tbuckley/cabot-search huggingface dataset:
Revolutionizing oncology patient enrollment in clinical trials: Just-in-time approach
Authors: M. B. Wiener, H. M. Newman, E. A. Spradley
Journal: Journal of Clinical Oncology (2007)

6577 Background: In the US, adult oncology patient enrollment in clinical trials is estimated at 4% (Cancer 2006; 106(2):426–33). This is a major bottleneck in the development of new cancer treatments, especially for rare indications, like stage IV pancreatic cancer in treatment-naive patients. To overcome the challenge of low enrollment in clinical trials, Pharmatech developed the Just-In-Time (JIT) approach. JIT expands the potential patient population and allows research sites to pre-identify patients using standard of care information prior to site activation. This differs from a traditional approach where sites are activated prior to screening for patients. We postulated the JIT approach would impact patient accrual. Methods: With the JIT approach, a central IRB-approved protocol was presented to 38 research-ready sites but only 8 sites with a potential patient obtained IRB-site approval over a 6 month period. Within 5–10 business days after identifying a potential patient, sites obtained IRB approval, investigators at the site were trained, received study materials, and dosed the first patient. We compared traditional site activation conducted by the sponsor to JIT approach in this study. Results: Traditional approach vs JIT approach: No.of patients enrolled: 42 vs 18; No.of months open: 19 vs 6; No. of sites open: 13 vs 8; No. of non-enrolling sites: 2 vs 0; Patient accrual rate (pts/mo/site): 0.17 vs 0.38. Sites participating in the JIT approach accrued subjects at &gt;2x the rate of traditionally activated sites. The JIT approach eliminated non-enrolling sites, increasing sites’ and sponsor's satisfaction with enrollment. JIT also enhanced patient options by providing access to a novel treatment alternative for this rare indication even at smaller research sites. Conclusions: With JIT, patient accrual rate, enrollment success and trial-related cost in a pancreatic cancer study were markedly better than with the traditional approach. Expanding JIT to other rare indications and to trials requiring specific genetic tumor-profiles will show whether these results are reproducible and whether JIT is a viable approach for trials with challenging eligibility criteria. No significant financial relationships to disclose.
Risk factors for respiratory failure in pneumococcal pneumonia: the importance of pneumococcal serotypes
Authors: Joaquín Burgos, Manel Luján, Maria Nieves Larrosa, Dionísia Fontanals, Guadalupe Bermudo, Ana Maria Planes, Mireia Puig, Jordi Rello, Vicenç Falcó, Albert Pahissa
Journal: European Respiratory Journal (2013)

Pneumococcal serotypes are one of the main determinants of pneumococcal disease severity; however, data about their implication in respiratory failure are scarce. We conducted an observational study of adults hospitalised with invasive pneumococcal pneumonia to describe the host- and pathogen-related factors associated with respiratory failure. Of 1258 adults with invasive pneumococcal disease, 615 (48.9%) had respiratory failure at presentation. Patients with respiratory failure were older (62.1 years versus 55.4 years, p&lt;0.001) and had a greater proportion of comorbid conditions. They also had a greater proportion of septic shock (41.7% versus 6.1%, p&lt;0.001), required admission to the intensive care unit more often (38.4% versus 4.2%, p&lt;0.001) and had a higher mortality (25.5% versus 3.5%, p&lt;0.001). After adjustment, independent risk factors for respiratory failure were: age &gt;50 years (OR 1.63, 95% CI 1.15–2.3), chronic lung disease (OR 1.54, 95% CI 1.1–2.15), chronic heart disease (OR 1.49, 95% CI 1.01–2.22) and infection caused by serotypes 3 (OR 1.97, 95% CI 1.23–3.16), 19A (OR 2.34, 95% CI 1.14–4.42) and 19F (OR 3.55, 95% CI 1.22–10.28). In conclusion, respiratory failure is a frequent complication of pneumococcal pneumonia and causes high morbidity and mortality. Pneumococcal serotypes 3, 19A and 19F are the main risk factors for this complication.
Electrical Control of Epilepsy
Authors: David J. Mogul, Wim van Drongelen
Journal: Annual Review of Biomedical Engineering (2014)

Epilepsy afflicts approximately 1–2% of the world's population. The mainstay therapy for treating the chronic recurrent seizures that are emblematic of epilepsy are drugs that manipulate levels of neuronal excitability in the brain. However, approximately one-third of all epilepsy patients get little to no clinical relief from this therapeutic regimen. The use of electrical stimulation in many forms to treat drug-refractory epilepsy has grown markedly over the past few decades, with some devices and protocols being increasingly used as standard clinical treatment. This article seeks to review the fundamental modes of applying electrical stimulation—from the noninvasive to the nominally invasive to deep brain stimulation—for the control of seizures in epileptic patients. Therapeutic practices from the commonly deployed clinically to the experimental are discussed to provide an overview of the innovative neural engineering approaches being explored to treat this difficult disease.
Establishment of Gene Copy Number-Specific Normal Ranges for Serum C4 and Its Utility for Interpretation in Patients With Chronically Low Serum C4 Concentrations
Authors: Audrey A. Margery-Muir, John D. Wetherall, Alison S. L. Castley, Meilyn Hew, Rebecca S. Whidborne, Dominic F. J. Mallon, Patricia Martinez, Campbell S. Witt
Journal: Arthritis & Rheumatology (2014)

To establish gene copy number (GCN)-specific normal ranges for serum C4 genes and to determine their utility with respect to the interpretation of chronically low serum C4 concentrations in patients with clinically quiescent systemic lupus erythematosus (SLE).C4 serum concentrations were estimated by automated turbidimetry, and C4 GCNs were determined using the TaqMan real-time polymerase chain reaction (PCR) analysis in 184 unselected individuals and in 10 patients with type 1 diabetes mellitus (DM) who were selected for the presence of only 2 copies of the C4 gene. C4 GCNs were also determined in 11 patients with clinically quiescent SLE who had chronically low serum C4 concentrations.A total of 33% of the variation in serum C4 concentrations could be accounted for by both C4A and C4B GCNs (R(2) = 0.30, P ≤ 0.0001). There was a median of 2 gene copies at the C4A locus (53.8%) and 2 at the C4B locus (58.7%). The median total number of C4 genes was 4 (55.4%). C4 GCN-specific normal ranges were established. A chronically low serum C4 concentration was explained by a low C4 GCN in 3 of 11 patients tested.This study establishes the feasibility of establishing C4 GCN-specific normal ranges using the TaqMan real-time PCR assay. Chronically low serum C4 concentrations in SLE patients are sometimes explained by low C4 GCNs.
Generalized pulmonary hyperinflation and Fallot's tetralogy in a neonate investigated by pulmonary physiological and radioisotopic methods.
Authors: S Godfrey, R Ronchetti, J Stocks, K Hallidie-Smith
Journal: Thorax (1975)

An infant is described who presented a complex cardiopulmonary problem which was evaluated with the help of new physiological techniques. the infant was born at term after an emergency Caesarian section for fetal distress and was found to have meconium aspiration. He remained persistently tachypnoeic and hypoxic despite high ambient oxygen. Chest radiography suggested cystic lesions at the lung bases, and lung function tests confirmed hyperinflation with delayed nitrogen washout. In addition the child had signs of Fallot9s tetralogy, and this diagnosis was confirmed by cardiac catheterization. Because of persistent hypoxia and tachypnoea disproportionate to the cardiac condition, the possibility of localized lung disease was considered. Regional lung function tests were carried out in the neonatal period and again at six months of age useing radioisotopic 13N given by both inhalation and injection. These studies showed gross ventilation/perfusion imbalance in the lungs, particularly marked at the bases, but with enough generalized abnormality to preclude the possibility of surgical intervention. The principles of the measurement of lung mechanics in the newborn by whole-body plethysmography, nitrogen washout, and regional radioisotopic spirometry are outlined. The particular value of these techniques in the evaluation of complex disorders is discussed, especially where both cardiac and pulmonary abnormalities are present.
Neoadjuvant Chemotherapy or Primary Surgery in Stage IIIC or IV Ovarian Cancer
Authors: Ignace Vergote, Claes G. Tropé, Frédéric Amant, Gunnar B. Kristensen, Tom Ehlen, Nick Johnson, René H.M. Verheijen, Maria E.L. van der Burg, Angel J. Lacave, Pierluigi Benedetti Panici, Gemma G. Kenter, Antonio Casado, Cesar Mendiola, Corneel Coens, Leen Verleye, Gavin C.E. Stuart, Sergio Pecorelli, Nick S. Reed
Journal: New England Journal of Medicine (2010)

Primary debulking surgery before initiation of chemotherapy has been the standard of care for patients with advanced ovarian cancer.We randomly assigned patients with stage IIIC or IV epithelial ovarian carcinoma, fallopian-tube carcinoma, or primary peritoneal carcinoma to primary debulking surgery followed by platinum-based chemotherapy or to neoadjuvant platinum-based chemotherapy followed by debulking surgery (so-called interval debulking surgery).Of the 670 patients randomly assigned to a study treatment, 632 (94.3%) were eligible and started the treatment. The majority of these patients had extensive stage IIIC or IV disease at primary debulking surgery (metastatic lesions that were larger than 5 cm in diameter in 74.5% of patients and larger than 10 cm in 61.6%). The largest residual tumor was 1 cm or less in diameter in 41.6% of patients after primary debulking and in 80.6% of patients after interval debulking. Postoperative rates of adverse effects and mortality tended to be higher after primary debulking than after interval debulking. The hazard ratio for death (intention-to-treat analysis) in the group assigned to neoadjuvant chemotherapy followed by interval debulking, as compared with the group assigned to primary debulking surgery followed by chemotherapy, was 0.98 (90% confidence interval [CI], 0.84 to 1.13; P=0.01 for noninferiority), and the hazard ratio for progressive disease was 1.01 (90% CI, 0.89 to 1.15). Complete resection of all macroscopic disease (at primary or interval surgery) was the strongest independent variable in predicting overall survival.Neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary debulking surgery followed by chemotherapy as a treatment option for patients with bulky stage IIIC or IV ovarian carcinoma in this study. Complete resection of all macroscopic disease, whether performed as primary treatment or after neoadjuvant chemotherapy, remains the objective whenever cytoreductive surgery is performed. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003636.)
Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial
Authors: Brent A Neuschwander-Tetri, Rohit Loomba, Arun J Sanyal, Joel E Lavine, Mark L Van Natta, Manal F Abdelmalek, Naga Chalasani, Srinivasan Dasarathy, Anna Mae Diehl, Bilal Hameed, Kris V Kowdley, Arthur McCullough, Norah Terrault, Jeanne M Clark, James Tonascia, Elizabeth M Brunt, David E Kleiner, Edward Doo
Journal: The Lancet (2014)
The Acute Care Undergraduate TEaching (ACUTE) Initiative: consensus development of core competencies in acute care for undergraduates in the United Kingdom
Authors: Gavin D. Perkins, Hannah Barrett, Ian Bullock, David A. Gabbott, Jerry P. Nolan, Sarah Mitchell, Alasdair Short, Christopher M. Smith, Gary B. Smith, Susan Todd, Julian F. Bion
Journal: Intensive Care Medicine (2005)
Demand for exercise training in patients with pulmonary arterial hypertension in Scotland
Authors: Alison MacKenzie, Martin Johnson
Journal: European Respiratory Journal (2015)

Despite significant advances in medical therapy, most patients with pulmonary arterial hypertension (PAH) remain symptomatic on treatment [1]. The recently published UK PAH national audit 2014 [2] demonstrates a 65% rate of failure of monotherapy at 2 years. New treatment strategies are therefore essential to improve morbidity and, if possible, mortality. Scottish patients with PAH wish to take part in dedicated and intensive exercise rehabilitation programmes <http://ow.ly/Owwai>
Interlaboratory agreement of toluene diisocyanate (TDI)-specific serum antibody results are strongly influenced by antigen characteristics
Authors: Z.L. Lummus, H.S. Park, W.E. Brown, A.T. Jolly, R.E. Biagini, M.A. Wanner, D.M. Lewis, A.L. Burkert, H. Daftarian, D.I. Bernstein
Journal: Journal of Allergy and Clinical Immunology (2003)
Differential Response of Glioma Cells to FOXO1-Directed Therapy
Authors: Cara J. Lau, Zaf Koty, Josephine Nalbantoglu
Journal: Cancer Research (2009)

Abstract Gliomas are the most common adult primary brain tumors, and the most malignant form, glioblastoma multiforme, is invariably fatal. The phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway is altered in most glioblastoma multiforme. PTEN, an important negative regulator of the PI3K-Akt pathway, is also commonly mutated in glioma, leading to constitutive activation of Akt. One ultimate consequence is phosphorylation and inactivation of FOXO forkhead transcription factors that regulate genes involved in apoptosis, cell cycle arrest, nutrient availability, DNA repair, stress, and angiogenesis. We tested the ability of a mutant FOXO1 factor that is not subject to Akt phosphorylation to overcome dysregulated PI3K-Akt signaling in two PTEN-null glioma cell lines, U87 and U251. Adenovirus-mediated gene transfer of the mutant FOXO1 successfully restored cell cycle arrest and induced cell death in vitro and prolonged survival in vivo in xenograft models of human glioma (33% survival at 1 year of animals bearing U251 tumors). However, U87 were much more resistant than U251 to mutant FOXO1-induced death, showing evidence of increased nuclear export and Akt-independent phosphorylation of FOXO1 at S249. A cyclin-dependent kinase 2 inhibitor decreased phosphorylation of S249 and rendered U87 cells significantly more susceptible to mutant FOXO1-induced death. Our results indicate that targeting FOXO1, which is at the convergence point of several growth factor receptor tyrosine kinase pathways, can effectively induce glioma cell death and inhibit tumor growth. They also highlight the importance of Akt-independent phosphorylation events in the nuclear export of FOXO1. [Cancer Res 2009;69(13):5433–40]
Allergic and nonallergic interactions between house dust mite allergens and airway mucosa
Authors: N Roche, TC Chinet, GJ Huchon
Journal: European Respiratory Journal (1997)

Asthma and allergy are extremely frequent diseases, affecting 5-10% and 30% of the population, respectively. The prevalence of asthma has increased in many developed countries, which may be due to several factors, including increased exposure to house dust mite (HDM) allergens. HDM to which humans are most frequently sensitized are Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Euroglyphus maynei. These mites multiply in carpets, bedding and upholstered furniture in a hot and humid atmosphere. The allergens are digestive enzymes of the mites. Several epidemiological studies have shown that an increase in exposure to HDMs is associated with an increase in the prevalence of sensitization and asthma, whereas mite avoidance leads to a decrease in respiratory symptoms of sensitized asthmatic subjects. Sensitized subjects have specific immunoglobulin G and E (IgG and IgE) humoral responses, as well as proliferative T-cell responses to HDM allergens. Experimental exposure to HDM allergens induces bronchoalveolar inflammatory responses, that are characterized by the recruitment and activation of eosinophils, mastocytes, neutrophils, monocytes and lymphocytes. The cysteine protease activity of Der p 1 (a major allergen of D. pteronyssinus) has been shown to increase airway mucosal permeability, and may thereby contribute to the pathogenesis of airway inflammation and hyperresponsiveness by nonimmunological mechanisms. These epidemiological and experimental data support the recommendations for mite avoidance, especially in persons at high risk of developing asthma.
An Address ON MASSIVE PULMONARY COLLAPSE
Authors: A. B. Soltau
Journal: BMJ (1925)

r MEDICAL JouILThe commonest tumour of the cerebrum is a glioma and its remoral is impossible.The relief which may be obtained by decompression is, however, sometimes very considerable, and of this the following case furnishes an example.A woman, aged 38, was sent to me with a history of severe frontal headaches extending over six years.A year before I saw her she suddenly fell down unconscious and had a series of violent convulsive attacks starting in the left arm.From this she recovered completely.It had for some time been noticed that she was somewhat unstable mentally, acting with excitable levity.She occasionally had, a tremor in the right arm and leg, and vision was failing.She was an excitable woman in abnormally high spirits.She had severe papilloedema, most marked on the right, but no changes in motion, sensation, or reflexes were discovered.A deep glioma of the right frontal region was diagnosed, and a large decompression in this region was performed, the brain being under very, high pressure.She recovered completely, her headaches disappeared, And she regained her normal health and vision; even the fundi became normal.For eighteen months she remained in excellent health, though a left hemiparesis and an enormous hernia very gradually developed.She then quite rapidly became comatose and died.Althou'gh a glioma cannot be removed it may degenerate in the centre and become cystic, and in such a case it is sometimes possible by aspiration of the cyst to give considerable relief to the patient.If the cyst is at all superficial and can be treated with formalin the relief may extend over a considerable period; in some of these cases the introduction of radium has given good results.In uch cases a decompression not only relieves the pressure but enables the cyst to be aspirated with facility.The following is an example:A man, aged 44, was referred to me by Dr. Riddoch with the story that six months previously he had had a sudden attack of fiddess, followed by pains in the back of the neck and difficulty Xspeakng, which lasted for a few minutes.Since then he had ad a few similar attacks, and six weeks before I saw him, after one of these, the right arm began to shake and the right side of the face to twitch.When this had passed off the arm remained weak and the difficulty in speech persisted.He was an intelligent man with marked apraxia and aphasia.There was slight weak- ness of the right side of the face and tongue, and spastic paresis of the r:ht arm and leg with increase in the deep reflexes.He rapidly became worse, complete right hemiplegia developed, he ras unable to move his tongue, and had increasing difficulty in *wallowing.He became very drowsy and the respirations ster- torous.Left temporal decompression was performed and a large cyst discovered lying deeply in the left frontal lobe, from which 44 c.cm. of turbid fluid was withdrawn.He made a remarkable recovery.His speech commenced to return in four days and he regained full power in his 'limbs.
Health care associated pneumonia versus community acquired pneumonia: Comparison of etiology, treatment and prognosis
Authors: Catia Araujo, Natalia Andre, Paula Raimundo, António Domingos
Journal: European Respiratory Journal (2012)

Introduction

Since 2005 and according to the ATS/IDSA, Health care associated pneumonia (HCAP), is a novel category of pneumonia that has been grouped into the group of nosocomial pneumonias, because differs from community-acquired pneumonia (CAP) concerning etiology, treatment and prognosis.

Objectives

The aim of this study was to compare the etiologic agents, therapeutic regimens and prognosis between HCAP and CAP.

Methods

We analyzed retrospectively the pneumonia admissions in the period of April 2010 to March 2011, in the Pulmonology Unit of a District Hospital.

We compared HCAP vs CAP regarding clinical and epidemiological characteristics, comorbilities, functional status, previous antibiotic treatment, risk stratification by Pneumonia Severity Index(PSI) and CURB 65 score, etiologic agents, therapeutic regimens, hospital length and mortality.

Results

A total of 221 patients has been included, 89 (40.3%) with HCAP and 132 (59.7%) with CAP.

Statistic significant differences favoring HCAP were observed in the following variables: older age (75,6 yr avr), presence of cerebrovascular disease (66,7%), poor functional status (74,1%), previous antibiotic treatment (53,9%), more severe disease (CURB65-2,2), predominance of gram negative bacteria (33,6%), higher mortality rate (68,4%) and initial empiric therapy (piperacilin/tazobactam plus aminoglicoside- 63,2%).

Conclusions

Our results confirm the greater severity and worse prognosis of HCAP. In this group the most frequent agents were the gram negative bacteria. Accordingly, the empirical antibiotic therapy should cover not only the usual CAP agents, but also the causative agents associated with nosocomial pneumonia.
Acting on Imperfect Evidence: How Much Regret Are We Ready to Accept?
Authors: Benjamin Djulbegovic, Andrew Frohlich, Charles L. Bennett
Journal: Journal of Clinical Oncology (2005)

Benjamin Djulbegovic H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida, Tampa, FL Andrew Frohlich and Charles L. Bennett, Jesse Brown VA Medical Center and the VA Midwest Center for Health Services Research and Policy Studies, the Division of Hematology/Oncology of the Department of Medicine, the Institute for Health Services Research and Policy Studies, and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL
The application of a numerical scoring system for evaluating the histological outcome in patients with chronic hepatitis B followed in long term
Authors: Gudrun Lindh, Ola Weiland, Hans Glaumann
Journal: Hepatology (1988)

A numerical scoring system was applied and compared with conventional histological classification to assess the histological outcome in 42 patients with chronic hepatitis B followed for 16 to 162 months (mean = 75 months). Four histological categories in the biopsies were assessed and scored: (i) piecemeal necrosis; (ii) lobular necrosis; (iii) portal inflammation, and (iv) fibrosis and cirrhosis. The sum of all four categories was defined as the “Histological Activity Index.” Altogether, 102 liver specimens, including 2 to 4 repeats from each patient, were investigated. A good correlation was noted between a high value of the Histological Activity Index score and several liver histology as monitored by conventional terminology for chronic hepatitis. Among patients, with HBeAg persistence, 8 of 14 (57%) deteriorated during follow-up as judged by an increase in the Histological Activity Index score compared to 3 of 13 (23%) of the patients with HBeAg seroconversion (0.5 &lt; p &lt; 0.1). Piecemeal necrosis has been postulated to be a predictive marker for the eventual development of cirrhosis. Here, we found that a low score for piecemeal necrosis in the initial liver biopsy was significantly less predictive of a high fibrosis score in the follow-up biopsy than was a high score for initial piecemeal necrosis (p &lt; 0.001). It is concluded that the scoring system used can be applied to monitor the histological long-term follow-up, especially when separated into its four constituent categories. It also offers a means of predicting a chronic hepatitis outcome.