tbuckley/cabot-search huggingface dataset:
S9 Equivalence Of Fluticasone Propionate/Salmeterol Delivered Via AirFluSal® Forspiro® And Seretide® Accuhaler® In Adolescent And Adult Asthma
Authors: P Kuna, I Gath, U Thyroff-Friesinger, S Jones
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Guideline-defined asthma control may be achieved and maintained in the majority of patients by treatment with a combination of a corticosteroid and a long-acting ß<sub>2</sub>-agonist. AirFluSal® Forspiro®, a multi-dose dry powder inhaler (mDPI), provides this proven combination of inhaled corticosteroid fluticasone propionate (FP) and a long-acting inhaled ß<sub>2</sub>-agonist salmeterol (Sal). This study compared the efficacy of AirFluSal® Forspiro® with Seretide® Accuhaler® in adolescent and adult patients with moderate-to-severe persistent asthma. <h3>Methods</h3> This study, conducted in 279 patients (12–65 years) with GINA guideline-defined moderate-to-severe persistent asthma, was undertaken as a double-blind, double-dummy, parallel-group, multicentre trial. Patients were randomised to 12 weeks treatment with AirFluSal® Forspiro® 500 µg/50 µg, or Seretide® Accuhaler® 500 µg/50 µg. Primary efficacy measures were the change from baseline of the forced expiratory volume in 1 s (FEV<sub>1</sub>) to show non-inferiority of AirFluSal® Forspiro® to Seretide® Accuhaler® (non-inferiority margin Δ = -0.200 L) and the area under the FEV<sub>1</sub> curve at study termination (AUC<sub>0–12</sub>). Secondary endpoints included mean changes in FEV<sub>1</sub>, FEV<sub>1</sub>% predicted, morning peak expiratory flow (PEF) and global evaluation of efficacy. Safety was assessed and patient preference for each device was rated using a visual analogue scale (VAS). <h3>Results</h3> Assessment of the effect of treatment on the absolute change in FEV<sub>1</sub> from baseline to study termination demonstrated non-inferiority between AirFluSal® Forspiro® and Seretide® Accuhaler® (difference in least squares mean [95% CI] = -0.032 L [-0.121;0.057]). Assessment of AUC<sub>0–12 </sub>at study termination demonstrated equivalence between devices. All secondary efficacy measures demonstrated comparable results for both inhalers, with no significant differences observed. The use of rescue medication and the average asthma symptom scores decreased from baseline in a similar manner for both devices. Overall safety profiles were equivalent. Patient ratings for each device were 81.97 ± 13.89 mm VAS for AirFluSal® Forspiro® and 79.67 ± 16.48 mm VAS for Seretide® Accuhaler® (data includes 276 patients randomised at baseline to use the devices at a dose of 100 µg/50 µg). <h3>Conclusions</h3> AirFluSal® Forspiro® shows therapeutic equivalence to Seretide® Accuhaler®, providing a proven combination treatment in an intuitive, easy-to-use device.
Bedside Diagnosis of Carotid-Artery Occlusive Disease
Authors: S. N. Groch, L. J. Hurwitz, I. S. Wright, F. McDowell
Journal: New England Journal of Medicine (1960)

RECENT advances in the therapy of certain types of cerebrovascular disease emphasize the necessity for early diagnosis.1 2 3 4 5 Occlusive disease of the carotid artery was found in 16 per cent of patients admitted to the hospital with the diagnosis of "stroke" in whom routine angiography was performed.6 Prompt diagnosis and institution of active therapy in this variety of cerebrovascular disease may at times prevent the development of catastrophic neurologic deficits. It has been our experience that the correct diagnosis can be established at the bedside in 80 per cent of cases and that cerebral angiography is not essential to a clinical . . .
67P Investigation of the interaction between non-small cell lung cancer cells and immortalised normal bronchial epithelial cells
Authors: K. O'Byrne, M.P. Barr, A. Urquhart, S.-L. Ryan, S.G. Gray, A. Davies, D. Richard, K. Gately, A.-M. Baird
Journal: Journal of Thoracic Oncology (2016)
Fibrous Dysplasia Presenting as a Cold Spot in 18F-FLT PET/CT Imaging
Authors: Zdenek Rehak, Beatrix Bencsikova, Iva Zambo, Tomas Kazda
Journal: Clinical Nuclear Medicine (2016)

Fibrous dysplasia (FD) is a benign bone lesion in which normal bone marrow is replaced by fibro-osseous tissue. The usual high fluorodeoxyglucose (18F-FDG) uptake in FD may lead to the misdiagnosis of bone malignancy. Herein, we describe the case of a 42-year old man with histologically verified FD of the pubic bone, which has been subsequently examined during follow-up for rectal cancer, using both 18F-FDG and fluorothymidine (18F-FLT) PET/CT imaging. The FD lesion was characterized by a high uptake of 18F-FDG (hot spot) but very low uptake of 18F-FLT (cold spot) as compared with the contralateral unaffected pubic bone.
Prolonged Administration of Ethacrynic Acid in Patients with Chronic Renal Disease
Authors: Clem W. Hagedorn, Arnold A. Kaplan, William H. Hulet
Journal: New England Journal of Medicine (1965)

EARLY reports on the administration of ethacrynic acid, or 2,3-dichloro-4-(2-methylene butyryl) phenoxyacetic acid,¶ for periods of a few days to several weeks have shown that the drug produces a marked diuresis in patients with either congestive heart failure or hepatic cirrhosis.1 2 3 4 Significant diuresis has also been observed in patients with the nephrotic syndrome.5 , 6 Because of our initial success with ethacrynic acid in the short-term treatment of nephrotic patients refractory to other natriuretic agents7 we continued the drug beyond the hospital period in an effort to maintain these patients free of edema at home and at work. Their response to the . . .
197PD: Identifying dosimetric predictors of toxicity in multiple lung tumors treated with stereotactic ablative radiotherapy (SABR)
Authors: H. Tekatli, S. Tetar, A. Warner, D. Palma, W. Verbakel, T. Nguyen, F. Spoelstra, S. Gaede, B. Slotman, S. Senan
Journal: Journal of Thoracic Oncology (2016)
Prognostic significance of HLA-A2 status in breast cancer patients
Authors: Z. Dehqanzada, M. T. Hueman, C. D. Shriver, S. Ponniah, G. E. Peoples
Journal: Journal of Clinical Oncology (2005)

9702 Background: HER2/neu (HER2) is a known prognostic factor in breast cancer and has been targeted by peptide vaccines. HLA-A2 (A2) is present in 40–50% of Caucasians. We are testing an A2-binding, HER2 peptide, E75, vaccine in node-positive (NP) and node-negative (NN) breast cancer patients. We have observed differences in known prognostic factors in these patients based on A2 status. Therefore, we have combined data from both trials to determine the prognostic significance of the A2 status. Methods: We have enrolled 98 patients into the NN (n=46) and NP (n=52) trials evaluating the E75 vaccine to induce HER2 immunity and prevent recurrence. Patients are enrolled and then HLA typed; clinical parameters should be evenly distributed. A2+ patients (n=46) have been vaccinated, and A2- patients (n=52) have been followed as controls. All pertinent clinical prognostic factors have been documented. Since the trial design is preventive, no requirement for HER2 over-expression exists. HER2 varied from 0–3+ (IHC). Patients can be categorized: A2-/HER2- (n=22), A2+/HER2- (n=19), A2-/HER2+ (n=28), and A2+/HER2+ (n=24). Results: Taken collectively, A2+ patients have fewer +ve nodes compared to A2- patients (mean=1.96 vs 2.69, p<0.3) despite having larger tumors (≥2 cm, 41% vs 33%), higher grade (grade 3, 41% vs 28%, p<0.17), and more ER-/PR- cancers (24% vs 15%), respectively. When assessed by HER2 status, differences are more apparent. If HER2-, the proportion of patients with +ve nodes is similar (36% vs 37%) between the A2- and A2+ groups; however, the median (range) number of +ve nodes is 4.5 (1–11) compared to 1 (1–5), respectively (p<0.15). If HER2+, 78% of the A2- patients are node +ve compared to only 67% of the A2+ (p<0.3) suggesting a trend related to A2 status. This trend is even more apparent in the HER2 3+ patients (n=24) with 92% of A2- patients being node +ve compared to 58% of A2+ patients (p<0.059). Conclusions: HLA-A2 appears protective in some breast cancer patients with A2+ patients developing more aggressive cancers prior to nodal metastasis. This protection is most apparent among HER2+ patients, particularly with HER2 over-expression. If confirmed in larger studies, these findings may have implications for risk assessment in breast cancer patients. No significant financial relationships to disclose.
Perinatal Transmission of the Agent of Human Granulocytic Ehrlichiosis
Authors: Harold W. Horowitz, Eitan Kilchevsky, Stuart Haber, Maria Aguero-Rosenfeld, Ramon Kranwinkel, Edward K. James, Susan J. Wong, Frederick Chu, Dionysios Liveris, Ira Schwartz
Journal: New England Journal of Medicine (1998)

Human granulocytic ehrlichiosis was first described in the United States, in the northern Midwest, in 1994.1 Human granulocytic ehrlichiosis is caused by an organism, still referred to as the agent of human granulocytic ehrlichiosis, that is similar to two animal pathogens, Ehrlichia phagocytophila and E. equi. 2–4 Transmission of human granulocytic ehrlichiosis occurs through the bites of ixodes ticks, which are the arthropod vectors for Borrelia burgdorferi and Babesia microti. 5,6 Human granulocytic ehrlichiosis is an acute, febrile, nonspecific illness that may be severe enough to cause hospitalization and even death, particularly in the elderly.1,7,8 We describe a . . .
Intravesical Bacillus Calmette-Guérin Versus Combination of Epirubicin and Interferon-α2a in Reducing Recurrence of Non–Muscle-invasive Bladder Carcinoma: FinnBladder-6 Study
Authors: Timo Marttila, Riikka Järvinen, Tapani Liukkonen, Erkki Rintala, Peter Boström, Marjo Seppänen, Teuvo Tammela, Pekka Hellström, Sirpa Aaltomaa, Markku Leskinen, Mika Raitanen, Eero Kaasinen
Journal: European Urology (2016)
Role of pharmacogenetic studies in early clinical development: Phase I studies with lapatinib
Authors: T. Z. Zaks, A. Akkari, L. Briley, M. Mosteler, A. G. Stead, K. M. Koch, C. Sampson, M. Ehm, E. Harris, A. Roses
Journal: Journal of Clinical Oncology (2006)

3029 Background: Rash and diarrhea are a class effect of ERBB1 inhibitors. These events are relatively mild with Lapatinib (a dual ERBB1/ERBB2 kinase inhibitor). Finding a genetic basis for patients who may be predisposed to these adverse events, from the outset of clinical development, may improve the understanding of the mechanisms of these side effects and may have implications for use and dosing. Methods: DNA was isolated from peripheral blood of 107 Caucasian subjects from eight monotherapy phase I studies including 73 healthy volunteers and 34 cancer patients, 100 of whom had associated pharmacokinetic data. 284 single nucleotide polymorphisms (SNPs) from five candidate genes of transporters (ABCB1, ABCG2) and enzymes (CYP 3A4 and 3A5, and 2C19) for which lapatinib is a substrate were genotyped and examined for associations with pharmacokinetic variables (dose-normalized AUC, Cmax, and Tmax) as well as rash (15 cases) and diarrhea (18 cases). Results: Skin rash and diarrhea in this phase I cohort were only mild, (i.e. grade I or II). Statistically significant associations were observed between 34 SNPs in CYP2C19, rash (22 SNPs) and diarrhea (6 SNPs), and between 15 SNPs in ABCB1 and Tmax. Notably, 3/3 subjects (2 healthy volunteers, one patient) homozygous for the CYP2C19*2 allele experienced both mild rash and diarrhea. Extensive linkage disequilibrium was observed among these associated SNPs. Conclusions: Our results suggest that it is possible to determine pharmacogenetic associations with side effect phenotypes during the earliest phase of clinical drug development. These results are currently being validated on a larger cohort of patients from phase II lapatinib clinical trials. [Table: see text]
Informed consent for neuroleptic therapy
Authors: J Deveaugh-Geiss
Journal: American Journal of Psychiatry (1979)

The author suggests that the frequency and severity of tardive dyskinesia in patients treated with neuroleptic drugs requires that informed consent be obtained from all patients receiving such treatment. The three basic conditions for obtaining informed consent are reviewed with discussion of some of the ethical problems encountered in the informed consent procedure. Most of these problems will be resolved if specific, written, informed consent is obtained from the patient, or his representative, within six weeks of initiating therapy, although in some cases questions may be raised about the very possibility of obtaining consent.
Chelation by Calcium Trisodium Pentetate in Workers Exposed to Lead
Authors: Heinrich G. Brugsgh, N. J. Colombo, L. D. Pagnotto
Journal: New England Journal of Medicine (1965)

THE goal of the industrial physician — to protect workers against lead poisoning through such measures as approved respirators, adequate plant ventilation and good personal hygiene1 — is not always obtainable. Even effective measures may be inadequate in the presence of unusually heavy exposures. In Massachusetts lead poisoning still occurs among workers employed in storage-battery plants, smelting plants, demolition work and painting, not to mention the high incidence of lead poisoning among children. Use of a chelating agent to remove lead from those suffering from or threatened by lead poisoning, therefore, still has a place in the therapeutic armamentarium.EDTA . . .
S65 The role of Src kinase in inspiratory resistive breathing-induced pulmonary inflammation
Authors: D Toumpanakis, P Zacharatos, T Michailidou, G Tsoukalas, T Vassilakopoulos
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Inspiratory resistive breathing (IRB), a hallmark of obstructive pulmonary diseases, is characterised by large negative intrathoracic pressures. IRB is shown to induce pulmonary inflammation in previously healthy rats. Src is a multifunctional kinase that is activated by phosphorylation upon mechanical stress and plays a significant role in inflammatory processes. The aim of our study was to investigate the role of Src in IRB-induced pulmonary inflammation. <h3>Methods</h3> Anaesthetised, tracheostomised rats were breathing spontaneously through a 2-way non rebreathing valve. The inspiratory port was connected to a resistance, setting peak tidal tracheal pressure at 50% of maximum (IRB). Quietly breathing animals served as controls. After 6 h of IRB, the mechanics of the respiratory system were assessed with the forced oscillation technique. Bronchoalveolar lavage (BAL) was performed to measure total and differential cell count and total protein levels. Phosphorylation of Src and ERK was detected in lung tissue samples by Western blot analysis at 30 min, 3 and 6 h of IRB. The Src inhibitor PP2 was administered intraperitoneally (1 mg/kg), 30 min prior to IRB, in a subgroup of animals. <h3>Results</h3> After 6 h of IRB, increased tissue elasticity was measured, compared to control. Increased BAL cellularity was also found (2-fold increase to control), due to raised numbers of both macrophages and neutrophils. Total protein levels were elevated in BAL fluid. Src activation was detected at 30 min of IRB (3-fold increase to control), while ERK was phosphorylated at 3 and 6 h. Inhibition of Src kinase attenuated the increase in tissue elasticity after 6 h of IRB. Following inhibition of Src kinase, the total cell number after 6 h of IRB was not increased compared to control. Neither macrophage nor neutrophil count was elevated after 6 h of IRB, following Src inhibition. Total protein levels were not altered by Src inhibition. Src inhibition attenuated the activation of ERK only at 3 h of IRB. <h3>Conclusion</h3> Src kinase activation partly mediates IRB-induced pulmonary inflammation.
OC-017 A comparison of non-invasive fibrosis scoring systems in patients with non-alcoholic fatty liver disease: Abstract OC-017
Authors: S McPherson, S Stewart, E Henderson, A Burt, C Day
Journal: Gut (2010)

<h3>Introduction</h3> Non-alcoholic fatty liver disease (NAFLD) affects approximately 30% of the population, with 3% having non-alcoholic steatohepatitis (NASH), which may progress to cirrhosis and liver failure. Accurate evaluation of liver fibrosis is important to identify patients who may develop complications. Liver biopsy is limited by its invasive nature. Therefore, several non-invasive strategies derived from simple clinical and laboratory parameters have been developed to identify patients with advanced fibrosis. The aim of this study was to compare the diagnostic performance of several non-invasive tests in patients with biopsy-proven NAFLD. <h3>Methods</h3> Patients who were reviewed in the Freeman Hospital liver clinic from 2003-2009 were included. Liver biopsies were assessed using the Kleiner score. The AST/ALT ratio, AST to platelet ratio index (APRI), BARD, FIB-4 and NAFLD fibrosis scores were calculated from blood tests taken within 6 months of liver biopsy. <h3>Results</h3> 145 patients (82 male (61%), mean age 51±12 years) were included. The mean BMI was 34.8±5 and 73 subjects (50%) had diabetes. 93 patients (64%) had NASH and 27 (19%) had advanced fibrosis (F3-4). The FIB-4 score had the best diagnostic accuracy for advanced fibrosis (AUROC 0.86), followed by AST/ALT ratio (AUROC 0.83), NAFLD fibrosis score (AUROC 0.81), BARD score (AUROC 0.77) and APRI (AUROC 0.67). Abstract OC-017 shows NPVs and PPVs for each test using specific cut-offs, along with the proportions of patients who could avoid liver biopsy by using each score. <h3>Conclusion</h3> The AST/ALT ratio, BARD, FIB-4 and NAFLD scores have good accuracy for excluding advanced fibrosis. Use of the ALT/AST ratio or FIB-4 score potentially allows liver biopsy to be avoided in a high proportion of patients with reasonable accuracy, meaning liver biopsy may be used in a more directed manner.
Case 12-2006
Authors: Fiona K. Gibbons, John A. Branda, Jo-Anne O. Shepard
Journal: New England Journal of Medicine (2006)

A 37-year-old physician was seen in the pulmonary clinic because of night sweats, hemoptysis, and a mass-like infiltrate visible in the lower lobe of the right lung on computed tomography (CT). He was otherwise in good health; a recent tuberculin skin test was negative, and the results of a physical examination and routine laboratory tests were normal. Antibiotics were prescribed, and the infiltrate resolved, but night sweats continued. CT repeated three months later disclosed new lesions in the same lobe. A diagnostic procedure was performed.
Randomized Phase III Noninferiority Study Comparing Two Radiotherapy Fractionation Schedules in Patients With Low-Risk Prostate Cancer
Authors: W. Robert Lee, James J. Dignam, Mahul B. Amin, Deborah W. Bruner, Daniel Low, Gregory P. Swanson, Amit B. Shah, David P. D’Souza, Jeff M. Michalski, Ian S. Dayes, Samantha A. Seaward, William A. Hall, Paul L. Nguyen, Thomas M. Pisansky, Sergio L. Faria, Yuhchyau Chen, Bridget F. Koontz, Rebecca Paulus, Howard M. Sandler
Journal: Journal of Clinical Oncology (2016)

Purpose Conventional radiotherapy (C-RT) treatment schedules for patients with prostate cancer typically require 40 to 45 treatments that take place from &gt; 8 to 9 weeks. Preclinical and clinical research suggest that hypofractionation—fewer treatments but at a higher dose per treatment—may produce similar outcomes. This trial was designed to assess whether the efficacy of a hypofractionated radiotherapy (H-RT) treatment schedule is no worse than a C-RT schedule in men with low-risk prostate cancer. Patients and Methods A total of 1,115 men with low-risk prostate cancer were randomly assigned 1:1 to C-RT (73.8 Gy in 41 fractions over 8.2 weeks) or to H-RT (70 Gy in 28 fractions over 5.6 weeks). This trial was designed to establish (with 90% power and an α of .05) that treatment with H-RT results in 5-year disease-free survival (DFS) that is not worse than C-RT by more than 7.65% (H-RT/C-RT hazard ratio [HR] &lt; 1.52). Results A total of 1,092 men were protocol eligible and had follow-up information; 542 patients were assigned to C-RT and 550 to H-RT. Median follow-up was 5.8 years. Baseline characteristics were not different according to treatment assignment. The estimated 5-year DFS was 85.3% (95% CI, 81.9 to 88.1) in the C-RT arm and 86.3% (95% CI, 83.1 to 89.0) in the H-RT arm. The DFS HR was 0.85 (95% CI, 0.64 to 1.14), and the predefined noninferiority criterion that required that DFS outcomes be consistent with HR &lt; 1.52 was met (P &lt; .001). Late grade 2 and 3 GI and genitourinary adverse events were increased (HR, 1.31 to 1.59) in patients who were treated with H-RT. Conclusion In men with low-risk prostate cancer, the efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41 fractions over 8.2 weeks, although an increase in late GI/genitourinary adverse events was observed in patients treated with H-RT.
S110 Efficacy and safety of nintedanib in patients with IPF beyond week 52: Data from the Phase II TOMORROW trial
Authors: L Richeldi, U Costabel, M Selman, Z Xu, T Kimura, S Stowasser, C Hallmann
Journal: Thorax (2015)

<h3>Introduction</h3> Period 1 of the TOMORROW trial was a phase II, randomised, placebo-controlled trial of four doses of nintedanib (50 mg qd, 50 mg bid, 100 mg bid, 150 mg bid) in patients with idiopathic pulmonary fibrosis (IPF) over 52 weeks. Results suggested that nintedanib 150 mg bid was associated with a reduced decline in forced vital capacity (FVC) and fewer acute exacerbations versus placebo. After completing period 1, patients could continue treatment in a further blinded treatment phase (period 2). <h3>Methods</h3> In period 2, patients treated with nintedanib in period 1 continued their dose, and placebo-treated patients switched to nintedanib 50 mg qd. Here we present descriptive data on FVC, acute exacerbations, mortality and adverse events for the nintedanib 150 mg bid and comparator (placebo/nintedanib 50 mg qd) groups during periods 1 and 2. <h3>Results</h3> Of 428 patients treated in period 1 (nintedanib 150 mg bid n = 85, placebo n = 85), 316 patients completed period 1 and 286 patients (nintedanib 150 mg bid n = 48, comparator n = 54) continued treatment in period 2. Mean total duration of exposure was 14.2 months for nintedanib 150 mg bid and 16.8 months for comparator. The mean observed change from baseline in FVC over time was consistently lower in the nintedanib 150 mg bid group compared with comparator across periods 1 and 2 (Figure 1). The incidence of acute exacerbations was lower in the nintedanib 150 mg bid group compared with comparator (3.2 vs. 13.4 per 100 patient-years). Overall, 14 patients (16.3%) died in the nintedanib 150 mg bid group and 19 patients (21.8%) died in the comparator group. The safety and tolerability of nintedanib 150 mg bid was similar between periods 1 and 2. The proportion of patients reporting an adverse event across periods 1 and 2 was similar in the nintedanib 150 mg bid and comparator groups (97.6% and 94.1%, respectively). <h3>Conclusion</h3> In the TOMORROW trial, the effect of nintedanib on slowing disease progression in patients with IPF was maintained up to week 76. No relevant changes in the safety and tolerability of nintedanib were observed with treatment up to week 76 compared with week 52.
Pulmonary Angiography in the Diagnosis of Thromboembolic Disease
Authors: Arthur A. Sasahara, Myron Stein, Morris Simon, David Littmann
Journal: New England Journal of Medicine (1964)

PULMONARY angiography is potentially the most positive means for diagnosing thromboembolism of the lung. The importance of such a procedure can hardly be overstated when one is dealing with a diagnosis that is missed more often than it is made1 and in which recurrences may subsequently prove to be fatal. Since current therapy has been shown to improve prognosis significantly2 early diagnosis becomes especially important.The present report was prompted by the successful use of pulmonary angiography in 8 of 11 patients in whom the diagnosis of thromboembolic disease was suspected. Five cases of the group studied are presented in . . .