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Background: Two monovalent mRNA vaccines, available in December 2020, were demonstrated to have high efficacy against both the original SARS-CoV-2 strain and variants circulating through the summer and into the fall of 2021. In the context of the Omicron/BA.1 variant, which was predominant from late fall 2021 into winter of 2022 in the United States, and subsequent Omicron subvariants that have been predominant thereafter, vaccine effectiveness of the monovalent mRNA vaccine option is attenuated., Objectives: We aim to investigate the relative effectiveness of the bivalent booster compared to the monovalent booster against SARS-CoV-2 infection in the 60 days following administration in Shelby County, TN., Design: This observational population-based cohort study utilizes COVID-19 surveillance data to identify adults who were vaccinated with a monovalent booster dose between August 1, 2022 and August 30, 2022 or a bivalent booster dose between September 1, 2022 and September 30, 2022. Both groups were followed for COVID-19 status for 60 days from their administration date., Methods: We calculated incidence rates with 95% confidence intervals and propensity-adjusted hazard ratios with 95% confidence intervals of COVID-19 diagnosis in the 60 days following administration of the booster dose between the bivalent group and the monovalent group. Stratified analysis was conducted by age group (18-34, 35-64, and 65+ years old)., Results: The incidence of reported SARS-CoV-2 infection was substantially higher for those who received the monovalent booster, across age groups. Overall, we observed a 51% lower hazard of infection during the study period among those who received the bivalent booster, compared to the monovalent booster., Conclusion: These results support and extend prior findings that the bivalent booster dose may be more effective in preventing infection against the Omicron sub-variants of SARS-CoV-2., (© The Author(s), 2024.)

Background: Biomarker-directed therapy requires biomarker testing. We assessed the patterns of epidermal growth factor receptor (EGFR) and programmed death ligand 1 (PDL1) testing in a non-small cell lung cancer (NSCLC) resection cohort. We hypothesized that testing would increase but be unevenly distributed across patient-, provider- and institution-level demographics., Methods: We examined the population-based Mid-South Quality of Surgical Resection (MS-QSR) cohort of NSCLC resections. We evaluated the proportions receiving EGFR and PDL1 testing before and after approval of biomarker-directed adjuvant therapy (2018-2020 vs. 2021-2022). We used association tests and logistic regression to compare factors., Results: From 2018 to 2022, 1,687 patients had NSCLC resection across 12 MS-QSR institutions: 1,045 (62%) from 2018 to 2020 and 642 (38%) from 2021 to 2022. From 2018 to 2020, 11% had EGFR testing versus 38% in 2021 to 2022 (56% in those meeting ADAURA trial inclusion criteria, P < 0.0001). From 2018 to 2020, 8% had PDL1 testing versus 20% in 2021 to 2022 (P < 0.0001). EGFR testing did not significantly differ by age (P = 0.07), sex (P = 0.99), race (P = 0.33), or smoking history (P = 0.28); PDL1 testing did not differ significantly by age (P = 0.47), sex (P = 0.41), race (P = 0.51), or health insurance (P = 0.07). Testing was significantly less likely in nonteaching and non-Commission on Cancer-accredited hospitals and after resection by cardiothoracic or general surgeons (vs. general thoracic surgeons; all P < 0.05)., Conclusions: EGFR and PDL1 testing increased after approval of biomarker-directed adjuvant therapies. However, testing rates were still suboptimal and differed by institutional- and provider-level factors., Impact: The association of institutional, pathologist, and surgeon characteristics with differences in testing demonstrate the need for more standardization in testing processes., (©2024 American Association for Cancer Research.)

Background: The emergency department (ED) is a vital source of healthcare for individuals living with sickle cell disease (SCD). Prior research indicates that during the COVID-19 pandemic some individuals with SCD avoided the ED for fear of acquiring COVID-19 or delayed visiting the ED by self-management of symptoms or pain crisis at home. The purpose of the current study was to understand ED utilization rates before and during the pandemic among individuals living with SCD., Methods: We conducted a retrospective cohort study using population-based SCD surveillance systems in California, Georgia, Michigan, and Tennessee to assess the impact of the pandemic on ED utilization among people with SCD by (1) analyzing trends in monthly ED utilization from January 2019 - December 2020, with specific attention given to immediate changes at the onset of the pandemic; and (2) calculating changes in the volume of utilization by comparing the total ED visits made from March - December 2020 to the same period in 2019, both overall and by demographic characteristics., Results: Across all states, a decline in ED utilization during the onset of the pandemic was seen, with the largest decline seen in those under age 10. By December 2020, utilization rates were higher than their lowest observed month of April 2020, but had not fully returned to pre-COVID levels. During the pandemic, ED visits in each state decreased by as much as 25%, and the number of people with any ED utilization decreased by as much as 26%., Conclusions: This study confirms and extends the existing literature related to the impact of the pandemic on healthcare utilization patterns in the US, in a unique population with increased healthcare needs., (© 2024. The Author(s).)

Abstract: Guidelines recommend transfer to adult health care within 6 months of completing pediatric care; however, this has not been studied in sickle cell disease (SCD). We hypothesized that longer transfer gaps are associated with increased resource utilization. Transfer gaps were defined as the time between the last pediatric and first adult visits. We estimated the association between varying transfer gaps and the rates of inpatient, emergency department (ED), and outpatient visits, using negative binomial regression. Health care utilization was evaluated in a mid-south comprehensive program for a follow-up period of up to 8 years (2012-2020) and was restricted to the first 2 years of adult health care. In total, 183 young adults (YAs) with SCD (51% male, 67% HbSS/HbSβ0-thalassemia) were transferred to adult health care between 2012 and 2018. YAs with transfer gaps ≥6 months compared with <2 months had 2.01 (95% confidence interval [CI], 1.31-3.11) times the rate of hospitalizations in the 8-year follow-up and 1.89 (95% CI, 1.17-3.04) when restricted to the first 2 years of adult health care. In the first 2 years of adult care, those with transfer gaps ≥6 months compared with <2 months, had 1.75 (95% CI, 1.10-2.80) times the rate of ED encounters. Those with gaps ≥2 to <6 months compared with <2 months had 0.71 (95 % CI, 0.53-0.95) times the rate of outpatient visits. Among YAs with SCD, a longer transfer gap was associated with increased inpatient and decreased outpatient encounters in adult health care and more ED encounters in the first 2 years of adult health care. Strategies to reduce the transfer gaps are needed., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Telehealth can be defined as using remote technologies to provide health care. It may increase access to care among people with sickle cell disease (SCD). This study examined (1) telehealth use, (2) characteristics of telehealth use, and (3) differences between telehealth users and nonusers among people with SCD during the COVID-19 pandemic. Methods: This was a retrospective analysis of Medicaid claims among four states [California (CA), Georgia (GA), Michigan (MI), Tennessee (TN)] participating in the Sickle Cell Data Collection program. Study participants were individuals ≥1 year old with SCD enrolled in Medicaid September 2019-December 2020. Telehealth encounters during the pandemic were characterized by provider specialty. Health care utilization was compared between those who did (users) and did not (nonusers) use telehealth, stratified by before and during the pandemic. Results: A total of 8,681 individuals with SCD (1,638 CA; 3,612 GA; 1,880 MI; and 1,551 TN) were included. The proportion of individuals with SCD that accessed telehealth during the pandemic varied across states from 29% in TN to 80% in CA. During the pandemic, there was a total of 21,632 telehealth encounters across 3,647 users. In two states (MI and GA), over a third of telehealth encounters were with behavioral health providers. Telehealth users had a higher average number of health care encounters during the pandemic: emergency department (pooled mean = 2.6 for users vs. 1.5 for nonusers), inpatient (1.2 for users vs. 0.6 for nonusers), and outpatient encounters (6.0 for users vs. 3.3 for nonusers). Conclusions: Telehealth was frequently used at the beginning of the COVID-19 pandemic by people with SCD. Future research should focus on the context, facilitators, and barriers of its implementation in this population.

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a mental health disorder that affects attention and behavior. People with ADHD frequently encounter challenges in social interactions, facing issues, like social rejection and difficulties in interpersonal relationships, due to their inattention, impulsivity, and hyperactivity., Methods: A National Longitudinal Survey of Youth (NLSY) database was employed to identify patterns of ADHD symptoms. The children who were born to women in the NLSY study between 1986 and 2014 were included. A total of 1,847 children in the NLSY 1979 cohort whose hyperactivity/inattention score was calculated when they were four years old were eligible for this study. A trajectory modeling method was used to evaluate the trajectory classes. Sex, baseline antisocial score, baseline anxiety score, and baseline depression score were adjusted to build the trajectory model. We used stepwise multivariate logistic regression models to select the risk factors for the identified trajectories., Results: The trajectory analysis identified six classes for ADHD, including (1) no sign class, (2) few signs since preschool being persistent class, (3) few signs in preschool but no signs later class, (4) few signs in preschool that magnified in elementary school class, (5) few signs in preschool that diminished later class, and (6) many signs since preschool being persistent class. The sensitivity analysis resulted in a similar trajectory pattern, except for the few signs since preschool that magnified later class. Children's race, breastfeeding status, headstrong score, immature dependent score, peer conflict score, educational level of the mother, baseline antisocial score, baseline anxious/depressed score, and smoking status 12 months prior to the birth of the child were found to be risk factors in the ADHD trajectory classes., Conclusion: The trajectory classes findings obtained in the current study can (a) assist a researcher in evaluating an intervention (or combination of interventions) that best decreases the long-term impact of ADHD symptoms and (b) allow clinicians to better assess as to which class a child with ADHD belongs so that appropriate intervention can be employed., Competing Interests: The authors declare no conflict of interest, financial or otherwise., (© 2024 The Author(s). Published by Bentham Open.)

Introduction: Early lung cancer detection programs improve surgical resection rates and survival but may skew toward more indolent cancers., Methods: Hypothesizing that differences in stage-stratified survival indicate differences in biological aggressiveness and possible length-time and overdiagnosis bias, we assessed a cohort who had curative-intent resection, categorized by diagnostic pathways: screening, incidental pulmonary nodule program, and non-program based. Survival was analyzed using Kaplan-Meier plots, log-rank tests, and Cox regression, comparing aggregate and stage-stratified survival across cohorts with Tukey's method for multiple testing., Results: Of 1588 patients, 111 patients (7%), 357 patients (22.5%), and 1120 patients (70.5%) were diagnosed through screening, pulmonary nodule, and non-program-based pathways; 0% versus 9% versus 6% were older than 80 years ( p  = 0.0048); 17%, 23%, and 24% had a Charlson Comorbidity score greater than or equal to 2 ( p  = 0.0143); 7%, 6%, and 9% had lepidic adenocarcinoma; 26%, 31%, and 34% had poorly or undifferentiated tumors ( p  = 0.1544); and 93%, 87%, and 77% had clinical stage I ( p < 0.0001).Aggregate 5-year survival was 87%, 72%, and 65% ( p  = 0.0009), including 95%, 74%, and 74% for pathologic stage I. Adjusted pairwise comparisons showed similar survival in screening and nodule program cohorts ( p  = 0.9905). Nevertheless, differences were significant between screening and non-program-based cohorts ( p  = 0.0007, adjusted hazard ratio 0.33 [95% confidence interval: 0.18-0.6]) and between nodule and nonprogram cohorts (adjusted hazard ratio 0.77 [95% confidence interval: 0.61-0.99]). Stage I comparisons yielded p  = 0.2256, 0.1131, and 0.911. In respective pathways, 0%, 2%, and 2% of patients with stage I disease who were older than 80 years had a Charlson score greater than or equal to 2 ( p  = 0.3849)., Conclusions: Neither length-time nor overdiagnosis bias was evident in NSCLC diagnosed through screening or incidental pulmonary nodule programs., Competing Interests: Dr. Matthew P. Smeltzer is a paid research consultant for the Association of Community Cancer Centers. Dr. Raymond U. Osarogiagbon holds patents for surgical specimen collection kit and stocks in Pfizer, Gilead Sciences, and Eli Lilly; is a paid research consultant for the American Cancer Society, the Association of Community Cancer Centers, Genentech/Roche, Biodesix, Lungevity Foundation, National Cancer Institute, Tryptych Healthcare Partners, and AstraZeneca; and is founder of Oncobox Device, Inc. The remaining authors declare no conflict of interest., (© 2024 Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer.)

Background: Hydroxyurea is an evidence-based disease-modifying therapy for sickle cell disease (SCD) but is underutilized. The Integration of Mobile Health into Sickle Cell Disease Care to Increase Hydroxyurea Utilization (meSH) multicenter study leveraged mHealth to deliver targeted interventions to patients and providers. SCD studies often underenroll; and recruitment strategies in the SCD population are not widely studied. Unanticipated events can negatively impact enrollment, making it important to study strategies that ensure adequate study accrual., Objective: The goal of this study was to evaluate enrollment barriers and the impact of modified recruitment strategies among patients and providers in the meSH study in response to a global emergency., Methods: Recruitment was anticipated to last 2 months for providers and 6 months for patients. The recruitment strategies used with patients and providers, new recruitment strategies, and recruitment rates were captured and compared. To document recruitment adaptations and their reasons, study staff responsible for recruitment completed an open-ended 9-item questionnaire eliciting challenges to recruitment and strategies used. Themes were extrapolated using thematic content analysis., Results: Total enrollment across the 7 sites included 89 providers and 293 patients. The study acceptance rate was 85.5% (382/447) for both patients and providers. The reasons patients declined participation were most frequently a lack of time and interest in research, while providers mostly declined because of self-perceived high levels of SCD expertise, believing they did not need the intervention. Initially, recruitment involved an in-person invitation to participate during clinic visits (patients), staff meetings (providers), or within the office (providers). We identified several important recruitment challenges, including (1) lack of interest in research, (2) lack of human resources, (3) unavailable physical space for recruitment activities, and (4) lack of documentation to verify eligibility. Adaptive strategies were crucial to alleviate enrollment disruptions due to the COVID-19 pandemic. These included remote approaching and consenting (eg, telehealth, email, and telephone) for patients and providers. Additionally, for patients, recruitment was enriched by simplification of enrollment procedures (eg, directly approaching patients without a referral from the provider) and a multitouch method (ie, warm introductions with flyers, texts, and patient portal messages). We found that patient recruitment rates were similar between in-person and adapted (virtual with multitouch) approaches (167/200, 83.5% and 126/143, 88.1%, respectively; P=.23). However, for providers, recruitment was significantly higher for in-person vs remote recruitment (48/50, 96% and 41/54, 76%, respectively, P<.001)., Conclusions: We found that timely adaptation in recruitment strategies secured high recruitment rates using an assortment of enriched remote recruitment strategies. Flexibility in approach and reducing the burden of enrollment procedures for participants aided enrollment. It is important to continue identifying effective recruitment strategies in studies involving patients with SCD and their providers and the impact and navigation of recruitment challenges., Trial Registration: ClinicalTrials.Gov NCT03380351; https://clinicaltrials.gov/study/NCT03380351., International Registered Report Identifier (irrid): RR2-10.2196/16319., (©Chinonyelum Nwosu, Hamda Khan, Rita Masese, Judith M Nocek, Siera Gollan, Taniya Varughese, Sarah Bourne, Cindy Clesca, Sara R Jacobs, Ana Baumann, Lisa M Klesges, Nirmish Shah, Jane S Hankins, Matthew P Smeltzer. Originally published in JMIR Formative Research (https://formative.jmir.org), 16.04.2024.)

Introduction: Lung cancer risk in screening age-ineligible persons with incidentally detected lung nodules is poorly characterized. We evaluated lung cancer risk in two age-ineligible Lung Nodule Program (LNP) cohorts., Methods: Prospective observational study comparing 2-year cumulative lung cancer diagnosis risk, lung cancer characteristics, and overall survival between low-dose computed tomography (LDCT) screening participants aged 50 to 80 years and LNP participants aged 35 to younger than 50 years (young) and older than 80 years (elderly)., Results: From 2015 to 2022, lung cancer was diagnosed in 329 (3.43%), 39 (1.07%), and 172 (6.87%) LDCT, young, and elderly LNP patients, respectively. The 2-year cumulative incidence was 3.0% (95% confidence intervals [CI]: 2.6%-3.4%) versus 0.79% (CI: 0.54%-1.1%) versus 6.5% (CI: 5.5%-7.6%), respectively, but lung cancer diagnosis risk was similar between young LNP and Lung CT Screening Reporting and Data System (Lung-RADS) 1 (adjusted hazard ratio [aHR] = 0.88 [CI: 0.50-1.56]) and Lung-RADS 2 (aHR = 1.0 [0.58-1.72]). Elderly LNP risk was greater than Lung-RADS 3 (aHR = 2.34 [CI: 1.50-3.65]), but less than 4 (aHR = 0.28 [CI: 0.22-0.35]). Lung cancer was stage I or II in 62.92% of LDCT versus 33.33% of young (p = 0.0003) and 48.26% of elderly (p = 0.0004) LNP cohorts; 16.72%, 41.03%, and 29.65%, respectively, were diagnosed at stage IV. The aggregate 5-year overall survival rates were 57% (CI: 48-67), 55% (CI: 39-79), and 24% (CI: 15-40) (log-rank p < 0.0001). Results were similar after excluding persons with any history of cancer., Conclusions: LNP modestly benefited persons too young or old for screening. Differences in clinical characteristics and outcomes suggest differences in biological characteristics of lung cancer in these three patient cohorts., (Copyright © 2023. Published by Elsevier Inc.)

Sickle cell disease (SCD) remains a public health priority in the United States because of its association with complex health needs, reduced life expectancy, lifelong disabilities, and high cost of care. A cross-sectional analysis was conducted to calculate the crude and race-specific birth prevalence for SCD using state newborn screening program records during 2016-2020 from 11 Sickle Cell Data Collection program states. The percentage distribution of birth mother residence within Social Vulnerability Index quartiles was derived. Among 3,305 newborns with confirmed SCD (including 57% with homozygous hemoglobin S or sickle β-null thalassemia across 11 states, 90% of whom were Black or African American [Black], and 4% of whom were Hispanic or Latino), the crude SCD birth prevalence was 4.83 per 10,000 (one in every 2,070) live births and 28.54 per 10,000 (one in every 350) non-Hispanic Black newborns. Approximately two thirds (67%) of mothers of newborns with SCD lived in counties with high or very high levels of social vulnerability; most mothers lived in counties with high or very high levels of vulnerability for racial and ethnic minority status (89%) and housing type and transportation (64%) themes. These findings can guide public health, health care systems, and community program planning and implementation that address social determinants of health for infants with SCD. Implementation of tailored interventions, including increasing access to transportation, improving housing, and advancing equity in high vulnerability areas, could facilitate care and improve health outcomes for children with SCD., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Sophia S. Horiuchi reports ownership of Natera stock and stock options and of Roche stock by her spouse. Mariam Kayle reports institutional support from Agios Medical Education Program and Novo Nordisk Independent Medical Education Activity to support the 11th Annual Sickle Cell Conference, September 8–9, 2023; receipt of consulting fees from Loyola University; receipt of honorarium for being an ad hoc reviewer from the National Institutes of Health (NIH), Center for Scientific Review, Social and Environmental Determinants of Health Study Section; and uncompensated membership in the American Society of Hematology Research Collaborative Data Hub Oversight Group, Sickle Cell Disease Subcommittee. Carri S. Polick reports support from the Veterans Administration and Duke University Clinical and Translational Science Institute. Ashima Singh reports institutional support from NIH, National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, and the Health Resources and Services Administration (HRSA) Sickle Cell Treatment Demonstration Program. John J. Strouse reports institutional support from the HRSA Southeast Region Coordinating Center Sickle Cell Treatment Demonstration Program and the North Carolina State Department of Health Sickle Cell Syndrome Program for the Duke Adult and Pediatric Sickle Cell Program; royalties from UpToDate for preparation of guidance on the use of hydroxyurea for sickle cell disease (SCD); consulting fees for GLG telephone consultation on SCD and Guidepoint telephone consultation on SCD; receipt of honoraria from the University of Rochester-Equity in Sickle Cell Disease Care; payment for medical legal expert testimony from Emory University in a case involving emergency department care of an adult with sickle beta thalassemia; travel support from the American Society of Hematology Sickle Cell Learning Community Meeting and Sickle Cell Disease Association of America Meeting to speak on behalf of the American Society of Hematology and travel support from the American Thrombosis Hemostasis Network Data Summit as an invited speaker on gene therapy for SCD: Design for Equity; payment for participation on a data safety monitoring board for disc medicines for phase 1 trial planning for bitopertin for SCD; and service as vice president of the Sickle Cell Adult Provider Network. No other potential conflicts of interest were disclosed.

Background: Despite its prognostic importance, poor pathologic nodal staging of lung cancer prevails. We evaluated the impact of 2 interventions to improve pathologic nodal staging., Methods: We implemented a lymph node specimen collection kit to improve intraoperative lymph node collection (surgical intervention) and a novel gross dissection method for intrapulmonary node retrieval (pathology intervention) in nonrandomized stepped-wedge fashion, involving 12 hospitals and 7 pathology groups. We used standard statistical methods to compare surgical quality and survival of patients who had neither intervention (group 1), pathology intervention only (group 2), surgical intervention only (group 3), and both interventions (group 4)., Results: Of 4019 patients from 2009 to 2021, 50%, 5%, 21%, and 24%, respectively, were in groups 1 to 4. Rates of nonexamination of lymph nodes were 11%, 9%, 0%, and 0% and rates of nonexamination of mediastinal lymph nodes were 29%, 35%, 2%, and 2%, respectively, in groups 1 to 4 (P < .0001). Rates of attainment of American College of Surgeons Operative Standard 5.8 were 22%, 29%, 72%, and 85%; and rates of International Association for the Study of Lung Cancer complete resection were 14%, 21%, 53%, and 61% (P < .0001). Compared with group 1, adjusted hazard ratios for death were as follows: group 2, 0.93 (95% CI, 0.76-1.15); group 3, 0.91 (0.78-1.03); and group 4, 0.75 (0.64-0.87). Compared with group 2, group 4 adjusted hazard ratio was 0.72 (0.57-0.91); compared with group 3, it was 0.83 (0.69-0.99). These relationships remained after exclusion of wedge resections., Conclusions: Combining a lymph node collection kit with a novel gross dissection method significantly improved pathologic nodal evaluation and survival., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Hydroxyurea reduces the frequency of vaso-occlusive complications, increases hemoglobin, and decreases mortality in sickle cell disease (SCD). Although current guidelines recommend escalation to maximum tolerated dose (MTD), the use of fixed low-dose hydroxyurea is common in low-resource countries. We conducted a systematic review and meta-analysis to evaluate the efficacy of escalated doses versus fixed low-dose of hydroxyurea in adults with SCD. Nine studies were included in the quantitative synthesis, four evaluating fixed low-dose and five evaluating escalated doses of hydroxyurea. Average daily doses of hydroxyurea in the fixed low-dose and escalated dose studies were ~10 and 22 mg/kg, respectively. There was no difference in the estimate of vaso-occlusive crisis rate between escalated and fixed low-dose studies (p = .73). The mean difference in hemoglobin from baseline to follow-up was greater for fixed low-dose than escalated dose studies (1.07 g/dL vs. 0.54 g/dL, p = .01). No difference was seen in the mean estimate of fetal hemoglobin. Despite limited eligible studies and substantial heterogeneity of effect between the studies for several outcomes, there appears to be clinical equipoise regarding the most appropriate hydroxyurea dosing regimen in adults with SCD. Controlled studies of hydroxyurea at MTD versus fixed low-dose in adults with SCD are required., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Sickle cell disease (SCD) is an inherited red blood cell disorder associated with frequent painful events and organ damage. Hydroxyurea (HU) is the recommended evidence-based treatment of SCD. However, among patients eligible for HU, prescription rates are low. Utilizing a scoping review approach, we summarized and synthesized relevant findings regarding provider barriers and facilitators to the prescription of HU in youth and adults with SCD and provided suggestions for future implementation strategies to improve prescription rates. Relevant databases were searched using specified search terms. Articles reporting provider barriers and/or facilitators to prescribing HU were included. A total of 10 studies met the inclusion criteria. Common barriers to the prescription of HU identified by providers included: doubts around patients' adherence to HU and their engaging in required testing, concerns about side effects, lack of knowledge, cost and patient concerns about side effects. Facilitators to the prescription of HU included beliefs in the effectiveness of HU, provider demographics and knowledge. Findings suggest significant provider biases exist, particularly in the form of negative perceptions towards patients' ability to adhere to taking HU and engaging in the required follow-up. Improving provider knowledge and attitudes towards HU and SCD may help improve low prescription rates., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Introduction: COVID-19 mRNA vaccine protection against the Omicron variant of SARS-CoV-2 has been shown to be attenuated. Previous research in Shelby County, Tennessee found that vaccine effectiveness might differ by age in the Omicron surge, a finding not reported for other variants. To assess whether patterns in vaccine effectiveness by age group differed on the basis of the predominant strain of SARS-CoV2, we evaluated vaccine effectiveness in Shelby County, Tennessee by age group in the Delta wave and Omicron BA.1 (Omicron) wave., Methods: Case and vaccination statuses of residents were assessed using COVID-19 surveillance data. Age was stratified as 18-34, 35-64, and ≥65 years. Vaccination groups included unvaccinated, fully vaccinated, and fully vaccinated + booster. Person time was counted in each wave by vaccination status until the time of a positive reported COVID-19 test or until the end of the study period., Results: Incidence of COVID-19 was much higher during the Omicron wave than during the Delta wave across all vaccination groups. During the Delta wave, among adults, 79.2% fewer cases were identified in those fully vaccinated and 94.8% fewer in those fully vaccinated + booster, compared with 40.2% and 66.7%, respectively, in the Omicron wave, compared with those who were unvaccinated., Conclusions: This study found evidence that vaccine effectiveness differed by age group during the Omicron wave, where the same pattern was not prominent in the Delta wave. Further analysis investigating the influence of behavior patterns and other potential confounders on vaccine effectiveness would be useful in further understanding the relationship between age and vaccine effectiveness., (© 2023 Published by Elsevier Inc. on behalf of The American Journal of Preventive Medicine Board of Governors.)

We explored the association of novel urinary biomarkers with albumin-creatinine ratio (ACR) in adults with sickle cell anaemia. Of 37 participants, 13 (35.2%) had persistent albuminuria (PA). Urinary levels of clusterin (p = 0.002), retinol-binding protein 4 (p = 0.008), alpha-1 microglobulin (p = 0.002) and angiotensinogen (p = 0.006) were significantly higher in participants with PA than in those without PA. Although univariate analysis showed significant associations between both alpha-1 microglobulin (p = 0.035) and angiotensinogen (p = 0.0021) with ACR, only angiotensinogen was associated with ACR in multivariable analysis (p = 0.04). Our results suggest that urinary angiotensinogen may identify sickle cell anaemia patients at risk for kidney disease., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Purpose: The quality and outcomes of curative-intent lung cancer surgery vary in populations. Surgeons are key drivers of surgical quality. We examined the association between surgeon-level intermediate outcomes differences, patient survival differences, and potential mitigation by processes of care., Patients and Methods: Using a baseline population-based surgical resection cohort, we derived surgeon-level cut points for rates of positive margins, nonexamination of lymph nodes, nonexamination of mediastinal lymph nodes, and wedge resections. Applying the baseline cut points to a subsequent cohort from the same population-based data set, we assign surgeons into three performance categories in reference to each metric: 1 (<25th percentile), 2 (25th-75th percentile), and 3 (>75th percentile). The sum of performance scores created three surgeon quality tiers: 1 (4-6, low), 2 (7-9, intermediate), and 3 (10-12, high). We used chi-squared, Wilcoxon-Mann-Whitney, and Kruskal-Wallis tests to compare patient characteristics between the baseline and subsequent cohorts and across surgeon tiers. We applied Cox proportional hazards models to examine the association between patient survival and surgeon performance tier, sequentially adjusting for clinical stage, patient characteristics, and four specific processes., Results: From 2009 to 2021, 39 surgeons performed 4,082 resections across the baseline and subsequent cohorts. Among 31 subsequent cohort surgeons, five were tier 1, five were tier 2, and 21 were tier 3. Tier 1 and 2 surgeons had significantly worse outcomes than tier 3 surgeons (hazard ratio [HR], 1.37; 95% CI, 1.10 to 1.72 and 1.19; 95% CI, 1.00 to 1.43, respectively). Adjustment for specific processes mitigated the surgeon-tiered survival differences, with adjusted HRs of 1.02 (95% CI, 0.8 to 1.3) and 0.93 (95% CI, 0.7 to 1.25), respectively., Conclusion: Readily accessible intermediate outcomes metrics can be used to stratify surgeon performance for targeted process improvement, potentially reducing patient survival disparities.

Objective: Population-level data on sickle cell disease (SCD) are sparse in the United States. The Centers for Disease Control and Prevention (CDC) is addressing the need for SCD surveillance through state-level Sickle Cell Data Collection Programs (SCDC). The SCDC developed a pilot common informatics infrastructure to standardize processes across states., Materials and Methods: We describe the process for establishing and maintaining the proposed common informatics infrastructure for a rare disease, starting with a common data model and identify key data elements for public health SCD reporting., Results: The proposed model is constructed to allow pooling of table shells across states for comparison. Core Surveillance Data reports are compiled based on aggregate data provided by states to CDC annually., Discussion and Conclusion: We successfully implemented a pilot SCDC common informatics infrastructure to strengthen our distributed data network and provide a blueprint for similar initiatives in other rare diseases., Competing Interests: Dr Matthew Smeltzer has worked as a paid research consultant for the Association of Community Cancer Centers. The findings and conclusions in this publication are those of the authors and do not necessarily represent the views of the North Carolina Department of Health and Human Services, Division of Public Health. No other authors have competing interests to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

The sickle cell mutation increases morbidity in those with sickle cell disease (SCD) and potentially sickle cell trait, impacting pulmonary, coagulation, renal, and other systems that are implicated in COVID-19 severity. There are no population-based registries for hemoglobinopathies, and they are not tracked in COVID-19 testing. We used COVID-19 test data from 2 states linked to newborn screening data to estimate COVID outcomes in people with SCD or trait compared with normal hemoglobin. We linked historical newborn screening data to COVID-19 tests, hospitalization, and mortality data and modeled the odds of hospitalization and mortality. Georgia's cohort aged 0 to 12 years; Michigan's, 0 to 33 years. Over 8% of those in Michigan were linked to positive COVID-19 results, and 4% in Georgia. Those with SCD showed significantly higher rates of COVID-19 hospitalization than the normal hemoglobin Black cohort, and Michigan had higher rates of mortality as well. Outcomes among those with the trait did not differ significantly from the normal hemoglobin Black group. People with SCD are at increased risk of COVID-19-related hospitalization and mortality and are encouraged to be vaccinated and avoid infection. Persons with the trait were not at higher risk of COVID-related severe outcomes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Low-dose computed tomography (LDCT) screening reduces lung cancer mortality, but current eligibility criteria underestimate risk in women and racial minorities. We evaluated the impact of screening criteria modifications on LDCT eligibility and lung cancer detection., Methods: Using data from a Lung Nodule Program, we compared persons eligible for LDCT by the following: U.S. Preventive Services Task Force (USPSTF) 2013 criteria (55-80 y, ≥30 pack-years of smoking, and ≤15 y since cessation); USPSTF2021 criteria (50-80 y, ≥20 pack-years of smoking, and ≤15 y since cessation); quit duration expanded to less than or equal to 25 years (USPSTF2021-QD25); reducing the pack-years of smoking to more than or equal to 10 years (USPSTF2021-PY10); and both (USPSTF2021-QD25-PY10). We compare across groups using the chi-square test or analysis of variance., Results: The 17,421 individuals analyzed were of 56% female sex, 69% white, 28% black; 13% met USPSTF2013 criteria; 17% USPSTF2021; 18% USPSTF2021-QD25; 19% USPSTF2021-PY10; and 21% USPSTF2021-QD25-PY10. Additional eligible individuals by USPSTF2021 (n = 682) and USPSTF2021-QD25-PY10 (n = 1402) were 27% and 29% black, both significantly higher than USPSTF2013 (17%, p < 0.0001). These additional eligible individuals were 55% (USPSTF2021) and 55% (USPSTF2021-QD25-PY10) of female sex, compared with 48% by USPSTF2013 (p < 0.05). Of 1243 persons (7.1%) with lung cancer, 22% were screening eligible by USPSTF13. USPSTF2021-QD25-PY10 increased the total number of persons with lung cancer by 37%. These additional individuals with lung cancer were of 57% female sex (versus 48% with USPSTF2013, p = 0.0476) and 24% black (versus 20% with USPSTF2013, p = 0.3367)., Conclusions: Expansion of LDCT screening eligibility criteria to allow longer quit duration and fewer pack-years of exposure enriches the screening-eligible population for women and black persons., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Importance: Guideline-concordant management of lung nodules promotes early lung cancer diagnosis, but the lung cancer risk profile of persons with incidentally detected lung nodules differs from that of screening-eligible persons., Objective: To compare lung cancer diagnosis hazard between participants receiving low-dose computed tomography screening (LDCT cohort) and those in a lung nodule program (LNP cohort)., Design, Setting, and Participants: This prospective cohort study included LDCT vs LNP enrollees from January 1, 2015, to December 31, 2021, who were seen in a community health care system. Participants were prospectively identified, data were abstracted from clinical records, and survival was updated at 6-month intervals. The LDCT cohort was stratified by Lung CT Screening Reporting and Data System as having no potentially malignant lesions (Lung-RADS 1-2 cohort) vs those with potentially malignant lesions (Lung-RADS 3-4 cohort), and the LNP cohort was stratified by smoking history into screening-eligible vs screening-ineligible groups. Participants with prior lung cancer, younger than 50 years or older than 80 years, and lacking a baseline Lung-RADS score (LDCT cohort only) were excluded. Participants were followed up to January 1, 2022., Main Outcomes and Measures: Comparative cumulative rates of lung cancer diagnosis and patient, nodule, and lung cancer characteristics between programs, using LDCT as a reference., Results: There were 6684 participants in the LDCT cohort (mean [SD] age, 65.05 [6.11] years; 3375 men [50.49%]; 5774 [86.39%] in the Lung-RADS 1-2 and 910 [13.61%] in the Lung-RADS 3-4 cohorts) and 12 645 in the LNP cohort (mean [SD] age, 65.42 [8.33] years; 6856 women [54.22%]; 2497 [19.75%] screening eligible and 10 148 [80.25%] screening ineligible). Black participants constituted 1244 (18.61%) of the LDCT cohort, 492 (19.70%) of the screening-eligible LNP cohort, and 2914 (28.72%) of the screening-ineligible LNP cohort (P < .001). The median lesion size was 4 (IQR, 2-6) mm for the LDCT cohort (3 [IQR, 2-4] mm for Lung-RADS 1-2 and 9 [IQR, 6-15] mm for Lung-RADS 3-4 cohorts), 9 (IQR, 6-16) mm for the screening-eligible LNP cohort, and 7 (IQR, 5-11) mm for the screening-ineligible LNP cohort. In the LDCT cohort, lung cancer was diagnosed in 80 participants (1.44%) in the Lung-RADS 1-2 cohort and 162 (17.80%) in the Lung-RADS 3-4 cohort; in the LNP cohort, it was diagnosed in 531 (21.27%) in the screening-eligible cohort and 447 (4.40%) in the screening-ineligible cohort. Compared with Lung-RADS 1-2, the fully adjusted hazard ratios (aHRs) were 16.2 (95% CI, 12.7-20.6) for the screening-eligible cohort and 3.8 (95% CI, 3.0-5.0) for the screening-ineligible cohort; compared with Lung-RADS 3-4, the aHRs were 1.2 (95% CI, 1.0-1.5) and 0.3 (95% CI, 0.2-0.4), respectively. The stage of lung cancer was I to II in 156 of 242 patients (64.46%) in the LDCT cohort, 276 of 531 (52.00%) in the screening-eligible LNP cohort, and 253 of 447 (56.60%) in the screening-ineligible LNP cohort., Conclusions and Relevance: In this cohort study, the cumulative lung cancer diagnosis hazard of screening-age persons enrolled in the LNP was higher than that in a screening cohort, irrespective of smoking history. The LNP provided access to early detection for a higher proportion of Black persons.

Purpose: Multidisciplinary lung cancer care is assumed to improve care delivery by increasing transparency, objectivity, and shared decision making; however, there is a lack of high-level evidence demonstrating its benefits, especially in community-based health care systems. We used implementation and team science principles to establish a colocated multidisciplinary lung cancer clinic in a large community-based health care system and evaluated patient experience and outcomes within and outside this clinic., Methods: We conducted a prospective frequency-matched comparative effectiveness study (ClinicalTrials.gov identifier: NCT02123797) evaluating the thoroughness of lung cancer staging, receipt of stage-appropriate treatment, and survival between patients receiving care in the multidisciplinary clinic and those receiving usual serial care. Target enrollment was 150 patients on the multidisciplinary arm and 300 on the serial care arm. We frequency-matched patients by clinical stage, performance status, insurance type, race, and age., Results: A total of 526 patients were enrolled: 178 on the multidisciplinary arm and 348 on the serial care arm. After adjusting for other factors, multidisciplinary patients had significantly higher odds (odds ratio [OR]: 2.3 [95% CI, 1.5 to 3.4]) of trimodality staging compared with serial care. Patients on the multidisciplinary arm also had higher odds of receiving invasive stage confirmation (OR: 2.0 [95% CI, 1.4 to 3.1]) and mediastinal stage confirmation (OR: 1.9 [95% CI, 1.3 to 2.8]). Additionally, patients receiving multidisciplinary care were significantly more likely to receive stage-appropriate treatment (OR: 1.8 [95% CI, 1.1 to 3.0]). We found no significant difference in overall or progression-free survival between study arms., Conclusion: The multidisciplinary clinic delivered significant improvements in evidence-based quality care on multiple levels. Even in the absence of a demonstrable survival benefit, these findings provide a strong rationale for recommending this model of care.

Purpose: Adult survivors of childhood acute lymphoblastic leukemia (ALL) have impaired adaptive physical function and poor health-related quality of life (HRQoL). Obesity may contribute to these impairments by increasing the physiological cost of walking. Due to treatment exposures during ALL therapy, survivors' cost of walking may be more impacted by obesity than the general population. Therefore, we examined associations between obesity, persistent motor neuropathy, and energy cost of walking; and examined associations between energy cost of walking, adaptive physical function, and HRQoL, in adult survivors of childhood ALL vs. community controls., Methods: Obesity was measured via body mass index (BMI) and body fat percentage. The physiological cost index (PCI) was calculated from the six-minute walk test. Adaptive physical functioning was measured using two tests: the timed up and go (TUG) test and the physical performance test. Persistent motor neuropathy was measured using the modified total neuropathy score; HRQoL was measured using the Short-Form-36 questionnaire. The associations between obesity and PCI were evaluated using multivariable linear regressions in adult survivors of childhood ALL ( n  = 1,166) and community controls ( n  = 491). Then, the associations between PCI, adaptive physical functioning and peripheral neuropathy were examined using multivariable linear regressions. Finally, to determine the association between obesity, and neuropathy on PCI, while accounting for potential lifestyle and treatment confounders, a three model, sequential linear regression was used., Results: Obese individuals (BMI > 40 kg/m 2 and excess body fat percentage [males: >25%; females: >33%]) had higher PCI compared to those with normal BMI and body fat percentage (0.56 ± 0.01 vs. 0.49 ± 0.009 beats/meter p  < .01; and 0.51 ± 0.007 vs. 0.48 ± .0006 beats/meter p  < .01, respectively). Treatment exposures did not attenuate this association. Increased PCI was associated with longer TUG time in survivors, but not community controls (6.14 ± 0.02 s vs. 5.19 ± 0.03 s, p  < .01). Survivors with PCI impairment >95th percentile of community controls had lower HRQoL compared to un-impaired ALL survivors: 46.9 ± 0.56 vs. 50.4 ± 1.08, respectively ( p  < .01)., Conclusion: Obesity was associated with increased PCI. Survivors with high PCI had disproportionately worse adaptive physical function and HRQoL compared to controls. Survivors with increased energy costs of walking may benefit from weight loss interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Wogksch, Finch, Nolan, Smeltzer, Mzayek, Goodenough, Pui, Inaba, Mulrooney, Kaste, Brinkman, Lanctot, Srivastava, Jefferies, Armstrong, Robison, Hudson and Ness.)

Introduction: Two mRNA vaccines approved in the U.S. have high efficacy against COVID-19 disease from the original strain of SARS-CoV-2. We evaluated the population-level association between vaccination status and COVID-19 infection by age group during the initial wave of the Omicron variant in a diverse population in the Mid-South U.S., Methods: In this observational population-based cohort study, vaccination information and positive COVID-19 cases in Shelby County, Tennessee, from December 12, 2021 through January 22, 2022 were collected from surveillance data at the Shelby County Health Department (Memphis, Tennessee). Exposure groups included individuals who were unvaccinated, were fully vaccinated, and were fully vaccinated + booster. We calculated incidence rates of COVID-19 diagnosis per person-year among county adult (aged 18+ years) residents in crude form and stratified by age group., Results: In this population-based study, we identified 64.56% fewer COVID-19 infections in the fully vaccinated + booster group and 41.08% fewer in the fully vaccinated group than in the unvaccinated group., Conclusions: These results confirm and extend the findings of recent immunologic and epidemiologic studies in a racially diverse region of the Mid-South U.S. In stratified analysis, we also found evidence suggesting that vaccine protection against Omicron may increase with age., (© 2022 The Authors.)

Purpose: Lung cancer screening saves lives, but implementation is challenging. We evaluated two approaches to early lung cancer detection-low-dose computed tomography screening (LDCT) and program-based management of incidentally detected lung nodules., Methods: A prospective observational study enrolled patients in the early detection programs. For context, we compared them with patients managed in a Multidisciplinary Care Program. We compared clinical stage distribution, surgical resection rates, 3- and 5-year survival rates, and eligibility for LDCT screening of patients diagnosed with lung cancer., Results: From 2015 to May 2021, 22,886 patients were enrolled: 5,659 in LDCT, 15,461 in Lung Nodule, and 1,766 in Multidisciplinary Care. Of 150, 698, and 1,010 patients diagnosed with lung cancer in the respective programs, 61%, 60%, and 44% were diagnosed at clinical stage I or II, whereas 19%, 20%, and 29% were stage IV ( P = .0005); 47%, 42%, and 32% had curative-intent surgery ( P < .0001); aggregate 3-year overall survival rates were 80% (95% CI, 73 to 88) versus 64% (60 to 68) versus 49% (46 to 53); 5-year overall survival rates were 76% (67 to 87) versus 60% (56 to 65) versus 44% (40 to 48), respectively. Only 46% of 1,858 patients with lung cancer would have been deemed eligible for LDCT by US Preventive Services Task Force (USPSTF) 2013 criteria, and 54% by 2021 criteria. Even if all eligible patients by USPSTF 2021 criteria had been enrolled into LDCT, the Nodule Program would have detected 20% of the stage I-II lung cancer in the entire cohort., Conclusion: LDCT and Lung Nodule Programs are complementary, expanding access to early lung cancer detection and curative treatment to different-risk populations. Implementing Lung Nodule Programs may alleviate emerging disparities in access to early lung cancer detection., Competing Interests: Raymond U. OsarogiagbonStock and Other Ownership Interests: Lilly, Pfizer, Gilead SciencesHonoraria: Medscape, BiodesixConsulting or Advisory Role: Association of Community Cancer Centers (ACCC), AstraZeneca, American Cancer Society, Triptych Health Partners, Genentech/Roche, National Cancer Institute, Lilly, LUNGevity, BiodesixPatents, Royalties, Other Intellectual Property: Two US and one China patents for lymph node specimen collection kit and method of pathologic evaluationOther Relationship: Oncobox Jeffrey WrightResearch Funding: INmune Bio, Alexion Pharmaceuticals Matthew P. SmeltzerOther Relationship: Association of Community Cancer Centers (ACCC)No other potential conflicts of interest were reported.

Background: Lung cancer management guidelines strive to improve outcomes. Theoretically, thorough staging promotes optimal treatment selection. We examined the association between guideline-concordant invasive mediastinal nodal staging, guideline-concordant treatment, and non-small cell lung cancer survival., Research Question: What is the current practice of invasive mediastinal nodal staging for patients with lung cancer in a structured multidisciplinary care environment? Is guideline-concordant staging associated with guideline-concordant treatment? How do they relate to survival?, Study Design and Methods: We evaluated patients with nonmetastatic non-small cell lung cancer diagnosed from 2014 through 2019 in the Multidisciplinary Thoracic Oncology Program of the Baptist Cancer Center, Memphis, Tennessee. We examined patterns of mediastinal nodal staging and stage-stratified treatment, grouping patients into cohorts with guideline-concordant staging alone, guideline-concordant treatment alone, both, or neither. We evaluated overall survival with Kaplan-Meier curves and Cox proportional hazards models., Results: Of 882 patients, 456 (52%) received any invasive mediastinal staging. Seventy-four percent received guideline-concordant staging; guideline-discordant staging decreased from 34% in 2014 to 18% in 2019 (P < .0001). Recipients of guideline-concordant staging were more likely to receive guideline-concordant treatment (83% vs 66%; P < .0001). Sixty-one percent received both guideline-concordant invasive mediastinal staging and guideline-concordant treatment; 13% received guideline-concordant staging alone; 17% received guideline-concordant treatment alone; and 9% received neither. Survival was greatest in patients who received both (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.26-0.63), followed by those who received guideline-concordant treatment alone (aHR, 0.60; 95% CI, 0.36-0.99), and those who received guideline-concordant staging alone (aHR, 0.64; 95% CI, 0.37-1.09) compared with neither (P < .0001, log-rank test)., Interpretation: Levels of guideline-concordant staging were high, were rising, and were associated with guideline-concordant treatment selection in this multidisciplinary care cohort. Guideline-concordant staging and guideline-concordant treatment were complementary in their association with improved survival, supporting the connection between these two processes and lung cancer outcomes., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

With the increasing number and variety of clinical trials and observational data analyses, producers and consumers of clinical research must have a working knowledge of an array of statistical methods. Our goal with this body of work is to highlight common types of data and analyses in clinical research. We provide a brief, yet comprehensive overview of common data types in clinical research and appropriate statistical methods for analyses. These include continuous data, binary data, count data, multinomial data, and time-to-event data. We include references for further studies and real-world examples of the application of these methods. In summary, we review common continuous and discrete data, summary statistics for said data, common hypothesis tests and appropriate statistical tests, and underlying assumption for the statistical tests. This information is summarized in tabular format, for additional accessibility.

Introduction: To evaluate the effects of the global coronavirus disease 2019 (COVID-19) pandemic on lung cancer trials, we surveyed investigators and collected aggregate enrollment data for lung cancer trials across the world before and during the pandemic., Methods: A Data Collection Survey collected aggregate monthly enrollment numbers from 294 global lung cancer trials for 2019 to 2020. A 64-question Action Survey evaluated the impact of COVID-19 on clinical trials and identified mitigation strategies implemented., Results: Clinical trial enrollment declined from 2019 to 2020 by 14% globally. Most reductions in enrollment occurred in April to June where we found significant decreases in individual site enrollment (p = 0.0309). Enrollment was not significantly different in October 2019 to December of 2019 versus 2020 (p = 0.25). The most frequent challenges identified by the Action Survey (N = 172) were fewer eligible patients (63%), decrease in protocol compliance (56%), and suspension of trials (54%). Patient-specific challenges included access to trial site (49%), ability to travel (54%), and willingness to visit the site (59%). The most frequent mitigation strategies included modified monitoring requirements (47%), telehealth visits (45%), modified required visits (25%), mail-order medications (25%), and laboratory (27%) and radiology (21%) tests at nonstudy facilities. Sites that felt the most effective mitigation strategies were telehealth visits (85%), remote patient-reported symptom collection (85%), off-site procedures (85%), and remote consenting (89%)., Conclusions: The COVID-19 pandemic created many challenges for lung cancer clinical trials conduct and enrollment. Mitigation strategies were used and, although the pandemic worsened, trial enrollment improved. A more flexible approach may improve enrollment and access to clinical trials, even beyond the pandemic., (Copyright © 2022. Published by Elsevier Inc.)

The high lethality of ovarian cancer in the United States and associated complexities of the patient journey across the cancer care continuum warrant an assessment of current practices and barriers to quality care in the United States. The objectives of this study were to identify and assess key components in the provision of high-quality care delivery for patients with ovarian cancer, identify challenges in the implementation of best practices, and develop corresponding quality-related recommendations to guide multidisciplinary ovarian cancer programs and practices. This multiphase ovarian cancer quality-care initiative was guided by a multidisciplinary expert steering committee, including gynecologic oncologists, pathologists, a genetic counselor, a nurse navigator, social workers, and cancer center administrators. Key partnerships were also established. A collaborative approach was adopted to develop comprehensive recommendations by identifying ideal quality-of-care program components in advanced epithelial ovarian cancer management. The core program components included: care coordination and patient education, prevention and screening, diagnosis and initial management, treatment planning, disease surveillance, equity in care, and quality of life. Quality-directed recommendations were developed across 7 core program components, with a focus on ensuring high-quality ovarian cancer care delivery for patients through improved patient education and engagement by addressing unmet medical and supportive care needs. Implementation challenges were described, and key recommendations to overcome barriers were provided. The recommendations emerging from this initiative can serve as a comprehensive resource guide for multidisciplinary cancer practices, providers, and other stakeholders working to provide quality-directed cancer care for patients diagnosed with ovarian cancer and their families., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Although the efficacy and safety profiles of both intranasal fentanyl and midazolam are well studied in pediatric patients, few studies examine their use in younger children., Objectives: To examine and report our experiences in a pediatric emergency department (ED) with intranasal fentanyl and midazolam in children aged 3 years and younger., Methods: This retrospective study investigated intranasal fentanyl and midazolam administration, alone and in combination, in children 3 years and younger treated in a pediatric ED., Results: Of 6198 patients included, 1762 received intranasal fentanyl alone, 1115 received intranasal midazolam alone, and 3321 received combination therapy. The median (interquartile range [IQR]) patient age was 2.2 (1.5-3) years. Initial median (IQR) fentanyl dose was 2.7 (2-3) µg/kg, with 13.3% receiving a repeat dose. Initial median (IQR) midazolam dose was 0.3 (0.2-0.3) mg/kg, with 3.3% receiving a second dose. Children receiving both fentanyl and midazolam had median (IQR) initial doses of 2.8 (2.1-3) µg/kg and 0.3 (0.2-0.3) mg/kg, respectively. Of these, 3.2% received repeat doses of both medications. Laceration repairs (33.8%) and incision and drainage (22.2%) accounted for the majority of indications. Only 2.9% (n = 178) received additional opioids. No serious adverse events requiring a reversal agent or respiratory support were reported., Conclusions: Intranasal fentanyl and midazolam, alone and in combination, can provide analgesia and anxiolysis to children aged 3 years and younger in the ED setting. Further prospective studies are needed to better evaluate their safety and efficacy in this younger population., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Sickle cell disease (SCD) leads to chronic and acute complications that require specialised care to manage symptoms and optimise clinical results. The National Heart Lung and Blood Institute (NHLBI) evidence-based guidelines assist providers in caring for individuals with SCD, but adoption of these guidelines by providers has not been optimal. The objective of this study was to identify barriers to treating individuals with SCD., Methods: The SCD Implementation Consortium aimed to investigate the perception and level of comfort of providers regarding evidence-based care by surveying providers in the regions of six clinical centres across the USA, focusing on non-emergency care from the providers' perspective., Results: Respondents included 105 providers delivering clinical care for individuals with SCD. Areas of practice were most frequently paediatrics (24%) or haematology/SCD specialist (24%). The majority (77%) reported that they were comfortable managing acute pain episodes while 63% expressed comfort with managing chronic pain. Haematologists and SCD specialists showed higher comfort levels prescribing opioids (100% vs 67%, p=0.004) and managing care with hydroxyurea (90% vs 51%, p=0.005) compared with non-haematology providers. Approximately 33% of providers were unaware of the 2014 NHLBI guidelines. Nearly 63% of providers felt patients' medical needs were addressed while only 22% felt their mental health needs were met., Conclusions: A substantial number of providers did not know about NHLBI's SCD care guidelines. Barriers to providing care for patients with SCD were influenced by providers' specialty, training and practice setting. Increasing provider knowledge could improve hydroxyurea utilisation, pain management and mental health support., Competing Interests: Competing interests: JSH receives research funding support from Global Blood Therapeutics and is received consultancy fees from Bluebird Bio, Forma Therapeutics, and Global Blood Therapeutics; JG receives research funding support from Pfizer; AK owns stock in Magenta Therapeutics., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We previously found that neurodevelopmental deficits commonly occurred in three-year-olds with sickle cell disease (SCD), but clinical significance was uncertain because a comparison group was lacking. Our objective in the current study was to prospectively compare neurodevelopment in three-year-old children with SCD to an age-appropriate control group. The Brigance Preschool Screen II is a neurodevelopmental screening examination which can be administered in 15-20 min. SCD patients (Group 1) were compared with community controls of similar age and ethnicity enrolled in daycare/preschool (Group 2). SCD patients who were receiving hydroxycarbamide treatment were also compared (Group 3). Two hundred forty-five three-year-olds were evaluated: Group 1, 111; Group 2, 114; and Group 3, 20. The below cut-off rate on the Brigance test was higher in Group 1 (73%) than in Group 2 (61%; P = 0·04). In multivariate analysis of Group 1 patients, only lower household income and more persons living in the home were independent predictors of this. Patients with SCD and matched controls had high rates of 'failing' the Brigance test. The below cut-off rate in untreated children with SCD was associated with low household income and increased number of persons living in the home., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Introduction: Complete and accurate pathology reports are vital to postoperative prognostication and management. We evaluated the impact of three interventions across a diverse group of hospitals on pathology reports of postresection NSCLC., Methods: We evaluated pathology reports for patients who underwent curative-intent surgical resection for NSCLC, at 11 institutions within four contiguous Dartmouth Hospital Referral Regions in Arkansas, Mississippi, and Tennessee from 2004 to 2020, for completeness and accuracy, before and after the following three quality improvement interventions: education (feedback to heighten awareness); synoptic reporting; and a lymph node specimen collection kit. We compared the proportion of pathology reports with the six most important items for postoperative management (specimen type, tumor size, histologic type, pathologic [p] T-category, pN-category, margin status) across the following six patient cohorts: preintervention control, postintervention with four different combinations of interventions, and a contemporaneous nonintervention external control., Results: In the postintervention era, the odds of reporting all key items were eight times higher than those in the preintervention era (OR = 8.3, 95 % confidence interval [CI]: 6.7-10.2, p < 0.0001). There were sixfold and eightfold increases in the odds of accurate pT- and pN-category reporting in the postintervention era compared with the preintervention era (pT OR = 5.7, 95 % CI: 4.7-6.9; pN OR = 8.0, 95 % CI: 6.5-10.0, both p < 0.0001). Within the intervention groups, the odds of reporting all six key items, accurate pT category, and accurate pN-category were highest in patients who received all three interventions., Conclusions: Gaps in the quality of NSCLC pathologic reportage can be identified, quantified, and corrected by rationally designed interventions., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: We compared NSCLC treatment and survival within and outside a multidisciplinary model of care from a large community health care system., Methods: We implemented a rigorously benchmarked "enhanced" Multidisciplinary Thoracic Oncology Conference (eMTOC) and used Tumor Registry data (2011-2017) to evaluate guideline-concordant care. Because eMTOC was located in metropolitan Memphis, we separated non-MTOC patient by metropolitan and regional location. We categorized National Comprehensive Cancer Network guideline-concordant treatment as "preferred," or "appropriate" (allowable under certain circumstances). We compared demographic and clinical characteristics across cohorts using chi-square tests and survival using Cox regression, adjusted for multiple testing. We also performed propensity-matched and adjusted survival analyses., Results: Of 6259 patients, 14% were in eMTOC, 55% metropolitan non-MTOC, and 31% regional non-MTOC cohorts. eMTOC had the highest rates of African Americans (34% versus 28% versus 22%), stages I to IIIB (63 versus 40 versus 50), urban residents (81 versus 78 versus 20), stage-preferred treatment (66 versus 57 versus 48), guideline-concordant treatment (78 versus 70 versus 63), and lowest percentage of nontreatment (6 versus 21 versus 28); all p values were less than 0.001. Compared with eMTOC, hazard for death was higher in metropolitan (1.5, 95% confidence interval: 1.4-1.7) and regional (1.7, 1.5-1.9) non-MTOC; hazards were higher in regional non-MTOC versus metropolitan (1.1, 1.0-1.2); all p values were less than 0.05 after adjustment. Results were generally similar after propensity analysis with and without adjusting for guideline-concordant treatment., Conclusions: Multidisciplinary NSCLC care planning was associated with significantly higher rates of guideline-concordant care and survival, providing evidence for rigorous implementation of this model of care., (© 2021 The Authors.)

Introduction: The adverse prognostic impact of poor pathologic nodal staging has stimulated efforts to heighten awareness of the problem through guidelines, without guidance on processes to overcome it. We compared heightened awareness (HA) of nodal staging quality versus a lymph node collection kit., Methods: We categorized curative-intent lung cancer resections from 2009 to 2020 in a population-based, nonrandomized stepped-wedge implementation study of both interventions, into preintervention baseline, HA, and kit subcohorts. We used differences in proportion and hazard ratios across the subcohorts to estimate the effect of the interventions on poor quality (nonexamination of nodes [pNX] or nonexamination of mediastinal lymph nodes) and attainment of quality recommendations of the National Comprehensive Cancer Network, the Commission on Cancer, and the proposed complete resection definition of the International Association for the Study of Lung Cancer across the three cohorts., Results: Of 3734 resections, 39% were preintervention, 40% kit, and 21% HA cases. Cohort proportions were the following: pNX, 11% (baseline) versus 0% (kit) versus 9% (HA); nonexamination of mediastinal lymph nodes, 27% versus 1% versus 22%; Commission on Cancer benchmark attainment, 14% versus 77% versus 30%; International Association for the Study of Lung Cancer-defined complete resection, 11% versus 58% versus 24%; National Comprehensive Cancer Network attainment, 23% versus 79% versus 35% (p < 0.001 for all, except pNX rate baseline versus HA). Survival rate was significantly higher for both interventions compared with baseline (p < 0.0001)., Conclusions: Resections with HA or the kit significantly improved surgical quality and outcomes, but the kit was more effective. We propose to conduct a prospective, institutional cluster-randomized clinical trial comparing both interventions., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: Suboptimal pathologic nodal staging prevails after curative-intent resection of lung cancer. We evaluated the impact of a lymph node specimen collection kit on lung cancer surgery outcomes in a prospective, population-based, staggered implementation study., Methods: From January 1, 2014, to August 28, 2018, we implemented the kit in three homogeneous institutional cohorts involving 11 eligible hospitals from four contiguous hospital referral regions. Our primary outcome was pathologic nodal staging quality, defined by the following evidence-based measures: the number of lymph nodes or stations examined, proportions with poor-quality markers such as nonexamination of lymph nodes, and aggregate quality benchmarks including the National Comprehensive Cancer Network criteria. Additional outcomes included perioperative complications, health care utilization, and overall survival., Results: Of 1492 participants, 56% had resection with the kit and 44% without. Pathologic nodal staging quality was significantly higher in the kit cases: 0.2% of kit cases versus 9.8% of nonkit cases had no lymph nodes examined; 3.2% versus 25.3% had no mediastinal lymph nodes; 75% versus 26% attained the National Comprehensive Cancer Network criteria (p < 0.0001 for all comparisons). Kit cases revealed no difference in perioperative complications or health care utilization except for significantly shorter duration of surgery, lower proportions with atelectasis, and slightly higher use of blood transfusion. Resection with the kit was associated with a lower hazard of death (crude, 0.78 [95% confidence interval: 0.61-0.99]; adjusted 0.85 [0.71-1.02])., Conclusions: Lung cancer surgery with a lymph node collection kit significantly improved pathologic nodal staging quality, with a trend toward survival improvement, without excessive perioperative morbidity or mortality., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Importance: The International Association for the Study of Lung Cancer (IASLC) has proposed a revision of the residual disease (R-factor) classification, to R0, 'R-uncertain', R1 and R2. We previously demonstrated longer survival after surgical resection with a lymph node specimen collection kit, and now evaluate R-factor redistribution as the mechanism of its survival benefit., Objective: We retrospectively evaluated surgical resections for lung cancer in the population-based observational 'Mid-South Quality of Surgical Resection' cohort from 2009-2019, including a full-cohort and propensity-score matched analysis., Results: Of 3,505 resections, 34% were R0, 60% R-uncertain, and 6% R1 or R2. The R0 percentage increased from 9% in 2009 to 56% in 2019 ( p < 0.0001). Kit cases were 66% R0 and 29% R-uncertain, compared to 14% R0 and 79% R-uncertain in non-kit cases ( p < 0.0001). Compared with non-kit resections, kit resections had 12.3 times the adjusted odds of R0 versus R-uncertainty.Of 2,100 R-uncertain resections, kit cases had lower percentages of non-examination of lymph nodes, 1% vs. 14% ( p < 0.0001) and non-examination of mediastinal lymph nodes, 8% vs. 35% ( p < 0.0001). With the kit, more R-uncertain cases had examination of stations 7 (43% vs. 22%, p < 0.0001) and 10 (67% vs. 45%, p < 0.0001).The adjusted hazard ratio (aHR) for kit cases versus non-kit cases was 0.75 (confidence interval [CI]: 0.66-0.85, p < 0.0001). In 2,100 subjects with R-uncertain resections, kit cases had an aHR of 0.79 versus non-kit cases ([CI: 0.64-0.99], p=0.0384); however, in the 1,199 R0 resections the survival difference was not significant (aHR: 0.85[0.68-1.07], p = 0.17)., Conclusions and Relevance: A lymph node kit increased overall survival by increasing R0, reducing the probability of R-uncertain resections, and diminishing extreme R-uncertainty., (© 2021 The Authors.)

Introduction: The American College of Surgeons Oncology Group Z0030 found no survival difference between patients with early stage NSCLC who had mediastinal nodal dissection or systematic sampling. However, a meta-analysis of 1980 patients in five randomized controlled trials from 1989 to 2007 associated better survival with nodal dissection. We tested the survival impact of the extent of nodal dissection in curative-intent resections for early stage NSCLC in a population-based observational cohort., Methods: Resections for clinical T1 or T2, N0 or nonhilar N1, M0 NSCLC in four contiguous United States Hospital Referral Regions from 2009 to 2019 were categorized into mediastinal nodal dissection, systematic sampling, and "neither" on the basis of of the evaluation of lymph node stations. We compared demographic and clinical characteristics, perioperative complication rates, and survival after assessing statistical interactions and confounding., Results: Of the 1942 eligible patients, 18% had nodal dissection, 6% had systematic sampling, and 75% had an intraoperative nodal evaluation that met neither standard. In teaching hospitals, nodal dissection was associated with a lower hazard of death than "neither" resections (0.57 [95% confidence interval: 0.41-0.79]) but not systematic sampling (0.74 [0.40-1.37]) after adjusting for multiple comparisons. There was no significant difference in hazard ratios at nonteaching institutions (p > 0.3 for all comparisons). Perioperative complication rates were not significantly worse after mediastinal nodal dissection or systematic sampling, compared with "neither," (p > 0.1 for all comparisons)., Conclusions: In teaching institutions, mediastinal nodal dissection was associated with superior survival over less-comprehensive pathologic nodal staging. There was no survival difference between teaching and nonteaching institutions, a finding that warrants further investigation., (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: Access to targeted therapies for lung cancer depends on the accurate identification of patients' biomarkers through molecular testing. The International Association for the Study of Lung Cancer (IASLC) conducted an international survey to evaluate perceptions on current practice and barriers to implementation of molecular testing., Methods: We distributed the survey to IASLC members and other health care professionals around the world. The survey included a seven-question introduction for all respondents, who then answered according to one of three tracks: (1) requesting tests and treating patients, (2) performing and interpreting assays, or (3) tissue acquisition. Barriers to implementing molecular testing were provided in free-response fields. The chi-square test was used for regional comparisons., Results: A total of 2537 respondents from 102 countries participated. Most respondents who test and treat patients believe that less than 50% of patients with lung cancer in their country receive molecular testing, but reported higher rates within their own practice. Although many results varied by region, the five most frequent barriers cited in all regions were cost, quality and standards, access, awareness, and turnaround time. Many respondents expressed dissatisfaction with the current state of molecular testing for lung cancer, including 41% of those performing and interpreting assays. Issues identified included trouble understanding results (37%) and the quality of the samples (23% reported >10% rejection rate). Despite concerns regarding the quality of testing, 47% in the performing and interpreting track stated there is no policy or strategy to improve quality in their country. In addition, 33% of respondents who request tests and treat patients were unaware of the most recent College of American Pathologists, IASLC, and Association for Molecular Pathology guidelines for molecular testing., Conclusions: Adoption of molecular testing for lung cancer is relatively low across the world. Barriers include cost, access, quality, turnaround time, and lack of awareness., (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: To eliminate them, non-small cell lung cancer (NSCLC) care and outcome disparities need to be better understood., Research Question: How does rurality interact with NSCLC care and outcome disparities?, Study Design and Methods: We examined guideline-concordant use of active treatment for NSCLC across five institutions in one community-based health care system spanning 44% of the Delta Regional Authority catchment area from 2011 to 2017. Institution- and patient-level rurality were based on Rural-Urban Commuting Area codes. Chi-squared, F-tests, and logistic regressions were used to analyze differences across institutions and rurality; survival was examined using log-rank tests and Cox regression., Results: Of 6,259 patients, 47% resided in rural areas; two of five institutions were rurally located and provided care for 20% of patients. Compared with rural residents at rural institutions, urban and rural residents attending urban institutions were more likely to receive stage-preferred treatment: OR 1.68 (95%CI, 1.44-1.96), and 1.33 (1.11-1.61), respectively, after adjusting for insurance, age, and clinical stage. Urban and rural residents attending urban institutions had a lower hazard of death compared with rural residents attending rural institutions: hazard ratio (HR) 0.69 (0.64-0.75) and 0.61 (0.55-0.67), respectively. Among recipients of stage-preferred treatment, care at urban institutions remained less hazardous: HR 0.7 (0.63-0.79). When further stratified by stage, care for late-stage patients at urban institutions remained less hazardous: HR 0.8 (0.71-0.91)., Interpretation: Rurality-associated treatment and survival disparities were present at the patient and institution levels, but the institution-level disparity was greater. Rural residents receiving care at urban institutions had similar outcomes to urban residents receiving care at urban hospitals. To overcome rurality-associated NSCLC survival disparity, interventions should preferentially target the institution level, including expanding access to higher-quality guideline-concordant care., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)