tbuckley/cabot-search huggingface dataset:
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
Authors: Bernard Zinman, Christoph Wanner, John M. Lachin, David Fitchett, Erich Bluhmki, Stefan Hantel, Michaela Mattheus, Theresa Devins, Odd Erik Johansen, Hans J. Woerle, Uli C. Broedl, Silvio E. Inzucchi
Journal: New England Journal of Medicine (2015)

The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known.We randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled empagliflozin group versus the placebo group. The key secondary composite outcome was the primary outcome plus hospitalization for unstable angina.A total of 7020 patients were treated (median observation time, 3.1 years). The primary outcome occurred in 490 of 4687 patients (10.5%) in the pooled empagliflozin group and in 282 of 2333 patients (12.1%) in the placebo group (hazard ratio in the empagliflozin group, 0.86; 95.02% confidence interval, 0.74 to 0.99; P=0.04 for superiority). There were no significant between-group differences in the rates of myocardial infarction or stroke, but in the empagliflozin group there were significantly lower rates of death from cardiovascular causes (3.7%, vs. 5.9% in the placebo group; 38% relative risk reduction), hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction), and death from any cause (5.7% and 8.3%, respectively; 32% relative risk reduction). There was no significant between-group difference in the key secondary outcome (P=0.08 for superiority). Among patients receiving empagliflozin, there was an increased rate of genital infection but no increase in other adverse events.Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care. (Funded by Boehringer Ingelheim and Eli Lilly; EMPA-REG OUTCOME ClinicalTrials.gov number, NCT01131676.).
Predisposing conditions to bacterial infections in chronic obstructive pulmonary disease.
Authors: H M Jansen, A P Sachs, L van Alphen
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

In normal airways, invasion of small numbers of pathogenic bacteria will not give rise to injury or local colonization. In chronic obstructive pulmonary disease, however, local conditions are changed, which may impair local defense systems and facilitate infection. These include: (1) factors promoting bacterial adherence and growth like the observed damaged airway epithelium in chronic bronchitis. The consequent changes in the composition of the epithelial lining fluid and impaired mucociliary clearance may be the most important pathophysiologic airway sequele in this respect; (2) aggravating generalized airway obstruction including mucus secretion, increase in mucus viscosity, and proliferation of submucosal smooth muscles, resulting in significant changes in airway geometry. This may change local conditions dramatically and so sustain factors promoting bacterial infections; (3) subversion of normally protective defense mechanisms into damaging host tissue at the mucosal level. Activated epithelial cell layers induce increased submucosal vascular leakage, edema, and inflammatory cell infiltration with subsequent tissue injury by locally produced cell products like free elastase. Specific bacterial products but also generally produced bacterial endotoxins may induce a local immune response resulting in the local production of high concentrations of antibodies and an invasion of specific effector cells. The role of these reactive cells or proteins may even be a primary one, in that they attack on (cellular) proteins, which increase their susceptibility for dysfunction in the defense line. For the clinicians, the new insights in the role of these aggravating factors in the development of recurrent bacterial airway infections in chronic bronchitis may be of major importance.(ABSTRACT TRUNCATED AT 250 WORDS)
P246 CURBO2–65 Has Better Correlation than CURB65 with Modified Early Warning Scoring System (MEWS)
Authors: C Molugu, W Falconer, A Singer, A Disney, P Stockton, V Peers, L McCulloch
Journal: Thorax (2013)

<h3>Introduction</h3> For patients admitted to hospital with pneumonia, CURB65 (confusion, Urea&gt;7, Respiratory Rate&gt;30 and Blood Pressure&lt;90/60) is used to assess severity of the pneumonia (1). MEWS is a score which informs about the physiological status of a patient thus about the patients overall clinical status. One would anticipate CURB65 to be correlated to MEWS however there is no evidence to support correlation particularly on admission. The body’s capability to maintain adequate oxygenation when affected by pneumonia is of paramount importance. Oxygen was originally excluded from CURB65 due to non-statistical significance for predicting mortality. We felt CURB65 may not correlate with MEWS on admission hence introduced a new score incorporating oxygen to CURB65 score - CURBO2–65. COPD patient’s with SATS &lt;88% or Non-COPD with &lt;94% would score 1 and any patient receiving supplemental oxygen to maintain their SATS in desired range would score 1. The maximum score for oxygenation is 2 and maximum score on CURBO2 65 is 7 instead of 5 as in CURB65. <h3>Method</h3> We retrospectively analysed all pneumonia patients (COPD and Non-COPD) admitted to hospital for 2 consecutive months (December 2012 and January2013). Data was collected from our Advancing Quality team who keep a record of all pneumonias admitted. CURB 65 score and MEWS was collected from the documentation on admission and CURBO2 65 was calculated by applying above criteria for oxygenation. <h3>Results</h3> <h3>Conclusion</h3> CURB65 does not have predictable corelation with MEWS on admission. By incorporating oxygen into CURB65 and converting to CURBO2 65, we demonstrated its enhanced capability to correlate with MEWS on admission.. Further validity prospective studies are required to confirm our findings. <h3>Reference</h3> Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study W S lim, M M van der Eerden, R Laing, W G Boersma, N Karalus, G I Town, SA lewis, J T Macfarlane
Ad lib caffeine consumption, symptoms of caffeinism, and academic performance
Authors: Kirby Gilliland, Dara Andress
Journal: American Journal of Psychiatry (1981)

The authors explored the relationship between ad lib caffeine consumption in college students and the incidence of caffeinism, characterized by heightened anxiety, depression, and various psychophysiological reactions. Students were randomly selected from four groups (abstainers from caffeine and low, moderate, and high consumers). A survey battery assessed the effects of caffeine, incidence of psychophysiological disorders, state-trait anxiety, and depression. The moderate and high consumer groups combined reported significantly higher trait anxiety and depression scores when compared with abstainers. The high consumer group also reported significantly higher levels of symptoms of caffeinism, higher frequency of psychophysiological disorders, and lower academic performance.
Symptoms of obsessive-compulsive disorder
Authors: J F Leckman, D E Grice, J Boardman, H Zhang, A Vitale, C Bondi, J Alsobrook, B S Peterson, D J Cohen, S A Rasmussen, W K Goodman, C J McDougle, D L Pauls
Journal: American Journal of Psychiatry (1997)

Obsessive-compulsive disorder encompasses a broad range of symptoms that represent multiple psychological domains, including perception, cognition, emotion, social relatedness, and diverse motor behaviors. The purpose of these analyses was to evaluate the correlational relationships of the symptoms of obsessive-compulsive disorder.This study examined the 13 a priori categories used to group types of obsessions and compulsions in the Yale-Brown Obsessive Compulsive Scale symptom checklist in two independent groups of patients with obsessive-compulsive disorder (N = 208 and N = 98). A principal-components factor analysis with varimax rotation was performed, followed by a series of other exploratory analyses.The two data sets yielded nearly identical results. Four factors--obsessions and checking, symmetry and ordering, cleanliness and washing, and boarding--emerged in each data set, in total accounting for more than 60% of the variance.Obsessive-compulsive disorder is a multidimensional and etiologically heterogeneous condition. The four symptom dimensions identified in this study are largely congruent with those identified in earlier reports. These factors may be of value in future genetic, neurobiological, and treatment response studies.
FACTORS INVOLVED IN THE INDUCTION OF NON-SPECIFIC RESISTANCE TO STREPTOCOCCAL INFECTION IN MICE BY ENDOTOXIN
Authors: J. Gabriel Michael, Benedict F. Massell
Journal: The Journal of Experimental Medicine (1962)

Endotoxins derived from several species of Gram-negative bacteria, while inducing non-specific resistance to typhoid bacilli in mice, failed to increase the resistance of these animals to infection with virulent strains of Group A streptococci. However, if administration of endotoxin was followed by injection of minute amounts of type-specific antiserum, a substantial degree of protection against the streptococcal pathogen was obtained. The same amount of type-specific antiserum given to the animals by itself did not have any effect on the outcome of the streptococcal infection. Fresh rabbit blood, obtained from animals pretreated with endotoxin, together with anti-M protein immune serum, was found strongly bactericidal for streptococci. These observations suggest that, at least with regard to streptococcal infection, both humoral and cellular factors are required for induction of non-specific resistance.
The Popularity of Benzodiazepines, Their Advantages, and Inadequate Pharmacological Alternatives—Reply
Authors: Mark Olfson, Marissa King, Michael Schoenbaum
Journal: JAMA Psychiatry (2015)

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
Induction of TRPC6 Channel in Acquired Forms of Proteinuric Kidney Disease
Authors: Clemens C. Mo[Combining Diaeresis]ller, Changli Wei, Mehmet M. Altintas, Jing Li, Anna Greka, Takamoto Ohse, Jeffrey W. Pippin, Maria P. Rastaldi, Stefan Wawersik, Susan Schiavi, Anna Henger, Matthias Kretzler, Stuart J. Shankland, Jochen Reiser
Journal: Journal of the American Society of Nephrology (2006)

Injury to podocytes and their slit diaphragms typically leads to marked proteinuria. Mutations in the TRPC6 gene that codes for a slit diaphragm-associated, cation-permeable ion channel have been shown recently to co-segregate with hereditary forms of progressive kidney failure. Herein is shown that induced expression of wild-type TRPC6 is a common feature of human proteinuric kidney diseases, with highest induction observed in membranous nephropathy. Cultured podocytes that are exposed to complement upregulate TRPC6 protein. Stimulation of receptor-operated channels in puromycin aminonucleoside-treated podocytes leads to increased calcium influx in a time- and dosage-dependent manner. Mechanistically, it is shown that TRPC6 is functionally connected to the podocyte actin cytoskeleton, which is rearranged upon overexpression of TRPC6. Transient in vivo gene delivery of TRPC6 into mice leads to expression of TRPC6 protein at the slit diaphragm and causes proteinuria. These studies suggest the involvement of TRPC6 in the pathology of nongenetic forms of proteinuric disease.
Oxaliplatin in Combination With Protracted-Infusion Fluorouracil and Radiation: Report of a Clinical Trial for Patients With Esophageal Cancer
Authors: Nikhil I. Khushalani, Cynthia Gail Leichman, Gary Proulx, Hector Nava, Lisa Bodnar, Donald Klippenstein, Alan Litwin, Judy Smith, Enriqueta Nava, Lakshmi Pendyala, Patrick Smith, William Greco, Joanne Berdzik, Harold Douglass, Lawrence Leichman
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To identify a dose and schedule of oxaliplatin (OXP) to be safely administered in combination with protracted-infusion (PI) fluorouracil (5-FU) and external-beam radiation therapy (XRT) for patients with primary esophageal carcinoma (EC). PATIENTS AND METHODS: Eligibility included therapeutically naïve EC patients with clinical disease stages II, III, or IV. Initial doses and schedules for cycle 1 consisted of OXP 85 mg/m 2 on days 1, 15, and 29; PI 5-FU 180 mg/m 2 for 24 hours for 35 days; and XRT 1.8 Gy in 28 fractions starting on day 8. At completion of cycle 1, eligible patients could undergo an operation or begin cycle 2 without XRT. Postoperative patients were eligible for cycle 2. Stage IV patients were allowed three cycles in the absence of disease progression. OXP and 5-FU increases were based on dose-limiting toxicity (DLT) encountered in cohorts of three consecutive patients. RESULTS: Thirty-eight eligible patients received therapy: 22 noninvasively staged as IV and 16 noninvasively staged as II and III. Thirty-six patients completed cycle 1, 29 patients started cycle 2, and 24 patients completed cycle 2. The combined-modality therapy was well tolerated, but DLT prevented OXP and 5-FU escalation. No grade 4 hematologic toxicity was noted. Eleven grade 3 and two grade 4 clinical toxicities were noted in eight patients. After cycle 1, 29 patients (81%) had no cancer in the esophageal mucosa. Thirteen patients underwent an operation with intent to resect the esophagus; five patients (38%) exhibited pathologic complete responses. CONCLUSION: OXP 85 mg/m 2 on days 1, 15, and 29 administered with PI 5-FU and XRT is safe, tolerable, and seems effective against primary EC. The role of OXP in multimodality regimens against EC deserves further evaluation.
A Naturally Occurring Human Minidysferlin Protein Repairs Sarcolemmal Lesions in a Mouse Model of Dysferlinopathy
Authors: Martin Krahn, Nicolas Wein, Marc Bartoli, William Lostal, Sébastien Courrier, Nathalie Bourg-Alibert, Karine Nguyen, Christophe Vial, Nathalie Streichenberger, Véronique Labelle, Danielle DePetris, Christophe Pécheux, France Leturcq, Pierre Cau, Isabelle Richard, Nicolas Lévy
Journal: Science Translational Medicine (2010)

A naturally occurring miniversion of the dysferlin protein found in a patient shows that gene therapy by minigene transfer may be possible in dysferlinopathies.
Physician-diagnosed asthma and drug utilization in the European Community Respiratory Health Survey
Authors: C Janson, S Chinn, D Jarvis, P Burney
Journal: European Respiratory Journal (1997)

The aim of this analysis was to estimate the geographical variation in the prevalence of physician-diagnosed asthma and treatment practice for asthma in young adults. The results are based on an ecological analysis of 34 centres in 14 countries, in which a total of 17,029 randomly selected subjects (52% females, age 20-48 yrs) underwent a structured interview and spirometry as part of the European Community Respiratory Health Survey. The sample was enriched with 2,903 symptomatic subjects when investigating treatment in subjects with physician-diagnosed asthma. The prevalence of physician-diagnosed asthma was highest in New Zealand and Australia (11-13%) and lowest in Erfurt, Germany (1.2%) and Spain (1.5-3.0%). The reported use of antiasthma medication in the last 12 months was also highest in New Zealand and Australia (12-16%) and correlated closely with the prevalence of diagnosed asthma (r=0.89, p&lt;0.001). Herbal remedies against breathing problems had been used by 13% of subjects in Hamburg but the reported use of alternative remedies for breathing problems was low in most other centres. The use of inhaled anti-inflammatory drugs in subjects with physician-diagnosed asthma ranged from 49% in the UK to 17% in Italy and correlated with the prevalence of doctors' consultations within the last 12 months (r=0.66, p&lt;0.05). The prevalence of anti-inflammatory treatment was positively related to the prevalence of nocturnal asthma symptoms (p&lt;0.05). We conclude that there is a wide geographical variation in the prevalence of physician-diagnosed asthma and use of antiasthma medication. The geographical variation in the use of anti-inflammatory drugs among individuals with diagnosed asthma may be related to variations in asthma severity, as well as differences in treatment practices between countries.
Role of Endothelin Receptor Antagonists in the Treatment of Pulmonary Arterial Hypertension
Authors: Steven H. Abman
Journal: Annual Review of Medicine (2008)

Pulmonary arterial hypertension (PAH) is a severe disease with marked morbidity and mortality for which therapeutic strategies have been limited. Basic research in vascular biology has implicated endothelin-1 (ET-1) and its receptors (ET(A) and ET(B)) in diverse preclinical models of PAH, and ET-1 has been shown to contribute significantly to PAH in human patients. Despite the complexity of roles of the ET receptors in the development or reversal of PAH in the laboratory, the introduction of endothelin receptor antagonists (ETRAs) to clinical medicine has substantially expanded our therapeutic approach toward severe PAH. This article briefly reviews preclinical data and the current status of ETRAs in the clinical management of PAH.
Cancer Stem Cell Niche: The Place to Be
Authors: Tijana Borovski, Felipe De Sousa E Melo, Louis Vermeulen, Jan Paul Medema
Journal: Cancer Research (2011)

Tumors are being increasingly perceived as abnormal organs that, in many respects, recapitulate the outgrowth and differentiation patterns of normal tissues. In line with this idea is the observation that only a small fraction of tumor cells is capable of initiating a new tumor. Because of the features that these cells share with somatic stem cells, they have been termed cancer stem cells (CSC). Normal stem cells reside in a "stem cell niche" that maintains them in a stem-like state. Recent data suggest that CSCs also rely on a similar niche, dubbed the "CSC niche," which controls their self-renewal and differentiation. Moreover, CSCs can be generated by the microenvironment through induction of CSC features in more differentiated tumor cells. In addition to a role in CSC maintenance, the microenvironment is hypothesized to be involved in metastasis by induction of the epithelial-mesenchymal transition, leading to dissemination and invasion of tumor cells. The localization of secondary tumors also seems to be orchestrated by the microenvironment, which is suggested to form a premetastatic niche. Thus, the microenvironment seems to be of crucial importance for primary tumor growth as well as metastasis formation. Combined with its role in the protection of CSCs against genotoxic insults, these data strongly put forward the niche as an important target for novel therapies.
Androgen Receptor Levels and Association with PIK3CA Mutations and Prognosis in Breast Cancer
Authors: Ana M. Gonzalez-Angulo, Katherine Stemke-Hale, Shana L. Palla, Mark Carey, Roshan Agarwal, Funda Meric-Berstam, Tiffany A. Traina, Clifford Hudis, Gabriel N. Hortobagyi, William L. Gerald, Gordon B. Mills, Bryan T. Hennessy
Journal: Clinical Cancer Research (2009)

To examine the androgen receptor (AR) levels in breast cancer and to assess the impact of AR expression on patient outcomes.Reverse-phase protein arrays were used to measure AR levels and a mass spectroscopy-based approach was used to detect PIK3CA mutations. Means and SDs were generated for AR levels. Linear regression models were used to determine if AR levels differed by tumor subtype and PIK3CA mutation status. Two-sample t tests were used to identify pair-wise differences. Survival probabilities were estimated with the use of the Kaplan-Meier product and log-rank test.The median age was 59 years (23-89 years). Significant differences in AR levels existed among different breast tumor subtypes (highest in estrogen receptor-positive and/or progesterone receptor-positive tumors) as well as by PIK3CA mutation status (P < 0.0001 for both). AR levels were significantly higher in breast tumors with kinase domain PIK3CA mutations versus tumors that are wild type or with PIK3CA helical mutations (P = 0.017 and P < 0.0001, respectively). In 347 patients, dichotomized AR level by the median was a significant prognostic factor of recurrence-free survival (P = 0.0002) and overall survival (P = 0.004). High AR levels were associated with a significantly improved recurrence-free survival in 207 patients with early-stage estrogen/progesterone receptor-positive tumors after adjuvant hormonal therapy. A trend (P = 0.07) was found toward higher AR expression in PIK3CA mutant versus PIK3CA wild-type triple-negative breast tumors.AR levels may represent a prognostic marker in breast cancers and may provide a valuable tool for selecting treatment. There was an association of PIK3CA mutation (kinase domain) with increased AR levels.
Evaluation of the Clinical Benefit of Permixon and Tamsulosin in Severe BPH Patients—PERMAL Study Subset Analysis
Authors: Frans Debruyne, Peter Boyle, Fernando Calais Da Silva, Jay G Gillenwater, Freddie C Hamdy, Paul Perrin, Pierre Teillac, Remigio Vela-Navarrete, Jean-Pierre Raynaud, Claude C Schulman
Journal: European Urology (2004)