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Low Dose CT screening (LDCT) 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.Using data from a Lung Nodule Program, we compared persons eligible for LDCT by: US Preventive Services Task Force (USPSTF) 2013 criteria (55-80 years, ≥30 pack-years of smoking, and ≤15 years since cessation (USPSTF2013); USPSTF 2021 (50-80 years, ≥20 pack-years of smoking, and ≤15 years since cessation (USPSTF2021); quit duration expanded to ≤25 years (USPSTF2021-QD25); reducing the pack-years of smoking to ≥10 (USPSTF2021-PY10); and both (USPSTF2021-QD25-PY10). We compare across groups using the chi-square test or Analysis of Variance.The 17,421 individuals analyzed were 56% female, 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-values0.0001). These additional eligible individuals were 55% (USPSTF2021) and 55% (USPSTF2021-QD25-PY10) female, compared to 48% by USPSTF2013 (p-values0.05). Of 1,243 (7.1%) persons 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 57% female (vs 48% with USPSTF2013, p-value= 0.0476) and 24% black (vs 20% with USPSTF2013, p-value= 0.3367).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.

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.

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.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?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.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).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.

BACKGROUND Hydroxyurea is an evidence-based disease-modifying therapy for sickle cell disease (SCD) but is underutilized. The Integration of Mobile Health (mHealth) into Sickle Cell Disease Care to Increase Hydroxyurea Utilization (meSH) multi-center study leveraged mHealth to deliver targeted interventions to patients and providers to foster hydroxyurea utilization. SCD studies often under enroll, and unanticipated events can negatively impact enrollment, making it important to study strategies that ensure adequate study accrual. OBJECTIVE This paper describes the challenges and adaptive strategies used to secure participant enrollment in the meSH study. Adaptive strategies were crucial to alleviate enrollment disruptions due to the COVID-19 pandemic. 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 In total, 89 providers and 293 patients enrolled across seven sites. Recruitment duration ranged from 2 to 7 for providers and 7 to 10 months for patients across sites. The study acceptance rate was 86% for both patients and providers. Patients mostly declined participation due to a lack of time and interest in research. Providers 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 and providers), staff meetings (providers), or within the office (providers). Recruitment challenge themes included: 1) lack of interest in research, 2) lack of human resources (e.g., shortage of study staff due to layoffs or resignations during the COVID-19 pandemic), 3) unavailable physical space for recruitment activities due to in-person activity restrictions, and 4) lack of documentation to verify eligibility. Because recruitment was slower than projected, strategies were adapted to include remote approaching and consenting (e.g., telehealth, email and telephone) for patients and providers. Additionally, for patients, recruitment was enriched by simplification of enrollment procedures (e.g., directly approaching patients without a referral from the provider) and a multi-touch method (i.e., warm introductions with flyers, text and patient portal messages). For patients, recruitment rates were similar between the in-person and adapted (virtual with multi-touch) approaches (83.5% and 88.1%, respectively, P=0.23). For providers, however, recruitment rate was higher for in-person versus remote recruitment (96.0% and 70.7%, respectively, P CONCLUSIONS The adapted recruitment strategies, implemented in response to the COVID-19 pandemic, secured a high recruitment rate, which was maintained among patients with SCD using an assortment of enriched remote recruitment strategies. For provider participants, e-mail-alone recruitment methods may not be sufficient to secure study enrollment. INTERNATIONAL REGISTERED REPORT RR2-10.2196/16319

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.

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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.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.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, p0.0001). 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 p0.0001). 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.Gaps in the quality of NSCLC pathologic reportage can be identified, quantified, and corrected by rationally designed interventions.

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.

More than 20,000 women are diagnosed with ovarian cancer each year in the United States, most with advanced stage disease.1 With five-year cause-specific survival of 47 percent, ovarian cancer is t...

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.

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.

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.

Introduction The International Association for the Study of Lung Cancer's (IASLC's) proposal to recategorize the residual tumor (R) classification for resected NSCLC needs validation. Methods Using a 2009 to 2019 population-based multi-institutional NSCLC resection cohort from the United States, we classified resections by Union for International Cancer Control (UICC) and IASLC R criteria and compared the distribution of R classification variables and their survival associations. Results Of 3361 resections, 95.3% were R0, 4.3% were R1, and 0.4% were R2 by UICC criteria; 33.3% were R0, 60.8% were R-uncertain, and 5.8% were R1/2 by IASLC criteria; 2044 patients (63.8%) migrated from UICC R0 to IASLC R-uncertain. Median survival was not reached, 69 (95% confidence interval [CI]: 64–77), and 25 (95% CI: 18–36) months, respectively, for patients with IASLC R0, R-uncertain, and R1 or R2 resections. Failure to achieve nodal dissection criteria caused 98% of migration to R-uncertainty, metastasis to the highest mediastinal node station, 5.8%. Compared with R0, R-uncertain resections with mediastinal nodes, no mediastinal nodes, and no nodes had adjusted hazard ratios of 1.28 (95% CI: 1.10–1.48), 1.47 (95% CI: 1.24–1.74), and 1.74 (95% CI: 1.37–2.21), respectively, suggesting a dose-response relationship between nodal R-uncertainty and survival. Accounting for mediastinal nodal involvement, the highest mediastinal station involvement was not independently prognostic. The incomplete resection variables were uniformly prognostic. Conclusions The proposed R classification recategorization variables were mostly prognostic, except the highest mediastinal nodal station involvement. Further categorization of R-uncertainty by severity of nodal quality deficit should be considered.

ImportanceGuideline-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.ObjectiveTo 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 ParticipantsThis 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 MeasuresComparative cumulative rates of lung cancer diagnosis and patient, nodule, and lung cancer characteristics between programs, using LDCT as a reference.ResultsThere 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 RelevanceIn 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.

ObjectivesSickle 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.MethodsThe 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.ResultsRespondents 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.ConclusionsA 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.

During transition from pediatrics to adult health care, young adults with sickle cell disease (SCD) face increased risk of severe morbidities and premature mortality.1 Sickle cell disease complications can be mitigated with hydroxyurea use.2 However, successful alleviation and prevention of SCD morbidities is contingent on initiation of and continued adherence to hydroxyurea therapy.3,4 With higher frequency of SCD-related complications among young adults, we examined the prevalence of hydroxyurea prescription among patients aged 18 to 25 years using statewide claims data. Understanding the patterns of hydroxyurea use in this patient population is key to potentially preventing the high burden of the disease accumulating among young adults.

Background Greater than one-half of children who are treated for acute lymphoblastic leukemia (ALL) develop ≥1 treatment-related medical conditions in their lifetime, many of which are known risk factors for diabetes mellitus. In the current study, the authors evaluated the prevalence and risk factors of diabetes mellitus among clinically assessed adult survivors of childhood ALL METHODS: The authors performed a retrospective evaluation of data from survivors of ALL and community controls who were enrolled in the St. Jude Lifetime Cohort Study between October 1, 2007, and June 30, 2016. Participants were adults with ≥10 years of survival of childhood ALL and community controls who completed clinical and laboratory evaluations. Data for the current analysis were abstracted from medical records. Exposures evaluated herein included chemotherapy and radiation exposures and medical history, including drug-induced diabetes mellitus. Results Of 1360 eligible adults who were ≥10-year survivors of childhood ALL, a total of 1044 completed the evaluations; these individuals had a mean age of 33.97±9.14 years and 50.86% were male. The 368 controls, 45.65% of whom were male, had a mean age of 35.33±10.21 years. Type 2 diabetes mellitus (T2DM) was found in approximately 7.47% of survivors and 3.80% of controls (odds ratio [OR], 2.07; 95% CI, 1.11-3.87). In adjusted models, among survivors, older age (OR, 1.05 for each additional year; 95% CI, 1.02-1.08), body mass index ≥30 kg/m2 (OR, 7.40; 95% CI, 2.61-20.97), and drug-induced diabetes mellitus occurring during ALL therapy (OR, 4.67; 95% CI, 2.53-8.61) were found to be associated with T2DM. Conclusions Adult survivors of childhood ALL are at an increased risk of T2DM. Adult survivors of childhood ALL who are of older age, with an overweight or obese body mass index, and/or who developed drug-induced diabetes mellitus during treatment should be closely monitored for T2DM during long-term follow-up.

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.To examine and report our experiences in a pediatric emergency department (ED) with intranasal fentanyl and midazolam in children aged 3 years and younger.This retrospective study investigated intranasal fentanyl and midazolam administration, alone and in combination, in children 3 years and younger treated in a pediatric ED.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.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.

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.

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.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.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% (p0.001 for all, except pNX rate baseline versus HA). Survival rate was significantly higher for both interventions compared with baseline (p0.0001).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.

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.

Due to fear of short-term toxicities, there is nonconsensus of hydroxycarbamide dosing strategy (escalated vs fixed-dosing methods), which contributes to its suboptimal use. We performed a meta-analysis to summarize the incidence rates of toxicities associated with both dosing methods. Summarized incidence rates could not be statistically compared between dosing methods due to sparse data. Summarized neutropenia and thrombocytopenia incidence rates were slightly higher when using escalated dosing than with fixed. Summarized reticulocytopenia was comparable. Summarized hepatic and renal toxicities' incidence rates were slightly higher when using fixed doses than with escalated. We recommend diligent and transparent reporting of toxicities.

Manuka honey, a wound treatment used to eradicate bacteria, resolve inflammation, and promote wound healing, is a current focus in the tissue engineering community as a tissue template additive. However, Manuka honey's effect on neutrophils during the inflammation-resolving phase has yet to be examined. This study investigates the effect of 0.5% and 3% Manuka honey on the release of cytokines, chemokines, and matrix-degrading enzymes from a dHL-60 neutrophil model in the presence of anti-inflammatory stimuli (TGF-β, IL-4, IL-4 +IL-13). We hypothesized that Manuka honey would reduce the output of pro-inflammatory signals and increase the release of anti-inflammatory signals. The results of this study indicate that 0.5% honey significantly increases the release of CXCL8/IL-8, CCL2/MCP-1, CCL4/MIP-1β, CCL20/MIP-3α, IL-4, IL-1ra, and FGF-13 while reducing Proteinase 3 release in the anti-inflammatory-stimulated models. However, 3% honey significantly increased the release of TNF-α and CXCL8/IL-8 while reducing the release of all other analytes. We replicated a subset of the most notable findings in primary human neutrophils, and the consistent results indicate that the HL-60 data are relevant to the performance of primary cells. These findings demonstrate the variable effects of Manuka honey on the release of cytokines, chemokines, and matrix-degrading enzymes of this model of neutrophil anti-inflammatory activity. This study reinforces the importance of tailoring the concentration of Manuka honey in a wound or tissue template to elicit the desired effects during the inflammation-resolving phase of wound healing. Future in vivo investigation should be undertaken to translate these results to a physiologically-relevant wound environment.

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. (c) 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Capecitabine and temozolomide (CAPTEM) have shown promising results in the treatment of neuroendocrine neoplasms (NEN). The aim of this study was to evaluate the outcome and role for CAPTEM in malignant neuroendocrine neoplasms. Data were obtained from NEN patients who received at least one cycle of CAPTEM between November 2010 and June 2018. The average number of cycles was 9.5. For analysis, 116 patients were included, of which 105 patients (91%) underwent prior treatment. Median progression free survival (PFS) and overall survival (OS) were 13 and 38 months, respectively. Overall response rate (ORR) was 21%. Disease control rate (DCR) was 73% in all patients. PFS, median OS, ORR, and DCR for pancreatic NENs (pNEN) vs. non-pNEN was 29 vs. 11 months, 35 vs. 38 months, 38% vs. 9%, and 77% vs. 71%, respectively. Patients with pNEN had a 50% lower hazard of disease progression compared to those with non-pNEN (adjusted Hazard Ratio: 0.498, p = 0.0100). A significant difference in PFS was found between Ki-67 &lt, 3%, Ki-67 3&ndash, 20%, Ki-67 &gt, 20&ndash, 54%, and Ki-67 &ge, 55% (29 vs. 12 vs. 7 vs. 5 months, p = 0.0287). Adverse events occurred in 74 patients (64%). Our results indicate that CAPTEM is associated with encouraging PFS, OS, and ORR data in patients with NENs.

Summary It has been well acknowledged that methods for secondary trait (ST) association analyses under a case–control design (ST$_{\text{CC}}$) should carefully consider the sampling process to avoid biased risk estimates. A similar situation also exists in the extreme phenotype sequencing (EPS) designs, which is to select subjects with extreme values of continuous primary phenotype for sequencing. EPS designs are commonly used in modern epidemiological and clinical studies such as the well-known National Heart, Lung, and Blood Institute Exome Sequencing Project. Although naïve generalized regression or ST$_{\text{CC}}$ method could be applied, their validity is questionable due to difference in statistical designs. Herein, we propose a general prospective likelihood framework to perform association testing for binary and continuous STs under EPS designs (STEPS), which can also incorporate covariates and interaction terms. We provide a computationally efficient and robust algorithm to obtain the maximum likelihood estimates. We also present two empirical mathematical formulas for power/sample size calculations to facilitate planning of binary/continuous STs association analyses under EPS designs. Extensive simulations and application to a genome-wide association study of benign ethnic neutropenia under an EPS design demonstrate the superiority of STEPS over all its alternatives above.

Background: Responsible for 25% of all US cancer deaths, lung cancer presents complex care-delivery challenges. Adoption of the highly recommended multidisciplinary care model suffers from a dearth of good quality evidence. Leading up to a prospective comparative-effectiveness study of multidisciplinary vs. serial care, we studied the implementation of a rigorously benchmarked multidisciplinary lung cancer clinic. Methods: We used a mixed-methods approach to conduct a patient-centered, combined implementation and effectiveness study of a multidisciplinary model of lung cancer care. We established a co-located multidisciplinary clinic to study the implementation of this care-delivery model. We identified and engaged key stakeholders from the onset, used their input to develop the program structure, processes, performance benchmarks, and study endpoints (outcome-related process measures, patient- and caregiver-reported outcomes, survival). In this report, we describe the study design, process of implementation, comparative populations, and how they contrast with patients within the local and regional healthcare system. Trial Registration: ClinicalTrials.gov Identifier: NCT02123797. Results: Implementation: The multidisciplinary clinic obtained an overall treatment concordance rate of 90% (target >85%). Satisfaction scores were high, with >95% of patients and caregivers rating themselves as being “very satisfied” with all aspects of care from the multidisciplinary team (patient/caregiver response rate >90%). The Reach of the multidisciplinary clinic included a higher proportion of minority patients, more women, and younger patients than the regional population. Comparative effectiveness: The comparative effectiveness trial conducted in the last phase of the study met the planned enrollment per statistical design, with 178 patients in the multidisciplinary arm and 348 in the serial care arm. The multidisciplinary cohort had older age and a higher percentage of racial minorities, with a higher proportion of stage IV patients in the serial care arm. Conclusions: This study demonstrates a comprehensive implementation of a multidisciplinary model of lung cancer care, which will advance the science behind implementing this much-advocated clinical care model.