tbuckley/cabot-search huggingface dataset:
Isoniazid Preventive Therapy in Contacts of Multidrug-Resistant Tuberculosis
Authors: Chuan-Chin Huang, Mercedes C. Becerra, Roger Calderon, Carmen Contreras, Jerome Galea, Louis Grandjean, Leonid Lecca, Rosa Yataco, Zibiao Zhang, Megan Murray
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: The World Health Organization recommends the use of isoniazid (INH) alone or in combination with rifapentine to treat latent tuberculosis infections. The recent rise of drug-resistant tuberculosis has complicated the choice of treatment regimen for latent tuberculosis infection.Objectives: To evaluate the effects of INH preventive therapy on the contacts of patients with multidrug-resistant tuberculosis.Methods: In a prospective cohort study conducted between September 2009 and August 2012, we identified 4,500 index patients with tuberculosis and 14,044 tuberculosis-exposed household contacts who we followed for 1 year for the occurrence of incident tuberculosis disease. Although Peruvian national guidelines specify that INH preventive therapy should be provided to contacts aged 19 years old or younger, only half this group received INH preventive therapy.Measurements and Main Results: Among 4,216 contacts under 19 years of age, 2,106 contacts (50%) initiated INH preventive therapy at enrollment. The protective effect of INH was more extreme in contacts exposed to drug-sensitive tuberculosis (adjusted hazard ratio, 0.30; 95% confidence interval, 0.18-0.48) and to multidrug-resistant tuberculosis (adjusted hazard ratio, 0.19; 95% confidence interval, 0.05-0.66) compared with those exposed to mono-INH-resistant tuberculosis (adjusted hazard ratio, 0.80; 95% confidence interval, 0.23-2.80). In the second independent study, tuberculosis occurred in none of the 76 household contacts who received INH preventive therapy compared with 3% (8 of 273) of those who did not.Conclusions: Household contacts who received INH preventive therapy had a lower incidence of tuberculosis disease even when they had been exposed to an index patient with multidrug-resistant tuberculosis. INH may have a role in the management of latent multidrug-resistant tuberculosis infection.
Toward better preparedness for the next pandemic
Authors: Lauren I. Shapiro, Grace R. Kajita, Julia H. Arnsten, Yaron Tomer
Journal: Journal of Clinical Investigation (2020)

New York City has been described as the epicenter of the COVID-19 pandemic in the United States. While health care workers are notably at increased risk for COVID-19 infection, the impact on resident physicians remains unclear. In this issue of the JCI, Breazzano et al. surveyed resident physicians for their exposure to COVID-19 during the exponential phase of the COVID-19 pandemic. The researchers also assessed how personal protective equipment and COVID-19 testing protected health care workers from infection. This study highlights resident physician experiences of the first COVID-19 wave that can inform and improve preparedness for upcoming COVID-19 surges and other future epidemics.
Prospection does not imply predictive processing
Authors: Piotr Litwin, Marcin Miłkowski
Journal: Behavioral and Brain Sciences (2020)

Abstract Predictive processing models of psychopathologies are not explanatorily consistent with the present account of abstract thought. These models are based on latent variables probabilistically mapping the structure of the world. As such, they cannot be informed by representational ontology based on mental objects and states. What actually is the case is merely some terminological affinity between subjective and informational uncertainty.
The Safety and Efficacy of Aspirin Discontinuation on a Background of a P2Y <sub>12</sub> Inhibitor in Patients After Percutaneous Coronary Intervention
Authors: Michelle L. O’Donoghue, Sabina A. Murphy, Marc S. Sabatine
Journal: Circulation (2020)

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor has been shown to reduce the risk of major adverse cardiovascular events (MACE) compared with aspirin alone after percutaneous coronary intervention (PCI) or acute coronary syndrome but with increased risk of bleeding. The safety of discontinuing aspirin in favor of P2Y12 inhibitor monotherapy remains disputed.A meta-analysis was conducted from randomized trials (2001-2020) that studied discontinuation of aspirin 1 to 3 months after PCI with continued P2Y12 inhibitor monotherapy compared with traditional dual antiplatelet therapy. Five trials were included; follow-up duration ranged from 12 to 15 months after PCI. Primary bleeding and MACE outcomes were the prespecified definitions in each trial.The study population included 32 145 patients: 14 095 (43.8%) with stable coronary artery disease and 18 046 (56.1%) with acute coronary syndrome. In the experimental arm, background use of a P2Y12 inhibitor included clopidogrel in 2649 (16.5%) and prasugrel or ticagrelor in 13 408 (83.5%) patients. In total, 820 patients experienced a primary bleeding outcome and 937 experienced MACE. Discontinuation of aspirin therapy 1 to 3 months after PCI significantly reduced the risk of major bleeding by 40% compared with dual antiplatelet therapy (1.97% versus 3.13%; hazard ratio [HR], 0.60 [95% CI, 0.45-0.79]), with no increase observed in the risk of MACE (2.73% versus 3.11%; HR, 0.88 [95% CI, 0.77-1.02]), myocardial infarction (1.08% versus 1.27%; HR, 0.85 [95% CI, 0.69-1.06]), or death (1.25% versus 1.47%; HR, 0.85 [95% CI, 0.70-1.03]). Findings were consistent among patients who underwent PCI for an acute coronary syndrome, in whom discontinuation of aspirin after 1 to 3 months reduced bleeding by 50% (1.78% versus 3.58%; HR, 0.50 [95% CI, 0.41-0.61]) and did not appear to increase the risk of MACE (2.51% versus 2.98%; HR, 0.85 [95% CI, 0.70-1.03]).Discontinuation of aspirin with continued P2Y12 inhibitor monotherapy reduces risk of bleeding when stopped 1 to 3 months after PCI. An increased risk of MACE was not observed after discontinuation of aspirin, including in patients with acute coronary syndrome.
OP0261-PARE BIOSIMILAR SWITCHING PROCESS - UK PATIENTS’ EXPERIENCE STUDY
Authors: C. Jacklin, A. Bosworth
Journal: Annals of the Rheumatic Diseases (2020)

Background: The introduction of 4 adalimumab biosimilars was challenging for the health service and patients alike. A group of patient organisations representing rheumatology, dermatology and gastroenterology patients worked with NHS England in producing materials for disseminating information to prescribers and patients to ensure smooth and appropriate transition to biosimilar products from the originator product as appropriate. These patient groups wanted to know how the ‘switch’ process was implemented and if shared decision making was practiced. Objectives: To gather patient feedback on biosimilar switch process and report findings back to NHS England as well as provide the patient organisations information to develop any future resources to help improve patient and physician shared decision making. Methods: A working group of the 4 organisations collaborated on designing an online survey asking questions around how the individual was communicated with regarding their treatment being switched to a biosimilar; was there any choice or perceived input into the decision making process; how queries or issues were handled and overall satisfaction on how the individual felt their personal preferences/needs were met. Results: 899 useable responses were gathered representing 52% Rheumatology patients; 42% Gastroenterology patients and 5% Dermatology patients with remaining 1% more complex specialties. More than half of patients were not asked for their consent before their treatment was switched to a biosimilar of adalimumab with only 40% giving consent 7% couldn’t remember or were unsure if consent was given. 75% were not at all satisfied or not satisfied with the ability to decline being switched with only 12% feeling that they had been given an option to decline being switched. Conclusion: Shared Decision Making (SDM) needs to be put into action not just words. There is a clear majority that are dissatisfied with the communication they had prior to the switch and are very dissatisfied with the lack of patient engagement in the decision-making process. NRAS, NASS, Crohn’s &amp; Colitis UK and the Psoriasis Association will continue to collaborate with NHS England and other stakeholders as appropriate to make Shared Decision Making a reality not just rhetoric. Acknowledgments: National Axial Spondyloarthritis Society UK; Crohns’ &amp; Colitis UK; Psorarsis Association, UK; National Rheumatoid Arthritis Society Disclosure of Interests: Clare Jacklin Grant/research support from: NRAS has received grants from pharmaceutical companies to carry out a number of projects, Consultant of: I have been paid a speakers fee to participate in advisory boards, in house training of staff and health professional training opportunities, Speakers bureau: Various pharma companies, Ailsa Bosworth Speakers bureau: a number of pharmaceutical companies for reasons of inhouse training, advisory boards etc.
Determinants of mortality in patients with cirrhosis and uncontrolled variceal bleeding
Authors: Rahul Kumar, Annarein J.C. Kerbert, M. Faisal Sheikh, Noam Roth, Joana A.F. Calvao, Monica D. Mesquita, Ana I. Barreira, Haqeeqat S. Gurm, Komal Ramsahye, Rajeshwar P. Mookerjee, Dominic Yu, Neil H. Davies, Gautam Mehta, Banwari Agarwal, David Patch, Rajiv Jalan
Journal: Journal of Hepatology (2020)
Covid-19: public health expertise is being sidelined
Authors: Marie Armitage
Journal: BMJ (2020)

<h3><b>Background</b></h3> Children with cerebral palsy (CP) are prone to secondary complications related to physical inactivity and poor cardiorespiratory capacity. This problem could be greatly attenuated through the use of video games that incorporate physical activity for 2 reasons: Video games already represent an important component of leisure time in younger people, and such games can lead to a high level of exercise intensity in people who are healthy. <h3><b>Objective</b></h3> The study objective was to evaluate exercise intensity in children with spastic diplegic CP and children who were typically developing while playing with an active video game console. <h3><b>Design</b></h3> This was a cross-sectional study. <h3><b>Methods</b></h3> Ten children (7–12 years old) with spastic diplegic CP (Gross Motor Function Classification System level I or II) and 10 children who were age matched and typically developing were evaluated in a movement analysis laboratory. Four games were played with the active video game console (jogging, bicycling, snowboarding, and skiing) for 40 minutes. Heart rate was recorded during the entire playing period with a heart rate belt monitor. Exercise intensity was defined as the percentage of heart rate reserve (HRR). In addition, lower extremity motion analysis was carried out during the final minute of the playing period for the jogging and bicycling games. <h3><b>Results</b></h3> No difference between groups was observed for any variables. A main effect of games was observed for the amount of time spent at an intensity greater than 40% of HRR. Specifically, more than 50% of the playing time for the jogging game and more than 30% of the playing time for the bicycling game were spent at an intensity greater than 40% of HRR. In addition, the jogging game produced a larger range of motion than the bicycling game. <h3><b>Limitations</b></h3> A limitation of this study was the relatively small and heterogeneous sample. <h3><b>Conclusions</b></h3> For all 4 games, similar exercise intensity levels were observed for children who were typically developing and children with CP, suggesting that children with CP could obtain exercise-related benefits similar to those obtained by children without CP while playing with an active video game console.
Opportunities to improve global health: using the strengths of the<i>BJSM</i>community to change lives for the better
Authors: Steve Aspinall, Allan Munro
Journal: British Journal of Sports Medicine (2020)

One of the founding principles of the British Association of Sport Rehabilitators and Trainers—BASRaT—was to improve the health of patients and the public with a clear focus on exercise for health and exercise rehabilitation. That goal has never been more important than it is today and it provided the inspiration for our cover image (figure 1). In the midst of a pandemic, attention will be inevitably and increasingly focused on the health of our respective nations and bring into sharp relief the challenges we face as an international community of medical and healthcare professionals. An effective response to these challenges will involve us all working together to improve our knowledge and to identify the best way to translate that into real improvements in public health.



Figure 1 
The British Association for Sport Rehabilitators and Trainers has a clear focus on exercise for health and rehabilitation.



Across the UK, organisations and professional bodies representing numerous healthcare professions have already started working more collaboratively, with the goals of the individual profession being subservient to finding ways to optimise rehabilitation and the prevention of ill health. Both the Arthritis and Musculoskeletal Alliance (ARMA) (http://arma.uk.net) and the Community Rehabilitation Alliance are just two examples of this in the UK. These alliances cut across professional boundaries, integrate healthcare systems and support the rights of patients …
Machine Learning Classifier Models Can Identify Acute Respiratory Distress Syndrome Phenotypes Using Readily Available Clinical Data
Authors: Pratik Sinha, Matthew M. Churpek, Carolyn S. Calfee
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Two distinct phenotypes of acute respiratory distress syndrome (ARDS) with differential clinical outcomes and responses to randomly assigned treatment have consistently been identified in randomized controlled trial cohorts using latent class analysis. Plasma biomarkers, key components in phenotype identification, currently lack point-of-care assays and represent a barrier to the clinical implementation of phenotypes.Objectives: The objective of this study was to develop models to classify ARDS phenotypes using readily available clinical data only.Methods: Three randomized controlled trial cohorts served as the training data set (ARMA [High vs. Low Vt], ALVEOLI [Assessment of Low Vt and Elevated End-Expiratory Pressure to Obviate Lung Injury], and FACTT [Fluids and Catheter Treatment Trial]; n = 2,022), and a fourth served as the validation data set (SAILS [Statins for Acutely Injured Lungs from Sepsis]; n = 745). A gradient-boosted machine algorithm was used to develop classifier models using 24 variables (demographics, vital signs, laboratory, and respiratory variables) at enrollment. In two secondary analyses, the ALVEOLI and FACTT cohorts each, individually, served as the validation data set, and the remaining combined cohorts formed the training data set for each analysis. Model performance was evaluated against the latent class analysis-derived phenotype.Measurements and Main Results: For the primary analysis, the model accurately classified the phenotypes in the validation cohort (area under the receiver operating characteristic curve [AUC], 0.95; 95% confidence interval [CI], 0.94-0.96). Using a probability cutoff of 0.5 to assign class, inflammatory biomarkers (IL-6, IL-8, and sTNFR-1; P < 0.0001) and 90-day mortality (38% vs. 24%; P = 0.0002) were significantly higher in the hyperinflammatory phenotype as classified by the model. Model accuracy was similar when ALVEOLI (AUC, 0.94; 95% CI, 0.92-0.96) and FACTT (AUC, 0.94; 95% CI, 0.92-0.95) were used as the validation cohorts. Significant treatment interactions were observed with the clinical classifier model-assigned phenotypes in both ALVEOLI (P = 0.0113) and FACTT (P = 0.0072) cohorts.Conclusions: ARDS phenotypes can be accurately identified using machine learning models based on readily available clinical data and may enable rapid phenotype identification at the bedside.
Liver X Receptor Alpha Activation Inhibits Autophagy and Lipophagy in Hepatocytes by Dysregulating Autophagy‐Related 4B Cysteine Peptidase and Rab‐8B, Reducing Mitochondrial Fuel Oxidation
Authors: Yun Seok Kim, Hyeon Joo Nam, Chang Yeob Han, Min Sung Joo, Kiseok Jang, Dae Won Jun, Sang Geon Kim
Journal: Hepatology (2020)

Background and Aims Fat accumulation results from increased fat absorption and/or defective fat metabolism. Currently, the lipid‐sensing nuclear receptor that controls fat utilization in hepatocytes is elusive. Liver X receptor alpha (LXRα) promotes accumulation of lipids through the induction of several lipogenic genes. However, its effect on lipid degradation is open for study. Here, we investigated the inhibitory role of LXRα in autophagy/lipophagy in hepatocytes and the underlying basis. Approach and Results In LXRα knockout mice fed a high‐fat diet, or cell models, LXRα activation suppressed the function of mitochondria by inhibiting autophagy/lipophagy and induced hepatic steatosis. Gene sets associated with “autophagy” were enriched in hepatic transcriptome data. Autophagy flux was markedly augmented in the LXRα knockout mouse liver and primary hepatocytes. Mechanistically, LXRα suppressed autophagy‐related 4B cysteine peptidase (ATG4B) and Rab‐8B, responsible for autophagosome and ‐lysosome formation, by inducing let‐7a and microRNA (miR)‐34a. Chromatin immunoprecipitation assay enabled us to find LXRα as a transcription factor of let‐7a and miR‐34a. Moreover, 3’ untranslated region luciferase assay substantiated the direct inhibitory effects of let‐7a and miR‐34a on ATG4B and Rab‐8B. Consistently, either LXRα activation or the let‐7a/miR‐34a transfection lowered mitochondrial oxygen consumption rate and mitochondrial transmembrane potential and increased fat levels. In obese animals or nonalcoholic fatty liver disease (NAFLD) patients, let‐7a and miR‐34a levels were elevated with simultaneous decreases in ATG4B and Rab‐8B levels. Conclusions LXRα inhibits autophagy in hepatocytes through down‐regulating ATG4B and Rab‐8B by transcriptionally activating microRNA let‐7a‐2 and microRNA 34a genes and suppresses mitochondrial biogenesis and fuel consumption. This highlights a function of LXRα that culminates in the progression of liver steatosis and steatohepatitis, and the identified targets may be applied for a therapeutic strategy in the treatment of NAFLD.
Safety and immunogenicity of the α-synuclein active immunotherapeutic PD01A in patients with Parkinson's disease: a randomised, single-blinded, phase 1 trial
Authors: Dieter Volc, Werner Poewe, Alexandra Kutzelnigg, Petra Lührs, Caroline Thun-Hohenstein, Achim Schneeberger, Gergana Galabova, Nour Majbour, Nishant Vaikath, Omar El-Agnaf, Dorian Winter, Eva Mihailovska, Andreas Mairhofer, Carsten Schwenke, Günther Staffler, Rossella Medori
Journal: The Lancet Neurology (2020)
QuantiFERON‐TB Gold conversion is not uncommon in patients with psoriasis undergoing anti‐tumour necrosis factor‐α therapy: reply from the author
Authors: A.P. Fernandez
Journal: British Journal of Dermatology (2020)

Linked Articles: Megna et al. Br J Dermatol 2020; 183:977–978. Ya et al. Br J Dermatol 2020; 182:800–802.
Emerging therapies in mantle cell lymphoma
Authors: Walter Hanel, Narendranath Epperla
Journal: Journal of Hematology & Oncology (2020)

Abstract Mantle cell lymphoma (MCL) is a rare, B cell non-Hodgkin’s lymphoma with highly heterogeneous clinical presentation and aggressiveness. First-line treatment consists of intensive chemotherapy with autologous stem cell transplant for the fit, transplant eligible patients, or less intensive chemotherapy for the less fit (and transplant-ineligible) patients. Patients eventually relapse with a progressive clinical course. Numerous therapeutic approaches have emerged over the last few years which have significantly changed the treatment landscape of MCL. These therapies consist of targeted approaches such as BTK and BCL2 inhibitors that provide durable therapeutic responses. However, the optimum combination and sequencing of these therapies is unclear and is currently investigated in several ongoing studies. Furthermore, cellular therapies such as chimeric antigen receptor (CAR) T cells and bispecific T cell engager (BiTe) antibodies have shown impressive results and will likely shape treatment approaches in relapsed MCL, especially after failure with BTK inhibitors. Herein, we provide a comprehensive review of past and ongoing studies that will likely significantly impact our approach to MCL treatment in both the frontline (for transplant eligible and ineligible patients) as well as in the relapsed setting. We present the most up to date results from these studies as well as perspectives on future studies in MCL.
Perinatal Hypoxia-Inducible Factor Stabilization Preserves Lung Alveolar and Vascular Growth in Experimental Bronchopulmonary Dysplasia
Authors: Kellen Hirsch, Elizabeth Taglauer, Gregory Seedorf, Carly Callahan, Erica Mandell, Carl W. White, Stella Kourembanas, Steven H. Abman
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Antenatal inflammation with placental dysfunction is strongly associated with high bronchopulmonary dysplasia (BPD) risk in preterm infants. Whether antenatal or postnatal HIF (hypoxia-inducible factor) augmentation can preserve lung structure and function and prevent pulmonary hypertension after intrauterine inflammation is controversial.Objectives: To determine whether antenatal or postnatal prolyl-hydroxylase inhibitor (PHi) therapy increases lung HIF expression, preserves lung growth and function, and prevents pulmonary hypertension in a rat model of chorioamnionitis-induced BPD caused by antenatal inflammation.Methods: Endotoxin (ETX) was administered to pregnant rats by intraamniotic injection at Embryonic Day 20, and pups were delivered by cesarean section at Embryonic Day 22. Selective PHi drugs, dimethyloxalylglycine or GSK360A, were administered into the amniotic space at Embryonic Day 20 or after birth by intraperitoneal injection for 2 weeks. Placentas and lung tissue were collected at birth for morphometric and Western blot measurements of HIF-1a, HIF-2a, VEGF (vascular endothelial growth factor), and eNOS (endothelial nitric oxide synthase) protein contents. At Day 14, lung function was assessed, and tissues were harvested to determine alveolarization by radial alveolar counts, pulmonary vessel density, and right ventricle hypertrophy (RVH).Measurements and Main Results: Antenatal PHi therapy preserves lung alveolar and vascular growth and lung function and prevents RVH after intrauterine ETX exposure. Antenatal administration of PHi markedly upregulates lung HIF-1a, HIF-2a, VEGF, and eNOS expression after ETX exposure.Conclusions: HIF augmentation improves lung structure and function, prevents RVH, and improves placental structure following antenatal ETX exposure. We speculate that antenatal or postnatal PHi therapy may provide novel strategies to prevent BPD due to antenatal inflammation.
COVID-19–related Mortality During the First 60 Days After Kidney Transplantation
Authors: Julio Pascual, Edoardo Melilli, Carlos Jiménez-Martín, Esther González-Monte, Sofía Zárraga, Alex Gutiérrez-Dalmau, Veronica López-Jiménez, Javier Juega, Miguel Muñoz-Cepeda, Inmaculada Lorenzo, Carme Facundo, María del Carmen Ruiz-Fuentes, Auxiliadora Mazuecos, Emilio Sánchez-Álvarez, Marta Crespo
Journal: European Urology (2020)