tbuckley/cabot-search huggingface dataset:
A phase III randomized, placebo-controlled, double-blind study of niraparib plus abiraterone acetate and prednisone versus abiraterone acetate and prednisone in patients with metastatic prostate cancer (MAGNITUDE).
Authors: Kim N. Chi, Dana E. Rathkopf, Gerhardt Attard, Matthew Raymond Smith, Eleni Efstathiou, David Olmos, Eric Jay Small, Ji Youl Lee, Deborah S. Ricci, Jason S. Simon, Xin Zhao, Nishi Kothari, Shinta Cheng, Shahneen Kaur Sandhu
Journal: Journal of Clinical Oncology (2020)

TPS5588 Background: Preclinical data suggest synergistic antitumor activity when the PARP inhibitor (PARPi) niraparib is combined with the androgen pathway inhibitor abiraterone acetate 1 . The addition of a PARPi to abiraterone acetate plus prednisone (AAP) showed improved radiographic progression-free survival (rPFS) vs AAP alone in patients with mCRPC regardless of DNA repair gene defect (DRD) status 2 . Interim results from a phase I study support safety and tolerability of niraparib 200 mg combined with AAP in patients with mCRPC 3 . The objective of this Phase III study is to compare the efficacy and safety of niraparib plus AAP versus AAP with placebo as first-line therapy for mCRPC. Methods: This ongoing multicenter MAGNITUDE study (NCT03748641) will open in approximately 300 sites across 28 countries and will enroll patients with mCRPC who have not received treatment in the metastatic castrate resistant setting other than ongoing androgen deprivation therapy [ADT] and ≤4 months of AAP. DRD status will be determined by plasma and tissue assays. The cohort with DRD (n=400) and the cohort without DRD (n=600) will each be randomized 1:1 to niraparib + AAP or placebo + AAP. The first patient was consented in February 2019 and enrollment is ongoing. The primary objective of the study is to compare radiographic progression-free survival (rPFS) as assessed by blinded independent central radiology review in each cohort and treatment group. To test superiority of the combination vs AAP, sample sizes were estimated to provide 92% power to detect HR≤0.65 rPFS in the cohort with DRD and 94% power to detect HR≤0.67 in rPFS in the cohort without DRD, both at a 2-tailed level of significance of 0.05. The secondary objectives are time to symptomatic progression, time to cytotoxic chemotherapy, and overall survival. Safety and pharmacokinetic profiles will be evaluated. 1 Rajendra N, et al. Cancer Res 2019;79(13 Suppl):Abstract nr 2134. 2 Clarke N, et al. Lancet Oncol. 2018;(7):975-986. 3 Saad, et al. Ann Oncol, 2018;29 (suppl 8), mdy284.043, https://doi.org/10.1093/annonc/mdy284.043 ) Clinical trial information: NCT03748641 .
Gene expression in circulating tumor cells (CTC) and plasma androgen receptor (<i>AR</i>) gene copy number (CN) for castration-resistant prostate cancer (CRPC) patients (pts) treated with cabazitaxel.
Authors: Giorgia Gurioli, Vincenza Conteduca, Umberto Basso, Giuseppe Fornarini, Alessandra Mosca, Maurizio Nicodemo, Giuseppe Luigi Banna, Cristian Lolli, Giuseppe Schepisi, Stefania Gargiulo, Amelia Altavilla, Sara Testoni, Emanuela Scarpi, Ugo De Giorgi
Journal: Journal of Clinical Oncology (2020)

154 Background: Cabazitaxel demonstrated overall survival (OS) benefit for the treatment of CRPC progressing after docetaxel. CTC profiling could help to establish novel predictive biomarkers. In this prospective study (NCT03381326), we evaluated the prognostic role of CTC biomarkers expression and the association with plasma AR CN in pts treated with cabazitaxel. Methods: We enrolled pts receiving cabazitaxel from January 2015 to December 2018. Plasma DNA was isolated and digital PCR was performed to assess AR CN status. CTC enrichment was evaluated with AdnaTest EMT-2/StemCell kit. Expression analyses using real time PCR were performed for 17 genes and CTC positivity (CTC+) was defined as the expression of at least 1 of the following 7 relevant markers: AR-V7, AKT, AR, EPCAM, PSMA, PI3KCA, PSCA. Results: We enrolled 100 pts, 80 fully evaluable for this analysis. Median age was 72 years (range 49-82). All pts received prior docetaxel and 85% prior abiraterone and/or enzalutamide. Median OS and progression-free survival (PFS) were 16.4 months (mo) (95% CI 11.1-27.0) and 6.7 mo (95% CI 5.2-8.3), respectively. Fifty-eight (72.5%) showed CTC+ at baseline, whose 15 (26%) had &gt;3 markers expressed in CTC. Significantly worse OS was observed in pts with &gt;3 markers expressed in CTC compared to those with ≤3 markers and CTC negative pts [4.7 mo vs 15.2 vs 31.7 mo respectively, hazard ratio (HR) 6.05 (95% CI 2.07-17.73), p=0.004]. No significant difference was observed for PFS and PSA response. AR-V7 was expressed in 11 (19%) CTC+ pts, whose 10 (91%) had &gt;3 markers expressed in CTC (p=0.0274), and 8 (73%) had plasma AR CN gain (p=0.048). A shorter OS was observed in AR-V7+ vs AR-V7- pts [10.6 vs 18.1 mo, HR 2.48 (95% CI 1.00-6.18), p=0.051]. Significantly worse OS and PFS were found in AR CN gain pts compared to AR normal [11.1 mo vs 27.0 mo, HR 2.28 (95% CI 1.19-4.38), p=0.013 and 5.9 mo vs 8.5 mo, HR 1.81 (95% CI 1.05-3.13), p=0.032], respectively. Conclusions: Liquid biopsy profiling may improve prognostication of CRPC patients treated with cabazitaxel. Further larger studies are warranted. Funding: Partially funded by Sanofi Genzyme. Clinical trial information: NCT03381326.
Zoonotic Virus Linked to Severe Encephalitis in Southern Germany
Authors: Bridget M. Kuehn
Journal: JAMA (2020)

A recent study suggested that Borna disease virus 1 (BoDV-1), which is carried by wild shrews in Germany, Austria, Switzerland, and Liechtenstein, could be a more common cause of severe or fatal encephalitis among people in endemic areas than previously realized.
Prospective community programme versus parent-driven care to prevent respiratory morbidity in children following hospitalisation with severe bronchiolitis or pneumonia
Authors: Catherine Ann Byrnes, Adrian Trenholme, Shirley Lawrence, Harley Aish, Julie Anne Higham, Karen Hoare, Aileen Elborough, Charissa McBride, Lyndsay Le Comte, Christine McIntosh, Florina Chan Mow, Mirjana Jaksic, Russell Metcalfe, Christin Coomarasamy, William Leung, Alison Vogel, Teuila Percival, Henare Mason, Joanna Stewart
Journal: Thorax (2020)

Background Hospitalisation with severe lower respiratory tract infection (LRTI) in early childhood is associated with ongoing respiratory symptoms and possible later development of bronchiectasis. We aimed to reduce this intermediate respiratory morbidity with a community intervention programme at time of discharge. Methods This randomised, controlled, single-blind trial enrolled children aged &lt;2 years hospitalised for severe LRTI to ‘intervention’ or ‘control’. Intervention was three monthly community clinics treating wet cough with prolonged antibiotics referring non-responders. All other health issues were addressed, and health resilience behaviours were encouraged, with referrals for housing or smoking concerns. Controls followed the usual pathway of parent-initiated healthcare access. After 24 months, all children were assessed by a paediatrician blinded to randomisation for primary outcomes of wet cough, abnormal examination (crackles or clubbing) or chest X-ray Brasfield score ≤22. Findings 400 children (203 intervention, 197 control) were enrolled in 2011–2012; mean age 6.9 months, 230 boys, 87% Maori/Pasifika ethnicity and 83% from the most deprived quintile. Final assessment of 321/400 (80.3%) showed no differences in presence of wet cough (33.9% intervention, 36.5% controls, relative risk (RR) 0.93, 95% CI 0.69 to 1.25), abnormal examination (21.7% intervention, 23.9% controls, RR 0.92, 95% CI 0.61 to 1.38) or Brasfield score ≤22 (32.4% intervention, 37.9% control, RR 0.85, 95% CI 0.63 to 1.17). Twelve (all intervention) were diagnosed with bronchiectasis within this timeframe. Interpretation We have identified children at high risk of ongoing respiratory disease following hospital admission with severe LRTI in whom this intervention programme did not change outcomes over 2 years. Trial registration number ACTRN12610001095055.
Antihypertensive Prescribing Cascades as High-Priority Targets for Deprescribing
Authors: Timothy S. Anderson, Michael A. Steinman
Journal: JAMA Internal Medicine (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Obsessive-Compulsive Behaviors in Autism—Reply
Authors: Dinah S. Reddihough, Catherine Marraffa, Andrew J. O. Whitehouse
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
In Vitro and In Vivo Profile of GB001, a Potent and Selective DP2 Antagonist for the Treatment of Moderate-Severe Asthma
Authors: Kristen Taylor Meadows, Susan Murphy, Tomas Salter-Cid, Sunil Sahdeo, Gregory Opiteck, Laura Carter, Hector Ortega, Luisa Salter-Cid
Journal: Journal of Allergy and Clinical Immunology (2020)
A real-world experience of immune checkpoint inhibitors (ICI) in metastatic renal cell carcinoma (mRCC).
Authors: Roy Elias, Nicholas Levonyak, Alana Christie, Isaac Alexander Bowman, Payal Kapur, Raquibul Hannan, Hans J. Hammers, James Brugarolas
Journal: Journal of Clinical Oncology (2020)

647 Background: ICI therapy has changed the treatment landscape in mRCC. Here we present the safety and efficacy of ICIs used in an academic medical center (UT Southwestern Medical Center) and affiliated county hospital (Parkland Hospital). Methods: All mRCC patients (pts) treated with at least one dose of ICI from 2014 - 2018 were identified. Baseline characteristics were collected at the start of ICI. Outcomes included objective response rate (ORR) as determined by RECISCT v1.1, time to next treatment (TNT) and overall survival (OS). Immune-related adverse events (irAE) were graded according to CTCAE v4.0. Kaplan-Meier methods and Cox proportional hazards regression models were used to estimate survival and generate hazard ratios (HR). Results: We identified 177 pts with mRCC, including 31 at the county hospital, who received at least one dose of ICI. 140 (79.1%) pts were intermediate or poor risk by IMDC, and 149 (84.2%) had clear cell histology. 127 (71.8%) received nivolumab monotherapy, 40 (22.6%) received ipilimumab and nivolumab, and 10 (5.6%) received ICI with a tyrosine kinase inhibitor. ICI was given in the 1 st line in 34 (19.2%) pts, 2 nd line in 77 (43.5%) pts, and the 3 rd or later line in 29 (16.4%) pts. The ORR was 18.6% (33/177), and there were 6 (3.4%) complete responses. The median TNT and OS was 8.9 (95% CI; 7.1-10.6) and 26.7 (95% CI; 22.4-30.9) months, respectively. In multivariate analysis (MVA) of TNT including sex, nephrectomy status, IMDC risk group, histology, and number of organs involved, only number of organs involved (HR: 1.27; 95% CI: 1.12-1.45; p = 0.0003) and non-ccRCC subtype (HR: 2.63; 95% CI: 1.63-4.24; p &lt;0.0001) retained statistical significance. MVA of OS revealed similar findings, with number of involved organs (HR: 1.49; 95% CI: 1.97-7.45; p &lt; 0.0001) and non-ccRCC subtype (HR: 3.83; 95% CI: 1.97-7.45; p &lt;0.0001) correlating with worse survival. irAEs were observed in 77 pts (43.5%) with 42 (23.7%) pts experiencing a grade 3/4 irAE. Conclusions: ICI therapy is safe and efficacious in the real world setting. Clinical and laboratory variables, including the IMDC risk score, do not consistently predict outcomes in this heterogeneous cohort.
Positive RT-PCR Test Results in Patients Recovered From COVID-19
Authors: Lan Lan, Dan Xu, Guangming Ye, Chen Xia, Shaokang Wang, Yirong Li, Haibo Xu
Journal: JAMA (2020)

This case series describes reverse transcriptase–polymerase chain reaction (RT-PCR) test results in 4 health professionals discharged from hospitalization or quarantine after 2 negative RT-PCR test results and resolution of clinical COVID-19 infection.
Detection of Hypertrophic Cardiomyopathy Using a Convolutional Neural Network-Enabled Electrocardiogram
Authors: Wei-Yin Ko, Konstantinos C. Siontis, Zachi I. Attia, Rickey E. Carter, Suraj Kapa, Steve R. Ommen, Steven J. Demuth, Michael J. Ackerman, Bernard J. Gersh, Adelaide M. Arruda-Olson, Jeffrey B. Geske, Samuel J. Asirvatham, Francisco Lopez-Jimenez, Rick A. Nishimura, Paul A. Friedman, Peter A. Noseworthy
Journal: Journal of the American College of Cardiology (2020)
KEYNOTE-046 (Part B): Effects of ADXS-PSA in combination with pembrolizumab on survival in metastatic, castration-resistant prostate cancer patients with or without prior exposure to docetaxel.
Authors: Mark N. Stein, Lawrence Fong, Anthony E. Mega, Elaine Tat Lam, John W. Heyburn, ANDRES A. GUTIERREZ, Megan Parsi, Surya Vangala, Naomi B. Haas
Journal: Journal of Clinical Oncology (2020)

126 Background: ADXS-PSA, an attenuated Listeria monocytogenes-based immunotherapy targeting prostate-specific antigen (PSA), is currently being evaluated in combination with pembrolizumab as a treatment for progressive metastatic castration-resistant prostate cancer (mCRPC) in the phase 1/2 KEYNOTE-046 trial (Part B). Methods: A total of 37 patients received 1x10 9 CFU + 200 mg pembro IV every 3 wks, for up to 2 yrs or until progression/toxicity. Results: At entry, patients were ~70 yrs with median a Gleason score of 9, and bone predominant disease (70%). MSI-High was negative in 36 pts who were able to be tested. Eighteen (48.6%) patients had received prior docetaxel, 15 pts of whom (83.3%) had also received 1-2 next generation hormonal agents (NGHAs). Nineteen (51.3%) had not received prior docetaxel and 16 of these pts (84.2%) had received 1-2 NGHAs. Overall, 16 out of 37 pts (43%) had a decreased PSA post-BL with 6/37 (16%) pts achieving a confirmed PSA reduction ≥50% from baseline. The median OS (months) for the whole group (37 pts) was 33.6 m (95% CI, range 15.4-33.6 months). The mOS for pts with and without prior exposure to docetaxel was 16 m (5.9 -33.6) and NR at 30 months of follow-up (15.4-NR), respectively. Prolonged survival was observed in pts regardless of prior therapies, microsatellite stable (MSS) status or PSA delta &lt;50% or ≥50%. Conclusions: Results with ADXS-PSA in combination with pembrolizumab in mCRPC, with or without prior docetaxel, show promising clinical activity to be further assessed in randomized studies. Clinical trial information: NCT02325557.
Standard Anthracycline Based Versus Docetaxel-Capecitabine in Early High Clinical and/or Genomic Risk Breast Cancer in the EORTC 10041/BIG 3-04 MINDACT Phase III Trial
Authors: Suzette Delaloge, Martine Piccart, Emiel Rutgers, Saskia Litière, Laura J. van ’t Veer, Franchette van den Berkmortel, Etienne Brain, Aleksandra Dudek-Peric, Miguel Gil-Gil, Patricia Gomez, Florentine S. Hilbers, Zaman Khalil, Susan Knox, Sherko Kuemmel, Georg Kunz, Anne Lesur, Jean-Yves Pierga, Peter Ravdin, Isabel T. Rubio, Mahasti Saghatchian, Tineke J. Smilde, Alastair M. Thompson, Giuseppe Viale, Gabriele Zoppoli, Peter Vuylsteke, Konstantinos Tryfonidis, Coralie Poncet, Jan Bogaerts, Fatima Cardoso
Journal: Journal of Clinical Oncology (2020)

MINDACT demonstrated that 46% of patients with early breast cancer at high clinical but low genomic risk on the basis of MammaPrint may safely avoid adjuvant chemotherapy. A second random assignment (R-C) compared docetaxel-capecitabine with an anthracycline-based regimen.R-C randomly assigned patients 1:1 between standard anthracycline-based regimens, with or without taxanes (control) and experimental docetaxel 75 mg/m2 intravenously plus oral capecitabine 825 mg/m2 two times per day for 14 days (DC) every 3 weeks for 6 cycles. The primary end point was disease-free survival (DFS). Secondary end points included overall survival and safety.Of 2,832 patients, 1,301 (45%) were randomly assigned, and 97% complied with R-C assignment. In the control arm, 29.6% only received taxanes (0.5% of N0 patients). DFS events (n = 148) were much less than required (n = 422) as a result of a lower-than-expected accrual and event rate. At 5 years of median follow-up, DFS was not different between DC (n = 652) and control (n = 649; 90.7% [95% CI, 88% to 92.8%] v 88.8% [95% CI, 85.9% to 91.1%]; hazard ratio [HR], 0.83 [95% CI, 0.60 to 1.15]; P = .26). Overall survival (HR, 0.91 [95% CI, 0.54 to 1.53]) and DFS in the clinical high and genomic high-risk subgroup (86.1% v 88.1%; HR, 0.83 [95% CI, 0.58 to 1.21]) were similar in both arms. DC led to more grade 1 neuropathy (27.1% v 11.2%) and more grade 2 hand/foot syndrome (28.5% v 3.3%) and diarrhea (13.7% v 5.8%). Serious cardiac events occurred in 9 patients (control, n = 4; DC, n = 5). Fifty-three patients developed second cancers (control, n = 32; DC, n = 21; leukemia: 2 v 1). Five treatment-related deaths occurred (control, 2 [0.3%]; DC, 3 [0.5%]).Although underpowered, this second randomization in MINDACT did not show any improvement in outcome or safety with the use of DC compared with anthracycline-based chemotherapy.
A Comparison of Hospitalized Patients With Heart Failure and Cancer Referred to Palliative Care
Authors: Albert Y Liu, David L. O’Riordan, Angela K. Marks, Kara E. Bischoff, Steven Z. Pantilat
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Growing evidence shows that palliative care (PC) improves treatment outcomes in patients with heart failure (HF), but few large-scale studies have prospectively evaluated the processes and outcomes associated with PC consultation for such patients in the real world. <h3>Objective</h3> To characterize processes and outcomes of PC consultations for hospitalized patients with HF compared with patients with cancer. <h3>Design, Setting, and Participants</h3> This cohort study of inpatient encounters at community and academic hospitals in the Palliative Care Quality Network enrolled participants between 2013 and 2017. Of a total of 135 197 patients, 57 272 adults with a primary diagnosis of HF or cancer receiving PC consultation were enrolled. Data analysis was performed from April 2018 to December 2019. <h3>Exposures</h3> Primary diagnosis of HF or cancer. <h3>Main Outcomes and Measures</h3> Symptom improvement and changes in care planning documentation after PC consultation. <h3>Results</h3> At the time of consultation, patients with HF were older (mean age, 75.3 years [95% CI, 75.0-75.5 years] vs 65.2 years [95% CI, 65.0-65.3 years];<i>P</i> &lt; .001), had lower Palliative Performance Scale scores (mean, 35.6% [95% CI, 35.3%-35.9%] vs 42.4% [95% CI, 42.2%-42.6%];<i>P</i> &lt; .001), and were more likely to be in a critical care unit (5808 of 16 741 patients [35.3%] vs 4985 of 40 531 patients [12.5%];<i>P</i> &lt; .001) or a telemetry or step-down unit (5802 of 16 741 patients [35.2%] vs 7651 of 40 531 patients [19.2%];<i>P</i> &lt; .001) compared with patients with cancer. Patients with HF were less likely than patients with cancer to be referred to PC within 24 hours of admission (6773 of 16 741 patients [41.2%] vs 19 348 of 40 531 patients [49.0%];<i>P</i> &lt; .001) and had longer hospitalizations before receiving PC consultation requests (mean, 4.6 days [95% CI, 4.4-4.8 days] vs 3.9 days [95% CI, 3.8-4.0 days];<i>P</i> &lt; .001). Patients with HF were referred less frequently for symptoms other than pain (1686 of 16 488 patients [10.2%] vs 8587 of 39 609 patients [21.7%];<i>P</i> &lt; .001), but were equally likely to report improvements in anxiety (odds ratio, 0.85; 95% CI, 0.71-1.02;<i>P</i> = .08) and more likely to report improvements in dyspnea (odds ratio, 2.17; 95% CI, 1.83-2.57;<i>P</i> &lt; .001) compared with patients with cancer. Patients with HF were less likely than those with cancer to be discharged alive (odds ratio, 0.78; 95% CI, 0.64-0.96;<i>P</i> = .02) or to be referred to hospice (odds ratio, 0.50; 95% CI, 0.47-0.53;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> These findings suggest that PC referral comes late for patients with HF and is used primarily to discuss care planning. Practitioners caring for patients with HF should consider involving PC experts earlier for symptom management.
Biomedical Research Meets Toxicology: How <i>In Vitro</i> Chromosome Instability Methods Can Contribute to Carcinogenicity Prediction
Authors: Ailine Stolz, Markus Becker, Elisa Wistorf, Norman Ertych
Journal: Cancer Research (2020)

Abstract Cancer is a major health concern and a leading cause of mortality. The reliable identification of carcinogens and understanding of carcinogenicity has become a main focus of biomedical research and regulatory toxicology. While biomedical research applies cellular in vitro methods to uncover the underlying mechanisms causing cancer, regulatory toxicology relies on animal testing to predict carcinogenicity of chemicals, often with limited human relevance. Exemplified by chromosome instability–mediated carcinogenicity, we discuss the need to combine the strengths of both fields to develop highly predictive and mechanism-derived in vitro methods that facilitate risk assessment in respect to relevant human diseases.