tbuckley/cabot-search huggingface dataset:
Abstract 15309: Resource Reduction by Use of Pediatric Chest Pain Standardized Clinical Assessment and Management Plan
Authors: Susan F Saleeb, Sarah R McLaughlin, Dionne A Graham, Kevin G Friedman, David R Fulton
Journal: Circulation (2015)

Using a Standardized Clinical Assessment and Management Plan (SCAMP) for pediatric patients presenting to clinic with chest pain, we evaluated the cost impact associated with implementation of the care algorithm. Previously, we analyzed charges for 406 patients (7-21 yrs) with chest pain seen in 2009, prior to introduction of the SCAMP, and predicted 21% reduction of overall charges had the SCAMP methodology been used. The SCAMP recommended an echocardiogram for history, exam, or ECG findings suggestive of a cardiac etiology for chest pain. Resource utilization for 1520 patients evaluated by the SCAMP from 12/11-4/14 was reviewed in this study. Compared to the 2009 cohort, patients evaluated in the SCAMP presented with similar rates of exertional chest pain (33%, SCAMP vs. 37%, 2009) and significant past medical history (1% vs. 1%). The SCAMP cohort had fewer abnormal physical exam findings (1% vs. 4%) and ECG abnormalities (3% vs. 6%), and more pertinent family history (4% vs. 1%). Echocardiograms were additionally recommended by the SCAMP for exertional syncope (1%), pain worse by supine position, or radiation to the back, jaw, or left arm (5%). Ancillary testing for concurrent symptoms was reduced compared to the 2009 cohort (Figure 1) and compared to predicted: Holter (4% vs. 6%), event monitors (3% vs. 8%), MRI (&lt;1% vs. 1%). Stress testing was not recommended though 4% underwent evaluation. Adherence to SCAMP guidelines for recommended testing approached 80%; slightly fewer echocardiograms were actually performed than recommended. Total testing charges were reduced by an estimated 30% ($740,000) despite a small increase in echocardiogram utilization, and overall charges were reduced by 17% by use of the Chest Pain SCAMP. Given the low incidence of cardiac disease historically as well as detected by the SCAMP algorithm (&lt;1%), further modifications to the algorithm should refine indications for echocardiography, particularly related to exertional symptoms.
Thomas Breuer and colleagues at GlaxoSmithKline respond to Peter Doshi
Authors: Thomas Breuer, Vincent Bauchau, Tatjana Poplazarova, Jens-Ulrich Stegmann
Journal: BMJ (2018)

We are writing to respond to The BMJ ’s feature article about the Pandemrix vaccine.”1 Our response focuses on some of the statements in the article as well the methodology on which the major premise of the article is based.

The statement by The BMJ that the available safety data were not disclosed to the public by the authorities or by GlaxoSmithKline is incorrect. During the pandemic, safety data available to GSK and the company’s analyses of those data were shared regularly with the authorities through weekly teleconferences and monthly written periodic safety update reports. Summaries of the information relating to all pandemic vaccines used in Europe were made available to the public weekly on the European …
GPs and technology: the good, the bad, and the ugly babies
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Technology was the buzz topic at this year’s conference of the Royal College of General Practitioners. College chair Helen Stokes-Lampard made it the centrepiece of her speech,1 in which, amid the ongoing debate over the pros and cons of online consulting and apps, she fiercely rejected the notion that GPs were “technophobic dinosaurs.”

Far from being afraid of innovation, GPs were, Stokes-Lampard argued, “bright, intelligent people who gladly embrace good, safe technology.” But she said that the NHS shouldn’t be sucked into adopting new technology and cited the “lovely baby” idea of Mary Dixon-Woods, professor of health services research at the University of Cambridge.2 Her theory has it that everyone believes their own …
ECG Response: November 10, 2015
Authors: Philip J Podrid
Journal: Circulation (2015)

ECG Challenge Response 1846ECG Challenge: A 67-year-old man with prostate cancer currently being treated with radiation therapy presents to the hospital with complaints of inability to urinate for the past 2 days.It is noted that he is obstructed, and a Foley catheter is inserted with difficulty.Several hours later, the patient develops shaking chills and diaphoresis and has a blood pressure of 89/60 mm Hg.It is felt that he has urosepsis and is started on antibiotics and pressors for early septic shock.As a result, he develops tachycardia, and an ECG (ECG A) is obtained.His temperature decreases, and his blood pressure increases to 120/80 mm Hg, at which time the pressors are discontinued.His heart rate is slower, and an ECG is repeated (ECG B).
Craving creativity: artists respond to addiction
Authors: Richard Hurley
Journal: BMJ (2018)

At first glance, the fat candy-pink drips from a melting ice lolly could well satisfy your desire for cold and sweet. But look closer: that colourful coating isn’t of sugar sprinkles but the multicolour plastic heads of spiky dressmaker’s pins. Reminiscent of advertising, the photograph Another Day on Earth (main picture) depicts …
Abstract 14653: Prevention of Diet-induced Metabolic Dysregulation, Inflammation and Atherosclerosis in Ldlr-/- Mice by Treatment With the ACL Inhibitor ETC-1002
Authors: Joshua P Samsoondar, Brian G Sutherland, Dawn E Telford, Cynthia G Sawyez, Jane Y Edwards, Sergey Filippov, Stephen L Pinkosky, Roger S Newton, Murray W Huff
Journal: Circulation (2015)

ETC-1002 (8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) is a novel LDL cholesterol-lowering compound. Preclinical studies revealed that ETC-1002 targets the liver where its metabolite, ETC-1002-CoA, inhibits the synthesis of sterols and fatty acids. The primary mechanism of action is through inhibition of hepatic ATP-citrate lyase (ACL). In the current study we tested the ability of ETC-1002 to prevent diet-induced metabolic dysregulation, inflammation and atherosclerosis in LDL receptor deficient (Ldlr-/-) mice. Ldlr-/- mice fed a high-fat high-cholesterol diet (42% kcal fat; 0.2% cholesterol; HFHC) developed hypercholesterolemia, hypertriglyceridemia, hyperglycemia, hyperinsulinemia, fatty liver and obesity over the 12 week study. ETC-1002 supplementation to the HFHC diet at 3, 10 and 30 mg/kg/d significantly attenuated these metabolic abnormalities in a dose-dependent manner. ETC-1002 + HFHC attenuated plasma triglyceride (up to 64%) and plasma cholesterol concentrations (up to 50%), and improved glucose homeostasis compared to HFHC alone as determined by glucose tolerance tests. Adiposity was attenuated up to 48% with treatment. In liver, ETC-1002 dose dependently prevented cholesterol and triglyceride accumulation up to 75% and 90%, respectively. Hepatic gene expression analysis revealed that treatment significantly reduced the expression of the inflammatory genes Tnfa, Il1b, Ccl3 and Nos2 as well as increased the expression of genes involved in mitochondrial (Cpt1a, 1.3-fold) and peroxisomal (Acox1, 4.1-fold) fatty acid beta-oxidation. ETC-1002 reduced aortic cholesterol ester content by up to 63% and robustly attenuated atherosclerotic lesion development in the aortic sinus by 48%. These studies demonstrate that ETC-1002 effectively prevents plasma and tissue lipid elevations and attenuates the onset of inflammation, leading to the prevention of atherosclerotic lesion development in a mouse model of metabolic dysregulation.
Ratio of metastatic to examined lymph nodes is a powerful predictor of overall survival in rectal cancer: An analysis of Intergroup 0114
Authors: M. O. Meyers, D. R. Hollis, R. J. Mayer, A. B. Benson, R. M. Goldberg, B. Cummings, L. L. Gunderson, J. A. Martenson, J. S. Macdonald, M. O’Connell, J. E. Tepper
Journal: Journal of Clinical Oncology (2007)

4006 Background: Lymph node (LN) metastasis is associated with decreased survival in rectal cancer. It has been suggested that at least 14 LN be evaluated for adequate staging. However, a large percentage of patients have fewer than the recommended number of LN examined. We hypothesized that LN ratio would be predictive of overall survival in rectal cancer. Methods: Data was analyzed from Intergroup 0114, a mature trial of postoperative adjuvant chemotherapy and radiation in T 3/4 and/or LN positive rectal cancer. Survival was the same for all arms allowing the entire group to be considered as one. The primary endpoint evaluated was overall survival. A proportional hazards model was used to determine the relative prognostic impact of LN ratio compared to number of LN examined, number of positive LN, number of negative LN and AJCC nodal stage. LN ratio was defined as the number of positive LN divided by the total number of LN examined. Four groups were analyzed based on proportion of positive LN: =0.25, &gt;0.25–0.50, &gt;0.50–0.75 and &gt;0.75. Results: 1,648 patients were evaluable. There were 251 T 1/2 , 1,251 T 3 and 146 T 4 tumors. 513 patients were N 0 , 743 N 1 and 392 N 2 . Median number of LN was 9. LN ratio was predictive of 5-year overall survival with rates of 0.71, 0.56, 0.50 and 0.43 respectively when analyzed by quartile (p&lt;0.0001). LN ratio remained significant when overall survival was analyzed by number of LN examined and grouped into &lt;10, &lt;15 and &gt;15 nodes evaluated (p&lt;0.0001 for all). LN ratio also predicted overall survival in N 1 (p=0.04) and N 2 (p=0.0002) disease. When comparing LN ratio (χ 2 =79.5, p&lt;0.0001) to number of LN examined (χ 2 =4.7, p=0.03), number of positive LN (χ 2 =38, p&lt;0.0001), number of negative LN (χ 2 =32, p&lt;0.0001) and AJCC nodal stage (χ 2 =55.5, p&lt;0.0001), LN ratio appears to be the strongest predictor of overall survival. Conclusion: LN ratio predicts overall survival in patients with resected rectal cancer. Importantly, this is true in patients who have had a small number of LN evaluated, in addition to those with a large number of LN examined. LN ratio also appears to be a stronger predictor of overall survival than other described LN prognostic factors. LN ratio may be a useful variable to stratify outcome in patients with node-positive rectal cancer. No significant financial relationships to disclose.
Physical Therapy or Arthroscopic Surgery for Treatment of Meniscal Tears
Authors: Laith Jazrawi, Heather T. Gold, Joseph D. Zuckerman
Journal: JAMA (2018)

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
Diagnosis and Management of Rheumatoid Arthritis
Authors: Daniel Aletaha, Josef S. Smolen
Journal: JAMA (2018)

<h3>Importance</h3> Rheumatoid arthritis (RA) occurs in about 5 per 1000 people and can lead to severe joint damage and disability. Significant progress has been made over the past 2 decades regarding understanding of disease pathophysiology, optimal outcome measures, and effective treatment strategies, including the recognition of the importance of diagnosing and treating RA early. <h3>Observations</h3> Early diagnosis and treatment of RA can avert or substantially slow progression of joint damage in up to 90% of patients, thereby preventing irreversible disability. The development of novel instruments to measure disease activity and identify the presence or absence of remission have facilitated new treatment strategies to arrest RA before joints are damaged irreversibly. Outcomes have been improved by recognizing the benefits of early diagnosis and early therapy with disease-modifying antirheumatic drugs (DMARDs). The treatment target is remission or a state of at least low disease activity, which should be attained within 6 months. Methotrexate is first-line therapy and should be prescribed at an optimal dose of 25 mg weekly and in combination with glucocorticoids; 40% to 50% of patients reach remission or at least low disease activity with this regimen. If this treatment fails, sequential application of targeted therapies, such as biologic agents (eg, tumor necrosis factor [TNF] inhibitors) or Janus kinase inhibitors in combination with methotrexate, have allowed up to 75% of these patients to reach the treatment target over time. New therapies have been developed in response to new pathogenetic findings. The costs of some therapies are considerable, but these costs are decreasing with the advent of biosimilar drugs (drugs essentially identical to the original biologic drugs but usually available at lower cost). <h3>Conclusions and Relevance</h3> Scientific advances have improved therapies that prevent progression of irreversible joint damage in up to 90% of patients with RA. Early treatment with methotrexate plus glucocorticoids and subsequently with other DMARDs, such as inhibitors of TNF, IL-6, or Janus kinases, improves outcomes and prevents RA-related disability. A treat-to-target strategy aimed at reducing disease activity by at least 50% within 3 months and achieving remission or low disease activity within 6 months, with sequential drug treatment if needed, can prevent RA-related disability.
Long‐term clinical safety of clindamycin and rifampicin combination for the treatment of hidradenitis suppurativa. A Critically Appraised Topic
Authors: J. Albrecht, P.A. Baine, B. Ladizinski, G.B. Jemec, M. Bigby
Journal: British Journal of Dermatology (2018)

Clinical question/scenario Can therapy with clindamycin and rifampicin be safely continued long term beyond the recommended 10-week course? Background Clindamycin and rifampicin are used in combination to treat hidradenitis suppurativa (HS). There is no data on the efficacy and safety of clindamycin/rifampicin combination therapy for HS beyond 10 weeks. Methods We identified the following major concerns that still lack a proper evidenced-based analysis: for rifampicin, drug-induced liver injury, interstitial nephritis, drug interaction and hepatic p450 3A4 enzyme induction; for clindamycin, the concern was community-acquired Clostridium difficile infection (CA-CDI); and experience with long-term treatment. Data sources were used as appropriate to answer the question. Systematic searches were used to assess the risk of CA-CDI and experience with long-term treatment with clindamycin. Results/identified evidence The risk for rifampicin-induced liver injury is highest in the first 6 weeks of treatment, whereas interstitial nephritis is primarily observed during intermittent treatment. Enzyme induction due to rifampicin is usually complete after about 2 weeks of treatment and reduces clindamycin blood levels by about 90%. Three meta-analyses identified antibiotic use as a risk factor for CA-CDI. Two of them assigned the highest risk to clindamycin. None of them stratified by length of treatment. There is extensive experience with rifampicin, primarily for the treatment of tuberculosis. Long-term experience with clindamycin is limited. Discussion and recommendation for clinical care The analysed risks associated with a combination of clindamycin and rifampicin for hidradenitis suppurative cluster within the first 10 weeks. Treatment can be continued beyond 10 weeks, if clinically necessary.
Elastase Exocytosis by Airway Neutrophils Is Associated with Early Lung Damage in Children with Cystic Fibrosis
Authors: Camilla Margaroli, Luke W. Garratt, Hamed Horati, A. Susanne Dittrich, Timothy Rosenow, Samuel T. Montgomery, Dario L. Frey, Milton R. Brown, Carsten Schultz, Lokesh Guglani, Anthony Kicic, Limin Peng, Bob J. Scholte, Marcus A. Mall, Hettie M. Janssens, Stephen M. Stick, Rabindra Tirouvanziam
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Neutrophils are recruited to the airways of individuals with cystic fibrosis (CF). In adolescents and adults with CF, airway neutrophils actively exocytose the primary granule protease elastase (NE), whose extracellular activity correlates with lung damage. During childhood, free extracellular NE activity is measurable only in a subset of patients, and the exocytic function of airway neutrophils is unknown.To measure NE exocytosis by airway neutrophils in relation to free extracellular NE activity and lung damage in children with CF.We measured lung damage using chest computed tomography coupled with the Perth-Rotterdam Annotated Grid Morphometric Analysis for Cystic Fibrosis scoring system. Concomitantly, we phenotyped blood and BAL fluid leukocytes by flow and image cytometry, and measured free extracellular NE activity using spectrophotometric and Förster resonance energy transfer assays. Children with airway inflammation linked to aerodigestive disorder were enrolled as control subjects.Children with CF but not disease control children harbored BAL fluid neutrophils with high exocytosis of primary granules, before the detection of bronchiectasis. This measure of NE exocytosis correlated with lung damage (R = 0.55; P = 0.0008), whereas the molecular measure of free extracellular NE activity did not. This discrepancy may be caused by the inhibition of extracellular NE by BAL fluid antiproteases and its binding to leukocytes.NE exocytosis by airway neutrophils occurs in all children with CF, and its cellular measure correlates with early lung damage. These findings implicate live airway neutrophils in early CF pathogenesis, which should instruct biomarker development and antiinflammatory therapy in children with CF.
Abstract MP014: Very Long Chain Saturated Fatty Acids and Diabetes Risk: Meta-Analysis of Cohort Studies in the FORCE Consortium
Authors: Amanda Fretts, Fumiaki Imamura, Chaoyu Yu, Alexis C Frazier-Wood, Maria Lankinen, Kalina Rajaobelina, Nathan L Tintle, Jyrki K Virtanen, Kerry Wong, Wei-Sin Yang, Dariush Mozaffarian, Rozenn Lemaitre
Journal: Circulation (2017)

Background: Circulating saturated fatty acids are biomarkers of diet and metabolism that may influence the pathogenesis of diabetes. Unlike palmitic acid (16:0), which has been extensively studied, little is known of the relationship of very long-chain saturated fatty acids (VLSFAs), with 20 carbons or more, to diabetes risk. Objective: To investigate the associations of circulating levels of VLSFA with incident diabetes. Methods: A meta-analysis was conducted within a consortium of prospective (cohort or nested case-control) studies having circulating measures of one or more VLSFAs, including arachidic acid (20:0), behenic acid (22:0) and lignoceric acid (24:0). Standardized analysis was conducted in each study using pre-specified models, exposures, outcomes, and covariates. Study-specific estimates were pooled using fixed effects meta-analysis. Results: Current findings were based on 9 participating studies, including 46,549 total participants and 13,750 incident diabetes. In multivariable-adjusted analyses, higher levels of all 3 VLSFAs were associated with lower risk of incident diabetes. Pooled RRs (95% CI) per interquintile range were 0.80 (0.71-0.90) for 20:0; 0.83 (0.76-0.91) for 22:0; and 0.70 (0.63-0.79) for 24:0, after adjustment for demographics, lifestyle factors and clinical conditions. Additional adjustments for circulating palmitic acid and triglyceride levels moved the RRs toward the null (illustrated for 24:0, in model 3 of the Figure ). Conclusions: Based on meta-analysis of results from several studies around the world, biomarker levels of VLSFA are associated with lower risk of incident diabetes, potentially mediated by effects on circulating triglycerides and 16:0.
Abstract 5084: Long Term Survival According to Weight Among Patients without Known Cardiac Disease and a Normal Stress SPECT: Extending the Spectrum of the Obesity Paradox
Authors: Padmakshi Singh, Azhar Supariwala, Rajeev Joshi, Apurva Badheka, Anupa Mandeva, Steven Lascher, Seth Uretsky, Alan Rozanski
Journal: Circulation (2008)
Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial
Authors: Niels WCJ van de Donk, Bronno van der Holt, Monique C Minnema, Edo Vellenga, Sandra Croockewit, Marie José Kersten, Peter A von dem Borne, Paula Ypma, Ron Schaafsma, Okke de Weerdt, Saskia K Klein, Michel Delforge, Mark-David Levin, Gerard M Bos, Kon-Siong G Jie, Harm Sinnige, Jules LLM Coenen, Esther G de Waal, Sonja Zweegman, Pieter Sonneveld, Henk M Lokhorst
Journal: The Lancet Haematology (2018)
microRNA-181a-5p antisense oligonucleotides attenuate osteoarthritis in facet and knee joints
Authors: Akihiro Nakamura, Yoga Raja Rampersaud, Sayaka Nakamura, Anirudh Sharma, Fanxing Zeng, Evgeny Rossomacha, Shabana Amanda Ali, Roman Krawetz, Nigil Haroon, Anthony V Perruccio, Nizar N Mahomed, Rajiv Gandhi, Jason S Rockel, Mohit Kapoor
Journal: Annals of the Rheumatic Diseases (2018)

We recently identified microRNA-181a-5p (miR-181a-5p) as a critical mediator involved in the destruction of lumbar facet joint (FJ) cartilage. In this study, we tested if locked nucleic acid (LNA) miR-181a-5p antisense oligonucleotides (ASO) could be used as a therapeutic to limit articular cartilage degeneration.We used a variety of experimental models consisting of both human samples and animal models of FJ and knee osteoarthritis (OA) to test the effects of LNA-miR-181a-5p ASO on articular cartilage degeneration. Histopathological analysis including immunohistochemistry and in situ hybridisation were used to detect key OA catabolic markers and microRNA, respectively. Apoptotic/cell death markers were evaluated by flow cytometry. qPCR and immunoblotting were applied to quantify gene and protein expression.miR-181a-5p expression was increased in human FJ OA and knee OA cartilage as well as injury-induced FJ OA (rat) and trauma-induced knee OA (mouse) cartilage compared with control cartilage, correlating with classical OA catabolic markers in human, rat and mouse cartilage. We demonstrated that LNA-miR-181a-5p ASO in rat and mouse chondrocytes reduced the expression of cartilage catabolic and chondrocyte apoptotic/cell death markers in vitro. Treatment of OA-induced rat FJ or mouse knee joints with intra-articular injections of in vivo grade LNA-miR-181a-5p ASO attenuated cartilage destruction, and the expression of catabolic, hypertrophic, apoptotic/cell death and type II collagen breakdown markers. Finally, treatment of LNA-miR-181a-5p ASO in cultures of human knee OA chondrocytes (in vitro) and cartilage explants (ex vivo) further demonstrated its cartilage protective effects.Our data demonstrate, for the first time, that LNA-miR-181a-5p ASO exhibit cartilage-protective effects in FJ and knee OA.