US Community Research Articles

Real-world assessment and treatment of locally advanced basal cell carcinoma: Findings from the RegiSONIC disease registry.

BackgroundLimited information is available regarding real-world treatment patterns and their effectiveness and safety in patients with locally advanced basal cell carcinoma, including patients not typically represented in clinical trials. The purpose of the current study was to describe how clinicians diagnose and treat locally advanced basal cell carcinoma in the United States.MethodsThis prospective, multicenter, observational registry study included patients with newly diagnosed, Hedgehog pathway inhibitor–naive locally advanced basal cell carcinoma without basal cell carcinoma nevus syndrome (n = 433) treated at 75 US academic and community practices, including dermatology, Mohs surgery, and medical oncology sites. The main outcomes of this study were treatment patterns and associated effectiveness and safety for patients with locally advanced basal cell carcinoma in real-world settings.ResultsDetermination of locally advanced basal cell carcinoma was mainly based on lesion size (79.6% of patients), histopathology (54.3%), extent of involvement (49.0%), and location (46.2%). Within 90 days of determination of locally advanced disease, 115 patients (26.6%) received vismodegib, 251 (58.0%) received surgery/other (non-vismodegib) treatment, and 67 (15.5%) had not yet received treatment (observation). Vismodegib-treated patients had a higher prevalence of high-risk clinical features predictive for locoregional recurrence than those with non-vismodegib treatment or observation. Clinical response rate was 85.1% with vismodegib and 94.9% with non-vismodegib treatment (primarily surgery). The most common adverse events with vismodegib were ageusia/dysgeusia, muscle spasms, alopecia, and weight loss. Rates of cutaneous squamous cell cancers were comparable between vismodegib and non-vismodegib treatment.ConclusionsThis prospective observational study offers insight on real-world practice, treatment selection, and outcomes for a nationally representative sample of US patients with locally advanced basal cell carcinoma. For patients with lesions that were not amenable to surgery, vismodegib treatment was associated with effectiveness and safety that was consistent with that observed in clinical trials.

Reducing the Duration of Untreated Psychosis (DUP) in a US Community: A Quasi-Experimental Trial.

ObjectiveDuration of Untreated Psychosis (DUP) remains unacceptably long and limits effectiveness of care. To determine whether an early detection campaign (“Mindmap”) can reduce DUP in a US community setting.MethodsIn this nonrandomized controlled trial, Mindmap targeted the catchment of one specialty first-episode service or FES (STEP, Greater New Haven) from 2015 to 2019, while usual detection efforts continued at a control FES (PREP, Greater Boston). Mindmap targeted diverse sources of delay through mass & social media messaging, professional outreach & detailing, and rapid enrollment of referrals. Both FES recruited 16–35 years old with psychosis onset ≤3 years. Outcome measures included DUP-Total (onset of psychosis to FES enrollment), DUP-Demand (onset of psychosis to first antipsychotic medication), and DUP-Supply (first antipsychotic medication to FES enrollment).Results171 subjects were recruited at STEP and 75 at PREP. Mindmap was associated with an increase in the number of referrals and in efficiency of engagement at STEP. Pre-campaign DUP (2014–2015) was equivalent, while Mindmap was associated with DUP reductions at STEP but not PREP. DUP-Total fell significantly in both the first and the second quartile (11.5 and 58.5 days reduction per campaign year, respectively). DUP-Demand and DUP-Supply fell in the third quartiles only (46.3 and 70.3 days reduction per campaign year, respectively). No reductions were detectable across all quartiles at PREP, but between site comparisons were not significant.ConclusionsThis is the first controlled demonstration of community DUP reduction in the US, and can inform future early detection efforts across diverse settings.

Snowmass 2021 Whitepaper: Proton Structure at the Precision Frontier

An overwhelming number of theoretical predictions for hadron colliders require parton distribution functions (PDFs), which are an important ingredient of theory infrastructure for the next generation of high-energy experiments. This whitepaper summarizes the status and future prospects for determination of high-precision PDFs applicable in a wide range of energies and experiments, in particular in precision tests of the Standard Model and in new physics searches at the high-luminosity Large Hadron Collider and Electron-Ion Collider. We discuss the envisioned advancements in experimental measurements, QCD theory, global analysis methodology, and computing that are necessary to bring unpolarized PDFs in the nucleon to the N2LO and N3LO accuracy in the QCD coupling strength. Special attention is given to the new tasks that emerge in the era of the precision PDF analysis, such as those focusing on the robust control of systematic factors both in experimental measurements and theoretical computations. Various synergies between experimental and theoretical studies of the hadron structure are explored, including opportunities for studying PDFs for nuclear and meson targets, PDFs with electroweak contributions or dependence on the transverse momentum, for incisive comparisons between phenomenological models for the PDFs and computations on discrete lattice, and for cross-fertilization with machine learning/AI approaches. [Submitted to the US Community Study on the Future of Particle Physics (Snowmass 2021).]

Descriptive Epidemiology and Outcomes of Hospitalizations With Complicated Urinary Tract Infections in the United States, 2018

BackgroundHospitalizations with complicated urinary tract infection (cUTI) in the United States have increased. Though most often studied as a subset of cUTI, catheter-associated UTI (CAUTI) afflicts a different population of patients and carries outcomes distinct from non-CA cUTI (nCAcUTI). We examined the epidemiology and outcomes of hospitalizations in these groups.MethodsWe conducted a cross-sectional multicenter study within the 2018 National Inpatient Sample (NIS) database, a 20% stratified sample of discharges from US community hospitals, to explore characteristics and outcomes of patients discharged with a UTI diagnosis. We divided cUTI into mutually exclusive categories of nCAcUTI and CAUTI. We applied survey methods to develop national estimates.ResultsAmong 2 837 385 discharges with a UTI code, 500 400 (17.6%, 19.8% principal diagnosis [PD]) were nCAcUTI and 126 120 (4.4%, 63.8% PD) were CAUTI. Though similar in age (CAUTI, 70.1 years; and nCAcUTI, 69.7 years), patients with nCAcUTI had lower comorbidity (mean Charlson, 4.3) than those with CAUTI (mean Charlson, 4.6). Median (interquartile range [IQR]) length of stay (LOS) was 5 (3–8) days in nCAcUTI and 5 (3–9) days in CAUTI. Overall median (IQR) hospital costs were similar in nCAcUTI ($9713 [$5923–$17 423]) and CAUTI ($9711 [$5969–$17 420]). Though low in both groups, hospital mortality was lower in nCAcUTI (2.8%) than in CAUTI (3.4%). Routine discharges home were higher in nCAcUTI (41.5%) than CAUTI (22.1%).ConclusionsThere are >626 000 hospital admissions with a cUTI, comprising ~1.8% of all annual admissions in the United States; 4/5 are nCAcUTI. Because CAUTI is frequently the reason for admission, preventive efforts are needed beyond the acute care setting.

Design Knowledge for Collaborative Health Information Systems for Substance Use Disorder

Opioid related addictions/deaths are a national problem threatening our social and economic welfare. While many community preventive efforts are implemented to reduce overdoses and deaths, they often fall short. This project takes a design science approach to tackle a serious societal challenge: develop a software-based solution to aid the efforts of a Southern US community engaged in battling the opioid crisis. Artifact design, development and evaluation occurred in multiple iterations and involved conducting exploratory and confirmatory stakeholder focus groups. The artifact presented herein represents a system that facilitates up-close and personal (and private and sensitive) communication to improve human mental health. The research supports the case for scenario-based design theorizing by developing context scenarios discussed with participants and then used to further elicit design knowledge in the form of principles, requirements, and solution features that map to each other. Further, the design process employed illustrates a practical means to align the solution design with real-world needs that address key human factors including meeting the requirements needed for working in fragile, human sensitive, social-health contexts. The resulting solution and design knowledge provide support for future development of information systems intended to support social programs for mental health and substance use disorder treatment and recovery services.

경제제재에 영향을 미치는 요인에 관한 연구

This paper is determined by the strategic choice of the actor and analyzed on theassumption that the strategic choice of the actor is restricted by structural conditions. In theprocess of denuclearization between North Korea and Iran, I could see that strategicinteraction between actors was a factor in determining the effect of denuclearization ofeconomic sanctions. At the same time, I emphasiz that the reason why North Korea and Iranwere able to withstand economic sanctions lies in the resilience power of structure . I thinkthat the resilience power of North Korea and Iran despite the strong US sanctions isultimately the role of China as a existence of supporting countries and the internal connectionforce between North Korea and Iran. In conclusion, to achieve the denuclearization of North Korea and Iran, the US needs toimprove relations with China. If the US-China resonance and coordination are strengthened,time will be saved in bringing China and Iran to denuclearization. In addition, the US and theinternational community should respect their shared belief that North Korea and Iran wereable to withstand economic sanctions, and increase their trust in each other based on theirhistorical background and understanding.

Real-World Outcomes Among Crizotinib-Treated Patients with ROS1-Positive Advanced Non-Small-Cell Lung Cancer: A Community Oncology-Based Observational Study.

BackgroundCrizotinib was the first oral targeted therapy approved by the US Food and Drug Administration (FDA), on 11 March 2016, for c-ros oncogene 1 (ROS1)-positive advanced non-small-cell lung cancer (NSCLC). Data to support long-term clinical benefit in a real-world setting are limited.ObjectiveThis study aimed to assess real-world clinical outcomes among patients with ROS1-positive advanced NSCLC treated with crizotinib in the US community oncology setting.Patients and MethodsWe conducted a retrospective cohort study using iKnowMed electronic health record data to identify adult patients with ROS1-positive advanced NSCLC who initiated crizotinib between 17 January 2013 (time of the addition of crizotinib for ROS1-positive NSCLC to National Comprehensive Cancer Network (NCCN) treatment guidelines) and 1 June 2019 with a potential follow-up period through 1 December 2019. Patient characteristics were assessed descriptively. Kaplan–Meier analyses were used to evaluate time to treatment discontinuation (TTD), time to next treatment (TTNT), and overall survival (OS). A Cox proportional hazards model was conducted to determine factors associated with OS.ResultsThe study cohort included 38 ROS1-positive patients treated with crizotinib. The median age was 68 years (interquartile range 60.0–73.0) and 65.8% were female. Over 50% were current/former smokers, and 18.4% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2. Overall, 21 (55.3%) patients remained on crizotinib, 10 (26.3%) had evidence of subsequent treatment, and 16 (42.1%) died. The median TTD, TTNT, and OS were 25.2 months [95% confidence interval (CI): 5.2–not reached (NR)], 25.0 months (95% CI 5.2–61.0), and 36.2 months (95% CI 15.9–NR), respectively. In a multivariate Cox regression model, ECOG performance status of 2 was associated with a 4.9-fold higher risk of death (hazard ratio = 4.9; 95% CI 1.1–21.4) compared to ECOG performance status of 0 or 1.ConclusionsThis ROS1-positive NSCLC real-world population was older and had a higher proportion of smokers and of patients with poorer ECOG performance status than those investigated in clinical trials. Nevertheless, our findings support the clinical benefit of crizotinib in this patient population with ROS1-positive advanced NSCLC.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11523-021-00860-z.

Critical assessment of initiatives in community college international education

AbstractIn the 1947 Truman Commission, Zook noted a validation of international education for US community colleges and specified two recommendations for the internationalization of US community colleges. The first recommendation was to embrace internationalization in the curriculum, and the second was to create an educational context in which students could gain an international understanding. This article critically assesses the extent to which US community colleges have met Zook's (1947) recommendations. The findings show that internationalization practices are supported by US community college leadership over time, are found in American Association of Community Colleges policies, are the subject of graduate student dissertations, and are the subject of research since the 1960s. The article concludes with a comprehensive set of recommendations for community colleges to support future actionable international agendas intended to serve the next generation of community colleges and their students.

Effect of Values Affirmation on Reducing Racial Differences in Adherence to Hypertension Medication

Stereotype threat, or the fear of confirming a negative stereotype about one's social group, may contribute to racial differences in adherence to medications by decreasing patient activation to manage chronic conditions. To examine whether a values affirmation writing exercise improves medication adherence and whether the effect differs by patient race. The Hypertension and Values trial, a patient-level, blinded randomized clinical trial, compared an intervention and a control writing exercise delivered immediately prior to a clinic appointment. Of 20 777 eligible, self-identified non-Hispanic Black and White patients with uncontrolled hypertension who were taking blood pressure (BP) medications, 3891 were approached and 960 enrolled. Block randomization by self-identified race ensured balanced randomization. Patients enrolled between February 1, 2017, and December 31, 2019, at 11 US safety-net and community primary care clinics, with outcomes assessed at 3 and 6 months. Analysis was performed on an intention-to-treat basis. From a list of 11 values, intervention patients wrote about their most important values and control patients wrote about their least important values. The primary outcome of adherence to BP medications was measured using pharmacy fill data (proportion of days covered >90%) at baseline, 3 months, and 6 months. The secondary outcome was systolic and diastolic BP. Patient activation to manage their health was also measured. Of 960 patients, 474 (286 women [60.3%]; 256 Black patients [54.0%]; mean [SD] age, 63.4 [11.9] years) were randomly assigned to the intervention group and 486 (288 women [59.3%]; 272 Black patients [56.0%]; mean [SD] age, 62.8 [12.0] years) to the control group. Baseline medication adherence was lower (318 of 482 [66.0%] vs 331 of 412 [80.3%]) and mean (SE) BP higher among Black patients compared with White patients (systolic BP, 140.6 [18.5] vs 137.3 [17.8] mm Hg; diastolic BP, 83.9 [12.6] vs 79.7 [11.3] mm Hg). Compared with baseline, pharmacy fill adherence did not differ between intervention and control groups at 3 months (odds ratio [OR], 0.91 [95% CI, 0.57-1.43]) or at 6 months (OR, 0.86 [95% CI, 0.53-1.38]). There were also no treatment effect differences in pharmacy fill adherence by patient race (Black patients at 3 months: OR, 1.08 [95% CI, 0.61-1.92]; at 6 months: OR, 1.04 [95% CI, 0.58-1.87]; White patients at 3 months: OR, 0.68 [95% CI, 0.33-1.44]; at 6 months: OR, 0.55 [95% CI, 0.24-1.27]). Immediately after the intervention, the median patient activation was higher in intervention patients than in control patients, but this difference was not statistically significant in an unadjusted comparison (75.0 [IQR, 65.5-84.8] vs 72.5 [IQR, 63.1-80.9]; P = .06). In adjusted models, the Patient Activation Measure score immediately after the intervention was significantly higher in the intervention patients than in control patients (mean difference, 2.3 [95% CI, 0.1-4.5]). A values affirmation intervention was associated with higher patient activation overall but did not improve adherence or blood pressure among Black and White patients with hypertension. ClinicalTrials.gov Identifier: NCT03028597.

1420. Descriptive Epidemiology of UTI Hospitalizations in the US, 2018

BackgroundIn parallel with an increase in antimicrobial resistance, urinary tract infections (UTI), one of the most common diagnoses among hospitalized patients in the US, have been on the rise. Though mostly emphasized as a hospital-acquired complication among patients with an indwelling catheter, quantification of the full contemporary burden of UTI-associated hospitalizations is limited. MethodsWe conducted a cross-sectional multicenter study within the National Inpatient Sample (NIS) database, a 20-percent stratified sample of discharges from US community hospitals, from 2018, to explore characteristics of patients discharged with a UTI diagnosis. We divided UTI into mutually exclusive categories of complicated (cUTI), uncomplicated (uUTI), and catheter-associated (CAUTI). We applied survey methods to develop national estimates. ResultsAmong 2,837,385 discharges with a UTI code, 77.9% were uUTI, 17.6% cUTI, and 4.4% CAUTI. Compared to patients with uUTI (mean age 69.0 years), those with CAUTI and cUTI were older (70.1 and 69.7 years), but had same comorbidity burden (mean Charlson 4.3) as cUTI (4.3) and lower than CAUTI (4.6). Compared to other geographic regions, the Northeast had the lowest proportion of uUTI (74.6%) and highest of cUTI (20.8%) while the South had highest uUTI (80.2%) and lowest cUTI (15.7%). Over 60% of all UTI, regardless of type, were in large, and nearly ½ in urban teaching, institutions, and >80% came through the emergency department. Antimicrobial resistance codes were infrequent, but extended spectrum beta-lactamase organisms were more common in CAUTI (2.7%) and cUTI (2.1%) than in uUTI (1.6%). Among the 83.0% of discharges whose UTI was a secondary diagnosis, sepsis was the most common principal diagnosis, ranging from 17.7% in uUTI to 22.3% in cUTI. Although relatively low across the board, hospital mortality was lowest in cUTI (2.8%) and highest in uUTI (3.9%). Discharges to a chronic care facility were most common in CAUTI (46.7%) and least common in cUTI (33.3%). ConclusionThere are nearly 3 million hospital admissions with a UTI, comprising fully 8% of all annual admissions in the US. Though most are considered uncomplicated, there are few differences in characteristics or outcomes across the categories. Disclosures Marya Zilberberg, MD, MPH, Cleveland Clinic (Consultant)J&J (Shareholder)Lungpacer (Consultant, Grant/Research Support)Merck (Grant/Research Support)scPharma (Consultant)Sedana (Consultant, Grant/Research Support)Spero (Grant/Research Support) Brian Nathanson, PhD, Lungpacer (Grant/Research Support)Merck (Grant/Research Support)Spero (Grant/Research Support) Kate Sulham, MPH, Spero Therapeutics (Consultant)

Retrospective Study of Real-World Treatment Patterns and Outcomes in Advanced/Metastatic Renal Cell Carcinoma Patients Receiving Lenvatinib/Everolimus after Heavy Pretreatment1

BACKGROUND: Lenvatinib with everolimus (“Len/Eve”) is approved for advanced/metastatic RCC following one antiangiogenic therapy. OBJECTIVE: This study evaluated patient characteristics, treatment patterns and overall survival (OS) with second-line or later (2L+) Len/Eve for advanced/metastatic RCC. METHODS: A retrospective observational study was conducted using electronic health records. Adult patients who initiated 2L+ Len/Eve for advanced/metastatic RCC from May 13, 2016 to July 31, 2019 were included. Patient characteristics and treatment patterns were assessed across the overall population and by post-immuno-oncology (IO) and post-tyrosine kinase inhibitors (TKI) groups. OS was estimated from Len/Eve initiation (i.e., index date) using Kaplan-Meier. RESULTS: Among the study population (n = 152), 44.1%received 2L/3L Len/Eve and median number of prior therapies was 3 (range:1–8). Median age was 63.2 years, 78.9%were Caucasian, 73.7%were male, and 56.6%had ECOG performance status 0/1. At initial diagnosis, 65.8%had stage IV disease. At index, 53.3%had an International Metastatic RCC Database Consortium risk score of intermediate/poor, 15.1%favorable, and 31.6%missing score. Sixty-five (42.8%) received IO-based regimens and 49.3%received TKIs directly before index. Median OS from index was 13.9 (95%CI: 9.5–16.5) months and 2L/3L and 4L+ were 12.1 (95%CI: 8.4–17.0) and 14.8 (95%CI: 8.9–22.5) months, respectively. Median OS for Len/Eve post-IO and post-TKI were 13.9 (95%CI: 8.4–21.3) and 14.8 (95%CI: 7.8–16.5) months, respectively. Conclusion: This study suggested that 2L+ Len/Eve has clinical effectiveness for advanced/metastatic RCC in a US community oncology setting. Future studies are needed to confirm the association of improved survival with 2L+ Len/Eve.

Real-world Clinical Effectiveness of Lenvatinib/Everolimus in a Heavily Pretreated Advanced/Metastatic Renal Cell Carcinoma Population in the US Community Oncology Setting

Few studies have evaluated real-world effectiveness of lenvatinib (Len)/everolimus (Eve) for advanced/metastatic renal cell carcinoma (a/mRCC). This study evaluated patient profiles and clinical outcomes of second- and subsequent-line (≥ 2L) Len/Eve for a/mRCC. A longitudinal retrospective study examined adult patients initiating ≥ 2L Len/Eve for a/mRCC from May 13, 2016, to July 31, 2019. Len/Eve clinical trial participants or those treated for other primary tumors were excluded. Outcomes included objective response rate, duration of response, progression-free survival (PFS), time to treatment discontinuation, and overall survival. Time-to-event outcomes were estimated using Kaplan-Meier methods. Seventy-nine patients were assessed: the median age was 64.8 years, 78.5% were Caucasian, 73.4% were male, 78.5% had an Eastern Cooperative Oncology Group performance status score of 0/1, 29.1% received 2L/3L Len/Eve, and the median number of prior lines of therapy was 3 (range, 1-8). At initial diagnosis, 55.7% had stage IV disease, 65.8% had International Metastatic risk scores of intermediate/poor, 19.0% favorable, and 15.2% with missing score. Thirty-one (39.2%) patients received immuno-oncology-based regimens, and 50.6% received tyrosine kinase inhibitors directly before Len/Eve initiation. The median time to treatment discontinuation was 5.7 months (95% CI, 3.3-6.9). The physician-assessed objective response rate was 55.7% (1.6% complete response and 54.1% with some degree of tumor shrinkage). The median duration of response was 9.7 months (95% CI, 5.8-17.1). The median PFS was 6.1 months (95% CI, 4.4-9.0). The median PFS for patients receiving Len/Eve post-immuno-oncology was 6.4 months (95% CI, 4.1-10.8) and for post-tyrosine kinase inhibitor 5.7 months (95% CI, 4.1-10.5). Median overall survival was 14.8 months (95% CI, 10.2-23.9). In this longitudinal retrospective study, Len/Eve showed real-world effectiveness in clinical practice in a heavily pretreated a/mRCC patient population.

Treatment Patterns and Overall Survival in HER2+ Metastatic Breast Cancer at US Community Oncology Practices

Aim: To describe real-world treatment patterns/outcomes among patients with HER2+ metastatic breast cancer (MBC). Materials & methods: Real-world treatments and overall survival (OS) were evaluated among adult women diagnosed with HER2+ MBC, with and without brain metastases (BMs), between 1 June 2012 and 31 May 2018 using electronic medical records from the Definitive Oncology Dataset. Results: Among 372 patients, 69% initiated first-line trastuzumab plus pertuzumab-based therapy; many therapy combinations were utilized in the second- to fourth-line. During follow-up (median 24.8 months), 18% of patients died (22% with and 16% without BMs). Mean OS was shortest among patients with BMs at MBC diagnosis in the third- and fourth-line. Conclusion: OS was poor, and no clear standard of care was observed among patients with HER2+ MBC progressing on trastuzumab-based therapies.

Understanding Factors Associated With Anaplastic Lymphoma Kinase Testing Delays in Patients With Non-Small Cell Lung Cancer in a Large Real-World Oncology Database.

With multiple therapeutic options available for patients with advanced non-small cell lung cancer, the timely ordering and return of results to determine therapy are of critical importance. To assess factors impacting anaplastic lymphoma kinase (ALK) test ordering and time to result delivery. A retrospective study using a de-identified electronic health record database was performed. Postdiagnosis ALK tests (n = 14 657) were analyzed from 14 197 patients with advanced non-small cell lung cancer diagnosed between January 2015 and May 2019. Time from non-small cell lung cancer diagnosis to ALK sample receipt in the laboratory was a surrogate for test order time. Test ordering was considered delayed if order time was more than 20 days. Turnaround time from sample received to test result was calculated and considered delayed if more than 10 days. Multivariable logistic regression was used to assess factors associated with order time and turnaround time delays. Median ALK test order time was 15 days, and 36.4% (5342) of all 14 657 orders were delayed. Factors associated with delays were non-fluorescence in situ hybridization testing, send-out laboratories, testing prior to 2018, nonadenocarcinoma histology, and smoking history. Median turnaround time was 9 days, and 40.3% (5906) of all 14 657 test results were delayed. Non-fluorescence in situ hybridization testing, tissue sample, and orders combining ALK with other biomarkers were associated with delayed ALK result reporting. This study provides a snapshot of real-world ALK test ordering and reporting time in US community practices. Multiple factors impacted both test ordering time and return of results, revealing opportunities for improvement. It is imperative that patients eligible for targeted therapy be identified in a timely fashion.

Real World Assessment of Treatment Patterns and Outcomes Among Multiple Myeloma Patients across Different Risk Stratification Criteria in the United States: A Retrospective Cohort Study

Background: Despite the development of highly active novel agents, high risk (HR) multiple myeloma (MM) patients continue to demonstrate relatively poor prognosis. Limited data is published on how treatment patterns with risk stratification systems have changed over time. Moreover, real world studies using electronic health records (EHRs) have not evaluated the performance of risk stratification systems with real world outcomes. This study aims to evaluate the ability to implement three different risk stratification systems - international staging system (ISS), revised ISS (R-ISS), and high-risk chromosomal abnormalities (HRCA, defined as presence of del(17)p, t(4;14) and/or t(4;16)) [Palumbo et al. 2015] - to characterize treatment patterns and associated outcomes [real world overall survival (rwOS) and real world progression free survival (rwPFS)] among newly diagnosed MM (NDMM) patients in the US community practice.Methods: This study used Flatiron Enhanced MM EHR de-identified database (New York, NY). Newly diagnosed MM patients (≥ 18 years) were diagnosed from January 2015 through June 2020 (cohort 1 - for studying treatment distribution) with follow-up through December 2020, and from January 2015 through December 2018 (cohort 2 - for rwOS and rwPFS), with follow-up through December 2020. Patients with malignancies other than MM were excluded. Proportion of rwOS was measured from treatment initiation until death, and median rwPFS was measured from treatment initiation until death, progression, or start of new line of therapy using Kaplan-Meier method.Results: A total of 1,979 and 1,382 patients were eligible in cohorts 1 and 2, respectively. In both the cohorts, approximately 18% (cohort 1: N=367, cohort 2: N=248), 41% (cohort 1: N=805, cohort 2: N=566), and 37% (cohort 1: N=738, cohort 2: N=508) were HR patients according to the R-ISS, ISS, and HRCA criteria, respectively. Approximately half of the HR patients were ≥70 years old (52% for R-ISS III and ISS III, and 47% for HRCA), with chronic kidney disease stage ≥3 by eGFR for 54% R-ISS III and ISS III, and 34% high risk CA, and ECOG score ≥2 for 18% R-ISS III, 19% ISS III, and 14% HRCA patients.Triplets were the most frequent treatment regimens (62% for R-ISS III and II, and 66% for R-ISS I; 59% for ISS III, and 65% for ISS II and I; 65% for HRCA and 61% for standard risk CA(SRCA) with proteasome inhibitors (PIs) / immunomodulatory agents (IMiDs) / dexamethasone being most common regimen across all the risk stratification criteria. Quadruplet agent use was higher in R-ISS III and ISS III categories (6.8% vs. 3.3% for R-ISS III vs. I; 6.3% vs. 2.8% for ISS III vs. I).The median rwPFS in HR patients were shorter than the lower risk subgroups (R-ISS III: 8.8 months [95% CI 7.1 - 11.0], R-ISS II: 12.1 months [95% CI 10.7 - 13.6], R-ISS I: 23.5 months [95% CI 13.8 - .]; ISS III: 10.4 months [95% CI 8.5 - 11.5], ISS II: 12.7 months [95% CI 10.7 - 14.3], ISS I: 16 months [95% CI 12.2 - 19.5]; HRCA: 10.1 months [95% CI 8.8 - 12.1], SRCA: 13.1 months [95% CI 11.3 - 14.8]).The 2-year rwOS was lower in the HR subgroups (R-ISS III: 0.65 [95% CI 0.59 - 0.70], R-ISS II: 0.79 [95% CI 0.76 - 0.81], R-ISS I: 0.91 [95% CI 0.85 - 0.95]; ISS III: 0.68 [95% CI 0.64 - 0.72], ISS II: 0.81 [95% CI 0.77 - 0.84], ISS I: 0.89 [95% CI 0.85 - 0.92]; HRCA: 0.75 [95% CI 0.71 - 0.79], SRCA: 0.79 [95% CI 0.76 - 0.81]).Discussion: This study found that median rwPFS and 2-year rwOS proportions were consistently lower among HR patients compared to the standard risk individuals. The majority of the HR patients were older, with decreased levels of physical functioning and worse indicators of end-organ damage including renal function, anemia, and hypercalcemia. Most patients received triplets with frequent use of PIs likely for aggressive disease control among HR patients. Some HR patients received more quads than lower risk patients suggesting treatment intensification, but HR patients also received stem cell transplants at a lower rate. Although a smaller proportion of patients have all the data collected needed for R-ISS classification, the consistent findings across treatment outcomes suggest that R-ISS is implementable in real world studies and has a greater discriminatory ability than ISS or HRCA alone. Overall, this study suggests that HR patients have relatively poor outcomes which calls for the study of risk-adapted implementation of novel therapies among this patient population in the US community practice settings. [Display omitted] DisclosuresRahman: Amgen Inc.: Current Employment, Current holder of stock options in a privately-held company. Kim: Amgen: Current Employment, Current equity holder in publicly-traded company. Mateus: Amgen Inc.: Current Employment, Other: Work at Amgen as a contract employee through DOCS. Keegan: Amgen Inc.: Current Employment, Current holder of stock options in a privately-held company.

Real-World Patterns of Molecular Genetic Testing Among Patients with Acute Myeloid Leukemia in US Community Oncology Settings

Introduction: Molecular genetic testing is essential to inform disease diagnosis, prognosis, and treatment selection for patients with acute myeloid leukemia (AML). The standard treatment is induction chemotherapy followed by post-remission consolidation therapy including chemotherapy and allogeneic hematopoietic stem cell transplantation. Since May 2017, targeted therapies such as midostaurin, ivosidenib, enasidenib, and gemtuzumab ozogamicin were introduced for the treatment of AML. The use of targeted therapies is driven in part by the results of molecular genetic testing. The aim of this study was to determine molecular genetic testing utilization among patients with AML before and after the introduction of targeted therapies in May 2017 within community oncology clinics.Methods: A retrospective observational cohort study was conducted using de-identified data from The US Oncology Network iKnowMed electronic health record database and chart review. The iKnowMed is an oncology-specific system that captures outpatient practice encounter history for patients under care, including (but not limited to) laboratory tests, diagnosis, therapy administration, line of therapy, staging, and performance status information. These structured data were supplemented by targeted chart review to capture unstructured data. All patients aged 18 years or older with newly diagnosed or relapsed/refractory AML who received treatment in The US Oncology Network from January 2014 through February 2019 were included in the study cohort. Patients enrolled in clinical trials were excluded. Patients were classified into two groups: those who received treatment prior to May 2017 and those who received it after May 2017. Molecular genetic testing included IDH1, IDH2, FLT3-ITD, FLT3-TDK and CD33 genes. We assessed the proportion of newly diagnosed or relapsed/refractory AML patients who received molecular genetic testing in the inpatient setting, outpatient setting and prior to treatment initiation before and after May 2017.Results: The study population consisted of 434 patients diagnosed with AML, of whom 313 had newly diagnosed and 121 had relapsed/refractory AML. The median age of the study cohort was 73 (interquartile range: 63.0, 79.0) years. Most of the study cohort were male (57.6%, n=250) and Caucasian (77.0%, n=334). Approximately 75% (235/313) of newly diagnosed patients (75.1%; 235/313) and 81.0% (98/121) of patients with relapsed/refractory AML had molecular genetic testing. The proportion of patients who had molecular genetic testing before and after May 2017 were similar for newly diagnosed AML patients (72.2% vs. 78.1%; p=0.2260) and relapsed/refractory AML patients (80.0% vs. 83.9%; p=0.6357). The proportion of newly diagnosed AML patients who received molecular genetic testing in the inpatient setting (18.5% vs. 23.8%; p=0.3403) and outpatient setting (49.4% vs. 51.0%; p=0.4223) did not change before and after May 2017. Likewise, among patients with relapsed/refractory AML, the proportion of molecular genetic testing in the inpatient setting (31.1% vs. 35.5%; p=0.8523) and outpatient setting (44.4% vs. 51.6%; p=0.7749) were similar before and after May 2017. In addition, the proportion of newly diagnosed AML patients (55.6% vs. 62.9%; p=0.3835) and relapsed/refractory AML patients (45.6% vs. 61.3%; p=0.3063) who received molecular genetic testing prior to AML treatment initiation did not change before and after May 2017. Time from test order date to test result availability was not significantly different before [mean (SD) =9.3 days (16.8)] and after May 2017 [mean (SD)=9.0 days (9.9)].Conclusion: Introduction of targeted therapies for AML did not increase molecular genetic testing rates nor improve the turnaround time for test result availability in newly diagnosed and relapsed refractory AML patients by February 2019. Two out of 5 patients did not have molecular genetic testing performed prior to initiation of AML therapy after May 2017 when targeted therapies became available. Patients age, comorbidities and drug access issues may have contributed to under-utilization of molecular genetic testing. Further research is needed to identify barriers to molecular genetic testing in patients with AML. DisclosuresSura: McKesson Life Sciences: Current Employment. Annavarapu: McKesson Life Sciences: Current Employment. Kwong: Daiichi Sankyo, Inc: Current Employment. Fliss: Daiichi Sankyo, Inc: Current Employment.

Clinical Characteristics and Late-Line Treatment Patterns of Patients with Chronic Myeloid Leukemia Who Received 2 Prior Lines of Tyrosine Kinase Inhibitor Therapy in US Community Oncology Practices

BACKGROUND: Current treatment guidelines recommend tyrosine kinase inhibitors (TKIs) as first-line and second-line treatment options for patients with chronic myeloid leukemia (CML). 1,2 However, approximately 20% of CML patients fail to respond to the first- and second-generation TKIs, and evidence-based guidelines for late-line treatment options after failure/intolerance to TKIs are limited. 3,4 Therefore, this study sought to describe the clinical characteristics and real-world treatment patterns of CML patients who received 2 prior lines of TKI therapy.METHODS: A retrospective cohort design was utilized to identify adult CML patients who initiated a new line of therapy (LOT) after 2 prior lines of TKI therapy between 4/2013 and 12/2020 in the Florida Cancer Specialists network's electronic health records (EHR) database. The index LOT date was the start date of a new CML treatment regimen in LOT≥3 after 2 prior lines of TKI therapy. Patients were followed until 1 of the following occurred: death, loss to follow-up (last structured activity in EHR), or end of study period (3/31/2021). Demographic and clinical characteristics were captured during the baseline period starting 3 months prior to the initial CML diagnosis until the index LOT date and included age, gender, race, Eastern Cooperative Oncology Group performance status (ECOG PS) and comorbidity burden. Treatment patterns of all available LOTs from initial CML diagnosis were investigated and the following metrics were captured: regimen details of systemic CML therapies, duration of LOT, treatment-free interval. This study was descriptive in nature and no inferential statistics were computed.RESULTS: A total of 157 patients who initiated a new CML treatment regimen in LOT≥3 after 2 previous lines of TKI therapy were included in this study. The median age of the study sample at initial CML diagnosis was 63.8 years, 57.3% of the sample were male, and 50.3% were White. At index LOT, 46.5% of the sample had an ECOG PS score of 0-1, 5.1% had ECOG PS score of 2-4, and 48.4% had an unknown ECOG PS score. The majority of the sample initiated the index LOT in LOT 3 (n=151; 96.2%) vs in LOT 4 (n=6; 3.8%). The median duration of the index LOT was 6.6 months with median follow-up from index LOT being 23.0 months. After 2 prior lines of TKI therapy, 93.0% of the sample continued on TKIs only, 1.3% initiated a non-TKI CML drug, and 5.7% received a combination of CML drugs. Dasatinib (31.2%) and imatinib (30.6%) were the most commonly used TKIs in the index LOT. There was significant variability in the treatment sequences across LOTs, however, 50.3% of the sample restarted the same TKI in their index LOT which had been used in a prior LOT. A total of 65 patients (41.4%) initiated a new LOT after the index LOT, and the treatment-free interval following the index LOT was 1.8 months, on average.CONCLUSIONS: The majority of the CML patients who received 2 prior lines of TKI therapy continue to cycle through additional LOTs containing TKIs, and half of the patients restart the same TKI used in a prior LOT. The findings of this study highlight the need for better novel therapies that can fill the treatment gap for CML patients who are refractory or intolerant to TKIs. REFERENCES1. Deininger MW, Shah NP, Altman JK, et al. Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2020;18(10):1385-1415.2. Hochhaus A, Saussele S, Rosti G, et al. Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl 4):iv41-iv51.3. Perrotti D, Jamieson C, Goldman J, et al. Chronic myeloid leukemia: mechanisms of blastic transformation. J Clin Invest. 2010;120(7):2254-2264.4. Cortes J, Lang F. Third-line therapy for chronic myeloid leukemia: current status and future directions. J Hematol Oncol. 2021;14(1):44. DisclosuresPatel: Novartis Pharmaceuticals Corporation: Research Funding. Raju: Xcenda LLC: Current Employment, Other: Xcenda LLC received research funding from Novartis Pharmaceuticals Corporation. Coutinho: Xcenda LLC: Current Employment, Other: Xcenda LLC received research funding from Novartis Pharmaceuticals Corporation. Maegawa: Novartis Pharmaceuticals Corporation: Current Employment, Current equity holder in publicly-traded company. Lunacsek: Xcenda LLC: Current Employment, Other: Xcenda LLC received research funding from Novartis Pharmaceuticals Corporation. Deyoung: Xcenda LLC: Current Employment, Other: Xcenda LLC received research funding from Novartis Pharmaceuticals Corporation. Iorga: Novartis Pharmaceuticals Corporation: Current Employment, Current equity holder in publicly-traded company. Cao: Novartis Pharmaceuticals Corporation: Current Employment, Current equity holder in publicly-traded company.

Neighborhood Poverty and Child Health: Investing in Communities to Improve Childhood Opportunity and Well-Being.

If ZIP code is more important than genetic code in determining one's health and opportunities, how can pediatricians enable healthy and opportunity-rich environments for all children? This paper introduces a broad network of organizations, policies, and financial resources that are working to improve ZIP codes by tackling poverty at the neighborhood level. The mission-driven US community development sector began with the War on Poverty in the 1960s and 70s and comprises a network of finance, real estate, and community-based organizations working together to overturn decades of racially motivated disinvestment, revitalize persistently marginalized, low-income communities, and enhance the lives of the people who live in them. Across the country, thousands of community development corporations, community development financial institutions, affordable housing developers, and regulated for-profit banks together invest over $300 billion annually in affordable housing, childcare and early learning facilities, recreation centers, community clinics, grocery stores, small businesses, and financial services for low-income families and neighborhoods. We present successful examples of community development efforts targeting child health and opportunity and highlight opportunities for pediatricians to advise, collaborate, and partner in order to accelerate and maximize the impact of billions of dollars invested in support of healthier neighborhoods where all children can grow and thrive.

Community Development Financial Institution (CDFI) program evaluation: a luxury but not a necessity?

ABSTRACT Community development financial institutions (CDFIs) are an integral component of US community economic development policy. These organizations differ in structure and client base, but they all seek to promote sustainable and equitable growth at the local level. By injecting capital into under-served markets, CDFIs facilitate development that may not otherwise occur. Attempts to measure and evaluate CDFI performance have often yielded disparate results. A systematic review of the literature reveals that capacity constraints have resulted in CDFI evaluations with wide variance in scope and rigor. Making comparisons across these institutions is difficult because there are few standardized performance metrics that could inform evaluations. Major CDFI funders in the philanthropic and public sectors often have competing demands and do not consistently use evaluations to guide their decisions. To incrementally advance CDFI research and promote a more accurate understanding of their impact, we recommend a shift towards utilization-focused evaluations (UFEs).

Daratumumab utilization and cost analysis among patients with multiple myeloma in a US community oncology setting.

Background: The introduction of daratumumab into the treatment of multiple myeloma has improved outcomes in patients;however, community oncologists often dose more frequently than the US FDA-approved label. Materials and methods: Integra analyzed its database to elucidate daratumumab treatment patterns and the impact of increased utilization on the cost of care for multiple myeloma. Results: Following week 24, 671 (65%) of 1037 patients remained on daratumumab-containing regimens, with 330 patients continuing more frequent treatments than the expected once-every-4-weeks dosing described in the standard dosing schedule. Patients received an average of 14% more daratumumab doses than the FDA-approved label indicates, increasing the 1-year daratumumab costs by an estimated US$31,353. Conclusion:Daratumumab is utilized more frequently than the FDA-recommended dosing, leading to higher multiple myeloma treatment costs.