tbuckley/cabot-search huggingface dataset:
Abstract P072: Elevated Liver Enzymes Are Associated With Incident Diabetes in Hispanic/Latino Adults: Results From HCHS/SOL
Authors: Simin Hua, Qibin Qi, Christina M Parrinello, Jorge R Kizer, Howard Strickler, Bharat Thyagarajan, Martha Daviglus, Gregory A Talavera, Neil Schneiderman, Scott J Cotler, Jianwen Cai, Robert Kaplan, Carmen R Isasi
Journal: Circulation (2019)

Introduction: Non-alcoholic fatty liver disease (NAFLD) as measured by ultrasonography or elevated liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT), has been associated with increased risk of incident diabetes. But such evidence is lacking in the Hispanic/Latino population, which has high prevalence of obesity and NAFLD. Methods: We conducted a prospective cohort study of 6928 adults of Hispanic/Latino background who had no diabetes at baseline (2008-2011). Incident diabetes was defined by self-reported diagnosis of diabetes, glucose measurements or antidiabetic medication use at repeat visits on average 6 years from baseline. We examined the associations of baseline liver enzymes (sex-specific quartiles of ALT, AST, GGT) with incident diabetes using survey-weighted Poisson regression with follow-up time as an offset. Results: The weighted mean age was 38 years at baseline. A total of 793 adults developed diabetes during 6 years of follow-up. After adjusting for demographics and socioeconomic status, versus the lowest quartile, highest quartiles of ALT, AST and GGT were significantly associated with 1.5 to 3.5-fold increased risk of incident diabetes. Further adjusting for behavioral variables including diet and exercise, cardiovascular risk factors and cardiovascular medication use, the associations were attenuated and remained statistically significant for ALT (RR quartile 4 vs 1: 1.42[95% CI 1.07-1.90], P-trend=0.001) and GGT (RR quartile 4 vs 1: 1.97[1.34-2.88], P-trend&lt;0.001) but not AST (RR quartile 4 vs 1: 1.28[0.96-1.70], P-trend=0.02). Adjusting for HOMA-IR further attenuated the associations, and GGT but not ALT remained significantly associated with incident diabetes. Conclusion: Elevated ALT and GGT levels are associated with increased risk of developing diabetes among Hispanics/Latinos. Additional work is needed to understand the relationship between NAFLD and diabetes risk in this population.
Letter to the Editor: Will Vitamin E Be the Hope of Patients With NASH and Advanced Fibrosis? The Reliability Is Worth Discussing
Authors: Jian He, Ai‐Min Leng
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. To the Editor: According to the study conducted by Vilar‐Gomez et al.,1 the nontransplant survival rate of patients with nonalcoholic steatohepatitis (NASH) with bridging necrosis and cirrhosis, a subtype of nonalcoholic fatty liver disease (NAFLD), was found to be improved by vitamin E. Vitamin E was also found to reduce the occurrence of liver decompensation. However, after a careful review of the literature and our own clinical experience, we propose two important factors that may affect these study results. According to recent studies, vitamin E can slow down the progression of NASH due to its antioxidation effect2; however, numerous antioxidant hepatoprotective agents already exist. In a study conducted by Yasushi et al.,3 glutathione was shown to help slow down the NAFLD process. In clinical work, especially for NASH with elevated transaminase, patients are more often advised to take antioxidant hepatoprotective agents, such as glutathione, diammonium glycyrrhizinate and polyene phosphatidyl choline, to reduce liver inflammation, repair liver damage, and reduce transaminase. In this study, the authors mentioned medication use for NAFLD metabolic risk factors (e.g., obesity, diabetes, hyperlipidemia) in the vitamin E intervention and nonintervention groups, but did not mention the use of antioxidant hepatoprotective agents (conditions for medication use are found in table 1 and supporting tables S2 and S3). From our perspective, the use of antioxidant hepatoprotective drugs may differ between vitamin E–treated and nontreated groups. Therefore, the conclusion would be more convincing if the researchers could provide more detailed information about the use of other antioxidant hepatoprotective drugs, to optimize their previous findings. In addition, as of right now, no drugs have been approved by the US Food and Drug Administration for the treatment of NAFLD.4 Therefore, not every patient will seek treatment with vitamin E. This retrospective study included only those patients who purchased vitamin E on their own. Therefore, it stands to reason that, compared with those who do not consume vitamin E, those who do may have a higher medical knowledge and pay more attention to their health. In addition, they may tend to choose a healthier lifestyle and be willing to take the initiative to seek help for their disease. In the management of chronic metabolic diseases, these actions are more conducive to disease process alleviation, which creates an important bias that affects the effectiveness of vitamin E in patients with NASH and advanced fibrosis.
Abstract 12743: Pioglitazone Decreases Plasma Fibroblast Growth Factor-21 Levels in Patients with Type 2 Diabetes
Authors: Kazutoshi Mawatari, Nobuhiro Tahara, Hideo Yasukawa, Toyoharu Oba, Takanobu Nagata, Sachiko Kyogoku, Hideki Ohshima, Tomoko Minami, Minori Mizoguchi, Yusuke Sugi, Hisashi Adachi, Tsutomu Imaizumi
Journal: Circulation (2012)

Background: Fibroblast growth factor-21 (FGF21) is a potent metabolic regulator, which has been shown to improve lipid metabolism, glucose metabolism, and insulin sensitivity. Recently, FGF21 was s...
A Surgical Handbook. For the Use of Students, Practitioners, House Surgeons and Dressers.
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
A statistical model for predicting neutropenic fever.
Authors: Ariel Ann Nelson, Daniel Eastwood, Tao Wang, Karen-Sue Carlson, Laura C. Michaelis, Marcelo C. Pasquini, Parameswaran Hari, Christopher R. Chitambar, Timothy S. Fenske, Mary Beth Graham, Mehdi Hamadani, Anita D'Souza, Ehab L. Atallah
Journal: Journal of Clinical Oncology (2015)

e18050 Background: Febrile neutropenia (FN) is a common occurrence associated with chemotherapy regimens used in patients with acute myelogenous leukemia (AML). To our knowledge, there is no evidence that supports the current definition of FN. The goal of this pilot study was to analyze patient fever data and develop a statistical prediction model to predict febrile neutropenia. Methods: We obtained temperature data from 68 hospitalized patients with AML undergoing chemotherapy. Plots were created showing temperature over time leading up to a fever event. Data was simplified to perform an ROC-like analysis to estimate sensitivity and specificity of decision rules that predict oncoming episodes of FN. Statistics on each patient series were used as variables in predicting fever onset in logistic regression analysis. Statistical analysis consisted of a generalized linear model with logit link (logistic regression) predicting fever at least 4 hours before onset, and used generalized estimating equations to adjust for correlated temperature measures within patient. Results: Fever curve plots suggest that there is an increase in average temperature at least 24 hours before the onset of fever by current definition. Significant identified predictors of fever included; maximum and minimum temperature within 24 hours, and the average of positive increases in temperature between subsequent measurements. A prediction score including, maximum temperature within 24 hours, minimum temperature within 24 hours, average of positive increases between subsequent measurements, and largest 24 hour increase was able to predict 86.1% of oncoming FN events 4 to 28 hours before onset and reject 67.4% of non-FN events. This rule has a negative predictive value of 96.2% and a positive predictive value of 33.7%. Conclusions: Our analysis demonstrates the feasibility of using temperature series data for early prediction of FN. A more comprehensive analysis is planned and is expected to result in higher sensitivities. If subsequent analysis proves to be significant this data may be used to develop future prospective clinical studies to evaluate new fever criteria and may alter our current definition and management of patients with FN.
Efficacy of alpha-1,3-galactosyltransferase-expressing allogeneic renal cell carcinoma immunotherapy in patients (pts) with refractory metastatic renal cell carcinoma (mRCC).
Authors: Andrew W Hahn, Charles G. Drake, Samuel R. Denmeade, Yousef Zakharia, Benjamin Louis Maughan, Eugene Paul Kennedy, Charles J. Link, Nicholas N. Vahanian, Hans J. Hammers, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2019)

590 Background: HyperAcute Renal (HAR) immunotherapy consists of two allogeneic renal cancer cell lines that have been genetically modified to express α(1,3)Gal, to which humans have an inherent pre-existing immunity. A previous report demonstrated that HAR is well tolerated in pts with mRCC (2017 GUASCO, abstract: 528). Herein, we report the efficacy of HAR immunotherapy in mRCC. Methods: Pts with refractory clear-cell mRCC were eligible for this phase 1 dose-escalation trial. Concomitant treatment (Rx) with other approved agents was permitted after initial 2 months (m) of HAR monotherapy. The trial followed a standard 3+3 design with cells injected intradermally weekly for 4 weeks then biweekly injections for 10 immunizations (150 x10 6 cells then escalated to 300 x10 6 cells). Co-primary objectives were safety and efficacy. Results: A total of 18 patients were enrolled (4 low dose, 14 high dose) between 06/2015 to 07/2016. Patients received a median of 1 systemic Rx prior to HAR immunotherapy, with 8 patients receiving 2 or more prior agents. IMDC risk categories at the time of initial metastatic disease were: favorable risk (33%), intermediate risk (66%), poor risk (0%). The ORR was 0% with a disease control rate of 50%. Median PFS for patients treated with HAR immunotherapy was 2.0 months (m) (range 1.7-30.3 m). For patients receiving the low dose HAR, median overall survival (OS) was 14.2 m (range 3.6-21.6 m), while median OS for high dose HAR was 25.3 m (5.8-29.3 m). At the time of data cutoff in 09/2018, 7 patients were still living. Detailed clinical data will be presented in the meeting. Conclusions: HAR immunotherapy in refractory mRCC was well tolerated and demonstrated potential efficacy for OS similar to currently approved salvage-line Rx. With a unique mechanism of action, HAR immunotherapy may be a candidate for inclusion in novel combinatorial regimens being developed in salvage therapy setting in pts with mRCC. Clinical trial information: NCT02035358.
Outcomes in a cohort of patients with a Gleason score 6 on radical prostatectomy specimen.
Authors: Elodie Le Bihan, Cedric Michel Lebacle, Thomas Bessede, Alexandre de la TAILLE, Laurent Salomon, Jacques Irani
Journal: Journal of Clinical Oncology (2019)

112 Background: This retrospective study evaluates the outcome of a cohort of patients who had a radical prostatectomy with GS 6 on the prostatic specimen. Methods: Consecutive cases were extracted from prostatectomy database of 2 teaching hospitals between 2000 and 2006 for a prostate cancer and were scored GS 6 on the specimen. Overall, specific, metastasis and PSA progression-free survivals were analyzed. Cox model was used to evaluate predictive factors. PSA progression was defined by a level of 0.2 ng/mL or above. Results: Mean age of the 616 analyzed patients was 62.8 yrs (SD 6.4). Mean initial PSA was 8.2 ng/mL (SD 8.0). In 46 cases (7.5%) grade 4 was described on pre-operative prostatic biopsies. Median total tumor length (TTL) was 3 mm (IQ 7.7). Pelvic lymphadenectomy was performed in 213 cases and no positive lymph node was diagnosed. Positive margin (R1) was diagnosed in 79 patients (12.8%). pT3a and pT3b stages were described in 65 and 11 cases (10.5% and 1.8%) respectively. Mean follow-up (FU) was 57.2 months (SD 48). None of the 4 deaths were attributed to prostate cancer. PSA progression was observed in 73 patients (11.8%) of whom 48 had a secondary treatment. One patient developed metastasis. Independent predictive factors of PSA progression were TTL on prostatic biopsy (p = 0.007), R1 status (p = 0.005) and seminal vesicles invasion (p = 0.005). Center, initial PSA, number of positive cores and GS on prostatic biopsy were not associated with outcome. Conclusions: No specific mortality was observed in this cohort of prostatectomy GS 6 prostate cancer patients with the limitation of an insufficient FU. The number of positive cores on pre-operative prostatic biopsies was not predictive of outcome which calls into question its use as criterion for active surveillance.
Electronic Health Record Data Quality Issues Are Not Remedied by Increasing Granularity of Diagnosis Codes
Authors: Ann Marie Navar
Journal: JAMA Cardiology (2019)

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 Cardiology 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 Cardiology journal
Storage and Disposal of Opioid Analgesics
Authors: Mitchell L. Doucette, Wendy C. Shields, R. Sterling Haring, Shannon Frattaroli
Journal: Annals of Internal Medicine (2019)

Letters19 March 2019Storage and Disposal of Opioid AnalgesicsMitchell L. Doucette, PhD, MS, Wendy C. Shields, MPH, R. Sterling Haring, DO, MPH, and Shannon Frattaroli, PhD, MPHMitchell L. Doucette, PhD, MSEastern Connecticut State University, Willimantic, Connecticut (M.L.D.)Search for more papers by this author, Wendy C. Shields, MPHThe Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (W.C.S., S.F.)Search for more papers by this author, R. Sterling Haring, DO, MPHVanderbilt University, Nashville, Tennessee (R.S.H.)Search for more papers by this author, and Shannon Frattaroli, PhD, MPHThe Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (W.C.S., S.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L18-0695 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We are strongly encouraged by the common goals held by Dr. Liberatore and colleagues. We acknowledge that our analysis did not contain product labels updated after 16 December 2016 because our data collection period ended in September 2016. The FDA updated their drug disposal information for opioid analgesic labels in an effort to combat the opioid crisis. As such, we investigated the effect of the FDA update within the random sample used for the original analysis. We gathered labeling information from DailyMed, which provides “trustworthy information about marketed drugs” and is the official provider of FDA label information ...Reference1. U.S. National Library of Medicine. DailyMed. 2018. Accessed at https://dailymed.nlm.nih.gov/dailymed/index.cfm on 1 October 2018. Google Scholar Author, Article, and Disclosure InformationAffiliations: Eastern Connecticut State University, Willimantic, Connecticut (M.L.D.)The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (W.C.S., S.F.)Vanderbilt University, Nashville, Tennessee (R.S.H.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-3381. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoStoring and Disposing of Opioid Analgesics: What Does Our Medicine Tell Us? Mitchell L. Doucette , Wendy C. Shields , R. Sterling Haring , and Shannon Frattaroli Storage and Disposal of Opioid Analgesics Mark A. Liberatore , Judith A. Racoosin , and Douglas C. Throckmorton Metrics 19 March 2019Volume 170, Issue 6Page: 432KeywordsAnalgesicsDisclosureDrug informationDrugsOpioids ePublished: 19 March 2019 Issue Published: 19 March 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Streamlining Detection of Fusion Genes in Colorectal Cancer: Having “Faith” in Precision Oncology in the (Tissue) “Agnostic” Era
Authors: Nicola Valeri
Journal: Cancer Research (2019)

Abstract The FDA recently granted tissue-agnostic approval for the first-in-class TRK inhibitor larotrectinib for patients whose tumors harbor fusions in neurotrophic receptor tyrosine kinases. These fusion genes have a frequency of less than 1% in unselected patients with colorectal cancer. Using a multiomics approach and a clinically annotated cohort of patients with colorectal cancer, Cocco and colleagues showed that patients with sporadic, RAS/BRAF wild-type, mismatch repair–deficient colorectal cancer tumors with MLH1 promoter methylation present fusions in kinase genes in 42% of cases and suggested a diagnostic framework to improve the selection of patients eligible for gene fusion testing. See related article by Cocco et al., p. 1047
A study of effects of concomitant administration of proton pump inhibitors (PPIs) and capecitabine (cape) on survival in early stage colorectal cancer (CRC) patients (pts).
Authors: Julia Sun, Alastair Ilich, Christina Kim, Michael Patvin Chu, Grace Wong, Sunita Ghosh, Jennifer L. Spratlin, Karen E. Mulder, Melanie Danilak, Carole Chambers, Michael B. Sawyer
Journal: Journal of Clinical Oncology (2015)

e17688 Background: Cape is used to treat CRC and other cancers. Many pts take PPIs for symptom control. TRIO-013, a study of cape/oxaliplatin +/- lapatinib in metastatic gastro-esophageal cancer, failed to show an increase in overall survival (OS). Ad hoc analysis of PPI effects in both arms showed negative impact on cape efficacy with PPI use. This study’s objectives are to report effects of PPIs on cape efficacy in early stage CRC and to explore how cape dose adjustments for toxicity impact survival outcomes. Methods: A retrospective study of all pts diagnosed with early stage CRC treated with adjuvant cape monotherapy between 2008 and 2012 was undertaken at the Cross Cancer Institute, Edmonton, Canada. Data was collected on demographics, medications, toxicities, and pt outcomes. Results: 298 pts were identified with 129 pts taking PPIs and 169 pts not taking PPIs. PPI pts had lower 5-yr OS rate vs. non-PPI pts – 72% vs 85% (HR 2.01, 95% CI 1.14-3.56, p = 0.02). 5- yr recurrence free survival (RFS) was 71% in PPI pts vs. 88% in non-PPI pts (HR 2.57, 95% CI 1.45-4.56, p-value = 0.001). Adjusting for age, gender, stage and ECOG, PPI pts still had poorer OS (HR 1.88, 95% CI 1.04-3.41, p = 0.04) and RFS (HR 2.24, 95% CI 1.25-4.04, p = 0.007). Cape dose modifications also impacted outcomes. Pts with dose delays due to toxicity had better 5-yr OS 90% vs. pts with no toxicity 82% vs. pts with toxicity requiring dose reductions 73% (p = 0.02). Corresponding 5-yr RFS was 100% vs. 84% vs. 67% (p = 0.006). Conclusions: PPIs impair cape efficacy possibly by altering gastric pH, preventing cape tablet dissolution, and therefore absorption, consistent with findings in TRIO-013. As oral anti-cancer therapies become more prevalent, in addition to food effect studies, phase I PPI-drug interaction studies are necessary to avoid negative impact on patient outcomes. In addition, pts with dose delays due to toxicity had better outcomes than pts with no toxicity and with dose reductions, suggesting toxicity from cape may be beneficial.
Presence of patient-relevant endpoints in trials of recently launched oncology drugs: What measuring stick do we use to measure value?
Authors: Akwasi Asabere, Jessica Li, Alex Bastian
Journal: Journal of Clinical Oncology (2015)

e17790 Background: The German health system assesses additional therapeutic benefit of drugs based on patient-relevant endpoints. With prices of cancer drugs under scrutiny in the US, a critical view of the relative value of new cancer therapies has increased, with various groups attempting to define how to capture this value. Little is known if the measures commonly deemed as patient-relevant are being included in trial designs of recently launched oncologics. Methods: A list of drugs (N = 68) approved in 2013 and 2014 was obtained from the FDA website. Non-oncology, pediatric and palliative drugs were excluded. The pivotal clinical studies (N = 27) for indications of the remaining drugs (n = 19) were identified from drug package inserts. Clinical data such as trial design and reported patient-relevant endpoints were obtained from package inserts, Clinicaltrials.gov registry, publications and ASCO abstracts. These endpoints were catalogued and analyzed to determine the presence or absence, as well as other defining features in the evidence base for newly approved cancer drugs in the US Results: Progression Free Survival (PFS), Overall Response Rate (ORR) and Overall Survival (OS) were the most commonly reported patient-relevant endpoints. 48% of studies reported all 3 measures, 22% reported 2 measures, and 26% reported 1 of the measures. One trial did not track any of these endpoints and, overall, no trial reported Disease Free Survival data. PFS was often reported as the primary endpoint (44% of trials), followed by ORR and OS, 41% and 15% of the time, respectively. Endpoints measuring palliation of cancer symptoms were reported in 37% of trials, with 80% of those for hematologic malignancies Conclusions: OS, the mortality endpoint deemed most relevant by the G-BA was not most commonly reported in trials for new oncology medications. The use of alternative endpoints may be required to fully appreciate the benefits of new oncology drugs. Future discussions about value of cancer drugs in the US will also have to include considerations for varying definitions and measurements of value in oncology trials