tbuckley/cabot-search huggingface dataset:
Cost-Effectiveness of Platelet Glycoprotein IIb/IIIa Inhibition With Eptifibatide in Patients With Non–ST-Elevation Acute Coronary Syndromes
Authors: Daniel B. Mark, Robert A. Harrington, A. Michael Lincoff, Robert M. Califf, Charlotte L. Nelson, Anastasios A. Tsiatis, Hope Buell, Kenneth W. Mahaffey, Linda Davidson-Ray, Eric J. Topol
Journal: Circulation (2000)

Background —In the PURSUIT trial, eptifibatide significantly reduced the 30-day incidence of death and myocardial infarction relative to placebo in 9461 patients with an acute coronary syndrome (unstable angina or non–Q-wave myocardial infarction). Methods and Results —We conducted a 2-part prospective economic substudy of the 3522 US patients enrolled in PURSUIT: (1) an empirical intention-to-treat comparison of medical costs (hospital plus physician) up to 6 months after hospitalization and (2) a lifetime cost-effectiveness analysis. The base-case cost-effectiveness ratio was expressed as the 1996 US dollars required to add 1 life-year with eptifibatide therapy. The 2 treatment arms had equivalent resource consumption and medical costs (exclusive of the cost of the eptifibatide regimen) during the index (enrollment) hospitalization ( P =0.78) and up to 6 months afterward ( P =0.60). The average wholesale price of the eptifibatide regimen was $1217, but a typical hospital discounted price was $1014. The estimated life expectancy from randomization in the US patients was 15.96 years for eptifibatide and 15.85 years for placebo, an incremental difference of 0.111. The incremental cost-effectiveness ratio for eptifibatide therapy in US PURSUIT patients was $16 491 per year of life saved. This result was robust through a wide range of sensitivity analyses. The cost-utility ratio for eptifibatide (using time trade-off defined utilities) was $19 693 per added quality-adjusted life-year. Conclusions —Based on the results observed in the US PURSUIT patients, the routine addition of eptifibatide to standard care for non–ST-elevation acute coronary syndrome patients is economically attractive by conventional standards.
Diagnostic approaches for paediatric tuberculosis by use of different specimen types, culture methods, and PCR: a prospective case-control study
Authors: Richard A Oberhelman, Giselle Soto-Castellares, Robert H Gilman, Luz Caviedes, Maria E Castillo, Lenka Kolevic, Trinidad Del Pino, Mayuko Saito, Eduardo Salazar-Lindo, Eduardo Negron, Sonia Montenegro, V Alberto Laguna-Torres, David AJ Moore, Carlton A Evans
Journal: The Lancet Infectious Diseases (2010)
Hydroxyproline and passive stiffness of pressure-induced hypertrophied kitten myocardium.
Authors: J F Williams, R D Potter, D L Hern, B Mathew, W P Deiss
Journal: Journal of Clinical Investigation (1982)

Passive stiffness and hydroxyproline content of myocardium hypertrophied by pressure-loading were determined in kittens 2, 8-16, and 24-52 wk after pulmonary artery banding, which initially elevated right ventricular systolic pressure by 10-15 mm Hg. Right ventricular mass increased by approximately 75%, three-quarters of which occurred during the first 2 wk after banding. Passive stiffness was assessed from resting length-tension relations of isometrically contracting isolated right ventricular papillary muscles. Stiffness constants, alpha and beta were determined from the relationship sigma = alpha (e beta epsilon - 1) where sigma = stress and epsilon = Lagrangian strain. Elastic stiffness (d sigma/d epsilon) was derived from: d sigma/d epsilon = beta sigma + beta alpha. Right ventricular hydroxyproline increased in proportion to muscle mass so that hydroxyproline concentration remained unchanged after banding. Both alpha, beta, and elastic stiffness-stress relations were similar to values in nonbanded controls. Thus, we did not observe an increase in passive stiffness or hydroxyproline concentration of pressure-stiffness or hydroxyproline concentration of pressure-induced hypertrophied myocardium in contrast to most previous studies.
Micro-simulation of a smallpox outbreak using official register data
Authors: L Brouwers, M Boman, M Camitz, K Mäkilä, A Tegnell
Journal: Eurosurveillance (2010)

To explore the efficacy of four vaccine-based policy strategies (ring vaccination, targeted vaccination, mass vaccination, and pre-vaccination of healthcare personnel combined with ring vaccination) for controlling smallpox outbreaks in Sweden, disease transmission on a spatially explicit social network was simulated. The mixing network was formed from high-coverage official register data of the entire Swedish population, building on the Swedish Total Population Register, the Swedish Employment Register, and the Geographic Database of Sweden. The largest reduction measured in the number of infections was achieved when combining ring vaccination with a pre-vaccination of healthcare personnel. In terms of per dose effectiveness, ring vaccination was by far the most effective strategy. The results can to some extent be adapted to other diseases and environments, including other countries, and the methods used can be analysed in their own right.
VAMP and Low-Dose, Involved-Field Radiation for Children and Adolescents With Favorable, Early-Stage Hodgkin’s Disease: Results of a Prospective Clinical Trial
Authors: Sarah S. Donaldson, Melissa M. Hudson, Kathleen R. Lamborn, Michael P. Link, Larry Kun, Amy Louise Billett, Karen C. Marcus, Craig A. Hurwitz, Jeffrey A. Young, Nancy J. Tarbell, Howard J. Weinstein
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To evaluate outcome and assess toxicity of children and adolescents with early-stage, favorable Hodgkin’s disease treated with vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and low-dose, involved-field radiation. PATIENTS AND METHODS: One hundred ten patients with clinical stages I and II, favorable (nonbulky) Hodgkin’s disease were treated with four cycles of VAMP chemotherapy and 15 Gy involved-field radiation for those who achieved a complete response, or 25.5 Gy for those who achieved a partial response to two cycles of VAMP. RESULTS: With a median follow-up of 5.6 years (range, 1.1 to 10.4 years), the 5-year survival and event-free survival were 99% (lower confidence limit [CL], 97.4%) and 93% (lower CL, 88.6%), respectively. Factors associated with event-free survival of 100% were complete response to two cycles of VAMP and histology other than nodular sclerosing Hodgkin’s disease (NSHD). No serious early or late toxicity has been observed. Patients presenting with clinical stages I and IIA, nonbulky disease involving fewer than three nodal sites have a projected survival and event-free survival of 100% and 97% (lower CL, 93%), respectively, at 5 years. CONCLUSION: Risk-adapted, combined-modality therapy using only four cycles of VAMP chemotherapy with 15 to 25.5 Gy of involved-field radiation for patients with early-stage/favorable Hodgkin’s disease is highly effective and without demonstrable late effects. These results indicate that pediatric patients with stages I and II favorable Hodgkin’s disease can be cured with limited therapy that does not include an alkylating agent, bleomycin, etoposide, or high-dose, extended-field radiation therapy.
Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans
Authors: Lisa M. Abegglen, Aleah F. Caulin, Ashley Chan, Kristy Lee, Rosann Robinson, Michael S. Campbell, Wendy K. Kiso, Dennis L. Schmitt, Peter J. Waddell, Srividya Bhaskara, Shane T. Jensen, Carlo C. Maley, Joshua D. Schiffman
Journal: JAMA (2015)

Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology.To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS).A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11). Human samples were collected at the University of Utah between June 2014 and July 2015.Ionizing radiation and doxorubicin.Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes.Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95% CI, 0%-5%]; African wild dog, 8% [95% CI, 0%-16%]; lion, 2% [95% CI, 0%-7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95% CI, 3.14%-6.49%), compared with humans, who have 11% to 25% cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis at higher rates than human lymphocytes proportional to TP53 status (ionizing radiation exposure: patients with LFS, 2.71% [95% CI, 1.93%-3.48%] vs human controls, 7.17% [95% CI, 5.91%-8.44%] vs elephants, 14.64% [95% CI, 10.91%-18.37%]; P < .001; doxorubicin exposure: human controls, 8.10% [95% CI, 6.55%-9.66%] vs elephants, 24.77% [95% CI, 23.0%-26.53%]; P < .001).Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage. These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression.
P12 Fluticasone propionate/formoterol fumarate combination therapy: treatment effects in patients by baseline asthma severity across the dose range
Authors: T McIver, B Grothe, M Jain, S Dissanayake
Journal: Thorax (2012)

<h3>Background</h3> A new asthma therapy containing a combination of the inhaled steroid fluticasone propionate (FLUT) and the long-acting β<sub>2</sub> agonist (LABA) formoterol fumarate (FORM) in a metered-dose inhaler has been developed (FLUT/FORM; <i>flutiform</i><sup>®</sup>). In a double-blind, double-dummy, randomised, multicentre, four arm parallel group study, the efficacy and safety of FLUT/FORM <i>vs.</i> FLUT and FORM administered concurrently (FLUT+FORM) was assessed. Here, we present efficacy results of a posthoc analysis that compared FLUT/FORM 500/20 µg with FLUT/FORM 100/10 µg (both twicedaily) by baseline asthma severity. <h3>Methods</h3> In total, 620 patients were randomised 1:1:1:1 to receive FLUT/FORM 500/20 µg, FLUT/FORM 100/10 µg, FLUT+FORM 500 µg + 24 µg or FLUT 500 µg. Randomisation was stratified by percentage predicted FEV1 at baseline [≥40 – ≤60% (‘severe asthma’; 52% of patients) <i>vs.</i> &gt;60% – ≤80% (‘moderate asthma’; 48% of patients)], allowing a post-hoc dichotomised analysis by baseline FEV1 severity of spirometric and symptom-based endpoints. <h3>Results</h3> There was no dose-response relationship between FLUT/FORM 500/20 µg and FLUT/FORM 100/10 µg for the spirometric variables overall or in either subgroup. Treatment effect differences between FLUT/FORM 500/20 µg and 100/10 µg, in favour of the high dose, were however evident for almost all symptom-based endpoints and were more pronounced in the severe asthma group. These included changes in: mean symptom scores, percentage symptomfree days, mean sleep disturbance scores, awakening free nights, percentage rescue medication-free days, percentage asthma control days, AQLQ score and the incidence of any asthma exacerbations. The differences between FLUT/FORM 500/20 µg and 100/10 µg in the severe asthma group were significant at the 5% level for sleep disturbance scores [treatment difference –0.138 (95% CI: –0.265, –0.012) <i>P</i>=0.032], percentage awakeningfree nights [treatment difference 11.754 (95% CI: 2.234, 21.274) <i>P</i>=0.016] and mean AQLQ score [treatment difference 0.302 (95% CI: 0.013, 0.591) <i>P</i>=0.041]. <h3>Conclusion</h3> High dose FLUT/FORM (500/20 µg) was consistently associated with greater symptomatic treatment benefit than low dose (100/10 µg) treatment in patients with severe asthma. These data provide a rationale for dose escalation with FLUT/FORM, which appears most likely to confer additional treatment benefit in patients with severe asthma.
An Identity Crisis for <i>fps/fes</i>: Oncogene or Tumor Suppressor?
Authors: Waheed Sangrar, Ralph A. Zirgnibl, Yan Gao, William J. Muller, Zongchao Jia, Peter A. Greer
Journal: Cancer Research (2005)

Abstract Fps/Fes proteins were among the first members of the protein tyrosine kinase family to be characterized as dominant-acting oncoproteins. Addition of retroviral GAG sequences or other experimentally induced mutations activated the latent transforming potential of Fps/Fes. However, activating mutations in fps/fes had not been found in human tumors until recently, when mutational analysis of a panel of colorectal cancers identified four somatic mutations in sequences encoding the Fps/Fes kinase domain. Here, we report biochemical and theoretical structural analysis demonstrating that three of these mutations result in inactivation, not activation, of Fps/Fes, whereas the fourth mutation compromised in vivo activity. These results did not concur with a classic dominant-acting oncogenic role for fps/fes involving activating somatic mutations but instead raised the possibility that inactivating fps/fes mutations might promote tumor progression in vivo. Consistent with this, we observed that tumor onset in a mouse model of breast epithelial cancer occurred earlier in mice targeted with either null or kinase-inactivating fps/fes mutations. Furthermore, a fps/fes transgene restored normal tumor onset kinetics in targeted fps/fes null mice. These data suggest a novel and unexpected tumor suppressor role for Fps/Fes in epithelial cells.
Bridging the Divide Between Health and Health Care
Authors: Stephen M. Shortell
Journal: JAMA (2013)

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
Neurocognitive function and dysfunction after hepatitis C therapy
Authors: Pablo Solis-Muñoz, Carlos Mingote-Adán, Jose Antonio Solís-Herruzo
Journal: Hepatology (2013)

We read with interest the elegant study by Kraus et al.1 in the August issue of Hepatology. We have some concerns with regard to possible bias due to confounding factors not taken into account in the study. It is well known that not only depression but also the emotional state of the patient and motivation alone can modify neurocognitive function. It is very common for interferon alpha (IFN-α) therapy to induce depression or dysthymia.2 The psychiatric adverse effects of IFN-α can last for a long period after ending therapy, whether the patient achieved sustained virological response (SVR) or not. The authors give no data about such an important and proven factor in cognitive test performance.3, 4 A depressed or dysthymic patient will not perform as well as an euthymic patient in the measured tasks (alertness, attention, vigilance and working memory), no matter how simple. No information is given with regard to the distribution in both groups of this side effect, what medication was used in case it appeared, or if they responded to the antidepressant medication. Furthermore, the study was not blinded and we assume the patients were informed of the progress of their antiviral therapy. This creates an unavoidable psychological bias. The authors explain that their excellent SVR rate (69% versus the usual 40 to 50%) is explained in part due to the motivation of the studied patients. However, they do not consider that the same factor influences the neuropsychological test they performed. Motivated patients, perhaps those who achieved SVR, perform better on the Test for Attentional Performance (TAP) as compared to unmotivated patients.5 Pablo SolÍs-Muñoz, M.D., Ph.D.1,3 Carlos Mingote-Adán, M.D., Ph.D.2 Jose Antonio SolÍs-Herruzo, M.D., Ph.D.3 1Angloamerican Medical Unit Gastroenterology and Hepatology Madrid, Spain 2PAIPSE, Department of Psychiatry University Hospital “12 de Octubre” Madrid, Spain 3Biomedical Research Unit of Gastroenterology and Hepatology University Hospital “12 de Octubre” Madrid, Spain
Expression of TP53 mutation-associated microRNAs predicts clinical outcome in head and neck squamous cell carcinoma patients
Authors: F. Ganci, A. Sacconi, N. Bossel Ben-Moshe, V. Manciocco, I. Sperduti, L. Strigari, R. Covello, M. Benevolo, E. Pescarmona, E. Domany, P. Muti, S. Strano, G. Spriano, G. Fontemaggi, Giovanni Blandino
Journal: Annals of Oncology (2013)
STUDIES IN BLOOD COAGULATION
Authors: C. M. Van Allen
Journal: The Journal of Experimental Medicine (1927)

The gross phenomena of normal blood coagulation have been studied for the purpose of obtaining methods for estimating certain characteristics of coagulation in connection with a malignant tumor of the rabbit. The technique is described for the estimation of clot formation rate and of clot retraction rate and extent. The range of normal and abnormal values secured by these procedures is given.
On the North West Frontier.
Authors: B A Ward
Journal: BMJ (1981)

There had been many political changes before my trip to Pakistan in January 1980, the most important being the invasion of Afghanistan by the Russians in December 1979. Thousands of refugees were now spilling over the border and the political outcome was uncertain. I was to spend my elective in Peshawar, North-west Frontier Province, about 25 km from the Khyber Pass and only 50 km from the Afghan border. I arrived in Rawal? pindi at dawn on a cold, rainy day. The airport was dirty and teeming with Pakistani soldiers, who were there to greet the foreign ministers attending an all-Islamic conference. It was a taste of the military strength I noticed as I travelled along the Af ghanistan Pakistan border. I also sampled the administrative dis? array when I was told my flight to Peshawar was fully booked and after much persuasion got a ticket to find the plane only half full. In the four hours I had to wait I experienced the difficulties that an un? accompanied woman faces in Islamic culture.
Variable mercaptopurine metabolism in children with leukaemia: a problem of non-compliance?
Authors: H A Davies, L Lennard, J S Lilleyman
Journal: BMJ (1993)

into the microalbuminuria range before it induces a rise in blood pressure.Insulin dependent diabetic patients who developed persistent or intermittent microalbuminuria were significantly more likely to have retinal lesions at baseline than those who remained normoalbuminuric.This difference was maintained at follow up and has also been shown by other workers.24In conclusion our study shows that raised albumin excretion rate and blood pressure are concomitant phenomena in insulin dependent diabetic patients progressing to microalbuminuria.A background of poor blood glucose control compounded with a rise in blood pressure and, to a lesser extent, a history of smoking are crucial determinants of this process.
Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number
Authors: Ric N Price, Anne-Catrin Uhlemann, Alan Brockman, Rose McGready, Elizabeth Ashley, Lucy Phaipun, Rina Patel, Kenneth Laing, Sornchai Looareesuwan, Nicholas J White, François Nosten, Sanjeev Krishna
Journal: The Lancet (2004)
Pravastatin does not affect insulin sensitivity and adipocytokines levels in healthy nondiabetic patients
Authors: Marie-Hélène Gannagé-Yared, Rabih R. Azar, Mireille Amm-Azar, Simon Khalifé, Myrna Germanos-Haddad, Ramy Neemtallah, Georges Halaby
Journal: Metabolism (2005)
Prescription of oxygen concentrators: adherence to published guidelines.
Authors: J P Dilworth, C M Higgs, P A Jones, R J White
Journal: Thorax (1989)

The indications for the prescription of oxygen concentrators have been assessed in 82 patients against the Department of Health guidelines, except that only one set of blood gas and spirometry measurements was required if the patient's condition was stable. Of the 49 patients recommended for this treatment by a chest physician, 41 (82%) fulfilled the requirements, compared with only 11 of 33 patients where the concentrator was recommended by a general practitioner or non-specialist physician. Eleven patients died within one month of prescription. The results show that many patients are being prescribed oxygen concentrators without assessment and underline the importance of full assessment and attention to prognosis before prescription.
Comparative loss of activity of recombinant secretory leukoprotease inhibitor and alpha 1-protease inhibitor caused by different forms of oxidative stress
Authors: C Vogelmeier, T Biedermann, K Maier, G Mazur, J Behr, F Krombach, R Buhl
Journal: European Respiratory Journal (1997)

Secretory leukoprotease inhibitor (SLPI) and alpha 1-protease inhibitor (alpha 1-PI) are powerful antiproteases currently under investigation for their potential to protect the lung from neutrophil elastase (NE). The aim of this study was to determine whether the recombinant form of SLPI (rSLPI) and alpha 1-PI show different grades of loss of inhibitory activity when exposed to reactive oxygen metabolites. We incubated rSLPI and alpha 1-PI with N-chlorosuccinimide (NCS), chloramines, activated polymorphonuclear leucocytes (PMNs) and activated alveolar macrophages (AMs). Under all conditions evaluated, both antiproteases were partially inactivated. The resulting anti-NE activity of rSLPI was not significantly different from that of alpha 1-PI after exposure to NCS (p &gt; 0.5), chloramines (p &gt; 0.6), activated PMNs (p &gt; 0.07) and activated AMs (p &gt; 0.9). In conclusion, recombinant secretory leukoprotease inhibitor and alpha 1-protease inhibitor lose antineutrophil elastase activity to a similar extent when exposed to conditions that may be present in inflammatory lung disorders.