tbuckley/cabot-search huggingface dataset:
Effect of an Electronic Medication Reconciliation Intervention on Adverse Drug Events
Authors: Robyn Tamblyn, Michal Abrahamowicz, David L. Buckeridge, Melissa Bustillo, Alan J. Forster, Nadyne Girard, Bettina Habib, James Hanley, Allen Huang, Siyana Kurteva, Todd C. Lee, Ari N. Meguerditchian, Teresa Moraga, Aude Motulsky, Lina Petrella, Daniala L. Weir, Nancy Winslade
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Adverse drug events (ADEs) account for up to 16% of emergency department (ED) visits and 7% of hospital admissions. Medication reconciliation is required for hospital accreditation because it can reduce medication discrepancies, but there is no evidence that reducing discrepancies reduces ADEs or other adverse outcomes. <h3>Objective</h3> To evaluate whether electronic medication reconciliation reduces ADEs, medication discrepancies, and other adverse outcomes compared with usual care. <h3>Design, Setting, and Participants</h3> This cluster randomized trial involved 3491 patients who were discharged from 2 medical units and 2 surgical units at the McGill University Health Centre, Montreal, Quebec, Canada, between October 2014 and November 2016. Data analysis took place from July 2017 to July 2019. <h3>Intervention</h3> The RightRx intervention electronically retrieved community drugs from the provincial insurer and aligned them with in-hospital drugs to facilitate reconciliation and communication at care transitions. <h3>Main Outcomes and Measures</h3> The primary outcome was ADEs in 30 days after discharge. Secondary outcomes included medication discrepancies, ED visits, hospital readmissions, and a composite outcome of ED visits, readmissions, and death up to 90 days after discharge. <h3>Results</h3> Of 4656 eligible patients, 3567 (76.6%) consented to participate (2060 [57.8%] men; mean [SD] age, 69.8 [14.9] years). Overall, 76 patients died during the hospital stay, so 3491 patients were included in the analysis. There was no significant difference in the risk of ADEs between intervention and control groups (76 [4.6%] vs 73 [4.0%]; OR, 0.97; 95% CI, 0.33-1.48), ED visits (433 [26.2%] vs 488 [26.6%]; OR, 0.83; 95% CI, 0.36-1.42), hospital readmission (170 [10.3%] vs 261 [14.2%]; OR, 0.22; 95% CI, 0.06-1.14), or the composite outcome (447 [27.0%] vs 506 [27.6%]; OR, 0.75; 95% CI, 0.34-1.27) at 30 days. Medication discrepancies were significantly reduced in the intervention group compared with the control group (437 [26.4%] vs 1029 [56.0%]; OR, 0.24; 95% CI, 0.12-0.57). Changes made to community medications (OR, 1.05; 95% CI, 1.01-1.10) and new medications (OR, 1.09; 95% CI, 1.01-1.18) were significant risk factors for ADEs. <h3>Conclusions and Relevance</h3> Electronic medication reconciliation reduced medication discrepancies but did not reduce ADEs or other adverse outcomes. Hospital accreditation should focus on interventions that reduce the risk of adverse events for patients with multiple changes to community medications. <h3>Trial Registration</h3> ClinicalTrials.gov identifier:NCT01179867
Vitamin B12 Deficiency-Related Pseudo-Thrombotic Microangiopathy Might be Misdiagnosed and Treated with Plasma Product Therapy: Review of the Literature and Analysis of the Reported Cases
Authors: Aung M Tun, Zin W Myint, Cristhiam Rojas Hernandez, Elizabeth Guevara, Kyaw Zin Thein, Thein Hlaing Oo
Journal: Blood (2017)
Prognostic value of an immune score combining intra- and peritumoral T-cell subset density in patients with pancreatic adenocarcinoma.
Authors: Simon Turcotte, Yannic McNicoll, Genevieve Soucy, Louis Gaboury, Real W. Lapointe, Franck Vandenbroucke-Menu
Journal: Journal of Clinical Oncology (2013)

4060 Background: Immune scoring based on T-cell subsets and density can add prognostic value to conventional TNM staging for patients with solid tumors, but limited data are available for pancreatic adenocarcinoma. Methods: Using tissue microarrays, CD3, CD4, CD8, CD45RO, and FOXP3 T-cells were quantified by immunohistochemistry in the intratumoral (IT) compartment and peritumoral (PT) parenchyma of 111 consecutively resected specimens. T-cell counts were correlated with patient overall survival, disease-free survival, and time to recurrence (OS, DFS, TTR) by Cox regression, controlling for clinicopathological factors. An immune score (IS) based on IT CD4 T-cell count &gt; median, PT CD8 T-cell count ≤ median, and IT/PT CD3 T-cell ratio &gt;1, grouped patients into high, intermediate, or low categories if all 3, 1 to 2, or none of these immune features were present, respectively. Results: Median follow-up time was 20 months, and 85% of patients either died or recurred during the study period. By univariate analysis, PT CD8 T-cell count was associated with shorter OS (p=0.02), whereas both IT CD4 T-cell count and IT/PT CD3 T-cell ratio were associated with longer OS (p=0.01 and p=0.05, respectively). Alone, none of these immune features predicted TTR. Combined into an IS, patients in the high (n=23), intermediate (n=60), or low (n=23) categories had significantly different OS (respective medians 30, 17, and 13 months, log-rank p=0.01), DFS (28, 16, and 12 months, p=0.01), and TTR (21, 14, and 10 months, p=0.02). By multivariate analysis, the association between IS and clinical outcomes was independent of tumor size, extra-pancreatic invasion, and nodal metastases (TNM staging). The IS discriminated outcomes among patients with nodal metastases (n=80), such that node-positive patients with a high IS had a median survival similar to node-negative patients (30 and 33 months, p=0.7). FOXP3 and CD45RO T-cell counts did not appear to add prognostic value to the IS. Conclusions: An immune score that combines specific T-cell location and density may have prognostic value in patients with resected pancreatic adenocarcinoma, independently from pathologic features currently used for staging.
Paul Leslie Gordon Townsend
Authors: Nigel Mercer, Antonio Orlando
Journal: BMJ (2019)

Paul Leslie Gordon Townsend was one of the fathers of reconstructive microsurgery nationally and internationally. He was born in Hendon and grew up in Radlett in Hertfordshire. His father was first an army officer and then an accountant. Paul could recall watching bombs dropping on London in the early years of the war. He was educated at Epsom College and took his medical degree at University College Hospital, London, during which time he took a group of fellow students to Russia. It must have been quite a challenge. The Bay of Pigs episode was in 1961 and the political climate between east and west at its most tense. He intercalated and passed his BSc with honours in 1960, followed by his medical degree in 1963.

He married Mary, whom he had met at UCH in 1967. In 1968, after he had passed obtained fellowship of the Royal College of Surgeons of England, they went to Canada, where he worked in British Columbia. He passed the FRCS Canada in 1972, but the couple decided to return to the UK. Paul worked as a registrar at Odstock Hospital in Salisbury and as a senior registrar at Frenchay …
The effectiveness of ovarian cancer screening in high-risk population and BRCA 1/2 carriers: A systematic review and meta-analysis.
Authors: David Fawunmi, Helene Gojon, Antonis Valachis
Journal: Journal of Clinical Oncology (2013)

1568 Background: The purpose of this study is to assess the effectiveness of different screening modalities in detecting ovarian cancer in high-risk women and BRCA 1/2 carriers. Methods: We searched through MEDLINE and ISI Web of Science, with no language or year restriction, to identify studies that used various screening modalities (Ca125, transvaginal ultrasound (TVUS) or combination) to detect ovarian cancer in high-risk women and BRCA 1/2 carriers. We summarized the sensitivity, specificity, and likelihood ratios of each screening modality. Results: Seven studies including BRCA 1/2 carriers and 12 studies including high-risk women were eligible for analysis. The pooled sensitivity of combined Ca125 and TVUS for BRCA 1/2 carriers was 47.6% (95% Confidence Interval (CI): 36.6%-58.8%). The pooled sensitivity of combined screening modality for high-risk population was 54% (95% CI: 43%-64-8%). The summary negative likelihood ratio for BRCA 1/2 carriers was 0.6 (95% CI: 0.48 – 0.75). In high-risk population (N = 12398) the rate of advanced stage incident screen-detected cancer was 56% (9 of 16 cancer) which is comparable to the rate of advanced stage in prevalent screening-detected cancer (18 of 32, 56%). In BRCA 1/2 carriers (N = 2356) no difference in stage distribution between incident screen-detected and interval cancer was found (26 of 31 cancer (84%) versus 24 of 27 (89%)). Conclusions: Despite annual combined screening with TVUS and Ca125, a high proportion of ovarian cancer in both BRCA 1/2 carriers and high-risk women are diagnosed in advanced stage. In addition, all screening modalities have an unacceptably low sensitivity. Therefore, it is unlikely that these screening modalities will reduce mortality from ovarian cancer. Further studies are needed to evaluate if more frequently screening more frequently than annually would offer a better chance of early-stage detection.
An outbreak of skin rash traced to a portable floating tank in Norway, May 2017
Authors: Susanne Hyllestad, Heidi Lange, Bernardo Guzman-Herrador, Emily MacDonald, Vidar Lund, Preben Aavitsland, Line Vold
Journal: Eurosurveillance (2019)

Despite concerns about infection risks of floating tanks, outbreaks have rarely been reported. In May 2017, an outbreak of skin rash occurred among visitors of a floating tank open for the public in Norway. We assessed the extent and cause of the outbreak and the risk factors for infection in a retrospective cohort study among the visitors of the floating tank using a standardized web-based questionnaire. An environmental investigation was conducted including microbiological analysis of the floating tank water. Of the 46 respondents to the questionnaire (61 distributed), 22 reported symptoms, most commonly palmar and plantar rash, swollen lymph nodes, ear canal pain and itching. None of the investigated risk factors, such as sex, age, duration of bathing or use of the shower after bathing, were significantly associated with illness. The results of the environmental investigation indicated that the water was heavily contaminated by P. aeruginosa and heterotrophic bacteria. The outbreak investigation highlights the need to ensure adequate hygienic operation of floating tanks. Awareness about responsibilities should be raised among the operators of floating tanks and relevant operational parameters for floating tanks should be made available for local health authorities.
Growth of hepatocellular adenoma during pregnancy: A prospective study
Authors: Marcia Patricia Gaspersz, Anne Julia Klompenhouwer, Mirelle Elmira Elizabeth Broker, Maarten Gerardus Josephus Thomeer, Susanna Maria van Aalten, Eric Steegers, Türkan Terkivatan, Harry de Koning, Robert Auke de Man, Jan Nicolaas Maria Ijzermans
Journal: Journal of Hepatology (2019)
Hepatic IRF2BP2 Mitigates Nonalcoholic Fatty Liver Disease by Directly Repressing the Transcription of ATF3
Authors: Jing Fang, Yan‐Xiao Ji, Peng Zhang, Lin Cheng, Yue Chen, Jun Chen, Yanfang Su, Xu Cheng, Yan Zhang, Tianyu Li, Xuehai Zhu, Xiao‐Jing Zhang, Xiang Wei
Journal: Hepatology (2019)

Although knowledge regarding the pathogenesis of nonalcoholic fatty liver disease (NAFLD) has profoundly grown in recent decades, the internal restrictive mechanisms remain largely unknown. We have recently reported that the transcription repressor interferon regulatory factor-2 binding protein 2 (IRF2BP2) is enriched in cardiomyocytes and inhibits pathological cardiac hypertrophy in mice. Notably, IRF2BP2 is abundantly expressed in hepatocytes and dramatically down-regulated in steatotic livers, whereas the role of IRF2BP2 in NAFLD is unknown.Herein, using gain-of-function and loss-of-function approaches in mice, we demonstrated that while hepatocyte-specific Irf2bp2 knockout exacerbated high-fat diet-induced hepatic steatosis, insulin resistance and inflammation, hepatic Irf2bp2 overexpression protected mice from these metabolic disorders. Moreover, the inhibitory role of IRF2BP2 on hepatosteatosis is conserved in a human hepatic cell line in vitro. Combinational analysis of digital gene expression and chromatin immunoprecipitation sequencing identified activating transcription factor 3 (ATF3) to be negatively regulated by IRF2BP2 in NAFLD. Chromatin immunoprecipitation and luciferase assay substantiated the fact that IRF2BP2 is a bona fide transcription repressor of ATF3 gene expression via binding to its promoter region. Functional studies revealed that ATF3 knockdown significantly relieved IRF2BP2 knockout-exaggerated hepatosteatosis in vitro.IRF2BP2 is an integrative restrainer in controlling hepatic steatosis, insulin resistance, and inflammation in NAFLD through transcriptionally repressing ATF3 gene expression.
David Sanders: worked with African liberation movements and governments in primary healthcare and child health and nutrition
Authors: Ned Stafford
Journal: BMJ (2019)

Credit: Louis Reynold: International People’s Health Movement People’s Health University in Kisumu, Kenya

In 2010 in Kisumu, Kenya, David Sanders was outside enjoying a break during the International People’s Health University (IPHU), an educational and research programme held regularly at various locations around the world for health activists. A young woman approached Sanders and asked whether she could have her picture taken with him (see photo).

Sanders, of course, was happy to pose with the woman. Louis Reynolds, Sanders’s long time friend and colleague, was recruited to snap what was intended to be one picture. It turned out, though, that one picture was not going to be enough. Sanders was a living legend in African health. With his friendly smile, charming personality, and pleasant demeanour, Sanders was a virtual magnet for people, including when his picture was being taken.

“All the people in the photo were IPHU participants,” Reynolds, a retired associate professor in paediatrics at the University of Cape Town, told The BMJ . “They came from a range of African countries. During a break, the young woman second from him on his left—wearing the white top—came up and asked me to photograph them together. That was the first photo in what became a series. The guy on David’s right then came up and asked to join in. As the others became aware of this, the group grew steadily, with me taking sequential photos. I had to keep stepping back to fit them all in.”

Reynolds added that Sanders “was able to connect with young people and inspire them and just make them happy.”

Countless people around the world who admired and were inspired by Sanders are now in mourning; he had a heart attack on 30 August 2019 while on holiday in Wales.

For nearly 40 years Sanders …
Abstract 16433: Protection Conferred by Y-chromosome Against Hypoxia-induced Pulmonary Hypertension is Not Due to Ddx3y Gene
Authors: Soban Umar, Mariam Barseghyan, Alex Centala, Yuichiro Itoh, Ryan Mackie, Arthur P Arnold, Mansoureh Eghbali
Journal: Circulation (2015)

Introduction: Pulmonary hypertension (PH) is a chronic pulmonary vascular disease characterized by elevated pulmonary arterial pressures and vascular remodelling leading to right ventricular failure. It is 4 times more likely to occur in females than males. The reasons for the female predominance or male protection are still not fully elucidated. Our previous work showed that in gonadectomized (GDX) Four Core Genotypes (FCG) mice (XX and XY males, XX and XY females, C57BL6/J), XY mice having a Y-chromosome (XYM, XYF) develop less severe PH than the XX mice lacking a Y-chromosome (XXM, XXF). Hypothesis: Protection against hypoxia-induced PH in gonadectomized mice is due to the presence of Y-chromosome and not due to the number of X-chromosomes. We also examined the role of a Y-chromosome gene Ddx3y, a cellular growth suppressor expressed consistently in the lungs and heart in protection against PH. Methods: Here we used GDX XY* C57BL/6J mouse model which allows us to have male mice with XY or XXY and female mice with XX or XO genotypes (n=5/group). In addition we also used XX female mice with and without a transgenic copy of Y-chromosome gene Ddx3y (n=10/group). Mice were gonadectomized at day-75 and 4-weeks after gonadectomy, were exposed to hypoxia (10% O2) for 3-weeks. RVSP was measured through direct catheterization. Results: In the GDX XY* model, right ventricular systolic pressure (RVSP) in mice with Y-chromosome (XY=33.5±0.6, XXY=32±2mmHg) was significantly lower than that of mice without a Y-chromosome (XO=38.7±2, XX=41.5±3.8, P&lt;0.05). We concluded that presence of Y-chromosome confers protection against PH in GDX mice. Four Y-chromosome genes are expressed consistently in the lungs and heart (Ddx3y, Kdm5d, Uty, Eif2x3y) and are thus candidate protective genes. We did not find a significant difference between the RVSP of XX mice with or without a transgenic copy of Ddx3y. Conclusions: We conclude that Y-chromosome confers protection against hypoxia-induced PH in GDX mice which is not due to Ddx3y gene. Next we plan to investigate effects of the other Y-chromosome candidate genes Kdm5d, Uty, and Eif2x3y.
Cardioprotective Role of the Mitochondrial ATP-Binding Cassette Protein 1
Authors: HosseinArdehali, BrianO’Rourke, EduardoMarbán
Journal: Circulation Research (2005)

The mechanism by which mitochondria exert protection against oxidant stress is not clear. We recently showed that a purified mitochondrial fraction containing 5 coimmunoprecipitating proteins (succinate dehydrogenase, adenine nucleotide translocator, ATP synthase, inorganic phosphate carrier, and mitochondrial ATP-binding cassette protein 1 or mABC1) displayed mitochondrial ATP-sensitive K+-channel activity. mABC1, a member of the ABC family of proteins, is the only protein in this complex whose function is not known. A yeast homologue of mABC1 protein, Mdl1p, was recently identified to have a novel role for induction of cellular resistance to oxidant stress. Based on these observations, we hypothesized that mABC1 plays a key role in protection of myocardial cells against oxidant stress. We studied the function of mABC1 by modulating the levels of this protein in neonatal rat cardiomyocytes using various molecular techniques, followed by assessment of cell viability and measurement of mitochondrial membra...
Shedding New Light on Platelet Extracellular Vesicles in Sickle Cell Disease
Authors: Elizabeth A. Middleton, Lorraine B. Ware, Matthew T. Rondina
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

In this issue of the Journal (pp.[33][34][35][36][37][38][39][40][41][42][43][44][45][46], Vats and colleagues demonstrate an important, previously unrecognized role of platelet extracellular vesicles (EVs) in driving IL-1b-dependent acute lung injury in sickle cell disease (SCD) (1).Platelets are anucleate cells released into the circulation through fragmentation from their parent cell, the megakaryocyte.Platelets are well known to trigger hemostasis through adhesion to subendothelial matrix substrates or activated endothelium (2, 3).Established and emerging evidence, however, also indicates that platelets are dynamic effector cells across immune and inflammatory continua, including roles during acute lung injury (4, 5).Infectious and noninfectious agents can trigger noncanonical platelet responses, as may occur in chronic inflammatory diseases, such as systemic lupus erythematosus and rheumatoid arthritis, and may contribute to lung injury.SCD is a monogenic disorder affecting millions worldwide and is characterized by the prevalence of hemoglobin S (Hgb S) rather than Hgb A. Hgb S can polymerize and cause "sickling" of the red blood cells under physiologic stressors such as infection, trauma, or hypoxemia.Red blood cell sickling can precipitate a vaso-occlusive crisis hallmarked by ischemia/infarction, pain, and hemolysis (6).Platelets have been implicated in the pathogenesis of SCD and its most serious pulmonary manifestation: acute chest syndrome (ACS).Histologic studies have found platelet thrombi and microthrombi occluding pulmonary arterioles in patients with SCD with ACS (7).Patients with SCD have higher numbers of circulating platelet-neutrophil aggregates under steady-state conditions and in response to LPS stimulation in vitro (8).Moreover, these heterotypic aggregates have been shown to cause arteriolar microthrombi in a murine model of SCD, mimicking features of vaso-occlusive crisis (8).Platelets possess receptors that aid in recognition of dangerassociated molecular pattern receptors and pathogen-associated molecular pattern receptors, including the TLRs (Toll-like receptors) 2, 4, and 9. TLR4 and its ligand LPS have been the best studied in platelets, although controversy remains with regard to LPS activation of classical platelet hemostatic responses (9, 10).However, LPS is known to stimulate noncanonical platelet function responses, including platelet mitochondrial respiration (10), the splicing of endogenous mRNAs (11), and the generation of platelet-leukocyte aggregates (12).Recently,
Bion-1301, a First-in-Class APRIL Neutralizing Antibody for the Treatment of Multiple Myeloma: Preclinical Safety, and Analysis of Pharmacokinetics — Pharmacodynamics Relationship
Authors: John Dulos, Lilian Driessen, Peter van Zandvoort, Jos van de Crommert, Justin Skoble, Nitya Nair, Britta Randlev, Eduard de Cock, Jeroen Elassaiss Schaap, Hans Eenennaam, Andrea van Elsas
Journal: Blood (2017)
Restenosis Following Angioplasty in the Swine Coronary Artery Is Inhibited By an Orally Active PDGF-Receptor Tyrosine Kinase Inhibitor, RPR101511A
Authors: GlendaBilder, TaraWentz, RobertLeadley, DilipAmin, LisaByan, BetseyO’Conner, SaulNeedle, HelenGalczenski, JefferyBostwick, CharlesKasiewski, MichaelMyers, AlfredSpada, LindaMerkel, CuongLy, PaulPersons, KennethPage, MarkPerrone, ChristopherDunwiddie
Journal: Circulation (1999)

Background—Platelet-derived growth factor (PDGF), a purported mediator of arterial response to injury, stimulates proliferation, chemotaxis, and matrix production by activation of its membrane receptor tyrosine kinase. Because these activities underlie restenosis, inhibition of the PDGF-receptor tyrosine kinase (PDGFr-TK) is postulated to decrease restenosis. Methods and Results—RPR101511A is a novel compound which selectively and potently inhibits the cell-free and in situ PDGFr-TK and PDGFr-dependent proliferation and chemotaxis in vascular smooth muscle cells (VSMC). To evaluate the effect of RPR101511A (30 mg · kg−1 · d−1 BID for 28 days following PTCA) on coronary restenosis, PTCA was performed in hypercholesterolemic minipigs whose left anterior descending (LAD) coronary artery had been injured by overdilation and denudation, yielding a previously existing lesion. Angiographically determined prePTCA minimal lumen diameters (MLD) were similar in vehicle and RPR101511A-treated pigs (1.98±0.09 versus 2...