Citations

Background: In 2014, the Affordable Care Act Medicaid Expansion (ME) increased Medicaid eligibility for adults with an income level up to 138% of the federal poverty level. In this study, we examined the impact of ME on mortality and amputation in patients with peripheral artery disease (PAD). Methods: The 100% MedPAR and Part-B Carrier files from 2011 to 2018 were queried to identify all fee-for-service Medicare beneficiaries with PAD using International Classification of Diseases codes. Our primary exposure was whether a state had adopted the ME on January 1, 2014. Our primary outcomes were the change in all-cause 1-year mortality and leg amputation. We used a state-level difference-in-differences (DID) analysis to compare the rates of the primary outcomes among patients who were in states (including the District of Columbia) who adopted ME ( n = 25) versus those who were in states that did not ( n = 26). We performed a subanalysis stratifying by sex, race, region, and dual-eligibility status. Results: Over the 8-year period, we studied 37,743,929 patients. The average unadjusted 1-year mortality decreased from 2011 to 2018 in both non-ME (9.5% to 8.7%, p < 0.001) and ME (9.1% to 8.3%, p < 0.001) states. The average unadjusted 1-year amputation rate did not improve in either the non-ME (0.86% to 0.87%, p = 0.17) or ME (0.69% to 0.69%, p = 0.65) states. Across the entire cohort, the DID model revealed that ME did not lead to a significant change in mortality ( p = 0.15) or amputation ( p = 0.34). Conclusion: Medicaid Expansion was not associated with reduced mortality or leg amputation in Medicare beneficiaries with PAD.

Abstract Apilimod dimesylate is a first-in-class phosphoinositide kinase, FYVE-type zinc finger-containing (PIKfyve) inhibitor with a favourable clinical safety profile and has demonstrated activity in preclinical C9orf72 and TDP-43 amyotrophic lateral sclerosis (ALS) models. In this ALS clinical trial, the safety, tolerability, CNS penetrance and modulation of pharmacodynamic target engagement biomarkers were evaluated. This phase 2a, randomized, double-blind, placebo-controlled, biomarker-end-point clinical trial was conducted in four US centres (ClinicalTrials.gov NCT05163886). Participants with C9orf72 repeat expansions were randomly assigned (2:1) to receive twice-daily oral treatment with 125 mg apilimod dimesylate capsules or matching placebo for 12 weeks, followed by a 12-week open-label extension. Safety was measured as the occurrence of treatment-emergent or serious adverse events attributable to the study drug and tolerability at trial completion or treatment over 12 weeks. Changes from baseline in plasma and CSF and concentrations of apilimod dimesylate and its active metabolites and of pharmacodynamic biomarkers of PIKfyve inhibition [soluble glycoprotein nonmetastatic melanoma protein B (sGPNMB) upregulation] and disease-specific CNS target engagement [poly(GP)] were measured. Between 16 December 2021 and 7 July 2022, 15 eligible participants were enrolled. There were no drug-related serious adverse events reported in the trial. Fourteen (93%) participants completed the double-blind period with 99% dose compliance [n = 9 (90%) apilimod dimesylate; n = 5 (100%) placebo]. At Week 12, apilimod dimesylate was measurable in CSF at 1.63 ng/ml [standard deviation (SD): 0.937]. At Week 12, apilimod dimesylate increased plasma sGPNMB by &gt;2.5-fold (P &lt; 0.001), indicating PIKfyve inhibition, and lowered CSF poly(GP) protein levels by 73% (P &lt; 0.001), indicating CNS tissue-level proof of mechanism. Apilimod dimesylate met prespecified key safety and biomarker end-points in this phase 2a trial and demonstrated CNS penetrance and pharmacodynamic target engagement. Apilimod dimesylate was observed to result in the greatest reduction in CSF poly(GP) levels observed to date in C9orf72 clinical trials.

Importance Among women diagnosed with primary breast cancer (BC) at or younger than age 40 years, prior data suggest that their risk of a second primary BC (SPBC) is higher than that of women who are older when they develop a first primary BC. Objective To estimate cumulative incidence and characterize risk factors of SPBC among young patients with BC. Design, Setting, and Participants Participants were enrolled in the Young Women’s Breast Cancer Study, a prospective study of 1297 women aged 40 years or younger who were diagnosed with stage 0 to III BC from August 2006 to June 2015. Demographic, genetic testing, treatment, and outcome data were collected by patient surveys and medical record review. A time-to-event analysis was used to account for competing risks when determining cumulative incidence of SPBC, and Fine-Gray subdistribution hazard models were used to evaluate associations between clinical factors and SPBC risk. Data were analyzed from January to May 2023. Main Outcomes and Measures The 5- and 10- year cumulative incidence of SPBC. Results In all, 685 women with stage 0 to III BC (mean [SD] age at primary BC diagnosis, 36 [4] years) who underwent unilateral mastectomy or lumpectomy as the primary surgery for BC were included in the analysis. Over a median (IQR) follow-up of 10.0 (7.4-12.1) years, 17 patients (2.5%) developed an SPBC; 2 of these patients had cancer in the ipsilateral breast after lumpectomy. The median (IQR) time from primary BC diagnosis to SPBC was 4.2 (3.3-5.6) years. Among 577 women who underwent genetic testing, the 10-year risk of SPBC was 2.2% for women who did not carry a pathogenic variant (12 of 544) and 8.9% for carriers of a pathogenic variant (3 of 33). In multivariate analyses, the risk of SPBC was higher among PV carriers vs noncarriers (subdistribution hazard ratio [sHR], 5.27; 95% CI, 1.43-19.43) and women with primary in situ BC vs invasive BC (sHR, 5.61; 95% CI, 1.52-20.70). Conclusions Findings of this cohort study suggest that young BC survivors without a germline pathogenic variant have a low risk of developing a SPBC in the first 10 years after diagnosis. Findings from germline genetic testing may inform treatment decision-making and follow-up care considerations in this population.

Purpose In the state of Hawaii, it has been shown that certain ethnic minority groups, such as Filipinos and Pacific Islanders, suffer disproportionally high rates of cardiovascular disease, evidence that local health-care systems and governing bodies fail to equally extend the human right to health to all. This study aims to examine whether these ethnic health disparities in cardiovascular disease persist even within an already globally disadvantaged group, the houseless population of Hawaii. Design/methodology/approach A retrospective chart review of records from Hawaii Houseless Outreach and Medical Education Project clinic sites from 2016 to 2020 was performed to gather patient demographics and reported histories of type II diabetes, obesity, hyperlipidemia, hypertension and other cardiovascular disease diagnoses. Reported disease prevalence rates were compared between larger ethnic categories as well as ethnic subgroups. Findings Unexpectedly, the data revealed lower reported prevalence rates of most cardiometabolic diseases among the houseless compared to the general population. However, multiple ethnic health disparities were identified, including higher rates of diabetes and obesity among Native Hawaiians and other Pacific Islanders and higher rates of hypertension among Filipinos and Asians overall. The findings suggest that even within a generally disadvantaged houseless population, disparities in health outcomes persist between ethnic groups and that ethnocultural considerations are just as important in caring for this vulnerable population. Originality/value To the best of the authors’ knowledge, this is the first comprehensive study focusing on ethnic health disparities in cardiovascular disease and the structural processes that contribute to them, among a houseless population in the ethnically diverse state of Hawaii.

AbstractBackgroundEmbryonal sarcoma of the liver (ESL) is a rare mesenchymal tumor most common in childhood; the optimal treatment approach is uncertain. The clinical features and outcomes of patients with ESL enrolled in a Children’s Oncology Group (COG) clinical trial that evaluated a risk‐based strategy for treating soft tissue sarcomas in patients aged <30 years were evaluated.MethodsThis subset analysis included patients with ESL enrolled in COG study ARST0332. Central review of records, pathology, and imaging confirmed the diagnosis, presenting features, and surgery extent and complications. All patients received dose‐intensive ifosfamide/doxorubicin chemotherapy, with cycle timing dependent on surgery and radiotherapy. Tumor resection occurred before study entry or after four cycles of chemotherapy; radiotherapy for residual tumor was optional.ResultsThirty‐nine eligible/evaluable patients with ESL were analyzed. All tumors were >10 cm in diameter; four were metastatic. Tumor resection was performed upfront in 23 and delayed in 16. Positive surgical margins (n = 6) and intraoperative tumor rupture (n = 6) occurred only in upfront resections. Eight patients received radiotherapy. Estimated 5‐year event‐free and overall survival were 79% (95% confidence interval [CI], 65%–93%) and 95% (95% CI, 87%–100%), respectively. Positive margins increased the local recurrence risk. One of 13 patients with documented hemorrhagic ascites and/or tumor rupture developed extrahepatic intra‐abdominal tumor recurrence.ConclusionsThe treatment strategy used in ARST0332 achieved favorable outcomes for patients with ESL despite a substantial proportion having high‐risk disease features. Deferring tumor resection until after neoadjuvant chemotherapy may decrease the risk of intraoperative tumor rupture and improve the likelihood of adequate surgical margins.

Abstract Objective To assess for improvement in comfort in participating in advocacy for migraine and headache disorders and knowledge needed for successful advocacy. Background The Advocacy Connection Team (ACT)‐Now program is an educational program offered through Miles for Migraine, a non‐profit advocacy organization. It is designed to teach headache fellows and patients advocacy skills. Methods In a cross‐sectional pre‐test–post‐test design, the 2021 ACT‐Now cohort of 98 participants were administered a set of 11 pre‐course survey questions identifying their role (healthcare provider/headache fellow or patient/caregiver), baseline knowledge of migraine‐related disability and stigma, and baseline engagement and comfort with advocating. The post‐course survey questions were the same as the pre‐course questions, with the addition of one question assessing knowledge of migraine‐related disability, additional questions addressing comfort levels advocating with insurance and policymakers, as well as creating an advocacy plan. Results For the pre‐course survey, 69 participants responded and for the post‐course survey, 40 participants responded. Compared to the pre‐course survey, participants were able to correctly identify epidemiological data about migraine following the ACT‐Now course (pre‐course 46% correct, post‐course 58% correct, p = 0.263). There was also an increase in the comfort level of participants in advocacy activities, including the creation of an advocacy action plan (pre‐course 23% were “very comfortable” advocating, post‐course 63%, p < 0.05). Conclusion These results demonstrate that ACT‐Now is effective at improving advocacy skills in a mixed cohort of patients and headache fellows, giving them the skills to create advocacy plans and engage with other patients and physicians, payers, and policymakers to create a more understanding, equitable and compassionate world for persons with migraine and other headache diseases.

AbstractPurposePepinemab, a humanized IgG4 monoclonal antibody, targets the SEMA4D (CD100) antigen to inhibit binding to its high‐affinity receptors (plexin B1/PLXNB1, plexin B2/PLXNB2) and low‐affinity receptor (CD72). SEMA4D blockade leads to increased cytotoxic T‐cell infiltration, delayed tumor growth, and durable tumor rejection in murine tumor models. Pepinemab was well tolerated and improved T cell infiltration in clinical studies in adults with refractory tumors. SEMA4D was identified as a strong candidate proto‐oncogene in a model of osteosarcoma. Based on these preclinical and clinical data, we conducted a phase 1/2 study to determine the recommended phase 2 dose (RP2D), pharmacokinetics, pharmacodynamics, and immunogenicity, of pepinemab in pediatric patients with recurrent/refractory solid tumors, and activity in osteosarcoma.Experimental designPepinemab was administered intravenously on Days 1 and 15 of a 28‐day cycle at 20 mg/kg, the adult RP2D. Part A (phase 1) used a Rolling 6 design; Part B (phase 2) used a Simon 2‐stage design in patients with osteosarcoma. Pharmacokinetics and target saturation were evaluated in peripheral blood.ResultsPepinemab (20 mg/kg) was well tolerated and no dose‐limiting toxicities were observed during Part A. There were no objective responses. Two patients with osteosarcoma achieved disease control and prolonged stable disease. Pepinemab pharmacokinetics were similar to adults.ConclusionsPepinemab (20 mg/kg) is safe, well tolerated and resulted in adequate and sustained target saturation in pediatric patients. Encouraging disease control in two patients with osteosarcoma warrants further investigation with novel combination strategies to modulate the tumor microenvironment and antitumor immune response.Clinical trial registryThis trial is registered as NCT03320330 at Clinicaltrials.gov.DisclaimerThe content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Abstract Background: Sub-Saharan African Immigrants (SSAI) represent one of the fastest-growing segments of the immigrant population in the United States (US). Between 2010 and 2018, the SSAI population in the US increased by 53%, significantly outpacing the 12% growth rate for the overall foreign-born population in the US during that time frame. Despite these growing numbers, little is published about the extent to which SSAIs adapt to health behaviors more common in the US or remain immersed in the values, beliefs and practices reflective of their country of origin. Importantly, no study has comprehensively examined the Social Determinants of Health (SDOH) among this population relative to their migration experiences and their influence on health-seeking behaviors and decision-making regarding prostate cancer care and treatment options. Methods: This qualitative study employed grounded theory and the social determinants of migrant heath framework to better understand the needs of SSAI prostate cancer survivors in the United States and how to effectively support these survivors. In-depth interviews were conducted with 8 survivors who live in the states of Florida and Minnesota. Findings: Some participants reported limited access to care and financial challenges paying for drugs. In terms of coping with diagnosis and treatment, most of the participants relied on their faith, a positive outlook about survivorship and support of family members. Some participants relied on the coaching and support of a loved one who experienced prostate cancer in the past. Erectile dysfunction severely impacted the sexual life of most participants as they experienced difficulty getting an erection. Conclusion: Participants expressed the benefit of belonging to support groups with other survivors for social and emotional support. As the number of immigrants from sub-Saharan continue to rise, so too will the demand for culturally tailored care to address and reduce disparities in survivorship among this sub-population. Citation Format: Ernest Kaninjing, Gladys Asiedu, Kaitlin Van Voorhis, Mary Ellen Young, Ebenezer Erefah, Emmanuel Agboola, Folakemi Odedina, Roxana Dronca, Kimlin Ashing, Solomon Rotimi, Che Ngufor, Arnola Merriweather, John McCall, Anthony Hill. Social determinants of migrant health factors impacting prostate cancer care and survivorship among sub-Saharan African immigrant men diagnosed with prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1310.