tbuckley/cabot-search huggingface dataset:
Underreporting of Symptomatic Adverse Events in Phase I Clinical Trials
Authors: Zachary W Veitch, Daniel Shepshelovich, Christina Gallagher, Lisa Wang, Albiruni R Abdul Razak, Anna Spreafico, Philippe L Bedard, Lillian L Siu, Lori Minasian, Aaron R Hansen
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Clinician reporting of symptomatic adverse events (AEs) in phase I trials uses the Common Terminology Criteria for Adverse Events (CTCAE). The utility of the patient-reported outcomes (PROs) version of the CTCAE (PRO-CTCAE) in this setting is unknown. This prospective, observational study compared patient- and clinician-reported symptomatic AEs in phase I patients. Methods Phase I study–eligible patients at Princess Margaret were surveyed with the PRO-CTCAE full-item library (78 symptomatic AEs) at baseline (BL), mid-cycle 1, and mid-cycle 2 (C2). Patient and trial characteristics, best response, and survival data were collected. Presence or absence of patient- (PRO-CTCAE) or clinician-reported symptomatic AEs were compared (kappa) at defined timepoints and overall (BL+ mid-cycle 1 + C2). Results Of 292 patients approached from May 2017 to January 2019, a total of 265 (90.8%) were consented, with 243 (91.7%) evaluable and 552 PRO-CTCAE surveys (completion rate = 98.7%) included in analyses. Evaluation of overall patient-reported symptomatic AEs identified 50 PRO-CTCAE and 11 CTCAE items with 10% or greater reporting frequency. Nineteen CTCAE items were reported as 1% or less despite matched PRO-CTCAE items reporting as 10% or greater. Underreported categories included sexual health, bodily emissions, and cognition. Clinician- relative to patient-reporting frequency (ratio) demonstrated 9 symptomatic AEs with a 50-fold or more lower clinician reporting rate. Overall patient–clinician agreement for individual symptomatic AEs ranged from poor (κ = 0.00-0.19) to moderate (κ = 0.40-0.59), with discordance driven by lack of clinician reporting. Dyspnea (κ = 0.54) and peripheral neuropathy (κ = 0.63) at BL and limb edema (κ = 0.55) at C2 demonstrated the highest patient–clinician agreement. Conclusions Poor to moderate patient–clinician agreement for symptomatic AEs suggests clinician underreporting in phase I trials. Analyses of severity and interference PRO categories are ongoing.
Overcoming Barriers to Treatment of Opioid Use Disorder
Authors: Yngvild Olsen, Ruchi M. Fitzgerald, Sarah E. Wakeman
Journal: JAMA (2021)

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
Abstract PS18-45: Association between tumor mutation profile and clinical outcomes among Hispanic Latina women with triple-negative breast cancer
Authors: Alexander Philipovskiy, Alok Dwivedi, Roberto Gamez, Richard McCallum, Zeina Nahleh, Renato Aguilera, Sumit Gaur
Journal: Cancer Research (2021)

Abstract Triple-negative breast cancer (TNBC) represents approximately 15-20% of all breast cancer types. It is more common among African American (AA) and Hispanic-Latina (HL) women and has more aggressive course. The biology of TNBC in HL women has been poorly characterized, but some data suggest that molecular drivers of breast cancer might be different. Chemotherapy remains the only option for those patients. There is no clinical tool to help medical oncologist with the decision about appropriate individual chemotherapy, as well as no way to predict long-term outcomes. The aim of the study was to characterize individual patient gene expression profiles and to identify the relationship with clinical outcomes.Patients and Methods: From 2012-2019, we collected formalin-fixed paraffin-embedded tumors (FFPE) from women with TNBC. All specimens were carefully examined by pathologists for adequacy and for a hormonal status. We analyzed gene mutation profiles of collected tumors and associated results with individual patient’s clinical history and outcomes.Results: Of 25 patients with TNBC, 24 (96%) identified as HL, one patient as NHL. Twenty-one (84%) had stage III/IV disease, and four (16%) had stage II at the diagnosis. Most commonly mutated genes were: TP53, Notch, AKT, MEP3K, PIK3CA and EGFR. Compared to other international cancer databases mostly included NHW, AA and Asian women, our study demonstrated statistically significant higher frequencies of those among HL women. With TNBC. Also a worse clinical course was among those patients whose tumor had mutations in Notch and PIK3CA. Conclusion: In conclusion, this study is the first to identify the most common genetic alterations among HL women with TNBC. Our data strongly support the notion that molecular drivers of breast cancer could be different in HL women. Therefore, a deeper understanding of the biological mechanisms behind Notch, PIK3CA mutation, might lead to a new treatment approach. Citation Format: Alexander Philipovskiy, Alok Dwivedi, Roberto Gamez, Richard McCallum, Zeina Nahleh, Renato Aguilera, Sumit Gaur. Association between tumor mutation profile and clinical outcomes among Hispanic Latina women with triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-45.
Abstract 2875: Long-Term Outcomes Following Vascular Surgery in Patients With Multivessel Coronary Artery Disease: Analysis of Randomized and Excluded Patients from the Coronary Artery Revascularization Prophylaxis (CARP) Trial
Authors: Santiago Garcia, Herbert B Ward, Thomas Moritz, Fred Littooy, Steve Goldman, Gordon Pierpont, Greg Larsen, Domenic Reda, Edward O McFalls
Journal: Circulation (2007)

Background: The Coronary Artery Revascularization Prophylaxis (CARP) Trial was a multicenter randomized study that showed no long-term survival benefit with revascularization prior to elective vascular surgery in patients with stable coronary artery disease (CAD). To determine whether subsets with high-risk anatomy benefited from preoperative revascularization, survival was determined in randomized and registry patients who underwent coronary angiography within 6 months of vascular surgery. Methods: Over a 4-year enrollment period, 4,876 patients were screened prior to vascular surgery and 1,048 (21.5%) had preoperative coronary angiography for either multiple cardiac risks or an abnormal preoperative stress test. The cohort included 462 randomized and 586 excluded patients and the probability of survival was determined at 2.5 years following vascular surgery. Results: Of 1,048 patients with preoperative coronary angiography, non-obstructive disease (&lt; 70%) was present in 192 (18.3%) and 1 vessel disease (VD) was present in 244 (23.3%), with a combined survival of 0.84. Previous bypass surgery (CABG) was present in 225 (21.5%), with a survival of 0.78. High risk coronary anatomy in patients without prior CABG included 2-VD in 204 (19.5%), 3-VD in 130 (12.4%) and an unprotected left main stenosis &gt; 50% in 48 (4.6%) patients. Their long-term survival according to the preoperative revascularization status is shown in the Table . Conclusions: The results demonstrate that an unprotected left main stenosis was present in 4.6% of high-risk patients presenting for vascular surgery and was the only anatomical subset that demonstrated a survival benefit with preoperative revascularization prior to vascular surgery. These data may warrant additional strategies to identify patients with unprotected left main disease either prior to or immediately following vascular surgery. Long-Term Probability of Survival at 2.5 Years Following Vascular Surgery
Ontogeny of Hepatic Transporters and Drug-Metabolizing Enzymes in Humans and in Nonclinical Species
Authors: B. D. van Groen, J. Nicolaï, A. C. Kuik, S. Van Cruchten, E. van Peer, A. Smits, S. Schmidt, S. N. de Wildt, K. Allegaert, L. De Schaepdrijver, P. Annaert, J. Badée
Journal: Pharmacological Reviews (2021)

The liver represents a major eliminating and detoxifying organ, determining exposure to endogenous compounds, drugs, and other xenobiotics. Drug transporters (DTs) and drug-metabolizing enzymes (DMEs) are key determinants of disposition, efficacy, and toxicity of drugs. Changes in their mRNA and protein expression levels and associated functional activity between the perinatal period until adulthood impact drug disposition. However, high-resolution ontogeny profiles for hepatic DTs and DMEs in nonclinical species and humans are lacking. Meanwhile, increasing use of physiologically based pharmacokinetic (PBPK) models necessitates availability of underlying ontogeny profiles to reliably predict drug exposure in children. In addition, understanding of species similarities and differences in DT/DME ontogeny is crucial for selecting the most appropriate animal species when studying the impact of development on pharmacokinetics. Cross-species ontogeny mapping is also required for adequate translation of drug disposition data in developing nonclinical species to humans. This review presents a quantitative cross-species compilation of the ontogeny of DTs and DMEs relevant to hepatic drug disposition. A comprehensive literature search was conducted on PubMed Central: Tables and graphs (often after digitization) in original manuscripts were used to extract ontogeny data. Data from independent studies were standardized and normalized before being compiled in graphs and tables for further interpretation. New insights gained from these high-resolution ontogeny profiles will be indispensable to understand cross-species differences in maturation of hepatic DTs and DMEs. Integration of these ontogeny data into PBPK models will support improved predictions of pediatric hepatic drug disposition processes. <h3>Significance Statement</h3> Hepatic drug transporters (DTs) and drug-metabolizing enzymes (DMEs) play pivotal roles in hepatic drug disposition. Developmental changes in expression levels and activities of these proteins drive age-dependent pharmacokinetics. This review compiles the currently available ontogeny profiles of DTs and DMEs expressed in livers of humans and nonclinical species, enabling robust interpretation of age-related changes in drug disposition and ultimately optimization of pediatric drug therapy.
Automatic multilabel detection of ICD10 codes in Dutch cardiology discharge letters using neural networks
Authors: Arjan Sammani, Ayoub Bagheri, Peter G. M. van der Heijden, Anneline S. J. M. te Riele, Annette F. Baas, C. A. J. Oosters, Daniel Oberski, Folkert W. Asselbergs
Journal: npj Digital Medicine (2021)

Abstract Standard reference terminology of diagnoses and risk factors is crucial for billing, epidemiological studies, and inter/intranational comparisons of diseases. The International Classification of Disease (ICD) is a standardized and widely used method, but the manual classification is an enormously time-consuming endeavor. Natural language processing together with machine learning allows automated structuring of diagnoses using ICD-10 codes, but the limited performance of machine learning models, the necessity of gigantic datasets, and poor reliability of terminal parts of these codes restricted clinical usability. We aimed to create a high performing pipeline for automated classification of reliable ICD-10 codes in the free medical text in cardiology. We focussed on frequently used and well-defined three- and four-digit ICD-10 codes that still have enough granularity to be clinically relevant such as atrial fibrillation (I48), acute myocardial infarction (I21), or dilated cardiomyopathy (I42.0). Our pipeline uses a deep neural network known as a Bidirectional Gated Recurrent Unit Neural Network and was trained and tested with 5548 discharge letters and validated in 5089 discharge and procedural letters. As in clinical practice discharge letters may be labeled with more than one code, we assessed the single- and multilabel performance of main diagnoses and cardiovascular risk factors. We investigated using both the entire body of text and only the summary paragraph, supplemented by age and sex. Given the privacy-sensitive information included in discharge letters, we added a de-identification step. The performance was high, with F1 scores of 0.76–0.99 for three-character and 0.87–0.98 for four-character ICD-10 codes, and was best when using complete discharge letters. Adding variables age/sex did not affect results. For model interpretability, word coefficients were provided and qualitative assessment of classification was manually performed. Because of its high performance, this pipeline can be useful to decrease the administrative burden of classifying discharge diagnoses and may serve as a scaffold for reimbursement and research applications.
Imbalance of TGF-β1/BMP-7 pathways induced by M2-polarized macrophages promotes hepatocellular carcinoma aggressiveness
Authors: Junya Ning, Yingnan Ye, Dechao Bu, Gang Zhao, Tianqiang Song, Pengpeng Liu, Wenwen Yu, Hailong Wang, Hui Li, Xiubao Ren, Guoguang Ying, Yi Zhao, Jinpu Yu
Journal: Molecular Therapy (2021)

The transforming growth factor-beta (TGF-β) signaling pathway is the predominant cytokine signaling pathway in the development and progression of hepatocellular carcinoma (HCC). Bone morphogenetic protein (BMP), another member of the TGF-β superfamily, has been frequently found to participate in crosstalk with the TGF-β pathway. However, the complex interaction between the TGF-β and BMP pathways has not been fully elucidated in HCC. We found that the imbalance of TGF-β1/BMP-7 pathways was associated with aggressive pathological features and poor clinical outcomes in HCC. The induction of the imbalance of TGF-β1/BMP-7 pathways in HCC cells could significantly promote HCC cell invasion and stemness by increasing inhibitor of differentiation 1 (ID1) expression. We also found that the microRNA (miR)-17-92 cluster, originating from the extracellular vesicles (EVs) of M2-polarized tumor-associated macrophages (M2-TAMs), stimulated the imbalance of TGF-β1/BMP-7 pathways in HCC cells by inducing TGF-β type II receptor (TGFBR2) post-transcriptional silencing and inhibiting activin A receptor type 1 (ACVR1) post-translational ubiquitylation by targeting Smad ubiquitylation regulatory factor 1 (Smurf1). In vivo, short hairpin (sh)-MIR17HG and ACVR1 inhibitors profoundly attenuated HCC cell growth and metastasis by rectifying the imbalance of TGF-β1/BMP-7 pathways. Therefore, we proposed that the imbalance of TGF-β1/BMP-7 pathways is a feasible prognostic biomarker and recovering the imbalance of TGF-β1/BMP-7 pathways might be a potential therapeutic strategy for HCC.
Abstract 16821: Comparison of 4 Years Clinical Outcome of Drug-Eluting Stent Implantation in High-Angled (≥70°) Bifurcation and Lower-Angled (≤70°) Bifurcation Lesion of Unprotected Left Main Coronary Arteries
Authors: Sunao Nakamura, Hisao Ogawa, Jang-Ho Bae, Yeo H Cahyadi, Wasan Udayachalerm, Damras Tresukosol, Sudaratana Tansuphaswadikul
Journal: Circulation (2010)

Background: The use of drug-eluting stent (DES) is associated with excellent clinical results in left main bifurcation lesions. However, there is limited angiographic and clinical follow-up data af...
Oxidized phosphatidylcholines found in multiple sclerosis lesions mediate neurodegeneration and are neutralized by microglia
Authors: Yifei Dong, Charlotte D’Mello, William Pinsky, Brian M. Lozinski, Deepak K. Kaushik, Samira Ghorbani, Dorsa Moezzi, Dennis Brown, Francisca C. Melo, Stephanie Zandee, Tina Vo, Alexandre Prat, Shawn N. Whitehead, V. Wee Yong
Journal: Nature Neuroscience (2021)
Development and Validation of Nomograms to Predict Local, Regional, and Distant Recurrence in Patients With Thin (T1) Melanomas
Authors: Mary-Ann El Sharouni, Tasnia Ahmed, Alexander H. R. Varey, Sjoerd G. Elias, Arjen J. Witkamp, Vigfús Sigurdsson, Karijn P. M. Suijkerbuijk, Paul J. van Diest, Richard A. Scolyer, Carla H. van Gils, John F. Thompson, Willeke A. M. Blokx, Serigne N. Lo
Journal: Journal of Clinical Oncology (2021)

Although the prognosis of patients with thin primary cutaneous melanomas (T1, ≤ 1.0 mm) is generally excellent, some develop recurrence. We sought to develop and validate a model predicting recurrences in patients with thin melanomas.A Dutch population-based cohort (n = 25,930, development set) and a cohort from an Australian melanoma treatment center (n = 2,968, validation set) were analyzed (median follow-up 6.7 and 12.0 years, respectively). Multivariable Cox models were generated for local, regional, and distant recurrence-free survival (RFS). Discrimination was assessed using Harrell's C-statistic for each outcome. Each nomogram performance was evaluated using calibration plots defining low-risk and high-risk groups as the lowest and top 5% of the nomogram risk score, respectively. The nomograms' C-statistics were compared with those of a model including the current American Joint Committee on Cancer staging parameters (T-stage and sentinel node status).Local, regional, and distant recurrences were found in 209 (0.8%), 503 (1.9%), and 203 (0.8%) Dutch patients, respectively, and 23 (0.8%), 61 (2.1%), and 75 (2.5%) Australian patients, respectively. C-statistics of 0.79 (95% CI, 0.75 to 0.82) for local RFS, 0.77 (95% CI, 0.75 to 0.78) for regional RFS, and 0.80 (95% CI, 0.77 to 0.83) for distant RFS were obtained for the development model. External validation showed C-statistics of 0.80 (95% CI, 0.69 to 0.90), 0.76 (95% CI, 0.70 to 0.82), and 0.74 (95% CI, 0.69 to 0.80), respectively. Calibration plots showed a good match between predicted and observed rates. Using the nomogram, the C-statistic was increased by 9%-12% for the development cohort and by 11%-15% for the validation cohort, compared with a model including only T-stage and sentinel node status.Most patients with thin melanomas have an excellent prognosis, but some develop recurrence. The presented nomograms can accurately identify a subgroup at high risk. An online calculator is available at www.melanomarisk.org.au.
Randomized controlled study using text messages to help connect new medicaid beneficiaries to primary care
Authors: David M. Levine, Pragya Kakani, Ateev Mehrotra
Journal: npj Digital Medicine (2021)

Abstract Accessing primary care is often difficult for newly insured Medicaid beneficiaries. Tailored text messages may help patients navigate the health system and initiate care with a primary care physician. We conducted a randomized controlled trial of tailored text messages with newly enrolled Medicaid managed care beneficiaries. Text messages included education about the importance of primary care, reminders to obtain an appointment, and resources to help schedule an appointment. Within 120 days of enrollment, we examined completion of at least one primary care visit and use of the emergency department. Within 1 year of enrollment, we examined diagnosis of a chronic disease, receipt of preventive care, and use of the emergency department. 8432 beneficiaries (4201 texting group; 4231 control group) were randomized; mean age was 37 years and 24% were White. In the texting group, 31% engaged with text messages. In the texting vs control group after 120 days, there were no differences in having one or more primary care visits (44.9% vs. 45.2%; difference, −0.27%; p = 0.802) or emergency department use (16.2% vs. 16.0%; difference, 0.23%; p = 0.771). After 1 year, there were no differences in diagnosis of a chronic disease (29.0% vs. 27.8%; difference, 1.2%; p = 0.213) or appropriate preventive care (for example, diabetes screening: 14.1% vs. 13.4%; difference, 0.69%; p = 0.357), but emergency department use (32.7% vs. 30.2%; difference, 2.5%; p = 0.014) was greater in the texting group. Tailored text messages were ineffective in helping new Medicaid beneficiaries visit primary care within 120 days.
50 Years of Behavioral Science in Diabetes: A 2020 Vision of the Future
Authors: Mary de Groot
Journal: Diabetes Care (2021)

This article is adapted from a speech Dr. de Groot delivered in June 2020 as President, Health Care &amp; Education, of the American Diabetes Association at the Association’s 80th Scientific Sessions, which was held online as a result of coronavirus disease 2019. Dr. de Groot is an Associate Professor of Medicine in the Division of Endocrinology, Diabetes and Metabolism at Indiana University (IU) School of Medicine. She serves as the Acting Director of the IU Diabetes Translational Research Center. Dr. de Groot is the 2020 recipient of the Rachmiel Levine Medal for Leadership from the American Diabetes Association. In the year 2020, we marked the 50th anniversary of the field of behavioral science in diabetes in the modern era. Over this relatively short period of time, this field has charted the psychosocial landscape of prediabetes and diabetes by establishing the prevalence and impact of emotional and behavioral aspects of diabetes. Interventions to address these conditions have been developed that span the T2 to T4 translational research spectrum ranging from the intrapsychic to population-based interventions. Policies ranging from standards of care to Medicare benefits have been implemented. A review of research in the area of diabetes and depression is provided as an example of innovations in this field. Behavior is the foundation of all interventions we make in diabetes and prediabetes. As a mature science, it is critical to stemming the tide of diabetes and its outcomes. To make additional strides, we must rebalance our focus and augment funding for behavioral interventions for individuals, communities, and health care systems in conjunction with other forms of treatment.
Fertility restoration in azoospermic cancer survivors from testicular VSELs that survive oncotherapy upon transplanting MSCs
Authors: Deepa Bhartiya, Indira Hinduja
Journal: Human Reproduction Update (2021)

Sir We read with great interest progress in the field of oncofertility for young pre-pubertal boys where sperm banking is not possible. Wyns et al. (2020) have comprehensively summarized progress made in the field of cryobanking immature testicular tissue (ITT) followed by either culture in vitro or autografting to obtain sperm for assisted reproduction. Culture of ITT has resulted in spermatogenesis, sperm and live births in mice but has not yet been successful in humans. Auto- or xenograft of the testicular tissue pieces allows an intact niche for the stem cells to differentiate into sperm. This approach has been successful and complete spermatogenesis has been reported in several animal species. Offspring have been obtained with sperm recovered from the grafts using ICSI but no significant breakthrough has yet been achieved in case of humans, although hope exists. However, the review from Wyns et al. does not cover progress made on...
Avacopan for the Treatment of ANCA-Associated Vasculitis
Authors: David R.W. Jayne, Peter A. Merkel, Thomas J. Schall, Pirow Bekker
Journal: New England Journal of Medicine (2021)

The C5a receptor inhibitor avacopan is being studied for the treatment of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.