tbuckley/cabot-search huggingface dataset:
Personalising add-on treatment with inhaled corticosteroids in patients with chronic obstructive pulmonary disease: a benefit–harm modelling study
Authors: Henock G Yebyo, Julia Braun, Dominik Menges, Gerben ter Riet, Mohsen Sadatsafavi, Milo A Puhan
Journal: The Lancet Digital Health (2021)

BackgroundSince the benefit–harm balance of adding inhaled corticosteroids to long-acting β2-agonists (LABA) and long-acting muscarinic antagonists (LAMA) for patients with chronic obstructive pulmonary disease is unclear, we evaluated this addition for a range of patient profiles.MethodsAnalyses considered the effects of low-to-moderate doses of inhaled corticosteroids, LABA, and LAMA compared with LABA and LAMA alone, outcome incidences, and preference weights assigned to averted moderate-to-severe exacerbations (benefit) and severe pneumonia, candidiasis, and dysphonia (harm). Using exponential models, we estimated the preference weight-adjusted 2-year net clinical benefit (ie, benefits outweighing harms) indices. Exacerbation risk thresholds for triggering inhaled corticosteroids, LABA, and LAMA were established when the probability of a 2-year net clinical benefit reached 60%. We estimated the proportion of patients benefiting from added inhaled corticosteroids using an externally validated prediction model for acute exacerbations in primary care.FindingsAdding low-to-moderate dose inhaled corticosteroids to LABA and LAMA provided a net clinical benefit in patients with a 2-year baseline exacerbation risk of 54–83%. Low-dose inhaled corticosteroids showed a net clinical benefit if the baseline risk was 40–91%, but not at higher doses. The benefit was modified by blood eosinophil count (BEC) and age. Although no net benefit was associated with a BEC of less than 150 cells per μL, patients with a BEC of 150 cells per μL or more had a net benefit from low-dose inhaled corticosteroids with a 2-year exacerbation risk of 32–95% in those aged 40–79 years and 41–93% in those older than 80 years. A moderate dose of inhaled corticosteroids showed a net benefit in patients younger than 80 years with a BEC of 150 cells per μL or more at 52–86% 2-year exacerbation risk. Depending on the subgroups, the proportion of patients with a net benefit from added inhaled corticosteroids ranged from 0 to 68%.InterpretationThe net clinical benefit of adding different inhaled corticosteroid doses to LABA and LAMA varies greatly with exacerbation risk, BEC, and age. Personalised treatment decisions based on these factors and predicted exacerbation risks might reduce overtreatment and undertreatment with inhaled corticosteroids.FundingNone.
AB0904-HPR RHEUMATOLOGY NURSING AND COVID19: FIRST WAVE EXPERIENCES
Authors: L. Cano Garcia, S. Garcia Diaz, S. P. Fernandez-Sanchez, C. Domínguez-Quesada, M. D. C. Ordoñez Cañizares, J. M. Martín Martín
Journal: Annals of the Rheumatic Diseases (2021)

Objectives: To know the impact of the first wave of COVID19 (March to June 2020) in the nursing activity in rheumatology and explore improvements in patient care during the pandemic situation. Methods: 2 surveys were sent to nurses working in the rheumatology area (Both in the Outpatient department and day care unit) during October 2020 in Spain. The first survey had 10 questions about what happened in the rheumatology units in the first wave of the COVID19 pandemic (March to June of 2020) and the second survey had 10 questions about the standards of quality of nursing care in times of pandemic. Google forms were used to collect and analyze data. Results: 32 nurses completed the survey (30 women (93.8%)) with an average age of 49.6 ± 10.2 years. 93.8% work in the outpatient clinics and 2(6.2%) in day care units. The main results of the effects of the first wave of the pandemic are as follow: 4(12.5%) nurses were transferred to other areas of the hospital, 27(84.4%) showed changes in their care activity; and in 12(37,5%) of the surveyed centers, (slightly less than half of the medical staff) left their usual activity to care for covid-19 patients. In June 2020, at the end of the first wave, 17(53.1%) reported more decompensated patients and 22(68.8%) reported that they had both telephone and face-to-face consultations; 15(46.9%) reported that their clinical activity had increased. Regarding the standards of quality during the pandemia: 27(84.4%) believed that rheumatology units should be strengthened,31(96.9%) reported the need to carry out COVID educational campaigns in rheumatic patients and 30(100%) stated that nursing education should lead that education; 31(96.7%) believed that telephone consultation should be on demand and by telephone, 25 (78.1%) considered it necessary to include video calls and the possibility of receiving reports in non-face to face care and photos. Finally, 23(71.9%) centers recorded nursing and medical telephone consultations in their medical records. Conclusion: The pandemic had a huge impact on nursing care for rheumatic patients, with difficulties associated with extra work load and changes in the dynamics of care. A readjustment of assistance has been necessary and audiovisual aids were necessary to improve telephone (non face to face) service. Disclosure of Interests: None declared
New COVID-19 Cases and Hospitalizations Among Adults, by Vaccination Status — New York, May 3–July 25, 2021
Authors: Eli S. Rosenberg, David R. Holtgrave, Vajeera Dorabawila, MaryBeth Conroy, Danielle Greene, Emily Lutterloh, Bryon Backenson, Dina Hoefer, Johanne Morne, Ursula Bauer, Howard A. Zucker
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Data from randomized clinical trials and real-world observational studies show that all three COVID-19 vaccines currently authorized for emergency use by the Food and Drug Administration* are safe and highly effective for preventing COVID-19-related serious illness, hospitalization, and death (1,2). Studies of vaccine effectiveness (VE) for preventing new infections and hospitalizations attributable to SARS-CoV-2, the virus that causes COVID-19), particularly as the B.1.617.2 (Delta) variant has become predominant, are limited in the United States (3). In this study, the New York State Department of Health linked statewide immunization, laboratory testing, and hospitalization databases for New York to estimate rates of new laboratory-confirmed COVID-19 cases and hospitalizations by vaccination status among adults, as well as corresponding VE for full vaccination in the population, across all three authorized vaccine products. During May 3-July 25, 2021, the overall age-adjusted VE against new COVID-19 cases for all adults declined from 91.7% to 79.8%. During the same period, the overall age-adjusted VE against hospitalization was relatively stable, ranging from 91.9% to 95.3%. Currently authorized vaccines have high effectiveness against COVID-19 hospitalization, but effectiveness against new cases appears to have declined in recent months, coinciding with the Delta variant's increase from <2% to >80% in the U.S. region that includes New York and relaxation of masking and physical distancing recommendations. To reduce new COVID-19 cases and hospitalizations, these findings support the implementation of a layered approach centered on vaccination, as well as other prevention strategies such as masking and physical distancing.
Room for methodological improvement in gait speed study for COPD patients
Authors: Naoto Kuroda, Akihiro Shiroshita, Yasushi Tsujimoto
Journal: European Respiratory Journal (2021)

<b>Regarding the gait speed study for COPD patients reported by J.A. Walsh and co-workers, there are 3 concerns: 1) lack of internal validation; 2) methodology of comparing model performance; and 3) a way of handling competing risks in the Fine and Gray model</b>https://bit.ly/3g6I8BN
Preventing Media-Based False Hopes—Reply
Authors: Mary O’Keeffe, Alexandra Barratt, Ray Moynihan
Journal: JAMA Internal Medicine (2021)

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 Journals 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
Asymmetric flow field-flow fractionation (AF4) with fluorescence and multi-detector analysis for direct, real-time, size-resolved measurements of drug release from polymeric nanoparticles
Authors: Sheyda Shakiba, Carlos E. Astete, Rafael Cueto, Debora F. Rodrigues, Cristina M. Sabliov, Stacey M. Louie
Journal: Journal of Controlled Release (2021)

Polymeric nanoparticles (NPs) are typically designed to enhance the efficiency of drug delivery by controlling the drug release rate. Hence, it is critical to obtain an accurate drug release profile. This study presents the first application of asymmetric flow field-flow fractionation (AF4) with fluorescence detection (FLD) to quantify release profiles of fluorescent drugs from polymeric NPs, specifically poly(lactic-co-glycolic acid) NPs loaded with enrofloxacin (PLGA-Enro NPs). In contrast to conventional measurements requiring separation of the NPs and dissolved drugs (typically by dialysis) prior to quantification, AF4 provides in situ removal of unincorporated drugs, while the judicious combination of online FLD and UV detection selectively provides the entrapped drug and PLGA NP concentrations, respectively, and hence the drug loading. NP size and shape factors are simultaneously obtained by online dynamic and multi-angle light scattering (DLS, MALS) detectors. The AF4 and dialysis approaches were compared to evaluate drug release from PLGA-Enro NPs containing a high proportion (≈ 94%) of unincorporated (burst release) drug at three temperatures spanning the glass transition temperature (Tg ≈ 33 °C) of the NPs. The AF4 method clearly captured the temperature dependence of the drug release relative to Tg (from no release at 20 °C to rapid release at 37 °C). In contrast, dialysis was not able to distinguish differences in the extent or rate of release of the entrapped drug because of interferences from the burst release, as well as the dialysis lag time, as supported through a diffusion model and validation experiments on purified NPs with low burst release. Finally, the multi-detector AF4 analysis yielded unique size-dependent release profiles across the entire NP size distribution, with smaller NPs showing faster release consistent with radial diffusion from the NPs. Overall, this study demonstrates the novel application and advantages of multi-detector AF4 methods, particularly AF4-FLD, to obtain direct, size-resolved release profiles of fluorescent drugs from polymeric NPs.
Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk
Authors: Marco Valgimigli, Enrico Frigoli, Dik Heg, Jan Tijssen, Peter Jüni, Pascal Vranckx, Yukio Ozaki, Marie-Claude Morice, Bernard Chevalier, Yoshinobu Onuma, Stephan Windecker, Pim A.L. Tonino, Marco Roffi, Maciej Lesiak, Felix Mahfoud, Jozef Bartunek, David Hildick-Smith, Antonio Colombo, Goran Stanković, Andrés Iñiguez, Carl Schultz, Ran Kornowski, Paul J.L. Ong, Mirvat Alasnag, Alfredo E. Rodriguez, Aris Moschovitis, Peep Laanmets, Michael Donahue, Sergio Leonardi, Pieter C. Smits
Journal: New England Journal of Medicine (2021)

The appropriate duration of dual antiplatelet therapy in patients at high risk for bleeding after the implantation of a drug-eluting coronary stent remains unclear.
Correspondence re: M. I. Bemhard, K. M. Hwang, K. A. Foon, A. M. Keenan, R. M. Kessler, J. M. Frincke, D. J. Tallam, M. G. Hanna, Jr., L. Peters, and R. K. Oldham. Localization of 111In- and 125I-labeled Monoclonal Antibody in Guinea Pigs Bearing Line 10 Hepatocarcinoma Tumors. Cancer Res., 43: 4429–4433, 1983–Reply
Authors: Michael Bernhard, Robert K. Oldham, Kenneth A. Foon, Andrew Keenan
Journal: Cancer Research (1984)
Cytogenetic Alterations Are Differently Associated with Disease Progression Depending on t(14;18) in Follicular Lymphoma
Authors: Akihiko Yokohama, Takeki Mitsui, Hiromi Koiso, Akio Saito, Kohtaro Toyama, Hiroaki Shimizu, Takuma Ishizaki, Yoko Hashimoto, Makiko Takizawa, Hiroyuki Irisawa, Kayoko Murayama, Morio Matsumoto, Takayuki Saito, Hiroshi Handa, Hirokazu Murakami, Norifumi Tsukamoto
Journal: Blood (2017)
Low-value health care in the COVID-19 pandemic
Authors: Joseph L Mathew
Journal: The Lancet Global Health (2021)

Low-value health care in the COVID-19 pandemicIn their Comment, Soumyadeep Bhaumik and colleagues 1 summarise the burden and consequences of non-evidence-based COVID-19 management in India, highlighting the need for evidence-informed guidelines on various aspects of clinical management and health care delivery.In India, there is a plethora of so-called guidelines on COVID-19 management and several other topics.However, most of these are administrative documents in which the processes and products are not necessarily based on scientific considerations.By contrast, the process of developing evidencebased guidelines includes a six-step approach: asking an answerable question, accessing literature, assimilating evidence, appraising the evidence for risk of bias, analysing the evidence (quantitively and qualitatively), and applying the evidence to develop a guideline.The products of such guidelines are actionable recommendations linked to the evidence, along with judgments on evidence strength, confidence in the evidence, benefits versus risk balance, implementation considerations, and alternative options.Viewed in this context, most of the current socalled COVID guidelines are not really guidelines.However, there are two rays of hope.The first is the COVID-19 Recommendations Map project, led by Holger Schünemann, involving institutions across developed and developing counties. 2Schünemann and colleagues created a portal providing free-of-charge, userfriendly access to a living map of COVID-19 recommendations, sourced from guidelines published globally.Users can search for guideline recommendations among more than 100 topics related to COVID-19, across eight management domains.
Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients—a multinational observational study by the European Confederation of Medical Mycology
Authors: Juergen Prattes, Joost Wauters, Daniele Roberto Giacobbe, Jon Salmanton-García, Johan Maertens, Marc Bourgeois, Marijke Reynders, Lynn Rutsaert, Niels Van Regenmortel, Piet Lormans, Simon Feys, Alexander Christian Reisinger, Oliver A. Cornely, Tobias Lahmer, Maricela Valerio, Laurence Delhaes, Kauser Jabeen, Joerg Steinmann, Mathilde Chamula, Matteo Bassetti, Stefan Hatzl, Riina Rautemaa-Richardson, Philipp Koehler, Katrien Lagrou, Martin Hoenigl, Yves Debaveye, Marisa H. Miceli, Jean-Jacques Tudesq, Gregor Paul, Robert Krause, Marina Linhofer, Jonas Frost, Peter Zechner, Matthias Kochanek, Philipp Eller, Jeffrey D. Jenks, Sara Volpi, Anne-Pauline Bellanger, P.Lewis White, Gustavo H. Goldman, Paul Bowyer, Antonis Rokas, Sara Gago, Paolo Pelosi, Chiara Robba, Jean-Pierre Gangneux, Cornelia Lass-Floerl, Marina Machado, Patricia Muñoz
Journal: Clinical Microbiology and Infection (2021)

Coronavirus disease 2019 (COVID-19) -associated pulmonary aspergillosis (CAPA) has emerged as a complication in critically ill COVID-19 patients. The objectives of this multinational study were to determine the prevalence of CAPA in patients with COVID-19 in intensive care units (ICU) and to investigate risk factors for CAPA as well as outcome.The European Confederation of Medical Mycology (ECMM) conducted a multinational study including 20 centres from nine countries to assess epidemiology, risk factors and outcome of CAPA. CAPA was defined according to the 2020 ECMM/ISHAM consensus definitions.A total of 592 patients were included in this study, including 11 (1.9%) patients with histologically proven CAPA, 80 (13.5%) with probable CAPA, 18 (3%) with possible CAPA and 483 (81.6%) without CAPA. CAPA was diagnosed a median of 8 days (range 0-31 days) after ICU admission predominantly in older patients (adjusted hazard ratio (aHR) 1.04 per year; 95% CI 1.02-1.06) with any form of invasive respiratory support (HR 3.4; 95% CI 1.84-6.25) and receiving tocilizumab (HR 2.45; 95% CI 1.41-4.25). Median prevalence of CAPA per centre was 10.7% (range 1.7%-26.8%). CAPA was associated with significantly lower 90-day ICU survival rate (29% in patients with CAPA versus 57% in patients without CAPA; Mantel-Byar p < 0.001) and remained an independent negative prognostic variable after adjusting for other predictors of survival (HR 2.14; 95% CI 1.59-2.87, p ≤ 0.001).Prevalence of CAPA varied between centres. CAPA was significantly more prevalent among older patients, patients receiving invasive ventilation and patients receiving tocilizumab, and was an independent strong predictor of ICU mortality.
Increased efficacy of dual proinflammatory cytokine blockade on acute GVHD while maintaining GVT effects
Authors: Lam T. Khuat, Logan V. Vick, Cordelia Dunai, Craig P. Collins, Shyam K. More, Catherine T. Le, Chien-Chun Steven Pai, Kevin M. Stoffel, Emanual Maverakis, Robert J. Canter, Arta M. Monjazeb, Dan L. Longo, Mehrdad Abedi, Eunju Choi, Bruce R. Blazar, Maneesh Dave, William J. Murphy
Journal: Blood (2021)
アミノ酸代謝の阻害はヒト白血病幹細胞を選択的に標的とする【JST・京大機械翻訳】
Authors: L Jones Courtney, M Stevens Brett, D’Alessandro Angelo, A Reisz Julie, Culp-Hill Rachel, Nemkov Travis, Pei Shanshan, Khan Nabilah, Adane Biniam, Ye Haobin, Krug Anna, Reinhold Dominik, Smith Clayton, DeGregori James, A Pollyea Daniel, T Jordan Craig
Journal: Cancer Cell (2018)
From DREAM to REALITI‐A and beyond: Mepolizumab for the treatment of eosinophil‐driven diseases
Authors: Ian D. Pavord, Elisabeth H. Bel, Arnaud Bourdin, Robert Chan, Joseph K. Han, Oliver N. Keene, Mark C. Liu, Neil Martin, Alberto Papi, Florence Roufosse, Jonathan Steinfeld, Michael E. Wechsler, Steven W. Yancey
Journal: Allergy (2021)

Abstract Effective treatment of inflammatory diseases is often challenging owing to their heterogeneous pathophysiology. Understanding of the underlying disease mechanisms is improving and it is now clear that eosinophils play a complex pathophysiological role in a broad range of type 2 inflammatory diseases. Standard of care for these conditions often still includes oral corticosteroids (OCS) and/or cytotoxic immune therapies, which are associated with debilitating side effects. Selective, biological eosinophil‐reducing agents provide treatment options that improve clinical symptoms associated with eosinophilic inflammation and reduce OCS use. Mepolizumab is a humanized monoclonal antibody that binds to and neutralizes interleukin‐5, the major cytokine involved in eosinophil proliferation, activation, and survival. Mepolizumab is approved for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. Additionally, the efficacy of add‐on mepolizumab has been observed in patients with severe chronic rhinosinusitis with nasal polyposis and chronic obstructive pulmonary disease with an eosinophilic phenotype. Here, we review the development, approval, and real‐world effectiveness of mepolizumab for the treatment of patients with severe eosinophilic asthma, from the DREAM to REALITI‐A studies, and describe how knowledge from this journey extended to the use of mepolizumab and other biologics across a broad spectrum of eosinophilic diseases.
A Comprehensive Comparison of Early-Onset and Average-Onset Colorectal Cancers
Authors: Andrea Cercek, Walid K Chatila, Rona Yaeger, Henry Walch, Gustavo Dos Santos Fernandes, Asha Krishnan, Lerie Palmaira, Anna Maio, Yelena Kemel, Preethi Srinivasan, Chaitanya Bandlamudi, Erin Salo-Mullen, Prince R Tejada, Kimeisha Belanfanti, Jesse Galle, Vijai Joseph, Neil Segal, Anna Varghese, Diane Reidy-Lagunes, Jinru Shia, Efsevia Vakiani, Sebastian Mondaca, Robin Mendelsohn, Melissa A Lumish, Felix Steinruecke, Nancy Kemeny, Louise Connell, Karuna Ganesh, Arnold Markowitz, Garrett Nash, Jose Guillem, J Joshua Smith, Phillip B Paty, Liying Zhang, Diana Mandelker, Ozge Birsoy, Mark Robson, Kenneth Offit, Barry Taylor, Michael Berger, David Solit, Martin Weiser, Leonard B Saltz, Julio Garcia Aguilar, Nikolaus Schultz, Luis A Diaz, Zsofia K Stadler
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background The causative factors for the recent increase in early-onset colorectal cancer (EO-CRC) incidence are unknown. We sought to determine if early-onset disease is clinically or genomically distinct from average-onset colorectal cancer (AO-CRC). Methods Clinical, histopathologic, and genomic characteristics of EO-CRC patients (2014-2019), divided into age 35 years and younger and 36-49 years at diagnosis, were compared with AO-CRC (50 years and older). Patients with mismatch repair deficient tumors, CRC-related hereditary syndromes, and inflammatory bowel disease were excluded from all but the germline analysis. All statistical tests were 2-sided. Results In total, 759 patients with EO-CRC (35 years, n = 151; 36-49 years, n = 608) and AO-CRC (n = 687) were included. Left-sided tumors (35 years and younger = 80.8%; 36-49 years = 83.7%; AO = 63.9%; P &amp;lt; .001 for both comparisons), rectal bleeding (35 years and younger = 41.1%; 36-49 years = 41.0%; AO = 25.9%; P = .001 and P &amp;lt; .001, respectively), and abdominal pain (35 years and younger = 37.1%; 36-49 years = 34.0%; AO = 26.8%; P = .01 and P = .005, respectively) were more common in EO-CRC. Among microsatellite stable tumors, we found no differences in histopathologic tumor characteristics. Initially, differences in TP53 and Receptor Tyrosine Kinase signaling pathway (RTK-RAS)alterations were noted by age. However, on multivariate analysis including somatic gene analysis and tumor sidedness, no statistically significant differences at the gene or pathway level were demonstrated. Among advanced microsatellite stable CRCs, chemotherapy response and survival were equivalent by age cohorts. Pathogenic germline variants were identified in 23.3% of patients 35 years and younger vs 14.1% of AO-CRC (P = .01). Conclusions EO-CRCs are more commonly left-sided and present with rectal bleeding and abdominal pain but are otherwise clinically and genomically indistinguishable from AO-CRCs. Aggressive treatment regimens based solely on the age at CRC diagnosis are not warranted.
26589 Spesolimab, an IL-36R inhibitor, may reduce symptoms of pain in patients with palmoplantar pustulosis – Results from a small pilot study
Authors: Andreas Pinter, Christian Boisvert-Huneault, A. David Burden, Kristian Reich, Knut Schäkel, Hongjie Deng, Tristan Gloede, Frank Baehner, Robert Bissonnette, Ulrich Mrowietz
Journal: Journal of the American Academy of Dermatology (2021)