tbuckley/cabot-search huggingface dataset:
Prevalence and Persistence of Cost-Related Medication Nonadherence Among Medicare Beneficiaries at High Risk of Hospitalization
Authors: Jorge L. De Avila, David O. Meltzer, James X. Zhang
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The unaffordability of drugs has been a persistent and elusive challenge in the US health care system. Little is known about the prevalence and persistence of cost-related medication nonadherence (CRN) in a population with high-cost, high-need resource utilization. <h3>Objective</h3> To evaluate the prevalence and persistence of CRN among Medicare beneficiaries at high risk of hospitalization as well as the characteristics associated with CRN in this population. <h3>Design, Setting, and Participants</h3> This cohort study used survey data from Medicare patients at high risk of hospitalization and with a life expectancy greater than 12 months at an urban academic medical center from November 6, 2012, to January 30, 2018. Patients were followed up for 12 months at 3-month intervals from baseline, for a total of 5 surveys. Data were analyzed from September 1, 2020, to January 5, 2021. <h3>Main Outcomes and Measures</h3> Self-reported CRN, using a metric of persistence and transiency. Based on the results of the 5 surveys, CRN was categorized as persistent (3 or more surveys), intermittent (2), transient (1), and any (1 or more). Multiple logistic regression analyses were used to evaluate factors associated with persistent and transient CRN. <h3>Results</h3> Of the 1655 Medicare beneficiaries followed up during the 15-month study period, 1036 (62.6%) were women and 1452 (87.7%) were Black or African American; 769 (46.5%) were younger than 65 years, and 886 (53.5%) were 65 years or older (mean [SD] age, 62.4 [15.9] years). A total of 374 patients (22.6%) reported CRN at baseline, 810 (48.9%) reported any CRN, and 230 (13.9%) reported persistent CRN (148 [19.2%] of those younger than 65 years and 82 [9.3%] of those 65 years or older). The 230 patients who had persistent CRN accounted for 28% of those who reported CRN at least once during the 15-month study period. Younger age (eg, &lt;50 years vs 75 years: adjusted odds ratio [AOR], 3.07; 95% CI, 1.61-5.86;<i>P</i> = .001), worse self-reported health (AOR, 1.59; 95% CI, 1.10-2.31;<i>P</i> = .01), and depression (AOR, 1.58; 95% CI, 1.11-2.24;<i>P</i> = .01) were associated with greater likelihood of persistent CRN. The population-adjusted prevalence of CRN was 53.6% (887 patients). <h3>Conclusions and Relevance</h3> The findings suggest that CRN is prevalent, moderately persistent, and variable in the Medicare population at high risk of hospitalization despite coverage by insurance. Longitudinal follow-up and refined predictive modeling of CRN appear to be needed to identify and target more precisely those with persistent CRN and to develop effective interventions.
P3BEP (ANZUP 1302): An international randomized phase III trial of accelerated versus standard BEP chemotherapy for male and female adults and children with intermediate and poor-risk metastatic germ cell tumors (GCTs).
Authors: Shalini Subramaniam, Guy C. Toner, Martin R. Stockler, Andrew James Martin, Farzana D. Pashankar, Ben Tran, Mark Jeffery, Danish Mazhar, Robert A Huddart, Euan Thomas Walpole, Amanda Gwendolyn Stevanovic, David Wyld, Fritha J. Hanning, Matthew James Wheater, Jay R. Balagtas, Simon Troon, Alison Jane Birtle, Jeff D. White, Peter S. Grimison
Journal: Journal of Clinical Oncology (2021)

TPS390 Background: Bleomycin, etoposide, and cisplatin (BEP) given 3-weekly x 4 is standard first-line chemotherapy for metastatic GCT categorised as intermediate risk or poor risk. Acceleration of standard regimens by shortening the cycle length improved cure rates in other cancers. We aim to determine the superiority of accelerated BEP versus standard BEP in this setting. Methods: This open label, randomised, phase III trial is conducted seamlessly in 2-stages. The primary endpoint for stage I (n=150) is complete response (CR); and for stage II (n=500) is progression free survival at 2 years (PFS2y). These sample sizes provide &gt;80% power with a two-sided type error rate of 5% to detect an absolute improvement of 25% in the CR rate (stage II) and of 7% in the PFS2y (stage II). The target population is males and females aged 11 to 45 with intermediate-risk or poor-risk metastatic GCT of the testis, ovary, retroperitoneum, or mediastinum. Participants are randomised (1:1) to 4 cycles of standard BEP (q3w) or accelerated-BEP (q2w) with cisplatin 20mg/m 2 D1-5, etoposide 100mg/m 2 D1-5, bleomycin 30 KIU weekly x 12, and pegylated G-CSF D6 or filgrastim daily. Study assessments are 30 days after completing chemotherapy, 6 months from randomisation, and after completion of all post-chemotherapy treatments (e.g. surgery). Tumour tissue and baseline blood samples are collected for translational substudies including assessment of favourable versus unfavourable rates of decline in the novel biomarker miR-371. As of 13 October 2020, 140 participants have been recruited from 25 ANZ sites, 14 UK sites (led by Cambridge Clinical Trials Unit), and 140 USA sites (led by Children’s Oncology Group). The first planned interim analysis for safety (n=76) identified no safety concerns. The stage I analysis is anticipated mid-2021. This international randomised trial of chemotherapy for intermediate and poor-risk metastatic GCT is the first to include adults and children of both sexes. ClinicalTrials.gov: NCT02582697 Clinical trial information: NCT02582697.
Conquering Atherosclerotic Cardiovascular Disease — 50 Years of Progress
Authors: Gary H. Gibbons, Christine E. Seidman, Eric J. Topol
Journal: New England Journal of Medicine (2021)

Interview with Dr. Gary Gibbons on progress in understanding, preventing, and treating atherosclerotic cardiovascular disease. (12:19)Download Substantial reductions in cardiovascular mortality in the United States reflect the power of a system that catalyzes the integration of basic science, translational research, technological innovation, evidence-based public policy, and public health practice.
Pinpointing uncharacterized prostate cancer in active surveillance patients through mpMRI biopsy.
Authors: Jacob W. Greenberg, Ganesh Sanekommu, William M. Hughes, Thomas M. Shelton, Christopher R. Koller, Caleb Natale, Stephanie Miller, Jonathan L. Silberstein, L. Spencer Krane
Journal: Journal of Clinical Oncology (2021)

210 Background: The UroNav fusion biopsy system allows for the real time visualization of the prostate using multi-parametric MRI (mpMRI) data. This technology has become a valuable instrument for staging prostate cancer at the time of PSA elevation. However, data is still yet emerging over the use of this tool for patients currently being followed on an active surveillance (AS) protocol. In this study we sought to evaluate the efficacy of the UroNav system in patients on AS. Methods: Patients were enrolled into our prospective study, at a single center institution, approved by the Southeast Louisiana Veterans Health Care System (SLVHCS) IRB. Inclusion criteria for this study was men previously enrolled in an active surveillance protocol with a life expectancy ≥10 years. Statical analysis was performed using R 4.0.2 (Ann Arbor, MI). Results: A total of 103 patients were entered into this study for analysis. These patients had a median age of 67.1(62.8 - 70.8) and BMI of 28.6(25.5 - 32.3). The clinical profiles of these patients were median PSA of 6.36(4.65 - 8.89) with a velocity slope of (0.065 (-0.14 - 0.27), TRUS volume of 39.5(32.2 - 56.8), PSAD of 0.15(0.09 - 0.23), and a PI-RAD score of 4(3 – 5). A logistic regression was performed using upgrading on UroNav or Template bx as the outcome. Patients with an increased PSA were more likely to upgrade of Bx (OR = 1.2 (1.05 - 1.39)). Additionally, patients with decreasing MRI volumes were also more likely to upgrade on Bx (OR = 0.97 (0.94 - 0.98)). A total of 42 (40%) patients upgraded on either MRI or Template bx from their initial AS workup. MRI found 13 (12.6%) patients with an upgraded GG that displayed consistent or benign disease on template. Conversely, template also found 13 (12.6%) unique patients who upgraded but were found to have constant or benign disease on mpMRI. Conclusions: mpMRI guided biopsy is a useful tool that can further assist physicians in characterizing prostate cancer in patients being concurrently followed on an active surveillance protocol. MRI is able to find clinically significant cancer that would have otherwise been missed on traditional template biopsies. [Table: see text]
Insights on oncologist and urologist gaps in bladder (UC) and kidney (RCC) cancer education.
Authors: Kinjal Parikh, Pan Chen
Journal: Journal of Clinical Oncology (2021)

358 Background: Treatment paradigms for bladder (UC) and kidney (RCC) cancers is evolving with the advent of novel treatment approaches, personalized medicine, and combinatorial strategies. As the medical literature in the space evolves, identifying oncologists’ (oncs) and urologists’ (uros) educational gaps is important to inform continuing medical education (CME) needs and, ultimately, to improve patient outcomes. Methods: Medscape Oncology conducted a 16 question, online, incentivized survey in June 2020 targeting genitourinary (GU) cancer physicians. Respondents’ confidentiality was maintained and responses were de-identified and aggregated for analysis. Results: Results are reported for 100 respondents (50 oncs &amp; 50 uros): In UC: Learners identified CME as mostly/very important for: Managing treatment related adverse events (trAEs) – 84% Clinical trial outcomes – 77% Timely/appropriate biomarker testing – 68% Understanding mechanism of action (MOA) and rationale of novel agents – 66% Treatment planning CME was considered mostly/very important for: All stages: non-muscle invasive (NMIBC), muscle-invasive (MIBC), and first line (1L) metastatic – 72%, 85%, 92% respectively Determining the optimal role for immunotherapy (IO) – 82% Sequencing therapies – 72% In subgroup analyses More oncs vs. uros identified biomarker testing and treatment selection as mostly/very important (p &lt; .01) More general oncs vs. GU oncs identified education on clinical trial outcomes and sequencing of therapies as mostly/very important (p &lt; .05) More uros vs. oncs identified NMIBC treatment education as mostly/very important (p &lt; .01) More low vs. high volume treaters identified education on sequencing and MIBC as mostly/very important (p &lt; .01) Rating % very experienced: Counseling on trAEs – 41% but mitigating AEs of FGFR therapies, ADCs, or IO was only: 16%, 19%, and 26% respectively In RCC: Learners identified CME as mostly/very important for: Selecting optimal 1L therapy – 80% Clinical trial outcomes – 77% Sequencing therapies – 69% Managing trAEs – 64% Understanding MOA and rationale of novel agents – 62% In subgroup analyses More general oncs vs. GU oncs identified importance of education on clinical trial outcomes and 1L treatment selection (p &lt; .05) More low vs. high volume treaters identified importance of education on 1L treatment selection and clinical trial outcomes (p &lt; .05) Rating % very experienced: Counseling on trAEs – 30% but mitigating AEs of targeted therapy or IO was only: 22% and 23% respectively Determining risk score – 22% Selecting 1L therapy – 28%. Conclusions: Medscape Oncology surveys provide valuable information to guide education for oncs and uros and individualize education unique to their treatment setting, patient volume, and practice coverage.
Association of Breast Cancer Irradiation With Cardiac Toxic Effects
Authors: Icro Meattini, Philip M. Poortmans, Marianne Camille Aznar, Carlotta Becherini, Elisabetta Bonzano, Daniela Cardinale, Daniel J. Lenihan, Livia Marrazzo, Giuseppe Curigliano, Lorenzo Livi
Journal: JAMA Oncology (2021)

<h3>Importance</h3> To promptly recognize and manage cardiovascular (CV) risk factors before, during, and after cancer treatment, decreasing the risk of cancer therapy–related cardiac dysfunction is crucial. After recent advances in breast cancer treatment, mortality rates from cancer have decreased, and the prevalence of survivors with a potentially higher CV disease risk has increased. Cardiovascular risks might be associated with the multimodal approach, including systemic therapies and breast radiotherapy (RT). <h3>Observations</h3> The heart disease risk seems to be higher in patients with tumors in the left breast, when other classic CV risk factors are present, and when adjunctive anthracycline-based chemotherapy is administered, suggesting a synergistic association. Respiratory control as well as modern RT techniques and their possible further refinement may decrease the prevalence and severity of radiation-induced heart disease. Several pharmacological cardioprevention strategies for decreasing cardiac toxic effects have been identified in several guidelines. However, further research is needed to ascertain the feasibility of these strategies in routine practice. <h3>Conclusions and Relevance</h3> This review found that evidence-based recommendations are lacking on the modalities for and intensity of heart disease screening, surveillance of patients after RT, and treatment of these patients. A multidisciplinary and multimodal approach is crucial to guide optimal management.
Avelumab (Ave) first-line (1L) maintenance plus best supportive care (BSC) versus BSC alone for advanced urothelial carcinoma (UC): JAVELIN Bladder 100 Japanese subgroup analysis.
Authors: Norihiko Tsuchiya, Yoshiaki Yamamoto, Hirotsugu Uemura, Hiro-Omi Kanayama, Masatoshi Eto, Hideaki Miyake, Thomas Powles, Mizuki Yoshida, Yuichiro Koide, Yoshiko Umeyama, Alessandra Di Pietro, Yoshihiko Tomita
Journal: Journal of Clinical Oncology (2021)

425 Background: A randomized phase III trial (JAVELIN Bladder 100; NCT02603432) to investigate avelumab (anti–PD-L1) as 1L maintenance therapy in patients with advanced UC met its primary objective, demonstrating significantly prolonged overall survival (OS) with Ave + BSC vs BSC alone in all randomized patients and in patients with PD-L1+ tumors. We report efficacy and safety in Japanese patients enrolled in this study. Methods: Eligible patients with unresectable locally advanced or metastatic UC that had not progressed with 4-6 cycles of gemcitabine with either cisplatin or carboplatin were randomized 1:1 to receive maintenance Ave (10 mg/kg IV every 2 weeks) + BSC or BSC alone, stratified by best response to 1L chemotherapy (complete/partial response vs stable disease) and by visceral vs nonvisceral disease when initiating 1L chemotherapy. The primary endpoint was OS, assessed from randomization in all randomized patients and in patients with PD-L1+ tumors (Ventana SP263 assay). Secondary endpoints included progression-free survival (PFS) per blinded independent central review and safety. Results: Japanese patients (n=73) were randomized to receive Ave + BSC (n=36) or BSC alone (n=37); 52.8% vs 62.2% had PD-L1+ tumors, respectively. Median OS (95% CI) was 24.7 months (18.2-not estimable [NE]) with Ave + BSC vs 18.7 months (12.8-33.0) with BSC alone (HR, 0.81 [95% CI; 0.409-1.585]) in all randomized patients and 18.6 months (9.4-NE) with Ave + BSC vs 19.4 months (11.7-33.0) with BSC alone (HR, 1.00 [95% CI, 0.413-2.412]) in patients with PD-L1+ tumors. Median PFS (95% CI) was 5.6 months (1.9-9.4) with Ave + BSC vs 1.9 months (1.9-3.8) with BSC alone (HR, 0.63 [95% CI, 0.358-1.113]) in all randomized patients and 5.6 months (1.8-11.2) with Ave + BSC vs 1.9 months (1.9-3.8) with BSC alone (HR, 0.62 [95% CI, 0.298-1.301]) in patients with PD-L1+ tumors. The most common treatment-emergent adverse events (all grade; grade ≥3) in the Ave + BSC arm were pyrexia (10 [27.8%]; 0), nasopharyngitis (7 [19.4%]; 0), and anemia (7 [19.4%]; 4 [11.1%]). Conclusions: Ave 1L maintenance + BSC was efficacious and tolerable in Japanese patients with advanced UC, and results were generally consistent with those in the overall population. Clinical trial information: NCT02603432.
Responsive Hydrogel Microcarrier‐Integrated Microneedles for Versatile and Controllable Drug Delivery
Authors: Lu Fan, Xiaoxuan Zhang, Xiaoyu Liu, Bo Sun, Ling Li, Yuanjin Zhao
Journal: Advanced Healthcare Materials (2021)

Abstract Stratagems of drug delivery are important for disease treatment and other biomedical areas. In this study, a novel stratagem is presented for versatile and controllable drug delivery by integrating photoresponsive drug delivery microspheres (PDDMs) into pyramid microneedle (MN) arrays. The PDDMs, containing black‐phosphorus (BP) and poly ( N ‐isopropylacrylamide) (pNIPAM), are generated by a flexible capillary microfluidic method. Benefiting from the high water content of the pNIPAM hydrogel, various bioactive substances can be loaded and maintain biological activity. Furthermore, due to the near‐infrared (NIR) absorption and conversion capabilities of the contained BP, the PDDMs can increase temperature, shrink volume, and release their encapsulated bioactives under the trigger of biocompatible NIR. In addition, as the PDDMs are stuffed into the solid MN arrays of porous ethoxylated trimethylolpropane triacrylate (ETPTA), the composited PDDMs–MNs system has enough mechanical strength to penetrate into the skin and can deliver drugs underneath the skin uniformly. Based on the resultant PDDMs–MNs, it is demonstrated that insulin can be controllably released to adjust blood glucose levels of streptozotocin (STZ)‐induced diabetic mice. Thus, it is believed that the PDDMs–MNs can act as an excellent drugs delivery system and will find many practical values in clinical medicine.
Parental death in childhood and pathways to increased mortality across the life course in Stockholm, Sweden: A cohort study
Authors: Ayako Hiyoshi, Lisa Berg, Alessandra Grotta, Ylva Almquist, Mikael Rostila
Journal: PLoS Medicine (2021)

Background Previous studies have shown that the experience of parental death during childhood is associated with increased mortality risk. However, few studies have examined potential pathways that may explain these findings. The aim of this study is to examine whether familial and behavioural factors during adolescence and socioeconomic disadvantages in early adulthood mediate the association between loss of a parent at age 0 to 12 and all-cause mortality by the age of 63. Methods and findings A cohort study was conducted using data from the Stockholm Birth Cohort Multigenerational Study for 12,615 children born in 1953, with information covering 1953 to 2016. Familial and behavioural factors at age 13 to 19 included psychiatric and alcohol problems in the surviving parent, receipt of social assistance, and delinquent behaviour in the offspring. Socioeconomic disadvantage in early adulthood included educational attainment, occupational social class, and income at age 27 to 37. We used Cox proportional hazard regression models, combined with a multimediator analysis, to separate direct and indirect effects of parental death on all-cause mortality. Among the 12,582 offspring in the study (men 51%; women 49%), about 3% experienced the death of a parent in childhood. During follow-up from the age of 38 to 63, there were 935 deaths among offspring. Parental death was associated with an elevated risk of mortality after adjusting for demographic and household socioeconomic characteristics at birth (hazard ratio [HR]: 1.52 [95% confidence interval: 1.10 to 2.08, p -value = 0.010]). Delinquent behaviour in adolescence and income during early adulthood were the most influential mediators, and the indirect associations through these variables were HR 1.03 (1.00 to 1.06, 0.029) and HR 1.04 (1.01 to 1.07, 0.029), respectively. After accounting for these indirect paths, the direct path was attenuated to HR 1.35 (0.98 to 1.85, 0.066). The limitations of the study include that the associations may be partly due to genetic, social, and behavioural residual confounding, that statistical power was low in some of the subgroup analyses, and that there might be other relevant paths that were not investigated in the present study. Conclusions Our findings from this cohort study suggest that childhood parental death is associated with increased mortality and that the association was mediated through a chain of disadvantages over the life course including delinquency in adolescence and lower income during early adulthood. Professionals working with bereaved children should take the higher mortality risk in bereaved offspring into account and consider its lifelong consequences. When planning and providing support to bereaved children, it may be particularly important to be aware of their increased susceptibility to delinquency and socioeconomic vulnerability that eventually lead to higher mortality.
Government’s new scientific research agency will be exempt from public contract rules and Freedom of Information Act
Authors: Elisabeth Mahase
Journal: BMJ (2021)

A new “high risk, high reward” scientific research agency being set up by the UK government will not have to comply with normal procurement rules and could be exempt from the Freedom of Information Act.

The Advanced Research and Invention Agency (ARIA) is being backed with £800m (€930m; $1.1bn) and will “fund the most inspiring inventors to turn their transformational ideas into new technologies, discoveries, products, and services,” the government has said.

But the new body will …
Placenta-derived IL-32β activates neutrophils to promote preeclampsia development
Authors: Dan Liu, Qiang Li, Hailin Ding, Guangfeng Zhao, Zhiyin Wang, Chenrui Cao, Yimin Dai, Mingming Zheng, Xiangyu Zhu, Qianwen Wu, Ya Wang, Honglei Duan, Huirong Tang, Xianyan Lu, Yayi Hou, Yali Hu
Journal: Cellular and Molecular Immunology (2021)

Abstract Immune activation at the maternal-fetal interface is a main pathogenic factor of preeclampsia (PE). Neutrophils (PMNs) are activated in PE patients, but the mechanism and consequences of PMN activation need to be further explored. Here, we demonstrated that interleukin-32 (IL-32) expression was significantly upregulated in syncytiotrophoblasts (STBs) and that IL-32β was the major isoform with increased expression in the placenta of severe PE (sPE) patients. Furthermore, the level of IL-32 expression in the placenta was correlated with its level in the serum of sPE patients, indicating that IL-32 in the serum is derived mainly from the placenta. Then, in vitro experiments showed that IL-32β could highly activate PMNs and that these IL-32β-activated PMNs were better able to adhere to endothelial cells (HUVECs) and enhance the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) in HUVECs, which could be reversed by preincubation with the NADPH oxidase inhibitor VAS 2870. In addition, we showed that IL-32β mainly activated PMNs by binding to proteinase 3. Finally, IL-32β administration induced a PE-like phenotype in a pregnant mouse model. This study provides evidence of the involvement of IL-32β in the pathogenesis of PE.
Characteristics of dermatology clinical trials 2007-2018: Insights from a systematic analysis of ClinicalTrials.gov
Authors: Justin L. Jia, Brandon E. Turner, Amee D. Azad, Malcolm Pyles Chelliah, Brannon T. Weeks, Hannah K. Rasmussen, Gefei A. Zhu, Matthew A. Lewis
Journal: Journal of the American Academy of Dermatology (2021)