 ranged from 12 deaths per 100,000 livebirths (11-14) for high-income regions to 546 (511-652) for sub-Saharan Africa. Accelerated progress will be needed to achieve the SDG goal; countries will need to reduce their MMRs at an annual rate of reduction of at least 7·5%. INTERPRETATION: Despite global progress in reducing maternal mortality, immediate action is needed to meet the ambitious SDG 2030 target, and ultimately eliminate preventable maternal mortality. Although the rates of reduction that are needed to achieve country-specific SDG targets are ambitious for most high mortality countries, countries that made a concerted effort to reduce maternal mortality between 2000 and 2010 provide inspiration and guidance on how to accomplish the acceleration necessary to substantially reduce preventable maternal deaths. FUNDING: National University of Singapore, National Institute of Child Health and Human Development, USAID, and the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction.

Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow.

Mouse conventional dendritic cells (cDCs) can be classified into two functionally distinct lineages: the CD8α(+) (CD103(+)) cDC1 lineage, and the CD11b(+) cDC2 lineage. cDCs arise from a cascade of bone marrow (BM) DC-committed progenitor cells that include the common DC progenitors (CDPs) and pre-DCs, which exit the BM and seed peripheral tissues before differentiating locally into mature cDCs. Where and when commitment to the cDC1 or cDC2 lineage occurs remains poorly understood. Here we found that transcriptional signatures of the cDC1 and cDC2 lineages became evident at the single-cell level from the CDP stage. We also identified Siglec-H and Ly6C as lineage markers that distinguished pre-DC subpopulations committed to the cDC1 lineage (Siglec-H(-)Ly6C(-) pre-DCs) or cDC2 lineage (Siglec-H(-)Ly6C(+) pre-DCs). Our results indicate that commitment to the cDC1 or cDC2 lineage occurs in the BM and not in the periphery.