tbuckley/cabot-search huggingface dataset:
Ledipasvir/sofosbuvir regimens for chronic hepatitis C infection: Insights from a work productivity economic model from the United States
Authors: Zobair M. Younossi, Yushan Jiang, Nathaniel J. Smith, Maria Stepanova, Rachel Beckerman
Journal: Hepatology (2015)

Patients with chronic hepatitis C (CHC) exhibit reduced work productivity owing to their disease. Historically, most regimens indicated for CHC genotype 1 (GT1) patients were administered with pegylated interferon (Peg-IFN) and/or ribavirin (RBV), which further compromised work productivity during treatment. The aim of this study was to model the impact of LDV/SOF (ledipasvir/sofosbuvir), the first Peg-IFN- and RBV-free regimen for CHC GT1 patients, on work productivity from an economic perspective, compared to receiving no treatment. The WPAI-SHP (Work Productivity and Activity Index-Specific Health Problem) questionnaire was administered to patients across the ION clinical trials (N = 1,923 U.S. patients). Before initiation of treatment, patients with CHC GT1 in the ION trials exhibited absenteeism and presenteeism impairments of 2.57% and 7.58%, respectively. Patients with cirrhosis exhibited greater work productivity impairment than patients without cirrhosis. In total, 93.21% of U.S. patients in the ION trials achieved SVR; these patients exhibited absenteeism and presenteeism impairments of 2.62% (P = 0.76, when compared to baseline) and 3.53% (P < 0.0001), respectively. Monetizing these data to the entire U.S. population, our model projects an annual societal cost of $7.1 billion owing to productivity loss in untreated GT1 CHC patients. Our model projects that, when compared to no treatment, treating all CHC GT1 patients with a regimen with very high viral eradication rates (LDV/SOF) would translate to annual productivity loss savings of $2.7 billion over a 1-year time horizon.Patients with untreated HCV impose a substantial societal burden owing to reduced work productivity. As a result of improvements in work productivity, treatment of CHC GT1 patients with LDV/SOF-based regimens is likely to result in significant cost savings from a societal perspective, relative to no treatment.
Predictors of failure of noninvasive ventilation (NIV) in acute respiratory failure due to chronic obstructive pulmonary disease
Authors: Catarina Ferreira, Catarina Dias, Mariana Mendes, Joaquim Moita
Journal: European Respiratory Journal (2013)

NIV in acute respiratory failure due to COPD is indiscutible but clinical and arterial blood gas parameters to initiate and maintain NIV are controversial.

Aims: Evaluate efficacy and identify predictors of NIV failure, defined as need of intubation or death during hospitalization, in acute exacerbation of COPD.

Methods: Observational study. Analyzed clinical and functional data of 41 patients (55 episodes of NIV) with Philips Respironics V60®.

Results: 85% male, mean age 72,2Y (±11,4), BMI 28,8 (±4,8) Kg/m², FEV1 40,9 (±14,8) %pred. Previous long term oxygen therapy in 70,9% and domiciliary NIV in 43,6%. NIV success in 85,5% (group 1) and failure in 14,5% (group 2). Pneumonia in 40,4% of success and 37,5% of failure group. Co-morbid conditions in 75% in both groups. Patients were significantly older in failure group (84,6±4,4 vs 70,1±10,8 yrs, p 0,05). There was no significantly difference between groups in pH, PaO2/FiO2 ratio, PaCO2 and vital signs at baseline or two hours after starting NIV. Average time to correction of acidemia of 15,1±12,2 hrs. Mean duration of NIV 5,9±4,5 days. Average hospital stay 10,8±7,6 days; 31% started domiciliary NIV. None of the patients underwent invasive mechanical ventilation. Overall mortality was 14,5% (8 patients).

Conclusions: In our group, age is the only factor associated with NIV failure, with mean age of death of 84,6 yrs. NIV has been successfully applied in acute exacerbations of COPD with critical values of pH and hypercapnia.
An Exploratory Case-Control Study of Brain Tumors in Adults
Authors: J D Burch, K J Craib, B C Choi, A B Miller, H A Risch, G R Howe
Journal: JNCI Journal of the National Cancer Institute (1987)

An exploratory study of brain tumors in adults was carried out using 215 cases diagnosed in Southern Ontario between 1979 and 1982, with an individually matched, hospital control series. Significantly elevated risks were observed for reported use of spring water, drinking of wine, and consumption of pickled fish, together with a significant protective effect for the regular consumption of any of several types of fruit. While these factors are consistent with a role for N-nitroso compounds in the etiology of these tumors, for several other factors related to this hypothesis, no association was observed. Occupation in the rubber industry was associated with a significant relative risk of 9.0, though no other occupational associations were seen. Two previously unreported associations were with smoking nonfilter cigarettes with a significant trend and with the use of hair dyes or sprays. The data do not support an association between physical head trauma requiring medical attention and risk of brain tumors and indicate that exposure to ionizing radiation and vinyl chloride monomer does not contribute any appreciable fraction of attributable risk in the population studied. The findings warrant further detailed investigation in future epidemiologic studies.
Drug use in English professional football
Authors: I Waddington, D Malcolm, M Roderick, R Naik
Journal: British Journal of Sports Medicine (2005)

Objectives: To examine several issues related to drug use in English professional football. More particularly the project sought to gather data on: players’ use of permitted supplements (mineral and vitamin pills and creatine); whether they sought advice, and if so from whom, about their use of supplements; their experience of and attitudes towards drug testing; their views on the extent of the use of banned performance enhancing and recreational drugs in football; and their personal knowledge of players who used such drugs. Methods: With the cooperation of the Professional Footballers Association (PFA), reply paid postal questionnaires were delivered to the home addresses of all 2863 members of the PFA. A total of 706 questionnaires were returned, a response rate of just under 25%. Results: Many players use supplements, although almost one in five players does so without seeking qualified professional advice from anyone within the club. Blood tests are rarely used to monitor the health of players. One third of players had not been tested for drugs within the preceding two years, and 60% felt that they were unlikely to be tested in the next year. The use of performance enhancing drugs appears to be rare, although recreational drugs are commonly used by professional footballers: 6% of respondents indicated that they personally knew players who used performance enhancing drugs, and 45% of players knew players who used recreational drugs. Conclusions: There is a need to ensure that footballers are given appropriate advice about the use of supplements in order to minimise the risk of using supplements that may be contaminated with banned substances. Footballers are tested for drugs less often than many other elite athletes. This needs to be addressed. The relatively high level of recreational drug use is not reflected in the number of positive tests. This suggests that many players who use recreational drugs avoid detection. It also raises doubts about the ability of the drug testing programme to detect the use of performance enhancing drugs.
Varicella infection is not associated with increasing prevalence of eczema: a U.S. population-based study
Authors: J.C. Li, J.I. Silverberg
Journal: British Journal of Dermatology (2015)

Journal Article Varicella infection is not associated with increasing prevalence of eczema: a U.S. population‐based study Get access J.C. Li, J.C. Li Department of Dermatology Feinberg School of Medicine at Northwestern University Suite 1600 676 N. St Clair St Chicago IL 60611 U.S.A Search for other works by this author on: Oxford Academic Google Scholar J.I. Silverberg J.I. Silverberg Departments of Dermatology, Preventive Medicine and Medical Social Sciences Feinberg School of Medicine at Northwestern University Chicago IL U.S.ANorthwestern Medicine Multidisciplinary Eczema Center Chicago IL U.S.A Correspondence Jonathan I. Silverberg. E‐mail: JonathanISilverberg@gmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 5, 1 November 2015, Pages 1169–1174, https://doi.org/10.1111/bjd.14028 Published: 01 November 2015
Evaluation of PNA-LNA PCR clamp method sensitivity for detection of key EGFR gene exon 19 and exon 21 mutations
Authors: Michal Skronski, Adam Szpechcinski, Paulina Jagus, Tomoaki Tanaka, Radoslaw Struniawski, Koichi Hagiwara, Joanna Chorostowska-Wynimko
Journal: European Respiratory Journal (2012)

Highly-sensitive, robust and reliable diagnostic method is crucial for clinically useful detection of EGFR mutations in NSCLC. Due to low sensitivity, direct sequencing is restricted for samples containing at least 50% of tumor cells. PNA-LNA PCR clamp represents allele-specific approach to gene analysis and demonstrates high accuracy and ability to detect mutant alleles present in low fraction of tumor cells.  Aim:  To compare the in vitro sensitivity of PNA-LNA PCR clamp method versus direct Sanger sequencing in detecting EGFR exon 19 deletions and exon 21 L858R mutation.  Methods:  Mutated DNA was isolated from cell lines harboring endogenous exon 19 deletion or L858R mutation. Sensitivity of direct Sanger sequencing and PNA-LNA PCR clamp method was analyzed in serial dilutions of mutant allele intermixed with wild-type DNA.  Results:  PNA-LNA PCR clamp method reliably detected both exon 19 deletion and L858R down to 1% DNA admixture level. Direct sequencing presented considerably lower sensitivity detecting only down to 50% of mutated exon 19 allele in DNA mixture and down to 5% in samples with L858R mutant allele.  Conclusions:  PNA-LNA PCR clamp method is the highly sensitive tool for detection of EGFR activating mutations. It might be particularly useful in heterogenous samples with low content of mutant allelle, like biopsy material. Direct sequencing presents lower sensitivity, limited by type of mutation.
A comparison of cardiac biopsy grades and ejection fraction estimations in patients receiving Adriamycin.
Authors: M S Ewer, M K Ali, B Mackay, S Wallace, M Valdivieso, S S Legha, R S Benjamin, T P Haynie
Journal: Journal of Clinical Oncology (1984)

One hundred fifty-eight patients receiving Adriamycin underwent 226 transjugular biopsy procedures. The specimens were evaluated by electron microscopy for evidence of drug-related cardiotoxicity. Ejection fraction determinations using echocardiographic or nuclear techniques at rest were available for 69% and 81% of the patients, respectively. Analysis of the data revealed a correlation between cumulative Adriamycin dose and biopsy grade (p less than 0.02). No similar relationship existed between cumulative Adriamycin dose and ejection fractions obtained at rest or between biopsy grades and ejection fractions. In patients who underwent serial endomyocardial biopsies and serial ejection fraction determinations, the correlation between changes in biopsy grade and ejection fraction was poor. A change in resting ejection fraction detected by either method did not reliably predict a change in biopsy grade. The poor correlation between ejection fractions and biopsy grades could be due in part to the sensitivity and specificity of the Adriamycin-related structural changes in contrast to the wider range of disease processes that can affect myocardial function, and to the fact that structural changes often precede the ejection fraction abnormalities. The greater sensitivity and specificity of the biopsy grade should prove useful in reducing the risks associated with evaluating new anthracyclines and potential myocardial protectors of Adriamycin toxicity.
A Value Framework for Cancer Screening: Advice for High-Value Care From the American College of Physicians
Authors: Russell P. Harris, Timothy J. Wilt, Amir Qaseem
Journal: Annals of Internal Medicine (2015)

Experts, professional societies, and consumer groups often recommend different strategies for cancer screening. These strategies vary in the intensity of their search for asymptomatic lesions and in their value. This article outlines a framework for thinking about the value of varying intensities of cancer screening. The authors conclude that increasing intensity beyond an optimal level leads to low-value screening and speculate about pressures that encourage overly intensive, low-value screening.
Optimal timing for initiation of highly active antiretroviral therapy in treatment-naïve human immunodeficiency virus-1-infected individuals presenting with AIDS-defining diseases: the experience of the PISCIS Cohort
Authors: C. Manzardo, A. Esteve, N. Ortega, D. Podzamczer, J. Murillas, F. Segura, L. Force, C. Tural, J. Vilaró, A. Masabeu, I. Garcia, M. Guadarrama, E. Ferrer, M. Riera, G. Navarro, B. Clotet, J.M. Gatell, J. Casabona, J.M. Miró
Journal: Clinical Microbiology and Infection (2012)
Catecholamines modulate podocyte function.
Authors: T B Huber, J Gloy, A Henger, P Schollmeyer, R Greger, P Mundel, H Pavenstädt
Journal: Journal of the American Society of Nephrology (1998)

The aim of this study was to investigate the influence of adrenoceptor agonists on the intracellular calcium activity ([Ca2+]i), membrane voltage (Vm), and ion conductances (Gm) in differentiated mouse podocytes. [Ca2+]i was measured by the Fura-2 fluorescence method in single podocytes. Noradrenaline and the alpha 1-adrenoceptor agonist phenylephrine induced a reversible and concentration-dependent biphasic increase of [Ca2+]i in podocytes (EC50 approximately 0.1 microM for peak and plateau), whereas the alpha 2-adrenoceptor agonist UK 14.304 did not influence [Ca2+]i. The [Ca2+]i response induced by noradrenaline was completely inhibited by the alpha 1-adrenoceptor antagonist prazosin (10 nM). In a solution with a high extracellular K+ (72.5 mM), [Ca2+]i was unchanged and the [Ca2+]i increase induced by noradrenaline was not inhibited by the L-type Ca2+ channel blocker nicardipine (1 microM). Vm and Gm were examined with the patch-clamp technique in the slow whole-cell configuration. Isoproterenol, phenylephrine, and noradrenaline depolarized podocytes and increased Gm. The order of potency for the adrenoceptor agonists was isoproterenol (EC50 approximately 1 nM) > noradrenaline (EC50 approximately 0.3 microM) > phenylephrine (EC50 approximately 0.5 microM). The beta 2-adrenoceptor antagonist ICI 118.551 (5 to 100 nM) inhibited the effect of isoproterenol on Vm. Stimulation of adenylate cyclase by forskolin mimicked the effect of isoproterenol on Vm and Gm (EC50 approximately 40 nM). Isoproterenol induced a time- and concentration-dependent increase of cAMP in podocytes. The effect of isoproterenol was unchanged in the absence of Na+ or in an extracellular solution with a reduced Ca2+ concentration, whereas it was significantly increased in an extracellular solution with a reduced Cl- concentration (from 145 to 32 mM). The data indicate that adrenoceptor agonists regulate podocyte function: They increase [Ca2+]i via an alpha 1-adrenoceptor and induce a depolarization via a beta 2-adrenoceptor. The depolarization is probably due to an opening of a cAMP-dependent Cl- conductance.
PICTURE: Clinical pattern and pneumococcal infections in patients with community-acquired pneumonia (CAP) admitted to emergency department
Authors: Francesco Blasi, Stafano Aliberti, Marco Mantero, Maria Moriondo, Francesco Nieddu, Chiara Azzari
Journal: European Respiratory Journal (2014)

PICTURE study is a single-centre observational cross-sectional and prospective study on clinical pattern and pneumococcal infections in patients with community-acquired pneumonia (CAP).  Primary objective: To describe the proportion of community-acquired pneumonia that is attributable to Streptococcus pneumoniae (SP) in hospitalized CAP patients.  Secondary objectives: To describe CAP attributable to SP according to socio-demographic and clinical variables;  To describe clinical evolution of CAP and correlation with serotype, bacteriaemic episodes and in hospital and 30days mortality  The serotype distribution and antibiotic resistance patterns of pneumococcal isolates (at admission or during hospitalization) have been evaluated. A total number of 193 patients, 59% males, mean (±SD) age 72.9 (±15.8) y, were enrolled; 14 patients died during hospitalization; 4 patients died after discharge; 7 patients were untraceable after discharge and 1 withdrew inform consent (after discharge). A total number of 35 patients (18%) had CAP due  to SP. Thirty-one samples were positive to SP and had typeable serotype -  (more than 1 serotype in each sample). In our series SP is the main cause of CAP. The 13-valent conjugate vaccine potentially covers more than 40% of the serotypes identified.
The influence of baseline exercise tolerance on long-term efficacy outcomes following endoscopic thermal vapor ablation (InterVapor™) in patients with heterogeneous emphysema
Authors: Arschang Valipour, Felix J.F. Herth, Armin Ernst, Peter Hopkins, Jim J. Egan, Franz Stanzel, Manfred Wagner, Christian Witt, Kim Baker, Mark H. Gotfried, Steven Kesten, Gregory Snell
Journal: European Respiratory Journal (2012)

Introduction: The NETT noted that baseline exercise tolerance may influence long-term outcomes following lung volume reduction. The association of baseline six minute walk distance (6MWD) to outcomes was examined in a study of endoscopic thermal vapor ablation in patients with heterogeneous emphysema.

Methods: Post hoc subgroup analysis from the Vapor trial, a multicenter single-arm trial of InterVapor (single upper lobe treatment at 10 cal/g) in patients with upper lobe emphysema. Inclusion: FEV1 15%-45% predicted, RV>150%, TLC>100%, 6MWD>140 m, DLCO>20%, prior pulmonary rehabilitation. Outcomes included spirometry, body plethysmography, lobar volume reduction (LoVR) by HRCT, SGRQ, mMRC dyspnea, and 6MWD. Endpoints were dichotomized based on two thresholds for baseline 6MWD.

Results: 44 patients received InterVapor. Demographics: 50% men, age 63 years, FEV1 0.86 L (31% predicted), SGRQ 59 units, 6MWD 300 m. Results at 6 and 12 months (mean change from baseline):

View this table:



Conclusion: Baseline 6MWD was associated with differences that were most prominent with the subsequent 6MWD and SGRQ at 12 months. Other outcomes showed no consistent pattern of association. A bias such as regression to the mean cannot be ruled out in this analysis.
Pirfenidone stabilizes pulmonary function and reduces 18F-FDG-uptake in restrictive allograft syndrome following lung transplantation
Authors: Robin Vos, Stijn Verleden, David Ruttens, Elly Vandermeulen, Hannelore Bellon, Jonas Yserbyt, Lieven Dupont, Olivier Gheysens, Nathalie De Raedt, Dirk Van Raemdonck, Bart Vanaudenaerde, Geert Verleden
Journal: European Respiratory Journal (2014)

Introduction: We recently reported stabilization of FVC and FEV1 with regression of subpleural consolidations and ground-glass opacities following pirfenidone (PFD) treatment for Restrictive Allograft Syndrome (RAS) after lung transplantation (LTx) (Vos et al. Am J Transplant, 2013). Increased 18F-FDG uptake was present at diagnosis of RAS in this case. In a second case of RAS treated with PFD presented herein, we sought to confirm our prior findings and to describe the PET/CT-evolution over time with PFD.

Methods: a 67-year old patient was diagnosed with RAS more than 10 years after SSLTx for emphysema. PFD in compassionate use was started add-on to his treatment with FK-MPA-steroids after informed consent and ethical approval. PET/CT was performed at start and after 3 months of PFD.

Results: After initiation of PFD stabilization of FVC, FEV1 and TLC as well as decreased 18F-FDG-uptake was seen (SUVmax right 5.10 before vs. 2.6 after PFD; SUVmax left 4.44 before vs. 2.4 after PFD). Because of severe subjective intolerance (headache, nausea and anorexia) PFD was stopped by the patient after 3.4 months, following which he opted for palliative sedation and finally succumbed 5 months after PFD had been started.

Conclusion: PFD may stabilize the decline in pulmonary function and decrease 18F-FDG-uptake in RAS following LTx, yet side-effects may make it difficult to tolerate treatment.

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Characteristics and predictors of mortality in patients with pleural infection
Authors: Rebecca Taylor, Stephen Murphy, Alice Melville
Journal: European Respiratory Journal (2011)

Background: Pleural infection is increasing in incidence and causes significant morbidity and mortality. Many UK patients are cared for by non-respiratory teams.

Aim of study: To characterise patients with pleural infection, assess standards of care and identify clinical variables predictive of outcome.

Methods: Case records of patients diagnosed with pleural infection were reviewed with reference to British Thoracic Society guidelines. Pleural infection was confirmed if pleural fluid was purulent or turbid with pH<7.20 and/or positive bacterial culture, with associated systemic features of infection.

Results: 45 cases were included, 69% male, median age (IQR) 72 (46-78) years. 36% had a recent pleural procedure prior to developing infection. 36% were immunosuppressed, 13% had an underlying malignancy. 73% were under respiratory care. Inpatient mortality was 20%. Outcomes varied between respiratory and non-respiratory care: Mortality: 9% v 50% OR (95% CI) 0.10 (0.019-0.51) p=0.006; Drain-related complications: 27% v 58% OR 0.26 (0.06-1.06) p=0.056; Length of stay: mean (SD) 18.3 (20.1) v 35.3 (28.8) days HR 4.16 (1.59-10.9) p=0.0035. On univariate analysis mortality was associated with increased age, high urea, low serum albumin and low pleural fluid protein level. On multivariate analysis mortality was predicted by age≥75 years OR 10.7 (1.75-66.6) p=0.010, albumin <30mg/dl OR 6.41 (1.47-35.7) p=0.032, and non-respiratory care OR 6.7 (1.07-42.4) p=0.041.

Conclusion: Pleural infections are often iatrogenic and associated with malignancy or immunosuppression. Complications with chest drains are common. Mortality is highest in older patients with low albumin. Patients under respiratory care have better outcomes.
Idiopathic pulmonary fibrosis: tracking the true occurrence is challenging
Authors: Jonathan M. Samet, David Coultas, Ganesh Raghu
Journal: European Respiratory Journal (2015)

Tracking patterns of disease incidence and mortality is fundamental to disease control. The story of lung cancer is exemplary; the 20th century epidemic of lung cancer was first detected in western countries as mortality rates rose; initially it affected males more than females; and rates were not uniform across regions and between countries [1]. The epidemiological studies, motivated by the changing patterns of lung cancer occurrence, identified smoking, and occupational and environmental agents as causes of this highly fatal malignancy. Lung cancer mortality rates, which are very close to incidence rates because of the high case-fatality rate of lung cancer, and incidence rates, tracked through cancer registries, have now fallen in the USA and much of Europe in response to successful tobacco control and reduction of exposures to occupational and environmental carcinogens. In the example of lung cancer, tracking of occurrence is facilitated by the close correspondence of mortality with incidence, such that mortality is a reasonable index of occurrence, by the long standing surveillance of cancer through population-based cancer registries in many countries of Europe and much of the USA [2], and by improved diagnosis of lung cancer by increasingly accurate diagnostic methods. IPF is not "just" a rare disease: better diagnosis and reporting by clinicians of this fatal disease is needed <http://ow.ly/P284a>