tbuckley/cabot-search huggingface dataset:
Costs of an emergency department-based accelerated diagnostic protocol vs hospitalization in patients with chest pain: a randomized controlled trial
Authors: R. R. Roberts
Journal: JAMA (1997)

Context.-More than 3 million patients are hospitalized yearly in the United States for chest pain. The cost is over $3 billion just for those found to be free of acute disease. New rapid diagnostic tests for acute myocardial infarction (AMI) have resulted in the proliferation of accelerated diagnostic protocols (ADPs) and chest pain observation units. Objective.-To determine whether use of an emergency department (ED)-based ADP can reduce hospital admission rate, total cost, and length of stay (LOS) for patients needing admission for evaluation of chest pain. Design.-Prospective randomized controlled trial comparing admission rate, total cost, and LOS for patients treated using ADP vs inpatient controls. Total costs were determined using empirically measured resource utilization and microcosting techniques. Setting.-A large urban public teaching hospital serving a predominantly African American and Hispanic population. Patients.-A sample of 165 patients was randomly selected from a larger consecutive sample of 429 patients with chest pain concurrently enrolled in an ADP diagnostic cohort trial. Eligible patients presented to the ED with clinical findings suggestive of AMI or acute cardiac ischemia (ACI) but at low risk using a validated predictive algorithm. Main Outcome Measures.-Primary outcomes measured for each subject were LOS and total cost of treatment. Results.-The hospital admission rate for ADP vs control patients was 45.2% vs 100% (P<.001). The mean total cost per patient for ADP vs control patients was $1528 vs $2095 (P<.001). The mean LOS measured in hours for ADP vs control patients was 33.1 hours vs 44.8 hours (P<.01). Conclusions.-In this trial, ADP saved $567 in total hospital costs per patient treated. Use of ED-based ADPs can reduce hospitalization rates, LOS, and total cost for low-risk patients with chest pain needing evaluation for possible AMI or ACl.
Preventing Burnout Among Academic Medicine Leaders
Authors: Susan L. Rosenthal
Journal: JAMA Pediatrics (2020)

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 Pediatrics 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 Pediatrics journal
218. Soluble Flt-1 Gene Delivery Using PEI-g-PEG-RGD Conjugate for Anti-Angiogenesis
Journal: Molecular Therapy (2005)

Top of pageAbstract
Angiogenesis is defined as the formation of new blood vessels from pre-existing microvessels. In particular, tumor growth and metastasis was found to be dependent on angiogenesis and hence, anti-angiogenic therapy has become a promising strategy for cancer treatment.

Anti-angiogenic therapy is used to inhibit tumor growth and metastasis by destroying neighboring blood vessels that supply tumor cells with oxygen and nutrients and also provide an exit route for tumors to enter the bloodstream. An angiogenic factor, VEGF, stimulates endothelial cell proliferation, migration and tube formation via the interaction with VEGF receptors, Flt-1 (fms-like tyrosine kinase-1) and/or flk-1/KDR (fetal liver kinase-1/kinase domain). The intervention to block VEGF action has been accomplished by a variety of methods including antibodies directed against its cognate receptors. One novel method to inhibit the angiogenic action of VEGF is the administration of soluble Flt-1 (sFlt-1), a potent, and selective inhibitor of VEGF. We have previously reported an angiogenic endothelial cell-targeted polymeric gene delivery system, PEI-g-PEG-RGD, developed by incorporating the |[alpha]||[nu]||[beta]|3/|[alpha]||[nu]||[beta]|5 integrin-binding RGD peptide, ACDCRGDCFC (single-letter amino acid code), into the cationic polymer, polyethyleneimine (PEI) via hydrophilic polyethylene glycol (PEG) spacer. These findings predicted that the gene carrier, PEI-g-PEG-RGD, might deliver genes coding sFlt-1 into an angiogenic endothelial cells expressing the |[alpha]||[nu]||[beta]|3/|[alpha]||[nu]||[beta]|5 integrins on their surface with a site-specific manner. In this study, we constructed the therapeutic gene coding sFlt-1 (pCMV-sFlt-1) and evaluated the effect of PEI-g-PEG-RGD / therapeutic gene for an ant-iangiogenic therapy.

To confirm the efficacy of the transgene, the transfected sFlt-1 should suppress the VEGF-driven proliferation of endothelial cells. An endothelial inhibition assay was performed using CADMECs. The PEI-g-PEG-RGD/pCMV-sFlt-1 complex inhibited the CADMEC proliferation by 63% compared with non-treated control thus confirming the PEI-g-PEG-RGD-mediated secretion of functionally active soluble Flt-1. In this report, we have used a genetic approach for expression of sFlt-1 that is an endogenously expressed, potent VEGF antagonist. We have evaluated the function of therapeutic gene carrier with an inhibition of endothelial cell proliferation assay. The complex of therapeutic gene and PEI-g-PEG-RGD conjugate efficiently inhibits proliferation of endothelial cells by blocking the binding of VEGF to the membrane bound Flt-1 receptor. The use of a non-viral gene carrier to deliver an anti-angiogenic gene can demonstrate a low continuous dosage through repeated injections which can be applied for future clinical use.
Activatable NIR-II photoacoustic imaging and photochemical synergistic therapy of MRSA infections using miniature Au/Ag nanorods
Authors: Zihan Mei, Duyang Gao, Dehong Hu, Huichao Zhou, Teng Ma, Liang Huang, Xin Liu, Rongqin Zheng, Hairong Zheng, Ping Zhao, Jianqiao Zhou, Zonghai Sheng
Journal: Biomaterials (2020)
Preclinical validation of a repurposed metal chelator as an early-intervention therapeutic for hemotoxic snakebite
Authors: Laura-Oana Albulescu, Melissa S. Hale, Stuart Ainsworth, Jaffer Alsolaiss, Edouard Crittenden, Juan J. Calvete, Chloe Evans, Mark C. Wilkinson, Robert A. Harrison, Jeroen Kool, Nicholas R. Casewell
Journal: Science Translational Medicine (2020)

Snakebite envenoming causes 138,000 deaths annually, and ~400,000 victims are left with permanent disabilities. Envenoming by saw-scaled vipers (Viperidae: Echis) leads to systemic hemorrhage and coagulopathy and represents a major cause of snakebite mortality and morbidity in Africa and Asia. The only specific treatment for snakebite, antivenom, has poor specificity and low affordability and must be administered in clinical settings because of its intravenous delivery and high rates of adverse reactions. This requirement results in major treatment delays in resource-poor regions and substantially affects patient outcomes after envenoming. Here, we investigated the value of metal ion chelators as prehospital therapeutics for snakebite. Among the tested chelators, dimercaprol (British anti-Lewisite) and its derivative 2,3-dimercapto-1-propanesulfonic acid (DMPS) were found to potently antagonize the activity of Zn2+-dependent snake venom metalloproteinases in vitro. Moreover, DMPS prolonged or conferred complete survival in murine preclinical models of envenoming against a variety of saw-scaled viper venoms. DMPS also considerably extended survival in a "challenge and treat" model, where drug administration was delayed after venom injection and the oral administration of this chelator provided partial protection against envenoming. Last, the potential clinical scenario of early oral DMPS therapy combined with a delayed, intravenous dose of conventional antivenom provided prolonged protection against the lethal effects of envenoming in vivo. Our findings demonstrate that the safe and affordable repurposed metal chelator DMPS can effectively neutralize saw-scaled viper venoms in vitro and in vivo and highlight the promise of this drug as an early, prehospital, therapeutic intervention for hemotoxic snakebite envenoming.
First-in-Human Trial of Epichaperome-Targeted PET in Patients with Cancer
Authors: Mark P.S. Dunphy, Christina Pressl, Nagavarakishore Pillarsetty, Milan Grkovski, Shanu Modi, Komal Jhaveri, Larry Norton, Bradley J. Beattie, Pat B. Zanzonico, Danuta Zatorska, Tony Taldone, Stefan O. Ochiana, Mohammad M. Uddin, Eva M. Burnazi, Serge K. Lyashchenko, Clifford A. Hudis, Jacqueline Bromberg, Heiko M. Schöder, Josef J. Fox, Hanwen Zhang, Gabriela Chiosis, Jason S. Lewis, Steven M. Larson
Journal: Clinical Cancer Research (2020)

Abstract Purpose: 124I-PU-H71 is an investigational first-in-class radiologic agent specific for imaging tumor epichaperome formations. The intracellular epichaperome forms under cellular stress and is a clinically validated oncotherapeutic target. We conducted a first-in-human study of microdose 124I-PU-H71 for PET to study in vivo biodistribution, pharmacokinetics, metabolism, and safety; and the feasibility of epichaperome-targeted tumor imaging. Experimental Design: Adult patients with cancer (n = 30) received 124I-PU-H71 tracer (201±12 MBq, &amp;lt;25 μg) intravenous bolus followed by PET/CT scans and blood radioassays. Results: 124I-PU-H71 PET detected tumors of different cancer types (breast, lymphoma, neuroblastoma, genitourinary, gynecologic, sarcoma, and pancreas). 124I-PU-H71 was retained by tumors for several days while it cleared rapidly from bones, healthy soft tissues, and blood. Radiation dosimetry is favorable and patients suffered no adverse effects. Conclusions: Our first-in-human results demonstrate the safety and feasibility of noninvasive in vivo detection of tumor epichaperomes using 124I-PU-H71 PET, supporting clinical development of PU-H71 and other epichaperome-targeted therapeutics.
Abstract A29: Differential regulation of apoptosis and senescence by the miR-449 family microRNAs and its implications in tumor microenvironments of NSCLC
Authors: Chun-Yu Cho, Shih-Ying Chung, Shuang-En Chuang
Journal: Cancer Research (2020)

Abstract MicroRNAs (miRNAs) play important roles in various biologic processes, and aberrant miRNA expression is one of the mechanisms of tumorigenesis. Previous studies indicate that oncogenic HPV infection interrupts the expression of tumor-suppressive miR-34a and contributes to the development of cervical cancer. In addition, the traditional Chinese medicine Gynostemma pentaphyllum (Thunb.) Makino may exert its pharmacologic effects through modifying the gut microbiota by regulating hepatic miR-34a expression. MiR-449 miRs are members of the tumor suppressor miR-34 family and are evolutionarily conserved. In this study, we demonstrated that, in lung cancer cells, ectopic expression of miR-449 family, including miR-449a, miR-449b, and miR-449c, decreased the levels of several G1 phase proteins including cyclin D1, cyclin D3, CDK4, and CDK6 via directly targeting their mRNA’s 3’-UTR. We also observed a differential induction of apoptosis vs. senescence by the miR-449 cluster. While miR-449a and miR-449c induced senescence, miR-449b induced apoptosis and sensitized cancer cells to apoptotic stimuli, such as serum deprivation. Interestingly, among this cluster miRNAs, only miR-449a could induce significant senescence-associated secretory phenotype (SASP), e.g., expression of IL-8, IL-6, IL-1b, and TNF-alpha. Moreover, we also found that miR-449a increased NF-kB phosphorylation at S276, but not phosphorylation site of S536, and promoted the expression of IL-8 mRNA. In this regard, the gut microbiota has been indicated to induce proinflammatory cytokines such as IL-8 to influence the outcomes of cancer patients. In addition to MRX34 (a miR-34a mimic) used in clinical trials, miR-449 family may also potentially become a new therapeutic candidate for NSCLC and other solid tumors’ treatment. Citation Format: Chun-Yu Cho, Shih-Ying Chung, Shuang-En Chuang. Differential regulation of apoptosis and senescence by the miR-449 family microRNAs and its implications in tumor microenvironments of NSCLC [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A29.
Abstract 11126: CT Angiography Based Fractional Flow Reserve Compared to Catheter-based Stress Diastolic Fractional Flow Reserve in Symptomatic Patients With Myocardial Bridges
Authors: Ayman Jubran, Ingela Schnittger, Jennifer A Tremmel, Vedant S Pargaonkar, Ian S Rogers, Christoph H Becker, Yang Shengwen, Domenico Mastrodicasa, Martin J Willemink, Dominik Fleischmann, Koen Nieman
Journal: Circulation (2019)

Introduction: Myocardial bridging (MB) is a common coronary artery variant. Although traditionally considered benign, MB may be associated with myocardial ischemia as a result of dynamic compressio...
Safety and immunogenicity of a Zika purified inactivated virus vaccine given via standard, accelerated, or shortened schedules: a single-centre, double-blind, sequential-group, randomised, placebo-controlled, phase 1 trial
Authors: Kathryn E Stephenson, Chen Sabrina Tan, Stephen R Walsh, Andrew Hale, Jessica L Ansel, Diane G Kanjilal, Kate Jaegle, Lauren Peter, Erica N Borducchi, Joseph P Nkolola, Tatenda Makoni, Rachel Fogel, Connor Bradshaw, Anna Tyler, Edward Moseley, Abishek Chandrashekar, Katherine E Yanosick, Michael S Seaman, Kenneth H Eckels, Rafael A De La Barrera, Jason Thompson, Peter Dawson, Stephen J Thomas, Nelson L Michael, Kayvon Modjarrad, Dan H Barouch
Journal: The Lancet Infectious Diseases (2020)
Does dose modification affect efficacy of first-line pazopanib in metastatic renal cell carcinoma?
Authors: Paolo Grassi, Giuseppe Procopio, Raffaele Ratta, Luca Porcu, Antonia Martinetti, Alessia Mennitto, Elena Verzoni
Journal: Journal of Clinical Oncology (2017)

512 Background: Pazopanib is a standard treatment for metastatic renal cell carcinoma (mRCC) and 800 mg/day is considered the optimal dose for mRCC patients (pts). However, some pts require a dose reduction due to toxicity. It remains unclear whether reduced-dose pazopanib is as effective as the standard dose in achieving a response. Methods: We retrospectively evaluated treatment duration, objective response rate (ORR), progression-free survival (PFS), and discontinuation rate in consecutive pts with mRCC treated with first-line pazopanib between 2011 and 2016 at the Istituto Nazionale Tumori of Milano, Italy. Three patient groups were compared: group 1 received the standard starting dose of 800 mg/day continously, group 2 received a dose reduced to 400 or 600 mg/day after starting with 800 mg/day, and group 3 received a reduced starting dose of 400 or 600 mg/day because of ECOG performance status = 2-3 and/or comorbidities. Results: We included 69 pts, with 34 in group 1, 19 in group 2, and 16 in group 3. Median age at diagnosis was 62 years, and 64% were male. Overall 13% and 87% of pts were classified as Heng good and intermediate-risk respectively. In 10 and 9 pts of the group 2, the dose was reduced to 600 and 400 mg/day respectively while 12 and 4 pts in the group 3 received a reduced initial dose of 400 and 600 mg/day respectively. After a median follow-up of 13.9 months (range 0.3-43.8), 27 (39.1%) pts showed progressive disease (PD) and 3 (4.3%) pts were dead. Incidence rate of PD or death was 2.5 (95% CI: 0.6-4.4; Hazard ratio [HR]:1) per 100 person-months in group 1; 4.0 (95% CI: 0-11.4; HR: 1.45) per 100 person-months in group 2 and 3.3 (95% CI: 0-6.8; HR: 1.19) per 100 person-months in group 3. Rates of discontinuation due to PD were 28% in group 1, 42% in group 2, and 44% in group 3. ORR was 44%, 11% and 19% in group 1, group 2, and group 3 respectively. Conclusions: Our results suggest that mRCC pts receiving a lower dose of first-line pazopanib might not have a meaningful PFS advantage compared with those receiving standard dose. These data highlight the importance of management of the treatment-related side effects that may eventually lead to optimal drug exposure.
Phosphodiesterase 5 (PDE5) restricts intracellular cGMP accumulation during enterotoxigenic <i>Escherichia coli</i> infection
Authors: Jennifer Foulke-Abel, Huimin Yu, Laxmi Sunuwar, Ruxian Lin, James M. Fleckenstein, James B. Kaper, Mark Donowitz
Journal: Gut Microbes (2020)

Diarrhea caused by enterotoxigenic Escherichia coli (ETEC) has a continuing impact on residents and travelers in underdeveloped countries. Both heat-labile (LT) and heat-stable (ST) enterotoxins contribute to pathophysiology via induction of cyclic nucleotide synthesis, and previous investigations focused on intracellular signal transduction rather than possible intercellular second messenger signaling. We modeled ETEC infection in human jejunal enteroid/organoid monolayers (HEM) and evaluated cyclic nucleotide pools, finding that intracellular cAMP was significantly increased but also underwent apical export, whereas cGMP was minimally retained intracellularly and predominantly effluxed into the basolateral space. LT and virulence factors including EatA, EtpA, and CfaE promoted ST release and enhanced ST-stimulated cGMP production. Intracellular cGMP was regulated by MK-571-sensitive export in addition to degradation by phosphodiesterase 5. HEMs had limited ST-induced intracellular cGMP accumulation compared to T84 or Caco-2 models. Cyclic nucleotide export/degradation demonstrates additional complexity in the mechanism of ETEC infection and may redirect understanding of diarrheal onset.
Overcoming Barriers to Prescribing Buprenorphine in the Emergency Department
Authors: Howard S. Kim, Elizabeth A. Samuels
Journal: JAMA Network Open (2020)

Kathryn F. Hawk, MD; Gail D'Onofrio, MD; Marek C. Chawarski, PhD; Patrick G. O'Connor, MD; Ethan Cowan, MD; Michael S. Lyons, MD; Lynne Richardson, MD; Richard E. Rothman, MD; Lauren K. Whiteside, MD; Patricia H. Owens, MS; Shara H. Martel, MPH; Edouard Coupet Jr, MD; Michael Pantalon, PhD; Leslie Curry, PhD; David A. Fiellin, MD; E. Jennifer Edelman, MD
Utilization and Cost of an Employer-Sponsored Comprehensive Primary Care Delivery Model
Authors: Sanjay Basu, Tyler Zhang, Alli Gilmore, Esha Datta, Eun Yeong Kim
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Primary care is increasingly delivered at or near workplaces, yet utilization and cost of employer-sponsored primary care services remain unknown. <h3>Objective</h3> To compare the health care utilization and cost of an employer-sponsored on-site, near-site, and virtual comprehensive primary care service delivery model with those of traditional community-based primary care. <h3>Design, Setting, and Participants</h3> This population-based cohort study of 23 518 commercially insured employees and dependents of an engineering and manufacturing firm headquartered in southern California was performed from January 1, 2016, to July 1, 2019. A subset of the population with most (≥50%) primary care visits through employer-sponsored on-site, near-site, or virtual care clinics was matched to a subset not having most such visits through the employer-sponsored clinics using propensity score matching (n = 1983 each). In sensitivity analyses, employees were matched to dependents at neighboring firms that lacked access to the employer-sponsored primary care delivery model (additional n = 1680). <h3>Exposures</h3> Integrated primary care, mental health, and physical therapy delivered through on-site, near-site, and virtual clinics. <h3>Main Outcomes and Measures</h3> Utilization (inpatient, outpatient, emergency department, pharmaceutical, radiology, and laboratory visits per 1000 member-months) and spending (2019 costs per member per month in US dollars) by service type. <h3>Results</h3> A total of 23 518 individuals (mean [SD] age, 27 [15] years; 14 604 [62.1%] male) were included in the full population sample and had been enrolled in the employer-sponsored health plan for a mean of 29 months (interquartile range, 14-48 months). Of eligible members, 5292 (22.5%) used the employer-sponsored services, with 2305 (9.8%) using them for most of their primary care. The mean (SD) cost of employer-sponsored service delivery was $87 ($32) per member month. Among the matched populations (mean [SD] age, 31 [11] years; 3349 [84.5%] male) of primary users vs control individuals, total spending was 45% lower per member per month (95% CI, 35%-55%; cost difference, −$167 per member per month; 95% CI, −$204 to −$130;<i>P</i> &lt; .001) among users after adjustment. The lower spending was associated with lower spending on non–primary care services, such as emergency department (−33%; 95% CI, −44% to −22%) and hospital visits (−16%; 95% CI, −22% to −10%), despite higher spending on primary care (109%; 95% CI, 102%-116%) and mental health (20%; 95% CI, 13%-27%). <h3>Conclusions and Relevance</h3> The findings suggest that individuals who used the models’ services for most of their primary care had lower total spending despite higher primary care spending, which may be associated with self-selection of lower-risk persons to the employer-sponsored services and/or with the use of comprehensive primary care.
Translating insights from neuropsychiatric genetics and genomics for precision psychiatry
Authors: Elliott Rees, Michael J. Owen
Journal: Genome Medicine (2020)

Abstract The primary aim of precision medicine is to tailor healthcare more closely to the needs of individual patients. This requires progress in two areas: the development of more precise treatments and the ability to identify patients or groups of patients in the clinic for whom such treatments are likely to be the most effective. There is widespread optimism that advances in genomics will facilitate both of these endeavors. It can be argued that of all medical specialties psychiatry has most to gain in these respects, given its current reliance on syndromic diagnoses, the minimal foundation of existing mechanistic knowledge, and the substantial heritability of psychiatric phenotypes. Here, we review recent advances in psychiatric genomics and assess the likely impact of these findings on attempts to develop precision psychiatry. Emerging findings indicate a high degree of polygenicity and that genetic risk maps poorly onto the diagnostic categories used in the clinic. The highly polygenic and pleiotropic nature of psychiatric genetics will impact attempts to use genomic data for prediction and risk stratification, and also poses substantial challenges for conventional approaches to gaining biological insights from genetic findings. While there are many challenges to overcome, genomics is building an empirical platform upon which psychiatry can now progress towards better understanding of disease mechanisms, better treatments, and better ways of targeting treatments to the patients most likely to benefit, thus paving the way for precision psychiatry.
Interactions between antiretroviral therapy and complementary and alternative medicine: a narrative review
Authors: C. Bordes, G. Leguelinel-Blache, J.-P. Lavigne, J.-M. Mauboussin, D. Laureillard, H. Faure, I. Rouanet, A. Sotto, P. Loubet
Journal: Clinical Microbiology and Infection (2020)