tbuckley/cabot-search huggingface dataset:
Phase II DORA Study of Olaparib with or without Durvalumab as a Chemotherapy-Free Maintenance Strategy in Platinum-Pretreated Advanced Triple-Negative Breast Cancer
Authors: Tira J. Tan, Sarah Sammons, Young-Hyuck Im, Lilin She, Kelly Mundy, Robert Bigelow, Tiffany A. Traina, Carey Anders, Joe Yeong, Ezequiel Renzulli, Sung-Bae Kim, Rebecca Dent
Journal: Clinical Cancer Research (2024)

Abstract Purpose: We explored the efficacy of PARP inhibition with or without programmed death ligand-1 (PD-L1) blockade as chemotherapy-free maintenance therapy for advanced triple-negative breast cancer (aTNBC) sensitive to platinum-based chemotherapy. Patients and Methods: In the phase II non-comparative DORA trial (NCT03167619), patients with ongoing stable disease (SD) or complete/partial response (CR/PR) to first- or second-line platinum-based chemotherapy for TNBC (≤10% estrogen/progesterone receptor expression) were randomized 1:1 to receive olaparib 300 mg twice daily with or without durvalumab 1,500 mg on day 1 every 4 weeks. The primary objective was to compare progression-free survival (PFS) versus a historical control of continued platinum-based therapy. Results: 45 patients were randomized (23 to olaparib alone, 22 to the combination; 3 with estrogen/progesterone receptor expression 1%–10%). At 9.8 months’ median follow-up, median PFS from randomization was 4.0 [95% confidence interval (CI), 2.6–6.1] months with olaparib and 6.1 (95% CI, 3.7–10.1) months with the combination, both significantly longer than the historical control (P = 0.0023 and P &amp;lt; 0.0001, respectively). Clinical benefit rates (SD ≥24 weeks or CR/PR) were 44% (95% CI, 23%–66%) and 36% (95% CI, 17%–59%) in the monotherapy and combination arms, respectively. Sustained clinical benefit was seen irrespective of germline BRCA mutation or PD-L1 status, but tended to be associated with CR/PR to prior platinum, particularly in the olaparib-alone arm. No new safety signals were reported. Conclusions: PFS was longer than expected with both regimens. A patient subset with wild-type BRCA platinum-sensitive aTNBC had durable disease control with chemotherapy-free maintenance.
Racial and Ethnic Disparities in Co-Occurrence of Nocturnal Hypertension and Nocturnal Blood Pressure Decreases
Authors: Neil Zhang, Tzu Yu Huang, Susan Cheng, Joseph E. Ebinger
Journal: JAMA Network Open (2024)

This cross-sectional study assesses racial and ethnic disparities in co-occurrence of nocturnal hypertension and blunted nocturnal decreases in blood pressure.
Administration’s Share of Personnel in Veterans Health Administration and Private Sector Care
Authors: Steffie Woolhandler, Andrew Toporek, Jian Gao, Eileen Moran, Andrew Wilper, David U. Himmelstein
Journal: JAMA Network Open (2024)

Importance Health care administrative overhead is greater in the US than some other nations but has not been assessed in the Veterans Health Administration (VHA). Objective To compare administrative staffing patterns in the VHA and private (non-VHA) sectors. Design, Setting, and Participants This cross-sectional study was conducted using US employment data from 2019, prior to pandemic-related disruptions in health care staffing, and was carried out between January 14 and August 10, 2023. A nationally representative sample of federal and nonfederal personnel in hospitals and ambulatory care settings from the American Community Survey (ACS), all employees reported in VHA personnel records, and personnel in health insurance carriers and brokers tabulated by the Bureau of Labor Statistics (BLS) were analyzed. Exposure VHA vs private sector health care employment, including 397 occupations grouped into 18 categories. Main Outcome and Measure The proportion of staff working in administrative occupations. Results Among 3 239 553 persons surveyed in the ACS, 122 315 individuals (weighted population, 12 501 185 individuals) were civilians working in hospitals or ambulatory care; of the weighted population, 12 156 988 individuals (mean age, 42.6 years [95% CI, 42.5-42.7 years]; 76.2% [95% CI, 75.9%-76.5%] females) were private sector personnel and 344 197 individuals (mean age, 46.2 years [95% CI, 45.7-46.7 years]; 63.8% [95% CI, 61.8%-65.8%] females) were federal employees. In clinical settings, administrative occupations accounted for 23.4% (95% CI, 23.1%-23.8%) of private sector vs 19.8% (95% CI, 18.1%-21.4%) of VHA personnel. After including 1 000 800 employees at private sector health insurers and brokers and 13 956 VHA Central Office personnel with administrative occupations, administration accounted for 3 851 374 of 13 157 788 private sector employees (29.3%) vs 77 500 of 343 721 VHA employees (22.5%). Physicians represented approximately 7% of personnel in the VHA (7.2% [95% CI, 6.1%-8.2%]) and private sector (6.5% [95% CI, 6.3%-6.7%]), while the VHA deployed more registered nurses (23.7% [95% CI, 21.6%-25.8%] vs 21.2% [95% CI, 20.9%-21.5%]) and social service personnel (6.3% [95% CI, 5.4%-7.1%] vs 4.9% [95% CI, 4.7%-5.0%]) than the private sector. Conclusions and Relevance In this study, administrative occupations accounted for a smaller share of personnel in the VHA compared with private sector care, a difference possibly attributable to the VHA’s simpler financing system. These findings suggest that if staffing patterns in the private sector mirrored those of the VHA, nearly 900 000 fewer administrative staff might be needed.
Inhibition of CSF-1R and IL-6R prevents conversion of cDC2s into immune incompetent tumor-induced DC3s boosting DC-driven therapy potential
Authors: Anouk M.D. Becker, Annika H. Decker, Georgina Flórez-Grau, Ghaith Bakdash, Rutger J. Röring, Suzan Stelloo, Michiel Vermeulen, Berber Piet, Erik H.J.G. Aarntzen, Martijn Verdoes, I. Jolanda M. de Vries
Journal: Cell Reports Medicine (2024)

The human dendritic cell (DC) family has recently been expanded by CD1c+CD14+CD163+ DCs, introduced as DC3s. DC3s are found in tumors and peripheral blood of cancer patients. Here, we report elevated frequencies of CD14+ cDC2s, which restore to normal frequencies after tumor resection, in non-small cell lung cancer patients. These CD14+ cDC2s phenotypically resemble DC3s and exhibit increased PD-L1, MERTK, IL-10, and IDO expression, consistent with inferior T cell activation ability compared with CD14− cDC2s. In melanoma patients undergoing CD1c+ DC vaccinations, increased CD1c+CD14+ DC frequencies correlate with reduced survival. We demonstrate conversion of CD5+/−CD1c+CD14− cDC2s to CD14+ cDC2s by tumor-associated factors, whereas monocytes failed to express CD1c under similar conditions. Targeted proteomics identified IL-6 and M-CSF as dominant drivers, and we show that IL-6R and CSF1R inhibition prevents tumor-induced CD14+ cDC2s. Together, this indicates cDC2s as direct pre-cursors of DC3-like CD1c+CD14+ DCs and provides insights into the importance and modulation of CD14+ DC3s in anti-tumor immune responses.
Refining the 8th edition TNM classification for EBV related nasopharyngeal carcinoma
Authors: Xiao-Jing Du, Gao-Yuan Wang, Xiao-Dong Zhu, Ya-Qian Han, Feng Lei, Liang-Fang Shen, Kun-Yu Yang, Lei Chen, Yan-Ping Mao, Ling-Long Tang, Ling Li, Zheng Wu, Gui-Qiong Xu, Qin Zhou, Jing Huang, Rui Guo, Yuan Zhang, Xu Liu, Guan-Qun Zhou, Wen-Fei Li, Cheng Xu, Li Lin, Yu-Pei Chen, Fo-Ping Chen, Xiao-Yu Liang, Si-Yuan Chen, Shu-Qi Li, Chun-Yan Cui, Ji-Bin Li, Jian Ren, Ming-Yuan Chen, Li-Zhi Liu, Ying Sun, Jun Ma
Journal: Cancer Cell (2024)

The AJCC/UICC TNM classification describes anatomic extent of tumor progression and guides treatment decisions. Our comprehensive analysis of 8,834 newly diagnosed patients with non-metastatic Epstein-Barr virus related nasopharyngeal carcinoma (NPC) from six Chinese centers indicates certain limitations in the current staging system. The 8th edition of the AJCC/UICC TNM classification inadequately differentiates patient outcomes, particularly between T2 and T3 categories and within the N classification. We propose reclassifying cases of T3 NPC with early skull-base invasion as T2, and elevating N1-N2 cases with grade 3 image-identified extranodal extension (ENE) to N3. Additionally, we suggest combining T2N0 with T1N0 into a single stage IA. For de novo metastatic (M1) NPC, we propose subdivisions of M1a, defined by 1–3 metastatic lesions without liver involvement, and M1b, characterized by >3 metastatic lesions or liver involvement. This proposal better reflects responses of NPC patients to the up-to-date treatments and their evolving risk profiles.
Cancer-associated fibroblast phenotypes are associated with patient outcome in non-small cell lung cancer
Authors: Lena Cords, Stefanie Engler, Martina Haberecker, Jan Hendrik Rüschoff, Holger Moch, Natalie de Souza, Bernd Bodenmiller
Journal: Cancer Cell (2024)

Despite advances in treatment, lung cancer survival rates remain low. A better understanding of the cellular heterogeneity and interplay of cancer-associated fibroblasts (CAFs) within the tumor microenvironment will support the development of personalized therapies. We report a spatially resolved single-cell imaging mass cytometry (IMC) analysis of CAFs in a non-small cell lung cancer cohort of 1,070 patients. We identify four prognostic patient groups based on 11 CAF phenotypes with distinct spatial distributions and show that CAFs are independent prognostic factors for patient survival. The presence of tumor-like CAFs is strongly correlated with poor prognosis. In contrast, inflammatory CAFs and interferon-response CAFs are associated with inflamed tumor microenvironments and higher patient survival. High density of matrix CAFs is correlated with low immune infiltration and is negatively correlated with patient survival. In summary, our data identify phenotypic and spatial features of CAFs that are associated with patient outcome in NSCLC.
We must consider ageing and frailty when sharing decision making in intensive care
Authors: Daniele Bryden, Jack Parry Jones, Jugdeep Dhesi, Simon Conroy
Journal: BMJ (2024)

Decisions to admit older, frail patients to critical care must pay particular attention to quality of life and the potential burden of care on patients.This burden may extend beyond surviving a critical illness.These decisions are not easy and require careful thought, clinical judgment, and communication.
Out-of-Pocket Costs and Outpatient Visits Among Patients With Cancer in High-Deductible Health Plans
Authors: Nicolas K. Trad, Fang Zhang, James Franklin Wharam
Journal: JAMA Oncology (2024)

Importance High-deductible health plans (HDHPs) have grown rapidly and may adversely affect access to comprehensive cancer care. Objective To evaluate the association of HDHPs with out-of-pocket medical costs and outpatient physician visits among patients with cancer. Design, Setting, and Participants Using 2003 to 2017 data from the deidentified Optum Clinformatics Data Mart database from individuals with employer-sponsored health coverage, adults aged 18 to 64 years with cancer who were enrolled in low-deductible (≤$500 annually) health plans during a baseline year were identified. Patients whose employers then mandated a switch to an HDHP (≥$1000 annual deductible) were assigned to the HDHP group, while contemporaneous individuals with cancer at baseline who had no option but to continue enrollment in low-deductible plans were assigned to the control group. The 2 groups were matched on demographic variables (age, sex, race and ethnicity, US Census region, rural vs urban, and neighborhood poverty level), cancer type, morbidity score, number of baseline physician visits by specialty type, baseline out-of-pocket costs, and employer characteristics. These cohorts were followed up for up to 3 years after the baseline year. Data were analyzed from July 2021 to December 2022. Exposures Employer-mandated HDHP enrollment. Main Outcomes and Measures Out-of-pocket medical expenditures and outpatient visits to primary care physicians, cancer specialists, and noncancer specialists. Results After matching, the sample included 45 708 patients with cancer (2703 patients in the HDHP group and 43 005 matched individuals in the control group); mean (SD) age in the HDHP and control groups was 52.9 (9.3) years and 52.9 (2.3) years, respectively, with 58.5% females in both groups. The matching procedure yielded variable weights for each individual in the control group, resulting in a weighted control group sample of 2703 patients. Patients with cancer who were switched to HDHPs experienced an increase in annual out-of-pocket medical expenditures of 68.1% (95% CI, 51.0%-85.3%; absolute increase, $1349.80 [95% CI, $1060.30-$1639.20]) after the switch compared with those who remained in traditional health plans. At follow-up, the number of oncology visits did not differ between the 2 groups (relative difference, 0.1%; 95% CI, −8.4% to 9.4%); however, the HDHP group had 10.8% (95% CI, −15.5% to −5.9%) fewer visits to primary care physicians and 5.9% (95% CI, −11.2% to −0.3%) fewer visits to noncancer specialists. Conclusions and Relevance Results of this cohort study suggest that after enrollment in HDHPs, patients with cancer experienced substantial increases in out-of-pocket medical costs. The number of visits to oncologists was unchanged during follow-up, but the number of visits to noncancer physicians was lower. These findings suggest that HDHPs are unlikely to unfavorably affect key oncology services but might lead to less comprehensive care of cancer survivors.
Availability of Long-Acting Injectable Buprenorphine at Substance Use Treatment Facilities in 2021
Authors: Nitin Vidyasagar, Samuel R. Bunting, Vineet M. Arora, Mim Ari
Journal: JAMA (2024)

This study assesses the proportion of US substance use and mental health care facilities that offered any medications for opioid use disorder and, specifically, long-acting injectable buprenorphine in 2021.
Impact on wine sales of removing the largest serving size by the glass: An A-B-A reversal trial in 21 pubs, bars, and restaurants in England
Authors: Eleni Mantzari, Minna Ventsel, Emily Pechey, Ilse Lee, Mark A. Pilling, Gareth J. Hollands, Theresa M. Marteau
Journal: PLoS Medicine (2024)

Background Interventions that alter aspects of the physical environments in which unhealthy behaviours occur have the potential to change behaviour at scale, i.e., across populations, and thereby decrease the risk of several diseases. One set of such interventions involves reducing serving sizes, which could reduce alcohol consumption. The effect of modifying the available range of serving sizes of wine in a real-world setting is unknown. W e aimed to assess the impact on the volume of wine sold of removing the largest serving size by the glass from the options available in licensed premises. Methods and findings The study was conducted between September 2021 and May 2022 in 21 licensed premises in England that sold wine by the glass in serving sizes greater than 125 ml (i.e., 175 ml or 250 ml) and used an electronic point of sale till system. It used an A-B-A reversal design, set over 3 four-weekly periods. “A” represented the nonintervention periods during which standard serving sizes were served and “B” the intervention period when the largest serving size for a glass of wine was removed from the existing range in each establishment: 250 ml (18 premises) or 175 ml (3 premises). The primary outcome was the daily volume of wine sold, extracted from sales data. Twenty-one premises completed the study, 20 of which did so per protocol and were included in the primary analysis. After adjusting for prespecified covariates, the intervention resulted in −420·8 millilitres (ml) (95% confidence intervals (CIs) −681·4 to −160·2 p = 0·002) or −7·6% (95% CI −12·3%, −2·9%) less wine being sold per day. There was no evidence that sales of beer and cider or total daily revenues changed but the study was not powered to detect differences in these outcomes. The main study limitation is that we were unable to assess the sales of other alcoholic drinks apart from wine, beer, and cider, estimated to comprise approximately 30% of alcoholic drinks sold in participating premises. Conclusions Removing the largest serving size of wine by the glass from those available reduced the volume of wine sold. This promising intervention for decreasing alcohol consumption across populations merits consideration as part of alcohol licensing regulations. Trial registration ISRCTN https://doi.org/10.1186/ISRCTN33169631 ; OSF https://osf.io/xkgdb .
Detecting Mpox Cases Through Wastewater Surveillance — United States, August 2022–May 2023
Authors: Carly Adams, Amy E. Kirby, Megan Bias, Aspen Riser, Karen K. Wong, Jeffrey W. Mercante, Heather Reese
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

In October 2022, CDC's National Wastewater Surveillance System began routine testing of U.S. wastewater for Monkeypox virus.Wastewater surveillance sensitivity, positive predictive value (PPV), and negative predictive value (NPV) for Monkeypox virus were evaluated by comparing wastewater detections (Monkeypox virus detected versus not detected) to numbers of persons with mpox in a county who were shedding virus.Case ascertainment was assumed to be complete, and persons with mpox were assumed to shed virus for 25 days after symptom onset.A total of 281 cases and 3,492 wastewater samples from 89 sites in 26 counties were included in the analysis.Wastewater surveillance in a single week, from samples representing thousands to millions of persons, had a sensitivity of 32% for detecting one or more persons shedding Monkeypox virus, 49% for detecting five or more persons shedding virus, and 77% for detecting 15 or more persons shedding virus.Weekly PPV and NPV for detecting persons shedding Monkeypox virus in a county were 62% and 80%, respectively.An absence of detections in counties with wastewater surveillance signified a high probability that a large number of cases were not present.Results can help to guide the public health response to Monkeypox virus wastewater detections.A single, isolated detection likely warrants a limited public health response.An absence of detections, in combination with no reported cases, can give public health officials greater confidence that no cases are present.Wastewater surveillance can serve as a useful complement to case surveillance for guiding the public health response to an mpox outbreak.* https://www.cdc.gov/poxvirus/mpox/response/2022/index.html† https://www.cdc.gov/nwss/wastewater-surveillance.html§ https://www.cdc.gov/poxvirus/mpox/cases-data/wastewater-surveillance.htmlgoal of this analysis was to evaluate the sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of wastewater surveillance for detecting mpox cases in the United States.
Can We Use Lung Function Thresholds and Respiratory Symptoms to Identify Pre-COPD? A Prospective, Population-based Cohort Study
Authors: Daniel J. Tan, Caroline J. Lodge, E. Haydn Walters, Dinh S. Bui, Jonathan Pham, Adrian J. Lowe, Gayan Bowatte, Don Vicendese, Bircan Erbas, David P. Johns, Alan L. James, Peter Frith, Garun S. Hamilton, Paul S. Thomas, Richard Wood-Baker, MeiLan K. Han, George R. Washko, Michael J. Abramson, Jennifer L. Perret, Shyamali C. Dharmage
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

The term "pre-chronic obstructive pulmonary disease" ("pre-COPD") refers to individuals at high risk of developing COPD who do not meet conventional spirometric criteria for airflow obstruction. New approaches to identifying these individuals are needed, particularly in younger populations.
Recurrent DDX41 mutation in very late relapse after allogeneic stem cell transplantation
Authors: Yasuhiro Kambara, Daichi Sadato, Takashi Toya, Akira Honda, Seiko Kato, Chizuko Hirama, Kyoko Haraguchi, Hiroaki Shimizu, Yuho Najima, Takeshi Kobayashi, Yoshiki Okuyama, Hironori Harada, Satoshi Takahashi, Mineo Kurokawa, Yuka Harada, Noriko Doki
Journal: Leukemia (2024)
The trajectory of very old critically ill patients
Authors: Bertrand Guidet, Helene Vallet, Hans Flaatten, Gavin Joynt, Sean M. Bagshaw, Susannah K. Leaver, Michael Beil, Bin Du, Daniel N. Forte, Derek C. Angus, Sigal Sviri, Dylan de Lange, Margaret S. Herridge, Christian Jung
Journal: Intensive Care Medicine (2024)
Lung Cancer Risks Associated with Occupational Exposure to Pairs of Five Lung Carcinogens: Results from a Pooled Analysis of Case-Control Studies (SYNERGY)
Authors: Ann Olsson, Liacine Bouaoun, Joachim Schüz, Roel Vermeulen, Thomas Behrens, Calvin Ge, Hans Kromhout, Jack Siemiatycki, Per Gustavsson, Paolo Boffetta, Benjamin Kendzia, Loredana Radoi, Christine Barul, Stefan Karrasch, Heinz-Erich Wichmann, Dario Consonni, Maria Teresa Landi, Neil E. Caporaso, Franco Merletti, Enrica Migliore, Lorenzo Richiardi, Karl-Heinz Jöckel, Wolfgang Ahrens, Hermann Pohlabeln, Guillermo Fernández-Tardón, David Zaridze, John K. Field, Jolanta Lissowska, Beata Świątkowska, John R. McLaughlin, Paul A. Demers, Miriam Schejbalova, Lenka Foretova, Vladimir Janout, Tamás Pándics, Eleonora Fabianova, Dana Mates, Francesco Forastiere, Kurt Straif, Thomas Brüning, Jelle Vlaanderen, Susan Peters
Journal: Environmental Health Perspectives (2024)

While much research has been done to identify individual workplace lung carcinogens, little is known about joint effects on risk when workers are exposed to multiple agents.
Cannabis Use Among Students in Grades 8, 10, and 12, by Sex — King County, Washington, 2008–2021
Authors: Precious Esie, Myduc Ta
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Cannabis use during adolescence is associated with poor outcomes, including cognitive impairment, cannabis use disorder, and impaired driving.To guide prevention and use reduction strategies, Public Health -Seattle & King County described recent trends in cannabis use by sex among King County, Washington students in grades 8, 10, and 12 and examined trends in sex-based differences.Data collected during seven 2008-2021 survey periods by the Healthy Youth Survey (administered by the Washington State Department of Health) and restricted to King County students in grades 8, 10, and 12 (range = 33,439-39,391 students per cycle) were analyzed.Prevalence estimates were generated and sex-based prevalence differences (PDs) in current use (≥1 day during the previous 30 days) and frequent use (≥6 days during the previous 30 days) were assessed.PD models used weighted generalized linear regression with an interaction between sex and survey year.During 2008-2021, cannabis use declined among both male and female students.During 2008-2014, cannabis use was higher among male students than among female students (e.g., PD in 2008 = 4.8%) and not significantly different during 2014-2016; however, in 2021, current-use prevalence was lower among male students than among female students for the first time (PD = -1.3%).Frequent-use prevalence was similar among males and females.By grade levels, the highest prevalence of both current and frequent cannabis use was observed among 12th grade students, followed by 10th and 8th graders.Sex-specific differences by grade mirrored overall patterns.Developing tailored interventions that consider potential differences in risk and protective factors by sex or gender identity could promote equity in youth (grades 8, 10, and 12) cannabis use reduction measures.