tbuckley/cabot-search huggingface dataset:
Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry
Authors: M. W. Donnino, J. D. Salciccioli, M. D. Howell, M. N. Cocchi, B. Giberson, K. Berg, S. Gautam, C. Callaway
Journal: BMJ (2014)

<b>Objective</b> To determine if earlier administration of epinephrine (adrenaline) in patients with non-shockable cardiac arrest rhythms is associated with increased return of spontaneous circulation, survival, and neurologically intact survival. <b>Design</b> Post hoc analysis of prospectively collected data in a large multicenter registry of in-hospital cardiac arrests (Get With The Guidelines-Resuscitation). <b>Setting</b> We utilized the Get With The Guidelines-Resuscitation database (formerly National Registry of Cardiopulmonary Resuscitation, NRCPR). The database is sponsored by the American Heart Association (AHA) and contains prospective data from 570 American hospitals collected from 1 January 2000 to 19 November 2009. <b>Participants</b> 119 978 adults from 570 hospitals who had a cardiac arrest in hospital with asystole (55%) or pulseless electrical activity (45%) as the initial rhythm. Of these, 83 490 arrests were excluded because they took place in the emergency department, intensive care unit, or surgical or other specialty unit, 10 775 patients were excluded because of missing or incomplete data, 524 patients were excluded because they had a repeat cardiac arrest, and 85 patients were excluded as they received vasopressin before the first dose of epinephrine. The main study population therefore comprised 25 095 patients. The mean age was 72, and 57% were men. <b>Main outcome measures</b> The primary outcome was survival to hospital discharge. Secondary outcomes included sustained return of spontaneous circulation, 24 hour survival, and survival with favorable neurologic status at hospital discharge. <b>Results</b> 25 095 adults had in-hospital cardiac arrest with non-shockable rhythms. Median time to administration of the first dose of epinephrine was 3 minutes (interquartile range 1-5 minutes). There was a stepwise decrease in survival with increasing interval of time to epinephrine (analyzed by three minute intervals): adjusted odds ratio 1.0 for 1-3 minutes (reference group); 0.91 (95% confidence interval 0.82 to 1.00; P=0.055) for 4-6 minutes; 0.74 (0.63 to 0.88; P&lt;0.001) for 7-9 minutes; and 0.63 (0.52 to 0.76; P&lt;0.001) for &gt;9 minutes. A similar stepwise effect was observed across all outcome variables. <b>Conclusions</b> In patients with non-shockable cardiac arrest in hospital, earlier administration of epinephrine is associated with a higher probability of return of spontaneous circulation, survival in hospital, and neurologically intact survival.
Effects of written action plan adherence on COPD exacerbation recovery
Authors: E. W. M. A. Bischoff, D. H. Hamd, M. Sedeno, A. Benedetti, T. R. J. Schermer, S. Bernard, F. Maltais, J. Bourbeau
Journal: Thorax (2010)

<h3>Background</h3> The effects of written action plans on recovery from exacerbations of chronic obstructive pulmonary disease (COPD) have not been well studied. The aims of this study were to assess the effects of adherence to a written action plan on exacerbation recovery time and unscheduled healthcare utilisation and to explore factors associated with action plan adherence. <h3>Methods</h3> This was a 1-year prospective cohort study embedded in a randomised controlled trial. Exacerbation data were recorded for 252 patients with COPD who received a written action plan for prompt treatment of exacerbations with the instructions to initiate standing prescriptions for both antibiotics and prednisone within 3 days of exacerbation onset. Following the instructions was defined as adherence to the action plan. <h3>Results</h3> From the 288 exacerbations reported by 143 patients, start dates of antibiotics or prednisone were provided in 217 exacerbations reported by 119 patients (53.8% male, mean age 65.4 years, post-bronchodilator forced expiratory volume in 1 s (FEV<sub>1</sub>) 43.9% predicted). In 40.1% of exacerbations, patients adhered to their written action plan. Adherence reduced exacerbation recovery time with statistical (p=0.0001) and clinical (−5.8 days) significance, but did not affect unscheduled healthcare utilisation (OR 0.94, 95% CI 0.49 to 1.83). Factors associated with an increased likelihood of adherence were influenza vaccination, cardiac comorbidity, younger age and lower FEV<sub>1</sub> as percentage predicted. <h3>Conclusions</h3> This study shows that adherence to a written action plan is associated with a reduction in exacerbation recovery time by prompt treatment. Knowing the factors that are associated with proper and prompt utilisation of an action plan permits healthcare professionals to better focus their self-management support on appropriate patients.
Identification of somatic mutations in EGFR/KRAS/ALK-negative lung adenocarcinoma in never-smokers
Authors: Jin Woo Ahn, Han Sang Kim, Jung-Ki Yoon, Hoon Jang, Soo Min Han, Sungho Eun, Hyo Sup Shim, Hyun-Jung Kim, Dae Joon Kim, Jin Gu Lee, Chang Young Lee, Mi Kyung Bae, Kyung Young Chung, Ji Ye Jung, Eun Young Kim, Se Kyu Kim, Joon Chang, Hye Ryun Kim, Joo Hang Kim, Min Goo Lee, Byoung Chul Cho, Ji Hyun Lee, Duhee Bang
Journal: Genome Medicine (2014)

Abstract Background Lung adenocarcinoma is a highly heterogeneous disease with various etiologies, prognoses, and responses to therapy. Although genome-scale characterization of lung adenocarcinoma has been performed, a comprehensive somatic mutation analysis of EGFR / KRAS / ALK -negative lung adenocarcinoma in never-smokers has not been conducted. Methods We analyzed whole exome sequencing data from 16 EGFR / KRAS / ALK -negative lung adenocarcinomas and additional 54 tumors in two expansion cohort sets. Candidate loci were validated by target capture and Sanger sequencing. Gene set analysis was performed using Ingenuity Pathway Analysis. Results We identified 27 genes potentially implicated in the pathogenesis of lung adenocarcinoma. These included targetable genes involved in PI3K/mTOR signaling ( TSC1 , PIK3CA , AKT2 ) and receptor tyrosine kinase signaling ( ERBB4 ) and genes not previously highlighted in lung adenocarcinomas, such as SETD2 and PBRM1 (chromatin remodeling), CHEK2 and CDC27 (cell cycle), CUL3 and SOD2 (oxidative stress), and CSMD3 and TFG (immune response). In the expansion cohort (N = 70), TP53 was the most frequently altered gene (11%), followed by SETD2 (6%), CSMD3 (6%), ERBB2 (6%), and CDH10 (4%). In pathway analysis, the majority of altered genes were involved in cell cycle/DNA repair ( P &lt;0.001) and cAMP-dependent protein kinase signaling ( P &lt;0.001). Conclusions The genomic makeup of EGFR / KRAS / ALK -negative lung adenocarcinomas in never-smokers is remarkably diverse. Genes involved in cell cycle regulation/DNA repair are implicated in tumorigenesis and represent potential therapeutic targets.
Targeted Drug Delivery to Flow-Obstructed Blood Vessels Using Mechanically Activated Nanotherapeutics
Authors: Netanel Korin, Matthew J. Gounis, Ajay K. Wakhloo, Donald E. Ingber
Journal: JAMA Neurology (2014)

Obstruction of normal blood flow, which occurs in a variety of diseases, including thromboembolism in stroke and atherosclerosis, is a leading cause of death and long-term adult disability in the Western world. This review focuses on a novel nanotherapeutic drug-delivery platform that is mechanically activated within blood vessels by high-fluid shear stresses to selectively target drugs to sites of vascular obstruction. In vitro and in vivo studies have shown that this approach can be used to efficiently lyse clots using a significantly lower amount of thrombolytic drug than is required when administered in a soluble formulation. This nanotherapeutic strategy can potentially improve both the efficacy and safety of thrombolytic drugs, particularly in patients who are at high risk for brain hemorrhage, and thus provide a new approach for the treatment of many life-threatening and debilitating vascular disorders.
Interaction of Epinephrine and Ouabain on Automaticity of Canine Purkinje Fibers
Authors: WARREN W. TSE, JAOK HAN
Journal: Circulation Research (1974)

The interaction of ouabain and epinephrine on diastolic depolarization of canine Purkinje fibers was studied using conventional microelectrode techniques. When the Purkinje fibers were treated with ouabain alone, they developed slow diastolic depolarization accompanied by a proportionate decrease in the maximum diastolic potential. When these digitalized Purkinje fibers were further treated with epinephrine, the rate of these changes was greatly accelerated, resulting in rapid spontaneous activity in some Purkinje fibers. The rate of development of increased automaticity observed in the preparations treated with both ouabain and epinephrine was two to three times faster than that observed in the preparations exposed to ouabain alone. Epinephrine alone at the same concentration caused minimal changes in diastolic depolarization of these preparations. Propranolol in a beta-receptor blocking dose prevented the potentiating effect of epinephrine but did not interfere with the effect of ouabain on diastolic depolarization of Purkinje fibers. It is concluded that epinephrine potentiates the ouabain-induced increase in automaticity of Purkinje fibers by stimulating beta receptors.
Primary Care–Relevant Interventions for Tobacco Use Prevention and Cessation in Children and Adolescents: A Systematic Evidence Review for the U.S. Preventive Services Task Force
Authors: Carrie D. Patnode, Elizabeth O'Connor, Evelyn P. Whitlock, Leslie A. Perdue, Clara Soh, Jack Hollis
Journal: Annals of Internal Medicine (2013)

Background: Interventions to prevent smoking uptake or encourage cessation among young persons might help prevent tobacco-related illness. Purpose: To review the evidence for the efficacy and harms of primary care–relevant interventions that aim to reduce tobacco use among children and adolescents. Data Sources: Three systematic reviews that collectively covered the relevant literature; MEDLINE, PsycINFO, the Cochrane Central Register of Controlled Trials, and the Database of Abstracts of Reviews of Effects through 14 September 2012; and manual searches of reference lists and gray literature. Study Selection: Two investigators independently reviewed 2453 abstracts and 111 full-text articles. English-language trials of behavior-based or medication interventions that were relevant to primary care and reported tobacco use, health outcomes, or harms were included. Data Extraction: One investigator abstracted data from good- and fair-quality trials into an evidence table, and a second checked these data. Data Synthesis: 19 trials (4 good-quality and 15 fair-quality) that were designed to prevent tobacco use initiation or promote cessation (or both) and reported self-reported smoking status or harms were included. Pooled analyses from a random-effects meta-analysis suggested a 19% relative reduction (risk ratio, 0.81 [95% CI, 0.70 to 0.93]; absolute risk difference, −0.02 [CI, −0.03 to 0.00]) in smoking initiation among participants in behavior-based prevention interventions compared with control participants. Neither behavior-based nor bupropion cessation interventions improved cessation rates. Findings about the harms related to bupropion use were mixed. Limitations: No studies reported health outcomes. Interventions and measures were heterogeneous. Most trials examined only cigarette smoking. The body of evidence was largely published 5 to 15 years ago. Conclusion: Primary care–relevant interventions may prevent smoking initiation over 12 months in children and adolescents. Primary Funding Source: Agency for Healthcare Research and Quality.
An Entirely Subcutaneous Implantable Cardioverter–Defibrillator
Authors: Gust H. Bardy, Warren M. Smith, Margaret A. Hood, Ian G. Crozier, Iain C. Melton, Luc Jordaens, Dominic Theuns, Robert E. Park, David J. Wright, Derek T. Connelly, Simon P. Fynn, Francis D. Murgatroyd, Johannes Sperzel, Jörg Neuzner, Stefan G. Spitzer, Andrey V. Ardashev, Amo Oduro, Lucas Boersma, Alexander H. Maass, Isabelle C. Van Gelder, Arthur A. Wilde, Pascal F. van Dessel, Reinoud E. Knops, Craig S. Barr, Pierpaolo Lupo, Riccardo Cappato, Andrew A. Grace
Journal: New England Journal of Medicine (2010)

Implantable cardioverter-defibrillators (ICDs) prevent sudden death from cardiac causes in selected patients but require the use of transvenous lead systems. To eliminate the need for venous access, we designed and tested an entirely subcutaneous ICD system.First, we conducted two short-term clinical trials to identify a suitable device configuration and assess energy requirements. We evaluated four subcutaneous ICD configurations in 78 patients who were candidates for ICD implantation and subsequently tested the best configuration in 49 additional patients to determine the subcutaneous defibrillation threshold in comparison with that of the standard transvenous ICD. Then we evaluated the long-term use of subcutaneous ICDs in a pilot study, involving 6 patients, which was followed by a trial involving 55 patients.The best device configuration consisted of a parasternal electrode and a left lateral thoracic pulse generator. This configuration was as effective as a transvenous ICD for terminating induced ventricular fibrillation, albeit with a significantly higher mean (+/-SD) energy requirement (36.6+/-19.8 J vs. 11.1+/-8.5 J). Among patients who received a permanent subcutaneous ICD, ventricular fibrillation was successfully detected in 100% of 137 induced episodes. Induced ventricular fibrillation was converted twice in 58 of 59 patients (98%) with the delivery of 65-J shocks in two consecutive tests. Clinically significant adverse events included two pocket infections and four lead revisions. After a mean of 10+/-1 months, the device had successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia.In small, nonrandomized studies, an entirely subcutaneous ICD consistently detected and converted ventricular fibrillation induced during electrophysiological testing. The device also successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia. (ClinicalTrials.gov numbers, NCT00399217 and NCT00853645.)
Multicenter Validation of a Gene Expression–Based Prognostic Signature in Lymph Node–Negative Primary Breast Cancer
Authors: John A. Foekens, David Atkins, Yi Zhang, Fred C.G.J. Sweep, Nadia Harbeck, Angelo Paradiso, Tanja Cufer, Anieta M. Sieuwerts, Dmitri Talantov, Paul N. Span, Vivianne C.G. Tjan-Heijnen, Alfredo F. Zito, Katja Specht, Heinz Hoefler, Rastko Golouh, Francesco Schittulli, Manfred Schmitt, Louk V.A.M. Beex, Jan G.M. Klijn, Yixin Wang
Journal: Journal of Clinical Oncology (2006)

We previously identified in a single-center study a 76-gene prognostic signature for lymph node-negative (LNN) breast cancer patients. The aim of this study was to validate this gene signature in an independent more diverse population of LNN patients from multiple institutions.Using custom-designed DNA chips we analyzed the expression of the 76 genes in RNA of frozen tumor samples from 180 LNN patients who did not receive adjuvant systemic treatment.In this independent validation, the 76-gene signature was highly informative in identifying patients with distant metastasis within 5 years (hazard ratio, [HR], 7.41; 95% CI, 2.63 to 20.9), even when corrected for traditional prognostic factors in multivariate analysis (HR, 11.36; 95% CI, 2.67 to 48.4). The actuarial 5- and 10-year distant metastasis-free survival were 96% (95% CI, 89% to 99%) and 94% (95% CI, 83% to 98%), respectively, for the good profile group and 74% (95% CI, 64% to 81%) and 65% (53% to 74%), respectively for the poor profile group. The sensitivity for 5-yr distant metastasis-free survival was 90%, and the specificity was 50%. The positive and negative predictive values were 38% (95% CI, 29% to 47%) and 94% (95% CI, 86% to 97%), respectively. The 76-gene signature was confirmed as a strong prognostic factor in subgroups of estrogen receptor-positive patients, pre- and postmenopausal patients, and patients with tumor sizes 20 mm or smaller. The subgroup of patients with estrogen receptor-negative tumors was considered too small to perform a separate analysis.Our data provide a strong methodologic and clinical multicenter validation of the predefined prognostic 76-gene signature in LNN breast cancer patients.
Perioperative Cardiovascular Care for Patients Undergoing Noncardiac Surgical Intervention
Authors: Kim A. Eagle, Prashant Vaishnava, James B. Froehlich
Journal: JAMA Internal Medicine (2015)

The field of perioperative medicine has garnered legitimacy during the past 3 decades. Adverse cardiovascular events in the perioperative period account for significant morbidity and mortality. Although testing patients preoperatively to detect ischemia and identify those who may benefit from modifications in care is a tempting strategy, risk assessment should account for posterior probability. Validated risk stratification tools, such as the Revised Cardiac Risk Index or the National Surgical Quality Improvement Program risk calculator, can assist in the identification of patients for whom preoperative noninvasive testing is justified and may change the plan of care. Furthermore, current guidelines emphasize that prophylactic coronary revascularization should not be performed exclusively for the purposes of reducing the risk of perioperative events. There has been enthusiasm for medical therapies that may reduce the risk of adverse cardiovascular events in the perioperative period. Current guidelines encourage the perioperative use of β-blockade in patients already receiving such therapy and caution against initiating such therapy on the day of the surgical procedure. Reduction of morbidity and mortality in the perioperative period relies on an understanding of the myriad physiological perturbations in this period and thoughtful selection of patients for further testing and treatment.
Studies with an enthesis index as a method of clinical assessment in ankylosing spondylitis.
Authors: M Mander, J M Simpson, A McLellan, D Walker, J A Goodacre, W C Dick
Journal: Annals of the Rheumatic Diseases (1987)

The histopathological characteristic of ankylosing spondylitis (AS) is the presence of chronic enthesitis. Our aim was to develop a clinical measurement of the severity of tenderness over entheses. The scoring system was based on the patients9 response to palpation over entheses easily accessible to examination. The enthesis index (EI) correlated with pain (r = 0.67, p less than 0.01) and stiffness (r = 0.46, p less than 0.05) scores. A single, blind, crossover study was conducted to determine the sensitivity of the index to change in clinical state associated with non-steroidal antirheumatic drug therapy and to record the interobserver variability. The index showed significantly lower scores after one week9s drug treatment (p less than 0.05). The EI is a convenient, non-invasive measure of disease severity in patients with AS. Potential applications include the assessment of enthesitis in other polyarthritides and a means of distinguishing clinically between severity of enthesitis and synovitis in different types of polyarthritis.
Palliative and end-of-life care for patients with severe COPD
Authors: J. R. Curtis
Journal: European Respiratory Journal (2007)

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. For many patients, maximal therapy for COPD produces only modest or incomplete relief of disabling symptoms and these symptoms result in a significantly reduced quality of life. Despite the high morbidity and mortality associated with severe COPD, many patients receive inadequate palliative care. There are several reasons for this. First, patient-physician communication about palliative and end-of-life care is infrequent and often of poor quality. Secondly, the uncertainty in predicting prognosis for patients with COPD makes communication about end-of-life care more difficult. Consequently, patients and their families frequently do not understand that severe COPD is often a progressive and terminal illness. The purpose of the present review is to summarise recent research regarding palliative and end-of-life care for patients with COPD. Recent studies provide insight and guidance into ways to improve communication about end-of-life care and thereby improve the quality of palliative and end-of-life care the patients receive. Two areas that may influence the quality of care are also highlighted: 1) the role of anxiety and depression, common problems for patients with COPD; and 2) the importance of advance care planning. Improving communication represents an important opportunity for the improvement of the quality of palliative and end-of-life care received by these patients.
CK2 Inhibits Apoptosis and Changes Its Cellular Localization Following Ionizing Radiation
Authors: Kazuhiko Yamane, Timothy J. Kinsella
Journal: Cancer Research (2005)

Abstract In this study, we show that CK2 (casein kinase II, CKII) participates in apoptotic responses following ionizing radiation (IR). Using HeLa human cervical carcinoma cells, we find that transfection of small interfering RNA against the CK2 α and/or α′ catalytic subunits results in enhanced apoptosis following IR damage as measured by flow cytometry techniques, compared with a control small interfering RNA. Within 2 to 6 hours of IR, CK2 α partially localizes to perinuclear structures, whereas a marked nuclear localization of α′ occurs. Treatment with a pan-caspase inhibitor or transfection of ARC (apoptosis repressor with caspase recruitment domain) suppresses the apoptotic response to IR in the CK2-reduced cells, indicating involvement of caspases. Additionally, we find that CK2 α and/or α′ reduction affects cell cycle progression independent of IR damage in this human cell line. However, the G2-M checkpoint following IR is not affected in CK2 α- and/or α′-reduced cells. Thus, our data suggest that CK2 participates in inhibition of apoptosis and negatively regulates caspase activity following IR damage.