tbuckley/cabot-search huggingface dataset:
Analysis of potential disparities in lung cancer clinical trial participation among Medicare beneficiaries.
Authors: Grace E. Mishkin, Luisa Franzini
Journal: Journal of Clinical Oncology (2021)

e18548 Background: Disparities in clinical trial participation can mean disparities in medical advances, and disproportionate participation is an ethical issue even if differential results are not expected. The disparate impact of Covid-19 highlighted the importance of representativeness in trials aiming to prevent or treat disease. Previous analyses suggest there are likely significant differences in cancer clinical trial participants by race, ethnicity, and age. However, these analyses generally compare trial demographics to broad population demographics. Methods: This analysis used the SEER-Medicare linked database with claims data from 2014-2016 to compare lung cancer clinical trial participants to similar lung cancer patients not participating in a treatment trial. We compared the race, ethnicity, sex, age, and number of comorbidities for Medicare beneficiaries with at least one claim for an active treatment for lung cancer to the demographics of Medicare beneficiaries with at least one claim coded with the National Clinical Trials (NCT) number for an active treatment trial in lung cancer. The relationship between clinical trial participation and demographic variables was assessed using chi-square tests for binary variables and t-tests for continuous variables and corrected for multiplicity. A logistic regression model was used to assess robustness of these findings. Clinical trial participants were hypothesized to be more likely to be White, non-Hispanic, and male, and have a lower mean age and fewer comorbidities than the comparable non-trial active treatment population. Results: We compared 1,624 lung cancer clinical trial patients to 34,077 active treatment lung cancer patients. Clinical trial participants were more likely than non-trial active treatment patients to be female (53.6% vs. 50.4%, p = 0.015) or Asian/Pacific Islander (13.0% vs. 5.2%, p &lt; 0.001) and less likely to be Black (5.2% vs. 9.0%, p &lt; 0.001) or White (76.5% vs. 81.4%, p &lt; 0.001). Trial participants had a lower mean age (70.7 vs. 73.7, p &lt; 0.001) and fewer comorbidities (3.0 vs. 4.6, p &lt; 0.001). There was not a significant difference by Hispanic ethnicity (5.2% vs. 4.4%, p = 0.106). The regression analyses supported these findings. Conclusions: Most analyses of clinical trials enrollment do not have a direct comparison group. Because this study is directly comparing lung cancer trial participants and non-participants from the same Medicare beneficiary population, the results fill a gap in our understanding of disparities in cancer clinical trial participation. Trial participants in this analysis were more representative than hypothesized, although the results supported previous findings that Black patients and older patients are underrepresented in cancer trials. There was also lower participation by White patients. Underrepresentation of patients with comorbidities may be due to trial eligibility criteria.
Delirium and long term cognition in critically ill patients
Authors: M Elizabeth Wilcox, Timothy D Girard, Catherine L Hough
Journal: BMJ (2021)

Abstract Delirium, a form of acute brain dysfunction, is very common in the critically ill adult patient population. Although its pathophysiology is poorly understood, multiple factors associated with delirium have been identified, many of which are coincident with critical illness. To date, no drug or non-drug treatments have been shown to improve outcomes in patients with delirium. Clinical trials have provided a limited understanding of the contributions of multiple triggers and processes of intensive care unit (ICU) acquired delirium, making identification of therapies difficult. Delirium is independently associated with poor long term outcomes, including persistent cognitive impairment. A longer duration of delirium is associated with worse long term cognition after adjustment for age, education, pre-existing cognitive function, severity of illness, and exposure to sedatives. Interestingly, differences in prevalence are seen between ICU survivor populations, with survivors of acute respiratory distress syndrome experiencing higher rates of cognitive impairment at early follow-up compared with mixed ICU survivor populations. Although cognitive performance improves over time for some ICU survivors, impairment is persistent in others. Studies have so far been unable to identify patients at higher risk of long term cognitive impairment; this is an active area of scientific investigation.
Flawed NHS records skew ethnic health data, says study
Authors: Adrian O’Dowd
Journal: BMJ (2021)

Flawed NHS records skew ethnic health data, says study Adrian O'Dowd NHS records too often fail to accurately record the ethnicity of patients in England so are presenting a misleading picture of health inequalities, a study concludes.The report, from the health think tank the Nuffield Trust, 1 warns that the problem could mean that deaths and admissions to hospital are being miscounted in the covid-19 pandemic, during which many people have raised concerns about disparities in mortality between ethnic groups. 1 Nuffield Trust.Ethnicity coding in English health service datasets.7
Cancer patient satisfaction with telehealth: Survey results from a large NCI-designated cancer institute.
Authors: Divya Natesan, Donna Niedzwiecki, Taofik Oyekunle, Aviva Emmons, Yousuf Zafar, Rachel Blitzblau
Journal: Journal of Clinical Oncology (2021)

1579 Background: Telehealth (TH) utilization for patients at our cancer institute increased in 2020 in response to the COVID-19 pandemic, however oncology-specific TH patient satisfaction is unknown. Methods: Monthly TH utilization at a single large NCI-designated institute from 3/1/2020-11/30/2020 was reviewed. Utilization was calculated as chargeable TH visits (new video, established video, phone) as a proportion of all consult/follow up visits. Patient satisfaction surveys for oncology TH visits for MD/PA/NP providers were reviewed from 4/1/2020-11/30/2020. Surveys were sent after every TH visit, unless the patient had a prior visit in the past 3 months. Percent (%) top box score (TBS) was defined as proportion of responses in the highest possible response category (i.e. very good). % TBS was reported for 14 survey items in 4 domains: technology, access, care provider (CP), and overall assessment. Satisfaction was assessed over time and according to patient factors: generation, gender, insurance type, employment status, and clinic site. The Cochrane-Armitage trend test was used to compare proportions of TBS responses across monthly time points. Results: TH comprised 21% (22,055/103,461) of all encounters in the study period. TH use increased from 9% in 3/2020 to a peak of 47% in 4/2020. In 11/2020, TH use was 18%. 28.0% (2,286/8,173) of TH patient surveys were returned. Multiple patient satisfaction metrics were improved over time (Table). Patients had higher satisfaction with phone compared to video visits with regards to technology (86% vs 76%) and access (80% vs 72%). Millennials (born 1981-1995) had higher satisfaction with access to TH (87%) compared to Gen X (1965-1980) (77%), Baby Boomer (1946-1964) (74%), and Silent Generation (1928-1945) (72%), however all generations had similar levels of satisfaction with technology (range 77-80%). Disabled patients had higher overall satisfaction of TH (82%) versus those working full time or retired (71%). Patients with commercial insurance had worse overall satisfaction of TH compared to other insurance types (65% vs 72%). Patients with encounters in genitourinary, thoracic, and endocrine oncology clinics had the highest levels of overall satisfaction (75%) compared to other clinics (69%). There were no observed differences in TH satisfaction according to gender. Conclusions: TH cancer patient satisfaction is high and has improved over time, however satisfaction differs by patient demographics. Further data are needed to best select patients appropriate for TH.[Table: see text]
Association between neutrophil-to-eosinophil ratio (NER) and efficacy outcomes in the JAVELIN Renal 101 study.
Authors: Matthew D. Tucker, Martin H Voss, Toni K. Choueiri, Mehmet Asim Bilen, Marc-Oliver Grimm, Paul D. Nathan, Christian K. Kollmannsberger, Yoshihiko Tomita, Bo Huang, Despina Thomaidou, Mariangela Mariani, Alessandra Di Pietro, Brian I. Rini
Journal: Journal of Clinical Oncology (2021)

4549 Background: Baseline NER has been reported to be associated with outcomes of immuno-oncology based combination treatment in advanced renal cell carcinoma (aRCC). We report outcomes by baseline NER of patients with aRCC in the JAVELIN Renal 101 trial who received avelumab + axitinib (A + Ax) or sunitinib (S). Methods: We calculated the median NER (mNER) for patients in the A + Ax and the S arms at the data cutoff (April 20, 2020) for the 3 rd interim analysis (IA3). Progression-free survival (PFS), overall survival (OS), and objective response (OR) by NER are reported. Multivariate Cox regression analyses of PFS and OS were also conducted. Results: At the IA3 cutoff date, the mNERs for the A + Ax arm (n = 383) and S arm (n = 396) were 29.2 and 27.0, respectively. OR, PFS and OS for both arms are summarized in the table below. Better observed treatment outcomes in OR (63.9% vs 55.2%) and median PFS (15.5 vs, 11.1 months) were observed for patients with a NER &lt; median vs. NER ≥ median in the A + Ax arm, while there were not major differences in outcome based on NER in the S arm. The stratified hazard ratio (HR) for PFS in patients with a NER &lt; median compared with those with a NER ≥ median in the A + Ax arm was 0.81 (95% CI, 0.630-1.035) and 0.93 (95% CI, 0.728-1.181) in the S arm. Patients with a NER &lt; median had improved OS compared with those with a NER ≥ median in the A + Ax arm (stratified HR, 0.67; 95% CI, 0.481-0.940) and the S arm (stratified HR, 0.57; 95% CI, 0.424-0.779). Multivariate analysis showed that a low NER was associated with longer PFS and OS by treating baseline NER as either a continuous variable or a binary variable (dichotomized by median). Conclusions: Baseline NER may be predictive of OR and PFS in aRCC patients treated with A + Ax, and prognostic for overall survival regardless of therapy. Clinical trial information: NCT02684006. [Table: see text]
A helicase-primase drug candidate with sufficient target tissue exposure affects latent neural herpes simplex virus infections
Authors: Christian Gege, Fernando J. Bravo, Nadja Uhlig, Timo Hagmaier, Rosanne Schmachtenberg, Julia Elis, Anke Burger-Kentischer, Doris Finkelmeier, Klaus Hamprecht, Thomas Grunwald, David I. Bernstein, Gerald Kleymann
Journal: Science Translational Medicine (2021)

More than 50% of the world population is chronically infected with herpesviruses. Herpes simplex virus (HSV) infections are the cause of herpes labialis (cold sores), genital herpes, and sight-impairing keratitis. Less frequently, life-threatening disseminated disease (encephalitis and generalized viremia) can also occur, mainly in immunocompromised patients and newborns. After primary infection, HSV persists for life in a latent state in trigeminal or sacral ganglia and, triggered by diverse stimuli, disease recurs in more than 30% of patients up to several times a year. Current therapy with nucleoside analogs targeting the viral polymerase is somewhat effective but limited by poor exposure in the nervous system, and latent infections are not affected by therapy. Here, we report on an inhibitor of HSV helicase-primase with potent in vitro anti-herpes activity, a different mechanism of action, a low frequency of HSV resistance, and a favorable pharmacokinetic and safety profile. Improved target tissue exposure results in superior efficacy in preventing and treating HSV infection and disease in animal models as compared to standard of care. Therapy of primary HSV infections with drug candidate IM-250 {(S)-2-(2',5'-difluoro-[1,1'-biphenyl]-4-yl)-N-methyl-N-(4-methyl-5-(S-methylsulfon-imidoyl)thiazol-2-yl)acetamide} not only reduces the duration of disease symptoms or time to healing but also prevents recurrent disease in guinea pigs. Treatment of recurrent infections reduces the frequency of recurrences and viral shedding, and, unlike nucleosidic drugs, IM-250 remains effective for a time after cessation of treatment. Hence, IM-250 has advantages over standard-of-care therapies and represents a promising therapeutic for chronic HSV infection, including nucleoside-resistant HSV.
Marijuana use among US adults with cancer: Findings from the 2018-2019 Behavioral Risk Factor Surveillance System.
Authors: Min Jee Lee, Ramzi Salloum, Arun Sharma
Journal: Journal of Clinical Oncology (2021)

12088 Background: Cancer survivors experiencing adverse effects from their cancer and treatment report decreased symptom burden with marijuana use. An increasing number of U.S. states have legalized marijuana use for both medical and recreational purposes. This study aimed to assess the prevalence of current marijuana use and to identify the factors associated with its use among US adults with cancer living in 17 U.S. states and territories. Methods: Data from the 2018-2019 Behavioral Risk Factor Surveillance System Marijuana Use module were analyzed. In 2018, 13 states (California, Florida, Idaho, Maryland, Minnesota, Montana, New Hampshire, North Dakota, Ohio, South Carolina, Tennessee, West Virginia, and Wyoming) and 2 territories (Guam and Puerto Rico) participated in the optional marijuana use module. In 2019, 12 states (California, Idaho, Illinois, Maryland, Minnesota, New Hampshire, North Dakota, South Carolina, Tennessee, Utah, West Virginia, and Wyoming) and 1 territory (Guam) participated in the optional marijuana use module. The analytic sample included 13,174 adults with cancer. The analysis was weighted to account for BRFSS’s complex survey design. The primary outcome was current marijuana use (in the past 30-days). Multivariable logistic regression was used to identify demographic, socioeconomic, clinical, and behavioral factors associated with marijuana use among US adults with cancer. Results: Overall, 9.2% of adult cancer survivors (n = 13,174; weighted 5.7 million; 37.9% men) reported marijuana recently current use, 51.3% of whom used it for medical reasons only, with 65.2% reporting smoking as the main method of administration. Adult cancer survivors were significantly more like to use marijuana if they were younger (odds ratio [OR] for 55-64 versus 18-44 years old: 0.60; 95% CI: 0.38-0.93; P &lt; 0.01); male (OR for female versus male: 0.65; 95% CI: 0.48-0.87; P &lt; 0.01); non-Hispanic Black race/ethnicity (OR: 2.00; 95% CI: 1.21-3.33; P &lt; 0.01); having depression (OR: 1.58; 95% CI: 1.17-2.14; P &lt; 0.01) and current (OR: 3.23; 95% CI: 2.20-4.74; P &lt; 0.01) or former tobacco smoker (OR: 2.40; 95% CI: 1.70-3.38; P &lt; 0.01) and binge drinker (OR: 2.25; 95% CI: 1.53-3.29; P &lt; 0.01). Conclusions: Among a large cohort of US adults with cancer, marijuana use was commonly reported and certain subgroups were at higher risk for marijuana use. Health professionals should identify the risk factors for elevated marijuana use, especially as more states legalize medical and recreational marijuana use despite uncertain health risks.
Phase 1/2 first-in-human (FIH) study of CPI-0209, a novel small molecule inhibitor of enhancer of zeste homolog 2 (EZH2) in patients with advanced tumors.
Authors: Nehal J. Lakhani, Martin Gutierrez, Linda R. Duska, Khanh Tu Do, Manish Sharma, Leena Gandhi, Kyriakos P. Papadopoulos, Jennifer Truong, Xiaolin Fan, Ji Hyun Lee, Suresh Bobba, Ronda Rippley, Rentian Wu, Jike Cui, Kaiming Sun, Jing Y. Wang, Patrick Trojer, Drew W. Rasco
Journal: Journal of Clinical Oncology (2021)

3104 Background: Enhancer of Zeste homolog 2 (EZH2) is a histone methyltransferase and the catalytic subunit of Polycomb Repressive Complex 2 (PRC2). EZH2 is frequently overexpressed in cancers and correlates with poor prognosis. CPI-0209 is an oral, small molecule, second-generation, selective inhibitor of EZH2 designed to achieve comprehensive target coverage through extended on-target residence time. The compound demonstrates more potent anti-tumor activity in preclinical cancer models, compared to first-generation EZH2 inhibitors. CPI-0209 is currently being evaluated in a Phase 1/2, open-label, FIH study (NCT04104776). Methods: Patients (pts) with advanced tumors were enrolled in a 3+3 design. Primary objective is to determine maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of CPI-0209. Secondary objectives are to evaluate the safety, PK, and PD in pts who received CPI-0209 QD in 28 days cycles (C). Results: As of December 16, 2020, 33 pts were treated: pancreatic cancer (n = 6), mesothelioma, breast, colorectal, and ovarian cancer (n = 5 each), leiomyosarcoma, melanoma, cholangiocarcinoma, prostate, bladder, endometrial clear cell and gastric cancer (n = 1 each). Pts received CPI-0209 at 50 mg (n = 4), 100 mg, 137.5 mg, and 187.5 mg (n = 6 each), 225 mg (n = 7), and 275 mg (n = 4) daily dose. Median treatment duration was 43 days (range 1-239); 4 pts are ongoing. Median age was 64 yrs (range 24-79); 15 (45%) pts were male. Patients were heavily pretreated, with 67% of pts had ≥ 3 prior lines of therapy. No dose limiting toxicities have been observed. The most frequent treatment-emergent adverse events (TEAEs) (≥10%) were fatigue (27%), diarrhea (24%), nausea (21%), abdominal pain, alopecia, anemia, thrombocytopenia, and dysgeusia (15% each), and vomiting, headache, decreased appetite, and alkaline phosphatase increased (12% each); usually grade 1 or 2 in severity. Thrombocytopenia was dose-dependent and not associated with bleeding or clinical sequalae. Three pts (9%) discontinued CPI-0209 due to TEAEs. Comprehensive target engagement (assessed by global reduction in H3K27me3 levels in monocytes) was observed within the first cycle at all dose levels. CPI-0209 also increased the expression of PRC2-controlled gene sets in blood in a dose-dependent manner. Updated safety, PK, PD, and preliminary efficacy results from Phase 1 will be presented. Conclusions: CPI-0209 achieved robust PD effects and a PK-PD relationship has been established. CPI-0209 monotherapy was generally well tolerated, and treatment related AEs were manageable and reversible. The MTD has not been reached. Clinical trial information: NCT04104776.
Interplay of Risk Factors and Coronary Artery Calcium for CHD Risk in Young Patients
Authors: Martin Bødtker Mortensen, Omar Dzaye, Henrik Bødtker, Flemming Hald Steffensen, Hans Erik Bøtker, Jesper Møller Jensen, Niels Peter Rønnow Sand, Michael Maeng, Kevin Kris Warnakula Olesen, Henrik Toft Sørensen, Helle Kanstrup, Ron Blankstein, Michael J. Blaha, Bjarne Linde Nørgaard
Journal: JACC. Cardiovascular imaging (2021)
Brain-gut axis dysfunction in the pathogenesis of traumatic brain injury
Authors: Marie Hanscom, David J. Loane, Terez Shea-Donohue
Journal: Journal of Clinical Investigation (2021)

Traumatic brain injury (TBI) is a chronic and progressive disease, and management requires an understanding of both the primary neurological injury and the secondary sequelae that affect peripheral organs, including the gastrointestinal (GI) tract. The brain-gut axis is composed of bidirectional pathways through which TBI-induced neuroinflammation and neurodegeneration impact gut function. The resulting TBI-induced dysautonomia and systemic inflammation contribute to the secondary GI events, including dysmotility and increased mucosal permeability. These effects shape, and are shaped by, changes in microbiota composition and activation of resident and recruited immune cells. Microbial products and immune cell mediators in turn modulate brain-gut activity. Importantly, secondary enteric inflammatory challenges prolong systemic inflammation and worsen TBI-induced neuropathology and neurobehavioral deficits. The importance of brain-gut communication in maintaining GI homeostasis highlights it as a viable therapeutic target for TBI. Currently, treatments directed toward dysautonomia, dysbiosis, and/or systemic inflammation offer the most promise.
Efficacy and safety of afatinib in advanced non-small cell lung cancer with EGFR mutations: A real-world study based meta-analysis.
Authors: Lemeng Zhang
Journal: Journal of Clinical Oncology (2021)

e21134 Background: This study aimed to explore the efficacy and safety of Afatinib in advanced EGFR mutation NSCLC patients based on real-world evidence. We also explore the effectiveness of tolerability-guided dose reduction on outcomes in the real-world setting. Methods: Eligible real-world studies from Pubmed, Emabse and Cochrane Library were included in this study. The quality assessment of the included studies was based on the guidelines of Cochrane. Then heterogeneity analysis was performed based on Cochran’s Q test and I 2 statistics. Results: A total of twenty-five studies were enrolled for this meta-analysis. Meanwhile, nine studies were included in qualitative descriptive analysis. The efficacy of DCR and ORR were 87.6 % (81.5, 92.7) and 58.9 % (48.8, 68.7). The pooled medium PFS was 12.45 months (10.36, 14.54), medium TTF was 15.42 months (13.62, 17.22) and medium OS was 31.67 (26.78, 36.56) months. The efficacy of afatinib in first-line only group was superior than those in second-line. The total incidence of adverse events for diarrhea, mucositis and skin rashes were 70.4 (60.1, 79.8)%, 36.5 (29.5, 43.8)% and 71.4 (64.4, 77.9)%, respectively. Meanwhile, the serious adverse reactions (Grade ≥3) for diarrhea, mucositis and skin rashes were 9.7 (6.8, 13.1)%, 2.1 (1.0, 3.6)% and 5.8 (4.5, 7.2)%, respectively. Furthermore, the different for PFS and OS between afatinib non-full dose group ( &lt; 40mg) and full dose group ( &gt; 40mg) was not significant (P &lt; 0.05). however, the ORR in full dose group was 78.5 % (66.7, 88.4), which was significantly higher in the non-full dose group 67.8 % (56.8, 77.9). Conclusions: Afatinib was a safe and effective TKI for real-world EGFR-mutated NSCLC patients, which was consistent with the results of RCT. Tolerability-guided dose adjustment might affect the efficacy of afatinib in real-world setting.