tbuckley/cabot-search huggingface dataset:
PF341 LUSUTROMBOPAG FOR TREATMENT OF THROMBOCYTOPENIA IN PATIENTS WITH CHRONIC LIVER DISEASE WHO ARE UNDERGOING PLANNED INVASIVE PROCEDURES: POOLED SAFETY ANALYSIS OF BLEEDING‐RELATED ADVERSE EVENTS
Authors: E.G. Giannini, T. Kano, T. Ochiai, R. Bentley, P. Shrestha
Journal: HemaSphere (2019)

Background: Thrombocytopenia is a common complication in patients with chronic liver disease. Furthermore, a low platelet count in chronic liver disease patients who require an invasive procedure is a serious condition that may be associated with an increased risk of bleeding during or after the procedure. Lusutrombopag is a thrombopoietin receptor agonist approved in Japan and US for improvement of thrombocytopenia, and in EU for severe thrombocytopenia, associated with chronic liver disease in patients undergoing planned invasive procedures. Aims: A pooled safety analysis was performed to assess differences in bleeding events following treatment with lusutrombopag without platelet transfusion or placebo with platelet transfusion. Methods: Safety data were pooled from 3 double‐blind, placebo‐controlled studies, in patients with thrombocytopenia associated with chronic liver disease undergoing a planned invasive procedure (Phase 2b: M0626 [Japan; JapicCTI‐121944]; Phase 3: L‐PLUS 1 [Japan; JapicCTI‐132323], L‐PLUS 2 [global; NCT02389621]). Patients enrolled in these studies were randomized to lusutrombopag 3 mg or placebo for up to 7 days prior to procedure. Platelet transfusion was administered if platelet count was &lt;50x10 9 /L no more than 2 days prior to procedure. Patients were classified into 1 of 4 subgroups: lusutrombopag with or without platelet transfusion or placebo with or without platelet transfusion. This analysis focused on patients in the lusutrombopag without platelet transfusion and placebo with platelet transfusion subgroups. Bleeding events were summarized pre‐, during, and post‐procedure. Results: Lower bleeding event rates, regardless of severity and timing of onset, were observed for lusutrombopag alone vs placebo+platelet transfusion ( Table ). Percent of patients with bleeding events was numerically higher with placebo+platelet transfusion vs lusutrombopag alone, both during (4.8% vs 3.2%) and post‐procedure (7.1% vs 4.0%). Percent of patients with bleeding events in liver‐related procedures was greater in the placebo+platelet transfusion arm (16.1%) vs lusutrombopag alone (11.1%), and a larger difference was seen with gastrointestinal‐related procedures in placebo+platelet transfusion (8.9%) vs lusutrombopag alone (2.0%). Summary/Conclusion: In this pooled analysis, a trend toward lower bleeding event rates was observed with lusutrombopag alone vs placebo+platelet transfusion, regardless of type of invasive procedure. image
FRI0482 RISK FACTORS FOR FRAGILITY FRACTURE IN PATIENTS WHO SMOKE: AN OBSERVATIONAL STUDY
Authors: Dominic Beith, Marwan Bukhari
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Smoking is a risk factor for osteoporosis and increases the likelihood of a fragility fracture. It is included in the FRAX™ tool, which is used as an aid for bone mineral density (BMD) referral and as a risk stratification for the propensity of developing a fragility fracture. The additive effect of other risk factors including demographics increasing the risk of fracture has not been explored in a large cohort. <h3>Objectives</h3> To investigate the additive predictors of fracture in patients who have smoking as their only risk for fracture, referred for BMD estimation. <h3>Methods</h3> Patients who were referred for bone mineral density (BMD) estimation in a scanner in the North West of England between June 2004 and October 2015 were included in the analysis. Patients with only smoking as a FRAX™ risk factor were then analysed. All patients have their other risk factors for fracture and demographics recorded at time of scan. All patients with other FRAX™ indications for scanning were excluded including Rheumatoid Arthritis, Excess Alcohol, Steroids, family history of fracture and Secondary Osteoporosis. Patients in the smoking group were divided into those that had experienced a fracture and those that had not before comparing with Chi-squared test for categorical variables and T-test for continuous variables. Univariate and multivariate logistic models were then fitted to examine predictors of fracture in this group. <h3>Results</h3> 35,759 patients were referred for scanning during the period. 4096 (11.45%) were referred with smoking as their only indication for scanning. Mean age at scan was 64.43 (SD 12.38) and 3244 (79%) of the cohort were females. 1663(40.60%) had a fracture. Fractures were more prevalent in males with 383 (44.95%) compared to 1280 (39.46%) in females (p=&lt;0.05). Univariate predictors shown in the Table 1 below. In the multivariate model, the only variables associated with increased fracture risk was increasing age at scan decreased BMD total left and increased percentage body fat. All other factors did not significantly increase fracture risk in this cohort. <h3>Conclusion</h3> Our study suggests that many risk factors are associated with fragility fractures in those with smoking as their only risk factor; the best predictor was age at scan, BMD and gender. The percentage body fat association with increased fracture risk is quite surprising and would need further study. Percentage body fact is not currently included in the FRAX™ tool. <h3>Disclosure of Interests</h3> Dominic Beith: None declared, Marwan Bukhari Speakers bureau: Bristol-Myers Squib, UCB celltech, Roche/Chugai, Pfizer, Abbvie, Merck, Mennarini, Sanofi-aventis, Eli-Lilly, Janssen and Novartis.
Population perception of mandatory childhood vaccination programme before its implementation, France, 2017
Authors: Pauline Mathieu, Arnaud Gautier, Jocelyn Raude, Thomas Goronflot, Titouan Launay, Marion Debin, Caroline Guerrisi, Clement Turbelin, Thomas Hanslik, Christine Jestin, Vittoria Colizza, Thierry Blanchon, Louise Rossignol
Journal: Eurosurveillance (2019)

BackgroundVaccination policy in France was previously characterised by the coexistence of eight recommended and three mandatory vaccinations for children younger than 2 years old. These 11 vaccines are now mandatory for all children born after 1 January 2018.AimTo study the French population's opinion about this new policy and to assess factors associated with a positive opinion during this changing phase.MethodsA cross-sectional survey about vaccination was conducted from 16 November-19 December 2017 among the GrippeNet.fr cohort. Data were weighted for age, sex and education according to the French population. Univariate and multivariate analyses were performed to identify factors associated with a favourable opinion on mandatory vaccines' extension and defined in the '3Cs' model by the World Health Organization Strategic Advisory Group of Experts working group on vaccine hesitancy.ResultsOf the 3,222 participants (response rate 50.5%) and after adjustment, 64.5% agreed with the extension of mandatory vaccines. It was considered a necessary step by 68.7% of the study population, while 33.8% considered it unsafe for children and 56.9% saw it as authoritarian. Factors associated with a positive opinion about the extension of mandatory vaccines were components of the confidence, complacency and convenience dimensions of the '3Cs' model.ConclusionsIn our sample, two thirds of the French population was in favour of the extension of mandatory vaccines for children. Perception of vaccine safety and benefits were major predictors for positive and negative opinions about this new policy.
Surgery or stereotactic body radiotherapy for early-stage lung cancer: two sides of the same coin?
Authors: Lawek Berzenji, Paul E. Van Schil
Journal: European Respiratory Journal (2019)

Currently, the standard of care for resectable, early-stage and functionally operable nonsmall cell lung cancer (NSCLC) is complete surgical resection [1]. However, for elderly patients and patients with multiple comorbidities, surgery may not be the preferred option due to higher surgical morbidity and mortality [2]. An alternative treatment for this group of patients is stereotactic body radiotherapy (SBRT), which administers a high local dose of radiation in fewer fractions as an ablative treatment [3]. In recent years, SBRT has gained in popularity as it has shown better local control rates and less toxicity to surrounding structures when compared to conventional fractionated radiotherapy (CFRT). This was confirmed by the recently published CHISEL phase III randomised controlled trial (RCT) [4].
Serotonergic pathology and disease burden in the premotor and motor phase of A53T α-synuclein parkinsonism: a cross-sectional study
Authors: Heather Wilson, George Dervenoulas, Gennaro Pagano, Christos Koros, Tayyabah Yousaf, Marina Picillo, Sotirios Polychronis, Athina Simitsi, Beniamino Giordano, Zachary Chappell, Benjamin Corcoran, Maria Stamelou, Roger N Gunn, Maria Teresa Pellecchia, Eugenii A Rabiner, Paolo Barone, Leonidas Stefanis, Marios Politis
Journal: The Lancet Neurology (2019)
PB2181 THE ROLE OF 18F-FDG PET/CT IN THE INITIAL DIAGNOSIS AND STAGING OF PATIENTS WITH MULTIPLE MYELOMA
Authors: I. Micheva, S. Dimitrova, S. Rangelova, B. Chaushev, L. Gercheva
Journal: HemaSphere (2019)

Background: Diagnostic imaging in multiple myeloma (MM) plays a pivotal role in staging and prognostic assessment as well as in planning and monitoring treatment. New imaging techniques such as magnetic resonance imaging (MRI), whole body FDG PET scanning and whole body CT combined with PET directly or by fusion offer the opportunity to precisely stage patients by anatomic and functional techniques. This has been accomplished by the development of the Durie/Salmon PLUS staging system (Durie/Salmon PLUS SS), based on the number of bone lesions and serum creatinine. Aims: The aim of the study was to evaluate the extent of bone disease and extramedullary involvement at the time of initial diagnosis using 18F-FDG PET/CT. Methods Materials and methods: 42 patients with newly diagnosed MM were included in the study. The stage of the disease was determined according to ISS. 18F-FDG PET/CT was used for the detection of the bone lesions and the stage was reassessed according to Durie–Salmon PLUS SS. Results: 42 patients were analyzed; 26 males and 16 females; median age 63.5 years (45- 83 years); 23 IgG, 8 IgA and 8 light chains MM, 3 non secretory MM. According to ISS 17 patients were stage 1, 11-stage 2 and 14-stage 3. According to Durie–Salmon PLUS SS 6 patients were in stage I A, 12 in stage II A, 9 patient in stage IB, 13 patients in stage IIIA and 2 in stage IIIB. 8 of the patients assessed in stage 1 according to ISS were reevaluated in a higher stage according to Durie–Salmon PLUS SS-5 in stage IIA and 3 in stage III A. 4 from the 11 patients in stage II ISS were evaluated as IA and IB according to Durie–Salmon PLUS SS, whether 4 were evaluated as IIIA. 2 from 14 of the patients assessed in stage 3 according to ISS were evaluated in IA and 4 in IIA according to Durie–Salmon PLUS SS. No correlation was found between stage according to Durie–Salmon PLUS SS and the MM Ig type, bone marrow plasma cell infiltration, LDH, and hemoglobin level. No correlation was found between the number of bone lesions and their activity (Deauville scoring system). The two staging systems had equal impact on the survival. Summary/Conclusion: 18F-FDG PET/CT has shown to have high sensitivity and specificity in patients with MM. Correct staging using 18F-FDG PET/CT can serve as a basis for clinical assessment and clinical decision-making. It ensures the avoidance of unnecessary treatment, initiation of early treatments for patients with overt bonedisease, and identification of poorer risk patients with >20 focal lesions and/or extramedullary disease.
C-Type Natriuretic Peptide Analogue Therapy in Children with Achondroplasia
Authors: Ravi Savarirayan, Melita Irving, Carlos A. Bacino, Bret Bostwick, Joel Charrow, Valerie Cormier-Daire, Kim-Hanh Le Quan Sang, Patricia Dickson, Paul Harmatz, John Phillips, Natalie Owen, Anu Cherukuri, Kala Jayaram, George S. Jeha, Kevin Larimore, Ming-Liang Chan, Alice Huntsman Labed, Jonathan Day, Julie Hoover-Fong
Journal: New England Journal of Medicine (2019)

Achondroplasia is a genetic disorder that inhibits endochondral ossification, resulting in disproportionate short stature and clinically significant medical complications. Vosoritide is a biologic analogue of C-type natriuretic peptide, a potent stimulator of endochondral ossification.
PS1280 FUNGAL INFECTIONS IN ACUTE MYELOID LEUKEMIA IN THE POSACONAZOLE ERA
Authors: C. Marini, A. Baldaia, P. Chorão, R. Bergantim, E. Aguiar, J. Cancela, F. Trigo, J.E. Guimarães
Journal: HemaSphere (2019)

Background: Posaconazole prophylaxis in patients with acute myeloid leukaemia (AML) changed the paradigm of fungal infections (FI). Aims: Description of FI and analysis of factors that might predispose to this type of infection in non‐allotransplant AML patients in the posaconazole era. Methods: Retrospective analysis of 144 consecutive non‐M3 AML patients diagnosed between January 2012 and June 2018 in a tertiary center and treated with intensive chemotherapy regimens with posaconazole prophylaxis, including autologous transplantation when performed in these patients. Multivariate regression analysis was performed to identify characteristics related to FI. Results: Median age at diagnosis was 52 years [19;71], 52% were females and 90% had an age‐adjusted Charlson score ≤3. Genetic risk group according to the European Leukemia Net 2017 classification was favourable in 28%, intermediate in 41% and adverse in 22%. Fourteen percent of patients (n = 20) had secondary AML. Patients were included since diagnosis and if completed remission‐induction intensive therapy up to transplant referral, the latter which occurred in 52% of patients (n = 75), with a median follow‐up of 7 months [1;81]. Only 7 patients had 1 episode of prophylaxis interruption, 3 due to mucositis and 4 out of our protocol. Median time of neutropenia per cycle was 26 days [5;180] and 10% of patients had &gt;2 episodes of prolonged neutropenia (defined as ≥28 consecutive days of &lt;500 neutrophils/microliter). Fungal infections were identified in 25 patients (17.4%) and classified according to EORTC criteria, with 5 proven, 13 probable and 7 possible infections. In 32% of patients FI occurred during remission‐induction (n = 8) of which 3 were diagnosed in the first week of neutropenia, 20% during consolidation treatment in first remission and 48% during relapse treatment. Of the confirmed infections, 3 were aspergillosis and 2 candidemia. Probable infections had pulmonary origin with no microbiology isolate or serologic positivity but identified by typical radiologic evidence; of these, broncho‐alveolar lavage and/or pulmonary biopsy was performed in 4 patients (31%) with negative results. For possible infections, antifungal therapy was initiated in a pre‐emptive manner for high risk patients with persistent fever despite large spectrum antibiotics. In a multivariate analysis, patients with FI had a higher odds of having relapsed AML and &gt;2 episodes of prolonged neutropenia during treatment (p = 0.049 and p = 0.011, respectively). There was no mortality related to FI in this cohort of patients. Summary/Conclusion: Despite posaconazole prophylaxis, FI is still prevalent in AML patients. Infection during salvage treatment for relapsed disease and &gt;2 previous periods of neutropenia exceeding 4 weeks should raise awareness for an increased risk of FI.
OP0030 RANDOMIZED CONTROLLED 24-WEEK TRIAL EVALUATING THE SAFETY AND EFFICACY OF BLINDED TAPERING VERSUS CONTINUATION OF LONG-TERM PREDNISONE (5 MG/D) IN PATIENTS WITH RHEUMATOID ARTHRITIS WHO ACHIEVED LOW DISEASE ACTIVITY OR REMISSION ON TOCILIZUMAB
Authors: Gerd Rüdiger Burmester, Frank Buttgereit, Corrado Bernasconi, Jose-Maria Alvaro-Gracia, Nidia Castro, Maxime Dougados, Cem Gabay, M. Jacob, van Laar, J. Michael Nebesky, Attila Pethoe-Schramm, Carlo Salvarani, Marc Y. Donath, Markus R. John
Journal: Annals of the Rheumatic Diseases (2019)

Results: Of the 651 and 327 pts randomized to receive UPA and ADA, 126 (19%) and 77 (24%), were considered NR and switched to ADA and UPA respectively.NR demographics were consistent with the overall randomized population.Of the switched pts, ~90% remained in the study through 6 mo ps.Patients switched to ADA (UPA-NR) achieved 59%/26%/12% improvements in ACR20/50/70 responses, and 35% achieved DAS28(CRP) £3.2 at 6 mos ps (Table ).Patients switched to UPA (ADA-NR) achieved 75%/49%/24% improvements in ACR20/50/ 70, and 54% achieved DAS28(CRP) £3.2 at 6 mo-consistent with data observed in a phase 3 study of UPA in bDMARD-IR RA pts. 4 The proportion (95% CI) of pts with infection and serious infection through 6 mos ps appeared consistent with those observed for ADA and UPA during comparable periods (ADA, switched from UPA: infection: 34.1 [26.43, 42.77], serious infection: 1.6 [0.44, 5.60]; UPA, switched from ADA: infection: 40.3 [30.02, 51.42], serious infection: 3.9 [1.33, 10.84] Conclusion: Data from this blinded, controlled study indicate that pts with initial non-response to either UPA or ADA can benefit from switching to the other therapy.No additional safety concerns were observed.These are the first data to demonstrate effectiveness of a TNF inhibitor following failure of a JAK inhibitor.
Ruxolitinib or Dasatinib in Combination with Chemotherapy for Patients with Relapsed/Refractory Philadelphia (Ph)-like Acute Lymphoblastic Leukemia: A Phase I-II Trial
Authors: Nitin Jain, Elias J. Jabbour, Patrick Zweider McKay, Farhad Ravandi, Koichi Takahashi, Tapan Kadia, William G Wierda, Michael E. Rytting, Cesar Nunez, Keyur Patel, Xinyan Lu, Guilin Tang, Sergej Naumovich Konoplev, Sa A. Wang, Lina Han, Beenu Thakral, Kathryn G. Roberts, April Deshmukh, Rebecca Garris, Jeffrey L. Jorgensen, Antonio Cavazos, Srdan Verstovsek, Guillermo Garcia-Manero, Susan M. O'Brien, Jorge E. Cortes, Charles G. Mullighan, Hagop M. Kantarjian, Marina Konopleva
Journal: Blood (2017)
Solutions to Reduce Unnecessary Imaging
Authors: Frederick A. Simeone
Journal: JAMA (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 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
Comparison of Bisphenol A and Bisphenol S Percutaneous Absorption and Biotransformation
Authors: Jiaying Liu, Jonathan W. Martin
Journal: Environmental Health Perspectives (2019)

Background: Bisphenol S (BPS) has been widely substituted for bisphenol A (BPA) on thermal papers, but little is known about its skin absorption. Objectives: We compared the percutaneous absorption and biotransformation of BPS and BPA in vitro and in a controlled human trial. Methods: Absorption and biotransformation of BPS and BPA were monitored across reconstructed human epidermis at two environmentally relevant doses over 25 h. In the human trial, five male participants handled thermal receipts containing BPS and washed their hands after 2 h. Urine (0–48 h) and serum (0–7.5h) were analyzed for target bisphenols, and one participant repeated the experiment with extended monitoring. BPS data were compared with published data for isotope-labeled BPA (BPA-d16) in the same participants. Results: At doses of 1.5 and 7.7 μg/cm2 applied to reconstructed human epidermis, the permeability coefficient of BPS (0.009 and 0.003cm/h, respectively) was significantly lower than for BPA (0.036 and 0.033cm/h, respectively), and metabolism of both bisphenols was negligible. In participants handling thermal receipts, the quantities of BPS and BPA-d16 on hands was significantly correlated with maximum urinary event flux (μg), but the slope was lower for BPS than BPA (β=0.12 and 1.1, respectively). As a proportion of total urinary bisphenol, free BPS [mean±standard deviation (SD): 6.9±2.8%] was higher than for free BPA (2.7±1.9%). Postexposure maximum urinary BPS concentrations (0.93 to 3.0 ng/mL; n=5) were in the 93–98th percentile range of BPS in background Canadians (0.91–3.2 ng/mL; n=467). Conclusion: Both the in vitro and human studies suggested lower percutaneous absorption of BPS compared with BPA, but a lower biotransformation efficiency of BPS should also be considered in its evaluation as a BPA substitute. https://doi.org/10.1289/EHP5044
Paclitaxel-Coated Balloons and Eluting Stents: Is There a Mortality Risk in Patients With Peripheral Artery Disease?
Authors: Joshua A. Beckman, Christopher J. White
Journal: Circulation (2019)

Paclitaxel drug-coated balloons and drug-eluting stents became commercially available for the treatment of intermittent claudication in 2015 and 2012, respectively. Both devices demonstrated superiority in limb revascularization compared with non-paclitaxel-coated devices and were rapidly accepted into clinical practice. In a recent systematic review and study-level meta-analysis, Katsanos et al reported a late all-cause mortality signal for patients in the drug-coated balloon and drug-eluting stent arms of randomized clinical trials for both devices. As a result of this safety signal, Vascular InterVentional Advances Physicians (VIVA), a not-for-profit 501c(3) organization, convened the Vascular Leaders Forum on March 1 and 2, 2019, in Washington, DC, to initiate an open and collaborative process of investigation into this finding. The Vascular Leaders Forum brought together 100 stakeholders, including an international group of representatives of cardiovascular medicine, interventional radiology, vascular medicine, and vascular surgery; oncologists; basic scientists; the Food and Drug Administration; the Centers for Medicare and Medicaid Services; and commercial manufacturers of these products. The Vascular Leaders Forum reviewed the natural history of peripheral arterial disease, the use of paclitaxel in peripheral arterial disease and other conditions, the harm signal noted by Katsanos et al, the impact of the methods chosen by Katsanos et al, possible mechanisms of harm, the role of the Food and Drug Administration in a setting like this one, and guidance for clinicians taking care of patients with symptomatic peripheral arterial disease. This document integrates the most current data to help establish an appropriate path forward to understand the risks and benefits associated with these technologies while ensuring the best treatment paradigm for patients.
Abstract 14472: Iron Deficiency Plays an Important Prognostic Role in the Cardiorenal Anemia Axis: A Pooled Multicenter Analysis
Authors: IJsbrand T Klip, Ewa A Jankoswka, Cristina Enjuanes, Adriaan A Voors, Waldemar Banasiak, Jordi Bruguera, Piotr Rozentryt, Lech Polonski, Dirk Jan van Veldhuisen, Piotr Ponikowski, Josep Comin-Colet, Peter van der Meer
Journal: Circulation (2013)

Background: Anemia, chronic kidney disease (CKD) and iron deficiency (ID) are frequently observed comorbidities in chronic heart failure (HF) and all independent predictors of outcome. The combinat...