tbuckley/cabot-search huggingface dataset:
Trial of Roflumilast Cream for Chronic Plaque Psoriasis
Authors: Mark G. Lebwohl, Kim A. Papp, Linda Stein Gold, Melinda J. Gooderham, Leon H. Kircik, Zoe D. Draelos, Steven E. Kempers, Mathew Zirwas, Kathleen Smith, David W. Osborne, Marie-Louise Trotman, Lynn Navale, Charlotte Merritt, David R. Berk, Howard Welgus
Journal: New England Journal of Medicine (2020)

Systemic oral phosphodiesterase type 4 (PDE-4) inhibitors have been effective in the treatment of psoriasis. Roflumilast cream contains a PDE-4 inhibitor that is being investigated for the topical treatment of psoriasis.In this phase 2b, double-blind trial, we randomly assigned adults with plaque psoriasis in a 1:1:1 ratio to use roflumilast 0.3% cream, roflumilast 0.15% cream, or vehicle (placebo) cream once daily for 12 weeks. The primary efficacy outcome was the investigator's global assessment (IGA) of a status of clear or almost clear at week 6 (assessed on a 5-point scale of plaque thickening, scaling, and erythema; a score of 0 indicates clear, 1 almost clear, and 4 severe). Secondary outcomes included an IGA score indicating clear or almost clear plus a 2-grade improvement in the IGA score for the intertriginous area and the change in the Psoriasis Area and Severity Index (PASI) score (range, 0 to 72, with higher scores indicating worse disease). Safety was also assessed.Among 331 patients who underwent randomization, 109 were assigned to roflumilast 0.3% cream, 113 to roflumilast 0.15% cream, and 109 to vehicle cream. An IGA score indicating clear or almost clear at week 6 was observed in 28% of the patients in the roflumilast 0.3% group, in 23% in the roflumilast 0.15% group, and in 8% in the vehicle group (P<0.001 and P = 0.004 vs. vehicle for roflumilast 0.3% and 0.15%, respectively). Among the approximately 15% of patients overall who had baseline intertriginous psoriasis of at least mild severity, an IGA score at week 6 indicating clear or almost clear plus a 2-grade improvement in the intertriginous-area IGA score occurred in 73% of the patients in the roflumilast 0.3% group, 44% of those in the roflumilast 0.15% group, and 29% of those in the vehicle group. The mean baseline PASI scores were 7.7 in the roflumilast 0.3% group, 8.0 in the roflumilast 0.15% group, and 7.6 in the vehicle group; the mean change from baseline at week 6 was -50.0%, -49.0%, and -17.8%, respectively. Application-site reactions occurred with similar frequency in the roflumilast groups and the vehicle group.Roflumilast cream administered once daily to affected areas of psoriasis was superior to vehicle cream in leading to a state of clear or almost clear at 6 weeks. Longer and larger trials are needed to determine the durability and safety of roflumilast in psoriasis. (Funded by Arcutis Biotherapeutics; ARQ-151 201 ClinicalTrials.gov number, NCT03638258.).
Does Nonsteroidal Antiinflammatory Drug Use Contribute Substantially to the Osteoarthritis–Cardiovascular Disease Association? Comment on the Article by Atiquzzaman et al
Authors: Chao Cheng, Hua Yang, Jianchun Liu, Zhihong Zhou
Journal: Arthritis & Rheumatology (2020)

Arthritis & RheumatologyVolume 72, Issue 9 p. 1582-1583 Letters Does Nonsteroidal Antiinflammatory Drug Use Contribute Substantially to the Osteoarthritis–Cardiovascular Disease Association? Comment on the Article by Atiquzzaman et al Chao Cheng, Yiyang Central Hospital and Clinical Medical Technology Demonstration Base for Minimally Invasive and Digital Orthopaedics in Hunan Province, Yiyang, ChinaSearch for more papers by this authorHua Yang, Yiyang Central Hospital and Clinical Medical Technology Demonstration Base for Minimally Invasive and Digital Orthopaedics in Hunan Province, Yiyang, ChinaSearch for more papers by this authorJianchun Liu, Yiyang Central Hospital and Clinical Medical Technology Demonstration Base for Minimally Invasive and Digital Orthopaedics in Hunan Province, Yiyang, ChinaSearch for more papers by this authorZhihong Zhou, orcid.org/0000-0002-7886-2319 Yiyang Central Hospital and Clinical Medical Technology Demonstration Base for Minimally Invasive and Digital Orthopaedics in Hunan Province, Yiyang, ChinaSearch for more papers by this author Chao Cheng, Yiyang Central Hospital and Clinical Medical Technology Demonstration Base for Minimally Invasive and Digital Orthopaedics in Hunan Province, Yiyang, ChinaSearch for more papers by this authorHua Yang, Yiyang Central Hospital and Clinical Medical Technology Demonstration Base for Minimally Invasive and Digital Orthopaedics in Hunan Province, Yiyang, ChinaSearch for more papers by this authorJianchun Liu, Yiyang Central Hospital and Clinical Medical Technology Demonstration Base for Minimally Invasive and Digital Orthopaedics in Hunan Province, Yiyang, ChinaSearch for more papers by this authorZhihong Zhou, orcid.org/0000-0002-7886-2319 Yiyang Central Hospital and Clinical Medical Technology Demonstration Base for Minimally Invasive and Digital Orthopaedics in Hunan Province, Yiyang, ChinaSearch for more papers by this author First published: 14 July 2020 https://doi.org/10.1002/art.41378Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume72, Issue9September 2020Pages 1582-1583 RelatedInformation
SAT0481 RELATIONSHIP BETWEEN SARCOPENIA AND BONE MINERAL DENSITY IN MEN WITH CORONARY HEART DISEASE
Authors: I. Grigoreva, T. Raskina, J. Averkieva, M. Letaeva, O. Malyshenko, K. Krivoshapova, V. Fanaskov
Journal: Annals of the Rheumatic Diseases (2020)

Objectives: To study the relationship of indicators of muscle mass, muscle strength and muscle function with bone mineral density (BMD) in men with coronary heart disease (CHD). Methods: 79 men aged over 50 years with verified CHD were examined (mean age 63 (57; 66) years). The BMD (g/cm 2 ) and T-criterion (standard deviation) of the femoral neck and lumbar spine (L1-L4) were evaluated using dual-energy x-ray absorptiometry (DXA) on the lunar Prodigy Primo bone densitometer (USA). To assess muscle mass, the total area (cm 2 ) of the lumbar muscles of the axial section at the level of the 3rd lumbar vertebra (L3) was determined using multispiral computed tomography on a 64-slice computer tomograph “Somatom Sensation 64” (Siemens AG Medical Solution, Germany). The ratio of the obtained index of the area of skeletal muscle to the square of the patient’s growth index determined the “musculoskeletal index L3” (SMI). The media considered the threshold value to be 52.4 cm 2 /m 2 . Evaluation of muscle strength was performed using a mechanical wrist dynamometer DC-25. Muscle function was examined using a short physical performance battery (SPPB). Results: The data obtained from the results of correlation analysis show that there is a reliable direct correlation between BMD and hand dynamometry indicators (r=0.250; p=0.026 for the right hand and r=0.247; p=0.028 for the left hand), the T-criterion of the femoral neck and hand dynamometry indicators (r=0.245; p=0.030 for the right hand and r=0.242; p=0.032 for the left hand). A similar relationship was established between the BMD of the lumbar vertebra and the parameters of dynamometry (r=0.237; p=0.036 for the right hand and r=0.228; p=0.043 for the left hand) and T-criterion for the lumbar region and dynamometry parameters (r=0.232; p=0.039 for the right hand and r=0.220; p=0.051 for the left hand). There is no significant relationship between densitometry scores and the result of SPPB tests. There was a significant direct relationship between the total SPPB score and the area of skeletal muscle at the L3 level (r=0.249, p=0.026), the total SPPB score and the musculoskeletal index (r=0.233, p=0.039). A similar relationship was established between the result of the chair lift test and the total area of skeletal muscle at the L3 level (r=0.262, p=0.019) and the musculoskeletal index (r=0.220, p=0.050). A significant negative relationship between walking speed and the musculoskeletal index was found (r= -0.260, p=0.021). The relationship between muscle mass and strength could not be traced. Conclusion: A decrease in muscle strength correlates with the severity of bone loss, while a decrease in muscle function correlates with a decrease in muscle mass. The results obtained confirm the probability of common mechanisms in the development of sarcopenia and osteoporosis in patients with CHD. Disclosure of Interests: None declared
Myocardial Injury in COVID-19—Can We Successfully Target Inflammation?
Authors: Georgios Giannopoulos, Dimitrios A. Vrachatis, Spyridon G. Deftereos
Journal: JAMA Cardiology (2020)

Tao Guo, MD; Yongzhen Fan, MD; Ming Chen, MD; Xiaoyan Wu, MD; Lin Zhang, MD; Tao He, MD; Hairong Wang, MD; Jing Wan, MD; Xinghuan Wang, MD; Zhibing Lu, MD
AB0307 DOES FCGR2A, FCGR3A AND FCGR3B POLYMORPHISM CAN PREDICT ANTI-DRUG ANTIBODIES APPARITION IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH TNF-BLOCKERS?
Authors: I. Mahmoud, M. Moalla, A. Ben Tekaya, S. Bouden, R. Tekaya, O. Saidane, I. Sfar, Y. Gorgi, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2020)

Background: Fc gamma receptors (FcγRs) play a major role in the regulation of humoral immune responses. Single-nucleotide polymorphisms (SNPs) of FCGR2A and FCGR3A and FCGR3B can impact the expression level, IgG affinity and function of the CD32 and CD16 FcγRs in response to their engagement by the Fc fragment of IgG. It was described in patient treated for rheumatoid arthritis (RA), that such a polymorphism may influence patients response to TNF-blockers. Objectives: In this study, we aimed to investigate whether the FCGR2A H131R (rs1801274), FCGR3A F158V (rs396991), and FCGR3B NA1/NA2 polymorphisms can be involved in the genesis of anti-drug-antibody ADAb to anti-TNF therapy in RA patients under etanercept (ETA), adalimumab (ADL) and infliximab (INF). Methods: We included 47 patients treated for RA under TNF-blockers. To assess the association between the FCGR2A H131R (rs1801274), FCGR3A F158V (rs396991), and FCGR3B NA1/NA2 polymorphisms and immunogenicity of TNF-blockers, we used allele contrast, the recessive model, the dominant model, and the homozygote contrast. Quantitative measurements of the ADAbs was carried out by a commercial enzyme-linked immunosorbent assay (ELISA) kit (Promonitor) ® after 6 months of treatment. Results: We involved 18 patients treated with ETA, 13 patients with ADL and 16 under INF. None of the patients under ETA has developed ADAb and respectively 1 and 7 patients developed immunogenicity with ADL and INF. We excluded patients under ETA from statistical study since they didn’t develop ADAb. A significant association was revealed between FCGR2A H131R polymorphism and immunogenicity of INF and ADL (table 1). Table 1. Association between FCGR2A polymorphism and immunogenicity to INF and ADL FCGR2A association with ADAb (n=29, crude analysis) Genotype ADAb=0 ADAb=1 OR (95% CI) P-value H/H 1 (4.8%) 3 (37.5%) 1.00 0.031 H/R-R/R 20 (95.2%) 5 (62.5%) 0.08 (0.01-0.98 ) There weren’t significant associations between ADAb’s development and FCGR3A F158V and FCGR3B NA1/NA2 polymorphism. Conclusion: FCGR2A R allele carriers show less susceptibility to develop ADAb to ADL and INF with follow-up times of 6 months. Our results provide an explanation for controversies in the relationships between FCGR2A H131R polymorphism and TNF-blockers response. Further studies with larger population of RA patients should be undertaken to confirm this hypothesis. References: None Disclosure of Interests: None declared
SP0171 Patient priorities at their first consultation
Authors: SC Stafford, NL Cox
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In the changing world of today's healthcare, it has now been recognised that the provision of services should allow patients participation and their say in priority setting. Patients are now much better informed about their disease, treatment available, and the quality of care to which they are entitled. To improve satisfaction we have to identify the goals and expectations for each patient as these may well differ from those the clinician or health professional may think them to be. <h3>Objectives</h3> To further explore these concepts and to identify the goals and expectations of each individual patient when they attended for their first consultation in the Rheumatology Out-Patient Department. <h3>Method</h3> A questionnaire was designed and sent to patients for completion prior to their attendance at their first consultation. Four domains were selected and the patients were asked to prioritise them in order of their goals and expectations from this consultation. 1) Pain Relief 2) Diagnosis 3) Outlook 4) Help/Other. An extra option was included for individual comments. 500 fully completed questionnaires were randomly selected from the patient notes in the clinic. The order of priority, patient's age, gender and diagnosis were recorded. The results were analysed by variance. <h3>Results</h3> The study consisted of 166 male and 334 female patients. Their overall First Choice of the categories was – Pain Relief 235(47%) Diagnosis 197(39.5%) Outlook 43(8.5%) Help/other 25(5%). These results varied by Gender, Age, Inflammatory and Degenerative, and to a lesser degree by Soft Tissue and Mixed Connective Disease. <h3>Conclusion</h3> The results suggest that overall relief of pain is of prime importance, especially amongst the elderly and those with R. A. Diagnosis is the main priority for those &lt;40 years and male patients with O. A. Outlook and Practical Help maybe of concern later but is rarely a priority at first consultation.
The Interaction of NEK2 with USP7 Causes Resistance to Proteasome Inhibitor in Multiple Myeloma
Authors: Reinaldo Franqui-Machin, Mu Hao, Bai Hua, Zhimin Gu, Xin Zhan, Hongwei Xu, Hasem Habelhah, Yogesh Jethava, Lugui Qiu, Ivana Frech, Guido J. Tricot, Fenghuang Zhan
Journal: Blood (2017)
Biological Mechanisms and Clinical Significance of <i>BAP1</i> Mutations in Human Cancer
Authors: Michele Carbone, J. William Harbour, James Brugarolas, Angela Bononi, Ian Pagano, Anwesha Dey, Thomas Krausz, Harvey I. Pass, Haining Yang, Giovanni Gaudino
Journal: Cancer Discovery (2020)

Abstract Among more than 200 BAP1-mutant families affected by the “BAP1 cancer syndrome,” nearly all individuals inheriting a BAP1 mutant allele developed one or more malignancies during their lifetime, mostly uveal and cutaneous melanoma, mesothelioma, and clear-cell renal cell carcinoma. These cancer types are also those that, when they occur sporadically, are more likely to carry somatic biallelic BAP1 mutations. Mechanistic studies revealed that the tumor suppressor function of BAP1 is linked to its dual activity in the nucleus, where it is implicated in a variety of processes including DNA repair and transcription, and in the cytoplasm, where it regulates cell death and mitochondrial metabolism. BAP1 activity in tumor suppression is cell type– and context-dependent. BAP1 has emerged as a critical tumor suppressor across multiple cancer types, predisposing to tumor development when mutated in the germline as well as somatically. Moreover, BAP1 has emerged as a key regulator of gene–environment interaction. This article is highlighted in the In This Issue feature, p. 1079
Epidemiological trends of tracheal, bronchus, and lung cancer at the global, regional, and national levels: a population-based study
Authors: Yujiao Deng, Peng Zhao, Linghui Zhou, Dong Xiang, Jingjing Hu, Yu Liu, Jian Ruan, Xianghua Ye, Yi Zheng, Jia Yao, Zhen Zhai, Shuqian Wang, Si Yang, Ying Wu, Na Li, Peng Xu, Dai Zhang, Huafeng Kang, Jun Lyu, Zhijun Dai
Journal: Journal of Hematology & Oncology (2020)

Abstract Background Investigations of disease incidence, mortality, and disability-adjusted life years (DALYs) are valuable for facilitating preventive measures and health resource planning. We examined the tracheal, bronchus, and lung (TBL) cancer burdens worldwide according to sex, age, and social development index (SDI) at the global, regional, and national levels. Methods We assessed the TBL cancer burden using data from the Global Burden of Disease (GBD) database, including 21 regions, 195 countries, and territories in the diagnostic period 1990–2017. The data of TBL cancer-related mortality and DALYs attributable to all known risk factors were also analyzed. Age-standardized rates (ASRs) and their estimated annual percentage changes (EAPCs) were calculated. Results Incident cases, deaths, and DALYs of TBL cancer increased worldwide (100.44%, 82.30%, and 61.27%, respectively). The age-standardized incidence rate (ASIR) was stable (EAPC = 0.02, 95% confidence interval [CI] − 0.03 to 0.08), but the age-standardized death (EAPC = − 0.34, 95%CI − 0.38 to − 0.3) and DALY rate decreased generally (EAPC = − 0.74, 95%CI − 0.8 to − 0.68). However, the change trend of ASIR and ASDR among sexes was on the contrary. China and the USA always had the highest incidence, mortality, and DALYs of TBL cancer. Significant positive correlations between ASRs and SDI were observed, especially among females. High (36.86%), high-middle (28.78%), and middle SDI quintiles (24.91%) carried the majority burden of TBL cancer. Tobacco remained the top cause of TBL cancer death and DALYs, followed by air pollution, the leading cause in the low-middle and low-SDI quintiles. Metabolic risk-related TBL cancer mortality and DALYs among females increased but was stable among males. The main ages of TBL cancer onset and death were &gt; 50 years, and the DALYs concentrated in 50 − 69 years. Conclusions To significantly reduce the growing burden of TBL cancer, treatment resources need to be skewed according to factors such as risks and geography, especially for high-risk groups and high-burden areas. Asia had the greatest TBL cancer burden, followed by high-income North America. Tobacco remains the leading cause of death and DALYs, followed by air pollution. Effective prevention measures against tobacco and air pollution should be strengthened.
Chronic thromboembolic pulmonary hypertension and totally implantable central venous access systems
Authors: Mitja Jevnikar, David Montani, Laurent Savale, Andrei Seferian, Etienne-Marie Jutant, Athénaïs Boucly, Mariana Preda, Jason Weatherald, Sophie Bulifon, Florence Parent, Philippe Brenot, Elie Fadel, Olivier Sitbon, Gérald Simonneau, Marc Humbert, Xavier Jaïs
Journal: European Respiratory Journal (2020)

<b>Long-term TICVAS implantation may contribute to the development of CTEPH and have a negative impact on perioperative survival after PEA. Clinicians should be aware of this potential late complication of TICVAS.</b>https://bit.ly/2OmonHZ
SAT0241 Health economic evaluation of rofecoxib versus conventional nsaids in the treatment of osteoarthritis in switzerland
Authors: SX Kong, JM Pellissier
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In randomised clinical trials, patients with osteoarthritis (OA) who received rofecoxib developed fewer clinically significant gastrointestinal (GI) adverse events than those received conventional NSAIDs. <h3>Objectives</h3> We estimated the economic implications of these results in Switzerland. <h3>Methods</h3> A model-based cost-effectiveness analysis was conducted, focusing on events related to serious GI complications (perforations, ulcers or bleeds or PUBs) and minor GI problems (e.g. dyspepsia) that imply healthcare resource use. The base case analysis had a one-year horizon. GI event probabilities were obtained from a pre-specified pooled analysis of the clinical trials of rofecoxib. The NSAID comparator was an aggregate of those commonly used in Switzerland. To extrapolate trial results to clinical practice, resource utilisation profiles for inpatient and outpatient care of GI events were developed using both the literature and expert opinions in UK, the United States and Canada. Weighted average drug costs of currently reimbursed medications were derived from IMS Health data. It was assumed that 20.6% of conventional NSAID users needed gastroprotective agents (GPAs) prophylactically based on published data in the UK and other countries. Efficacy of concomitant use of GPAs in preventing NSAID-associated PUBs was inferred from the literature. A 75% reduction in prophylactic GPA prescription rates with VIOXX was assumed for the base case. Sensitivity analyses explored the effects of varying drug costs, efficacy of GPAs and rates of concomitant GPA use. <h3>Results</h3> Our base case analysis showed that in Switzerland, it would save 0.64 Swiss Francs per patient per day by switching conventional NSAIDs to rofecoxib for the treatment of OA. The iatrogenic cost factor for NSAIDs was 1.75. Results were robust over a range of model assumptions. The cost per PUB avoided ranged from an added cost of 5,951 Swiss Francs (assuming 0% of GPA use with NSAIDs) to a saving of 16,013 (assuming 50%), with a saving of 2,522 Swiss Francs at base case (20.6% GPA use with NSAIDs). <h3>Conclusion</h3> Based upon this analysis of serious and minor GI events for OA patients in Switzerland, rofecoxib represents a cost-effective therapeutic option compared to NSAIDs due to cost savings in GI problems and reduction in use of GPAs.
Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury
Authors: Sean M Bagshaw, Ron Wald, Neill K J Adhikari, Rinaldo Bellomo, Bruno R da Costa, Didier Dreyfuss, Bin Du, Martin P Gallagher, Stéphane Gaudry, Eric A Hoste, François Lamontagne, Michael Joannidis, Giovanni Landoni, Kathleen D Liu, Daniel F McAuley, Shay P McGuinness, Javier A Neyra, Alistair D Nichol, Marlies Ostermann, Paul M Palevsky, Ville Pettilä, Jean-Pierre Quenot, Haibo Qiu, Bram Rochwerg, Antoine G Schneider, Orla M Smith, Fernando Thomé, Kevin E Thorpe, Suvi Vaara, Matthew Weir, Amanda Y Wang, Paul Young, Alexander Zarbock
Journal: New England Journal of Medicine (2020)

Acute kidney injury is common in critically ill patients, many of whom receive renal-replacement therapy. However, the most effective timing for the initiation of such therapy remains uncertain.