Enrollment Eligibility Research Articles

Smartphone App-Based Remote Monitoring Challenges in Patients with Cardiac Resynchronization Therapy Defibrillators—A Multicenter Study

Background/Objectives: Remote monitoring (RM) cardiac implantable electronic devices for adults delivers improved patient outcomes. However, previously used bedside transmitters are not optimal due to deficient patient adherence. The goal of this study was to evaluate the efficacy of RM regarding the connectivity of smartphone app-based solutions, adherence to scheduled automatic follow-ups, and prevalence of alert-based events. Methods: We evaluated the adult heart failure (HF) population with an implanted cardiac resynchronization therapy defibrillator (CRT-D) divided into two arms: with app-based RM (abRM) and without app-based RM (control). Results: A total of 81 patients (median age of 69.0) were included in our study. Sixty-five patients received a CRT-D with abRM functionality, and sixteen did not. Twelve patients had no smartphone, and two provided no consent, resulting in their transfer to the control group. Finally, the abRM arm consisted of 51 patients, while 30 patients were in the control group. The median period of follow-up lasted 12 months. Among abRM patients, 98.0% successfully transmitted their first scheduled follow-up, and 80.4% were continuously monitored. Alert-based events were mainly related to arrhythmic events and device functionality with significantly shorter median times to notification (1 day vs. 101 days; p < 0.0001) in the abRM group. Conclusions: Our study showed a high level of compliance with timely initial transmission and adherence to scheduled remote follow-ups. Patient enrollment eligibility was a major challenge due to the limited accessibility of smartphones in the population. App-based RM demonstrated an accurate notification of events and patient-initiated transmissions in emergencies, regardless of location.

Evaluating enrollment processes and eligibility criteria of manufacturer free-drug patient assistance programs for oral anticancer agents used in hematologic malignancies.

117 Background: Increasing costs of oral anticancer agents (OAAs) pose a major barrier to patient adherence and consequently treatment effectiveness. While patient assistance programs (PAPs) may help cover costs, eligibility requirements for these programs are anecdotally reported to be non-transparent and enrollment processes burdensome, limiting their accessibility to patients. Thus, we evaluated the eligibility criteria and enrollment processes of manufacturer free-drug PAPs. Methods: A prospective review of manufacturer free-drug PAPs available for OAAs used in hematologic malignancies was conducted between October 2023 and February 2024. Available PAPs were identified using three online databases: RxAssist, NeedyMeds, and Association of Community Cancer Centers . Financial support program websites were assessed to gather information on eligibility requirements, enrollment processes, and other PAP characteristics. Results: For the 45 OAAs evaluated, 23 manufacturer free-drug PAPs were identified. All PAPs had insurance and income eligibility requirements which varied between programs. Uninsured patients were eligible for all programs, with 4% of programs restricting eligibility to only uninsured patients. The most common income eligibility threshold was 500% federal poverty limit, and requirement details were unavailable for 43.5% of programs. Enrollment could be initiated online, via downloadable form, and by phone-call, with 61% of programs having all three methods of enrollment initiation available to providers (17% to patients), 35% having two to providers (22% to patients), and 4% having only one to providers (52% to patients). Of note, 9% of programs offered no way for patients to independently initiate enrollment. Enrollment for all programs required both patient and provider inputs, and submission methods for some or all enrollment documentation included fax, online portal, email, and mail, with 4% of programs having four methods of submission available, 26% having three, 52% having two, and 17% having only one. Conclusions: The pathways for patients or providers to enroll in Patient Assistance Programs (PAPs) are complex and inconsistent across different programs, often requiring more action from providers than patients. Additionally, there is frequently a lack of transparency in the eligibility requirements for manufacturer free-drug PAPs.

Clonal monocytosis of renal significance

Clonal monocytosis reflects a preneoplastic or neoplastic sustained increase in the absolute monocyte count in the absence of reactive causes. Causes of clonal monocytosis include clonal cytopenias with monocytosis and acute and chronic myeloid neoplasms. Chronic myelomonocytic leukemia is a prototypical myelodysplastic/myeloproliferative overlap neoplasm in adults, characterized by sustained peripheral blood monocytosis. Renal abnormalities, including acute kidney injury and chronic kidney disease, are frequent in patients with chronic myelomonocytic leukemia and are predictors of worse outcomes. In addition, acute kidney injury/chronic kidney disease often limits eligibility for allogeneic stem cell transplantation or enrollment in clinical trials. In this review, we highlight clonal monocytosis-related etiologies that give rise to acute kidney injury and chronic kidney disease, with special emphasis on chronic myelomonocytic leukemia and lysozyme-induced nephropathy. Monocytes produce lysozyme, which, in excess, can accumulate in and damage the proximal renal tubular epithelium. Early identification of this etiology and a timely reduction in monocyte counts can salvage renal function. Other etiologies of renal injury associated with clonal monocytosis include direct renal infiltration by monocytes, renal extramedullary hematopoiesis, myeloproliferative neoplasm-associated glomerulopathy, autoimmune (membranous nephropathy, minimal change disease) and paraneoplastic manifestations, thrombotic microangiopathy, obstructive nephropathy due to myeloproliferation, and urate nephropathy due to tumor lysis syndrome. We propose to group these mechanistic etiologies of renal injury as clonal monocytosis of renal significance and provide guidance on their diagnosis and management.

Data quality in a survey of registered medical cannabis users with cancer: nonresponse and measurement error.

Cannabis use among individuals with cancer is best understood using survey self-report. As cannabis remains federally illegal, surveys could be subject to nonresponse and measurement issues impacting data quality. We surveyed individuals using medical cannabis for a cancer-related condition in the Minnesota Medical Cannabis Program (MCP). Although survey responders are older, there are no differences by race and ethnicity, gender, or receipt of reduced cannabis registry enrollment fee. Responders made a more recent purchase and more recently completed an independent symptom assessment for the registry than nonresponders, suggesting some opportunity for nonresponse error. Among responders, self-report and MCP administrative data with respect to age, race, gender, registry certification, and cannabis purchase history were similar. Responders were less likely to report receipt of Medicaid than would be expected based on registry low-income enrollment eligibility. Although attention should be paid to potential for nonresponse error, surveys are a reliable tool to ascertain cannabis behavior patterns in this population.

A deprescribing programme aimed to optimise blood glucose-lowering medication in older people with type 2 diabetes mellitus, the OMED2-study: the study protocol for a randomised controlled trial

BackgroundOlder patients with type 2 diabetes mellitus (T2D) have an increased risk of hypoglycaemic episodes when using sulphonylureas or insulin. In the Netherlands, guidelines exist for reducing glucose-lowering medication in older patients. However, evidence is lacking that a medication reduction in older patients can be safely pursued. Here, we will examine if promoting the deprescribing of insulin/sulphonylureas with a deprescribing programme (DPP) in general practice affects T2D-complications in older overtreated patients.MethodsWe will perform a 1:1 cluster randomised controlled trial in 86 general practices in the Netherlands. The DPP will consist of education sessions with general practitioners and practice nurses about reducing glucose-lowering medication in older patients (≥ 70 years). Topics of the sessions include the necessity of deprescribing, tools to initiate deprescribing and strategies to discuss deprescribing with patients (shared decision making). The DPP further includes a support programme with practice visits. The study will employ a selection tool to identify possibly overtreated older patients from the electronic medical records of the general practitioner. Eligibility for enrolment in the study will be based on HbA1c targets indicated by the Dutch guidelines, which depend on age, diabetes duration, presence of frailty, and life expectancy. The control group will provide usual care. We aim to include 406 patients. The follow-up period will be 2 years. For the primary outcome, the effect of the DPP on T2D-complications will be assessed by counting the cumulative incidence of events related to under- and overtreatment in T2D as registered in the electronic medical records. We shall perform an intention-to-treat analysis and an analysis including only patients for whom deprescribing was initiated. The implementation of the DPP in general practice will be evaluated quantitatively and qualitatively using the Extended Normalisation Process Theory (ENPT) and the Reach, Efficacy – Adoption, Implementation and Maintenance (RE-AIM) model. Other secondary outcomes include quality of life, cognitive functioning, events related to overtreatment or undertreatment, biomarkers of health, amount of blood glucose-lowering medication prescriptions, and cost-effectiveness.DiscussionThis study will provide insight into the safety and feasibility of a programme aimed at deprescribing sulphonylureas/insulin in older people with T2D who are treated in general practice.Trial registrationISRCTN Registry, ISRCTN50008265, registered 09 March, 2023.

Patterns of disease-modifying therapy utilization before, during, and after pregnancy and postpartum relapses in women with multiple sclerosis

BackgroundPregnancy is a common consideration for people with multiple sclerosis (pwMS); MS onset is typically between 20 and 45 years of age, during potential child-bearing years. Pregnancy and postpartum care are a significant factor influencing disease-modifying therapy (DMT) selection for many pwMS. To date, few DMTs are considered safe to continue during pregnancy and real-world treatment patterns before, during, and after pregnancy remain uncharacterized. Evolving guidance is needed regarding how to optimize management of the pregnancy and postpartum periods considering the changing DMT landscape. This analysis in two large claims databases describes DMT utilization for the treatment of MS before, during, and after pregnancy and relapse patterns during pregnancy and postpartum. MethodsIn this retrospective, observational study, the US MarketScan Commercial and Medicaid claims database was assessed for female patients aged 18–55 years with ≥1 insurance claim submitted under the diagnosis code of MS from 01 January 2016–30 April 2021 and continuous enrollment eligibility from ≥6 months prior to pregnancy date (preconception) through 6 months of follow-up following delivery (postpartum period). Comorbid conditions were examined preconception and postpartum, including anxiety and depression. Moderate/severe relapse was defined as MS-related hospitalization, or an outpatient visit and one claim within 7 days of the visit with steroids or total plasma exchange. ResultsA total of 944 patients (mean [standard deviation] age, 32.4 [5.0] years) were eligible; 688 (73%) were commercially insured and 256 (27%) received Medicaid. Compared with commercially-insured patients, use of DMTs was lower among Medicaid patients at 6 months preconception (25.4% vs 40.4%; p < 0.001), with similar patterns observed both during pregnancy and postpartum. Overall, prevalence of DMT use declined sharply during pregnancy, from 36.3% of patients in the 6 months preconception to 17.9%, 5.3%, and 5.8% in trimesters 1, 2 and 3, respectively. Postpartum DMT utilization increased to 20.9% at 0–3 months and 24.4% at 4–6 months. Of all patients in the preconception period, the most frequently used DMTs were glatiramer acetate (14.3%), dimethyl fumarate (6.0%), interferon (5.2%), and natalizumab (4.9%). Due to small sample size, information was limited for anti-CD20s and alemtuzumab. The proportion of patients with any moderate/severe relapse declined over pregnancy (preconception, n = 82 [8.7%]; pregnancy, n = 25 [2.6%]), but increased postpartum (n = 94 [10.0%]). Of the 889 patients who stopped DMT during pregnancy, the risk of postpartum relapses was lower in the patients who resumed DMT postpartum (10/192) than in patients who did not (76/697) (5.2% vs 10.9%; odds ratio, 0.455 [95% confidence interval 0.216–0.860], p = 0.018). Cases of postpartum depression and anxiety were significantly lower in commercially-insured patients vs Medicaid patients (postpartum depression, 13.7% vs 27.0%, p < 0.01; postpartum anxiety, 16.3% vs 30.5%, p < 0.01). ConclusionDMT utilization declined sharply during pregnancy; it gradually increased postpartum but remained below pre-pregnancy use. The proportion of pwMS experiencing a moderate/severe relapse and number of relapses declined over pregnancy but increased postpartum. Reinitiation of DMT during the postpartum period was associated with lower risk of relapses, supporting a role for early reinitiation of DMT postpartum. Study supported byBiogen

Active surveillance of immunization adverse effects: a multicentre, open-label, three-arm randomized uncontrolled trial in Ethiopia.

Participant-centred active adverse event following immunization (AEFI) surveillance can offer real-time vaccine safety data and help in signal detection. This study aimed to evaluate the effectiveness of participant-centred active adverse events (AEs) surveillance following measles immunization in Gedeo Zone health facilities in Ethiopia. An open-label, multicentred, three-arm randomized uncontrolled trial was conducted from 1 June to 21 October 2023. After assessing enrolment eligibility, the study participants were randomized into three groups (short message service [SMS], telephone interview, and diary card). They were expected to report AEs in children 1week after receiving immunization. Binary and multivariable logistic regression and χ2 tests were used to analyse the data. Among the 396 participants randomized into the three groups, 80.8% (320 participants) reported back about their children's AE status. Participants in the telephone interview group exhibited a substantially superior response rate (93.2% of 132 participants; p<0.00001) compared with the SMS (71.2%) and diary card (78%) groups. The likelihood of reporting the status of AEs experienced by children was lower by 77% (adjusted odds ratio 0.23 [95% confidence interval 0.1 to 0.52], p-value <0.00001) in the diary card group compared with the telephone interview group. In this study, a telephone interview was found to be the best method for AEFI reporting. Participant-centred active AE surveillance could potentially permit more rapid identification of emerging safety signals. Trial registration: https://clinicaltrials.gov/ct2/show/NCT05803538.

Abstract PO3-02-02: A prospective, international, observational, real-world evidence database, and collaborative platform for Investigator-Initiated Studies in Early-Stage Breast Cancer tested with MammaPrint and BluePrint– the FLEX Study

Abstract TIPS SABCS 2023 A prospective, international, observational, real-world evidence database, and collaborative platform for Investigator-Initiated Studies in Early-Stage Breast Cancer tested with MammaPrint and BluePrint– the FLEX Study Background: Clinical trials have been an invaluable tool in providing improvements in the discovery, treatment, and quality of life for various diseases and disorders including breast cancer, which impacts millions of people each year. The MammaPrint 70-gene assay along with BluePrint 80-gene subtype analysis are tools to provide such improvements in treatment planning. Historically, patient trial populations have not been racially diverse. Current efforts are focused on improving diversity and inclusion to promote efficacy and health equity across all races/ethnicities. Given recent publications supporting the ability of MammaPrint and BluePrint to identify genomic differences in outcomes of black women with breast cancer, the ongoing multi-center FLEX trial (NCT03053193) has proven to be an unparalleled source for improvement in breast cancer care. With a target of 30,000 enrolled patients, the collaborative research network within FLEX will use MammaPrint, BluePrint, full transcriptome, and clinical data to explore clinical and genomic differences in (sub)populations of interest to promote and advance precision medicine for patients with early-stage breast cancer. Methods: FLEX is the first of its kind to link clinical data with full transcriptome data. It is a prospective, observational trial that enrolls patients who are ≥ 18 years old with histologically proven stage I-III breast cancer with up to 3 positive lymph nodes. Patient eligibility for study enrollment include standard of care MammaPrint testing with or without BluePrint and consent to clinically annotated full transcriptome data collection. The study’s infrastructure facilitates the generation of hypotheses for targeted sub-studies that are important for breast cancer management. The FLEX network fosters collaboration with 99 active sites, including Canada, Greece, and Israel. All proposed substudies are vetted and approved by both internal and external research and scientific review committees. Since launching in April 2017, 13,547 patients have been enrolled including those who have been historically underrepresented in trials (Black n =1032; Latin n= 373; AAPI n =276), 43 investigator initiated sub-studies have been approved and are in progress on a varied number of approaches like MammaPrint/Blueprint clinical utilities, racial disparities, neoadjuvant treatment planning in ER+, and or HER2+ breast cancer with 31 abstracts accepted in national and international congresses. Five ongoing sub-studies within FLEX address differences in underlying biology and treatment response/management among Black, Latina, and Asian American patients with early-stage breast cancer. These studies provide a broader understanding of how differential gene expression patterns, identified with MammaPrint and BluePrint, are unique to racial/ethnic groups and can impact treatment outcomes. Overall, the FLEX study strives to use MammaPrint, BluePrint, and newly developed immune signature, ImPrint, along with full transcriptome data to improve precision medicine in early-stage breast cancer. Citation Format: JJ Alberty-Oller, Lee Riley, Laila Samiian, Sarah Thayer, Olexiy Aseyev, Karen Tedesco, Victoria Poillucci, William Audeh, Danijela Jelovac, Joyce O'Shaughnessy. A prospective, international, observational, real-world evidence database, and collaborative platform for Investigator-Initiated Studies in Early-Stage Breast Cancer tested with MammaPrint and BluePrint– the FLEX Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-02.

Area Vulnerability and Disparities in Therapy for Patients With Metastatic Renal Cell Carcinoma.

Area-level measures of sociodemographic disadvantage may be associated with racial and ethnic disparities with respect to receipt of treatment for metastatic renal cell carcinoma (mRCC) but have not been investigated previously, to our knowledge. To assess the association between area-level measures of social vulnerability and racial and ethnic disparities in the treatment of US Medicare beneficiaries with mRCC from 2015 through 2019. This retrospective cohort study included Medicare beneficiaries older than 65 years who were diagnosed with mRCC from January 2015 through December 2019 and were enrolled in fee-for-service Medicare Parts A, B, and D from 1 year before through 1 year after presumed diagnosis or until death. Data were analyzed from November 22, 2022, through January 26, 2024. Five different county-level measures of disadvantage and 4 zip code-level measures of vulnerability or deprivation and segregation were used to dichotomize whether an individual resided in the most vulnerable quartile according to each metric. Patient-level factors included age, race and ethnicity, sex, diagnosis year, comorbidities, frailty, Medicare and Medicaid dual enrollment eligibility, and Medicare Part D low-income subsidy (LIS). The main outcomes were receipt and type of systemic therapy (oral anticancer agent or immunotherapy from 2 months before to 1 year after diagnosis of mRCC) as a function of patient and area-level characteristics. Multivariable regression analyses were used to adjust for patient factors, and odds ratios (ORs) from logistic regression and relative risk ratios (RRRs) from multinomial logistic regression are reported. The sample included 15 407 patients (mean [SD] age, 75.6 [6.8] years), of whom 9360 (60.8%) were men; 6931 (45.0%), older than 75 years; 93 (0.6%), American Indian or Alaska Native; 257 (1.7%), Asian or Pacific Islander; 757 (4.9%), Hispanic; 1017 (6.6%), non-Hispanic Black; 12 966 (84.2%), non-Hispanic White; 121 (0.8%), other; and 196 (1.3%), unknown. Overall, 8317 patients (54.0%) received some type of systemic therapy. After adjusting for individual factors, no county or zip code-level measures of social vulnerability, deprivation, or segregation were associated with disparities in treatment. In contrast, patient-level factors, including female sex (OR, 0.78; 95% CI, 0.73-0.84) and LIS (OR, 0.48; 95% CI, 0.36-0.65), were associated with lack of treatment, with particularly limited access to immunotherapy for patients with LIS (RRR, 0.25; 95% CI, 0.14-0.43). Associations between individual-level factors and treatment in multivariable analysis were not mediated by the addition of area-level metrics. Disparities by race and ethnicity were consistently and only observed within the most vulnerable areas, as indicated by the top quartile of each vulnerability deprivation index. In this cohort study of older Medicare patients diagnosed with mRCC, individual-level demographics, including race and ethnicity, sex, and income, were associated with receipt of systemic therapy, whereas area-level measures were not. However, individual-level racial and ethnic disparities were largely limited to socially vulnerable areas, suggesting that efforts to improve racial and ethnic disparities may be most effective when targeted to socially vulnerable areas.

White Matter Alterations in Military Service Members With Remote Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) is the signature injury experienced by military service members and is associated with poor neuropsychiatric outcomes. Yet, there is a lack of reliable clinical tools for mTBI diagnosis and prognosis. To examine the white matter microstructure and neuropsychiatric outcomes of service members with a remote history of mTBI (ie, mTBI that occurred over 2 years ago) using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI). This case-control study examined 98 male service members enrolled in a study at the National Intrepid Center of Excellence. Eligible participants were active duty status or able to enroll in the Defense Enrollment Eligibility Reporting system, ages 18 to 60 years, and had a remote history of mTBI; controls were matched by age. Remote history of mTBI. White matter microstructure was assessed using a region-of-interest approach of skeletonized diffusion images, including DTI (fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity) and NODDI (orientation dispersion index [ODI], isotropic volume fraction, intra-cellular volume fraction). Neuropsychiatric outcomes associated with posttraumatic stress disorder (PTSD) and postconcussion syndrome were assessed. A total of 65 male patients with a remote history of mTBI (mean [SD] age, 40.5 [5.0] years) and 33 age-matched male controls (mean [SD] age, 38.9 [5.6] years) were included in analysis. Compared with the control cohort, the 65 service members with mTBI presented with significantly more severe PTSD-like symptoms (mean [SD] PTSD CheckList-Civilian [PCL-C] version scores: control, 19.0 [3.8] vs mTBI, 41.2 [11.6]; P < .001). DTI and NODDI metrics were altered in the mTBI group compared with the control, including intra-cellular volume fraction of the right cortico-spinal tract (β = -0.029, Cohen d = 0.66; P < .001), ODI of the left posterior thalamic radiation (β = -0.006, Cohen d = 0.55; P < .001), and ODI of the left uncinate fasciculus (β = 0.013, Cohen d = 0.61; P < .001). In service members with mTBI, fractional anisotropy of the left uncinate fasciculus was associated with postconcussion syndrome (β = 5.4 × 10-3; P = .003), isotropic volume fraction of the genu of the corpus callosum with PCL-C (β = 4.3 × 10-4; P = .01), and ODI of the left fornix and stria terminalis with PCL-C avoidance scores (β = 1.2 × 10-3; P = .02). In this case-control study of military-related mTBI, the results suggest that advanced magnetic resonance imaging techniques using NODDI can reveal white matter microstructural alterations associated with neuropsychiatric symptoms in the chronic phase of mTBI. Diffusion trends observed throughout widespread white matter regions-of-interest may reflect mechanisms of neurodegeneration as well as postinjury tissue scarring and reorganization.

Overview and Design of the Child Maltreatment in Military Families Life Course Study

Objective This report presents an overview of the objectives, design, and analytic strategy of the Child Maltreatment in Military Families Life Course Study, an investigation of factors associated with child maltreatment in active duty military families. Method The study uses a case-control retrospective research design and discrete-time survival methodology to examine service member demographic characteristics, family characteristics, military-related characteristics, and military family life events associated with child maltreatment incidents that meet the Department of Defense definition of child abuse or neglect. The sample includes all active duty families with a first occurrence of child maltreatment anytime between Fiscal Year (FY) 2009 and FY 2018 (n = 28,684), and a representative sample of control families with children under age of 18 during the same period (n = 589,417). Analyses include child maltreatment and domestic abuse data from the Family Advocacy Program Central Registry; sponsor socio-demographic, military-related, and family data from the Active Duty Military Personnel Master and Defense Enrollment Eligibility Reporting System data files; deployment data from the Contingency Tracking System; and mental health data from the Medical Data Repository. Results and Conclusions Study results identify risk and protective factors associated with child maltreatment in military families, subgroups at elevated risk of child maltreatment, and periods of heightened risk during the military family life course. These results are expected to improve the ability to identify families most at-risk for particular types of child maltreatment and inform prevention strategies that promote the health and safety of military families.

‘You have to go hunting for information’: Barriers to service utilization among expectant and parenting youth with experience in foster care

AbstractUnique service needs exist for expectant or parenting youth with foster care histories (EPY) and their families. Informed by Critical Ecological Systems Theory (CEST), this exploratory qualitative study presents findings from an inductive content analysis of in‐depth interviews and focus groups with EPY and service providers. The study included nine in‐depth face‐to‐face interviews with service providers (n = 5) and EPY (n = 4) as well as five focus groups with service providers (n = 23) and three with EPY (n = 7) to identify the characteristics of service providers, agencies and systems that may act as barriers to service utilization among EPY with a foster care history (n = 10) or juvenile justice history (n = 1). Service provider characteristics included negative attitudes towards EPY and/or those with child welfare experiences. Agency characteristics included a lack of workforce diversity, employee turnover, lack of training about diverse communities, restrictive enrolment processes and eligibility requirements, lack of childcare and transportation and limited accessibility of services. System characteristics included a lack of up‐to‐date information about existing services, territorialism, funding sources that do not prioritize interagency collaboration and a lack of communication/coordination among agencies. Implications include hiring and retaining a diverse workforce, providing training about diverse communities and implicit biases concerning young parents, developing navigation services specifically for EPY and developing processes for sharing data and communicating across systems that interact with EPY.

Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): One-Year Safety and Efficacy Outcomes from a Multicenter Phase I Trial

The combination of immunotherapy and single-fraction stereotactic radiosurgery (SRS) for treatment of metastatic brain disease has yielded symptomatic radiation necrosis rates as high as 20% (PMID: 29327059). Consequently, the Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI) multicenter phase I trial (registered at clinicaltrials.gov, NCT04047602) was created to address whether reduced-dose SRS can improve morbidity without compromising efficacy. In this report we present our one-year findings. Eligibility for RADREMI enrollment required brain metastases patients with: a) Histologically-confirmed primary malignancy, b) Receipt of immunotherapy within 30 days of SRS, c) 1-10 MRI-visible brain metastases, d) Estimated median survival of at least 6 months (via disease-specific graded prognostic assessment), and e) No history of whole brain radiation therapy. Reduced-dose SRS utilized 18 Gy for lesions 0-2 cm, 14 Gy for lesions 2.1-3 cm, and 12 Gy for lesions 3.1-4 cm. Symptomatic radiation necrosis was defined as imaging findings consistent with radiation necrosis combined with clinical symptoms requiring steroid administration and/or operative intervention. Local control was defined by Response Assessment in Neuro-Oncology (RANO) criteria. From December 18, 2019 to June 30, 2022, 54 lesions in 17 patients were treated on RADREMI with at least one-year of follow-up. One-year local control occurred in 52 of 54 lesions and in 15 of 17 patients, yielding control rates of 96% per lesion and 88% per patient. Radiographic radiation necrosis occurred in 2 of 54 lesions (4%). No symptomatic radiation necrosis occurred. Our findings of concurrent immunotherapy + reduced-dose SRS at one-year post-treatment revealed excellent local control (96%) with no symptomatic radiation necrosis, and minimal radiographic radiation necrosis. These results attest to the durability of the safety and efficacy of reduced-dose SRS with immunotherapy for metastatic brain disease.

Medicare Advantage Enrollment and Disenrollment Among Persons With Alzheimer Disease and Related Dementias

Large enrollment growth has been observed in the Medicare Advantage program, but less is known about enrollment patterns among persons with Alzheimer disease and related dementias (ADRD). To evaluate patterns in Medicare Advantage enrollment and disenrollment among beneficiaries with or without ADRD. This cross-sectional study used 6 national data sources between January 1, 2011, and December 31, 2018. Analyses were performed between June 2021 and August 2022. The cohort comprised US Medicare beneficiaries with acute or postacute care utilization between 2013 and 2018. ADRD diagnosis from an acute or postacute care encounter Medicare data source. Enrollment in Medicare Advantage, disenrollment from Medicare Advantage to traditional Medicare, and contract exit (leaving a Medicare Advantage contract for traditional Medicare or a different Medicare Advantage contract). The 32 796 872 Medicare beneficiaries in the cohort had a mean (SD) age of 74.0 (12.5) years and included 18 228 513 females (55.6%). Enrollment in Medicare Advantage among beneficiaries with ADRD increased from 24.7% (95% CI, 24.7%-24.8%) in 2013 to 33.0% (95% CI, 32.9%-33.1%) in 2018, an absolute increase of 8.3 percentage points and a 33.4% relative increase after adjusting for demographic characteristics, comorbid conditions, and utilization and including county fixed effects. Among beneficiaries without ADRD, enrollment in Medicare Advantage increased by 8.2 percentage points from 27.6% (95% CI, 27.6%-27.6%) in 2013 to 35.8% (95% CI, 35.8%-35.8%) in 2018, a 29.7% relative increase over the study period. Beneficiaries with ADRD were 1.4 times as likely to disenroll from their Medicare Advantage contract to traditional Medicare (4.4% vs 3.2% in 2017-2018; P < .001) in adjusted analyses. Regardless of ADRD status, beneficiaries had similar rates of switching to a new Medicare Advantage contract. Differences in contract exit rates were associated with higher rates of disenrollment from Medicare Advantage to traditional Medicare among beneficiaries with ADRD vs those without ADRD (16.3% [95% CI, 16.2%-16.3%] vs 15.1% [95% CI, 15.1%-15.1%]). Beneficiaries with ADRD and dual eligibility for Medicaid enrollment had higher rates of contract exit than those without dual eligibility (19.7% [95% CI, 19.6%-19.7%] vs 14.9% [95% CI, 14.8%-14.9%]), and these differences were even greater than those among beneficiaries without ADRD and with and without dual-eligibility status, respectively (18.3% [95% CI, 18.2%-18.3%] vs 13.8% [95% CI, 13.7%-13.8%]). In this cross-sectional study of the Medicare population with acute and postacute care use, beneficiaries with ADRD had increasing enrollment in the Medicare Advantage program, proportional to the growth in overall enrollment, but their disenrollment from Medicare Advantage in the following year remained higher compared with beneficiaries without ADRD. The findings highlight the need to understand the factors associated with higher disenrollment rates and determine whether such rates reflect access or quality challenges for beneficiaries with ADRD.

Perspectives of VA healthcare from rural women veterans not enrolled in or using VA healthcare.

Women Veterans have unique healthcare needs and often experience comorbid health conditions. Despite this, many women Veterans are not enrolled in the Veterans Health Administration (VHA) and do not use VHA services. Underutilization of VHA services may be particularly prevalent among rural women Veterans, who may experience unique barriers to using VHA care. Nonetheless, knowledge of rural women Veterans and their experiences remains limited. We sought to understand rural women Veterans' perceptions and needs related to VHA healthcare, including barriers to enrolling in and using VHA services, and perspectives on how to communicate with rural women Veterans about VHA services. Rural women Veterans were recruited through community engagement with established partners and a mass mailing to rural women Veterans not enrolled in or using VHA healthcare. Ten virtual focus groups were conducted with a total of twenty-nine rural women Veterans (27 not enrolled in VHA care and 2 who had not used VHA care in the past 5 years) in 2021. A thematic inductive analytic approach was used to analyze focus group transcripts. Primary themes regarding rural women Veterans' perceptions of barriers to enrollment and use of VHA healthcare included: (1) poor communication about eligibility and the process of enrollment; (2) belief that VHA does not offer sufficient women's healthcare services; and (3) inconvenience of accessing VHA facilities. Although VHA has substantially expanded healthcare services for women Veterans, awareness of such services and the nuances of eligibility and enrollment remains an impediment to enrolling in and using VHA healthcare among rural women Veterans. Recommended strategies include targeted communication with rural women Veterans not enrolled in VHA care to increase their awareness of the enrollment process, eligibility, and expansion of women's healthcare services. Creative strategies to address access and transportation barriers in rural locations are also needed.

Ethical challenges in first-in-human trials of the artificial placenta and artificial womb: not all technologies are created equally, ethically.

Artificial placenta and artificial womb technologies to support extremely premature neonates are advancing toward clinical testing in humans. Currently, no recommendations exist comparing these approaches to guide study design and optimal enrollment eligibility adhering to principles of research ethics. In this paper, we will explore how scientific differences between the artificial placenta and artificial womb approaches create unique ethical challenges to designing first-in-human trials of safety and provide recommendations to guide ethical study design for initial human translation.

FLEX, a real-world evidence full transcriptome study of 30,000 patients with early-stage breast cancer.

TPS621 Background: Clinical trials have been an invaluable tool in providing improvements in the discovery, treatment, and quality of life for various diseases and disorders including breast cancer, which impacts millions of people each year. Historically, patient trial populations have not been racially diverse due to several factors such as bias, healthcare distrust, access, and eligibility criteria. However, current efforts are focused on improving diversity and inclusion to promote efficacy and health equity across all races/ethnicities. The ongoing, multi-center FLEX trial (NCT03053193), which pairs clinical data and full transcriptome expression data, seeks to enroll 30,000 patients to accelerate real world research. Due to the size of the database, it is also expected to capture patients typically underrepresented in clinical trials. Methods: FLEX is the first of its kind, prospective, observational trial that enrolls patients who are ≥ 18 years old with histologically proven stage I-III breast cancer with up to 3 positive lymph nodes. Patient eligibility for study enrollment include standard of care MammaPrint testing with or without BluePrint and consent to clinically annotated full transcriptome data collection. The study infrastructure facilitates the generation of hypotheses for targeted sub-studies. The FLEX network fosters collaboration with 114 sites, including one site in Greece and Israel, encouraging participating investigators to initiate sub-studies that can address research questions that are important for breast cancer management. All proposed sub-studies are vetted and approved by Research and Scientific Review Committees. Since launching in April 2017, 12,569 patients have been enrolled including those who have been historically underrepresented in trials (African American n= 1025; Latin n= 341; Asian n=156). Forty-two investigator initiated sub-studies have been approved and are in progress, with 40 abstracts accepted in national and international congresses. Five ongoing sub-studies within FLEX address differences in underlying biology and treatment response/management among African American, Latina, and Asian American patients with early-stage breast cancer. These studies provide a broader understanding of how differential gene expression patterns unique to racial/ethnic groups can impact treatment outcomes. With the large FLEX database, enrollment and sub-studies are extended to other racial/ethnic groups that are underrepresented in clinical trials, but not limited to specific groups. Overall, the FLEX study strives to use full transcriptome data to improve precision medicine in early-stage breast cancer. Clinical trial information: NCT03053193 .

How patient-clinician education can strengthen partnerships and promote tangible actions to improve clinical trial diversity in breast and lung cancer trials.

6510 Background: Some of the greatest disparities in cancer care are related to clinical trial access for our patients. To address the racial/ethnic disparities in breast and lung cancer clinical trials, a tethered educational initiative was designed to empower patients, assess current clinician perceptions/practices, and improve awareness of real-world perspectives of clinical trials. Methods: Two, one-hour online, interactive, video-based programs were designed for patients, caregivers, and providers. This patient/caregiver program was hosted on CancerCoachLive and MedLive in November, 2022, while the provider program was hosted on ClinicalSeriesLive in December, 2022 and will remain on-demand until December 2023. This initiative was conducted in collaboration with TOUCH, the Black Breast Cancer Alliance, BlackDoctors.org, Moffitt Cancer Center, CancerCare, and the Lung Cancer Research Foundation. Herein, we report on an analysis from patients and providers regarding clinical trial diversity, behavioral impact, and qualitative insights. Results: As of data cut-off (02/10/23), 1,425 participants have engaged across both educational programs. Of participating patients, 46% were non-White (non-Hispanic), 36% were in remission, 36% were not on active treatment, and 29% were newly diagnosed. Following the program 81% were motivated to take one or more actions over the next two months: the most common actions being to research clinical trials (38%) or discuss clinical trials with a clinician (19%). Post-activity, 79% were confident to very confident discussing clinical trials with a clinician. Critical data related to clinician preferences was assessed and demonstrated a 23% increase in confidence from pre- to post-activity in improving diversity in clinical trial participation with preferences observed in both breast and lung cancers to offer clinical trials for newly diagnosed and second recurrence settings. Of those who are being offered clinical trials in the community setting, there was a higher likelihood for patients to be offered a clinical trial if their subtype was HER2+ breast cancer subtype or NSCLC with an actionable mutation. Data collection continues as this initiative is ongoing. Qualitative data including clinician write-in examples of behavioral impact and patient perspectives from the interviews will be shared. Conclusions: The outcomes discussed herein reveal a willingness from patients/caregivers to engage in clinical trial discussions and participate in clinical trials, if eligible. These educational programs positively impacted clinician motivation to address barriers to enrollment and clinical trial eligibility with their patients. Real-world accounts of patient experiences provide different perspectives that can help improve approaches to improve clinical trial diversity.

PSMA PET findings in an “EMBARK-like” cohort of patients with high-risk non-metastatic hormone-sensitive prostate cancer: A single center post-hoc retrospective analysis.

5091 Background: The EMBARK trial is a phase 3, randomized, study evaluating use of enzalutamide with or without concomitant leuprolide in non-metastatic castrate sensitive prostate cancer patients. Eligibility status for the trial relied upon conventional imaging which under detects metastatic disease in comparison to PSMA-PET imaging. The aim of this post-hoc retrospective analysis was to describe the PSMA-PET findings in a patient population representative of the EMBARK trial. Methods: This was a post-hoc, retrospective analysis of 5 prospective studies of PSMA PET conducted at UCLA from 2016 to 2021 that included patients with recurrent PCa following RP, RT or SRT. Patients were included if they met eligibility for enrollment in the EMBARK trial at the time of their PSMA scan defined as the following: Rising PSA at a level above 1.0ng/mL (post RP and SRT) or 2.0ng/mL &gt; nadir (post-RT), PSA doubling time ≤ 9 months, Serum testosterone ≥ 150 ng/dL. Exclusion criteria constituted: distant metastatic disease as assessed by radiographic imaging, prior hormonal therapy or systemic therapy for prostate cancer. PSMA PET findings (PROMISE miTNM stage, number of lesions) were collected from the clinical imaging reports. Descriptive statistics were used (median, range). Results: From 2002 patients screened, 146 patients were included in the analysis. Median time from primary therapy to PSMA PET was 39 (2.1-261) months. Median pre-scan PSA levels and PSA doubling time in patients who underwent RP (n=85), dRT (n=22), post-RP SRT (n=39) and overall (n=146) were 2.4 ng/mL (1-72.1), 8.3 ng/mL (2.37-202), 2.58 ng/ml (1.1-32.3), 2.7 ng/mL (1-202), and 3.5 months (1-9), 3.3 months (1-9), 4.4 months (1-9), 3.7 (1-9) months, respectively. PSMA-PET was positive in 80%, 41%, 85%, 83% of the RP, dRT, RP + SRT and overall populations, respectively. Poly-metastatic disease (≥5 lesions) was found in 19%, 32%, 21% and 21% of cases, respectively. PSMA-PET detected disease only localized to the prostate fossa (miT+N0M0) in 7%, 32%, 0% and 9% respectively. PSMA-PET detected pelvic nodal disease (miTxN1M0) in 40% 18% 28% and 34% respectively. PSMA PET detected any distant metastatic disease (miTxNxM1) in 33%, 41% 56% and 40% respectively. PSMA-PET detected metastatic nodal only disease (N1 and/or M1a) in 58% 32% 74% and 39% and osseous disease (M1b) in 19% 23% 31% and 23% cases respectively. Conclusions: In this “EMBARK-like” cohort of patients with high-risk nmCS PCa and PSA DT &lt; 9 months, PSMA PET was positive in 83% of patients, detected M1 disease in 40% of patients and over one-fifth of cases presented with 5 or more lesions. PSMA-PET provides novel additional risk stratification for patients with high-risk nmCS PCa without distant metastasis based on conventional imaging. Further studies are needed to assess its independent prognostic value and use for treatment guidance. Clinical trial information: NCT03582774 .

Prevalence of Eye and Vision Disorders in the Military Health System, Fiscal Year 2018.

Eye and vision disorders are estimated to impact 7.08 million people in the United States, including 1.62 million under the age of 40. This study uses the Vision and Eye Health Surveillance System (VEHSS) case definitions to assess the burden of eye and vision disorders in a universally insured, nationally representative population. This retrospective, cross-sectional study applied the VEHSS case definitions to TRICARE claims data collected from the Military Health System Data Repository and Defense Enrollment Eligibility Reporting System during 2018. Beneficiaries aged 0-64 years during the fiscal year 2018 were identified with inpatient and outpatient codes matching to the VEHSS diagnostic case definitions, which were organized into 17 categories of eye and vision disorders classified by the ICD-10. Beneficiaries were recorded only once per category but allowed to match to multiple categories. Analyses included descriptive statistics of patient demographics and prevalence of eye disorders. We identified 4,548,897 TRICARE Prime/Plus beneficiaries (54.86% men and 45.14% women), of whom 22.93% were diagnosed with at least one disorder in 2018. Of those with a diagnosis, the majority were men (50.13%), adults (74.91%), and of or sponsored by a senior enlisted rank (57.83%), used as socioeconomic proxy. Disorders of refraction and accommodation were most prevalent, followed by infectious and inflammatory diseases. Potentially preventable and treatable conditions, including amblyopia and strabismus, infectious and inflammatory disease, and diabetic complications, affected up to 22% of those with vision disorders. This study represents the first use of VEHSS measures in a universally insured, socioeconomically diverse population. Identification of potentially treatable or preventable conditions indicates significant opportunity to mitigate the burden of eye and vision disorders in the Military Health System.