tbuckley/cabot-search huggingface dataset:
Association Between Insomnia Symptoms and Mortality
Authors: Yanping Li, Xuehong Zhang, John W. Winkelman, Susan Redline, Frank B. Hu, Meir Stampfer, Jing Ma, Xiang Gao
Journal: Circulation (2013)

Background— Insomnia complaints are common in older adults and may be associated with mortality risk. However, evidence regarding this association is mixed. Thus, we prospectively examined whether men with insomnia symptoms had an increased risk of mortality during 6 years of follow-up. Methods and Results— A prospective cohort study of 23 447 US men participating in the Health Professionals Follow-Up Study and free of cancer, reported on insomnia symptoms in 2004, were followed through 2010. Deaths were identified from state vital statistic records, the National Death Index, family reports, and the postal system. We documented 2025 deaths during 6 years of follow-up (2004–2010). The multivariable-adjusted hazard ratios of total mortality were 1.25 (95% confidence interval [CI], 1.04–1.50) for difficulty initiating sleep, 1.09 (95% CI, 0.97–1.24) for difficulty maintaining sleep, 1.04 (95% CI, 0.88–1.22) for early-morning awakenings, and 1.24 (95% CI, 1.05–1.46) for nonrestorative sleep, comparing men with those symptoms most of the time with men without those symptoms, after adjusting for age, lifestyle factors, and presence of common chronic conditions. Men with difficulty initiating sleep and nonrestorative sleep most of the time had a 55% (hazard ratio, 1.55; 95% CI, 1.19–2.04; P -trend=0.01) and 32% (hazard ratio, 1.32; 95% CI, 1.02–1.72; P -trend=0.002) increased risk of cardiovascular disease mortality, respectively, relative to men without those symptoms. Conclusion— Some insomnia symptoms, especially difficulty initiating asleep and nonrestorative sleep, are associated with a modestly higher risk of mortality.
A pragmatic randomised trial of stretching before and after physical activity to prevent injury and soreness
Authors: Gro Jamtvedt, Robert D Herbert, Signe Flottorp, Jan Odgaard-Jensen, Kari Håvelsrud, Alex Barratt, Erin Mathieu, Amanda Burls, Andrew D Oxman
Journal: British Journal of Sports Medicine (2009)

Objective To determine the effects of stretching before and after physical activity on risks of injury and soreness in a community population. Design Internet-based pragmatic randomised trial conducted between January 2008 and January 2009. Setting International. Participants A total of 2377 adults who regularly participated in physical activity. Interventions Participants in the stretch group were asked to perform 30 s static stretches of seven lower limb and trunk muscle groups before and after physical activity for 12 weeks. Participants in the control group were asked not to stretch. Main outcome measurements Participants provided weekly on-line reports of outcomes over 12 weeks. Primary outcomes were any injury to the lower limb or back, and bothersome soreness of the legs, buttocks or back. Injury to muscles, ligaments and tendons was a secondary outcome. Results Stretching did not produce clinically important or statistically significant reductions in all-injury risk (HR=0.97, 95% CI 0.84 to 1.13), but did reduce the risk of experiencing bothersome soreness (mean risk of bothersome soreness in a week was 24.6% in the stretch group and 32.3% in the control group; OR=0.69, 95% CI 0.59 to 0.82). Stretching reduced the risk of injuries to muscles, ligaments and tendons (incidence rate of 0.66 injuries per person-year in the stretch group and 0.88 injuries per person-year in the control group; HR=0.75, 95% CI 0.59 to 0.96). Conclusion Stretching before and after physical activity does not appreciably reduce all-injury risk but probably reduces the risk of some injuries, and does reduce the risk of bothersome soreness. Trial registration anzctr.org.au 12608000044325.
Methotrexate: the gold standard without standardisation
Authors: J. Kay, R. Westhovens
Journal: Annals of the Rheumatic Diseases (2009)

Even in the current era of biological targeted therapies, methotrexate (MTX) remains the initial preferred antirheumatic drug and is widely prescribed for patients with rheumatoid arthritis (RA). The combination of its perceived efficacy, acceptable safety profile and low cost, as well as decades of clinical experience with its use that have been accumulated by current and previous generations of rheumatologists, make MTX the cornerstone of treatment for RA and the anchor drug for combination with each of the newer biological agents.

Four papers in this journal1–4 provide general guidance for the use of MTX, its optimal dose and route of administration and its potential toxicity ( see articles on pages 1086, 1094, 1100 and 1105 ). This “3E Initiative,” supported by an unrestricted educational grant from Abbott, began with an extensive systematic literature review (Evidence) that was discussed by each of 17 national scientific committees (Expertise). These national groups combined to form a broad international panel of experts who shared (Exchange) the individual national recommendations. While acknowledging changes in MTX use over time and in different geographical regions, the authors propose consensus guidelines for the use of MTX to manage patients with RA.

Of the “Evidence” accumulated by the authors’ search of the medical literature, nearly half (9/19) of the studies of MTX use that were included in their meta-analysis had been published during the last decade of the 20th century.4 The authors acknowledge that, during this era, MTX was prescribed at lower doses than are currently used. Also, folic acid supplementation was not administered as systematically and MTX doses were escalated less rapidly than is the current custom. In addition, the disease-modifying antirheumatic drugs (DMARDs) with which MTX was combined in these studies included DMARDs not commonly used in current clinical practice (such as intramuscular …
Pulmonary Epithelial Cell Injury and Alveolar–Capillary Permeability in Berylliosis
Authors: YOSHIKAZU INOUE, ELIZABETH BARKER, ELAINE DANILOFF, NOBUOKI KOHNO, KUNIO HIWADA, LEE S. NEWMAN
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Inhaled beryllium induces specific sensitization and nonspecific effects leading to chronic beryllium disease (CBD). It is not known whether beryllium induces epithelial cell injury and increases alveolar-capillary leak. We hypothesize that lung injury is an early event in this disease and that markers of lung injury reflect severity of CBD. We measured serum and bronchoalveolar lavage fluid (BALF) KL-6 level, a marker of epithelial cell injury, and BALF/serum albumin, a marker of alveolar-capillary permeability, in 26 patients with CBD, 15 beryllium-sensitized subjects without disease (BeS), and 32 control subjects (Ctrl). We examined the association of these markers, BAL cellularity, pulmonary function, gas exchange, serum angiotensin-converting enzyme, chest radiograph, the effects of glucocorticoid therapy, and clinical course. BALF/serum albumin and serum KL-6 increased in CBD and were discriminative markers for CBD. BALF KL-6 and BALF/serum albumin reflected mainly lung cellular and granulomatous inflammation. Serum KL-6, like BALF KL-6, was associated with permeability change and reflected functional and radiologic abnormalities. Serum KL-6 detected early lung injury in BeS. Epithelial injury and permeability changes occur early in CBD, indicating disease severity. Monitoring of these events with serum KL-6 may be useful for management of CBD.
Effectiveness of nurse delivered endoscopy: findings from randomised multi-institution nurse endoscopy trial (MINuET)
Authors: J. Williams, I. Russell, D. Durai, W. Y. Cheung, A. Farrin, K. Bloor, S. Coulton, G. Richardson
Journal: BMJ (2009)

<b>Objective</b> To compare the clinical effectiveness of doctors and nurses in undertaking upper and lower gastrointestinal endoscopy. <b>Design</b> Pragmatic trial with Zelen's randomisation before consent to minimise distortion of existing practice. <b>Setting</b> 23 hospitals in the United Kingdom. In six hospitals, nurses undertook both upper and lower gastrointestinal endoscopy, yielding a total of 29 centres. <b>Participants</b> 67 doctors and 30 nurses. Of 4964 potentially eligible patients, we randomised 4128 (83%) and recruited 1888 (38%) from July 2002 to June 2003. <b>Interventions</b> Diagnostic upper gastrointestinal endoscopy and flexible sigmoidoscopy, undertaken with or without sedation, with the standard preparation, techniques, and protocols of participating hospitals. After referral for either procedure, patients were randomised between doctors and nurses. <b>Main outcome measures</b> Gastrointestinal symptom rating questionnaire (primary outcome), gastrointestinal endoscopy satisfaction questionnaire and state-trait anxiety inventory (all analysed by intention to treat); immediate and delayed complications; quality of examination and corresponding report; patients' preferences for operator; and new diagnoses at one year (all analysed according to who carried out the procedure). <b>Results</b> There was no significant difference between groups in outcome at one day, one month, or one year after endoscopy, except that patients were more satisfied with nurses after one day. Nurses were also more thorough than doctors in examining the stomach and oesophagus. While quality of life scores were slightly better in patients the doctor group, this was not statistically significant. <b>Conclusions</b> Diagnostic endoscopy can be undertaken safely and effectively by nurses. <b>Trial registration</b> International standard RCT 82765705
Building a Personalized Medicine Infrastructure at a Major Cancer Center
Authors: Funda Meric-Bernstam, Carol Farhangfar, John Mendelsohn, Gordon B. Mills
Journal: Journal of Clinical Oncology (2013)

Our understanding of cancer biology is rapidly increasing, as is the availability and affordability of high throughput technologies for comprehensive molecular characterization of tumors and the individual's own genetic makeup. Thus, the time is right to implement personalized molecular medicine for all patients with cancer. Personalized approaches span the full cancer care spectrum from risk stratification to prevention, screening, therapy, and survivorship programs. Several molecular therapeutics have entered clinical trials creating a huge opportunity to couple genomic markers with this emerging drug tool kit. The number of patients managed in major cancer centers creates a challenge to the implementation of genomic technologies required to successfully deliver on the promise of personalized cancer care. This requires a major investment in infrastructure to facilitate rapid deployment of multiplex, cost-effective, and tissue-sparing assays relevant across multiple tumor lineages in the Clinical Laboratory Improvement Amendments (CLIA) environment. Efforts must be made to ensure that assays are accessible to patients most likely to be enrolled onto molecular-marker-driven trials and that the tests are billable and payable, which will make them accessible to a wide range of patients. As the number of patients and aberrations increase, it will become critical to provide decision support for genomic medicine. Institutional commitment is needed to optimize accessibility and quality of research biopsies and to facilitate novel personalized cancer therapy trials. This article will focus on the challenges and opportunities that accompany the building of infrastructure for personalized cancer therapy.
An unusual case of congenital short trachea with very long bronchi mimicking bronchial asthma
Authors: F Ravenna
Journal: Thorax (2002)

Case reports of a short trachea with early branching of the main bronchi are uncommon. The case is presented of a 64 year old woman with upper airway obstruction due to this anatomical abnormality which caused breathlessness and wheezing that was misdiagnosed (and treated) as bronchial asthma for many years.
Effect of long-term digoxin therapy on autonomic function in patients with chronic heart failure
Authors: Henry Krum, Thomas Bigger, Rochelle L. Goldsmith, Milton Packer
Journal: Journal of the American College of Cardiology (1995)

Objectives.This study was conducted to determine the effect of long-term digoxin therapy on autonomic function in patients with mild to moderate chronic heart failure. Background.Chronic heart failure is characterized by increased sympathetic activity and decreased parasympathetic activity. Intravenous digitalis has been found to reduce sympathetic activity immediately in these patients, but whether short-term neurohormonal effects are sustained during long-term oral therapy has not been assessed. Methods.We determined sympathetic activity in 26 patients with heart failure by measuring plasma norepinephrine levels and parasympathetic activity from variables of heart period variability derived from 24-h ambulatory electrocardiographic Holter recordings obtained before and after 4 to 8 weeks of digoxin therapy. Results.After digoxin therapy, plasma norepinephrine decreased significantly from a mean ± SEM of 552 ± 80 to 390 ± 37 ng/ml. In addition, the RR interval increaed significantly from 719 ± 19 to 771 ± 20 ms. High frequency power increased from 84 ± 24 to 212 ± 72ms2, and the root mean square of successive differences in RR interval increased from 203 ± 1.8 to 27.0 ± 3.4 ms, indicating a substantial increase in parasympathetic activity. Low frequency power, an index of baroreflex activity, was also significantly increased (239 ± 80 to 482 ± 144 ms2) by digoxin therapy. Conclusions.These results indicate 1) that long-term therapy with digoxin acts to ameliorate the autonomic dysfunction of patients with heart failure, and 2) that the short-term neurohormonal effects of digoxin are sustained during prolonged treatment with the drug.
Inclusion of patients with acute leukemia in clinical trials: a prospective multicenter survey of 1066 cases
Authors: A. Dechartres, S. Chevret, J. Lambert, F. Calvo, V. Lévy
Journal: Annals of Oncology (2010)

Background: To estimate the prevalence of adults and children with acute leukemia (AL) included in clinical trials and to determine factors associated with noninclusion.Patients and methods: All patients with AL admitted to the 17 departments managing AL in Paris area from 2005 to 2007 were prospectively included. Clinical data, therapeutic decisions, and enrollment in trials were recorded. Reasons that prevented accrual were identified.Results: A total of 1066 admissions with AL (85% of adults) were recorded, and 34 trials were open. In adults, the rate of inclusion in a trial was 25% [95% confidence interval (CI) 21% to 28%] for acute myeloid leukemia (AML) and 23% (95% CI 17% to 29%) for acute lymphoid leukemia (ALL). In children, the rate of inclusion was 58% (95% CI 41% to 73%) for AML and 64% (95% CI 55% to 72%) for ALL. The rate of inclusion varied across centers, with a significant increase when they were involved in clinical research. Patients included in trials differed significantly from those not included according to age, primary/secondary AL, leukemia type, results of cytogenetic analyses, and stage of disease.Conclusions: The rate of inclusion is higher than in oncology. This difference may be explained by management in specialized centers often involved in clinical research.
Oxygen toxicity during artificial ventilation
Authors: R. A. L. Brewis
Journal: Thorax (1969)

Repeated pulmonary collapse and changes suggestive of a severe alveolar-capillary diffusion defect were observed over a period of 20 days in a patient who was receiving artificial ventilation because of status epilepticus. Profound cyanosis followed attempts to discontinue assisted ventilation. The Bird Mark 8 respirator employed was found to be delivering approximately 90% oxygen on the air-mix setting and pulmonary oxygen toxicity was suspected. Radiological improvement and progressive resolution of the alveolar-capillary block followed gradual reduction of the inspired concentration over nine days. The management and prevention of this complication are discussed. The inspired oxygen concentration should be routinely monitored in patients receiving intermittent positive pressure ventilation, and the concentration should not be higher than that required to maintain adequate oxygenation. The Bird Mark 8 respirator has an inherent tendency to develop high oxygen concentrations on the air-mix setting, and the machine should therefore be driven from a compressed air source unless high concentrations of oxygen are essential.
Investigation of the origin of the impedance cardiogram by means of exchange transfusion with stroma free haemoglobin solution in the dog
Authors: K. R Visser, R. Lamberts, W. G Zijlstra
Journal: Cardiovascular Research (1990)

PURPOSE OF INVESTIGATION - To determine the contribution of variations in orientation of erythrocytes (orientation effect) to the heart synchronous variations in thoracic impedance in impedance cardiography. DESIGN - The blood of four dogs was gradually replaced by stroma free haemoglobin solution, causing a decrease in resistivity and orientation effect. The decrease in orientation effect was used to determine the contribution of the orientation effect using an extended form of the "parallel conductor" model of the thorax (parallel connection of a tissue admittance Yt and a blood conductance Gb). SUBJECTS - Four adult splenectomised mongrel dogs. MEASUREMENTS and RESULTS - Packed cell volume and resistivity at body temperature of every volume of circulating fluid removed was measured. Real and imaginary parts of the transthoracic impedance and the modulus of the heart synchronous impedance variations were measured just before each exchange. The parallel conductor model was extended to account for the influence on Gb of packed cell volume and orientation of erythrocytes. Applying this extended model, the average variations in Gb at a packed cell volume of 40% were estimated to be 7.46%:3.03% due to volume variations, 4.43% due to orientation effect. After further extending the model to account for the influence of small changes in blood pressure and heart rate, the average volume variations were estimated to range from 2.8% to 3.3% and the average orientation effect from 4.1% to 4.7% at a packed cell volume of 40%. CONCLUSION - Resistivity of the blood is far from constant and the contributions of variations in blood conductivity and volume to the heart synchronous thoracic impedance are of comparable magnitude. The contribution of the volume variations is the sum of the volume variations in the contributing intrathoracic vessels. The effects of variations in orientation are added up in proportion to the relative volumes of the contributing vessels. The extensions of the parallel conductor model brought out all physiological factors determining the heart synchronous thoracic impedance variations: pulse pressures and flows, mean pressures and flows, compliances of all contributing blood vessels, packed cell volume and heart rate, as well as the relevant properties of blood: the relations between volume, flow and orientation effect and the change in orientation effect during decelerating flow.
Measuring tumor response and shape change on CT: esophageal cancer as a paradigm
Authors: L.H. Schwartz, J.A.C. Colville, M.S. Ginsberg, L. Wang, M. Mazumdar, J. Kalaigian, H. Hricak, D. Ilson, G.K. Schwartz
Journal: Annals of Oncology (2006)
Effects of pyrazinamide, probenecid, and benzbromarone on renal excretion of oxypurinol.
Authors: T Yamamoto, Y Moriwaki, S Takahashi, M Suda, K Higashino
Journal: Annals of the Rheumatic Diseases (1991)

The effects of pyrazinamide, probenecid, and benzbromarone on renal excretion of oxypurinol were investigated. Pyrazinamide decreased the mean (SEM) fractional clearance of oxypurinol from 19.2 (2.1) to 8.8 (1.5). Probenecid increased the fractional clearance of oxypurinol from 14.1 (3.5) to 24.8 (4.1). Benzbromarone increased the fractional clearance of oxypurinol from 15.6 (2.3) to 33.8 (2.8). These results suggest that oxypurinol may be secreted by 9an organic acid system9 and that oxypurinol is reabsorbed at a putative postsecretory site of the renal tubules.
Mutations in HFE2 cause iron overload in chromosome 1q–linked juvenile hemochromatosis
Authors: George Papanikolaou, Mark E Samuels, Erwin H Ludwig, Marcia L E MacDonald, Patrick L Franchini, Marie-Pierre Dubé, Lisa Andres, Julie MacFarlane, Nikos Sakellaropoulos, Marianna Politou, Elizabeta Nemeth, Jay Thompson, Jenni K Risler, Catherine Zaborowska, Ryan Babakaiff, Christopher C Radomski, Terry D Pape, Owen Davidas, John Christakis, Pierre Brissot, Gillian Lockitch, Tomas Ganz, Michael R Hayden, Y Paul Goldberg
Journal: Nature Genetics (2003)
Substance use disorders, psychiatric disorders, and mortality after release from prison: a nationwide longitudinal cohort study
Authors: Zheng Chang, Paul Lichtenstein, Henrik Larsson, Seena Fazel
Journal: The Lancet Psychiatry (2015)

High mortality rates have been reported in people released from prison compared with the general population. However, few studies have investigated potential risk factors associated with these high rates, especially psychiatric determinants. We aimed to investigate the association between psychiatric disorders and mortality in people released from prison in Sweden.
Myeloid-Specific Krüppel-Like Factor 2 Inactivation Increases Macrophage and Neutrophil Adhesion and Promotes Atherosclerosis
Authors: Jerry B Lingrel, Robyn Pilcher-Roberts, Joshua E. Basford, Palanikumar Manoharan, Jon Neumann, Eddy S. Konaniah, Ramprasad Srinivasan, Vladimir Y. Bogdanov, David Y. Hui
Journal: Circulation Research (2012)

Rationale: Hemizygous deficiency of the transcription factor Krüppel-like factor 2 (KLF2) has been shown previously to augment atherosclerosis in hypercholesterolemic mice. However, the cell type responsible for the increased atherosclerosis due to KLF2 deficiency has not been identified. This study examined the consequence of myeloid cell-specific KLF2 inactivation in atherosclerosis. Methods and Results: Cell-specific knockout mice were generated by Cre/ loxP recombination. Macrophages isolated from myeloid-specific Klf2 knockout ( myeKlf2 −/− ) mice were similar to myeKlf2 +/+ macrophages in response to activation, polarization, and lipid accumulation. However, in comparison to myeKlf2 +/+ macrophages, myeKlf2 −/− macrophages adhered more robustly to endothelial cells. Neutrophils from myeKlf2 −/− mice also adhered more robustly to endothelial cells, and fewer myeKlf2 −/− neutrophils survived in culture over a 24-hour period in comparison with myeKlf2 +/+ neutrophils. When myeKlf2 −/− mice were mated to Ldlr −/− mice and then fed a high fat and high cholesterol diet, significant increase in atherosclerosis was observed in the myeKlf2 −/− Ldlr −/− mice compared with myeKlf2 +/+ Ldlr −/− littermates. The increased atherosclerosis in myeKlf2 −/− Ldlr −/− mice was associated with elevated presence of neutrophils and macrophages, with corresponding increase of myeloperoxidase as well as chlorinated and nitrosylated tyrosine epitopes in their lesion areas compared with myeKlf2 +/+ Ldlr −/− mice. Conclusions: This study documents a role for myeloid KLF2 expression in modulating atherosclerosis. The increased neutrophil accumulation and atherosclerosis progression with myeloid-specific KLF2 deficiency also underscores the importance of neutrophils in promoting vascular oxidative stress and atherosclerosis. Collectively, these results suggest that elevating KLF2 expression may be a novel strategy for prevention and treatment of atherosclerosis.