tbuckley/cabot-search huggingface dataset:
CDH1 on Multigene Panel Testing: Look Before You Leap
Authors: Bryson W Katona, Dana Farengo Clark, Susan M Domchek
Journal: JNCI Journal of the National Cancer Institute (2019)

Multigene panel testing (MGPT) has become a critical component of cancer risk assessment in clinical practice. As technology and access improve and costs decrease, more individuals than ever are undergoing MGPT for genetic evaluation. One gene that deserves special consideration when included on MGPT is CDH1, which codes for the cell-cell adhesion protein E-cadherin. Pathogenic and likely pathogenic germline variants in CDH1 have been associated with hereditary diffuse gastric cancer syndrome, and in highly penetrant families, testing for these variants is critical for proper risk management. However, recent data demonstrated that gastric cancer penetrance in unselected CDH1 carriers may be lower than expected. Further complicating matters are the lack of effective screening strategies for gastric cancer and recommendation for risk-reducing total gastrectomy in CDH1 carriers. Therefore, the discovery of an unexpected pathogenic or likely pathogenic CDH1 variant on multigene panel testing, when testing for CDH1 would not normally be considered based on personal or family history alone, creates dilemmas for both patients and providers. In this commentary, we highlight the potential for unexpected CDH1 variants on MGPT, outline the uncertainties associated with these variants, and emphasize the importance of pretest counseling regarding the potential for an unexpected CDH1 variant. Although CDH1 testing is often important for clinical decision-making, individuals and providers need to be aware of the potential for an unexpected CDH1 variant when CDH1 is included on MGPT for cancer risk assessment.
Emergency Department Visits for Opioid Overdoses Among Patients With Cancer
Authors: Vikram Jairam, Daniel X Yang, James B Yu, Henry S Park
Journal: JNCI Journal of the National Cancer Institute (2019)

Patients with cancer may be at risk of high opioid use due to physical and psychosocial factors, although little data exist to inform providers and policymakers. Our aim is to examine overdoses from opioids leading to emergency department (ED) visits among patients with cancer in the United States.
Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI
Authors: Benjamin C. Blount, Mateusz P. Karwowski, Peter G. Shields, Maria Morel-Espinosa, Liza Valentin-Blasini, Michael Gardner, Martha Braselton, Christina R. Brosius, Kevin T. Caron, David Chambers, Joseph Corstvet, Elizabeth Cowan, Víctor R. De Jesús, Paul Espinosa, Carolina Fernandez, Cory Holder, Zsuzsanna Kuklenyik, Jennifer D. Kusovschi, Cody Newman, Gregory B. Reis, Jon Rees, Chris Reese, Lalith Silva, Tiffany Seyler, Min-Ae Song, Connie Sosnoff, Carleen R. Spitzer, Denise Tevis, Lanqing Wang, Cliff Watson, Mark D. Wewers, Baoyun Xia, Douglas T. Heitkemper, Isaac Ghinai, Jennifer Layden, Peter Briss, Brian A. King, Lisa J. Delaney, Christopher M. Jones, Grant T. Baldwin, Anita Patel, Dana Meaney-Delman, Dale Rose, Vikram Krishnasamy, John R. Barr, Jerry Thomas, James L. Pirkle
Journal: New England Journal of Medicine (2019)

The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung.BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015. Using the BAL fluid, we performed isotope dilution mass spectrometry to measure several priority toxicants: vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes.State and local health departments assigned EVALI case status as confirmed for 25 patients and as probable for 26 patients. Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group. No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 of 47 of the case patients (64%).Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States. (Funded by the National Cancer Institute and others.).
Trends in Prescription Analgesic Use Among Adults With Musculoskeletal Conditions in the United States, 1999-2016
Authors: Andrew Stokes, Kaitlyn M. Berry, Katherine Hempstead, Dielle J. Lundberg, Tuhina Neogi
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Monitoring trends in prescription analgesic use among adults with musculoskeletal conditions provides insight into how changing prescribing practices, guidelines, and policy measures may affect those who need pain management. <h3>Objective</h3> To evaluate trends in prescription opioid use and nonopioid analgesic use among adults with functional limitations attributable to musculoskeletal conditions. <h3>Design, Setting, and Participants</h3> This repeated cross-sectional study uses data from the National Health and Nutrition Examination Study from 1999 to 2016. Data were analyzed from January to July 2019. The participants were adults aged 30 to 79 years who reported functional limitations due to back or neck problems and/or arthritis or rheumatism. <h3>Main Outcomes and Measures</h3> Any use of a prescription opioid or exclusive use of a prescription nonopioid analgesic. <h3>Results</h3> In this population of 7256 adults with 1 or more functional limitations attributable to a musculoskeletal condition (4226 women [59.9%]; 3508 [74.4%] non-Hispanic white individuals; median [interquartile range] age, 63 [53-70] years), opioid use and exclusive nonopioid analgesic use exhibited approximately reciprocal patterns of change from 1999 to 2016. Opioid use increased significantly (difference in prevalence for 2015-2016 vs 1999-2000, 7.2%; 95% CI, 1.3% to 13%;<i>P</i>for trend = .002), and exclusive use of nonopioid analgesics decreased significantly (difference in prevalence for 2015-2016 vs 1999-2000, −13%; 95% CI, −19% to −7.5%;<i>P</i>for trend &lt; .001) during this period. The increase in any opioid use was driven by long-term rather than short-term use. A crossover in the prevalence of opioid use and exclusive use of nonopioid analgesics occurred between 2003 and 2006, after which opioid use was more prevalent. Between 2013 and 2016, decreases in opioid use were observed among men (difference in prevalence for 2015-2016 vs 2013-2014, −11%; 95% CI, −21% to 1.8%) and participants with less than a high school education (difference, −15%; 95% CI, −24% to −6.1%). During this same period, exclusive nonopioid analgesic use also decreased markedly across the population (difference, −5.3%; 95% CI, −9.1% to −1.5%). <h3>Conclusions and Relevance</h3> The substitution of opioids for nonopioid analgesics between 2003 and 2006 may have occurred as evidence emerged on the cardiovascular risks associated with nonopioid analgesics. Reductions in opioid use between 2013 and 2016 were most substantial among those with low socioeconomic status, who may encounter barriers in accessing alternatives. Despite those decreases, opioid use remained more prevalent in 2015 to 2016 than in 1999 to 2000, suggesting a potentially long tail for the opioid epidemic.
Income Inequality and Psychiatric Admission in a Rich Country: Happiness Does Not Guarantee Mental Health Equity
Authors: Vikram Patel
Journal: JAMA Psychiatry (2019)

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 Psychiatry 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 Psychiatry journal
Age of Red Blood Cells for Transfusion in Critically Ill Pediatric Patients
Authors: Zoe K. McQuilten, D. James Cooper
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Jonathan Miller: theatre and opera director, broadcaster, communicator, and doctor
Authors: Penny Warren
Journal: BMJ (2019)

Photo credit: Ballard/Evening Standard/Getty Images

In 1956 medical student Jonathan Miller was invited to direct the University College Hospital Christmas show. He rose to the challenge: his 12 Days of Christmas brought the house down. A gifted mimic with a piercing intellect, Miller said he was helped by learning in medicine to study small details in people’s body language.

Miller used to say much of his career was the result of “yielding to unsolicited invitations,” or, as his family put it, “he couldn’t resist being asked to come out and play.” In 1960, while a house surgeon at University College Hospital he was asked to take part in “Beyond the Fringe” with Alan Bennett, Peter Cook, and Dudley Moore, and had to accept.

The revue was a huge success, igniting the satire boom. It ran for three years, transferring from Edinburgh to London and then to New York, and marked the start of Miller’s glittering artistic career. He became the artistic director at London’s Old Vic theatre, directed more than 50 operas around the world, presented numerous TV and …
Health Care Expenditures Among Adults With Diabetes After Oregon’s Medicaid Expansion
Authors: Stephan R. Lindner, Miguel Marino, Jean O’Malley, Heather Angier, Steffani R. Bailey, Megan Hoopes, Rachel Springer, K. John McConnell, Jennifer DeVoe, Nathalie Huguet
Journal: Diabetes Care (2019)

To compare trends in Medicaid expenditures among adults with diabetes who were newly eligible due to the Affordable Care Act (ACA) Medicaid expansion to trends among those previously eligible.Using Oregon Medicaid administrative data from 1 January 2014 to 30 September 2016, a retrospective cohort study was conducted with propensity score-matched Medicaid eligibility groups (newly and previously eligible). Outcome measures included total per-member per-month (PMPM) Medicaid expenditures and PMPM expenditures in the following 12 categories: inpatient visits, emergency department visits, primary care physician visits, specialist visits, prescription drugs, transportation services, tests, imaging and echography, procedures, durable medical equipment, evaluation and management, and other or unknown services.Total PMPM Medicaid expenditures for newly eligible enrollees with diabetes were initially considerably lower compared with PMPM expenditures for matched previously eligible enrollees during the first postexpansion quarter (mean values $561 vs. $793 PMPM, P = 0.018). Within the first three postexpansion quarters, PMPM expenditures of the newly eligible increased to a similar but slightly lower level. Afterward, PMPM expenditures of both groups continued to increase steadily. Most of the overall PMPM expenditure increase among the newly eligible was due to rapidly increasing prescription drug expenditures.Newly eligible Medicaid enrollees with diabetes had slightly lower PMPM expenditures than previously eligible Medicaid enrollees. The increase in PMPM prescription drug expenditures suggests greater access to treatment over time.
Transition of Macrophages to Fibroblast-Like Cells in Healing Myocardial Infarction
Authors: Nezam Haider, Lisardo Boscá, H. Reinier Zandbergen, Jason C. Kovacic, Navneet Narula, Silvia González-Ramos, María Fernandez-Velasco, Sudhanshu Agrawal, Marta Paz-García, Sudhir Gupta, Kristine DeLeon-Pennell, Valentin Fuster, Borja Ibañez, Jagat Narula
Journal: Journal of the American College of Cardiology (2019)
Assessing the evidence–practice gap for heart failure in China: the Heart Failure Registry of Patient Outcomes (HERO) study design and baseline characteristics
Authors: Li Li, Rong Liu, Chao Jiang, Xin Du, Mark D. Huffman, Carolyn S.P. Lam, Anushka Patel, Graham S. Hillis, Craig S. Anderson, Changsheng Ma, Xiaoyan Zhao, Xiaofang Wang, Ling Li, Jianzeng Dong
Journal: European Journal of Heart Failure (2019)

Abstract Background Registry studies in high‐income countries have defined contemporary management of heart failure (HF), but few such data exist in the large aging population of China. We report the study design and baseline characteristics of the Heart Failure Registry of Patient Outcomes (HERO) study, undertaken to determine evidence–practice gaps in the management of HF in a broad and representative population of China. Methods and results The HERO study is a prospective, longitudinal, seasonally‐rotating, multicentre registry study of patients hospitalized with acute HF who are followed up over 12 months. Patients were recruited on the basis of primary admission clinical diagnosis of acute HF at 73 hospitals in Henan, the largest and most socio‐economically diverse province in China, from November 2017 to November 2018; follow‐up is ongoing. For each patient, data obtained through interview and medial record review by independent clinical research staff include: socio‐demographics, clinical features, diagnostic investigations, and treatment, with a subset of patients providing blood samples for future biomarker investigation. Surviving patients are scheduled to be followed up by telephone at 2 weeks, and 3, 6 and 12 months post‐admission, or until death or study withdrawal. A total of 5620 patients (mean age 72 ± 12 years; 50% female) with acute HF were recruited from 8 provincial‐, 22 municipal‐, and 43 county‐level hospitals. Patients had co‐morbid hypertensive (48%), coronary (29%), or metabolic (20%) diseases. Among 3147 patients who had echocardiography, 54%, 20% and 25% of patients had ejection fraction of ≥50%, 40–50%, and &lt; 40%, respectively. In‐hospital or 3‐day post‐discharge mortality was 3.2% (182/5620). Death or readmission rate from the 4th day post‐discharge to first follow‐up (median 32 days) was 22.4% (977/4368). Conclusions The HERO study provides a unique opportunity to profile evidence–practice gaps across a broad spectrum of patients with acute HF in China.
Human Cytomegalovirus miRNAs Regulate TGF-β to Mediate Myelosuppression while Maintaining Viral Latency in CD34+ Hematopoietic Progenitor Cells
Authors: Meaghan H. Hancock, Lindsey B. Crawford, Andrew H. Pham, Jennifer Mitchell, Hillary M. Struthers, Andrew D. Yurochko, Patrizia Caposio, Jay A. Nelson
Journal: Cell Host & Microbe (2019)
Microbial biogeography and ecology of the mouth and implications for periodontal diseases
Authors: Diana M. Proctor, Katie M. Shelef, Antonio Gonzalez, Clara L. Davis, Les Dethlefsen, Adam R. Burns, Peter M. Loomer, Gary C. Armitage, Mark I. Ryder, Meredith E. Millman, Rob Knight, Susan P. Holmes, David A. Relman
Journal: Periodontology 2000 (2019)

Abstract In humans, the composition of microbial communities differs among body sites and between habitats within a single site. Patterns of variation in the distribution of organisms across time and space are referred to as “biogeography.” The human oral cavity is a critical observatory for exploring microbial biogeography because it is spatially structured, easily accessible, and its microbiota has been linked to the promotion of both health and disease. The biogeographic features of microbial communities residing in spatially distinct, but ecologically similar, environments on the human body, including the subgingival crevice, have not yet been adequately explored. The purpose of this paper is twofold. First, we seek to provide the dental community with a primer on biogeographic theory, highlighting its relevance to the study of the human oral cavity. We summarize what is known about the biogeographic variation of dental caries and periodontitis and postulate that disease occurrence reflects spatial patterning in the composition and structure of oral microbial communities. Second, we present a number of methods that investigators can use to test specific hypotheses using biogeographic theory. To anchor our discussion, we apply each method to a case study and examine the spatial variation of the human subgingival microbiota in 2 individuals. Our case study suggests that the composition of subgingival communities may conform to an anterior‐to‐posterior gradient within the oral cavity. The gradient appears to be structured by both deterministic and nondeterministic processes, although additional work is needed to confirm these findings. A better understanding of biogeographic patterns and processes will lead to improved efficacy of dental interventions targeting the oral microbiota.
Brothers in Arms: ABCA1- and ABCG1-Mediated Cholesterol Efflux as Promising Targets in Cardiovascular Disease Treatment
Authors: Sanne J. C. M. Frambach, Ria de Haas, Jan A. M. Smeitink, Gerard A. Rongen, Frans G. M. Russel, Tom J. J. Schirris
Journal: Pharmacological Reviews (2019)

Atherosclerosis is a leading cause of cardiovascular disease worldwide, and hypercholesterolemia is a major risk factor. Preventive treatments mainly focus on the effective reduction of low-density lipoprotein cholesterol, but their therapeutic value is limited by the inability to completely normalize atherosclerotic risk, probably due to the disease complexity and multifactorial pathogenesis. Consequently, high-density lipoprotein cholesterol gained much interest, as it appeared to be cardioprotective due to its major role in reverse cholesterol transport (RCT). RCT facilitates removal of cholesterol from peripheral tissues, including atherosclerotic plaques, and its subsequent hepatic clearance into bile. Therefore, RCT is expected to limit plaque formation and progression. Cellular cholesterol efflux is initiated and propagated by the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1. Their expression and function are expected to be rate-limiting for cholesterol efflux, which makes them interesting targets to stimulate RCT and lower atherosclerotic risk. This systematic review discusses the molecular mechanisms relevant for RCT and ABCA1 and ABCG1 function, followed by a critical overview of potential pharmacological strategies with small molecules to enhance cellular cholesterol efflux and RCT. These strategies include regulation of ABCA1 and ABCG1 expression, degradation, and mRNA stability. Various small molecules have been demonstrated to increase RCT, but the underlying mechanisms are often not completely understood and are rather unspecific, potentially causing adverse effects. Better understanding of these mechanisms could enable the development of safer drugs to increase RCT and provide more insight into its relation with atherosclerotic risk. SIGNIFICANCE STATEMENT: Hypercholesterolemia is an important risk factor of atherosclerosis, which is a leading pathological mechanism underlying cardiovascular disease. Cholesterol is removed from atherosclerotic plaques and subsequently cleared by the liver into bile. This transport is mediated by high-density lipoprotein particles, to which cholesterol is transferred via ATP-binding cassette transporters ABCA1 and ABCG1. Small-molecule pharmacological strategies stimulating these transporters may provide promising options for cardiovascular disease treatment.
Drug induced liver injury: East versus West – a systematic review and meta-analysis
Authors: En Xian Sarah Low, Qishi Zheng, Edwin Chan, Seng Gee Lim
Journal: Clinical and Molecular Hepatology (2019)

Drug induced liver injury (DILI) may be different in the East compared to the West due to differing disease prevalence, prescribing patterns and pharmacogenetic profiles. To review existing literature on causative agents of DILI in the East compared to the West, a comprehensive literature search was performed on electronic databases: MEDLINE/PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure without language restrictions. Studies which involve patients having DILI and reported the frequency of causative agents were included. A random effects model was applied to synthesize the current evidence using prevalence of class-specific and agent-specific causative drugs with 95% confidence intervals. Of 6,914 articles found, 12 showed the distribution of drugs implicated in DILI in the East with a total of 33,294 patients and 16 in the West with a total of 26,069 DILI cases. In the East, the most common agents by class were anti-tuberculosis drugs (26.6%), herbal and alternative medications (25.3%), and antibiotics (15.7%), while in the West, antibiotics (34.9%), cardiovascular agents (17.3%), and non-steroidal anti-inflammatory drugs (12.5%) were the commonest. For individual agents, the most common agents in the East were isoniazid-rifampicin-pyrazinamide (25.4%), phenytoin (3.5%), and cephalosporin (2.9%) while in the West, amoxicillin-potassium clavulanate combination acid (11.3%), nimesulide (6.3%), and ibuprofen (6.1%) were the commonest. There was significant heterogeneity due to variability in single-centre compared to multi-centre studies. Differences in DILI in the East versus the West both in drug classes and individual agents are important for clinicians to recognize.