tbuckley/cabot-search huggingface dataset:
Projected Prevalence of Actionable Pharmacogenetic Variants and Level A Drugs Prescribed Among US Veterans Health Administration Pharmacy Users
Authors: Catherine Chanfreau-Coffinier, Leland E. Hull, Julie A. Lynch, Scott L. DuVall, Scott M. Damrauer, Francesca E. Cunningham, Benjamin F. Voight, Michael E. Matheny, David W. Oslin, Michael S. Icardi, Sony Tuteja
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Implementation of pharmacogenetic testing to guide drug prescribing has potential to improve drug response and prevent adverse events. Robust data exist for more than 30 gene-drug pairs linking genotype to drug response phenotypes; however, it is unclear which pharmacogenetic tests, if implemented, would provide the greatest utility for a given patient population. <h3>Objectives</h3> To project the proportion of veterans in the US Veterans Health Administration (VHA) with actionable pharmacogenetic variants and evaluate how testing might be associated with prescribing decisions. <h3>Design, Setting, and Participants</h3> This cross-sectional study included veterans who used national VHA pharmacy services from October 1, 2011, to September 30, 2017. Data analyses began April 26, 2018, and were completed February 6, 2019. <h3>Exposures</h3> Receipt of level A drugs based on VHA pharmacy dispensing records. <h3>Main Outcomes and Measures</h3> Projected prevalence of actionable pharmacogenetic variants among VHA pharmacy users based on variant frequencies from the 1000 Genomes Project and veteran demographic characteristics; incident number of level A prescriptions, and proportion of new level A drug recipients projected to carry an actionable pharmacogenetic variant. <h3>Results</h3> During the study, 7 769 359 veterans (mean [SD] age, 58.1 [17.8] years; 7 021 504 [90.4%] men) used VHA pharmacy services. It was projected that 99% of VHA pharmacy users would carry at least 1 actionable pharmacogenetic variant. Among VHA pharmacy users, 4 259 153 (54.8%) received at least 1 level A drug with 1 188 124 (15.3%) receiving 2 drugs, and 912 189 (11.7%) receiving 3 or more drugs. The most common incident prescriptions during the study were tramadol (923 671 new recipients), simvastatin (533 928 new recipients), citalopram (266 952 new recipients), and warfarin (205 177 new recipients). Gene-drug interactions projected to have substantial clinical impacts in the VHA population include the interaction of<i>SLCO1B1</i>with simvastatin (1 988 956 veterans [25.6%]),<i>CYP2D6</i>with tramadol (318 544 veterans [4.1%]), and C<i>YP2C9</i>or<i>VKORC1</i>with warfarin (7 163 349 veterans [92.2%]). <h3>Conclusions and Relevance</h3> Clinically important pharmacogenetic variants are highly prevalent in the VHA population. Almost all veterans would carry an actionable variant, and more than half of the population had been exposed to a drug affected by these variants. These results suggest that pharmacogenetic testing has the potential to affect pharmacotherapy decisions for commonly prescribed outpatient medications for many veterans.
The Problem With Oxygen
Authors: Gaetan Sgro
Journal: Annals of Internal Medicine (2019)

Ad Libitum4 June 2019The Problem With OxygenGaetan Sgro, MDGaetan Sgro, MDVA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania (G.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M19-0357 Audio Reading - “The Problem With Oxygen” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “The Problem With Oxygen“ by Gaetan Sgro, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Paris 1945stings upon breaking the surface... Author, Article, and Disclosure InformationAffiliations: VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania (G.S.)Current Author Address: Gaetan Sgro, MD; e-mail, gaetan.[email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “The Problem With Oxygen” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “The Problem With Oxygen“ by Gaetan Sgro, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 4 June 2019Volume 170, Issue 11Page: 812KeywordsDustLungsMemoryOxygenPregnancyRiversStrokeThorax ePublished: 4 June 2019 Issue Published: 4 June 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Circadian rhythm of exhaled biomarkers in health and asthma
Authors: Maxim Wilkinson, Robert Maidstone, Andrew Loudon, John Blaikley, Iain R. White, Dave Singh, David W. Ray, Royston Goodacre, Stephen J. Fowler, Hannah J. Durrington
Journal: European Respiratory Journal (2019)

<b>Exhaled volatile chemicals and fractional exhaled nitric oxide oscillate over 24 h, highlighting the importance of time of day in diagnostic sampling and suggesting potential applications for chronotyping.</b>http://bit.ly/2YZGXbH
Optimal dose of selective serotonin reuptake inhibitors, venlafaxine, and mirtazapine in major depression: a systematic review and dose-response meta-analysis
Authors: Toshi A Furukawa, Andrea Cipriani, Philip J Cowen, Stefan Leucht, Matthias Egger, Georgia Salanti
Journal: The Lancet Psychiatry (2019)

Depression is the single largest contributor to non-fatal health loss worldwide. Second-generation antidepressants are the first-line option for pharmacological management of depression. Optimising their use is crucial in reducing the burden of depression; however, debate about their dose dependency and their optimal target dose is ongoing. We have aimed to summarise the currently available best evidence to inform this clinical question.
Safety and efficacy of the use of lumen-apposing metal stents in the management of postoperative fluid collections: a large, international, multicenter study
Authors: Juliana Yang, Jeremy H. Kaplan, Amrita Sethi, Enad Dawod, Reem Z. Sharaiha, Austin Chiang, Thomas Kowalski, Jose Nieto, Ryan Law, Hazem Hammad, Sachin Wani, Mihir S. Wagh, Dennis Yang, Peter V. Draganov, Ahmed Messallam, Qiang Cai, Vladimir Kushnir, Natalie Cosgrove, Ali Mir Ahmed, Andrea Anderloni, Douglas G. Adler, Nikhil A. Kumta, Satish Nagula, Frank P. Vleggaar, Shayan Irani, Carlos Robles-Medranda, Abdul Hamid El Chafic, Rishi Pawa, Olaya Brewer, Omid Sanaei, Mohamad Dbouk, Vikesh K. Singh, Vivek Kumbhari, Mouen A. Khashab
Journal: Endoscopy (2019)

Abstract Background Multiple studies have examined the use of lumen-apposing metal stents (LAMSs) for the drainage of peripancreatic fluid collections. Data on the use of LAMSs for postoperative fluid collections (POFCs) are scarce. POFCs may lead to severe complications without appropriate treatment. We aimed to study the outcomes (technical success, clinical success, rate/severity of adverse events, length of stay, recurrence) of the use of LAMSs for the drainage of POFCs. Methods This international, multicenter, retrospective study involved 19 centers between January 2012 and October 2017. The primary outcome was clinical success. Secondary outcomes included technical success and rate/severity of adverse events using the ASGE lexicon. Results A total of 62 patients were included during the study period. The most common etiology of the POFCs was distal pancreatectomy (46.8 %). The mean (standard deviation) diameter was 84.5 mm (30.7 mm). The most common indication for drainage was infection (48.4 %) and transgastric drainage was the most common approach (82.3 %). Technical success was achieved in 60/62 patients (96.8 %) and clinical success in 57/62 patients (91.9 %) during a median (interquartile range) follow-up of 231 days (90 – 300 days). Percutaneous drainage was needed in 8.1 % of patients. Adverse events occurred intraoperatively in 1/62 patients (1.6 %) and postoperatively in 7/62 (11.3 %). There was no procedure-related mortality. Conclusion This is the largest study on the use of LAMSs for POFCs. It suggests good clinical efficacy and safety of this approach. The use of LAMSs in the management of POFCs is a feasible alternative to percutaneous and surgical drainage.
Hartmann's procedure versus sigmoidectomy with primary anastomosis for perforated diverticulitis with purulent or faecal peritonitis (LADIES): a multicentre, parallel-group, randomised, open-label, superiority trial
Authors: Daniël P V Lambrichts, Sandra Vennix, Gijsbert D Musters, Irene M Mulder, Hilko A Swank, Anton G M Hoofwijk, Eric H J Belgers, Hein B A C Stockmann, Quirijn A J Eijsbouts, Michael F Gerhards, Bart A van Wagensveld, Anna A W van Geloven, Rogier M P H Crolla, Simon W Nienhuijs, Marc J P M Govaert, Salomone di Saverio, André J L D'Hoore, Esther C J Consten, Wilhelmina M U van Grevenstein, Robert E G J M Pierik, Philip M Kruyt, Joost A B van der Hoeven, Willem H Steup, Fausto Catena, Joop L M Konsten, Jefrey Vermeulen, Susan van Dieren, Willem A Bemelman, Johan F Lange, WC Hop, BC Opmeer, JB Reitsma, RA Scholte, EWH Waltmann, DA Legemate, JF Bartelsman, DW Meijer, Ç Ünlü, AB Kluit, Y El-Massoudi, RJCLM Vuylsteke, PJ Tanis, R Matthijsen, SW Polle, SM Lagarde, SS Gisbertz, O Wijers, JDW van der Bilt, MA Boermeester, R Blom, JAH Gooszen, MHF Schreinemacher, T van der Zande, MMN Leeuwenburgh, SAL Bartels, WLEM Hesp, L Koet, GP van der Schelling, E van Dessel, MLP van Zeeland, MMA Lensvelt, H Nijhof, S Verest, M Buijs, JH Wijsman, LPS Stassen, M Klinkert, MFG de Maat, G Sellenraad, J Jeekel, GJ Kleinrensink, T Tha-In, WN Nijboer, MJ Boom, PCM Verbeek, C Sietses, MWJ Stommel, PJ van Huijstee, JWS Merkus, D Eefting, JSD Mieog, D van Geldere, GA Patijn, M de Vries, M Boskamp, A Bentohami, TS Bijlsma, N de Korte, D Nio, H Rijna, J Luttikhold, MH van Gool, JF Fekkes, GJM Akkersdijk, G Heuff, EH Jutte, BA Kortmann, JM Werkman, W Laméris, L Rietbergen, P Frankenmolen, WA Draaisma, MAW Stam, MS Verweij, TM Karsten, H Rijna, LC de Nes, S Fortuin, SM de Castro, A Doeksen, MP Simons, GI Koffeman, EP Steller, JB Tuynman, P Boele van Hensbroek, M Mok, SR van Diepen, KWE Hulsewé, J Melenhorst, JHMB Stoot, S Fransen, MN Sosef, J van Bastelaar, YLJ Vissers, TPD Douchy, CE Christiaansen, R Smeenk, AM Pijnenburg, V Tanaydin, HTC Veger, SHEM Clermonts, M Al-Taher, EJR de Graaf, AG Menon, M Vermaas, HA Cense, E Jutte, TM Karsten, MJ Wiezer, AB Smits, M Westerterp, HA Marsman, ER Hendriks, O van Ruler, EJC Vriens, JM Vogten, CC van Rossem, D Ohanis, E Tanis, J van Grinsven, JK Maring, J Heisterkamp, MGH Besselink, IHM Borel Rinkes, IQ Molenaar, JJA Joosten, V Jongkind, GMP Diepenhorst, MC Boute, M Smeenge, K Nielsen, JJ Harlaar, MDP Luyer, G van Montfort, JF Smulders, F Daams, E van Haren, GAP Nieuwenhuijzen, GJ Lauret, ITA Pereboom, RA Stokmans, A Birindelli, E Bianchi, S Pellegrini, I Terrasson, A Wolthuis, A de Buck van Overstraeten, S Nijs
Journal: The Lancet. Gastroenterology & hepatology (2019)
Design and Evaluation of an External Control Arm Using Prior Clinical Trials and Real-World Data
Authors: Steffen Ventz, Albert Lai, Timothy F. Cloughesy, Patrick Y. Wen, Lorenzo Trippa, Brian M. Alexander
Journal: Clinical Cancer Research (2019)

Abstract Purpose: We discuss designs and interpretable metrics of bias and statistical efficiency of “externally controlled” trials (ECT) and compare ECT performance to randomized and single-arm designs. Experimental Design: We specify an ECT design that leverages information from real-world data (RWD) and prior clinical trials to reduce bias associated with interstudy variations of the enrolled populations. We then used a collection of clinical studies in glioblastoma (GBM) and RWD from patients treated with the current standard of care to evaluate ECTs. Validation is based on a “leave one out” scheme, with iterative selection of a single-arm from one of the studies, for which we estimate treatment effects using the remaining studies as external control. This produces interpretable and robust estimates on ECT bias and type I errors. Results: We developed a model-free approach to evaluate ECTs based on collections of clinical trials and RWD. For GBM, we verified that inflated false positive error rates of standard single-arm trials can be considerably reduced (up to 30%) by using external control data. Conclusions: The use of ECT designs in GBM, with adjustments for the clinical profiles of the enrolled patients, should be preferred to single-arm studies with fixed efficacy thresholds extracted from published results on the current standard of care.
Abstract 19144: Echocardiographic Assessment of Structural and Hemodynamic Changes in Hypertensive Pregnancy
Authors: Mi-Jeong Kim, Kyoung-Im Cho, Se-Jung Yoon, Jung-Hyun Choi, Mi-Seung Shin
Journal: Circulation (2015)

Introduction: Pregnancy induces dramatic cardiovascular changes to meet the metabolic needs for mother and fetus. Eccentric left ventricular hypertrophy (LVH) is known as the normal cardiac response to handle the increasing circulatory volume during pregnancy. Cardiac adaptation would be modified in pregnancy complicated by hypertension. Methods: Data from 193 consecutive pregnant women were analyzed. Clinical and echocardiographic data were compared in normotensive and hypertensive women. Results: Left ventricular mass index was significantly higher in hypertensive women than normotensive ones (87±17 vs 78±16, p&lt;0.001, Fig.1A). Diastolic function measured by the ratio of early mitral blood to annular velocity (E/E’) was impaired in hypertensive women (11.0±3.0 vs 9.2±2.5, p&lt;0.001, Fig.1B). Such change was more prominent in women with gestational hypertension (GHW) than those with chronic hypertension (CHW). Obesity was independent factor associated with LVH in both normotensive and hypertensive women (Fig.1C). Overt eccentric LVH was more frequent than concentric remodeling/hypertrophy (25% vs 8.4%) in GHW, while the result was opposite in CHW (14% vs 23%, Fig.1D). Conclusion: Hypertensive pregnancy is associated with significant LVH and diastolic dysfunction. Obesity accentuates hypertension-related cardiac remodeling. While eccentric LVH is prominent in GHW, pre-existing chronic hypertension appears to induce concentric LV geometry.
Complication Rates in a Study of Invasive Diagnostic Procedures for Lung Abnormalities
Authors: Stephen J. Halliday, Matthew C. Aboudara, Fabien Maldonado
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
A pH-responsive platform combining chemodynamic therapy with limotherapy for simultaneous bioimaging and synergistic cancer therapy
Authors: Jianmin Xiao, Guilong Zhang, Rui Xu, Hui Chen, Huijuan Wang, Geng Tian, Bin Wang, Chi Yang, Guo Bai, Zhiyuan Zhang, Hongyi Yang, Kai Zhong, Duohong Zou, Zhengyan Wu
Journal: Biomaterials (2019)
Clinical and Antitumor Immune Responses in Relapsed/Refractory Follicular Lymphoma Patients after Intranodal Injections of IFNα-Dendritic Cells and Rituximab: a Phase I Clinical Trial
Authors: M. Christina Cox, Luciano Castiello, Mauro Mattei, Laura Santodonato, Giuseppina D'Agostino, Elena Muraro, Debora Martorelli, Caterina Lapenta, Arianna Di Napoli, Francesca Di Landro, Michela Cangemi, Antonio Pavan, Paolo Castaldo, Stefan Hohaus, Simona Donati, Enrica Montefiore, Cinzia Berdini, Davide Carlei, Domenica M. Monque, Luigi Ruco, Daniela Prosperi, Agostino Tafuri, Francesca Spadaro, Paola Sestili, Massimo Spada, Riccardo Dolcetti, Stefano M. Santini, Carmela Rozera, Eleonora Aricò, Imerio Capone, Filippo Belardelli
Journal: Clinical Cancer Research (2019)

This study was aimed at evaluating the feasibility, safety, immunologic and clinical responses in patients with follicular lymphoma treated with monocyte-derived dendritic cells generated in the presence of IFNα and GM-CSF (IFN-DC) in combination with low doses of rituximab.Firstly, we analyzed in vitro and in vivo the immunologic properties of IFN-DC against follicular lymphoma. Thus, we performed a phase I trial in 8 patients with refractory and relapsed follicular lymphoma based on sequential intranodal injections of low-dose of rituximab and unloaded IFN-DC and report the safety, clinical, and immunologic results of the enrolled patients.Preclinical studies indicated that IFN-DC can synergize with rituximab leading to increased cytotoxicity and T-cell tumor infiltration. The clinical evaluation showed that the combined treatment was totally safe. The overall response rate was 50%, PET-negative complete response rate 37%, and remission is still ongoing in 2/4 of responding patients (median follow-up 26 months, range 11-47). Notably, following the combined therapy all patients showed induction/enhancement of T-cell responses by CD107 degranulation or IFNγ ELISPOT assay against patient-specific tumor IGHV sequences.These results represent the proof-of-principle on the effectiveness of unloaded IFN-DC in inducing durable clinical responses and promoting induction of tumor-specific peripheral T cells, thus suggesting the occurrence of an effective endogenous antitumor vaccination. The overall findings indicate that some unique properties of IFN-DC can be successfully exploited to induce/enhance antitumor responses, thus representing a valuable antitumor strategy for novel and more effective combination therapies in patients with cancer.
Exercise Benefits in Pulmonary Hypertension
Authors: Alejandro Santos-Lozano, Carmen Fiuza-Luces, David Fernández-Moreno, Francisco Llavero, Joaquín Arenas, Juan Antonio López, Jesús Vázquez, Pilar Escribano-Subías, José L. Zugaza, Alejandro Lucia
Journal: Journal of the American College of Cardiology (2019)
A novel way to avoid reoperation for biliary strictures after liver transplantation: cholangioscopy-assisted guidewire placement
Authors: Florian Rainer, Andreas Blesl, Walter Spindelboeck, Peter Schemmer, Peter Fickert, Florian Schreiber
Journal: Endoscopy (2019)

Biliary tract complications after liver transplantation remain a major therapeutic issue significantly affecting graft and patient survival [1]. Strictures of the bile duct account for about 40 % of biliary complications after liver transplantation [2]. Today, endoscopic retrograde cholangiography (ERC) has widely replaced surgery and percutaneous techniques as the treatment of choice for such patients [3]. However, highly fibrotic strictures of the anastomotic region frequently preclude passage of the guidewire. In these cases, percutaneous transhepatic cholangiography (PTC), endoscopic ultrasound-guided biliary drainage, or indication for resection of the stenosis-bearing extrahepatic biliary segment with subsequent biliodigestive anastomosis are applied, all of which are associated with increased morbidity.
Abstract 15800: Identification of a Novel Transcript and Regulatory Mechanism for Microsomal Triglyceride Transfer Protein
Authors: Takashi Suzuki, Judy J Brown, Larry L Swift
Journal: Circulation (2015)

Microsomal triglyceride transfer protein (MTP) is heterodimeric protein complex consisting of a unique 97 kDa protein with lipid transfer activity and the ubiquitous 58 kDa protein disulfide isomerase. The complex is essential for assembly of triglyceride-rich apolipoprotein (apo) B-containing lipoproteins. In tissues that do not synthesize apoB nor assemble lipoproteins, it is presumed to serve specialized needs in lipid trafficking, such as in the lipidation of CD1d in antigen presenting cells, including adipocytes. Previous studies in our laboratory identified a novel isoform of MTP in mice that we named MTP-B. MTP-B has an alternative first exon (Ex1B) located 2.7 kbp upstream of the first exon (Ex1A) of MTP-A, the canonical isoform of MTP. The two mature isoforms, though nearly identical in sequence and function, have different tissue expression patterns. In this study, we have identified another splice variant, MTP-C, that contains both exons Ex1B and Ex1A. PCR analysis revealed that MTP-C mRNA is expressed in a number of tissues including liver, ovary, heart, kidney, brain and testis. In CHO and HEK 293 cells transfected with MTP-C, protein expression was less than 15% of that found when the cells were transfected with MTP-A or MTP-B. In silico analysis of the 5’ untranslated region (UTR) of MTP-C revealed six ATGs (uATGs) upstream of the translation initiation site for MTP-A, which is the only viable start site in frame with the main open reading frame (ORF), and three potential upstream ORFs (uORFs). Since uATGs and uORFs are generally associated with repressed translational efficiency, we inserted the 5’ UTR of MTP-C into a pGL3 vector between the SV40 promoter and luciferase reporter gene and transfected it into CHO cells. Luciferase activity was significantly reduced (45.5 ± 6.4%) compared to pGL3-Control vector transfected cells. This suggests the reduced protein expression observed in MTP-C transfected cells resulted in part from decreased translation efficiency. We conclude that uORFs in the 5’ UTR of MTP-C repress translation, providing a mechanism to fine tune MTP levels to meet the needs of the cell. uORFs in human MTP-C could represent novel therapeutic targets for regulation of MTP expression and plasma lipid levels.