tbuckley/cabot-search huggingface dataset:
The Clinical Inadequacy of the Placebo Model and the Development of an Alternative Conceptual Framework
Authors: Giovanni A. Fava, Jenny Guidi, Chiara Rafanelli, Karl Rickels
Journal: Psychotherapy and Psychosomatics (2017)

Placebo effects are often attributed to clinical interactions and contextual factors that affect expectations of the patient about the treatment and result in symptom changes. The prevailing conceptualization consists of an undifferentiated placebo response that needs to be minimized in controlled investigations and maximized in clinical practice. However, treatment outcome is the cumulative result of the interaction of several classes of variables with a selected treatment: living conditions (housing, nutrition, work environment, social support), patient characteristics (age, sex, genetics, general health conditions, personality, well-being), illness features and previous therapeutic experience, self-management, and treatment setting (physician's attitude and attention, illness behavior). Such variables may be therapeutic or countertherapeutic, and are unlikely to be simply additive. In certain patients their interactive combination may lead to clinical improvement, whereas in other cases it may produce no effect, and, in a third group, it may lead to worsening of the condition. Maximizing patients' expectations does not necessarily result in sustained effects and, in due course, may actually lead to worsening of the condition (violation of expectations). In this paper, we outline a multifactorial conceptual model that may have implications for the design of clinical trials as well as for clinical practice, with special reference to psychopharmacology and psychotherapy. The effects of drug treatment may be potentiated by specific nonpharmacological treatment strategies, and this synergism may disclose significant differences against placebo. Medical outcomes may be unsatisfactory not because technical interventions are missing, but because our conceptual models and thinking are inadequate.
TCT-5 Complete versus Culprit only lesion intervention in ACS Patients with multi-vessel disease: Incidence and outcomes from The London Heart Attack Group
Authors: Krishnaraj Rathod, Sudheer Koganti, Ajay Jain, Charles Knight, Anthony Mathur, Alexander Sirker, Constantinos O’Mahony, Andrew Wragg, Daniel Jones
Journal: Journal of the American College of Cardiology (2017)
Abstract 17485: Decreases in Plasma Phosphatidylinositol Species Partially Explain the Reduction in Cardiovascular Events After Pravastatin Therapy in Secondary Prevention
Authors: Piyushkumar A Mundra, Christopher K Barlow, Paul J Nestel, Elizabeth H Barnes, Adrienne Kirby, Peter Thompson, David R Sullivan, Zahir H Alshehry, Natalie A Mellett, Kevin Huynh, Malcolm J McConville, Gerard Wong, Bronwyn A Kingwell, John Simes, Andrew M Tonkin, Peter J Meikle
Journal: Circulation (2016)

Introduction:  Statin therapy in secondary prevention leads to a reduced risk of future cardiovascular disease (CVD) events. This is explained, in part, by the dramatic reduction in circulating low density lipoprotein cholesterol (LDL-C). However, the effect of statins on circulating lipid species and the independent effect on risk reduction are less well defined. Lipidomic studies on large clinical cohorts can help to define these effects.   Methods:  Plasma lipids (345 species) were measured using mass spectrometry on baseline and one year follow up samples from an unbiased subcohort (n=4991) from the Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) Study. The pravastatin treatment effect on future CVD events and CVD death (from year 1) was calculated using a Cox regression model with treatment as the predictor and adjusting for 21 baseline clinical risk factors. The proportion of the treatment effect explained by baseline levels and changes in individual lipid species, changes in LDL-C or both was determined by subsequent adjustment for these covariates. Within the treatment group, Cox regression was used to identify changes in lipid species associated with future CVD events and CVD death adjusting for the clinical risk factors.   Results:  The pravastatin treatment effect was 22.6% for CVD events. Baseline levels and reduction in the phosphatidylinositol species PI(36:2) and PI(36:3) accounted for the greatest reduction in the pravastatin treatment effect (from 22.6% to 10.5% and 13.6% respectively) corresponding to 53.5% and 39.5% of the treatment effect accounted for by these phosphatidylinositol species. Larger reductions in treatment effect were seen after also adjusting for the change in LDL-C (82.2% and 67.7% respectively). Stronger effects were observed for CVD death. The changes in PI(36:2) and PI(36:3) were associated with future CVD events after adjustment for clinical risk factors.   Conclusion:  Reduction of phosphatidylinositol species during the first year of treatment were associated with CVD events and accounted for over half of the benefit of pravastatin in the LIPID study. Participants in who the levels of phosphatidylinositol were not reduced by treatment with pravastatin were at increased risk of future events.
Adjuvant Pazopanib Does Not PROTECT Against Recurrence of High-Risk, Initially Localized Renal Cell Cancer but Does Provide Novel Insights
Authors: Grant D. Stewart, Bradley C. Leibovich, Sylvie Negrier, Robert A. Figlin
Journal: Journal of Clinical Oncology (2017)

GD Stewart has received educational grants from Pfizer and Intuitive Surgical; consultancy fees from Pfizer, EUSA Pharma and Cambridge Medical Robotics; Travel expenses from Pfizer and Speaker fees from Pfizer. RA Figlin has received research funding from Peloton, BMS, Argos Therapeutics, Exilexis, and Cerulean; consulting fees from Novartis, Pfizer, Nektar, Peloton, Calithera, and Acceleron.  S Negrier reports honoraria from Pfizer, Novartis, EUSA Pharma, Ipsen Biotech and Bristol-Myers Squibb.  BC Leibovich declares no conflicts of interest.
BP Measurement in Clinical Practice: Time to SPRINT to Guideline-Recommended Protocols
Authors: Paul E. Drawz, Joachim H. Ix
Journal: Journal of the American Society of Nephrology (2017)

Hypertension is the leading chronic disease risk factor in the world and is especially important in patients with CKD, nearly 90% of whom have hypertension. Recently, in the Systolic BP Intervention Trial (SPRINT), intensive lowering of clinic systolic BP to a target <120 mm Hg, compared with a standard BP target of <140 mm Hg, reduced risk for cardiovascular disease and all-cause mortality. However, because BP was measured unobserved using an automated device, some investigators have questioned the ability to translate SPRINT results into routine clinical practice, in which measurement of BP is typically less standardized. In this review, we discuss the BP measurement techniques used in major observational studies and clinical trials that form the evidence base for our current approach to treating hypertension, evaluate the effect of measurement technique on BP readings, and explore how ambulatory BP data from the SPRINT trial may inform this discussion. We conclude by arguing for implementation of guideline-recommended BP measurement techniques in routine clinical practice.
TV: Have a Heart
Authors: G. Yamey
Journal: BMJ (2000)

The Mark Thomas Comedy Product , Channel 4, Thursday 20 January

Demand for heart and kidney transplants continues to outweigh supply. The pharmaceutical industry thinks it has the solution: it has seen the future, and the future is pigs.

Xenotransplantation may have left the realms of science fiction, but there are still many obstacles to its use. The chief one is transplant rejection. We could in theory use monkey organs in the hope of reducing the rejection response, except that monkeys are endangered and the risk of transmitting diseases from primates to man is unacceptably high. And this is where the pig comes in. The animal is in plentiful supply, and its organs are just the right size.

But why should the human body accept a pig's parts? It won't of course, unless it's a very special kind of swine. Pharmaceutical companies are competing to produce a genetically engineered …
Squalene protects mice bone marrow hematopoietic and mesenchymal stem cells against high-dose cisplatin in vivo by restoring antioxidant balance: implications in cancer chemotherapy
Authors: Bikul Das, Herman Yeger, Sylvain Baruchel
Journal: Cancer Research (2006)

1128  Background: There is an urgent need to develop selective cytoprotective agent to protect normal tissues without protecting malignant tumors from cytotoxic chemotherapy. We have previously shown that squalene, an isoprenoid antioxidant showed in vitro cytoprotective activity in a bone marrow versus neuroblastoma model of cisplatin-induced toxicity (Das B et al. Eur J Cancer, 2003; 39:2556-2565). Here we investigated the in vivo cytoprotection of squalene in a mouse model of cisplatin-toxicity against normal versus neuroblastoma xenograft. Methods: cisplatin (8-15mg/kg body weight) was injected i.p. to Balb/c mice with or without squalene (100mg/kg mixed with Intralipid) 3hrs before cisplatin injection. Bone marrow was collected five days after drug injection, and CFU assays were performed. Toxicity to mesenchymal stem cells was measured by culturing mesenchymal colonies in special mesencult media (Stem Cell Inc. Vancouver BC). Renal toxicity was measured by plasma BUN level. Oxidative stress parameter was measured by measuring GSH, GST, SOD, and GSpx activities by established biochemical methods (Chemicon International, USA). Results: cisplatin, 15mg/kg dose reduced BM colony formation by 51%, whereas the addition of squalene reduced BM colony formation by only 15%, suggesting 36% protection (p
Heart stents for stable angina show no benefit over placebo, study finds
Authors: Jacqui Wise
Journal: BMJ (2017)

Percutaneous coronary intervention (PCI) is not significantly better than a placebo procedure in improving exercise capacity or symptoms even in patients with severe coronary stenosis, research has found.

The ORBITA study, published in the Lancet ,1 is the first double blind randomised controlled trial to directly compare stenting with placebo in patients with stable angina who are receiving high quality drug treatment.

Coronary artery stents are life saving in patients with myocardial infarction. For patients with stable coronary artery disease who get pain only on exertion, guidelines recommend antianginal medicine as first line therapy, and PCI is reserved for the many patients who remain symptomatic.

A …
Renal Dysfunction Influences the Diagnostic and Prognostic Performance of High-Sensitivity Cardiac Troponin I
Authors: Ian Gunsolus, Yader Sandoval, Stephen W. Smith, Anne Sexter, Karen Schulz, Charles A. Herzog, Fred S. Apple
Journal: Journal of the American Society of Nephrology (2017)

Export Measures of cardiac troponin (cTn) may have lower specificity for myocardial infarction in patients with CKD. We examined the diagnostic accuracy of baseline and serial high-sensitivity cTnI (hs-cTnI) measurements for myocardial infarction and 30- and 180-day mortality according to renal function. hs-cTnI was measured (Abbott assay) using sex-specific 99th percentiles (women, 16 ng/L; men, 34 ng/L) in 1555 adults presenting to the emergency department with symptoms suggesting ischemia (NCT02060760). Myocardial infarction was adjudicated along universal definition classification. Renal function did not significantly affect sensitivity or negative predictive values. Specificity decreased with impaired renal function from 93%–95% with normal function (eGFR≥90 ml/min per 1.73 m2; n=722) to 57%–61% with severely impaired renal function (eGFR<30 ml/min per 1.73 m2; n=81) and 40%–41% on dialysis (n=78). Positive predictive values decreased with decreasing renal function from 51%–57% with normal function to 27%–42% with severely impaired function and 15%–32% on dialysis. Receiver operating characteristic curve areas trended lower at baseline and 3 hours with renal impairment. Mortality increased significantly with increasing hs-cTnI tertile (1.3%, 6.0%, and 10.4%, respectively). Patients with hs-cTnI concentration exceeding concentrations in the 99th percentiles had a mortality rate (11.7%) significantly higher than that of patients with concentrations between 99th percentile concentrations and limit of detection (6.2%) or below limit of detection (1.1%). Renal dysfunction and dialysis reduced the rule-in performance but not the rule-out performance of hs-cTnI for myocardial infarction, and mortality increased in patients with higher hs-cTnI concentrations and any level of renal dysfunction.
TLR9 agonists enhance the efficacy of cancer vaccines
Authors: Luigi Aurisicchio, Elisa Scarselli, Daniela Peruzzi, Sridhar Dharmapuri, Antonella Biondo, Antonella Conforti, Saverio Giampaoli, Arthur Fridman, Ansuman Bagchi, Ekambar Kandimalla, Sudhir Agrawal, Gennaro Ciliberto, Nicola La Monica
Journal: Cancer Research (2008)

4994   We have recently developed a genetic vaccination platform based on the use of muscle DNA electroporation and adenovirus which has been shown to be effective in eliciting immune response against several viral antigens. The application of this technology to tumor associated antigens (TAA), such as Carcinoembryonic antigen (CEA) and Her2/Neu in immunologically tolerant mice resulted in the induction of measurable antigen-specific responses. Importantly, vaccines have led to significant therapeutic effects that supported the progression of the cancer vaccine program towards clinical trials. However, the general belief of cancer immunologists is that vaccination  per se  might have a limited impact on late-stage patients and combination therapies are needed to synergize with cancer vaccines.  One of the most promising targets for therapeutic immune activation is TLR9, which detects unmethylated CpG dinucleotides present in viral and prokaryotic genomes, which are generally methylated in host DNA.  Here, we have tested the ability of second generation TLR9 agonists such as immunomodulatory oligonucleotides (IMOs) to synergize with cancer genetic vaccine candidates and peptides to target TAAs.  We show that association of cancer vaccines and IMOs was strongly effective in inducing and enhancing cellular and humoral immune response against TAAs. Most importantly, treatment resulted in significant therapeutic effect and delayed time to disease progression in BALB/NeuT transgenic mice affected by  in situ  mammary carcinoma and treated with HER2 vaccine and IMO combination. The antitumoral effect was associated with several immunologic parameters: increase in natural immunity, in the percentage of cell mediated immune responders and antibody isotype switch. Interestingly, we have identified a immunogenic B cell linear epitope within HER2 and vaccine-induced antibodies directed to such epitope were shown to be predictive of clinical outcome and could be evaluated as potential biomarkers.  These results strongly support the integration of IMOs into genetic cancer vaccine clinical trials .
TCT-572 Similarities and Differences between Bare Metal and Drug Eluting In-Stent Restenosis: observations from the REWARDS ISR Registry
Authors: Rebecca Torguson, Corey Shea, Kyle Buchanan, Linzhi Xu, Itsik Ben-Dor, Lowell Satler, Ron Waksman
Journal: Journal of the American College of Cardiology (2017)
Gut Microbiota Perturbations in Reactive Arthritis and Postinfectious Spondyloarthritis
Authors: Julia Manasson, Nan Shen, Helga R. Garcia Ferrer, Carles Ubeda, Isa Iraheta, Adriana Heguy, Joan M. Von Feldt, Luis R. Espinoza, Abraham Garcia Kutzbach, Leopoldo N. Segal, Alexis Ogdie, Jose C. Clemente, Jose U. Scher
Journal: Arthritis & Rheumatology (2017)

Reactive arthritis (ReA) is an inflammatory disorder occurring several weeks after gastrointestinal or genitourinary tract infections. HLA-B27 positivity is considered a risk factor, although it is not necessarily predictive of disease incidence. Among nongenetic factors, the intestinal microbiome may play a role in disease susceptibility. The objective of this study was to characterize the gut microbiota and host gene interactions in ReA and postinfectious spondyloarthritis.Adult subjects with peripheral spondyloarthritis and control subjects with preceding infections who did not develop arthritis were prospectively recruited from a geographic region with a high prevalence of ReA. Clinical variables, HLA status, and 16S ribosomal RNA gene sequencing of intestinal microbiota were analyzed.Subjects with ReA showed no significant differences from controls in gut bacterial richness or diversity. However, there was a significantly higher abundance of Erwinia and Pseudomonas and an increased prevalence of typical enteropathogens associated with ReA. Subjects with ultrasound evidence of enthesitis were enriched in Campylobacter, while subjects with uveitis and radiographic sacroiliitis were enriched in Erwinia and unclassified Ruminococcaceae, respectively; both were enriched in Dialister. Host genetics, particularly HLA-A24, were associated with differences in gut microbiota diversity irrespective of disease status. We identified several co-occurring taxa that were also predictive of HLA-A24 status.This is the first culture-independent study characterizing the gut microbial community in postinfectious arthritis. Although bacterial factors correlated with disease presence and clinical features of ReA, host genetics also appeared to be a major independent driver of intestinal community composition. Understanding of these gut microbiota-host genetic relationships may further clarify the pathogenesis of postinfectious spondyloarthritides.
TCT-349 Three-Year Major Clinical Outcomes between First-Generation versus Second-Generation Drug-Eluting Stents in Acute Myocardial Infarction: Propensity Score Matched Analysis
Authors: Yong Hoon Kim, Seung-Woon Rha, Ae-Young Her, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Ahmed Mashaly, Won Young Jang, Woo Hyeun Kim, Eun Jin Park, Ja Yeon Choi, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Eung Ju Kim, Chang Gyu Park, Hong-Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2017)
Analysis of the PD-1/PD-L1 Axis Points to Association of Unfavorable Recurrent Mutations with PD-L1 Expression in AML
Authors: Malgorzata Zajac, Joanna Zaleska, Anna Dolnik, Anna Siwiec, Olga Jankowska-Lecka, Radoslaw Mlak, Marzanna Ciesielka, Tomasz Gromek, Bozena Sokolowska, Norbert Grzasko, Maria Soroka-Wojtaszko, Aneta Szudy-Szczyrek, Maria Majdan, Marek Hus, Lars Bullinger, Krzysztof Giannopoulos
Journal: Blood (2016)
Global Health
Authors: Satish Gopal
Journal: JAMA (2017)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Bigger Data, Harder Questions—Opportunities Throughout Mental Health Care
Authors: Adam M. Chekroud
Journal: JAMA Psychiatry (2017)

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
Online Serum PFOA Calculator for Adults
Authors: Scott M. Bartell
Journal: Environmental Health Perspectives (2017)

Perfluorooctanoic acid (PFOA) is a persistent environmental contaminant that has been detected in >100 public water systems in the United States alone. A variety of epidemiological investigations of PFOA have been published, mostly using measured or modeled serum PFOA concentrations as the exposure metric. Comparison of drinking water PFOA concentrations to those study findings or to typical serum concentrations requires pharmacokinetic modeling. This brief communication describes an online Javascript calculator that easily plots the expected serum PFOA concentration over time and at steady state for adults after starting or stopping consumption of PFOA-contaminated water. Two examples of usage are provided, including increasing serum PFOA after ongoing consumption of contaminated water at the federal limit, and decreasing serum PFOA after carbon filtration began in a contaminated water system. https://doi.org/10.1289/EHP2820.
TCT-173 Myocardial infarction in a real-world population of diabetes and non-diabetes patients after coronary computed tomography angiography
Authors: Kevin Kris Warnakula Olesen, Anders Hammerich Riis, Lene Hüche Nielsen, Flemming Hald Steffensen, Bjarne Norgaard, Troels Thim, T. Henrik Sørensen, Michael Maeng
Journal: Journal of the American College of Cardiology (2017)
Unnecessary Use of Inferior Vena Cava Filters
Authors: Rohit V. Goswamy, Abhishek Maiti, Miguel A. Escobar
Journal: JAMA Internal Medicine (2017)

This Teachable Moment examines the case of a woman in her 20s with ulcerative colitis, unprovoked deep vein thromboses, and pulmonary embolism who had been taking coumadin and presented with acute-onset left-sided pleuritic chest pain for 3 days.