tbuckley/cabot-search huggingface dataset:
Prediction Models for Suicide Attempts and Deaths
Authors: Bradley E. Belsher, Derek J. Smolenski, Larry D. Pruitt, Nigel E. Bush, Erin H. Beech, Don E. Workman, Rebecca L. Morgan, Daniel P. Evatt, Jennifer Tucker, Nancy A. Skopp
Journal: JAMA Psychiatry (2019)

Suicide prediction models have the potential to improve the identification of patients at heightened suicide risk by using predictive algorithms on large-scale data sources. Suicide prediction models are being developed for use across enterprise-level health care systems including the US Department of Defense, US Department of Veterans Affairs, and Kaiser Permanente.To evaluate the diagnostic accuracy of suicide prediction models in predicting suicide and suicide attempts and to simulate the effects of implementing suicide prediction models using population-level estimates of suicide rates.A systematic literature search was conducted in MEDLINE, PsycINFO, Embase, and the Cochrane Library to identify research evaluating the predictive accuracy of suicide prediction models in identifying patients at high risk for a suicide attempt or death by suicide. Each database was searched from inception to August 21, 2018. The search strategy included search terms for suicidal behavior, risk prediction, and predictive modeling. Reference lists of included studies were also screened. Two reviewers independently screened and evaluated eligible studies.From a total of 7306 abstracts reviewed, 17 cohort studies met the inclusion criteria, representing 64 unique prediction models across 5 countries with more than 14 million participants. The research quality of the included studies was generally high. Global classification accuracy was good (≥0.80 in most models), while the predictive validity associated with a positive result for suicide mortality was extremely low (≤0.01 in most models). Simulations of the results suggest very low positive predictive values across a variety of population assessment characteristics.To date, suicide prediction models produce accurate overall classification models, but their accuracy of predicting a future event is near 0. Several critical concerns remain unaddressed, precluding their readiness for clinical applications across health systems.
Association of Patisiran, an RNA Interference Therapeutic, With Regional Left Ventricular Myocardial Strain in Hereditary Transthyretin Amyloidosis
Authors: Masatoshi Minamisawa, Brian Claggett, David Adams, Arnt V. Kristen, Giampaolo Merlini, Michel S. Slama, Angela Dispenzieri, Amil M. Shah, Rodney H. Falk, Verena Karsten, Marianne T. Sweetser, Jihong Chen, Richard Riese, John Vest, Scott D. Solomon
Journal: JAMA Cardiology (2019)

Patients with cardiac amyloidosis demonstrate reduced myocardial strain with associated sparing of the cardiac apex. In the APOLLO randomized clinical trial, patisiran, an RNA interference therapeutic that inhibits transthyretin synthesis, improved left ventricular (LV) global longitudinal strain (LV GLS) compared with placebo in patients with hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy and evidence of cardiac involvement.To evaluate the treatment association of patisiran with regional LV myocardial strain in cardiac manifestation in hATTR amyloidosis.This exploratory analysis of APOLLO, a randomized, double-blind, placebo-controlled, phase 3, multicenter international clinical trial that was conducted from December 2013 to January 2016, included patients with hATTR amyloidosis with polyneuropathy who were randomized 2:1 to receive patisiran or placebo. The prespecified cardiac subpopulation (126 of 225 [56%]) comprised patients with a baseline LV wall thickness of 13 mm or more and no history of hypertension or aortic valve disease. This post hoc data analysis was performed between September 2018 and January 2019.Placebo or patisiran, 0.3 mg/kg, via intravenous infusion once every 3 weeks for 18 months.The association of patisiran with LV regional longitudinal strain at 18 months.Of the 126 patients included in the prespecified cardiac subpopulation, 36 patients (28.6%) received placebo (median [interquartile range] age, 62 [57-72] years) and 90 patients (71.4%) received patisiran (median [interquartile range] age, 60 [54-66] years); 98 (77.8%) were men, 28 (22.2%) were from North America, and 43 (34.1%) were from Western Europe. At baseline, LV GLS was impaired and regional longitudinal strains were lowest in the basal segments with apical sparing. There were no differences in regional longitudinal strains between the treatment groups at baseline. Patisiran improved the absolute GLS (least-squares mean [SE] difference, 1.4% [0.6%]; 95% CI, 0.3%-2.5%; P = .02) compared with placebo at 18 months, with the greatest differential increase observed in the basal region (overall least-squares mean [SE] difference, 2.1% [0.8%]; 95% CI, 0.6%-3.6%; P = .006) and no significant differences in the mid and apical regions among groups.Patisiran prevented the deterioration of LV GLS over 18 months, driven primarily by attenuating disease progression in the basal region, suggesting that basal longitudinal strain may be a more sensitive marker of treatment associations with the cardiac manifestation in hATTR amyloidosis and that basal region may be influenced by disease-modifying therapies more than other ventricular regions.ClinicalTrials.gov identifier: NCT01960348.
Population-based assessment of surrogate endpoints (SE) in stage I-III colon (CCa) and rectal cancers (RCa).
Authors: Richard M. Lee-Ying, Caroline Speers, Gillian Gresham, Yarrow Jean McConnell, Winson Y. Cheung, Hagen F. Kennecke
Journal: Journal of Clinical Oncology (2015)

3538 Background: In adjuvant CCa trials, 3 year disease free survival (3Y DFS) is a validated SE of 5 year overall survival (5Y OS), but this SE is less established in RCa. Effective systemic therapies introduced since 2004 may diminish the association between 3Y DFS and 5Y OS. The objective of this study was to measure SE in CCa and RCa in a population based setting, stratifying by tumor stage and era of diagnosis. Methods: Patients diagnosed with stage I-III CCa and RCa referred to any 1 of 5 regional cancer centers in British Columbia between 1990 and 2009 were followed by the GI Outcomes Unit. Clinical, pathological, and treatment characteristics were prospectively collected. R2 resections and early relapses were excluded. Relapses were classified as loco regional (LR) or distant. DFS and OS were measured from the date of definitive surgery until relapse or death. Correlation between DFS and OS endpoints was determined using Pearson’s r coefficients. Hazard ratios (HR) were generated using multivariate Cox regression and compared between DFS and OS. 5Y OS HR was compared to calculated 5Y OS using 3Y DFS rates and the validated SE model. Results: Of 9147 referred patients with early stage CCa or RCa, 9031 were eligible, with 5357 CCa and 3674 RCa. The median age was 67, 55% were male, 17/34/49% had stage I/II/III disease, respectively, 51% received adjuvant chemotherapy and 87% of RCa received radiation. There were 2494 (28%) relapses of which 90% were distant. The correlation between HR for DFS and OS, 3Y DFS and 5Y OS, and 3Y LR DFS and 5Y OS were all very strong in the total population, for CCa and RCa, across stages and eras (Table 1). Predicted 5Y OS HR were similar to the observed HR where all estimates fell within the observed confidence intervals. Conclusions: A strong association between 3Y DFS and 5Y OS was observed in this population-based cohort, which did not differ between CCa and RCa. Correlations remained significant when stratified by tumor stage and treatment era. 3Y LR DFS was a strong surrogate of 5Y OS in RCa. Pearson's r. DFS vs OS 3Y DFS vs 5Y OS 3Y LR DFS vs 5Y OS All 0.93 0.84 0.87 CCa 0.93 0.83 0.87 RCa 0.92 0.84 0.87 Stage I 0.96 0.86 0.88 II 0.94 0.81 0.85 III 0.92 0.84 0.88 Era ≤ 2004 0.94 0.85 0.87 > 2004 0.90 0.82 0.87
FOLFOXIRI with or without bevacizumab as first-line treatment for unresectable liver-only metastatic colorectal cancer patients with RAS mutation-type.
Authors: Yanhong Deng, Huabin Hu, Guanjian Liu, Yue Cai, Jianwei Zhang, Meijin Huang, Lei Wang, Lan Ping, Jianping Wang
Journal: Journal of Clinical Oncology (2015)

TPS3624 Background: For liver limited metastatic colorectal cancers, complete resection of liver metastases is the only potentially curative treatment and can significantly improve overall survival. The current goal of medical treatment for colorectal cancer with initially unresectable liver metastases is to maximize the rate of secondary resection. This phase II study is to explore whether FOLFOXIRI plus bevacizumab compared with FOLFOXIRI alone as first-line treatment could improve radical resectability in patients with RAS mutaion-type, unresectable liver-only metastatic colorectal cancer. Methods: The primary endpoint is the conversion rate of liver metastases, which is defined as the proportion of patients who had a curative liver treatment following protocol treatment, i.e., liver metastases that can be radical resected with or without ablation with no postoperative evidence of residual malignant disease. Secondary endpoints include safety, objective response rate, overall survival, progression free survival, quality of life and an assessment of predictive molecular markers of response. 160 cases of patients meet inclusion criteria and are enrolled in the trial will be randomized to two therapy groups: experimental arm A (FOLFOXIRI plus bevacizumab) or control arm B (FOLFOXIRI alone) in a 1:1 allocation ratio, stratifying for centers, ECOG status, synchronous or metachronous metastases, and a risk score derived from Nordlinger. All patients will receive the study treatment regimen every 2 weeks, and a total of the maximum of 12 cycles. CT scan or MRI of the abdomen will be performed after 2 or 3 cycles of therapy to assess clinical response and resectability of liver metastases by multidisciplinary team including hepatic surgeon. If liver metastases are not deemed to be resectable at this assessment, but tumor assessment demonstrates stable disease or partial response, therapy will continue with re-assessment for clinical response and resectability after the next cycle. Clinical trial information: NCT02350530.
Evaluation of a genomic classifier in primary tumor and lymph node metastases in pre- and post-radical prostatectomy tissue specimens from patients with lymph node positive prostate cancer.
Authors: Hak J. Lee, Elana Godebu, Omer Raheem, Song Wang, Kasra Yousefi, Lucia L.C. Lam, Zaid Haddad, Mohammed Alshalalfa, Elai Davicioni, Ahmed Shabaik, Christopher J. Kane
Journal: Journal of Clinical Oncology (2015)

e16087 Background: Genomic Classifiers (GC) are in common use to predict outcomes for men with prostate cancer (PCA). The Decipher test is a validated genomic classifier (GC) that predicts early metastasis after radical prostatectomy (RP). We sought to evaluate whether the GC scores of pre-treatment diagnostic needle biopsy (Bx) and RP can actually predict the metastatic lesion in patients with lymph node positive (LN+) PCA. Methods: Twenty-five LN+ PCA pts who underwent RP and extended LN dissection from a single institution from 2001-2009 were identified and analyzed for genomic aberrations in Bx, prostate and LN samples. Tissue specimens for Bx, RP and LN were available for 13, 22 and 19 pts, respectively. GC results were calculated for a total of 62 patient specimens that passed quality control. Concordance of risk groups was performed using validated cut-points for low ( < 0.45), intermediate (0.45-0.6) and high ( > 0.6) GC score. PCA markers (ERG+, ETS+ or non-ETS/SPINK1+) were used to determine subtype and clonal relationship between Bx, RP and LN. Results: Pre-operatively, 91% of pts were NCCN high and very high-risk groups. Post-operatively, 77% of patients had Gleason ≥ 9 disease and 86% were pT3 or greater stage. Median GC in RP was 0.76 (IQR: 0.63 - 0.80) and 0.85 (IQR: 0.61-0.91) in LN. Median GC in Bx was 0.64 (IQR: 0.48-0.73) and the Bx with the highest Gleason grade and percent tumor cells had 86% concordance with both RP and LN GC risk. Forty-one percent were ERG+, 17% ETS+ and 39% non-ETS/SPINK1+ in prostate specimens. The clonal subtype in RP and LN tumors was the same in 83% of pts. Conclusions: In our cohort, most pts with LN metastases at RP were classified as high GC risk in Bx, RP and LN specimens. There was a high Bx to RP and LN genomic concordance of 86% in Bx specimens with highest Gleason grade and percent tumor cells. Predicting the presence of LN metastasis could be useful for accurate pre-treatment staging and optimization of radical, neo- and adjuvant therapy.
Abstract 013: Cumulative Socioeconomic Disadvantage Across Life Course and Risk of Hospitalization for Heart Failure or Atrial Fibrillation and Mediating Pathways: Prospective Findings From the Moli-Sani Study
Authors: Marialaura Bonaccio, Augusto Di Castelnuovo, Simona Costanzo, Amalia De Curtis, Mariarosaria Persichillo, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello
Journal: Circulation (2019)

Introduction: There is lack of data on the association of socioeconomic (SES) disadvantage experienced across life course with the risk of heart failure (HF) or atrial fibrillation (AF). Moreover, little is known on the mechanisms through which SES inequalities shape disease risk. Hypothesis: We assessed the hypothesis of an association between cumulative socioeconomic disadvantage (CSD) with risk of first hospitalization for HF or AF in a large general population-based cohort of Italians, and tested several sets of potential mediators in explaining such associations. Methods: Longitudinal analysis on 21,756 HF- or AF-free men and women (aged≥35 y) recruited in the Moli-sani Study cohort, Italy (2005-2010). A score to estimate CSD over life-course was computed by using childhood SES factors (hot water, overcrowding, housing), 3-level educational attainment, and adulthood SES indicators (occupation, overcrowding, housing). Five sets of pathways were tested as potential mediators: baseline health conditions, lifestyles, and traditional, inflammatory and novel markers of CVD risk (listed in Table). First hospital admissions were recorded by direct linkage with hospital discharge forms. Hazard ratios with 95% confidence intervals (95% CIs) were calculated using multivariable Cox-proportional hazard models. Results: Over a median follow up of 8.2 years, we recorded 836 and 504 admissions to hospital for HF and AF, respectively. A 1-point increment in CSD was associated with 16% and 6% increased risk of HF and AF, respectively. Risk estimates associated with highest CSD, as compared to lowest CSD group, were 2.55 (1.76-3.70) and 1.60 (1.08-2.38) for risk of HF and AF, respectively. Part of such associations was explained by novel biomarkers of CVD risk and baseline lifestyles (Table). Conclusions: HF and AF risks are shaped by cumulative socioeconomic disadvantage across the life course in a large Mediterranean population. Lifestyles and novel markers of CVD risk account for the largest proportion of such associations.
Immune pathomechanism and classification of drug hypersensitivity
Authors: Werner J. Pichler
Journal: Allergy (2019)

Abstract Drug hypersensitivity reactions ( DHR ) are based on distinct mechanisms and are clinically heterogeneous. Taking into account that also off‐target activities of drugs may lead to stimulations of immune or inflammatory cells, three forms of DHR were discriminated: the allergic‐immune mechanism relies on the covalent binding of drugs/chemicals to proteins, which thereby form new antigens, to which a humoural and/or cellular immune response can develop. In IgE‐mediated drug allergies, a possible tolerance mechanism to the drug during sensitization and the need of a covalent hapten‐carrier link for initiation, but not for elicitation of IgE‐mediated reactions is discussed. The p‐i (“pharmacological interaction with immune receptor”) concept represents an off‐target activity of drugs with immune receptors ( HLA or TCR ), which can result in unorthodox, alloimmune‐like stimulations of T cells. Some of these p‐i stimulations occur only in carriers of certain HLA alleles and can result in clinically severe reactions. The third form of DHR (“pseudo‐allergy”) is represented by drug interactions with receptors or enzymes of inflammatory cells, which may lead to their direct activation or enhanced levels of inflammatory products. Specific IgE or T cells are not involved. This classification is based on the action of drugs and is clinically useful, as it can explain differences in sensitizations, unusual clinical symptoms, dependence on drug concentrations, predictability and immunological and pharmacological cross‐reactivities in DHR .
Sites of metastasis (mets) and association with clinical outcomes (CO) in metastatic renal cell carcinoma (mRCC) patients (pts) treated with cabozantinib (cabo).
Authors: Dylan J Martini, Julie M. Shabto, Yuan Liu, Bradley Curtis Carthon, Alexandra Speak, Elise Hitron, Greta Russler, Sarah Caulfield, Kenneth Ogan, Wayne Harris, Viraj A. Master, Omer Kucuk, Mehmet Asim Bilen
Journal: Journal of Clinical Oncology (2019)

585 Background: Cabo is approved for the treatment for mRCC. We investigated the association of sites of mets and clinical outcomes (CO) in mRCC pts treated with cabo. Methods: We performed a retrospective analysis of 65 mRCC pts treated with cabo at Winship Cancer Institute from 2016 to 2018. Overall survival (OS) and progression-free survival (PFS) were measured from first dose of cabo to date of death and clinical or radiographic progression, respectively. Objective response was defined as a complete response (CR) or partial response (PR). Sites of mets were obtained from radiology and clinic notes and included bone, lymph node, brain, lung, and liver. Univariate analysis (UVA) and multivariate analysis (MVA) was performed using Cox proportional hazard or logistic regression model. Results: The median age was 63 years and most (68%) were males. The majority of pts (79%) had ccRCC and 48% received at least 2 prior systemic treatments. The distribution of mets were: bone (42%), lymph node (69%), brain (6%), lung (83%), and liver (40%). The UVA and MVA of association between sites of mets and CO are presented in Table. Pts with bone mets had significantly longer OS in UVA and trended towards longer OS and PFS in MVA compared to pts without bone mets. Conclusions: Bone mets may be a prognostic factor for improved CO in mRCC pts treated with cabo. Larger studies are needed to validate the results of this study. UVA and MVA† of bone metastases and CO. [Table: see text]
Single-Cell RNA Sequencing Discloses Distinct Transcriptomic Profiling in Essential Thrombocythemia
Authors: Chia-Chen Hsu, Cih-En Huang, Ying-Ju Chen, Yuying Wu, Hsing-Yi Tsou, Chian-Pei Li, Wei-Hsuan Chuang, Yi-Hua Lai, Yi-Hsuan Lin, Chih-Cheng Chen
Journal: Blood (2018)
Interpreting the Prognostic Value of Unrecognized Myocardial Infarction Among Older Adults—Reply
Authors: Tushar Acharya, Lenore Launer, Andrew E. Arai
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
Autism Risk and Serotonin Reuptake Inhibitors—Reply
Authors: Magdalena Janecka, Sven Sandin, Abraham Reichenberg
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
A phase 0/1 biomarker and pharmacodynamic study of roflumilast and prednisone in patients with B-cell hematologic malignancies.
Authors: Alex V Mejia, Ricardo Aguiar, Anand B. Karnad, John G. Kuhn, Ivan Alexander Reveles, Stephanie Hodges, Suhasini Avvaru, Sumit Madan, Kevin Kelly, Steven D. Weitman
Journal: Journal of Clinical Oncology (2015)

e13601 Background: Many B-cell malignancies are driven by the B-cell receptor (BCR). Therapeutic targeting of the BCR has been successfully implemented, but the limited number of complete responders and acquired resistance indicate the need for the development of novel strategies. We have previously shown that inhibition of phosphodiesterase 4 (PDE4) can inhibit the BCR activated pathways, namely SYK and PI3K-AKT, and reduce growth of B-cell malignancies. These observations resulted in a biomarker-focused clinical trial of Roflumilast (R), a PDE4 inhibitor, in patients with relapsed/refractory B-cell malignancies. Methods: The objectives of this study were to determine the pharmacodynamics of R on biomarkers of PDE4, safety, pharmacokinetics/pharmacogenomics (PK/PG), and efficacy. Ten patients (pts) with B-cell malignancies were treated with R (500 mcg) daily for 21 days and prednisone (60 mg/m2) on Days 8-14 for cycle 1. Blood was collected for assessment of biomarkers and for PK/PG. Adverse events (AE) and disease assessments were conducted throughout the study. Results: Ten pts were enrolled and treated (6-NHL, 2-CLL, 2-MM). The median number of cycles was 4 (1-13). Treatment was generally well tolerated with most AEs being grade 1 or 2. There was 1 PR and 5 pts with prolonged SD. The effects of R on AKT activity was analyzed in two CLL pts, a responder and a non-responder. In these assays, we found a correlation between clinical activity and suppression of phospho-AKT levels. Trough levels (Ctss) of R and its active n-oxide metabolite (RNO) were assessed (LC/MS) on Day 8. Mean Ctss (ng/mL) levels for R/RNO were 8.2 (2.2-17.4) & 37.2 (12-74.5). Conclusions: This biomarker study shows that it is possible to modulate AKT activity through inhibition of PDE4. Treatment was well tolerated and associated with clinical activity. Clinical trial information: NCT01888952.