tbuckley/cabot-search huggingface dataset:
Addressing the COVID-19 Pandemic in Populations With Serious Mental Illness
Authors: Benjamin G. Druss
Journal: JAMA Psychiatry (2020)

With Serious Mental IllnessThe coronavirus disease 2019 (COVID-19) pandemic will present an unprecedented stressor to patients and health care systems across the globe.Because there is currently no vaccine or treatment for the underlying infection, current health efforts are focused on providing prevention and screening, maintaining continuity of treatment for other chronic conditions, and ensuring access to appropriately intensive services for those with the most severe symptoms. 1isasters disproportionately affect poor and vulnerable populations, and patients with serious mental illness may be among the hardest hit.High rates of smoking in this population may raise the risk of infection and confer a worse prognosis among those who develop the illness. 2 Residential instability and homelessness can raise the risk of infection and make it harder to identify, follow up, and treat those who are infected. 3Individuals with serious mental illnesses who are employed may have challenges taking time off from work and may lack sufficient insurance coverage to cover testing or treatment.Small social networks may limit opportunities to obtain support from friends and family members should individuals with serious mental illness become ill.Taken together, these factors may lead to elevated infection rates and worse prognoses in this population.What strategies are available to mitigate the outcome of this epidemic among patients with serious mental illness?Federal preparedness policies developed in the wake of complex disasters have increasingly embraced the notion of whole community preparedness, which supports building and supporting structures at multiple levels to prepare and respond, particularly for vulnerable populations. 4Within the public mental health care system, this includes engagement with mental health service users, clinicians, and federal and state policies.
An Intrapatient Concordance Study of Mismatch Repair Protein Immunohistochemical Staining Patterns in Patients With Muir-Torre Syndrome
Authors: Cuong V. Nguyen, Kevin J. Gaddis, Michael R. Stephens, John T. Seykora, Emily Y. Chu
Journal: JAMA Dermatology (2020)

<h3>Importance</h3> Appropriate use criteria for Muir-Torre syndrome (MTS) screening suggest that mismatch repair protein (MMRP) immunohistochemical (IHC) testing is usually appropriate in patients with 2 or more sebaceous neoplasms (SNs). While MTS is known to be caused by a germline mutation in mismatch repair genes, data are limited as to whether individual sebaceous tumors in these patients with multiple lesions show identical MMRP IHC staining patterns. <h3>Objective</h3> To determine concordance of MMRP IHC staining patterns in lesions of patients with MTS who have multiple SNs. <h3>Design, Setting, and Participants</h3> This retrospective single-center case series evaluated 38 SNs in 11 patients with MTS confirmed by genetic testing for MMRP IHC staining patterns. Tumor sites were classified as either facial or extrafacial. Data were collected between January 1, 2007, and January 1, 2018. <h3>Main Outcomes and Measures</h3> In each patient, MMRP IHC staining patterns for SNs were compared with one another to evaluate intrapatient concordance between lesions, and to the patient's known germline mutation. <h3>Results</h3> A total of 11 patients (7 women and 4 men) with MTS, with a mean (SD) age of 59.3 (10.6) years at time of SN biopsy, were identified. There was high concordance between MMRP IHC staining results (2-4 lesions per patient) and the patient's mutation status, with 36 of 38 total lesions (95%) matching (sensitivity, 94.7%; 95% CI, 82.3%-99.4%). Extrafacial site tumors represented 16 of 38 total lesions (42%) and demonstrated 100% concordance of IHC results to germline mutation. Only 1 of 11 patients (9%) demonstrated discordant results, with both lesions in this patient occurring on a facial site. <h3>Conclusions and Relevance</h3> In patients with known MTS, SNs present with highly concordant MMRP IHC staining profiles across multiple lesions. There is also a strong association with underlying germline mutations. A diagnosis of MTS might be supported by MMRP IHC when the pretest probability is high.
Laboratory investigation results influence Physician’s Global Assessment (PGA) of disease activity in SLE
Authors: Cynthia Aranow, Anca Askanase, Shereen Oon, Molla Huq, Alicia Calderone, Eric F Morand, Mandana Nikpour
Journal: Annals of the Rheumatic Diseases (2020)

Objective To evaluate the impact of laboratory results on scoring of the Physician Global Assessment (PGA) of disease activity in systemic lupus erythematosus. Methods Fifty clinical vignettes were presented via an online survey to a group of international lupus experts. For each case, respondents scored the PGA pre and post knowledge of laboratory test results (pre-lab and post-lab PGAs). Agreement between individual assessors and relationships between pre-lab and post-lab PGAs, and PGAs and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) were determined. Respondents were also asked about factors they incorporate into their PGA determinations. Results Sixty surveys were completed. The inter-rater PGA reliability was excellent (pre-lab intraclass correlation coefficient (ICC) 0.98; post-lab ICC 0.99). Post-lab PGAs were higher than pre-lab PGAs: median (IQR) pre-lab PGA 0.5 (1.05), post-lab PGA 1 (1.3) (p&lt;0.001), with a median (IQR) difference of 0.2 (0.45). In general, all abnormal labs including elevated anti-double stranded DNA antibody level (dsDNA) and low complement impacted PGA assessment. Cases with weakest correlations between pre-lab and post-lab PGA were characterised by laboratory results revealing nephritis and/or haematological manifestations. Both pre-lab and post-lab PGAs correlated with SLEDAI-2K. However, a significantly stronger correlation was observed between post-lab PGA and SLEDAI-2K. Multiple factors influenced PGA determinations. Some factors were considered by an overwhelming majority of lupus experts, with less agreement on others. Conclusions We found excellent inter-rater reliability for PGAs in a group of international lupus experts. Post-lab PGA scores were higher than pre-lab PGA scores, with a significantly stronger correlation with the SLEDAI-2K. Our findings indicate that PGA scoring should be performed with knowledge of pertinent laboratory results.
SPOP negatively regulates Toll-like receptor-induced inflammation by disrupting MyD88 self-association
Authors: Yun-Hong Hu, Yang Wang, Fei Wang, Yan-Ming Dong, Wan-Ling Jiang, Ya-Ping Wang, Xing Zhong, Li-Xin Ma
Journal: Cellular and Molecular Immunology (2020)

Abstract Toll-like receptor (TLR) signaling pathways need to be tightly controlled to avoid excessive inflammation and unwanted damage to the host. Myeloid differentiation primary response gene 88 (MyD88) is a critical adaptor of TLR signaling. Here, we identified the speckle-type POZ protein (SPOP) as a MyD88-associated protein. SPOP was recruited to MyD88 following TLR4 activation. TLR4 activation also caused the translocation of SPOP from the nucleus to the cytoplasm. SPOP depletion promoted the aggregation of MyD88 and recruitment of the downstream signaling kinases IRAK4, IRAK1 and IRAK2. Consistently, overexpression of SPOP inhibited the TLR4-mediated activation of NF-κB and production of inflammatory cytokines, whereas SPOP depletion had the opposite effects. Furthermore, knockdown of SPOP increased MyD88 aggregation and inflammatory cytokine production upon TLR2, TLR7 and TLR9 activation. Our findings reveal a mechanism by which MyD88 is regulated and highlight a role for SPOP in limiting inflammatory responses.
Quality of Life with weekly platinum-based chemotherapy in newly diagnosed Ovarian Cancer: the ICON8 phase III randomised controlled clinical trial
Authors: S Blagden, A D Cook, C Poole, L Howells, I A McNeish, A Dean, J W Kim, D M O’Donnell, J Hook, E C James, I R White, T Perren, R Lord, G Dark, H M Earl, M Hall, R Kaplan, J A Ledermann, A R Clamp
Journal: The Lancet Oncology (2020)
Abstract 102: Inhaled Nitric Oxide Mitigates Pulmonary Hypertension and Improves Cerebral Hemodynamics During Prolonged Cardiopulmonary Pesuscitation in a Swine Model of Pediatric Cardiac Arrest
Authors: Constantine D Mavroudis, Ryan W Morgan, Tiffany S Ko, Marco M Hefti, William P Landis, Tiffany W Boorady, Alexandra M Marquez, Michael Karlsson, Daniel J Licht, Robert A Berg, Vinay M Nadkarni, Robert M Sutton, Todd J Kilbaugh
Journal: Circulation (2018)

Introduction: Pulmonary hypertension may play a role in preventing ROSC during prolonged CPR. Targeted pulmonary vasodilation with inhaled nitric oxide (iNO) during CPR may improve pulmonary blood flow and improve outcomes. The purpose of this study was to study the effects of iNO in a randomized, blinded, placebo controlled, pediatric swine model of asphyxial cardiac arrest. Hypothesis: Animals treated with iNO will have lower pulmonary artery pressure, improved systemic hemodynamics, and increased cerebral blood flow during prolonged CPR compared to control. Methods: Four-week-old piglets (n=10) that underwent seven minutes of asphyxia, induction of VF, and 10 minutes of CPR were randomized to either iNO (20 ppm) or placebo in a blinded fashion starting one min into CPR and needed more than 1 defibrillation attempt. Defibrillation was attempted after 10 minutes of CPR. Animals that did not achieve ROSC by 20 minutes were euthanized. Invasive pulmonary and systemic hemodynamics, and both invasive and noninvasive cerebral hemodynamics were continuously measured. Data described as mean ± SD and compared using a generalized estimating equation regression model. Results: All 5 iNO-treated animals and 2/5 placebo-treated animals achieved ROSC. Those treated with iNO had lower mean pulmonary artery pressures (29.5 ± 9.1 vs. 48.3 ± 5.6 mmHg, p=0.04); higher mean aortic pressures (51.9 ± 6.4 vs. 35.5 ± 4.4 mmHg, p=0.01); higher cerebral blood flow (invasive: 230.4 ± 57.4 vs. 28.7 ± 42.1 % baseline, p&lt;0.001; noninvasive: 58.4 ± 10.9 vs. 32.4 ± 8.1 % baseline, p=0.02); and higher cerebral tissue oxygenation (invasive: 33.1 ± 13.0 vs. 1.2 ± 9.8 mmHg, p=0.01; noninvasive: 38.0 ± 4.2 vs. 26.2 ± 3.1%, p=0.005) compared with placebo. Conclusions: Treatment with iNO during prolonged CPR results in lower pulmonary artery pressure, improved systemic hemodynamics, and increased cerebral blood flow and oxygenation. Pulmonary vasodilation may have an important role during prolonged CPR for asphyxial cardiac arrests.
Towards a better understanding of the ‘physical activity paradox’: the need for a research agenda
Authors: Pieter Coenen, Maaike A Huysmans, Andreas Holtermann, Niklas Krause, Willem van Mechelen, Leon M Straker, Allard J van der Beek
Journal: British Journal of Sports Medicine (2020)

Several studies have suggested that a ‘physical activity (PA) paradox’ may exist—that is, the well documented beneficial health effects of leisure-time physical activity (LTPA) are not found for occupational physical activity (OPA). A BJSM editorial has outlined potential explanations for such a paradox.1 A recent systematic review has provided some empirical evidence that men, but not women, engaging in high (compared with low) level OPA have an 18% (95% CI 5% to 34%) increased risk of all-cause mortality.2 Nonetheless, the existence of this paradox has been questioned in a discussion paper by Professor Roy Shephard.3 Below we expand on three limitations this discussion paper raised and suggest a research agenda for generating more conclusive evidence regarding this paradox.

The current evidence originated from certain regions including Scandinavia, Spain, Iran and Israel. It was suggested that this restricted geographical representation weakens the evidence. However, relatively good working conditions in western European and Scandinavian countries could attenuate the negative health effects of OPA. Studies from countries with higher work demands and/or higher environmental temperatures are likely to provide evidence for even larger negative health effects. Apart from physical work demands, other factors (eg, LTPA or socioeconomical gradients) may also vary between countries and may have an impact on the association between OPA and health. The restricted origin of evidence also raises the possibility …
Association Between Preoperative Metformin Exposure and Postoperative Outcomes in Adults With Type 2 Diabetes
Authors: Katherine M. Reitz, Oscar C. Marroquin, Mazen S. Zenati, Jason Kennedy, Mary Korytkowski, Edith Tzeng, Stephen Koscum, David Newhouse, Ricardo Martinez Garcia, Jennifer Vates, Timothy R. Billiar, Brian S. Zuckerbraun, Richard L. Simmons, Stephen Shapiro, Christopher W. Seymour, Derek C. Angus, Matthew R. Rosengart, Matthew D. Neal
Journal: JAMA Surgery (2020)

Adults with comorbidity have less physiological reserve and an increased rate of postoperative mortality and readmission after the stress of a major surgical intervention.To assess postoperative mortality and readmission among individuals with diabetes with or without preoperative prescriptions for metformin.This cohort study obtained data from the electronic health record of a multicenter, single health care system in Pennsylvania. Included were adults with diabetes who underwent a major operation with hospital admission from January 1, 2010, to January 1, 2016, at 15 community and academic hospitals within the system. Individuals without a clinical indication for metformin therapy were excluded. Follow-up continued until December 18, 2018.Preoperative metformin exposure was defined as 1 or more prescriptions for metformin in the 180 days before the surgical procedure.All-cause postoperative mortality, hospital readmission within 90 days of discharge, and preoperative inflammation measured by the neutrophil to leukocyte ratio were compared between those with and without preoperative prescriptions for metformin. The corresponding absolute risk reduction (ARR) and adjusted hazard ratio (HR) with 95% CI were calculated in a propensity score-matched cohort.Among the 10 088 individuals with diabetes who underwent a major surgical intervention, 5962 (59%) had preoperative metformin prescriptions. A total of 5460 patients were propensity score-matched, among whom the mean (SD) age was 67.7 (12.2) years, and 2866 (53%) were women. In the propensity score-matched cohort, preoperative metformin prescriptions were associated with a reduced hazard for 90-day mortality (adjusted HR, 0.72 [95% CI, 0.55-0.95]; ARR, 1.28% [95% CI, 0.26-2.31]) and hazard of readmission, with mortality as a competing risk at both 30 days (ARR, 2.09% [95% CI, 0.35-3.82]; sub-HR, 0.84 [95% CI, 0.72-0.98]) and 90 days (ARR, 2.78% [95% CI, 0.62-4.95]; sub-HR, 0.86 [95% CI, 0.77-0.97]). Preoperative inflammation was reduced in those with metformin prescriptions compared with those without (mean neutrophil to leukocyte ratio, 4.5 [95% CI, 4.3-4.6] vs 5.0 [95% CI, 4.8-5.3]; P < .001). E-value analysis suggested robustness to unmeasured confounding.This study found an association between metformin prescriptions provided to individuals with type 2 diabetes before a major surgical procedure and reduced risk-adjusted mortality and readmission after the operation. This association warrants further investigation.
Covid-19: Trump threatens to stop funding WHO amid “China-centric” claims
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Donald Trump has warned that the US could stop funding the World Health Organization, as he accused it of being “China-centric” and of calling “every shot wrong.”

Speaking at a press conference on 7 April, President Trump criticised WHO for its decisions on covid-19 and said that the US could put a “very powerful” freeze on funding for the organisation.

He said, “The WHO receives a vast amount of money from the US. We pay for a majority, the biggest portion of their money. They actually criticised and disagreed with my travel ban at the time I did it. They were wrong, they have been wrong about a lot of things. They had a lot of information early and they didn’t want to divulge. They seemed very China-centric . . .

“We will be looking into …
Targeting the Transcriptional Addiction of Leukemia Stem Cells By a New Class of Protein Kinase Inhibitors
Authors: Yinon Ben-Neriah, Avanthika Venkatachalam, Avner Fink, Eric Hung, Joseph Vacca, Frank Mercurio, Moshe Oren, Eli Pikarsky, Irit Snir-Alkalay, Waleed Minzel
Journal: Blood (2017)
Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline
Authors: Nadine M. Tung, Judy C. Boughey, Lori J. Pierce, Mark E. Robson, Isabelle Bedrosian, Jill R. Dietz, Anthony Dragun, Judith Balmana Gelpi, Erin W. Hofstatter, Claudine J. Isaacs, Ismail Jatoi, Elaine Kennedy, Jennifer K. Litton, Nina A. Mayr, Rubina D. Qamar, Mark G. Trombetta, Brittany E. Harvey, Mark R. Somerfield, Dana Zakalik
Journal: Journal of Clinical Oncology (2020)

To develop recommendations for management of patients with breast cancer (BC) with germline mutations in BC susceptibility genes.The American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology convened an Expert Panel to develop recommendations based on a systematic review of the literature and a formal consensus process.Fifty-eight articles met eligibility criteria and formed the evidentiary basis for the local therapy recommendations; six randomized controlled trials of systemic therapy met eligibility criteria.Patients with newly diagnosed BC and BRCA1/2 mutations may be considered for breast-conserving therapy (BCT), with local control of the index cancer similar to that of noncarriers. The significant risk of a contralateral BC (CBC), especially in young women, and the higher risk of new cancers in the ipsilateral breast warrant discussion of bilateral mastectomy. Patients with mutations in moderate-risk genes should be offered BCT. For women with mutations in BRCA1/2 or moderate-penetrance genes who are eligible for mastectomy, nipple-sparing mastectomy is a reasonable approach. There is no evidence of increased toxicity or CBC events from radiation exposure in BRCA1/2 carriers. Radiation therapy should not be withheld in ATM carriers. For patients with germline TP53 mutations, mastectomy is advised; radiation therapy is contraindicated except in those with significant risk of locoregional recurrence. Platinum agents are recommended versus taxanes to treat advanced BC in BRCA carriers. In the adjuvant/neoadjuvant setting, data do not support the routine addition of platinum to anthracycline- and taxane-based chemotherapy. Poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and talazoparib) are preferable to nonplatinum single-agent chemotherapy for treatment of advanced BC in BRCA1/2 carriers. Data are insufficient to recommend PARP inhibitor use in the early setting or in moderate-penetrance carriers. Additional information available at www.asco.org/breast-cancer-guidelines.
Creating a Framework for Conducting Randomized Clinical Trials during Disease Outbreaks
Authors: Natalie E. Dean, Pierre-Stéphane Gsell, Ron Brookmeyer, Forrest W. Crawford, Christl A. Donnelly, Susan S. Ellenberg, Thomas R. Fleming, M. Elizabeth Halloran, Peter Horby, Thomas Jaki, Philip R. Krause, Ira M. Longini, Sabue Mulangu, Jean-Jacques Muyembe-Tamfum, Martha C. Nason, Peter G. Smith, Rui Wang, Ana M. Henao-Restrepo, Victor De Gruttola
Journal: New England Journal of Medicine (2020)

Responding to Global Infectious Disease Outbreaks As in the ongoing Covid-19 pandemic, global outbreaks of infectious illnesses often develop quickly and resolve in unpredictable ways. In this repo...
Another Targeted Therapy for Patients With Multiple Myeloma
Authors: Rebecca Voelker
Journal: JAMA (2020)

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External Validation of the 2019 Briganti Nomogram for the Identification of Prostate Cancer Patients Who Should Be Considered for an Extended Pelvic Lymph Node Dissection
Authors: Giorgio Gandaglia, Alberto Martini, Guillaume Ploussard, Nicola Fossati, Armando Stabile, Pieter De Visschere, Hendrik Borgmann, Isabel Heidegger, Fabian Steinkohl, Alexander Kretschmer, Giancarlo Marra, Romain Mathieu, Cristian Surcel, Derya Tilki, Igor Tsaur, Massimo Valerio, Roderick Van den Bergh, Piet Ost, Paolo Gontero, Francesco Montorsi, Alberto Briganti
Journal: European Urology (2020)
Introduction: Fake News, Science, and the Growing Multiplicity and Duplicity of Information Sources
Authors: Lawrence W. Green, Ross C. Brownson, Jonathan E. Fielding
Journal: Annual Review of Public Health (2020)

The difference in difference (DID) design is a quasi-experimental research design that researchers often use to study causal relationships in public health settings where randomized controlled trials (RCTs) are infeasible or unethical. However, causal ...Read More