tbuckley/cabot-search huggingface dataset:
Patient information on covid-19 vaccines—a vaccine centre lottery
Authors: Anthony C Cartwright, Mary Tompkins, Jenny Boncey, Christine Hastie, Rosalind Grant, Diane Leakey, Ian G Simpson, Sarah Cockbill, Beth Taylor, Mike Beaman, Joan Craig, Carol Ann Lange
Journal: BMJ (2021)

Members of the Royal Pharmaceutical Society’s retired pharmacists group committee have been collating our experiences of being vaccinated against covid-19. We live in England, Wales, and Scotland. Our experience probably represents the range of practice in UK centres.

Information being given out varies by centre. Some are not giving out any information, others are handing out Public Health England or Scotland leaflets, yet others are giving out the Information for the recipient …
POS1287 ANXIETY, DEPRESSION, FIBROMYALGIA SYNDROME AND PAIN INTENSITY IN PATIENTS WITH LOW BACK PAIN
Authors: R. Dhahri, A. Dghaies, M. Slouma, L. Metoui, I. Gharsallah, I. Dorgham, R. Ayari, Y. Mallat, K. Amri
Journal: Annals of the Rheumatic Diseases (2021)

Background: Common low back pain (LBP) is a common health problem affecting 50 to 80% of working age adults resulting in significant personal, social and occupational impairment. Chronic pain has a negative impact on quality of life and psychological well-being. Objectives: The aim of this study was to examine the relationship between anxiety, depression and pain intensity in patients with low back pain in a population made of military agents. Methods: It was an analytical cross-sectional study including 50 patients with at least three months of LBP, in the department of rheumatology and orthopedics at the Military Hospital of Tunis between January 1st and March 31, 2020. All patients had a standardized clinical assessment. Patients completed the «hospital anxiety and depression scale» (HADS) and the «Fibromyalgia Rapid Screening Tool» (FIRST) to evaluate psychological impact of chronic LBP. Pain intensity was assessed using a visual analog scale (VAS). Results: The mean age of the patients was 41.9 ± 8.4 years and the sex ratio was 4.5. LBP duration was 66.4 months. The mean lumbar visual analog scale (VAS) was 4.5 ± 1.9, and the root VAS was 2.6 ± 2.5. Neuropathic pain was found in 26% of patients. Abnormal level of anxiety and depression were found in 58% and 62% of the patients respectively. Out of them 20% and 26% were borderline abnormal for anxiety and depression respectively, while 38% (16.4%) and 36% were certainly abnormal for anxiety and depression respectively. Twelve percent of the patients had fibromyalgia syndrome associated with LBP as they had a FIRST score ≥5. Positive correlations were found between lumbar VAS and HAD anxiety/depression scores (r = 0.35; p&lt;0.01/ r = 0.3; p = 0.04). Positive correlations were also found between root VAS and HAD anxiety/depression (R= 0.38; P&lt;0.01/ R=0.29; P=0.03). There was positive correlations between Fibromyalgia syndrome (FIRST scale) and lumbar VAS (r= 0.42; p=0.01) and root VAS (R= 0.29; P&lt;0.01). Conclusion: The results of this study showed that anxiety, depression and fibromyalgia syndrome are not only frequent with patient suffering from chronic LBP but they are also correlated to the pain intensity. As a consequence, assessment of and intervention in anxiety, depression symptoms and fibromyalgia syndrome is crucial in the provision of pain-relief nursing treatment in patients with low back pain. Disclosure of Interests: None declared
Public Trust and Willingness to Vaccinate Against COVID-19 in the US From October 14, 2020, to March 29, 2021
Authors: Michael Daly, Andrew Jones, Eric Robinson
Journal: JAMA (2021)

Govind Persad, JD, PhD; Ezekiel J. Emanuel, MD, PhD; Samantha Sangenito, MPA; Aaron Glickman, MPA; Steven Phillips, MD, MPH; Emily A. Largent, JD, PhD, RN
Northern Ireland: Doctors oppose plans for duty of candour failures to carry criminal sanctions
Authors: Abi Rimmer
Journal: BMJ (2021)

The BMA has spoken out against proposals that could lead to criminal sanctions for doctors in Northern Ireland who fail to be open and honest with patients when things go wrong.

The same would apply to doctors who witness a colleague making a mistake and do not report it. Tom Black, chair of the BMA’s Northern Ireland Council, warned that the proposal would create a hostile working environment, especially for junior doctors.

In England, doctors must comply with the General Medical Council’s (GMC) duty of candour guidance.1 This states that they must be open and honest with patients …
POS0826 SKIN LIMITED IGA VASCULITIS IN ADULTS
Authors: A. Hočevar, J. Ostrovrsnik, K. Perdan-Pirkmajer, M. Tomsic, Z. Rotar
Journal: Annals of the Rheumatic Diseases (2021)

Background: IgA vasculitis (IgAV) could be limited to skin or evolve into a systemic disease, affecting characteristically joints, gastrointestinal tract and/or kidneys. Objectives: We aimed to look for differences between adult IgAV patients with disease limited to skin compared to systemic IgAV. Methods: Medical records of histologically proven adult IgAV cases, diagnosed between January 2010 and December 2020 at our secondary/tertiary rheumatology centre were analyzed. Results: During the 132-month observation period we identified 328 new IgAV cases (59.5% males, median (IQR) age 64.3 (45.1; 76.1) years). Ninety-four (40.2%) patients had skin limited disease, and the rest systemic IgAV. Clinical differences between skin limited and systemic adult IgAV are presented in table 1. Adults with IgAV limited to skin were significantly older, had less commonly skin lesions above the waistline and a lower level of C reactive protein compared to patients with a systemic disease. There were no differences in the frequency of skin necroses between the compared IgAV subgroups. The frequency of potential vasculitis triggers (prior infections, new medications, malignancy) was similar between the compared subgroups. Table 1. Clinical characteristics of IgA vasculitis patients with skin limited and systemic disease Clinical characteristics Skin limited IgAV (94) Systemic IgAV (234) P value Male gender (%) 54.3 61.5 0.263 Age (years)* 68.0 (55.0-80.5) 61.5 (41.7-75.8) 0.007 Current smoker (%) 13.8 21.8 0.123 Antecedent infection (%) 28.7 33.8 0.434 New medication 23.4 23.5 1.0 History of cancer 12.8 10.7 0.569 Symptom duration (days)* 7 (5-21) 8 (5-14) 0.756 Purpura above waistline 36.2 55.6 0.002 Skin necroses (%) 52.1 45.7 0.329 ESR /mm/h) * 32 (18-52) 34 (17-53) 0.873 CRP (g/l) * 13.5 (1-32) 30 (11-68) &lt;0.001 Elevated serum IgA (%) 50.6 49.1 0.892 Legend: * median and IQR; Follow up data were available for 250 (76.2%) patients. During the follow up of median (IQR) 12.5 (6.8 – 22.4) months 35 patients relapsed (13/70 (18.6%) with skin limited IgAV and 22/180 (12.2%) with systemic IgAV, p= 0.224). Conclusion: Skin limited IgAV was associated with older age and less extensive skin puprura in adults. However, relapses of purpura were as common as in systemic IgAV. Disclosure of Interests: None declared
Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1
Authors: Claudia Vivori, Panagiotis Papasaikas, Ralph Stadhouders, Bruno Di Stefano, Anna Ribó Rubio, Clara Berenguer Balaguer, Serena Generoso, Anna Mallol, José Luis Sardina, Bernhard Payer, Thomas Graf, Juan Valcárcel
Journal: Genome biology (2021)

Abstract Background Somatic cell reprogramming is the process that allows differentiated cells to revert to a pluripotent state. In contrast to the extensively studied rewiring of epigenetic and transcriptional programs required for reprogramming, the dynamics of post-transcriptional changes and their associated regulatory mechanisms remain poorly understood. Here we study the dynamics of alternative splicing changes occurring during efficient reprogramming of mouse B cells into induced pluripotent stem (iPS) cells and compare them to those occurring during reprogramming of mouse embryonic fibroblasts. Results We observe a significant overlap between alternative splicing changes detected in the two reprogramming systems, which are generally uncoupled from changes in transcriptional levels. Correlation between gene expression of potential regulators and specific clusters of alternative splicing changes enables the identification and subsequent validation of CPSF3 and hnRNP UL1 as facilitators, and TIA1 as repressor of mouse embryonic fibroblasts reprogramming. We further find that these RNA-binding proteins control partially overlapping programs of splicing regulation, involving genes relevant for developmental and morphogenetic processes. Conclusions Our results reveal common programs of splicing regulation during reprogramming of different cell types and identify three novel regulators of this process and their targets.
Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants
Authors: Sachin Bhagchandani, Jeremiah A. Johnson, Darrell J. Irvine
Journal: Advanced Drug Delivery Reviews (2021)

Imidazoquinoline derivatives (IMDs) and related compounds function as synthetic agonists of Toll-like receptors 7 and 8 (TLR7/8) and one is FDA approved for topical antiviral and skin cancer treatments. Nevertheless, these innate immune system-activating drugs have potentially much broader therapeutic utility; they have been pursued as antitumor immunomodulatory agents and more recently as candidate vaccine adjuvants for cancer and infectious disease. The broad expression profiles of TLR7/8, poor pharmacokinetic properties of IMDs, and toxicities associated with systemic administration, however, are formidable barriers to successful clinical translation. Herein, we review IMD formulations that have advanced to the clinic and discuss issues related to biodistribution and toxicity that have hampered the further development of these compounds. Recent strategies aimed at enhancing safety and efficacy, particularly through the use of bioconjugates and nanoparticle formulations that alter pharmacokinetics, biodistribution, and cellular targeting, are described. Finally, key aspects of the biology of TLR7 signaling, such as TLR7 tolerance, that may need to be considered in the development of new IMD therapeutics are discussed.
Failure to seroconvert after two doses of BNT162b2 SARS-CoV-2 vaccine in a patient with uncontrolled HIV
Authors: Emma Touizer, Aljawharah Alrubayyi, Chloe Rees-Spear, Natasha Fisher-Pearson, Sarah A Griffith, Luke Muir, Pierre Pellegrino, Laura Waters, Fiona Burns, Sabine Kinloch, Sarah Rowland-Jones, Ravindra K Gupta, Richard Gilson, Dimitra Peppa, Laura E McCoy
Journal: The Lancet HIV (2021)
Lachnospiraceaeのヒト由来分離株間の機能的およびゲノム変動は種間および種内多様性を明らかにする【JST・京大機械翻訳】
Authors: T Sorbara Matthew, R Littmann Eric, Fontana Emily, U Moody Thomas, E Kohout Claire, Gjonbalaj Mergim, Eaton Vincent, Seok Ruth, M Leiner Ingrid, G Pamer Eric
Journal: Cell Host & Microbe (2020)
Abstract 2710: Emergency Room Utilization of Continuous Intravenous Furosemide Together With the American Heart Association Get With the Guideline Heart Failure Care (GWTG-HF) Decreases Length of Stay for Hospitalized Heart Failure Patients at St. Joseph’s Regional Medical Center (SJRMC)
Authors: Robert T Faillace, James Pruden, David Adinaro, Lorraine Marut, Ilene Matza, Lucena Sarimento, Kathleen Cahill, Eileen Bogdanowicz, Deborah Smith, John Manke
Journal: Circulation (2007)

The main goals of therapy for hospitalized congestive heart failure (CHF) patients are to achieve euvolemia and to administer optimal standards of care. No study to date has examined ways to implement use of continuous intravenous furosemide (IVF) in the Emergency Room (ER) and ensure that each CHF patient consistently receives optimal standards of care throughout their hospitalization. Therefore, we hypothesized that a multi-disciplinary team approach with coordination of care from ER arrival to discharge (DC) with use of the AHA GWTG-HF Program will decrease length of stay (LOS) and provide optimal care for CHF patients as compared to usual care. METHODS: GWTG-HF was operational in 2006 with a multi-disciplinary team consisting of a Physician Champion, Advanced Practice Nurses (APNs), Case Managers and RNs. In June of 2006 the IVF program was implemented in coordination with the ER, Cardiology and Medicine Departments. ER physicians were prompted by an electronic medical record provider order entry (EMR-POE) CHF order set. GWTG-HF APNs followed these patients throughout their hospitalization. We compared the average LOS of CHF patients who received usual care in 2005 (Group I) to CHF patients who received IVF and GWTG-HF care from 6/06 to 4/07 (Group II). RESULTS: CHF cases in Group I equaled 773 as compared to 212 cases in Group II. Average LOS in I was 6.7 days as compared to 5.5 days in II (p = 0.001). Overall compliance with GWTG-HF Core Measures in 2006 was 98%. CONCLUSIONS: 1. Implementation of IVF in the ER with an EMR-POE order set helps ensure utilization of IVF in the ER at time of admission for CHF patients; 2. A multi-disciplinary team approach with use of IVF along with GWTG-HF is associated with a significant decrease in the LOS as compared to usual care; 3. A multi-disciplinary team approach to care for the CHF patient is superior to usual care with regards to LOS; and 4. GWTG-HF is associated with a high compliance with standards of hospitalized CHF care.
Counseling and Behavioral Interventions for Healthy Weight and Weight Gain in Pregnancy
Authors: Amy G. Cantor, Rebecca M. Jungbauer, Marian McDonagh, Ian Blazina, Nicole E. Marshall, Chandler Weeks, Rongwei Fu, Erin S. LeBlanc, Roger Chou
Journal: JAMA (2021)

<h3>Importance</h3> Counseling and active behavioral interventions to limit excess gestational weight gain (GWG) during pregnancy may improve health outcomes for women and infants. The 2009 National Academy of Medicine (NAM; formerly the Institute of Medicine) recommendations for healthy GWG vary according to prepregnancy weight category. <h3>Objective</h3> To review and synthesize the evidence on benefits and harms of behavioral interventions to promote healthy weight gain during pregnancy to inform the US Preventive Services Task Force recommendation. <h3>Data Sources</h3> Ovid MEDLINE and the Cochrane Library to March 2020, with surveillance through February 2021. <h3>Study Selection</h3> Randomized clinical trials and nonrandomized controlled intervention studies focused on diet, exercise, and/or behavioral counseling interventions on GWG. <h3>Data Extraction and Synthesis</h3> Independent data abstraction and study quality rating with dual review. <h3>Main Outcomes and Measures</h3> Gestational weight–related outcomes; maternal and infant morbidity and mortality; harms. <h3>Results</h3> Sixty-eight studies (N = 25 789) were included. Sixty-seven studies evaluated interventions during pregnancy, and 1 evaluated an intervention prior to pregnancy. GWG interventions were associated with reductions in risk of gestational diabetes (43 trials, n = 19 752; relative risk [RR], 0.87 [95% CI, 0.79 to 0.95]; absolute risk difference [ARD], −1.6%) and emergency cesarean delivery (14 trials, n = 7520; RR, 0.85 [95% CI, 0.74 to 0.96]; ARD, −2.4%). There was no significant association between GWG interventions and risk of gestational hypertension, cesarean delivery, or preeclampsia. GWG interventions were associated with decreased risk of macrosomia (25 trials, n = 13 990; RR, 0.77 [95% CI, 0.65 to 0.92]; ARD, −1.9%) and large for gestational age (26 trials, n = 13 000; RR, 0.89 [95% CI, 0.80 to 0.99]; ARD, −1.3%) but were not associated with preterm birth. Intervention participants experienced reduced weight gain across all prepregnancy weight categories (55 trials, n = 20 090; pooled mean difference, −1.02 kg [95% CI, −1.30 to −0.75]) and demonstrated lower likelihood of GWG in excess of NAM recommendations (39 trials, n = 14 271; RR, 0.83 [95% CI, 0.77 to 0.89]; ARD, −7.6%). GWG interventions were associated with reduced postpartum weight retention at 12 months (10 trials, n = 3957; mean difference, −0.63 kg [95% CI, −1.44 to −0.01]). Data on harms were limited. <h3>Conclusions and Relevance</h3> Counseling and active behavioral interventions to limit GWG were associated with decreased risk of gestational diabetes, emergency cesarean delivery, macrosomia, and large for gestational age. GWG interventions were also associated with modest reductions in mean GWG and decreased likelihood of exceeding NAM recommendations for GWG.
POS1240 HYDROXYCHLOROQUINE CARDIOTOXICITY: A CASE-CONTROL STUDY COMPARING PATIENTS WITH COVID19 AND PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: S. Mancuso, F. R. Spinelli, L. Agati, M. R. Ciardi, F. Natalucci, E. Molteni, S. Truglia, V. Riccieri, R. Priori, C. M. Mastroianni, F. Conti
Journal: Annals of the Rheumatic Diseases (2021)

Background: Antimalarials have been associated with QT prolongation in COVID19 patients but are generally safe in patients with rheumatologic disease. Objectives: Aim of the study was to compare the prevalence of QTc prolongation between COVID19 and Systemic Lupus Erythematosus (SLE) patients treated with hydroxychloroquine (HCQ). Methods: We included consecutive patients with SARS-CoV-2 infection confirmed by nasopharyngeal swab and patients taking HCQ for SLE. A prolonged QTc was defined as an increase in QTc intervals &gt;60 ms (compared with baseline) or as a QTc of ≥500 ms. Results: We enrolled 58 COVID19 patients (median age 70.5 years, IQR 25). HCQ, without or with azithromycin, was given to 26 (44.8%) and 15 patients (25.9%), respectively; 17 (29.3%) had not received either drug. The median baseline QTc was 432 (IQR 36) and prolonged QTc was observed in 15 (26%) patients (12 QTc≥500 ms and 3 patients ΔQTc&gt;60 ms). We didn’t find significant differences in QTc prolongation among the three treatment groups. Baseline QTc (OR 111.5) and D-dimer (OR 78.3) were independently associated to QTc prolongation. Compared to the 50 SLE patients (median age of 38.5 years, IQR 22), chronically treated with HCQ, patients with COVID19 showed significantly longer QTc (p &lt; 0.001) (Table 1). Conclusion: This is the first study demonstrating that, differently from COVID19 patients, patients with SLE are not susceptible to HCQ-induced long QT syndrome and arrhythmia. The combined arrhythmogenic effect of SARS-CoV-2 infection and HCQ could account for the excess of QTc prolongation and fatal arrhythmias described in patients with COVID19. Table 1. Difference in clinical and demographic features between Systemic Lupus Erythematosus and COVID19 patients. Demographic Features SLE patients Covid-19 patients p-Value N° 50 58 Female 43 23 &lt; 0.001 Age (years) 45 (17) 70.5 (25) &lt; 0.001 Comorbidities N % Hypertension 15 (30) 24 (48) 0.2 Cardiovascular diseses 8 (16) 13 (22.4) 0.4 COPD 1 (2) 9 (15.5) 0.016 Thyroid disease 8 (16) 8 (13.8) 0.75 Chronic kidney disease 4 (8) 5 (8.6) 0.91 Population characteristics Median (IQR ) HCQ (mg/die) 400 (125) 400 &lt; 0.001 HCQ Time (days) 3255 (5790) 7 &lt; 0.001 QTc (ms) SLEDAI-2K SDI 432 (36.25) 0 (4) 0 395 (80) - - &lt; 0.001 - - Disclosure of Interests: None declared
The novel tumor suppressor gene Hint1 may play a role in DNA damage responses by modulating the activity of Tip60
Authors: Haiyang Li, Adayabalam Balajee, Tao Su, Tom Hei, I. Weinstein
Journal: Cancer Research (2007)

1084  In previous studies we demonstrated that Hint1, which encodes a histidine triad protein, is a novel haploinsufficient tumor suppressor gene (Li, H., et al., Oncogene25, 713-721, 2006). In subsequent studies we have obtained evidence that the HINT1 protein plays a role in chromosome stability and the response of cells to DNA damage. Thus, we found that when compared to wild type (+/+) mouse embryo fibroblasts (MEF) Hint1 (+/-) and Hint1 (-/-) MEFs displayed frequent formation of micronuclei, unequal division, bulging, chromatin bridges, and multinucleation. Furthermore, after induction of DNA double strand breaks by ionizing radiation the Hint1 deficient cells had decreased levels of ATM acetylation, when compared to the wild type cells.The Hint1 deficient cells also displayed impaired activation of the ATM/ATR-Chk1/Chk2 DNA damage response pathways. In addition, the Hint1 deficient cells showed altered patterns of histone modifications after ionizing radiation, including decreased acetyl-H2AX foci formation and prolonged retention of phospho-H2AX foci. The Tip60 protein has been implicated in acetylation of ATM and H2AX. In addition HINT1 is a component of the Tip60 histone acetyltransferase complex (Weiske, J. and Huber, O. J. Biol. Chem.281, 27356-27366, 2006). Therefore, we postulate that HINT1 plays a role in chromatin remodeling and cellular responses to DNA double strand breaks by modulating the protein acetylating activity of Tip60. This function of Hint1 may contribute to its role as a tumor suppressor gene.
Venetoclax Combined With FLAG-IDA Induction and Consolidation in Newly Diagnosed and Relapsed or Refractory Acute Myeloid Leukemia
Authors: Courtney D. DiNardo, Curtis A. Lachowiez, Koichi Takahashi, Sanam Loghavi, Lianchun Xiao, Tapan Kadia, Naval Daver, Maria Adeoti, Nicholas J. Short, Koji Sasaki, Sa Wang, Gautam Borthakur, Ghayas Issa, Abhishek Maiti, Yesid Alvarado, Naveen Pemmaraju, Guillermo Montalban Bravo, Lucia Masarova, Musa Yilmaz, Nitin Jain, Michael Andreeff, Elias Jabbour, Guillermo Garcia-Manero, Steven Kornblau, Farhad Ravandi, Marina Y. Konopleva, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2021)

Sixty percent of newly diagnosed patients with acute myeloid leukemia (ND-AML) receiving frontline therapy attain a complete response (CR), yet 30%-40% of patients relapse. Relapsed or refractory AML (R/R-AML) remains a particularly adverse population necessitating improved therapeutic options. This phase Ib/II study evaluated the safety and efficacy of fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin combined with the B-cell lymphoma-2 inhibitor venetoclax in ND-AML and R/R-AML.The phase IB portion (PIB) enrolled patients with R/R-AML using a 3 + 3 dose escalation and de-escalation algorithm for identification of maximum tolerated dose and dose-limiting toxicities. The phase II portion enrolled patients into two arms to evaluate response and time-to-event end points: phase IIA (PIIA): ND-AML and phase IIB (PIIB): R/R-AML.Sixty-eight patients have enrolled to date (PIB, 16; PIIA, 29; PIIB, 23). Median age was 46 years (range, 20-73). Grade 3 and 4 adverse events occurring in ≥ 10% of patients included febrile neutropenia (50%), bacteremia (35%), pneumonia (28%), and sepsis (12%). The overall response rate for PIB, PIIA, and PIIB was 75%, 97%, and 70% with 75%, 90%, and 61%, respectively, achieving a composite CR. Measurable residual disease-negative composite CR was attained in 96% of ND-AML and 69% of R/R-AML patients. After a median follow-up of 12 months, median overall survival (OS) for both PII cohorts was not reached. Fifty-six percent of patients proceeded to allogeneic hematopoietic stem-cell transplantation (ND-AML, 69%; R/R-AML, 46%). In R/R-AML, allogeneic hematopoietic stem-cell transplantation resulted in a significant improvement in OS (median OS, NR; 1-year OS, 87%). One-year survival post-HSCT was 94% in ND-AML and 78% in R/R-AML.Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin + venetoclax represents an effective intensive treatment regimen in ND-AML and R/R-AML patients, associated with deep remissions and a high rate of transition to successful transplantation.