tbuckley/cabot-search huggingface dataset:
Patient factors and temporal trends associated with COVID-19 in-hospital mortality in England: an observational study using administrative data
Authors: Annakan V Navaratnam, William K Gray, Jamie Day, Julia Wendon, Tim W R Briggs
Journal: The Lancet Respiratory Medicine (2021)

Analysis of the effect of COVID-19 on the complete hospital population in England has been lacking. Our aim was to provide a comprehensive account of all hospitalised patients with COVID-19 in England during the early phase of the pandemic and to identify the factors that influenced mortality as the pandemic evolved.This was a retrospective exploratory analysis using the Hospital Episode Statistics administrative dataset. All patients aged 18 years or older in England who completed a hospital stay (were discharged alive or died) between March 1 and May 31, 2020, and had a diagnosis of COVID-19 on admission or during their stay were included. In-hospital death was the primary outcome of interest. Multilevel logistic regression was used to model the relationship between death and several covariates: age, sex, deprivation (Index of Multiple Deprivation), ethnicity, frailty (Hospital Frailty Risk Score), presence of comorbidities (Charlson Comorbidity Index items), and date of discharge (whether alive or deceased).91 541 adult patients with COVID-19 were discharged during the study period, among which 28 200 (30·8%) in-hospital deaths occurred. The final multilevel logistic regression model accounted for age, deprivation score, and date of discharge as continuous variables, and sex, ethnicity, and Charlson Comorbidity Index items as categorical variables. In this model, significant predictors of in-hospital death included older age (modelled using restricted cubic splines), male sex (1·457 [1·408-1·509]), greater deprivation (1·002 [1·001-1·003]), Asian (1·211 [1·128-1·299]) or mixed ethnicity (1·317 [1·080-1·605]; vs White ethnicity), and most of the assessed comorbidities, including moderate or severe liver disease (5·433 [4·618-6·392]). Later date of discharge was associated with a lower odds of death (0·977 [0·976-0·978]); adjusted in-hospital mortality improved significantly in a broadly linear fashion, from 52·2% in the first week of March to 16·8% in the last week of May.Reductions in the adjusted probability of in-hospital mortality for COVID-19 patients over time might reflect the impact of changes in hospital strategy and clinical processes. The reasons for the observed improvements in mortality should be thoroughly investigated to inform the response to future outbreaks. The higher mortality rate reported for certain ethnic minority groups in community-based studies compared with our hospital-based analysis might partly reflect differential infection rates in those at greatest risk, propensity to become severely ill once infected, and health-seeking behaviours.None.
Effective engagement and involvement with community stakeholders in the co-production of global health research
Authors: Doreen Tembo, Gary Hickey, Cristian Montenegro, David Chandler, Erica Nelson, Katie Porter, Lisa Dikomitis, Mary Chambers, Moses Chimbari, Noni Mumba, Peter Beresford, Peter O Ekiikina, Rosemary Musesengwa, Sophie Staniszewska, Tina Coldham, Una Rennard
Journal: BMJ (2021)

Doreen Tembo and colleagues argue that small changes as well as larger system-wide changes can strengthen citizens' contribution to knowledge in health research Involving a broad range of individual and collective perspectives in global health research outside of academic research is gaining increasing recognition as a mechanism for achieving a greater impact. This activity goes by many names (box 1). In the global north or a high income country, it is commonly called "patient and public involvement," "engagement," or "participation." In low and middle income countries or the global south, these participatory processes are termed "community engagement," "participation," and "community engagement and involvement."123 Co-production, a core feature of community engagement and involvement, is common to health research in both the global north and south, with a range of potential benefits. It helps to ensure that health research contributes to building knowledge and generating innovations that benefit users of research.4 For research that drives change and reduces the waste of resources,5 co-production should start from the earliest stages, when problems are identified and priorities defined.6 Such an approach supports research that is ethical, specific, and appropriate to the local community.789101112 Involvement of end users in the design of projects has also been shown to improve recruitment of participants and research methods, making implementation and the impact of the research results more likely.913 Box 1 ### Terminology for partnering with communities Many terms are used to describe how researchers form partnerships with non-academic communities. The lack of universally agreed and defined terms can lead to a lack of clarity about shared values and scope of activities, and relevance to other researchers and communities. It can also hamper discovery and synthesis of evidence from the literature. The UK National Institute for Health Research (NIHR) distinguishes between terminologies … RETURN TO TEXT
Targeting cell-intrinsic metabolism for antifibrotic therapy
Authors: Helene Gilgenkrantz, Ariane Mallat, Richard Moreau, Sophie Lotersztajn
Journal: Journal of Hepatology (2021)

In recent years, there have been major advances in our understanding of the mechanisms underlying fibrosis progression and regression, and how coordinated interactions between parenchymal and non-parenchymal cells impact on the fibrogenic process. Recent studies have highlighted that metabolic reprogramming of parenchymal cells, immune cells (immunometabolism) and hepatic stellate cells is required to support the energetic and anabolic demands of phenotypic changes and effector functions. In this review, we summarise how targeting cell-intrinsic metabolic modifications of the main fibrogenic cell actors may impact on fibrosis progression and we discuss the antifibrogenic potential of metabolically targeted interventions.
The role of neutrophils in viral clearance during respiratory syncytial virus (RSV) disease
Authors: Gemma Saint, Brian Flanagan, Paul McNamara, Rosalind Smyth
Journal: European Respiratory Journal (2013)

Background: Neutrophils are the most numerous cell in the airway during RSV bronchiolitis. We have found neutrophils in bronchoalveolar lavage (BAL) from infants with RSV disease contain RSV proteins. I hypothesise that neutrophils may play a vital role in viral clearance in the airway.

Methods: Highly purified neutrophils from whole blood of healthy adult donors were incubated with A2 strain RSV in the presence of GM-CSF, used as a neutrophil pro-survival factor. Samples were taken at 2, 4, 6 and 20 hours for quantitative PCR of RSV N gene and FACS analysis of RSV F, G and N protein.

Results: Interaction of RSV and neutrophils was shown in vitro, with neutrophils being RSV F, G and N protein positive by FACS analysis. Quantitative PCR revealed a 1000-2000 fold increase in RSV N gene expression compared to the L32 housekeeping gene, maximal between 2-4 hours with some inter-donor variability. This expression reduced in all experiments by 20 hours, suggesting that RSV phagocytosis was occurring followed by degradation. I have gone on to show that the uptake is autologous serum dependant, with a strong dose response. Uptake is 5-fold higher when comparing 0.1% serum with 10% serum (p<0.05).

Conclusion: Phagocytosis of complement-opsonized bacteria, assisted by antibodies, is a well-documented role for the neutrophil. Here we have shown a similar process may be involved in viral clearance as part of the immune response to viral invasion. Experiments are on-going investigating whether a relative complement or antibody insufficiency may contribute to the susceptibility of infants to severe RSV disease.
Abstract SP151: BRCA and homologous recombination deficiency mediated mutagenesis in breast cancer
Authors: A Tutt
Journal: Cancer Research (2021)

Abstract The genes BRCA1, BRCA2 and PALB2 genes are the major high penetrance risk alleles in breast cancer have function in a DNA repair mechanism called homologous recombination (HR). These and a wider group of other genes including the RAD51 paralogues and kinase regulators of HR can also be subject to somatic mutation or epigenetic modification in cancer and, usually in the setting of bi-allelic inactivation, effect the use of HR. The dysregulation of BRCA1 by methylation of its regulatory region is frequent occurring, in approximately 30% of sporadic basal-like breast cancers. While there is evidence that BRCA1 silencing causes functional HR deficiency, there is also evidence suggesting this may be more “plastic” and subject to change to maintain cell fitness and DNA replication capacity under the evolutionary pressures that cancer cells are subjected to during progression and therapyexposure.HR deficient cancers change to use of other DNA break and DNA replication fork repair mechanisms that are mutagenic. A number of methods based on tumor genome sequencing have been developed to assesssomatic mutational signatures. These methods have revealed pathognomonic “scars” or “tattoos” indicating exposure to HR deficiency during breast cancer evolution and the variable performance of mutational signatures in the contexts of genetic and epigenetic loss of HR function. HR deficiency induced mutagenesis can also inactivate genes that negatively regulate HR, or re-activate (reversion mutation) the previously inactivated HR gene, driving a reversal of HR deficiency. As this changes a cell’s DNA repair phenotype and its ability to handle to therapeutic damage, these are increasingly found to be relevant to the development of resistance to DNA interacting drugs such as platinums and PARP inhibitors as well as to emerging DNA damage response (DDR) targeting therapeutics. In the setting of resistance both the residual HR deficiency induced genome landscape or the altered use of the DNA damage response in breast cancer cells may offer new vulnerabilities, enhanced in tumor cells, that are subject to targeted DDR directed or immunotherapy therapy and inform combination or sequential therapy approaches and associated patient selection biomarkers now being assessed in the clinic. Citation Format: A Tutt. BRCA and homologous recombination deficiency mediated mutagenesis in breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP151.
Site versus Core Laboratory SYNTAX score variability
Authors: Carlos Collet, Yosuke Miyazaki, Daniele Andreini, Antonio Bartorelli, Jeroen Sonck, Johan De Mey, Bert Vandeloo, Taku Asano, Yuki Katagiri, Ulf Teichgraeber, Torsten Doenst, Marie-Angele Morel, Yoshinobu Onuma, Patrick Serruys
Journal: Journal of the American College of Cardiology (2018)
Socioeconomic inequalities in the quality of primary care under Brazil's national pay-for-performance programme: a longitudinal study of family health teams
Authors: Roxanne Kovacs, Jorge O Maia Barreto, Everton Nunes da Silva, Josephine Borghi, Søren Rud Kristensen, Deivson Rayner T Costa, Luciano Bezerra Gomes, Garibaldi D Gurgel, Juliana Sampaio, Timothy Powell-Jackson
Journal: The Lancet Global Health (2021)

BackgroundMany governments have introduced pay-for-performance programmes to incentivise health providers to improve quality of care. Evidence on whether these programmes reduce or exacerbate disparities in health care is scarce. In this study, we aimed to assess socioeconomic inequalities in the performance of family health teams under Brazil's National Programme for Improving Primary Care Access and Quality (PMAQ).MethodsFor this longitudinal study, we analysed data on the quality of care delivered by family health teams participating in PMAQ over three rounds of implementation: round 1 (November, 2011, to March, 2013), round 2 (April, 2013, to September, 2015), and round 3 (October, 2015, to December, 2019). The primary outcome was the percentage of the maximum performance score obtainable by family health teams (the PMAQ score), based on several hundred (ranging from 598 to 914) indicators of health-care delivery. Using census data on household income of local areas, we examined the PMAQ score by income ventile. We used ordinary least squares regressions to examine the association between PMAQ scores and the income of each local area across implementation rounds, and we did an analysis of variance to assess geographical variation in PMAQ score.FindingsOf the 40 361 family health teams that were registered as ever participating in PMAQ, we included 13 934 teams that participated in the three rounds of PMAQ in our analysis. These teams were located in 11 472 census areas and served approximately 48 million people. The mean PMAQ score was 61·0% (median 61·8, IQR 55·3–67·9) in round 1, 55·3% (median 56·0, IQR 47·6–63·4) in round 2, and 61·6% (median 62·7, IQR 54·4–69·9) in round 3. In round 1, we observed a positive socioeconomic gradient, with the mean PMAQ score ranging from 56·6% in the poorest group to 64·1% in the richest group. Between rounds 1 and 3, mean PMAQ performance increased by 7·1 percentage points for the poorest group and decreased by 0·8 percentage points for the richest group (p<0·0001), with the gap between richest and poorest narrowing from 7·5 percentage points (95% CI 6·5 to 8·5) to –0·4 percentage points over the same period (–1·6 to 0·8).InterpretationExisting income inequalities in the delivery of primary health care were eliminated during the three rounds of PMAQ, plausibly due to a design feature of PMAQ that adjusted financial payments for socioeconomic inequalities. However, there remains an important policy agenda in Brazil to address the large inequities in health.FundingUK Medical Research Council, Newton Fund, and CONFAP (Conselho Nacional das Fundações Estaduais de Amparo à Pesquisa).
The Effect of Surgical Treatment on Obstructive Sleep Apnea—Reply
Authors: Stuart MacKay, R. Doug McEvoy, Edward M. Weaver
Journal: JAMA (2021)

In Reply Drs Alderman and Agbetile raise several concerns about our SAMS trial findings,1 specifically that the 6-month surgical improvements may not persist over time, that long-term cardiovascular outcomes were not assessed, and that there should be a mortality benefit with OSA surgery.
Abstract 13183: The Nuclear Sirtuin, Sirt6 Mitigates Muscle Atrophy Associated With Cancer
Authors: Sadhana Samant, Vinod Pillai, Abhinav Kanwal, Mahesh P Gupta
Journal: Circulation (2018)

Introduction: Many terminal diseases are accompanied with involuntary muscle loss, termed as cachexia. Cachectic cancer patients are also vulnerable to develop cardiomyopathy. Previously, we observ...
Trained Immunity: Reprogramming Innate Immunity in Health and Disease
Authors: Siroon Bekkering, Jorge Domínguez-Andrés, Leo A.B. Joosten, Niels P. Riksen, Mihai G. Netea
Journal: Annual Review of Immunology (2021)

Traditionally, the innate and adaptive immune systems are differentiated by their specificity and memory capacity. In recent years, however, this paradigm has shifted: Cells of the innate immune system appear to be able to gain memory characteristics after transient stimulation, resulting in an enhanced response upon secondary challenge. This phenomenon has been called trained immunity. Trained immunity is characterized by nonspecific increased responsiveness, mediated via extensive metabolic and epigenetic reprogramming. Trained immunity explains the heterologous effects of vaccines, which result in increased protection against secondary infections. However, in chronic inflammatory conditions, trained immunity can induce maladaptive effects and contribute to hyperinflammation and progression of cardiovascular disease, autoinflammatory syndromes, and neuroinflammation. In this review we summarize the current state of the field of trained immunity, its mechanisms, and its roles in both health and disease.
Abstract 17258: The Relationship Between D-Dimer Levels and Deep Venous Thrombosis in COVID-19: An Analysis From a Quaternary Academic Medical Center in New York City
Authors: Mahesh V Madhavan, Aakriti Gupta, Behnood Bikdeli, Björn Redfors, Jessica Hennessey, Matthew Lawlor, Timothy J Poterucha, Ani Nalbandian, Elissa Driggin, Pierre Elias, Lauren S Ranard, Shayan Nabavi Nouri, Li Jianhua, Matthew T Finn, Joseph Ingrassia, Andrew Eisenberger, Amirali Masoumi, Nir Uriel, Martin B Leon, Ajay J Kirtane, Sahil Parikh, Sanjum Sethi
Journal: Circulation (2020)

Background: D-Dimer values may be elevated in hyperinflammatory or prothrombotic states and are frequently measured in patients with coronavirus disease 2019 (COVID-19). Many institutional algorithms and ongoing studies suggest using D-Dimer cutoffs to initiate anticoagulation. The relationship between D-Dimer levels and deep venous thrombosis (DVT) has not been extensively studied specifically in patients with COVID-19. Methods: We retrospectively studied patients hospitalized at our institution between 2/1/20-5/19/20 for COVID-19 who underwent lower extremity venous doppler imaging. After stratifying by presence of DVT, baseline characteristics, vital signs, and laboratory values were assessed. We assessed the association between peak D-Dimer levels and diagnosis of DVT during admission. Upper limit D-Dimer value for the hospital’s laboratory assay was &gt;20 mg/dL. Results: Of the 2677 patients admitted, 514 underwent lower extremity imaging, out of whom 186 (36.2%) were diagnosed with DVT. Other than history of cancer, which was more common in patients with a diagnosis of DVT (14.7% vs. 6.3%, p&lt;0.01), baseline characteristics and presentation vital signs were similar between groups. Median peak D-Dimer levels were similar in patients with and without diagnosis of DVT [18.5 mg/dL, IQR: 6.4-20.0 vs. 12.2 mg/dL, IQR: 3.7-20, p = 0.80]. Density plots of initial D-Dimer values grouped by presence of DVT are presented in Figure 1. Conclusions: In this analysis of patients hospitalized with COVID-19, DVT was frequently diagnosed in patients who underwent imaging. There was considerable overlap of peak D-Dimer values in patients with and without documented DVT. As such, elevation in D-Dimer values alone should not prompt routine initiation of therapeutic anticoagulation in COVID-19 patients. Data from prospective clinical trials and registries regarding optimal antithrombotic practices in this patient population is needed.
Advance Directive Utilization Decreases Aggressive End-of-Life Care in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation
Authors: Kathryn Cappell, Annie Park, Vandana Sundaram, Parveen Shiraz, Patricia Jenkins, Vyjeyanthi Periyakoil, Lori S. Muffly
Journal: Blood (2017)
Muscarinic Cholinergic Receptor Agonist and Peripheral Antagonist for Schizophrenia
Authors: Stephen K. Brannan, Sharon Sawchak, Andrew C. Miller, Jeffrey A. Lieberman, Steven M. Paul, Alan Breier
Journal: New England Journal of Medicine (2021)

The muscarinic receptor agonist xanomeline has antipsychotic properties and is devoid of dopamine receptor–blocking activity but causes cholinergic adverse events. Trospium is a peripherally restricted muscarinic receptor antagonist that reduces peripheral cholinergic effects of xanomeline. The efficacy and safety of combined xanomeline and trospium in patients with schizophrenia are unknown.
Screening the Older Population for Atrial Fibrillation—Have We Moved the Needle Forward?
Authors: Roopinder K. Sandhu, Christine Albert
Journal: JAMA Cardiology (2021)

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Adjuvant Chemotherapy in Patients With Early-Stage Non–Small Cell Lung Cancer
Authors: Kentaro Inamura
Journal: JAMA Oncology (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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal