tbuckley/cabot-search huggingface dataset:
Association of the Paediatric Admission Quality of Care score with mortality in Kenyan hospitals: a validation study
Authors: Charles Opondo, Elizabeth Allen, Jim Todd, Mike English
Journal: The Lancet Global Health (2018)

BackgroundMeasuring the quality of hospital admission care is essential to ensure that standards of practice are met and continuously improved to reduce morbidity and mortality associated with the illnesses most responsible for inpatient deaths. The Paediatric Admission Quality of Care (PAQC) score is a tool for measuring adherence to guidelines for children admitted with acute illnesses in a low-income setting. We aimed to explore the external and criterion-related validity of the PAQC score by investigating its association with mortality using data drawn from a diverse sample of Kenyan hospitals.MethodsWe identified children admitted to Kenyan hospitals for treatment of malaria, pneumonia, diarrhoea, or dehydration from datasets from three sources: an observational study, a clinical trial, and a national cross-sectional survey. We extracted variables describing the process of care provided to patients at admission and their eventual outcomes from these data. We applied the PAQC scoring algorithm to the data to obtain a quality-of-care score for each child. We assessed external validity of the PAQC score by its systematic replication in datasets that had not been previously used to investigate properties of the PAQC score. We assessed criterion-related validity by using hierarchical logistic regression to estimate the association between PAQC score and the outcome of mortality, adjusting for other factors thought to be predictive of the outcome or responsible for heterogeneity in quality of care.FindingsWe found 19 065 eligible admissions in the three validation datasets that covered 27 hospitals, of which 12 969 (68%) were complete cases. Greater guideline adherence, corresponding to higher PAQC scores, was associated with a reduction in odds of death across the three datasets, ranging between 9% (odds ratio 0·91, 95% CI 0·84–0·99; p=0·031) and 30% (0·70, 0·63–0·78; p<0·0001) adjusted reduction per unit increase in the PAQC score, with a pooled estimate of 17% (0·83, 0·78–0·89; p<0·0001). These findings were consistent with a multiple imputation analysis that used information from all observations in the combined dataset.InterpretationThe PAQC score, designed as an index of the technical quality of care for the three commonest causes of admission in children, is also associated with mortality. This finding suggests that it could be a meaningful summary measure of the quality of care for common inpatient conditions and supports a link between process quality and outcome. It might have potential for application in low-income countries with similar disease profiles and in which paediatric practice recommendations are based on WHO guidelines.FundingThe Wellcome Trust.
Protein kinases G are essential downstream mediators of the antifibrotic effects of sGC stimulators
Authors: Alexandru-Emil Matei, Christian Beyer, Andrea-Hermina Györfi, Alina Soare, Chih-Wei Chen, Clara Dees, Christina Bergmann, Andreas Ramming, Andreas Friebe, Franz Hofmann, Oliver Distler, Georg Schett, Jörg H W Distler
Journal: Annals of the Rheumatic Diseases (2018)

Stimulators of soluble guanylate cyclase (sGC) are currently investigated in clinical trials for the treatment of fibrosis in systemic sclerosis (SSc). In this study, we aim to investigate the role of protein kinases G (PKG) as downstream mediators of sGC-cyclic guanosine monophosphate (cGMP) in SSc.Mice with combined knockout of PKG1 and 2 were challenged with bleomycin and treated with the sGC stimulator BAY 41-2272. Fibroblasts were treated with BAY 41-2272 and with the PKG inhibitor KT 5823.PKG1 and 2 are upregulated in SSc in a transforming growth factor-β1 (TGFβ1)-dependent manner, as an attempt to compensate for the decreased signalling through the sGC-cGMP-PKG pathway. Inhibition or knockout of PKG1 and 2 abrogates the inhibitory effects of sGC stimulation on fibroblast activation in a SMAD-independent, but extracellular signal-regulated kinase (ERK)-dependent manner. In vivo, sGC stimulation fails to prevent bleomycin-induced fibrosis in PKG1 and 2 knockout mice.Our data provide evidence that PKGs are essential mediators of the antifibrotic effects of sGC stimulators through interfering with non-canonical TGFβ signalling. TGFβ1 promotes its profibrotic effects through inhibition of sGC-cGMP-PKG signalling, sGC stimulation exerts its antifibrotic effects by inhibition of TGFβ1-induced ERK phosphorylation.
Abstract 10832: Variability of LDL-C Lowering Responses to Statin Therapy in Achievement of ACC/AHA Target Levels
Authors: Peter P Toth, Harold Bays, Michel Farnier, Erin Jensen, Joanne Tomassini, Adam Polis, JoAnne Foody, Andrew Tershakovec
Journal: Circulation (2015)

Objective: The recently published ACC/AHA 2013 cholesterol guidelines do not specify lipid target levels, but rather treatment of patients classified by cardiovascular risk to achieve LDL-C reductions of ≥50% and ≥30 - &lt;50% with high and moderate intensity statin therapy respectively. This analysis evaluated the variability of treatment responses to statin therapy for these parameters in statin-naïve patients with hypercholesterolemia (HC). Methods: Data pooled from 14 randomized, controlled, double-blind clinical trials in HC patients were categorized per the 4 risk groups specified by ACC/AHA 2013 guidelines: 1) atherosclerotic cardiovascular disease (ASCVD), 2) baseline LDL-C &gt;190 mg/dL, 3) diabetes (DM) and 4) 10 year ASCVD risk ≥7.5% (no ASCVD or DM). Mean % change from baseline in LDL-C, the percentage of patients who attained LDL-C reductions of ≥50% and ≥30 - &lt;50% and variability of LDL-C lowering responses on recommended therapy among risk groups were assessed. Results: Mean % LDL-C changes from baseline ranged from -49.5 to -52.2% and -37.7 to -40.5% on high and moderate intensity statins, respectively across risk groups (Figure). The percentages of patients who achieved LDL-C reductions of ≥50% on high intensity statins were 62 - 70%, and who attained reductions ≥30 - &lt;50% were 52 - 60% (77 - 89% for ≥30%) on moderate intensity therapy. The variability of % changes from baseline in LDL-C (SE = 0.7 to 2.1) and proportions of patients who achieved target LDL-C reductions were generally similar across risk groups for high and medium intensity statins. Conclusion: In this analysis, only 2/3 of patients achieved LDL-C reductions ≥50% on high intensity statins and ~80% of patients attained reductions ≥30% on moderate statin therapy. These results highlight the importance of assessing the response of patients to cholesterol lowering therapy when following the AHA/ACC guidelines and consideration of alternatives for those patients in need of greater LDL-C lowering.
Diverse genetic-driven immune landscapes dictate tumor progression through distinct mechanisms
Authors: Marco Bezzi, Nina Seitzer, Tomoki Ishikawa, Markus Reschke, Ming Chen, Guocan Wang, Caitlin Mitchell, Christopher Ng, Jesse Katon, Andrea Lunardi, Sabina Signoretti, John G Clohessy, Jiangwen Zhang, Pier Paolo Pandolfi
Journal: Nature Medicine (2018)
Prevention of Attacks of Hereditary Angioedema (HAE) with Subcutaneous C1-Esterase Inhibitor (C1-INH [SC]) by Anatomical Location: Results From the Phase III COMPACT Study (NCT01912456)
Authors: Donald S. Levy, Joseph Chiao, Henrike Feuersenger, Timothy Craig, Hilary J. Longhurst, Marco Cicardi, Bruce L. Zuraw, Iris Jacobs
Journal: Journal of Allergy and Clinical Immunology (2018)
Genetic Background of Iris Melanomas and Iris Melanocytic Tumors of Uncertain Malignant Potential
Authors: Natasha M. van Poppelen, Jolanda Vaarwater, Hardeep S. Mudhar, Karen Sisley, Ian G. Rennie, Paul Rundle, Tom Brands, Quincy C.C. van den Bosch, Hanneke W. Mensink, Annelies de Klein, Emine Kiliç, Robert M. Verdijk
Journal: Ophthalmology (2018)
Disease Severity and Baseline Characteristics of Patients Receiving Mepolizumab or Omalizumab in Employer Claims Database: A real-world experience
Authors: Beth Hahn, Jean-Pierre Llanos-Ackert, Hector Ortega, Elizabeth Packnett, Debra Irwin, Ellen Riehle, Christina Chebili, Christopher Bell
Journal: Journal of Allergy and Clinical Immunology (2018)
Controlled attenuation parameter and alcoholic hepatic steatosis: Diagnostic accuracy and role of alcohol detoxification
Authors: Maja Thiele, Vanessa Rausch, Gabriele Fluhr, Maria Kjærgaard, Felix Piecha, Johannes Mueller, Beate Katharina Straub, Monica Lupșor-Platon, Victor De-Ledinghen, Helmut Karl Seitz, Sönke Detlefsen, Bjørn Madsen, Aleksander Krag, Sebastian Mueller
Journal: Journal of Hepatology (2018)
Extracellular Vesicles Provide a Means for Tissue Crosstalk during Exercise
Authors: Martin Whitham, Benjamin L. Parker, Martin Friedrichsen, Janne R. Hingst, Marit Hjorth, William E. Hughes, Casey L. Egan, Lena Cron, Kevin I. Watt, Rhiannon P. Kuchel, Navind Jayasooriah, Emma Estevez, Tim Petzold, Catherine M. Suter, Paul Gregorevic, Bente Kiens, Erik A. Richter, David E. James, Jørgen F.P. Wojtaszewski, Mark A. Febbraio
Journal: Cell Metabolism (2018)
Safety and Efficacy of Ruxolitinib (rux) in an Open-Label, Multicenter, Expanded Treatment Protocol in Patients (Pts) with Polycythemia Vera (PV) Who Are Hydroxyurea (HU) Resistant or Intolerant and for Whom No Alternative Treatments Are Available
Authors: Timothy Devos, Gian Matteo Pica, Hacene Zerazhi, Jan Van Droogenbroeck, Sorin Visanica, Enrique Báez de la Fuente, Brian Leber, Antonio Medina de Almeida, Dana Ranta, Tomasa Martinez, Jean-Jacques Kiladjian, Linda Chrit, Zhaoyu Yin, Julian Perez Ronco, Lynda Foltz
Journal: Blood (2017)
Myopia Prevention and Outdoor Light Intensity in a School-Based Cluster Randomized Trial
Authors: Pei-Chang Wu, Chueh-Tan Chen, Ken-Kuo Lin, Chi-Chin Sun, Chien-Neng Kuo, Hsiu-Mei Huang, Yi-Chieh Poon, Meng-Ling Yang, Chau-Yin Chen, Jou-Chen Huang, Pei-Chen Wu, I-Hui Yang, Hun-Ju Yu, Po-Chiung Fang, Chia-Ling Tsai, Shu-Ti Chiou, Yi-Hsin Yang
Journal: Ophthalmology (2018)
Gasdermin D Flashes an Exit Signal for IL-1
Authors: Teneema Kuriakose, Thirumala-Devi Kanneganti
Journal: Immunity (2018)

The IL-1 family of cytokines follows an unconventional pathway of secretion mostly associated with inflammatory cell death. In this issue of Immunity, (Evavold et al., 2017) report gasdermin D pores as channels for active IL-1 release in live phagocytic cells.
Daratumumab, Bortezomib, and Dexamethasone (DVd) Versus Bortezomib and Dexamethasone (Vd) in Relapsed or Refractory Multiple Myeloma (RRMM): Updated Efficacy and Safety Analysis of Castor
Authors: Andrew Spencer, Vania T M Hungria, Maria-Victoria Mateos, Ajay Nooka, Jane Estell, Wolney G Barreto, Paolo Corradini, Chang-Ki Min, Eva Medvedova, Piruntha Thiyagarajah, William Deraedt, Christopher Chiu, Jordan Schecter, Katja C. Weisel
Journal: Blood (2017)
Combination of BR101801 and Venetoclax Demonstrates Synergistic Activity in DLBCL Cell Lines Harboring Double Hit and Double Expressor Alterations
Authors: Hahn-Sun Jung, Nam Hoon Kim, Jinsang Wang, Mi Kwon Son, Baek-Kyung Kim, Byeongwook Jeon, Yeonseo Choi, Jayhyuk Myung, Dal-Hyun Kim
Journal: Blood (2017)
Inverse Correlation of Vδ2-T-Cell Recovery with EBV Reactivation after Haploidentical Hematopoietic Stem Cell Transplantation
Authors: Jiangying Liu, Bian Zhilei, Xiaoyu Wang, Lan-Ping Xu, Qiang Fu, Ying-Jun Chang, Yu Wang, Xiaohui Zhang, Xiao-Jun Huang
Journal: Blood (2017)
IMC-A12 enhances the efficacy of cetuximab + gemcitabine therapy in human pancreatic carcinoma xenografts.
Authors: Marie Prewett, Christopher Damoci, Rajiv Bassi, Dale Ludwig, Daniel Hicklin, James Tonra
Journal: Cancer Research (2007)

652  The epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF-1R) pathways play an important role in growth and survival of pancreatic tumor cells. We have previously demonstrated the efficacy of the fully human IgG1 anti-EGFR mAb cetuximab in combination with gemcitabine in preclinical models of pancreatic carcinoma. In this study, we studied the antitumor activity of the human IgG1 anti-IGF-1R mAb IMC-A12 when combined with cetuximab + gemcitabine in human pancreatic tumor xenograft models. Mice bearing established BxPC-3, L3.7pL, or MiaPaCa-2 pancreatic xenografts were treated with 1) IMC-A12 (40mg/kg, i.p., 3x/week), 2) cetuximab (40mg/kg, i.p., 3x/week), 3) gemcitabine (150mg/kg, i.p., q7d), 4) cetuximab + gemcitabine, or 5) IMC-A12 + cetuximab + gemcitabine. IMC-A12 had significant efficacy in BxPC-3 and MiaPaCa-2 (T/C% = 41% and 37%, respectively) but minimal efficacy in the L3.7pL model (T/C% = 91%). Cetuximab + gemcitabine therapy had significant efficacy in all three models (T/C% = 17%, 23%, and 46% for BxPC-3, L3.7pL, and MiaPaCa-2, respectively). Adding IMC-A12 to cetuximab + gemcitabine therapy significantly increased the anti-tumor effects (P
Interest in the Ketogenic Diet Grows for Weight Loss and Type 2 Diabetes
Authors: Jennifer Abbasi
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 11595: Predicting Appropriate Shocks In Patients With Heart Failure: Patient Level Meta-analysis From SCD-HeFT and Madit II
Authors: Emily P Zeitler, Sana M Al-Khatib, Daniel J Friedman, Joo Yoon Han, Gust H Bardy, J. T Bigger, Alfred E Buxton, Arthur J Moss, Kerry L Lee, Richard Steinman, Paul Dorian, Alfred Hallstrom, Riccardo Cappato, Alan H Kadish, Peter J Kudenchuk, Daniel B Mark, Lurdes Y Inoue, Gillian D Sanders
Journal: Circulation (2016)

Background: Some patients implanted with a primary prevention implantable cardioverter defibrillator (ICD) due to heart failure receive an appropriate shock, but no precise tools exist to predict this outcome. Methods: Using patient level data from the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), we identified patients with any appropriate ICD shock. A variety of clinical and demographic variables were included in a logistic regression model to predict appropriate ICD shocks (Table). Results: There were 1,463 patients randomized to ICD from the two included trials; 285 (19%) had ≥1 appropriate shock over a median follow up of 2.59 years. Compared with patients with no appropriate shocks, patients who received any appropriate ICD shock tended to have NYHA class II or III heart failure symptoms, beta blocker therapy, lower LVEF, wider QRS duration, and a single versus dual chamber ICD (79% of all patients had a single chamber ICD). Other comorbidities were similar between groups. Significant independent predictors of appropriate ICD shocks included NYHA class (NYHA II vs I: OR 1.65, 95% CI 1.07-2.55; NYHA III vs I: OR 1.74, 95% CI 1.10-2.76), LVEF based on one unit change (higher vs lower LVEF: OR 0.96, 95% CI 0.94-0.98), beta blocker therapy (presence vs absence: OR 0.96, 95% CI 0.94-0.98), and single chamber ICD (OR 1.67, 95% CI 1.13-2.45). Conclusion: In this meta-analysis of patient level data from MADIT-II and SCD-HeFT, appropriate ICD shocks were significantly predicted by NYHA class, LVEF, beta blocker therapy, and single chamber ICD. There is a compelling need for a large, prospective study to better define the risk of appropriate ICD shocks in patients meeting criteria for a primary prevention ICD. Until such time, stratification of patients by these factors may better define risk for potentially mortal rhythm events that might be prevented by a primary prevention ICD.
Monthly Buprenorphine Injection Approved for Opioid Use Disorder
Authors: Rebecca Voelker
Journal: JAMA (2018)

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
Results of a phase 1 study of single agent RX-3117: An oral antimetabolite nucleoside to treat solid tumors.
Authors: Drew W. Rasco, Christine Peterson, Reza Mazhari, Ely Benaim, Jaime R. Merchan
Journal: Journal of Clinical Oncology (2016)

2555 Background: RX-3117 is an oral small-molecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by uridine cytidine kinase 2. RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. Emerging data from a Phase 1 clinical study of RX-3117 as a single agent in subjects with solid tumors is described below. Methods: The Phase 1 study (NCT02030067) is designed to evaluate safety, tolerability and pharmacokinetics (PK) following increasing doses and schedules of RX-3117 in eligible subjects (aged ≥ 18 years) with relapsed/refractory solid tumors. Primary objectives include safety and tolerability to determine the MTD and a recommended phase 2 dose and schedule (RP2D); secondary objectives were PK and antitumor activity (RECIST v1.1). Subjects received oral RX-3117 3, 5 or 7 times per week for 3 weeks followed by 1 week of rest or 4 weeks without a rest for up to 8 cycles. Plasma concentrations were measured using a validated LC-MS/MS assay, and noncompartmental pharmacokinetic parameters were calculated using WinNonlin, Version 6.4. Results: As of Jan 2016, 41 subjects have been enrolled (26 Females, 15 males). Eleven subjects experienced stable disease for 1 to 10 cycles; with 7 subjects receiving treatment from 104 to 276 days. A tumor burden reduction was seen in 3 subjects with pancreatic, breast and mesothelioma cancers. RX-3117 PK demonstrated a dose proportional exposure and was rapidly absorbed without a marked lag time, and with a median Tmax between 2 to 3 hours; accumulation was generally minimal. The most frequent related adverse events were moderate to severe anemia, mild to moderate fatigue and nausea, mild diarrhea, vomiting, and anorexia. Dose limiting toxicity of anemia was observed at 2000 mg administered 3 times per week. The recommended phase 2 dose and schedule will be 700 mg 5 times per week. Conclusions: Data from this study RX-3117 is safe and well tolerated at the doses and schedules tested. Early anti-tumor activity has been observed in pancreas, colorectal and mesothelioma cancers. A 2 stage Phase 2A design for pancreatic and bladder cancers is ongoing. Clinical trial information: NCT02030067.
Therapeutic effects of gefitinib-encapsulated thermosensitive injectable hydrogel in intervertebral disc degeneration
Authors: Zongyou Pan, Heng Sun, Binbin Xie, Dongdong Xia, Xiaoan Zhang, Dongsheng Yu, Jun Li, Yuzi Xu, Zuhua Wang, Yan Wu, Xiaolei Zhang, Yafei Wang, Qianbao Fu, Wei Hu, Yang Yang, Varitsara Bunpetch, Weiliang Shen, Boon Chin Heng, Shufang Zhang, Hongwei Ouyang
Journal: Biomaterials (2018)
Comparing the Outcomes of Sleeve Gastrectomy and Roux-en-Y Gastric Bypass for Severe Obesity
Authors: David Arterburn, Anirban Gupta
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal