tbuckley/cabot-search huggingface dataset:
Provider- and system-level barriers to surveillance for hepatocellular carcinoma among patients with chronic liver disease.
Authors: Eliza W. Beal, Leva Gorji, Jaclyn Volney, Lindsey Sova, Allan Tsung, Ann Scheck McAlearney
Journal: Journal of Clinical Oncology (2022)

404 Background: Most cases of hepatocellular carcinoma (HCC) occur in patients with known risk factors. Expert society guidelines recommend HCC surveillance with ultrasound with or without serum alpha fetoprotein every 6 months for these patients, but less than 20% undergo recommended surveillance. The objective of this study was to identify provider- and system-level barriers to surveillance from the provider perspective and to examine the role of provider knowledge and attitudes. Providers’ suggestions for potential interventions to improve HCC surveillance were also elicited. Methods: Qualitative research methods were employed. Purposive sampling was used to invite providers from the Departments of Internal Medicine and Family and Community Medicine who provide primary care, and from the Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition to participate. A semi-structured interview guide was used. Transcribed interviews were analyzed to reveal emergent themes. Results: 22 providers were interviewed including primary care providers, general gastroenterologists and hepatologists. These providers spend a median of 70% (range 20% - 100%) of their time in clinical practice, versus research and administrative responsibilities, and have been in practice a median of 7 years (range 1.8 – 25 years). Provider-level barriers to HCC surveillance identified by participants included variable provider comfort managing chronic liver disease; relationships between primary care, gastroenterology, infectious disease and hepatology; if/how providers discuss HCC surveillance with high-risk patients; provider knowledge of guidelines and outcomes from HCC surveillance; and specific provider-level barriers including time in clinic, competing issues in clinic, deferral of responsibility to another provider, the provider-patient relationship, and time spent on patient education. System-level barriers to HCC surveillance included the absence of relevant technology tools, insurance denial of surveillance imaging, difficulty scheduling surveillance studies and the COVID-19 pandemic. Provider suggestions for interventions included patient navigation, use of technology, education for patients and primary care providers, partnering with primary care practices, and media campaigns. Conclusions: Important barriers to HCC surveillance and opportunities for intervention to improve HCC surveillance rates in high-risk patients were identified. Future research should focus on the design, testing and implementation of interventions to target provider- and system-level barriers.
HLA-independent T cell receptors for targeting tumors with low antigen density
Authors: Jorge Mansilla-Soto, Justin Eyquem, Sascha Haubner, Mohamad Hamieh, Judith Feucht, Noémie Paillon, Andrés Ernesto Zucchetti, Zhuoning Li, Maria Sjöstrand, Pieter L. Lindenbergh, Michelle Saetersmoen, Anton Dobrin, Mathieu Maurin, Archana Iyer, Andreina Garcia Angus, Matthew M. Miele, Zeguo Zhao, Theodoros Giavridis, Sjoukje J. C. van der Stegen, Fella Tamzalit, Isabelle Rivière, Morgan Huse, Ronald C. Hendrickson, Claire Hivroz, Michel Sadelain
Journal: Nature Medicine (2022)
A randomized phase III trial of mFOLFOX7 or CapeOX plus bevacizumab versus 5-FU/<i>l</i>-LV or capecitabine plus bevacizumab as initial therapy in elderly patients with metastatic colorectal cancer: JCOG1018 study (RESPECT).
Authors: Tetsuya Hamaguchi, Atsuo Takashima, Junki Mizusawa, Yasuhiro Shimada, Fumio Nagashima, Masahiko Ando, Hitoshi Ojima, Tadamichi Denda, Jun Watanabe, Katsunori Shinozaki, Hideo Baba, Masako Asayama, Tadao Fukushima, Toshiki Masuishi, Ken Nakata, Shunsuke Tsukamoto, Hiroshi Katayama, Kenichi Nakamura, Haruhiko Fukuda, Yukihide Kanemitsu
Journal: Journal of Clinical Oncology (2022)

10 Background: It is uncertain if the addition of oxaliplatin (OX) to fluoropyrimidine plus bevacizumab (BEV) is suitable as initial therapy in elderly patients (pts) with metastatic colorectal cancer (MCRC). Therefore, we conducted a randomized controlled trial to confirm the superiority of the addition of OX in terms of progression-free survival (PFS). This JCOG trial was originally planned as a paralell study with NCCTG, but the NCCTG trial was terminated early. Methods: Key eligibility criteria included unresectable metastatic colorectal cancer, and histologically confirmed adenocarcinoma, aged 70-74 with PS 2 or 75 or older with ECOG PS 0-2. Eligible pts were randomized (1:1) to either no addition of OX or addition. Whether using 5-FU+levoleucovorin calcium (5-FU/ l-LV) or capecitabine (CAPE) was declared before study entry; options included 5-FU/ l-LV+BEV (C), CAPE+BEV (D), mFOLFOX7+BEV (E), or CapeOX+BEV (F). 5-FU/ l-LV regimen omitted bolus 5-FU from the original sLV5FU regimen. The dose of CAPE was adjusted by estimated creatinine clearance. The primary endpoint was PFS. The planned sample size was 250 pts in total to detect a hazard ratio (HR) of 0.75, with a one-sided alpha of 5% and 70% power. The decision rule is that the primary endpoint is met, and the point estimate of HR of overall survival (OS) is less than 0.8. Results: Between Sep 2012 and Mar 2019, 251 pts were randomized. 125 pts were allocated to no addition of OX and 126 pts to addition. Median age was 79, aged 70-74/75-79/80-84/85+:5%/45%/37%/13%, PS 0/1/2:53%/39%/7%. Of 251 pts, 241 pts had PFS events and 223 pts had OS events. Median PFS (mPFS) was 9.4 months (M) (95%CI 8.3–10.3) in no addition of OX and 10.0M (9.0–11.2) in addition (HR 0.837, 90.5%CI [0.673–1.042], one-sided p = 0.086). Median OS was 21.3M (18.7-24.3) in no addition and 19.7M (15.5–25.5) in addition of OX (HR 1.054 [0.810–1.372]). Response rate was 29.5% (21.2-38.8) in no addition of OX and 47.7% (38.1-57.5) in addition. Proportion of pts whose EQ-5D scores improved from baseline to post-treatment in overall score did not differ (odds ratio 0.94 (0.51-1.75)). The deaths of 1 pt in no addition of OX and in 3 pts in addition were deemed treatment-related. Conclusions: The addition of OX has no survival benefit over no addition. OX was not recommended for elderly MCRC pts as initial therapy. Clinical trial information: UMIN000008866.[Table: see text]
Efmoroctocog Alfa: A Review in Haemophilia A
Authors: James E. Frampton
Journal: Drugs (2021)

Efmoroctocog alfa (Elocta®, Eloctate®, Eloctate™), an extended half-life (EHL) recombinant factor VIII (rFVIII)-Fc fusion protein, is approved for the treatment and prophylaxis of bleeding in patients with haemophilia A. The efficacy of efmoroctocog alfa in the prevention and treatment of bleeding in previously treated patients (PTPs) and previously untreated patients (PUPs) with severe haemophilia A has been demonstrated in phase III studies; this includes its use in the perioperative setting (in PTPs). Furthermore, the effectiveness of efmoroctocog alfa in clinical practice has been confirmed in numerous real-world studies; compared with conventional, standard half-life (SHL) FVIII products, prophylaxis with this EHL FVIII product achieved similar or reduced bleeding rates with fewer injections. Efmoroctocog alfa was generally well tolerated; inhibitors occurred in approximately one-third of PUPs in a phase III study. Efmoroctocog alfa is an established and effective EHL FVIII replacement therapy for the management of haemophilia A. Compared with SHL FVIII products, EHL FVIII products such as efmoroctocog alfa have the potential to optimise prophylactic outcomes by decreasing the burden of treatment or increasing the level of bleed protection. Coagulation factor VIII (FVIII) replacement therapy is the mainstay of haemophilia A treatment; FVIII prophylaxis is the standard of care for severe disease. EHL rFVIII products have been developed to decrease the burden and/or increase the effectiveness of prophylaxis compared with conventional FVIII/rFVIII products which, due to their shorter half-lives, require more frequent injections. Efmoroctocog alfa (Elocta®, Eloctate®, Eloctate™), a first-in-class rFVIII-Fc fusion protein with a half-life ≈ 1.4−1.8 times longer than that of conventional FVIII/rFVIII preparations, is approved for the prophylaxis and treatment of bleeding in patients with haemophilia A in various countries worldwide. The efficacy of efmoroctocog alfa has been demonstrated in phase III trials in patients with severe haemophilia A, and its effectiveness, particularly as FVIII prophylaxis, has been confirmed in numerous studies in clinical practice. The rate of formation of neutralizing anti-FVIII antibodies (inhibitors) with efmoroctocog alfa is similar to that with other FVIII/rFVIII products. Based on a large body of clinical trial and real-world data, efmoroctocog alfa is an established and effective EHL FVIII replacement therapy for the management of haemophilia A.
PERCUTANEOUS ABSORPTION OF 1-NAPHTHOL-(14C) IN MAN
Authors: R. A. HARKNESS, G. W. BEVERIDGE, D. W. DAVIDSON
Journal: British Journal of Dermatology (2006)

SUMMARY.— The percutaneous absorption of 1-naphthol-[1-14C] has been studied in 3 men. This compound was rapidly metabolized and excreted in the urine largely as 1-naphthol conjugated with glucuronic acid; small quantities of radioactivity were present in the sulphate fraction. The results suggest that absorption was efficient; 65.0–23.8% of the applied dose could not be recovered from the skin. Large systemic doses could thus be administered through the skin. The relevance of the findings to an understanding of toxicity due to these compounds is discussed.
Lasker awards honor old and new research
Journal: JAMA (1981)

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
Evaluation of SN-38 PK profile in patients with RAS wild-type metastatic colorectal cancer treated with a combination of SCO-101 and FOLFIRI.
Authors: Jakob Hagen Vasehus Schou, Nicklas Roest, Morten Ladekarl, Jens Bo Rode Hansen, Maj Hedtjaern, Peter Michael Vestlev
Journal: Journal of Clinical Oncology (2022)

185 Background: The FOLFIRI regimen (5-fluorouracil, leucovorin and irinotecan) is a predominant treatment regimen for metastatic colorectal cancer. To optimize the benefit for the patients, it would be desirable to increase the efficacy of irinotecan by increasing the exposure of SN-38 (the active metabolite of irinotecan) to the cancer cells, while maintaining a good safety profile. The oral drug SCO-101, that is currently being developed by Scandion Oncology A/S, was tested in an early clinical trial (CORIST-trial, ClinicalTrials.gov identifier: NCT04247256). SCO-101 is an inhibitor of ABCG2, UGT1A1 and SRPK1. The CORIST trial was set up to address the safety, tolerability, and efficacy of SCO-101 given orally for 6 days followed by FOLFIRI at varying doses from day 5 to 7, in a biweekly schedule, in patients with metastatic colorectal cancer who have formerly been treated with FOLFIRI and afterwards progressed. The first part of the study was a dose-finding study, where the impact of SCO-101 on the pharmacokinetics (PK) of SN-38 was studied. Methods: 12 patients from the dose-finding part of the CORIST study received 150 mg SCO-101 for 6 days and 45 – 80% of the recommended dose of FOLFIRI. 6 of the patients had RAS wild-type tumors and these patients are the subject of the current analysis. Blood for PK analysis was sampled from the patients at 1, 2, 4, 8, 24, 48, and 96 hours after treatment with FOLFIRI and SCO-101. The blood samples were analyzed for Cmax, T½ and AUC (0-24h) of SCO-101, irinotecan and SN-38. Results: The PK of SN-38 from the patients in the study, normalized to a dose of irinotecan of 90 mg/m2 showed a T½ day 5 of 19 hours (SD 5,7) a Cmax of 60 ng/ml (SD 20,6) and an AUC_0-24h of 1415 hxng/ml (SD: 670). The results were compared to SN-38 data from treatment with irinotecan at 180 mg/m2, which is used in standard doses of FOLFIRI and the data is presented in the table. The data analysis showed an increased T½, increased Cmax and increased AUC of SN-38 when combining SCO-101 with 90 mg/m2 irinotecan, compared to SN-38 PK data from standard irinotecan treatment of 180 mg/m2. The toxicity profile of the patients treated with 90 mg irinotecan/m2 (50% FOLFIRI) showed only grade 1 and 2 adverse events. Conclusions: SCO-101 in combination with FOLFIRI has demonstrated the ability to modulate the PK profile of SN-38 in mCRC patients with RAS wild-type tumors, by significantly increasing the half-life, the peak plasma concentration, and area under the curve of SN-38. The combined treatment was well tolerated, and the drug is now being tested for efficacy in the CORIST trial.[Table: see text]
Acute Renal Failure
Authors: Robert W. Schrier
Journal: JAMA (1982)

<h3>Acute Renal Failure Defined</h3> The term<i>acute renal failure</i>can be used for any situation in which the patient's BUN and creatinine levels rise. However, I favor a more restrictive use of the term for situations in which the rise in BUN and creatinine levels are not reversible immediately by altering extrarenal factors. For example, when volume depletion occurs (eg, diarrhea) and the kidney is hypoperfused, there is increased tubular back-diffusion of urea into the circulation, with a resultant rise in BUN level. We use the term<i>prerenal azotemia</i>for this condition. The BUN concentration returns to normal within 24 hours if volume repletion is effected. The BUN level also will rise with bladder-outlet obstruction (eg, prostatic hypertrophy), since the accompanying slower flow of fluid through the renal tubules is also associated with back-diffusion of urea. This situation is termed<i>postrenal azotemia</i>, and a bladder catheter to relieve the obstruction
Surgery for atrial fibrillation using epicardial radiofrequency catheter ablation with and without cardiopulmonary bypass. Results at one year Jo�o Melo, Teresa Santiago, Pedro Adrag�o, Jos� Neves, Miguel Abecasis, Manuel M. Ferreira. Santa Cruz Hospital, Carmaxide, Portugal, Heart Institute, Carnaxide, Portugal
Journal: Journal of the American College of Cardiology (2001)
Publisher Correction: Ventral striatal islands of Calleja neurons control grooming in mice
Authors: Yun-Feng Zhang, Luigim Vargas Cifuentes, Katherine N. Wright, Janardhan P. Bhattarai, Julia Mohrhardt, David Fleck, Emma Janke, Chunjie Jiang, Suna L. Cranfill, Nitsan Goldstein, Mary Schreck, Andrew H. Moberly, Yiqun Yu, Benjamin R. Arenkiel, J. Nicholas Betley, Wenqin Luo, Johannes Stegmaier, Daniel W. Wesson, Marc Spehr, Marc V. Fuccillo, Minghong Ma
Journal: Nature Neuroscience (2022)
Randomized, phase 3 study of second-line tislelizumab versus chemotherapy in advanced or metastatic esophageal squamous cell carcinoma, RATIONALE 302: Asia subgroup.
Authors: Kuaile Zhao, Sung-Bae Kim, Ken Kato, Chih-Hung Hsu, Sheng Hu, Feng Wang, Takashi Kojima, Young Saing Kim, Eric Van Cutsem, Jaffer A. Ajani, Liyun Li, Ningning Ding, Aiyang Tao, Lin Shen
Journal: Journal of Clinical Oncology (2022)

279 Background: In the global Phase 3 study RATIONALE 302 (NCT03430843), tislelizumab (TIS) demonstrated statistically and clinically significant improvement in overall survival (OS) vs chemotherapy (chemo) (median OS 8.6 vs 6.3 months; HR 0.70, 95% CI 0.57–0.85; p=0.0001) in patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC). Here, we report data from the Asia subgroup. Methods: Eligible patients who had disease progression after first-line systemic therapy were randomized 1:1 to receive TIS 200 mg intravenously once every three weeks or chemo (paclitaxel, docetaxel, or irinotecan) until disease progression, intolerable toxicity, or withdrawal. The primary endpoint was OS in all randomized patients (Intent-to-treat population). The key secondary endpoint was OS in patients with PD-L1 Tumor Area Positivity Score* ≥ 10%; other secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), health-related quality of life, and safety. Results: Of the 512 randomized patients, 404 (79%) were enrolled from China, Taiwan, Japan, and Korea and constituted the Asia subgroup (n=201 TIS, n=203 chemo). At data cut-off (December 1, 2020), median follow-up was 6.9 months in the Asia subgroup. Median OS was 8.5 months with TIS vs 6.3 months with chemo (HR 0.73; 95% CI 0.59, 0.90). Median PFS was 1.5 months with TIS vs 1.7 months with chemo (HR 0.81; 95% CI 0.64, 1.02). TIS resulted in a higher ORR (20.4% [95% CI 15.1, 26.6] vs 9.4% [95% CI 5.7, 14.2]) and longer median DoR (7.4 vs 4.0 months; HR 0.42, 95% CI 0.21, 0.84) vs chemo. In the safety analysis set (n=201 TIS, n=191 chemo), patients treated with TIS had fewer treatment-related adverse events (TRAEs) (74.1% vs 95.3%), fewer ≥ Grade 3 TRAEs (19.4% vs 57.1%), fewer serious TRAEs (15.4% vs 20.9%), and a similar incidence of TRAEs leading to death (2.5% vs 2.6%) vs chemo. Conclusions: In the Asia subgroup, TIS improved OS and tumor response vs chemo as second-line treatment in patients with advanced or metastatic ESCC and showed a well-tolerated safety profile. These findings were consistent with published results in the overall population. *The TAP score methodology has been previously referred to as visually-estimated combined positive score (vCPS) and was previously presented at the American Society of Clinical Oncology 2021, June 4–8, 2021, ESMO World Gastrointestinal Congress 2021, June 30–July 3, 2021, and The Chinese Society of Clinical Oncology 2021, September 25–29, 2021. Clinical trial information: NCT03430843.
Medical Jargon
Authors: Hugh H. Hussey
Journal: JAMA (1976)

Only some authors whose manuscripts are accepted for publication in<i>JAMA</i>or an equivalent journal and who see them again after they have undergone copy editing appreciate fully the diligence of copy editors in improving punctuation, grammar, and composition and in eliminating jargon. Among the errors made frequently by physicianwriters is the failure to be fully descriptive of regions and parts. A few examples should illustrate the point. An author will write about the "upper abdomen," by which he must imply that there is also at least a "lower abdomen" and perhaps a "middle" one. Another author will have something to say about the "upper arm." It is difficult to know whether he means "arm," "shoulder," or "upper<i>part</i>of the arm." (As everyone knows, the upper extremity is made up of an arm, a forearm, a hand, and some intervening joints.) Other favorites include anatomic structures such as the
Questions and Answers
Journal: JAMA (1982)

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Medical News
Journal: JAMA (1925)

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Authors: Sudhakar George, James Cockburn, Tim C. Clayton, Peter Ludman, James Cotton, James Spratt, Simon Redwood, Mark de Belder, Adam de Belder, Jonathan Hill, Angela Hoye, Nick Palmer, Sudhir Rathore, Anthony Gershlick, Carlo Di Mario, David Hildick-Smith
Journal: Journal of the American College of Cardiology (2014)
THE COLD WINTER AND THE MORTALITY RATE.
Journal: JAMA (1904)

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